Quantum I/f noise in infrared detectors and scanning tunneling microscopes

NASA Astrophysics Data System (ADS)

Truong, Amanda Marie

Noise is, by definition, any random and persistent disturbance, which interferes with the clarity of a signal. Modern electronic devices are designed to limit noise, and in most cases the classical forms of noise have been eliminated or greatly reduced through careful design. However, there is a fundamental, quite unavoidable type of noise, called quantum l/f noise, which occurs at low frequencies and is a fundamental consequence of the discrete nature of the charge carriers themselves. This quantum l/f noise is present in any physical cross section or process rate, such as carrier mobility, diffusion rates and scattering processes. Although quantum l/f noise has been observed for nearly a century, there has been much debate over its origin and formulation. But as modern electronic devices require greater levels of performance and detection, the l/f noise phenomenon has moved to the forefront, becoming the subject of intense research. Here, for the first time, the quantum l/f fluctuations present in both the dark current of the Quantum Well Intersubband Photodetector and the tunneling current of the Scanning Tunneling Microscope are investigated. Using the quantum l/f theory, the quantum l/f noise occurring in each of these devices is formulated. The theoretical noise results are then compared with the experimental findings of various authors with very good agreement. This important work provides a foundation for understanding quantum l/f noise and its causes in the QWIP and STM devices, and could ultimately lead to improved technology and noise reduction in these devices and others.

The lactoferricin B-derived peptide, LfB17-34, induces melanogenesis in B16F10 cells.

PubMed

Huang, Hsiu-Chin; Lin, Hsuan; Huang, Min-Chuan

2017-03-01

Lactoferricin B (LfcinB), a peptide of bovine lactoferrin (LfB), exhibits multiple biological functions, including antimicrobial, antiviral, antioxidant and immunomodulatory activities. However, the role of LfcinB-related peptides in melanogenesis remains unclear. In this study, a set of five LfcinB-related peptides was examined. We found that LfB17‑34, an 18-mer LfcinB-derived peptide, increased melanogenesis in B16F10 melanoma cells without significantly affecting cell viability. LfB17‑34 increased in vitro tyrosinase activity and melanin content in a dose-dependent manner. The results of RT-qPCR and western blot analyses showed that LfB17‑34 increased the mRNA and protein expression of tyrosinase and tyrosinase-related protein 1 (Trp1). Moreover, LfB17‑34 inhibited the phosphorylation of MAPK/Erk, but not p38 and Akt, and constitutively active MEK was able to reverse the LfB17-34-enhanced pigmentation, melanin content, and tyrosinase activity, suggesting a role of Erk signaling in the process of LfB17‑34-mediated pigmentation. Taken together, these results suggest that LfB17‑34 induces melanogenesis in B16F10 cells primarily through increased tyrosinase expression and activity and that LfB17‑34 could be further developed for the treatment of hypopigmentation disorders.

The lactoferricin B-derived peptide, LfB17-34, induces melanogenesis in B16F10 cells

PubMed Central

Huang, Hsiu-Chin; Lin, Hsuan; Huang, Min-Chuan

2017-01-01

Lactoferricin B (LfcinB), a peptide of bovine lactoferrin (LfB), exhibits multiple biological functions, including antimicrobial, antiviral, antioxidant and immuno-modulatory activities. However, the role of LfcinB-related peptides in melanogenesis remains unclear. In this study, a set of five LfcinB-related peptides was examined. We found that LfB17-34, an 18-mer LfcinB-derived peptide, increased melanogenesis in B16F10 melanoma cells without significantly affecting cell viability. LfB17-34 increased in vitro tyrosinase activity and melanin content in a dose-dependent manner. The results of RT-qPCR and western blot analyses showed that LfB17-34 increased the mRNA and protein expression of tyrosinase and tyrosinase-related protein 1 (Trp1). Moreover, LfB17-34 inhibited the phosphorylation of MAPK/Erk, but not p38 and Akt, and constitutively active MEK was able to reverse the LfB17-34-enhanced pigmentation, melanin content, and tyrosinase activity, suggesting a role of Erk signaling in the process of LfB17-34-mediated pigmentation. Taken together, these results suggest that LfB17-34 induces melanogenesis in B16F10 cells primarily through increased tyrosinase expression and activity and that LfB17-34 could be further developed for the treatment of hypopigmentation disorders. PMID:28204812

Serum disposition of bovine lactoferrin after oral and anal administration and its proteolytic cleavage by gastric transit in rainbow trout (Oncorhynchus mykiss W.).

PubMed

Cecchini, Stefano; Caputo, Anna R

2009-01-01

Several studies have shown an immunomodulatory effect of orally administered bovine lactoferrin (LF) in fish, but the process of digestion was not characterized. In the present study, we investigated the fate of bovine LF after oral and anal administration, and studied the appearance of intact LF in the bloodstream and its proteolytic attack during the gastric transit in rainbow trout (Oncorhynchus mykiss) held at 9 degrees C and 18 degrees C. Data obtained showed the presence of intact bovine LF in the bloodstream only after anal administration in fish held at 18 degrees C and the presence of several peptides derived from bovine LF in the gastric content. Immunoblotting analysis showed that only a part of bovine LF-derived peptides reacted with the applied anti-bovine LF antibody. The concentration of intact bovine LF, after 30 min of administration, in the gastric content of fish reared at 18 degrees C, being extremely low, if any, led us to suspect that the immunoregulatory effect of dietary bovine LF shown in fish by several authors is not due to the intact form but to bioactive fragments, originated by the proteolytic attack during the gastric transit, as demonstrated in higher vertebrates.

Nutritional composition analysis of meat from human lactoferrin transgenic bulls.

PubMed

Zhao, Jie; Xu, Jianxiang; Wang, Jianwu; Li, Ning

2013-01-01

Transgenic technology has many potential advantages in food production. However, the transgenic technology process may influence the composition of food products derived from genetically engineered (GE) animals, which may be adverse to human health. Therefore, it is very important to research the compositions of GE animal products. Here, we analyzed the compositions of meat from the offspring of human lactoferrin (hLF) transgenic cows, which can express human lactoferrin proteins in their mammary gland. Six hLF transgenic bulls and three wide-type (WT) bulls, 10 months of age, were slaughtered for meat composition analysis. To determine the comparative health of hLF bulls for meat analysis, hematological analyses, organ/body weight analyses and pathology analyses were conducted. Results of the meat analysis show that there were no significant differences in the hematological parameters, organ/body weight ratios of hLF and WT bulls (P>0.05), and histopathological examination of the main organs of hLF bulls revealed no abnormalities. Nutrient parameters of meat compositions of hLF and WT bulls did not show any significant differences (P>0.05). All of these results suggest that the hLF transgene did not have an impact on the meat nutrient compositions of hLF bulls.

Effect of friction stir welding on microstructure and corrosion behavior of LF6 aluminum alloy

NASA Astrophysics Data System (ADS)

Ghauri, Faizan Ali; Farooq, A.; Ahmad, A.; Deen, K. M.

2017-03-01

The LF6 aluminum alloy plates were joined by friction stir welding method. The tool rotational (1180 rpm) and transverse speed (0.56 mm s-1) were kept constant during welding of 4 mm thick plates. The microstructural features, hardness and tensile properties of the welded samples were determined to evaluate the structural integrity in comparison with the base metal. The electrochemical behavior of base metal (BM), thermo-mechanically affected zone (TMAZ) and weld nugget zone (WNZ) was also investigated by potentiodynamic polarization and electrochemical impedance spectroscopy in 3.5% NaCl solution. The microstructural study revealed significant grain refinement and agglomeration of β (Mg2Al3) intermetallic precipitates in the WNZ. The relatively higher hardness and a decrease in the ductility (3%) also assured the formation of precipitates β precipitates in the WNZ welded samples. The fracture surface of welded sample also revealed the existence of β precipitates within the elongated dimples which may be considered as the crack initiation sites. The relatively lower corrosion rate (23.68 mpy) and higher charge transfer resistance (403 Ω cm2) of BM compared to WNZ could be associated with the galvanic dissolution of Al-matrix through competitive charge transfer and relaxation (adsorption/desorption of intermediate species) processes specifically at the vicinity of the β precipitates.

Bovine lactoferrin digested with human gastrointestinal enzymes inhibits replication of human echovirus 5 in cell culture.

PubMed

Furlund, Camilla B; Kristoffersen, Anja B; Devold, Tove G; Vegarud, Gerd E; Jonassen, Christine M

2012-07-01

Many infant formulas are enriched with lactoferrin (Lf) because of its claimed beneficial effects on health. Native bovine Lf (bLf) is known to inhibit in vitro replication of human enteroviruses, a group of pathogenic viruses that replicate in the gut as their primary infection site. On the basis of a model digestion and human gastrointestinal enzymes, we hypothesized that bLf could retain its antiviral properties against enterovirus in the gastrointestinal tract, either as an intact protein or through bioactive peptide fragments released by digestive enzymes. To test our hypothesis, bLf was digested with human gastric juice and duodenal juice in a 2-step in vitro digestion model. Two gastric pH levels and reduction conditions were used to simulate physiological conditions in adults and infants. The antiviral activity of native bLf and of the digested fractions was studied on echovirus 5 in vitro, using various assay conditions, addressing several mechanisms for replication inhibition. Both native and digested bLf fractions revealed a significant inhibitory effect, when added before or simultaneously with the virus onto the cells. Furthermore, a significant stronger sustained antiviral effect was observed when bLf was fully digested in the gastric phase with fast pH reduction to 2.5, compared with native bLf, suggesting the release of antiviral peptides from bLf during the human digestion process. In conclusion, this study demonstrates that bLf may have a role in the prevention of human gastrointestinal virus infection under physiological conditions and that food containing bLf may protect against infection in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of technological treatments on bovine lactoferrin: An overview.

PubMed

Franco, Indira; Pérez, María Dolores; Conesa, Celia; Calvo, Miguel; Sánchez, Lourdes

2018-04-01

Lactoferrin (LF) is a multifunctional protein that exerts important activities in the neonate through its presence in milk, and also in other external mucosas, acting as a defense protein of innate immunity. The addition of bovine LF to infant formula and also to other functional products and cosmetics has increased during the last decades. Consequently, it is essential to know the effect that the technological processes, necessary to elaborate those products, have on LF activity. In this study, we have revised the effect of classical treatments on lactoferrin structure and activity, such as heat treatment or drying, and also of emerging technologies, like high pressure or pulsed electric field. The results of the studies included in this review indicate that LF stability is dependent on its level of iron-saturation and on the characteristics of the treatment media. Furthermore, the studies revised here reveal that the non-thermal treatments are interesting alternatives to the traditional ones, as they protect better the structure and activity of lactoferrin. It is also clear the need for research on LF encapsulation by different ways, to protect its properties before it reaches the intestine. All this knowledge would allow designing processes less harmful for LF, thus maintaining all its functionality. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human Lumbar Ligamentum Flavum Anatomy for Epidural Anesthesia: Reviewing a 3D MR-Based Interactive Model and Postmortem Samples.

PubMed

Reina, Miguel A; Lirk, Philipp; Puigdellívol-Sánchez, Anna; Mavar, Marija; Prats-Galino, Alberto

2016-03-01

The ligamentum flavum (LF) forms the anatomic basis for the loss-of-resistance technique essential to the performance of epidural anesthesia. However, the LF presents considerable interindividual variability, including the possibility of midline gaps, which may influence the performance of epidural anesthesia. We devise a method to reconstruct the anatomy of the digitally LF based on magnetic resonance images to clarify the exact limits and edges of LF and its different thickness, depending on the area examined, while avoiding destructive methods, as well as the dissection processes. Anatomic cadaveric cross sections enabled us to visually check the definition of the edges along the entire LF and compare them using 3D image reconstruction methods. Reconstruction was performed in images obtained from 7 patients. Images from 1 patient were used as a basis for the 3D spinal anatomy tool. In parallel, axial cuts, 2 to 3 cm thick, were performed in lumbar spines of 4 frozen cadavers. This technique allowed us to identify the entire ligament and its exact limits, while avoiding alterations resulting from cutting processes or from preparation methods. The LF extended between the laminas of adjacent vertebrae at all vertebral levels of the patients examined, but midline gaps are regularly encountered. These anatomical variants were reproduced in a 3D portable document format. The major anatomical features of the LF were reproduced in the 3D model. Details of its structure and variations of thickness in successive sagittal and axial slides could be visualized. Gaps within LF previously studied in cadavers have been identified in our interactive 3D model, which may help to understand their nature, as well as possible implications for epidural techniques.

GPU simulation of nonlinear propagation of dual band ultrasound pulse complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kvam, Johannes, E-mail: johannes.kvam@ntnu.no; Angelsen, Bjørn A. J., E-mail: bjorn.angelsen@ntnu.no; Elster, Anne C., E-mail: elster@ntnu.no

In a new method of ultrasound imaging, called SURF imaging, dual band pulse complexes composed of overlapping low frequency (LF) and high frequency (HF) pulses are transmitted, where the frequency ratio LF:HF ∼ 1 : 20, and the relative bandwidth of both pulses are ∼ 50 − 70%. The LF pulse length is hence ∼ 20 times the HF pulse length. The LF pulse is used to nonlinearly manipulate the material elasticity observed by the co-propagating HF pulse. This produces nonlinear interaction effects that give more information on the propagation of the pulse complex. Due to the large difference inmore » frequency and pulse length between the LF and the HF pulses, we have developed a dual level simulation where the LF pulse propagation is first simulated independent of the HF pulse, using a temporal sampling frequency matched to the LF pulse. A separate equation for the HF pulse is developed, where the the presimulated LF pulse modifies the propagation velocity. The equations are adapted to parallel processing in a GPU, where nonlinear simulations of a typical HF beam of 10 MHz down to 40 mm is done in ∼ 2 secs in a standard GPU. This simulation is hence very useful for studying the manipulation effect of the LF pulse on the HF pulse.« less

Correlation Between Low Frequency Auroral Kilometric Radiation (AKR) and Auroral Structures

NASA Technical Reports Server (NTRS)

Paxamickas, Katherine A.; Green, James L.; Gallagher, Dennis L.; Boardsen, Scott; Mende, Stephen; Frey, Harald; Reinisch, Bodo W.

2005-01-01

Auroral Kilometric Radiation (AKR) is a radio wave emission that has long been associated with auroral activity. AKR is normally observed in the frequency range from -60 - 600 kHz. Low frequency AKR (or LF-AKR) events are characterized as a rapid extension of AKR related emissions to 30 kHz or lower in frequency for typically much less than 10 minutes. LF-AKR emissions predominantly occur within a frequency range of 20 kHz - 30 kHz, but there are LF-AKR related emissions that reach to a frequency of 5 kHz. This study correlates all instances of LF-AKR events during the first four years of observations from the IMAGE spacecraft's Radio Plasma Imager (WI) instrument with auroral observations from the wideband imaging camera (WIC) onboard IMAGE. The correlation between LF-AKR occurrence and WIC auroral observations shows that in the 295 confirmed cases of LF-AKR emissions, bifurcation of the aurora is seen in 74% of the cases. The bifurcation is seen in the dusk and midnight sectors of the auroral oval, where AKR is believed to be generated. The polarization of these LF-AKR emissions has yet to be identified. Although LF-AKR may not be the only phenomena correlated with bifurcated auroral structures, bifurcation will occur in most instances when LF-AKR is observed. The LF-AKR emissions may be an indicator of specific auroral processes sometimes occurring during storm-time conditions in which field-aligned density cavities extend a distance of perhaps 5-6 RE tailward from the Earth for a period of 10 minutes or less.

Remembering 'zeal' but not 'thing': reverse frequency effects as a consequence of deregulated semantic processing.

PubMed

Hoffman, Paul; Jefferies, Elizabeth; Ralph, Matthew A Lambon

2011-02-01

More efficient processing of high frequency (HF) words is a ubiquitous finding in healthy individuals, yet frequency effects are often small or absent in stroke aphasia. We propose that some patients fail to show the expected frequency effect because processing of HF words places strong demands on semantic control and regulation processes, counteracting the usual effect. This may occur because HF words appear in a wide range of linguistic contexts, each associated with distinct semantic information. This theory predicts that in extreme circumstances, patients with impaired semantic control should show an outright reversal of the normal frequency effect. To test this prediction, we tested two patients with impaired semantic control with a delayed repetition task that emphasised activation of semantic representations. By alternating HF and low frequency (LF) trials, we demonstrated a significant repetition advantage for LF words, principally because of perseverative errors in which patients produced the previous LF response in place of the HF target. These errors indicated that HF words were more weakly activated than LF words. We suggest that when presented with no contextual information, patients generate a weak and unstable pattern of semantic activation for HF words because information relating to many possible contexts and interpretations is activated. In contrast, LF words are associated with more stable patterns of activation because similar semantic information is activated whenever they are encountered. Copyright © 2011 Elsevier Ltd. All rights reserved.

MiR-21 promotes fibrosis and hypertrophy of ligamentum flavum in lumbar spinal canal stenosis by activating IL-6 expression.

PubMed

Sun, Chao; Tian, Jiwei; Liu, Xinhui; Guan, Guoping

2017-08-26

The molecular mechanism underlying the fibrosis of ligamentum flavum(LF) in patients with lumbar spinal canal stenosis(LSCS) remains unknown. MicroRNAs are reported to play important roles in regulating fibrosis in different organs. The present study aimed to identify fibrosis related miR-21 expression profile and investigate the pathological process of miR-21 in the fibrosis of LF hypertrophy and associated regulatory mechanisms. 15 patients with LSCS underwent surgical treatment were enrolled in this study. For the control group, 11 patients with lumbar disc herniation(LDH) was included. The LF thickness was measured on MRI. LF samples were obtained during the surgery. Fibrosis score was assessed by Masson's trichrome staining. The expression of miR-21 in LF tissues were determined by RT-PCR. Correlation among LF thickness, fibrosis score, and miR-21 expression was analyzed. In addition, Lentiviral vectors for miR-21 mimic were constructed and transfected into LF cells to examine the role of miR-21 in LF fibrosis. Types I and III collagen were used as indicators of fibrosis. IL-6 expression in LF cells after transfection was investigated by RT-PCR and ELISA. Patients in two groups showed similar outcomes regarding age, gender, level of LF tissue. The thickness and fibrosis score of LF in the LSCS group were significantly greater than those in LDH group (all P < 0.05). Similarly, the expression of miR-21 in LSCS group was substantially higher than that in LDH group(P < 0.05). Furthermore, the miR-21 expression exhibited positive correlations with the LF thickness (r = 0.595, P < 0.05) and fibrosis score (r = 0.608, P < 0.05). Of note, miR-21 over-expression increased the expression levels of collagen I and III (P < 0.05). Also, IL-6 expression and secretion in LF cells was elevated after transfection of miR-21 mimic. MiR-21 is a fibrosis-associated miRNA and promotes inflammation in LF tissue by activating IL-6 expression, leading to LF fibrosis and hypertrophy. Copyright © 2017 Elsevier Inc. All rights reserved.

Escherichia coli LF82 differentially regulates ROS production and mucin expression in intestinal epithelial T84 cells: implication of NOX1.

PubMed

Elatrech, Imen; Marzaioli, Viviana; Boukemara, Hanane; Bournier, Odile; Neut, Christel; Darfeuille-Michaud, Arlette; Luis, José; Dubuquoy, Laurent; El-Benna, Jamel; My-Chan Dang, Pham; Marie, Jean-Claude

2015-05-01

Increased reactive oxygen species (ROS) production is associated with inflamed ileal lesions in Crohn's disease colonized by pathogenic adherent-invasive Escherichia coli LF82. We investigated whether such ileal bacteria can modulate ROS production by epithelial cells, thus impacting on inflammation and mucin expression. Ileal bacteria from patients with Crohn's disease were incubated with cultured epithelial T84 cells, and ROS production was assayed using the luminol-amplified chemiluminescence method. The gentamicin protection assay was used for bacterial invasion of T84 cell. The expression of NADPH oxidase (NOX) subunits, mucin, and IL-8 was analyzed by quantitative real-time PCR and Western blots. Involvement of NOX and ROS was analyzed using diphenyleneiodonium (DPI) and N-acetylcysteine (NAC). Among different bacteria tested, only LF82 induced an increase of ROS production by T84 cells in a dose-dependent manner. This response was inhibited by DPI and NAC. Heat- or ethanol-attenuated LF82 bacteria and the mutant LF82ΔFimA, which does not express pili type 1 and poorly adheres to epithelial cells, did not induce the oxidative response. The LF82-induced oxidative response coincides with its invasion in T84 cells, and both processes were inhibited by DPI. Also, we observed an increased expression of NOX1 and NOXO1 in response to LF82 bacteria versus the mutant LF82ΔFimA. Furthermore, LF82 inhibited mucin gene expression (MUC2 and MUC5AC) in T84 cells while increasing the chemotactic IL-8 expression, both in a DPI-sensitive manner. Adherent-invasive E. coli LF82 induced ROS production by intestinal NADPH oxidase and altered mucin and IL-8 expression, leading to perpetuation of inflammatory lesions in Crohn's disease.

Impact of the Maillard reaction on the antioxidant capacity of bovine lactoferrin.

PubMed

Joubran, Yousef; Mackie, Alan; Lesmes, Uri

2013-12-15

Studies raise the notion that the Maillard reaction (MR) may be harnessed to modify the antioxidant capacity of alimentary proteins. However, little is known about the impact of MR on bioactive proteins. Glucose and fructose were used as model moieties reacting with lactoferrin (LF). UV absorbance and SDS-PAGE analyses were used to monitor MR progression during 36 h of mild thermal processing (60 °C, 79% RH). FTIR and CD did not reveal changes in LF structure; However, dynamic light scattering showed MR increased mean particle sizes and sample turbidity at 3

Development and Application of a Low Frequency Near-Field Interferometric-TOA 3D Lightning Mapping Array

NASA Astrophysics Data System (ADS)

Lyu, F.; Cummer, S. A.; Weinert, J. L.; McTague, L. E.; Solanki, R.; Barrett, J.

2014-12-01

Lightning processes radiated extremely wideband electromagnetic signals. Lightning images mapped by VHF interferometry and VHF time of arrival lightning mapping arrays enable us to understand the lightning in-cloud detail development during the extent of flash that can not always be captured by cameras because of the shield of cloud. Lightning processes radiate electromagnetically over an extremely wide bandwidth, offering the possibility of multispectral lightning radio imaging. Low frequency signals are often used for lightning detection, but usually only for ground point location or thunderstorm tracking. Some recent results have demonstrated lightning LF 3D mapping of discrete lightning pulses, but imaging of continuous LF emissions have not been shown. In this work, we report a GPS-synchronized LF near field interferometric-TOA 3D lightning mapping array applied to image the development of lightning flashes on second time scale. Cross-correlation, as used in broadband interferometry, is applied in our system to find windowed arrival time differences with sub-microsecond time resolution. However, because the sources are in the near field of the array, time of arrival processing is used to find the source locations with a typical precision of 100 meters. We show that this system images the complete lightning flash structure with thousands of LF sources for extensive flashes. Importantly, this system is able to map both continuous emissions like dart leaders, and bursty or discrete emissions. Lightning stepped leader and dart leader propagation speeds are estimated to 0.56-2.5x105 m/s and 0.8-2.0x106 m/s respectively, which are consistent with previous reports. In many aspects our LF images are remarkably similar to VHF lightning mapping array images, despite the 1000 times difference in frequency, which may suggest some special links between the LF and VHF emission during lightning processes.

LANDFIRE 2010 - updated data to support wildfire and ecological management

USGS Publications Warehouse

Nelson, Kurtis J.; Connot, Joel A.; Peterson, Birgit E.; Picotte, Joshua J.

2013-01-01

Wildfire is a global phenomenon that affects human populations and ecosystems. Wildfire effects occur at local to global scales impacting many people in different ways (Figure 1). Ecological concerns due to land use, fragmentation, and climate change impact natural resource use, allocation, and conservation. Access to consistent and current environmental data is a constant challenge, yet necessary for understanding the complexities of wildfire and ecological management. Data products and tools from the LANDFIRE Program help decision-makers to clarify problems and identify possible solutions when managing fires and natural resources. LANDFIRE supports the reduction of risk from wildfire to human lives and property, monitoring of fire danger, prediction of fire behavior on active incidents, and assessment of fire severity and impacts on natural systems [1] [2] [3]. LANDFIRE products are unique in that they are nationally consistent and provide the only complete geospatial dataset describing vegetation and wildland fuel information for the entire U.S. As such, LANDFIRE data are useful for many ecological applications [3]. For example, LANDFIRE data were recently integrated into a decision-support system for resource management and conservation decision-making along the Appalachian Trail. LANDFIRE is a joint effort between the U.S. Department of the Interior Office of Wildland Fire, U.S. Department of Agriculture Forest Service Fire & Aviation Management, and The Nature Conservancy. To date, seven versions of LANDFIRE data have been released, with each successive version improving the quality of the data, adding additional features, and/or updating the time period represented by the data. The latest version, LANDFIRE 2010 (LF 2010), released mid-2013, represents circa 2010 landscape conditions and succeeds LANDFIRE 2008 (LF 2008), which represented circa 2008 landscape conditions. LF 2010 used many of the same processes developed for the LF 2008 effort [3]. Ongoing refinement of the LANDFIRE vegetation and fuel data is necessary to improve the quality and usability of the data and to capture landscape disturbance. LANDFIRE relies on Landsat multi-spectral imagery to produce and update vegetation and fuel data. The deep Landsat archive provides data needed for vegetation classification, change analysis, and historical disturbance characterization, for which LANDFIRE has used more than 24,000 image scenes since the program’s inception. In addition, LF 2010 used airborne and spaceborne lidar, and spaceborne synthetic aperture radar (SAR) to map vegetation structure in areas where ground-based field information was lacking, including Alaska and U.S.-affiliated islands in the Caribbean and the Pacific. The mapping of insular areas is new for the 2010 data release; previous versions of LANDFIRE were limited to the conterminous U.S., Alaska, and Hawaii.

In situ monitoring of cocrystals in formulation development using low-frequency Raman spectroscopy.

PubMed

Otaki, Takashi; Tanabe, Yuta; Kojima, Takashi; Miura, Masaru; Ikeda, Yukihiro; Koide, Tatsuo; Fukami, Toshiro

2018-05-05

In recent years, to guarantee a quality-by-design approach to the development of pharmaceutical products, it is important to identify properties of raw materials and excipients in order to determine critical process parameters and critical quality attributes. Feedback obtained from real-time analyses using various process analytical technology (PAT) tools has been actively investigated. In this study, in situ monitoring using low-frequency (LF) Raman spectroscopy (10-200 cm -1 ), which may have higher discriminative ability among polymorphs than near-infrared spectroscopy and conventional Raman spectroscopy (200-1800 cm -1 ), was investigated as a possible application to PAT. This is because LF-Raman spectroscopy obtains information about intermolecular and/or lattice vibrations in the solid state. The monitoring results obtained from Furosemide/Nicotinamide cocrystal indicate that LF-Raman spectroscopy is applicable to in situ monitoring of suspension and fluidized bed granulation processes, and is an effective technique as a PAT tool to detect the conversion risk of cocrystals. LF-Raman spectroscopy is also used as a PAT tool to monitor reactions, crystallizations, and manufacturing processes of drug substances and products. In addition, a sequence of conversion behaviors of Furosemide/Nicotinamide cocrystals was determined by performing in situ monitoring for the first time. Copyright © 2018 Elsevier B.V. All rights reserved.

How much will it cost to eradicate lymphatic filariasis? An analysis of the financial and economic costs of intensified efforts against lymphatic filariasis.

PubMed

Kastner, Randee J; Sicuri, Elisa; Stone, Christopher M; Matwale, Gabriel; Onapa, Ambrose; Tediosi, Fabrizio

2017-09-01

Lymphatic filariasis (LF), a neglected tropical disease (NTD) preventable through mass drug administration (MDA), is one of six diseases deemed possibly eradicable. Previously we developed one LF elimination scenario, which assumes MDA scale-up to continue in all countries that have previously undertaken MDA. In contrast, our three previously developed eradication scenarios assume all LF endemic countries will undertake MDA at an average (eradication I), fast (eradication II), or instantaneous (eradication III) rate of scale-up. In this analysis we use a micro-costing model to project the financial and economic costs of each of these scenarios in order to provide evidence to decision makers about the investment required to eliminate and eradicate LF. Costing was undertaken from a health system perspective, with all results expressed in 2012 US dollars (USD). A discount rate of 3% was applied to calculate the net present value of future costs. Prospective NTD budgets from LF endemic countries were reviewed to preliminarily determine activities and resources necessary to undertake a program to eliminate LF at a country level. In consultation with LF program experts, activities and resources were further reviewed and a refined list of activities and necessary resources, along with their associated quantities and costs, were determined and grouped into the following activities: advocacy and communication, capacity strengthening, coordination and strengthening partnerships, data management, ongoing surveillance, monitoring and supervision, drug delivery, and administration. The costs of mapping and undertaking transmission assessment surveys and the value of donated drugs and volunteer time were also accounted for. Using previously developed scenarios and deterministic estimates of MDA duration, the financial and economic costs of interrupting LF transmission under varying rates of MDA scale-up were then modelled using a micro-costing approach. The elimination scenario, which includes countries that previously undertook MDA, is estimated to cost 929 million USD (95% Credible Interval: 884m-972m). Proceeding to eradication is anticipated to require a higher financial investment, estimated at 1.24 billion USD (1.17bn-1.30bn) in the eradication III scenario (immediate scale-up), with eradication II (intensified scale-up) projected at 1.27 billion USD (1.21bn-1.33bn), and eradication I (slow scale-up) estimated at 1.29 billion USD (1.23bn-1.34bn). The economic costs of the eradication III scenario are estimated at approximately 7.57 billion USD (7.12bn-7.94bn), while the elimination scenario is projected to have an economic cost of 5.21 billion USD (4.91bn-5.45bn). Countries in the AFRO region will require the greatest investment to reach elimination or eradication, but also stand to gain the most in cost savings. Across all scenarios, capacity strengthening and advocacy and communication represent the greatest financial costs, whereas mapping, post-MDA surveillance, and administration comprise the least. Though challenging to implement, our results indicate that financial and economic savings are greatest under the eradication III scenario. Thus, if eradication for LF is the objective, accelerated scale-up is projected to be the best investment.

Lymphatic filariasis patient identification in a large urban area of Tanzania: An application of a community-led mHealth system.

PubMed

Mwingira, Upendo; Chikawe, Maria; Mandara, Wilfred Lazarus; Mableson, Hayley E; Uisso, Cecilia; Mremi, Irene; Malishee, Alpha; Malecela, Mwele; Mackenzie, Charles D; Kelly-Hope, Louise A; Stanton, Michelle C

2017-07-01

Lymphatic filariasis (LF) is best known for the disabling and disfiguring clinical conditions that infected patients can develop; providing care for these individuals is a major goal of the Global Programme to Eliminate LF. Methods of locating these patients, knowing their true number and thus providing care for them, remains a challenge for national medical systems, particularly when the endemic zone is a large urban area. A health community-led door-to-door survey approach using the SMS reporting tool MeasureSMS-Morbidity was used to rapidly collate and monitor data on LF patients in real-time (location, sex, age, clinical condition) in Dar es Salaam, Tanzania. Each stage of the phased study carried out in the three urban districts of city consisted of a training period, a patient identification and reporting period, and a data verification period, with refinements to the system being made after each phase. A total of 6889 patients were reported (133.6 per 100,000 population), of which 4169 were reported to have hydrocoele (80.9 per 100,000), 2251 lymphoedema-elephantiasis (LE) (43.7 per 100,000) and 469 with both conditions (9.1 per 100,000). Kinondoni had the highest number of reported patients in absolute terms (2846, 138.9 per 100,000), followed by Temeke (2550, 157.3 per 100,000) and Ilala (1493, 100.5 per 100,000). The number of hydrocoele patients was almost twice that of LE in all three districts. Severe LE patients accounted for approximately a quarter (26.9%) of those reported, with the number of acute attacks increasing with reported LE severity (1.34 in mild cases, 1.78 in moderate cases, 2.52 in severe). Verification checks supported these findings. This system of identifying, recording and mapping patients affected by LF greatly assists in planning, locating and prioritising, as well as initiating, appropriate morbidity management and disability prevention (MMDP) activities. The approach is a feasible framework that could be used in other large urban environments in the LF endemic areas.

Optical design and development of a snapshot light-field laryngoscope

NASA Astrophysics Data System (ADS)

Zhu, Shuaishuai; Jin, Peng; Liang, Rongguang; Gao, Liang

2018-02-01

The convergence of recent advances in optical fabrication and digital processing yields a generation of imaging technology-light-field (LF) cameras which bridge the realms of applied mathematics, optics, and high-performance computing. Herein for the first time, we introduce the paradigm of LF imaging into laryngoscopy. The resultant probe can image the three-dimensional shape of vocal folds within a single camera exposure. Furthermore, to improve the spatial resolution, we developed an image fusion algorithm, providing a simple solution to a long-standing problem in LF imaging.

Plasma lactoferrin levels in newborn preterm infants with sepsis.

PubMed

Decembrino, Lidia; DeAmici, Mara; De Silvestri, Annalisa; Manzoni, Paolo; Paolillo, Piermichele; Stronati, Mauro

2017-12-01

Lactoferrin (Lf) is one of the major proteins of all exocrine secretions with a role in the antinfective process. Our aim was to evaluate how plasma Fl levels may change in response to infection in newborn preterm infants. A total of 15 (8 females, 7 males) newborn preterm infants with a postnatal age >72 h of life, underwent to blood culture and others markers of infection, for suspected sepsis, were enrolled in the study. We found that Lf serum concentration was significantly lowest in four neonates (26.7%) with confirmed sepsis than in 11 (73.3%) with clinical sepsis. The AUC was 0.90 (95%CI: 0.63-0.99). The optimal cutoff for Lf was <1.2 μg/ml with a sensibility of 100% and a specificity of 81.8%. Lf serum concentration was positively correlated with WBC or neutrophil (Spearman rho = 0.69 and 0.49, respectively). Serum Lf could prove a promising, sensitive and specific marker in the diagnostic approach to infants with suspected sepsis, thanks to its role in defense mechanisms and physiological functions of the immune system. Low levels of Lf in sepsis may suggest an immature response due to suboptimal leukocites activity in newborn preterm infants.

Response of human limbal epithelial cells to wounding on 3D RAFT tissue equivalents: effect of airlifting and human limbal fibroblasts.

PubMed

Massie, Isobel; Levis, Hannah J; Daniels, Julie T

2014-10-01

Limbal epithelial stem cell deficiency can cause blindness but may be treated by human limbal epithelial cell (hLE) transplantation, normally on human amniotic membrane. Clinical outcomes using amnion can be unreliable and so we have developed an alternative tissue equivalent (TE), RAFT (Real Architecture for 3D Tissue), which supports hLE expansion, and stratification when airlifted. Human limbal fibroblasts (hLF) may be incorporated into RAFT TEs, where they support overlying hLE and improve phenotype. However, the impact of neither airlifting nor hLF on hLE function has been investigated. hLE on RAFT TEs (±hLF and airlifting) were wounded using heptanol and re-epithelialisation (fluorescein diacetate staining), and percentage putative stem cell marker p63α and proliferative marker Ki67 expression (wholemount immunohistochemistry), measured. Airlifted, hLF- RAFT TEs were unable to close the wound and p63α expression was 7 ± 0.2% after wounding. Conversely, non-airlifted, hLF- RAFT TEs closed the wound within 9 days and p63α expression was higher at 22 ± 5% (p < 0.01). hLE on both hLF- and hLF+ RAFT TEs (non-airlifted) closed the wound and p63α expression was 26 ± 8% and 36 ± 3% respectively (ns). Ki67 expression by hLE increased from 1.3 ± 0.5% before wounding to 7.89 ± 2.53% post-wounding for hLF- RAFT TEs (p < 0.01), and 0.8 ± 0.08% to 17.68 ± 10.88% for hLF+ RAFT TEs (p < 0.05), suggesting that re-epithelialisation was a result of proliferation. These data suggest that neither airlifting nor hLF are necessarily required to maintain a functional epithelium on RAFT TEs, thus simplifying and shortening the production process. This is important when working towards clinical application of regenerative medicine products. Copyright © 2014 Elsevier Ltd. All rights reserved.

High-Frequency Neuromuscular Electrical Stimulation Increases Anabolic Signaling.

PubMed

Mettler, Joni A; Magee, Dillon M; Doucet, Barbara M

2018-03-16

Neuromuscular electrical stimulation (NMES) is commonly used in rehabilitation settings to increase muscle mass and strength. However, the effects of NMES on muscle growth are not clear and no human studies have compared anabolic signaling between low-frequency (LF-) and high-frequency (HF-) NMES. The purpose of this study was to determine the skeletal muscle anabolic signaling response to an acute bout of LF- and HF-NMES. Eleven young healthy volunteers (6 men; 5 women) received an acute bout of LF- (20 Hz) and HF- (60 Hz) NMES. Muscle biopsies were obtained from the vastus lateralis muscle prior to the first NMES treatment and 30-mins following each NMES treatment. Phosphorylation of the following key anabolic signaling proteins was measured by Western blot and proteins are expressed as a ratio of phosphorylated to total: mammalian target of rapamycin (mTOR), p70-S6 kinase 1 (S6K1), and eukaryotic initiation factor 4E binding protein 1 (4E-BP1). Compared to Pre-NMES, phosphorylation of mTOR was upregulated 40.2% for LF-NMES (P = 0.018) and 68.4% for HF-NMES (P < 0.0001) and HF-NMES was 29.3% greater than LF-NMES (P = 0.026). Phosphorylation of S6K1 after HF-NMES was 96.6% higher than Pre-NMES (P = 0.001), was not different between Pre-NMES and LF-NMES (although was 50.4% higher after LF-) or LF- and HF-NMES (P > 0.05). There were no differences between treatment conditions for 4E-BP1 phosphorylation (P > 0.05). An acute bout of LF- and HF-NMES upregulated anabolic signaling with HF-NMES producing a greater anabolic response compared to LF-NMES, suggesting that HF-stimulation may provide a stronger stimulus for processes that initiate muscle hypertrophy. Additionally, the stimulation frequency parameter should be considered by clinicians in the design of optimal NMES treatment protocols.

Laboratory simulations of fluid-induced seismicity in shallow volcanic faults

NASA Astrophysics Data System (ADS)

Fazio, Marco; Benson, Philip; Vinciguerra, Sergio; Meredith, Philip

2015-04-01

Seismicity is a key tool used for monitoring fracturing and faulting in around volcanoes, with a particular emphasis placed on the frequency (Long period or Low Frequency, LF events) thought to be due to fluid movement, as compared to Volcano-Tectonic activity driven by pure fracture. To better understand these fundamental processes this research presents new rock deformation experiments designed to simulate shallow volcano-tectonic pressure/temperature conditions, linking pore fluid flow to the induced seismicity. A particular emphasis is placed on the conditions of pressure and temperature required to stimulate LF activity. Our setup imposes a rapid pore pressure release or "venting" via a small pre-drilled axial conduit to stimulate rapid fluid movement through an established fracture damage zone via a two stage process. Firstly experiments are conducted to generate a through-going shear fracture, with pore fluid connectivity to this fracture enhanced via the axial conduit. The shear failure is imaged via AE location with ~mm scale accuracy. The second stage vents pore fluid pressure via an electrical solenoid valve. We find that this second stage is accompanied by a swarm of LF activity akin to Long Period (LP) activity on active volcanoes. We find that a significant change in the dominant frequency of LF events is recorded as pore fluid pressure decrease through, and beyond, the water boiling point and the transition between LF and VLF occurred at the pressure at which the superheated water turn to vapour. In addition, we observe a significant dependence of the recorded LF upon the fluid flow rate. Finally, we present new data using low frequency (200 kHz) AE sensors, in conjunction with our standard 1 MHz-central-frequency sensors, which permit us to better constraint LF and VLF events with lower attenuation, and hence an improved characterization of these LF seismic signals. Data are used to forecast the final time of failure via the fracture forecast methods of Kilburn (2004), showing a good correlation between measured sample failure time and the forecast time based on AE event rate. Our data showed little change in forecast accuracy when using LF data compared to regular HF data, illustrating the importance of newly fracturing surfaces in the application of such models.

Laboratory simulations of fluid-induced seismicity in shallow volcanic faults

NASA Astrophysics Data System (ADS)

Fazio, M.; Benson, P. M.; Vinciguerra, S.

2014-12-01

Seismicity is a key tool used for monitoring fracturing and faulting in around volcanoes, with a particular emphasis placed on the frequency (Long period or Low Frequency, LF events) thought to be due to fluid movement, as compared to Volcano-Tectonic activity driven by pure fracture. To better understand these fundamental processes this research presents new rock deformation experiments designed to simulate shallow volcano-tectonic pressure/temperature conditions, linking pore fluid flow to the induced seismicity. A particular emphasis is placed on the conditions of pressure and temperature required to stimulate LF activity. Our setup imposes a rapid pore pressure release or "venting" via a small pre-drilled axial conduit to stimulate rapid fluid movement through an established fracture damage zone via a two stage process. Firstly experiments are conducted to generate a through-going shear fracture, with pore fluid connectivity to this fracture enhanced via the axial conduit. The shear failure is imaged via AE location with ~mm scale accuracy. The second stage vents pore fluid pressure via an electrical solenoid valve. We find that this second stage is accompanied by a swarm of LF activity akin to Long Period (LP) activity on active volcanoes. We find that a significant change in the dominant frequency of LF events is recorded as pore fluid pressure decrease through, and beyond, the water boiling point and the transition between LF and VLF occurred at the pressure at which the superheated water turn to vapour. In addition, we observe a significant dependence of the recorded LF upon the fluid flow rate. Finally, we present new data using low frequency (200 kHz) AE sensors, in conjunction with our standard 1 MHz-central-frequency sensors, which permit us to better constraint LF and VLF events with lower attenuation, and hence an improved characterization of these LF seismic signals. Data are used to forecast the final time of failure via the fracture forecast methods of Kilburn (2004), showing a good correlation between measured sample failure time and the forecast time based on AE event rate. Our data showed little change in forecast accuracy when using LF data compared to regular HF data, illustrating the importance of newly fracturing surfaces in the application of such models.

Responsiveness of emulsions stabilized by lactoferrin nano-particles to simulated intestinal conditions.

PubMed

Meshulam, Dafna; Lesmes, Uri

2014-01-01

There is an upsurge of interest in the use of nano-particles to fabricate emulsions and modulate their functionality, with particular emphasis on modulating emulsion digestive fate. Food grade nano-particles formed through controlled processing and electrostatic biopolymer interactions are yet to be systematically studied for their ability to stabilize emulsions and modulate emulsion digestibility. This study focused on the responsiveness of emulsions stabilized by lactoferrin (LF) nano-particles (NPs) and dietary fibers to key digestive parameters. Compared to native LF, LF-NPs comprised emulsion exhibited elevated creaming rates as evident from accelerated stability tests performed by analytical centrifugation. The electrostatic deposition of alginate or carrageenan onto the LF-NPs significantly improved the stability of the corresponding emulsions. Further, the use of various nano-particles showed to have both beneficial and deleterious effects on emulsion responsiveness to pH (2.0 < pH < 10.0), CaCl2 (0-40 mM) and bile (0-25 mg mL(-1)). Simulated pH-stat lipolysis experiments show that the use of LF or LF-NPs had no marked effect on lipolysis. Intriguingly, the use of LF-NPs and alginate reduced emulsion lipolysis by 14% while the use of LF-NPs and carrageenan increased lipolysis by 10%. Microscopy images as well as droplet characterization in terms of size and charge indicate that the altered emulsion responsiveness may be due to physical differences in emulsion properties (e.g. droplet size) and overall organization during digestion (e.g. aggregation vs. coalescence). Overall, this study's insights could prospectively be used to harness protein nano-particles to tweak emulsion behavior during digestion.

Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson's disease treatment.

PubMed

Bi, Chenchen; Wang, Aiping; Chu, Yongchao; Liu, Sha; Mu, Hongjie; Liu, Wanhui; Wu, Zimei; Sun, Kaoxiang; Li, Youxin

Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box-Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD.

Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment

PubMed Central

Bi, Chenchen; Wang, Aiping; Chu, Yongchao; Liu, Sha; Mu, Hongjie; Liu, Wanhui; Wu, Zimei; Sun, Kaoxiang; Li, Youxin

2016-01-01

Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)–poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box–Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD. PMID:27994458

Great Ears: Low-Frequency Sensitivity Correlates in Land and Marine Leviathans.

PubMed

Ketten, D R; Arruda, J; Cramer, S; Yamato, M

2016-01-01

Like elephants, baleen whales produce low-frequency (LF) and even infrasonic (IF) signals, suggesting they may be particularly susceptible to underwater anthropogenic sound impacts. Analyses of computerized tomography scans and histologies of the ears in five baleen whale and two elephant species revealed that LF thresholds correlate with basilar membrane thickness/width and cochlear radii ratios. These factors are consistent with high-mass, low-stiffness membranes and broad spiral curvatures, suggesting that Mysticeti and Proboscidea evolved common inner ear adaptations over similar time scales for processing IF/LF sounds despite operating in different media.

How much will it cost to eradicate lymphatic filariasis? An analysis of the financial and economic costs of intensified efforts against lymphatic filariasis

PubMed Central

Kastner, Randee J.; Sicuri, Elisa; Stone, Christopher M.; Matwale, Gabriel; Onapa, Ambrose; Tediosi, Fabrizio

2017-01-01

Introduction Lymphatic filariasis (LF), a neglected tropical disease (NTD) preventable through mass drug administration (MDA), is one of six diseases deemed possibly eradicable. Previously we developed one LF elimination scenario, which assumes MDA scale-up to continue in all countries that have previously undertaken MDA. In contrast, our three previously developed eradication scenarios assume all LF endemic countries will undertake MDA at an average (eradication I), fast (eradication II), or instantaneous (eradication III) rate of scale-up. In this analysis we use a micro-costing model to project the financial and economic costs of each of these scenarios in order to provide evidence to decision makers about the investment required to eliminate and eradicate LF. Methodology/Key findings Costing was undertaken from a health system perspective, with all results expressed in 2012 US dollars (USD). A discount rate of 3% was applied to calculate the net present value of future costs. Prospective NTD budgets from LF endemic countries were reviewed to preliminarily determine activities and resources necessary to undertake a program to eliminate LF at a country level. In consultation with LF program experts, activities and resources were further reviewed and a refined list of activities and necessary resources, along with their associated quantities and costs, were determined and grouped into the following activities: advocacy and communication, capacity strengthening, coordination and strengthening partnerships, data management, ongoing surveillance, monitoring and supervision, drug delivery, and administration. The costs of mapping and undertaking transmission assessment surveys and the value of donated drugs and volunteer time were also accounted for. Using previously developed scenarios and deterministic estimates of MDA duration, the financial and economic costs of interrupting LF transmission under varying rates of MDA scale-up were then modelled using a micro-costing approach. The elimination scenario, which includes countries that previously undertook MDA, is estimated to cost 929 million USD (95% Credible Interval: 884m-972m). Proceeding to eradication is anticipated to require a higher financial investment, estimated at 1.24 billion USD (1.17bn-1.30bn) in the eradication III scenario (immediate scale-up), with eradication II (intensified scale-up) projected at 1.27 billion USD (1.21bn-1.33bn), and eradication I (slow scale-up) estimated at 1.29 billion USD (1.23bn-1.34bn). The economic costs of the eradication III scenario are estimated at approximately 7.57 billion USD (7.12bn-7.94bn), while the elimination scenario is projected to have an economic cost of 5.21 billion USD (4.91bn-5.45bn). Countries in the AFRO region will require the greatest investment to reach elimination or eradication, but also stand to gain the most in cost savings. Across all scenarios, capacity strengthening and advocacy and communication represent the greatest financial costs, whereas mapping, post-MDA surveillance, and administration comprise the least. Conclusions/Significance Though challenging to implement, our results indicate that financial and economic savings are greatest under the eradication III scenario. Thus, if eradication for LF is the objective, accelerated scale-up is projected to be the best investment. PMID:28949987

Pilot assessment of soil-transmitted helminthiasis in the context of transmission assessment surveys for lymphatic filariasis in Benin and Tonga.

PubMed

Chu, Brian K; Gass, Katherine; Batcho, Wilfrid; 'Ake, Malakai; Dorkenoo, Améyo M; Adjinacou, Elvire; Mafi, 'Eva; Addiss, David G

2014-02-01

Mass drug administration (MDA) for lymphatic filariasis (LF) programs has delivered more than 2 billion treatments of albendazole, in combination with either ivermectin or diethylcarbamazine, to communities co-endemic for soil-transmitted helminthiasis (STH), reducing the prevalence of both diseases. A transmission assessment survey (TAS) is recommended to determine if MDA for LF can be stopped within an evaluation unit (EU) after at least five rounds of annual treatment. The TAS also provides an opportunity to simultaneously assess the impact of these MDAs on STH and to determine the frequency of school-based MDA for STH after community-wide MDA is no longer needed for LF. Pilot studies conducted in Benin and Tonga assessed the feasibility of a coordinated approach. Of the schools (clusters) selected for a TAS in each EU, a subset of 5 schools per STH ecological zone was randomly selected, according to World Health Organization (WHO) guidelines, for the coordinated survey. In Benin, 519 children were sampled in 5 schools and 22 (4.2%) had STH infection (A. lumbricoides, T. trichiura, or hookworm) detected using the Kato-Katz method. All infections were classified as light intensity under WHO criteria. In Tonga, 10 schools were chosen for the coordinated TAS and STH survey covering two ecological zones; 32 of 232 (13.8%) children were infected in Tongatapu and 82 of 320 (25.6%) in Vava'u and Ha'apai. All infections were light-intensity with the exception of one with moderate-intensity T. trichiura. Synchronous assessment of STH with TAS is feasible and provides a well-timed evaluation of infection prevalence to guide ongoing treatment decisions at a time when MDA for LF may be stopped. The coordinated field experiences in both countries also suggest potential time and cost savings. Refinement of a coordinated TAS and STH sampling methodology should be pursued, along with further validation of alternative quantitative diagnostic tests for STH that can be used with preserved stool specimens.

Effect of bovine lactoferrin on Chlamydia trachomatis infection and inflammation.

PubMed

Sessa, Rosa; Di Pietro, Marisa; Filardo, Simone; Bressan, Alessia; Rosa, Luigi; Cutone, Antimo; Frioni, Alessandra; Berlutti, Francesca; Paesano, Rosalba; Valenti, Piera

2017-02-01

Chlamydia trachomatis is an obligate, intracellular pathogen responsible for the most common sexually transmitted bacterial disease worldwide, causing acute and chronic infections. The acute infection is susceptible to antibiotics, whereas the chronic one needs prolonged therapies, thus increasing the risk of developing antibiotic resistance. Novel alternative therapies are needed. The intracellular development of C. trachomatis requires essential nutrients, including iron. Iron-chelating drugs inhibit C. trachomatis developmental cycle. Lactoferrin (Lf), a pleiotropic iron binding glycoprotein, could be a promising candidate against C. trachomatis infection. Similarly to the efficacy against other intracellular pathogens, bovine Lf (bLf) could both interfere with C. trachomatis entry into epithelial cells and exert an anti-inflammatory activity. In vitro and in vivo effects of bLf against C. trachomatis infectious and inflammatory process has been investigated. BLf inhibits C. trachomatis entry into host cells when incubated with cell monolayers before or at the moment of the infection and down-regulates IL-6/IL-8 synthesized by infected cells. Six out of 7 pregnant women asymptomatically infected by C. trachomatis, after 30 days of bLf intravaginal administration, were negative for C. trachomatis and showed a decrease of cervical IL-6 levels. This is the first time that the bLf protective effect against C. trachomatis infection has been demonstrated.

Low-frequency magnetic fields do not aggravate disease in mouse models of Alzheimer's disease and amyotrophic lateral sclerosis

PubMed Central

Liebl, Martina P.; Windschmitt, Johannes; Besemer, Anna S.; Schäfer, Anne-Kathrin; Reber, Helmut; Behl, Christian; Clement, Albrecht M.

2015-01-01

Low-frequency magnetic fields (LF-MF) generated by power lines represent a potential environmental health risk and are classified as possibly carcinogenic by the World Health Organization. Epidemiological studies indicate that LF-MF might propagate neurodegenerative diseases like Alzheimer's disease (AD) or amyotrophic lateral sclerosis (ALS). We conducted a comprehensive analysis to determine whether long-term exposure to LF-MF (50 Hz, 1 mT) interferes with disease development in established mouse models for AD and ALS, namely APP23 mice and mice expressing mutant Cu/Zn-superoxide dismutase (SOD1), respectively. Exposure for 16 months did not aggravate learning deficit of APP23 mice. Likewise, disease onset and survival of SOD1G85R or SOD1G93A mice were not altered upon LF-MF exposure for ten or eight months, respectively. These results and an extended biochemical analysis of protein aggregation, glial activation and levels of toxic protein species suggests that LF-MF do not affect cellular processes involved in the pathogenesis of AD or ALS. PMID:25717019

Nitrogen losses and chemical parameters during co-composting of solid wastes and liquid pig manure.

PubMed

Vázquez, M A; de la Varga, D; Plana, R; Soto, M

2017-07-04

The aim of this research was to study nitrogen losses during the treatment of the liquid fraction (LF) of pig manure by co-composting and to establish the best conditions for compost production with higher nitrogen and low heavy metal contents. Windrows were constituted with the solid fraction (SF) of pig manure, different organic waste (SF of pig manure, sawdust and grape bagasse) as co-substrate and Populus spp. wood chips as bulking material and watered intensely with the LF. Results show that nitrogen losses ranged from 30% to 66% of initial nitrogen and were mainly governed by substrate to bulking mass ratio and liquid fraction to substrate (LF/S) ratio, and only secondarily by operational parameters. Nitrogen losses decreased from 55-65% at low LF/S ratios (1.7-1.9 m 3 /t total solids (TS)) to 30-39% at high LF/S ratios (4.4-4.7 m 3 /t TS). Therefore, integrating the LF in the composting process at high LF/S ratios favoured nitrogen recovery and conservation. Nitrogen in the fine fraction (ranging from 27% to 48% of initial nitrogen) was governed by operational parameters, namely pH and temperature. Final compost showed low content in most heavy metals, but Zn was higher than the limits for compost use in agriculture. Zn content in the obtained compost varied from 1863 to 3269 mg/kg dm, depending on several factors. The options for obtaining better quality composts from the LF of pig manure are selecting co-substrates with low heavy metal content and using them instead of the SF of pig manure.

Mineral magnetism of atmospheric dust over southwest coast of India: Impact of anthropogenic activities and implications to public health

NASA Astrophysics Data System (ADS)

Warrier, Anish Kumar; Shankar, R.; Manjunatha, B. R.; Harshavardhana, B. G.

2014-03-01

We have used rock magnetic techniques in this study to assess atmospheric pollution at five stations in and around Mangalore city on the southwestern coast of India. Samples of dust were collected from two suburban areas (Thokkottu and Pumpwell located respectively ~ 10 km and 3 km from the city center), the city center itself (Milagres) and industrial/port areas (Panambur and Mangalore Refinery and Petrochemicals Limited (MRPL)). Low-frequency magnetic susceptibility (χlf), frequency-dependent susceptibility (χfd), susceptibility of anhysteretic remanent magnetization (χARM) and isothermal remanent magnetization (IRM 20 to 1000 mT) were determined on 23 dust samples and inter-parametric ratios calculated. Results show that samples from suburban areas (particularly Thokkottu) are characterized by low χlf (< 314.1 × 10- 8 m3 kg- 1) and up to 6% χfd, suggesting low levels of pollution and the presence of pedogenic magnetite possibly derived from soils by wind erosion. However, the average χlf of Milagres, Panambur and MRPL dust samples is high by factors of 9.2, 3.3 and 2.6 compared to that of the Thokkottu sample. The Milagres sample contains magnetically "soft" minerals like magnetite, possibly indicating its derivation from motor vehicle exhaust. In contrast, the Panambur dust sample is characterized by magnetically "hard" minerals such as hematite and goethite as it has an 8-fold higher HIRM value compared to the Thokkottu sample. This magnetic signature is perhaps the result of dust particles derived from the grinding of hematite-rich iron ore by the Kudremukh Iron Ore Company Limited (KIOCL) at Panambur and its storage and export through the nearby New Mangalore Port. However, the dust sample from MRPL has magnetically "soft" minerals like magnetite. This magnetic mineral may have originated from petroleum refining processes at MRPL. Particulate pollution from industrial activities and motor vehicle exhaust is a threat to human health and is known to cause cardiovascular and respiratory ailments. Therefore, the pollution levels brought out by this study warrant a comprehensive epidemiological study in the area of study.

Identification, Characterization and Expression Profiling of Stress-Related Genes in Easter Lily (Lilium formolongi)

PubMed Central

Howlader, Jewel; Park, Jong-In; Robin, Arif Hasan Khan; Sumi, Kanij Rukshana; Nou, Ill-Sup

2017-01-01

Biotic and abiotic stresses are the major causes of crop loss in lily worldwide. In this study, we retrieved 12 defense-related expressed sequence tags (ESTs) from the NCBI database and cloned, characterized, and established seven of these genes as stress-induced genes in Lilium formolongi. Using rapid amplification of cDNA ends PCR (RACE-PCR), we successfully cloned seven full-length mRNA sequences from L. formolongi line Sinnapal lily. Based on the presence of highly conserved characteristic domains and phylogenetic analysis using reference protein sequences, we provided new nomenclature for the seven nucleotide and protein sequences and submitted them to GenBank. The real-time quantitative PCR (qPCR) relative expression analysis of these seven genes, including LfHsp70-1, LfHsp70-2, LfHsp70-3, LfHsp90, LfUb, LfCyt-b5, and LfRab, demonstrated that they were differentially expressed in all organs examined, possibly indicating functional redundancy. We also investigated the qPCR relative expression levels under two biotic and four abiotic stress conditions. All seven genes were induced by Botrytis cinerea treatment, and all genes except LfHsp70-3 and LfHsp90 were induced by Botrytis elliptica treatment; these genes might be associated with disease tolerance mechanisms in L. formolongi. In addition, LfHsp70-1, LfHsp70-2, LfHsp70-3, LfHsp90, LfUb, and LfCyt-b5 were induced by heat treatment, LfHsp70-1, LfHsp70-2, LfHsp70-3, LfHsp90, and LfCyt-b5 were induced by cold treatment, and LfHsp70-1, LfHsp70-2, LfHsp70-3, LfHsp90, LfCy-b5, and LfRab were induced by drought and salt stress, indicating their likely association with tolerance to these stress conditions. The stress-induced candidate genes identified in this study provide a basis for further functional analysis and the development of stress-resistant L. formolongi cultivars.

Community-based trial of annual versus biannual single-dose ivermectin plus albendazole against Wuchereria bancrofti infection in human and mosquito populations: study protocol for a cluster randomised controlled trial.

PubMed

de Souza, Dziedzom K; Ahorlu, Collins S; Adu-Amankwah, Susan; Otchere, Joseph; Mensah, Sedzro K; Larbi, Irene A; Mensah, George E; Biritwum, Nana-Kwadwo; Boakye, Daniel A

2017-10-02

The Global Programme for the Elimination of Lymphatic Filariasis (GPELF) has been in operation since the year 2000, with the aim of eliminating the disease by the year 2020, following five to six rounds of effective annual mass drug administration (MDA). The treatment regimen is ivermectin (IVM) in combination with diethylcarbamazine (DEC) or albendazole (ALB). In Ghana, MDA has been undertaken since 2001. While the disease has been eliminated in many areas, transmission has persisted in some implementation units that had experienced 15 or more rounds of MDA. Thus, new intervention strategies could eliminate residual infection in areas of persistent transmission and speed up the lymphatic filariasis (LF)-elimination process. This study, therefore, seeks to test the hypothesis that biannual treatment of LF-endemic communities will accelerate the interruption of LF in areas of persistent transmission. A cluster randomised trial will be implemented in LF-endemic communities in Ghana. The interventions will be yearly or twice-yearly MDA delivered to entire endemic communities. Allocation to study group will be by clusters identified using the prevalence of LF. Clusters will be randomised to one of two groups: receiving either (1) annual treatment with IVM + ALB or (2) annual MDA with IVM + ALB, followed by an additional MDA 6 months later. The primary outcome measure is the prevalence of LF infection, assessed by four cross-sectional surveys. Entomological assessments will also be undertaken to evaluate the transmission intensity of the disease in the study clusters. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, microfilaria prevalence will be assessed longitudinally. A nested process evaluation, using semi-structured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system. It is expected that this study will add to the existing evidence on the need for alternative intervention strategies for the elimination of LF in Ghana and in other African countries that are facing similar challenges or are at the beginning of their LF-elimination programmes. ClinicalTrials.gov, ID: NCT03036059 . Registered on 26 January 2017. Pan African Clinical Trials Registry, ID: PACTR201702002012425 . Registered on 23 February 2017.

Association between heart rhythm and cortical sound processing.

PubMed

Marcomini, Renata S; Frizzo, Ana Claúdia F; de Góes, Viviane B; Regaçone, Simone F; Garner, David M; Raimundo, Rodrigo D; Oliveira, Fernando R; Valenti, Vitor E

2018-04-26

Sound signal processing signifies an important factor for human conscious communication and it may be assessed through cortical auditory evoked potentials (CAEP). Heart rate variability (HRV) provides information about heart rate autonomic regulation. We investigated the association between resting HRV and CAEP. We evaluated resting HRV in the time and frequency domain and the CAEP components. The subjects remained at rest for 10 minutes for HRV recording, then they performed the CAEP examinations through frequency and duration protocols in both ears. Linear regression indicated that the amplitude of the N2 wave of the CAEP in the left ear (not right ear) was significantly influenced by standard deviation of normal-to-normal RR-intervals (17.7%) and percentage of adjacent RR-intervals with a difference of duration greater than 50 milliseconds (25.3%) time domain HRV indices in the frequency protocol. In the duration protocol and in the left ear the latency of the P2 wave was significantly influenced by low (LF) (20.8%) and high frequency (HF) bands in normalized units (21%) and LF/HF ratio (22.4%) indices of HRV spectral analysis. The latency of the N2 wave was significantly influenced by LF (25.8%), HF (25.9%) and LF/HF (28.8%). In conclusion, we promote the supposition that resting heart rhythm is associated with thalamo-cortical, cortical-cortical and auditory cortex pathways involved with auditory processing in the right hemisphere.

Lactoferrin and oral diseases: current status and perspective in periodontitis

PubMed Central

Berlutti, Francesca; Pilloni, Andrea; Pietropaoli, Miriam; Polimeni, Antonella; Valenti, Piera

2012-01-01

Summary Lactoferrin (Lf), an iron-binding glycoprotein able to chelate two ferric ions per molecule, is a component of human secretions synthesized by exocrine glands and neutrophils in infection/inflammation sites. Lactoferrin in saliva represents an important defence factor against bacterial injuries including those related to Streptococcus mutans and periodontopathic bacteria through its ability to decrease bacterial growth, biofilm development, iron overload, reactive oxygen formation and inflammatory processes. A growing body of research suggests that inflammatory periodontal disease involves a failure of resolution pathways to restore tissue homeostasis. There is an important distinction between anti-inflammation and resolution; anti-inflammation is pharmacologic intervention in inflammatory pathways, whereas resolution involves biologic pathways restoring inflammatory homeostasis. An appropriate regulation of pro-inflammatory cytokine synthesis might be useful in reducing periodontal tissue destruction. Recently, the multi-functional IL-6 is emerging as an important factor able to modulate bone, iron and inflammatory homeostasis. Here, we report an overview of Lf functions as well as for the first time Lf anti-inflammatory ability against periodontitis in in vitro model and observational clinical study. In in vitro model, represented by gingival fibroblasts infected with Prevotella intermedia, Lf exerted a potent anti-inflammatory activity. In the observational clinical trial performed through bovine Lf (bLf) topically administered to volunteers suffering from periodontitis, bLf decreased cytokines, including IL-6 in crevicular fluid, edema, bleeding, pocket depth, gingival and plaque index, thus improving clinical attachment levels. Even if other clinical trials are required, these results provide strong evidence for a instead of an therapeutic potential of this multifunctional natural protein. PMID:22545184

An anthrax toxin variant with an improved activity in tumor targeting

PubMed Central

Wein, Alexander N.; Peters, Diane E.; Valivullah, Zaheer; Hoover, Benjamin J.; Tatineni, Aparna; Ma, Qian; Fattah, Rasem; Bugge, Thomas H.; Leppla, Stephen H.; Liu, Shihui

2015-01-01

Anthrax lethal toxin (LT) is an A-B type toxin secreted by Bacillus anthracis, consisting of the cellular binding moiety, protective antigen (PA), and the catalytic moiety, lethal factor (LF). To target cells, PA binds to cell-surface receptors and is then proteolytically processed forming a LF-binding competent PA oligomer where each LF binding site is comprised of three subsites on two adjacent PA monomers. We previously generated PA-U2-R200A, a urokinase-activated PA variant with LF-binding subsite II residue Arg200 mutated to Ala, and PA-L1-I210A, a matrix metalloproteinase-activated PA variant with subsite III residue Ile210 mutated to Ala. PA-U2-R200A and PA-L1-I210A displayed reduced cytotoxicity when used singly. However, when combined, they formed LF-binding competent heterogeneous oligomers by intermolecular complementation, and achieved high specificity in tumor targeting. Nevertheless, each of these proteins, in particular PA-L1-I210A, retained residual LF-binding ability. In this work, we screened a library containing all possible amino acid substitutions for LF-binding site to find variants with activity strictly dependent upon intermolecular complementation. PA-I207R was identified as an excellent replacement for the original clockwise-side variant, PA-I210A. Consequently, the new combination of PA-L1-I207R and PA-U2-R200A showed potent anti-tumor activity and low toxicity, exceeding the performance of the original combination, and warranting further investigation. PMID:26584669

CDKL5 regulates flagellar length and localizes to the base of the flagella in Chlamydomonas

PubMed Central

Tam, Lai-Wa; Ranum, Paul T.; Lefebvre, Paul A.

2013-01-01

The length of Chlamydomonas flagella is tightly regulated. Mutations in four genes—LF1, LF2, LF3, and LF4—cause cells to assemble flagella up to three times wild-type length. LF2 and LF4 encode protein kinases. Here we describe a new gene, LF5, in which null mutations cause cells to assemble flagella of excess length. The LF5 gene encodes a protein kinase very similar in sequence to the protein kinase CDKL5. In humans, mutations in this kinase cause a severe form of juvenile epilepsy. The LF5 protein localizes to a unique location: the proximal 1 μm of the flagella. The proximal localization of the LF5 protein is lost when genes that make up the proteins in the cytoplasmic length regulatory complex (LRC)—LF1, LF2, and LF3—are mutated. In these mutants LF5p becomes localized either at the distal tip of the flagella or along the flagellar length, indicating that length regulation involves, at least in part, control of LF5p localization by the LRC. PMID:23283985

Low-frequency sound affects active micromechanics in the human inner ear

PubMed Central

Kugler, Kathrin; Wiegrebe, Lutz; Grothe, Benedikt; Kössl, Manfred; Gürkov, Robert; Krause, Eike; Drexl, Markus

2014-01-01

Noise-induced hearing loss is one of the most common auditory pathologies, resulting from overstimulation of the human cochlea, an exquisitely sensitive micromechanical device. At very low frequencies (less than 250 Hz), however, the sensitivity of human hearing, and therefore the perceived loudness is poor. The perceived loudness is mediated by the inner hair cells of the cochlea which are driven very inadequately at low frequencies. To assess the impact of low-frequency (LF) sound, we exploited a by-product of the active amplification of sound outer hair cells (OHCs) perform, so-called spontaneous otoacoustic emissions. These are faint sounds produced by the inner ear that can be used to detect changes of cochlear physiology. We show that a short exposure to perceptually unobtrusive, LF sounds significantly affects OHCs: a 90 s, 80 dB(A) LF sound induced slow, concordant and positively correlated frequency and level oscillations of spontaneous otoacoustic emissions that lasted for about 2 min after LF sound offset. LF sounds, contrary to their unobtrusive perception, strongly stimulate the human cochlea and affect amplification processes in the most sensitive and important frequency range of human hearing. PMID:26064536

A systematic review of factors that shape implementation of mass drug administration for lymphatic filariasis in sub-Saharan Africa.

PubMed

Silumbwe, Adam; Zulu, Joseph Mumba; Halwindi, Hikabasa; Jacobs, Choolwe; Zgambo, Jessy; Dambe, Rosalia; Chola, Mumbi; Chongwe, Gershom; Michelo, Charles

2017-05-22

Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF) elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA) region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs) through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Mass drug administration for lymphatic filariasis elimination programmes should design their implementation strategies differently based on specific contextual factors to improve implementation outcomes. Successfully achieving this requires undertaking formative research on the possible constraining and inhibiting factors, and incorporating the findings in the design and implementation of MDA for LF.

Microscopic Evolution of Laboratory Volcanic Hybrid Earthquakes

PubMed Central

Ghaffari, H. O.; Griffith, W. A.; Benson, P. M.

2017-01-01

Characterizing the interaction between fluids and microscopic defects is one of the long-standing challenges in understanding a broad range of cracking processes, in part because they are so difficult to study experimentally. We address this issue by reexamining records of emitted acoustic phonon events during rock mechanics experiments under wet and dry conditions. The frequency spectrum of these events provides direct information regarding the state of the system. Such events are typically subdivided into high frequency (HF) and low frequency (LF) events, whereas intermediate “Hybrid” events, have HF onsets followed by LF ringing. At a larger scale in volcanic terranes, hybrid events are used empirically to predict eruptions, but their ambiguous physical origin limits their diagnostic use. By studying acoustic phonon emissions from individual microcracking events we show that the onset of a secondary instability–related to the transition from HF to LF–occurs during the fast equilibration phase of the system, leading to sudden increase of fluid pressure in the process zone. As a result of this squeezing process, a secondary instability akin to the LF event occurs. This mechanism is consistent with observations of hybrid earthquakes. PMID:28074878

Inhibitory effects of bovine lactoferrin and lactoferricin B on Enterobacter sakazakii.

PubMed

Wakabayashi, Hiroyuki; Yamauchi, Koji; Takase, Mitsunori

2008-03-01

The susceptibility of Enterobacter sakazakii, a food-borne pathogen, to several metal-bound forms of bovine lactoferrin (LF), pepsin-hydrolyzed LF (LF-hyd), and LF-derived peptide lactoferricin B (LFcin B) was tested. MIC and MBC testing revealed that 4 strains of E. sakazakii show susceptibility to apo- and Cu-LF, LF-hyd, and LFcin B, but not to Fe-LF, similarly to Escherichia coli. A growth curve test indicated that E. sakazakii was inhibited in a dose-dependent manner by apo-LF at 0.5 to 8 mg/ml. Even after being heated at 80 degrees C, LF at above 1 mg/ml inhibited the bacterial growth. These results suggest that bovine LF-related compounds may be useful for the inhibition of E. sakazakii in foods.

Effect of iron saturation level of lactoferrin on osteogenic activity in vitro and in vivo.

PubMed

Wang, X Y; Guo, H Y; Zhang, W; Wen, P C; Zhang, H; Guo, Z R; Ren, F Z

2013-01-01

We studied the effect of iron saturation level on the osteogenic activity of lactoferrin (LF) in vitro and in vivo. Different iron saturation levels of LF (1.0, 9.0, 38, 58, and 96%) were prepared as the following samples: apo-LF, LF-9, LF-38, LF-58, and holo-LF. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we observed that the stimulating osteoblast proliferation activity of LF in vitro decreased with increasing iron saturation level at 100 and 1,000 μg/mL. In vivo, 4-wk-old ICR Swiss male mice were randomly divided into 4 groups: blank control (physiological saline), negative control (BSA), apo-LF, and holo-LF. Four groups of mice were injected subcutaneously with physiological saline, BSA, apo-LF, or holo-LF over the calvarial surface twice a day for 5 consecutive days at a dose of 4 mg/kg per day. Bone histomorphometry showed that new bone formation (assessed using tetracycline-HCl labels) tended to be stronger with apo-LF than with holo-LF. Using fluorescence spectroscopy and circular dichroism measurements, we found that exposure of tryptophan increased, α-helix content increased, but β-structure content decreased with increasing iron saturation level. These findings indicated that the osteogenic activity of LF decreases with increasing iron saturation level in vitro and in vivo, which may be related to conformational changes in LF. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Nuclear and cytoplasmic delivery of lactoferrin in glioma using chitosan nanoparticles: Cellular location dependent-action of lactoferrin.

PubMed

Tammam, Salma N; Azzazy, Hassan M E; Lamprecht, Alf

2018-08-01

Lactoferrin (Lf) exerts anti-cancer effects on glioma, however, the exact mechanism remains unclear. Despite possessing a nuclear localization sequence (NLS), Lf was found to allocate only in the cytoplasm of glioma 261. Lf was therefore loaded into nuclear and cytoplasmic targeted nanoparticles (NPs) to determine whether nuclear delivery of Lf would enhance its anti-cancer effect. Upon treatment with 300 and 800 µg/mL Lf loaded chitosan NPs, nuclear targeted Lf-NPs showed 1.3 and 2.7 folds increase in cell viability, whereas cytoplasmic targeted Lf-NPs at 300 µg/mL decreased cell viability by 0.8 folds in comparison to free Lf and controls. Results suggest that the cytotoxicity of Lf on glioma is attributable to its cytoplasmic allocation. Nuclear delivery of Lf induced cell proliferation rather than cytotoxicity, indicating that the mode of action of Lf in glioma is cell location dependent. This calls for caution about the general use of Lf as an anti-cancer protein. Copyright © 2018. Published by Elsevier B.V.

Lactoferrin: Balancing Ups and Downs of Inflammation Due to Microbial Infections.

PubMed

Drago-Serrano, Maria Elisa; Campos-Rodríguez, Rafael; Carrero, Julio César; de la Garza, Mireya

2017-03-01

Lactoferrin (Lf) is a glycoprotein of the primary innate immune-defense system of mammals present in milk and other mucosal secretions. This protein of the transferrin family has broad antimicrobial properties by depriving pathogens from iron, or disrupting their plasma membranes through its highly cationic charge. Noteworthy, Lf also exhibits immunomodulatory activities performing up- and down-regulation of innate and adaptive immune cells, contributing to the homeostasis in mucosal surfaces exposed to myriad of microbial agents, such as the gastrointestinal and respiratory tracts. Although the inflammatory process is essential for the control of invasive infectious agents, the development of an exacerbated or chronic inflammation results in tissue damage with life-threatening consequences. In this review, we highlight recent findings in in vitro and in vivo models of the gut, lung, oral cavity, mammary gland, and liver infections that provide experimental evidence supporting the therapeutic role of human and bovine Lf in promoting some parameters of inflammation and protecting against the deleterious effects of bacterial, viral, fungal and protozoan-associated inflammation. Thus, this new knowledge of Lf immunomodulation paves the way to more effective design of treatments that include native or synthetic Lf derivatives, which may be useful to reduce immune-mediated tissue damage in infectious diseases.

Atmospheric-pressure diffuse dielectric barrier discharges in Ar/O2 gas mixture using 200 kHz/13.56 MHz dual frequency excitation

NASA Astrophysics Data System (ADS)

Liu, Y.; Starostin, S. A.; Peeters, F. J. J.; van de Sanden, M. C. M.; de Vries, H. W.

2018-03-01

Atmospheric-pressure diffuse dielectric barrier discharges (DBDs) were obtained in Ar/O2 gas mixture using dual-frequency (DF) excitation at 200 kHz low frequency (LF) and 13.56 MHz radio frequency (RF). The excitation dynamics and the plasma generation mechanism were studied by means of electrical characterization and phase resolved optical emission spectroscopy (PROES). The DF excitation results in a time-varying electric field which is determined by the total LF and RF gas voltage and the spatial ion distribution which only responds to the LF component. By tuning the amplitude ratio of the superimposed LF and RF signals, the effect of each frequency component on the DF discharge mechanism was analysed. The LF excitation results in a transient plasma with the formation of an electrode sheath and therefore a pronounced excitation near the substrate. The RF oscillation allows the electron trapping in the gas gap and helps to improve the plasma uniformity by contributing to the pre-ionization and by controlling the discharge development. The possibility of temporally modifying the electric field and thus the plasma generation mechanism in the DF discharge exhibits potential applications in plasma-assisted surface processing and plasma-assisted gas phase chemical conversion.

Lactoferrin: Balancing Ups and Downs of Inflammation Due to Microbial Infections

PubMed Central

Drago-Serrano, Maria Elisa; Campos-Rodríguez, Rafael; Carrero, Julio César; de la Garza, Mireya

2017-01-01

Lactoferrin (Lf) is a glycoprotein of the primary innate immune-defense system of mammals present in milk and other mucosal secretions. This protein of the transferrin family has broad antimicrobial properties by depriving pathogens from iron, or disrupting their plasma membranes through its highly cationic charge. Noteworthy, Lf also exhibits immunomodulatory activities performing up- and down-regulation of innate and adaptive immune cells, contributing to the homeostasis in mucosal surfaces exposed to myriad of microbial agents, such as the gastrointestinal and respiratory tracts. Although the inflammatory process is essential for the control of invasive infectious agents, the development of an exacerbated or chronic inflammation results in tissue damage with life-threatening consequences. In this review, we highlight recent findings in in vitro and in vivo models of the gut, lung, oral cavity, mammary gland, and liver infections that provide experimental evidence supporting the therapeutic role of human and bovine Lf in promoting some parameters of inflammation and protecting against the deleterious effects of bacterial, viral, fungal and protozoan-associated inflammation. Thus, this new knowledge of Lf immunomodulation paves the way to more effective design of treatments that include native or synthetic Lf derivatives, which may be useful to reduce immune-mediated tissue damage in infectious diseases. PMID:28257033

Integrated Surveys of Neglected Tropical Diseases in Southern Sudan: How Much Do They Cost and Can They Be Refined?

PubMed Central

Kolaczinski, Jan H.; Hanson, Kara; Robinson, Emily; Picon, Diana; Sabasio, Anthony; Mpakateni, Martin; Lado, Mounir; Moore, Stephen; Petty, Nora; Brooker, Simon

2010-01-01

Background Increasing emphasis on integrated control of neglected tropical diseases (NTDs) requires identification of co-endemic areas. Integrated surveys for lymphatic filariasis (LF), schistosomiasis and soil-transmitted helminth (STH) infection have been recommended for this purpose. Integrated survey designs inevitably involve balancing the costs of surveys against accuracy of classifying areas for treatment, so-called implementation units (IUs). This requires an understanding of the main cost drivers and of how operating procedures may affect both cost and accuracy of surveys. Here we report a detailed cost analysis of the first round of integrated NTD surveys in Southern Sudan. Methods and Findings Financial and economic costs were estimated from financial expenditure records and interviews with survey staff using an ingredients approach. The main outcome was cost per IU surveyed. Uncertain variables were subjected to univariate sensitivity analysis and the effects of modifying standard operating procedures were explored. The average economic cost per IU surveyed was USD 40,206 or USD 9,573, depending on the size of the IU. The major cost drivers were two key categories of recurrent costs: i) survey consumables, and ii) personnel. Conclusion The cost of integrated surveys in Southern Sudan could be reduced by surveying larger administrative areas for LF. If this approach was taken, the estimated economic cost of completing LF, schistosomiasis and STH mapping in Southern Sudan would amount to USD 1.6 million. The methodological detail and costing template provided here could be used to generate cost estimates in other settings and readily compare these to the present study, and may help budget for integrated and single NTDs surveys elsewhere. PMID:20644619

A geometrical shift results in erroneous appearance of low frequency tissue eddy current induced phase maps.

PubMed

Mandija, Stefano; van Lier, Astrid L H M W; Katscher, Ulrich; Petrov, Petar I; Neggers, Sebastian F W; Luijten, Peter R; van den Berg, Cornelis A T

2016-09-01

Knowledge on low frequency (LF) tissue conductivity is relevant for various biomedical purposes. To obtain this information, LF phase maps arising from time-varying imaging gradients have been demonstrated to create a LF conductivity contrast. Essential in this methodology is the subtraction of phase images acquired with opposite gradient polarities to separate LF and RF phase effects. Here we demonstrate how sensitive these subtractions are with respect to geometrical distortions. The effect of geometrical distortions on LF phase maps is mathematically defined. After quantifying typical geometrical distortions, their effects on LF phase maps are evaluated using conductive phantoms. For validation, electromagnetic simulations of LF phase maps were performed. Even sub-voxel distortions of 10% of the voxel size, measured for a typical LF MR sequence, cause leakage of RF phase into LF phase of several milli-radians, leading to a misleading pattern of LF phase maps. This leakage is mathematically confirmed, while simulations indicate that the expected LF phase should be in order of micro-radians. The conductivity scaling of LF phase maps is attributable to the RF phase leakage, thus dependent on the RF conductivity. In fact, simulations show that the LF phase is not measurable. Magn Reson Med 76:905-912, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Pilot Assessment of Soil-Transmitted Helminthiasis in the Context of Transmission Assessment Surveys for Lymphatic Filariasis in Benin and Tonga

PubMed Central

Chu, Brian K.; Gass, Katherine; Batcho, Wilfrid; 'Ake, Malakai; Dorkenoo, Améyo M.; Adjinacou, Elvire; Mafi, 'Eva; Addiss, David G.

2014-01-01

Background Mass drug administration (MDA) for lymphatic filariasis (LF) programs has delivered more than 2 billion treatments of albendazole, in combination with either ivermectin or diethylcarbamazine, to communities co-endemic for soil-transmitted helminthiasis (STH), reducing the prevalence of both diseases. A transmission assessment survey (TAS) is recommended to determine if MDA for LF can be stopped within an evaluation unit (EU) after at least five rounds of annual treatment. The TAS also provides an opportunity to simultaneously assess the impact of these MDAs on STH and to determine the frequency of school-based MDA for STH after community-wide MDA is no longer needed for LF. Methodology/Principal Findings Pilot studies conducted in Benin and Tonga assessed the feasibility of a coordinated approach. Of the schools (clusters) selected for a TAS in each EU, a subset of 5 schools per STH ecological zone was randomly selected, according to World Health Organization (WHO) guidelines, for the coordinated survey. In Benin, 519 children were sampled in 5 schools and 22 (4.2%) had STH infection (A. lumbricoides, T. trichiura, or hookworm) detected using the Kato-Katz method. All infections were classified as light intensity under WHO criteria. In Tonga, 10 schools were chosen for the coordinated TAS and STH survey covering two ecological zones; 32 of 232 (13.8%) children were infected in Tongatapu and 82 of 320 (25.6%) in Vava'u and Ha'apai. All infections were light-intensity with the exception of one with moderate-intensity T. trichiura. Conclusions Synchronous assessment of STH with TAS is feasible and provides a well-timed evaluation of infection prevalence to guide ongoing treatment decisions at a time when MDA for LF may be stopped. The coordinated field experiences in both countries also suggest potential time and cost savings. Refinement of a coordinated TAS and STH sampling methodology should be pursued, along with further validation of alternative quantitative diagnostic tests for STH that can be used with preserved stool specimens. PMID:24551267

Antimicrobial potential for the combination of bovine lactoferrin or its hydrolysate with lactoferrin-resistant probiotics against foodborne pathogens.

PubMed

Chen, P-W; Jheng, T T; Shyu, C-L; Mao, F C

2013-03-01

Previous reports have shown that several probiotic strains can resist the antibacterial activity of bovine lactoferrin (bLf), but the results are inconsistent. Moreover, a portion of orally administered apo-bLf is digested in vivo by pepsin to yield bLf hydrolysate, which produces stronger antibacterial activity than that observed with apo-bLf. However, whether bLf hydrolysate affects the growth of probiotic strains is unclear. Therefore, various probiotic strains in Taiwan were collected and evaluated for activity against apo-bLf and bLf hydrolysate in vitro. Thirteen probiotic strains were evaluated, and the growth of Lactobacillus acidophilus ATCC 4356, Lactobacillus salivarius ATCC 11741, Lactobacillus rhamnosus ATCC 53103, Bifidobacterium longum ATCC 15707, and Bifidobacterium lactis BCRC 17394 were inhibited by both apo-bLf and bLf hydrolysate. The growth of 8 strains were not affected by apo-bLf and bLf hydrolysate, including L. rhamnosus ATCC 7469, Lactobacillus reuteri ATCC 23272, Lactobacillus fermentum ATCC 11739, Lactobacillus coryniformis ATCC 25602, L. acidophilus BCRC 14065, Bifidobacterium infantis ATCC 15697, Bifidobacterium bifidum ATCC 29521, and Pediococcus acidilactici ATCC 8081. However, apo-bLf and its hydrolysate inhibited the growth of foodborne pathogens, including Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, and Enterococcus faecalis. Moreover, the supernatants produced by L. fermentum, B. lactis, and B. longum inhibited the growth of most pathogens. Importantly, a combination of apo-bLf or bLf hydrolysate with the supernatants of cultures of the organisms described above showed synergistic or partially synergistic effects against the growth of most of the selected pathogens. In conclusion, several probiotic strains are resistant to apo-bLf and bLf hydrolysate, warranting clinical studies to evaluate the antimicrobial potential for the combination of apo-bLf or its hydrolysate with specific probiotics. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Preparation and characterization of cobalt-substituted anthrax lethal factor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saebel, Crystal E.; Carbone, Ryan; Dabous, John R.

2011-12-09

Highlights: Black-Right-Pointing-Pointer Cobalt-substituted anthrax lethal factor (CoLF) is highly active. Black-Right-Pointing-Pointer CoLF can be prepared by bio-assimilation and direct exchange. Black-Right-Pointing-Pointer Lethal factor binds cobalt tightly. Black-Right-Pointing-Pointer The electronic spectrum of CoLF reveals penta-coordination. Black-Right-Pointing-Pointer Interaction of CoLF with thioglycolic acid follows a 2-step mechanism. -- Abstract: Anthrax lethal factor (LF) is a zinc-dependent endopeptidase involved in the cleavage of mitogen-activated protein kinase kinases near their N-termini. The current report concerns the preparation of cobalt-substituted LF (CoLF) and its characterization by electronic spectroscopy. Two strategies to produce CoLF were explored, including (i) a bio-assimilation approach involving the cultivation of LF-expressingmore » Bacillus megaterium cells in the presence of CoCl{sub 2}, and (ii) direct exchange by treatment of zinc-LF with CoCl{sub 2}. Independent of the method employed, the protein was found to contain one Co{sup 2+} per LF molecule, and was shown to be twice as active as its native zinc counterpart. The electronic spectrum of CoLF suggests the Co{sup 2+} ion to be five-coordinate, an observation similar to that reported for other Co{sup 2+}-substituted gluzincins, but distinct from that documented for the crystal structure of native LF. Furthermore, spectroscopic studies following the exposure of CoLF to thioglycolic acid (TGA) revealed a sequential mechanism of metal removal from LF, which likely involves the formation of an enzyme: Co{sup 2+}:TGA ternary complex prior to demetallation of the active site. CoLF reported herein constitutes the first spectroscopic probe of LF's active site, which may be utilized in future studies to gain further insight into the enzyme's mechanism and inhibitor interactions.« less

Antibacterial activity of recombinant human lactoferrin from rice: effect of heat treatment.

PubMed

Conesa, Celia; Rota, Carmen; Castillo, Eduardo; Pérez, María-Dolores; Calvo, Miguel; Sánchez, Lourdes

2009-06-01

The antibacterial activity of recombinant human lactoferrin from rice (rhLF) compared with that of human milk lactoferrin (hLF) was evaluated against Escherichia coli O157:H7, Salmonella Enteritidis and Listeria monocytogenes. The hydrolysates of rhLF and hLF were found to be more active than native proteins against E. coli O157:H7, and their activity was independent of their iron saturation. The effect of different heat treatments on the antibacterial activity of apo-rhLF was studied and compared with hLF. We observed that an HTST pasteurization treatment did not affect the antimicrobial activity of lactoferrin against the pathogens studied. Furthermore, the activity of apo-rhLF and hLF against E. coli O157:H7 and L. monocytogenes in UHT milk and whey was assayed, finding a decrease in the number of bacteria, although lower than that observed in a broth medium. This study shows the similar antibacterial activity of rhLF and hLF which is important in order to consider the addition of rhLF as a supplement in special products.

Comparative analysis of virulence traits between a Legionella feeleii strain implicated in Pontiac fever and a strain that caused Legionnaires' disease.

PubMed

Wang, Changle; Saito, Mitsumasa; Tanaka, Tamami; Amako, Kazunobu; Yoshida, Shin-ichi

2015-12-01

Legionella strains of the same species and serogroup are known to cause Legionnaires' disease (a potentially fatal atypical pneumonia) or Pontiac fever (a mild, flu-like disease), but the bacterial factors that define these dramatic differences in pathology have not been elucidated. To gain a better understanding of these factors, we compared the characteristics of Legionella feeleii strains that were isolated from either a sample of freshwater implicated in an outbreak of Pontiac fever (ATCC 35072, serogroup 1, LfPF), or a patient with Legionnaires' disease (ATCC 38549, serogroup 2, LfLD). Growth of LfPF and LfLD in BYE broth was slower than the positive control, Legionella pneumophila strain JR32. However, LfLD grew faster than LfPF at 42 °C. After in vitro infection to J774 murine or U937 human macrophage cell lines and A549 human lung epithelial cell line, LfLD showed a higher cell infection rate, stronger internalization by host cells, and greater cytotoxicity than that of LfPF. Large amounts of IL-6 and IL-8 were secreted by human host cells after infection with LfLD, but not with LfPF. LfLD possessed mono-polar flagellum while LfPF was unflagellated. When LfLD was cultured at 25, 30 and 37 °C, the bacteria had higher motility rate at lower temperatures. Based on our results, this is the first study that showed distinct characteristics between LfPF and LfLD, which may give important leads in elucidating differences in their virulence. Copyright © 2015 Elsevier Ltd. All rights reserved.

GALAXIES IN FILAMENTS HAVE MORE SATELLITES: THE INFLUENCE OF THE COSMIC WEB ON THE SATELLITE LUMINOSITY FUNCTION IN THE SDSS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Quan; Libeskind, N. I.; Tempel, E., E-mail: qguo@aip.de

We investigate whether the satellite luminosity function (LF) of primary galaxies identified in the Sloan Digital Sky Survey (SDSS) depends on whether the host galaxy is in a filament or not. Isolated primary galaxies are identified in the SDSS spectroscopic sample, and potential satellites (that are up to four magnitudes fainter than their hosts) are searched for in the much deeper photometric sample. Filaments are constructed from the galaxy distribution by the Bisous process. Isolated primary galaxies are divided into two subsamples: those in filaments and those not in filaments. We examine the stacked mean satellite LF of both themore » filament and nonfilament samples and find that, on average, the satellite LF of galaxies in filaments is significantly higher than those of galaxies not in filaments. The filamentary environment can increase the abundance of the brightest satellites (M {sub sat.} < M {sub prim.} + 2.0) by a factor of ∼2 compared with nonfilament isolated galaxies. This result is independent of the primary galaxy magnitude, although the satellite LF of galaxies in the faintest magnitude bin is too noisy to determine if such a dependence exists. Because our filaments are extracted from a spectroscopic flux-limited sample, we consider the possibility that the difference in satellite LF is due to a redshift, color, or environmental bias, finding these to be insufficient to explain our result. The dependence of the satellite LF on the cosmic web suggests that the filamentary environment may have a strong effect on the efficiency of galaxy formation.« less

Galaxies in Filaments have More Satellites: The Influence of the Cosmic Web on the Satellite Luminosity Function in the SDSS

NASA Astrophysics Data System (ADS)

Guo, Quan; Tempel, E.; Libeskind, N. I.

2015-02-01

We investigate whether the satellite luminosity function (LF) of primary galaxies identified in the Sloan Digital Sky Survey (SDSS) depends on whether the host galaxy is in a filament or not. Isolated primary galaxies are identified in the SDSS spectroscopic sample, and potential satellites (that are up to four magnitudes fainter than their hosts) are searched for in the much deeper photometric sample. Filaments are constructed from the galaxy distribution by the Bisous process. Isolated primary galaxies are divided into two subsamples: those in filaments and those not in filaments. We examine the stacked mean satellite LF of both the filament and nonfilament samples and find that, on average, the satellite LF of galaxies in filaments is significantly higher than those of galaxies not in filaments. The filamentary environment can increase the abundance of the brightest satellites (M sat. < M prim. + 2.0) by a factor of ~2 compared with nonfilament isolated galaxies. This result is independent of the primary galaxy magnitude, although the satellite LF of galaxies in the faintest magnitude bin is too noisy to determine if such a dependence exists. Because our filaments are extracted from a spectroscopic flux-limited sample, we consider the possibility that the difference in satellite LF is due to a redshift, color, or environmental bias, finding these to be insufficient to explain our result. The dependence of the satellite LF on the cosmic web suggests that the filamentary environment may have a strong effect on the efficiency of galaxy formation.

Identification and polymorphism discovery of the cathelicidins, Lf-CATHs in ranid amphibian (Limnonectes fragilis).

PubMed

Yu, Haining; Cai, Shasha; Gao, Jiuxiang; Zhang, Songyan; Lu, Yiling; Qiao, Xue; Yang, Hailong; Wang, Yipeng

2013-12-01

To protect themselves against the invasion of microorganisms, amphibians, especially the Rana frogs, are possibly equipped with complex combinations of antimicrobial peptides (AMPs). The two major AMP families, ranid skin secretion AMPs and cathelicidins might together constitute the host innate immune system of amphibians. Cathelicidins are a group of cationic peptides found in leukocytes and epithelial cells, and they play a central role in the early innate immune defense found in virtually all species of mammals. However, they have rarely been reported from amphibians. Here, we report the identification and discovery of polymorphism cathelicidins in Limnonectes fragilis. The expression profile indicated high cathelicidin transcript levels in frog spleen, liver and kidney, but lower levels in lung, skin and stomach. According to the amphibian's unique proteolytic pattern, R125 and L121 of the prepropeptides are predicted to be the processing positions for protease to generate the mature peptides, Lf-CATH1 and -2, respectively. Both consist of 30 amino acid residues, of which two were cysteines positionally conserved among a few known amphibian cathelicidins. Homology modeling analysis revealed that Lf-CATH1 and -2 adopt a tertiary structure with a mostly α helix that is representative of small cationic cathelicidin family peptides. Recombinant Lf-CATH1 (rLf-CATH1) was produced in Escherichia coli. Synthetic Lf-CATH1 and -2 displayed potent antimicrobial activities in vitro against a broad spectrum of microorganisms, including standard and clinically isolated drug-resistant strains, while showing neglectable hemolysis and cytotoxicities. © 2013 FEBS.

Anticancer activities of bovine and human lactoferricin-derived peptides.

PubMed

Arias, Mauricio; Hilchie, Ashley L; Haney, Evan F; Bolscher, Jan G M; Hyndman, M Eric; Hancock, Robert E W; Vogel, Hans J

2017-02-01

Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly-Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency.

Intestinal lactoferrin receptor: presence and specificity during development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davidson, L.A.; Lonnerdal, B.L.

1986-03-01

As the major iron-binding protein in breast milk, lactoferrin (Lf) has been suggested to play a role in Fe absorption from milk. The authors previous work has validated the use of the Rhesus monkey as a model for studying this role of Lf. They have identified a specific Lf receptor on the brush border (BB) of juvenile Rhesus small intestine (s.i.) which may facilitate Fe uptake into the mucosal cell. In this study the authors examined the presence and specificity of the Lf receptor during development. BB membrane vesicles were prepared from fetal (113 d gestation), infant (3 m), andmore » adult (12 y) Rhesus s.i.; Binding assays were performed by incubating BB vesicles with 59-Fe-Lf and filtering through a 0.22 ..mu..m filter. The fetal and infant tissues were found to possess receptors with a high affinity for Lf. This early ontogeny indicates the importance of the receptor to the infant. Adult s.i. contained Lf receptors in all regions. Since the adult has no dietary intake of Lf, the receptor may play a role in Fe homeostasis via biliary Lf excretion or may simply continue to be expressed throughout life. The receptors were examined for their affinity for purified bovine Lf and human transferrin, both of which are similar in structure to Lf. No binding was found for either, demonstrating the specificity of the receptor for Lf. The presence of the Lf receptor in fetal tissue and its specificity for Lf implies it is essential for adequate Fe nutrition of the suckling infant.« less

Lysophosphatidic Acid Induces Ligamentum Flavum Hypertrophy Through the LPAR1/Akt Pathway.

PubMed

Zhou, Tangjun; Du, Lin; Chen, Chen; Han, Chen; Li, Xunlin; Qin, An; Zhao, Changqing; Zhang, Kai; Zhao, Jie

2018-01-01

Hypertrophic ligamentum flavum (LF) is a major cause of lumbar spinal stenosis. Our previous work showed that high levels of lysophosphatidic acid (LPA) expression are positively correlated with LF hypertrophy. This study aimed to further unveil how LPA regulates LF hypertrophy Methods: We studied LPAR1 expression in human LF cells using PCR and western blotting. Cell viability cell cycle, apoptosis rate and molecular mechanisms were assayed in LPAR1 knockdown or overexpression LF cells. LF hypertrophy and the molecular mechanism was confirmed in human samples and in in vivo studies. The expression of LPA and its receptor LPAR1 is significantly higher in tissues or cells harvested from hypertrophic LF compared to healthy controls. Moreover, LPA promoted LF cell proliferation by interacting with LPAR1. This conclusion is supported by the fact that depletion or overexpression of LPAR1 changed the effect of LPA on LF cell proliferation. LPA also inhibits apoptosis in LF cells through the receptor LPAR1. Importantly, we demonstrated that the LPA-LPAR1 interaction initiated Akt phosphorylation and determined cell proliferation and apoptosis. Our in vitro findings were supported by our in vivo evidence that lyophilized LPA significantly induced LF hypertrophy via the LPAR1-Akt signaling pathway. More importantly, targeted inhibition of LPAR1 by Ki16425 with a gel sponge implant effectively reduced LPA-associated LF hypertrophy. Taken together, these data indicate that LPA binds to the receptor LPAR1 to induce LF cell proliferation and inhibit apoptosis by activating AKT signaling cascades. Targeting this signaling cascade with Ki16425 is a potential therapeutic strategy for preventing LF hypertrophy. LPA-LPAR1-Akt activation is positively correlated with the proliferation and survival of LF cells. LPAR1 could be a target for new drugs and the development of new therapeutic methods for treating LF hypertrophy. © 2018 The Author(s). Published by S. Karger AG, Basel.

Aerosol Combustion Synthesis of Nanopowders and Processing to Functional Thin Films

NASA Astrophysics Data System (ADS)

Yi, Eongyu

In this dissertation, the advantages of liquid-feed flame spray pyrolysis (LF-FSP) process in producing nanoparticles (NPs) as well as processing the produced NPs to ceramic/polymer nanocomposite films and high density polycrystalline ceramic films are demonstrated. The LF-FSP process aerosolizes alcohol solutions of metalloorganic precursors by oxygen and combusts them at > 1500 °C. The combustion products are rapidly quenched ( 10s of ms) to < 400 °C, producing NPs with the same compositions as those of the precursor solutions. The high specific surface areas of NPs enable formulation of ceramic/polymer/interface(phase) ternary nanocomposites in which the interphase can be the determining factor of the final net properties. In ceramic processing, NPs show increased sinterability and provide access to small average grain sizes with fine control of microstructures, compared to when micron sized powders are used. Therefore, synthesis, processing, and characterization of NPs, NP derived nanocomposites and ceramic monoliths are of great interest. We first compare the LF-FSP to commercial FSP process by producing fumed silica. Combusting spirocyclic alkoxysilanes or Si(OEt)4 by LF-FSP process produced fumed silica very similar to SiCl4 derived products. Given LF-FSP approach does not require the containment constraints of the SiCl4 process and precursors are synthesized from rice hull ash, the reported approach represents a sustainable, green and potentially lower cost alternative. We then show the versatility of NPs in formulating flexible ceramic/polymer nanocomposites (BaTiO3/epoxy) with superior properties. Volume fractions of the BaTiO3 filler and composite film thicknesses were controlled to adjust the net dielectric constant and the capacitance. Measured net dielectric constants further deviated from theory, with increasing solids loadings, due to NP agglomeration. Wound nanocomposite capacitors showed ten times higher capacitance compared to the commercial counterpart. Following series of studies explore the use of flame made NPs in processing Li+ conducting membranes. Systematic doping studies were conducted in the LiTi2(PO4)3 system to modify the lattice constant, conduction channel width, and sintering behavior by introducing Al3+ and Si4+ dopants. Excess Li2O content was also adjusted to observe its effect on final microstructures and phase compositions. Improved densification rates were found in Li1.7 Al0.3Ti1.7Si0.4P2.6O 12 composition and thin films (52+/-1 microm) with conductivities of 0.3-0.5 mS cm-1 were achieved. Li6.25M0.25La3Zr2O12 (M = Al3+, Ga3+) thin films (25-28 microm) with conductivities of 0.2-1.3 mS cm-1 were also successfully processed using flame made NPs, overcoming processing challenges extant, resulting in significantly reduced energy input required for densification. Heating schedules, sintering atmospheres, and types of substrates were controlled to observe their effect on the sintering behavior. Furthermore, green film thicknesses were found to be a crucial variable determining the final microstructures and phase compositions due to the varying Li2O loss rates with change in thicknesses (surface/volume ratios). Using fully decomposed NP mixtures (Li2CO3/off-stoichiometric La2Zr2O 7), as obtained by LF-FSP, provides an ideal approach to use high surface/reaction energy and liquid phase sintering to drive densification.

Lactoferrin inhibits melanogenesis by down-regulating MITF in melanoma cells and normal melanocytes.

PubMed

Ishii, Nanase; Ryu, Mizuyuki; Suzuki, Yasushi A

2017-02-01

The aim of this study was to evaluate the effect of bovine lactoferrin (bLf) on melanin-producing cells and to elucidate its mechanism of action. We tested the anti-melanogenic effect of bLf on a 3-dimensional cultured pigmentation skin model and confirmed a 20% reduction in pigmentation, suggesting that bLf was transdermally absorbed and it suppressed melanin production. Treatment of human melanoma cells with bLf resulted in a significant, dose-dependent suppression of melanin production. Apo-bLf and holo-bLf suppressed melanogenesis to the same degree as bLf. The key feature behind this anti-melanogenic effect of bLf was the down-regulation of the microphthalmia-associated transcription factor (MITF), leading to the suppression of tyrosinase activity. Treatment with bLf resulted in both decreased expression of MITF mRNA and enhanced degradation of MITF protein. However, the primary effector was enhanced phosphorylation of extracellular signal-regulated kinase (ERK), leading to the phosphorylation and degradation of MITF. Our finding that bLf suppresses melanin production in melanocytes indicates that bLf is a possible candidate for application as a skin-whitening agent.

Human Lactoferrin and Peptides Derived from a Surface-Exposed Helical Region Reduce Experimental Escherichia coli Urinary Tract Infection in Mice

PubMed Central

Håversen, Liliana A.; Engberg, Inga; Baltzer, Lars; Dolphin, Gunnar; Hanson, Lars Å.; Mattsby-Baltzer, Inger

2000-01-01

Lactoferrin (LF) is a multifunctional immunoregulatory protein that has been associated with host defense at mucosal surfaces through its antibacterial properties. The antibacterial and anti-inflammatory properties of LF were further explored with an animal model of experimental urinary tract infection. Bovine LF (bLF), human LF (hLF), and synthetic peptide sequences based on the antibacterial region of hLF (amino acid residues 16 to 40 [HLD1] and 18 to 40 [HLD2]) were given orally to female mice 30 min after the instillation of 108 Escherichia coli bacteria into the urinary bladder. The control groups received phosphate-buffered saline or water. C3H/Tif mice were treated with hLF or bLF, and C3H/HeN mice were treated with bLF only. The numbers of bacteria in the kidneys and bladder of C3H/Tif and C3H/HeN mice were significantly reduced 24 h later by the LF treatments compared to the findings for the control group. The hLF-treated group showed the strongest reduction compared with the vehicle-treated-group (P values were 0.009 and 0.0001 for the kidneys and bladder, respectively). The urinary leukocyte response was diminished in the hLF-treated group. The hLF treatment also significantly reduced the urinary interleukin-6 (IL-6) levels at 2 h and the systemic IL-6 levels at 24 h after infection (P values were 0.04 and < 0.002, respectively). In the bLF-treated animals, no such strong anti-inflammatory effects were obtained. In another series of experiments, C3H/Tif mice perorally treated with HLD1 or HLD2 also showed reduced numbers of bacteria in the kidneys compared with the vehicle-treated mice, although the results were significantly different only for HLD2 (P < 0.01). Analysis of urine from hLF-fed C3H/Tif mice showed that hLF was excreted into the urinary tract at 2 h after feeding. Testing of the in vitro bactericidal activity of LF (1 mg/ml) or the peptides (0.1 mg/ml) in mouse urine against the E. coli bacteria revealed moderate killing only by HLD2. In conclusion, these results demonstrate for the first time that oral administration of hLF or peptides thereof is effective in reducing infection and inflammation at a remote site, the urinary tract, possibly through transfer of hLF or its peptides to the site of infection via renal secretion. The antibacterial mechanism is suggested to involve bactericidal capacities of LF, fragments thereof, or its peptides. PMID:10992490

STS-114 Discovery Return to Flight: International Space Station Processing Overview

NASA Technical Reports Server (NTRS)

2005-01-01

Bruce Buckingham, NASA Public Affairs, introduces Scott Higgenbotham, STS-114 Payload Manager. Higgenbotham gives a power point presentation on the hardware that is going to fly in the Discovery Mission to the International Space Station. He presents a layout of the hardware which includes The Logistics Flight 1 (LF1) launch package configuration Multipurpose Logistics Module (MPLM), External Stowage Platform-2 (ESP-2) and the Lightweight Mission Peculiar Equipment Support Structure Carrier (LMC). He explains these payloads in detail. The LF-1 team is also shown in the International Space Station Processing Facility. This presentation ends with a brief question and answer period.

The end of a monolith: Deconstructing the Cnn-Polo interaction.

PubMed

Eisman, Robert C; Phelps, Melissa A S; Kaufman, Thomas C

2016-04-02

In Drosophila melanogaster a functional pericentriolar matrix (PCM) at mitotic centrosomes requires Centrosomin-Long Form (Cnn-LF) proteins. Moreover, tissue culture cells have shown that the centrosomal localization of both Cnn-LF and Polo kinase are co-dependent, suggesting a direct interaction. Our recent study found Cnn potentially binds to and is phosphorylated by Polo kinase at 2 residues encoded by Exon1A, the initiating exon of a subset of Cnn isoforms. These interactions are required for the centrosomal localization of Cnn-LF in syncytial embryos and a mutation of either phosphorylation site is sufficient to block localization of both mutant and wild-type Cnn when they are co-expressed. Immunoprecipitation experiments show that Cnn-LF interacts directly with mitotically activated Polo kinase and requires the 2 phosphorylation sites in Exon1A. These IP experiments also show that Cnn-LF proteins form multimers. Depending on the stoichiometry between functional and mutant peptides, heteromultimers exhibit dominant negative or positive trans-complementation (rescue) effects on mitosis. Additionally, following the completion of meiosis, Cnn-Short Form (Cnn-SF) proteins are required for polar body formation in embryos, a process previously shown to require Polo kinase. These findings, when combined with previous work, clearly demonstrate the complexity of cnn and show that a view of cnn as encoding a single peptide is too simplistic.

The end of a monolith: Deconstructing the Cnn-Polo interaction

PubMed Central

2016-01-01

ABSTRACT In Drosophila melanogaster a functional pericentriolar matrix (PCM) at mitotic centrosomes requires Centrosomin-Long Form (Cnn-LF) proteins. Moreover, tissue culture cells have shown that the centrosomal localization of both Cnn-LF and Polo kinase are co-dependent, suggesting a direct interaction. Our recent study found Cnn potentially binds to and is phosphorylated by Polo kinase at 2 residues encoded by Exon1A, the initiating exon of a subset of Cnn isoforms. These interactions are required for the centrosomal localization of Cnn-LF in syncytial embryos and a mutation of either phosphorylation site is sufficient to block localization of both mutant and wild-type Cnn when they are co-expressed. Immunoprecipitation experiments show that Cnn-LF interacts directly with mitotically activated Polo kinase and requires the 2 phosphorylation sites in Exon1A. These IP experiments also show that Cnn-LF proteins form multimers. Depending on the stoichiometry between functional and mutant peptides, heteromultimers exhibit dominant negative or positive trans-complementation (rescue) effects on mitosis. Additionally, following the completion of meiosis, Cnn-Short Form (Cnn-SF) proteins are required for polar body formation in embryos, a process previously shown to require Polo kinase. These findings, when combined with previous work, clearly demonstrate the complexity of cnn and show that a view of cnn as encoding a single peptide is too simplistic. PMID:27096551

Continental-scale, data-driven predictive assessment of eliminating the vector-borne disease, lymphatic filariasis, in sub-Saharan Africa by 2020.

PubMed

Michael, Edwin; Singh, Brajendra K; Mayala, Benjamin K; Smith, Morgan E; Hampton, Scott; Nabrzyski, Jaroslaw

2017-09-27

There are growing demands for predicting the prospects of achieving the global elimination of neglected tropical diseases as a result of the institution of large-scale nation-wide intervention programs by the WHO-set target year of 2020. Such predictions will be uncertain due to the impacts that spatial heterogeneity and scaling effects will have on parasite transmission processes, which will introduce significant aggregation errors into any attempt aiming to predict the outcomes of interventions at the broader spatial levels relevant to policy making. We describe a modeling platform that addresses this problem of upscaling from local settings to facilitate predictions at regional levels by the discovery and use of locality-specific transmission models, and we illustrate the utility of using this approach to evaluate the prospects for eliminating the vector-borne disease, lymphatic filariasis (LF), in sub-Saharan Africa by the WHO target year of 2020 using currently applied or newly proposed intervention strategies. METHODS AND RESULTS: We show how a computational platform that couples site-specific data discovery with model fitting and calibration can allow both learning of local LF transmission models and simulations of the impact of interventions that take a fuller account of the fine-scale heterogeneous transmission of this parasitic disease within endemic countries. We highlight how such a spatially hierarchical modeling tool that incorporates actual data regarding the roll-out of national drug treatment programs and spatial variability in infection patterns into the modeling process can produce more realistic predictions of timelines to LF elimination at coarse spatial scales, ranging from district to country to continental levels. Our results show that when locally applicable extinction thresholds are used, only three countries are likely to meet the goal of LF elimination by 2020 using currently applied mass drug treatments, and that switching to more intensive drug regimens, increasing the frequency of treatments, or switching to new triple drug regimens will be required if LF elimination is to be accelerated in Africa. The proportion of countries that would meet the goal of eliminating LF by 2020 may, however, reach up to 24/36 if the WHO 1% microfilaremia prevalence threshold is used and sequential mass drug deliveries are applied in countries. We have developed and applied a data-driven spatially hierarchical computational platform that uses the discovery of locally applicable transmission models in order to predict the prospects for eliminating the macroparasitic disease, LF, at the coarser country level in sub-Saharan Africa. We show that fine-scale spatial heterogeneity in local parasite transmission and extinction dynamics, as well as the exact nature of intervention roll-outs in countries, will impact the timelines to achieving national LF elimination on this continent.

Lactoferrin Expression in Human and Murine Ocular Tissue.

PubMed

Rageh, Abrar A; Ferrington, Deborah A; Roehrich, Heidi; Yuan, Ching; Terluk, Marcia R; Nelson, Elizabeth F; Montezuma, Sandra R

2016-07-01

Lactoferrin (LF) is a multifunctional protein known to provide innate defense due to its antimicrobial and anti-inflammatory properties. In the eye, LF has been identified in the tears and vitreous humor. Its presence in other ocular tissues has not been determined. Our aim is to assess the presence of LF in the cornea, iris, retina and retinal pigment epithelium (RPE) of humans and mice. To test for the endogenous production of LF, reverse transcription polymerase chain reaction was performed in cultured human cells from the cornea and RPE and in murine tissues. To confirm LF localization in specific ocular tissue, immunohistochemistry was performed on flat mounts of cornea, retina and RPE in human donor eyes. The presence of LF was assessed by western blotting in human and mouse ocular tissue and human culture cells (cornea and RPE). To verify antibody specificity, purified human LF and transferrin (TF) were used on 1D and 2D western blots. LF gene expression was confirmed in the cornea and RPE cell cultures from humans, suggesting that LF is an endogenously produced protein. PCR results from mouse ocular tissue showed LF expression in cornea, iris, RPE, but not in retina. These results were also consistent with immunohistochemical localization of LF in human donor tissue. Antibody reaction for human LF was specific and western blotting showed its presence in the cornea, iris and RPE tissues. A faint reaction for the retina was observed but was likely due to contamination from other ocular tissues. Multiple commercially available antibodies for murine LF cross-reacted with TF, so no reliable results were obtained for murine western blot. LF is expressed in multiple eye tissues of humans and mice. This widespread expression and multifunctional activity of LF suggests that it may play an important role in protecting eye tissues from inflammation-associated diseases.

A novel LDL-mimic nanocarrier for the targeted delivery of curcumin into the brain to treat Alzheimer's disease.

PubMed

Meng, Fanfei; Asghar, Sajid; Gao, Shiya; Su, Zhigui; Song, Jue; Huo, Meirong; Meng, Weidong; Ping, Qineng; Xiao, Yanyu

2015-10-01

In this study, a novel low density lipoprotein (LDL)-mimic nanostructured lipid carrier (NLC) modified with lactoferrin (Lf) and loaded with curcumin (Cur) was designed for brain-targeted delivery, and its effect on controlling the progression of Alzheimer's disease (AD) in rats was evaluated. NLC with the composition resembling the lipid portion of LDL was prepared by using solvent evaporation method. Lf was adsorbed onto the surface of NLC via electrostatic interaction to yield Lf modified-NLC (Lf-mNLC) as the LDL-mimic nanocarrier. In order to make sure more Lf was adsorbed on the surface of NLC, negatively charged carboxylated polyethylene glycol (100) monostearate (S100-COOH) was synthesized and anchored into NLC. Different levels of S100-COOH (0-0.02 mmol) and Lf modified NLC (0.5-2.5 mg/mL of Lf solution) were prepared and characterized. The uptake and potential cytotoxicities of different preparations were investigated in the brain capillary endothelial cells (BCECs). An AD model of rats was employed to evaluate the therapeutic effects of Lf-mNLC. The results indicate that Lf-mNLC with a high level of Lf showed the maximum uptake in BCECs (1.39 folds greater than NLC) as cellular uptake of Lf-mNLC by BCECs was found to be mediated by the Lf receptor. FRET studies showed Cur still wrapped inside NLC after uptake by BCECs, demonstrating stability of the carrier as it moved across the BBB. Ex vivo imaging studies exposed Lf-mNLC could effectively permeate BBB and preferentially accumulate in the brain (2.78 times greater than NLC). Histopathological evaluation confirmed superior efficacy of Lf-mNLC in controlling the damage associated with AD. In conclusion, Lf-mNLC is a promising drug delivery system for targeting therapy of brain disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibitory Effects of Lactoferrin on Growth and Biofilm Formation of Porphyromonas gingivalis and Prevotella intermedia▿

PubMed Central

Wakabayashi, Hiroyuki; Yamauchi, Koji; Kobayashi, Tetsuo; Yaeshima, Tomoko; Iwatsuki, Keiji; Yoshie, Hiromasa

2009-01-01

Lactoferrin (LF) is an iron-binding antimicrobial protein present in saliva and gingival crevicular fluids, and it is possibly associated with host defense against oral pathogens, including periodontopathic bacteria. In the present study, we evaluated the in vitro effects of LF-related agents on the growth and biofilm formation of two periodontopathic bacteria, Porphyromonas gingivalis and Prevotella intermedia, which reside as biofilms in the subgingival plaque. The planktonic growth of P. gingivalis and P. intermedia was suppressed for up to 5 h by incubation with ≥130 μg/ml of human LF (hLF), iron-free and iron-saturated bovine LF (apo-bLF and holo-bLF, respectively), and ≥6 μg/ml of bLF-derived antimicrobial peptide lactoferricin B (LFcin B); but those effects were weak after 8 h. The biofilm formation of P. gingivalis and P. intermedia over 24 h was effectively inhibited by lower concentrations (≥8 μg/ml) of various iron-bound forms (the apo, native, and holo forms) of bLF and hLF but not LFcin B. A preformed biofilm of P. gingivalis and P. intermedia was also reduced by incubation with various iron-bound bLFs, hLF, and LFcin B for 5 h. In an examination of the effectiveness of native bLF when it was used in combination with four antibiotics, it was found that treatment with ciprofloxacin, clarithromycin, and minocycline in combination with native bLF for 24 h reduced the amount of a preformed biofilm of P. gingivalis compared with the level of reduction achieved with each agent alone. These results demonstrate the antibiofilm activity of LF with lower iron dependency against P. gingivalis and P. intermedia and the potential usefulness of LF for the prevention and treatment of periodontal diseases and as adjunct therapy for periodontal diseases. PMID:19451301

Comparison of the larynx-associated lymphoid tissue in the false vocal cords and subglottis in pediatric autopsies.

PubMed

Rossi e Silva, Renata Calciolari; Olegário, Janainna Grazielle Pacheco; Abate, Débora Tavares de Rezende e Silva; Salge, Ana Karina Marques; Peres, Luiz César; Corrêa, Rosana Rosa Miranda; Castro, Eumenia Costa da Cunha; Teixeira, Vicente de Paula Antunes

2012-12-15

The aim this work was to compare the distribution of cellular phenotypes of the LF in the FVC to the ones in the subglottic region in pediatric autopsy, relating this distribution to age and different causes of death. We analyzed 60 larynges of newborns and children autopsied in the period from 1993 to 2003. The fragments were prepared in order to perform histochemical and immunohistochemical techniques. The morphological analysis showed cases that presented LF only in FVC (35%), LF only in the subglottic region (20%), lack of LF in FVC (30%) and lymphoid aggregates, which did not characterize an LF (15%). The cases of LF in the subglottic region were significantly younger compared to the ones that presented LF in the FVC (p=0.017). The LF in the subglottic region was bigger than the LF in the FVC (p=0.020). There was no significant difference between the cause of death and cellular phenotype for both FVC and the subglottic region. In conclusion, the cells that make up the LF in the FVC in newborns and children younger than one year have functional characteristics similar to LF cells in the subglottic region, suggesting that there are similarities with LALT. Copyright © 2012 Elsevier GmbH. All rights reserved.

Lactoferrin delivery systems: approaches for its more effective use.

PubMed

Onishi, Hiraku

2011-11-01

Recently, pharmacotherapy has advanced extensively, but there are still many refractory diseases which cannot be solved fully by existing therapeutic agents. Therefore, alternative medicine and health foods are now attracting much attention, for example, lactoferrin (LF): a multifunctional glycoprotein. As LF is non-toxic and low-cost, its application in healthcare and therapeutics is expected to be widespread. In this review, LF's general basic features are described. The interaction of LF with its receptors activates the immune system, including cytokine production and balance. In particular, the immune activation of orally administered LF is considered as a new strategy for the treatment of refractory diseases, such as inflammatory bowel disease, virus infection and tumor metastasis. Also mentioned are the problems associated with the use of LF. As LF is degraded rapidly in the body due to enzymatic hydrolysis, high amounts or frequent dosing is required; an appropriate delivery system may improve these problems and increase its efficiency. Chemical modifications, such as PEGylation, can enhance the stability of LF in the body, resulting in increased efficacy. Also, liposomes and enteric or microparticulate formulations can promote the function of LF in oral administration due to target site delivery and protection of LF from enzymatic hydrolysis. These delivery systems are expected to improve the utility of LF.

The dominant expression of functional human lactoferrin in transgenic cloned goats using a hybrid lactoferrin expression construct.

PubMed

Yu, Huiqing; Chen, Jianquan; Sun, Wei; Liu, Siguo; Zhang, Aimin; Xu, Xujun; Wang, Xuebin; He, Zhuzi; Liu, Guohui; Cheng, Guoxiang

2012-10-31

Human Lactoferrin (hLF) is an iron-binding protein with multiple physiological functions. As the availability of natural hLF is limited, alternative means of producing this biopharmaceutical protein have been extensively studied. Here we report on the dominant expression of recombinant human lactoferrin (rhLF) in transgenic cloned goats using a novel optimised construct made by fusing a 3.3 kb hLF minigene to the regulatory elements of the β-casein gene. The transgenic goat produced more than 30 mg/ml rhLF in its milk, and rhLF expression was stable during the entire lactation cycle. The rhLF purification efficiency from whole goat milk is approximately 70%, and its purity is above 98%. Compared with natural hLF, the rhLF from transgenic goats has similar biological characteristics including molecular mass, N-terminal sequence, isoelectric point, immunoreactivity and digestive stability. More importantly, the purified rhLF showed specific anti-tumour activity in the mouse model of melanoma experimental metastasis. Therefore, our study shows that the large-scale production of functional rhLF in transgenic goat milk could be an economical and promising source of human therapeutic use in the future. Copyright © 2012. Published by Elsevier B.V.

Comparison of Adverse Events and Hospital Length of Stay Associated With Various Amphotericin B Formulations

PubMed Central

Wade, Rolin L.; Chaudhari, Paresh; Natoli, Jaime L.; Taylor, Robert J.; Nathanson, Brian H.; Horn, David

2013-01-01

Purpose: Patients with invasive fungal infections are often treated initially with conventional amphotericin B deoxycholate (CAB), followed by a switch to lipid-based formulations of amphotericin B (LF-AMB). Our study examined adverse events and hospital length of stay (LOS) among adults who received LF-AMB exclusively or CAB followed by LF-AMB (CAB/LF-AMB). Methods: Data were extracted from the Cerner Health Facts database. The study included adults with evidence of infection by Aspergillus, Candida, or Cryptococcus in addition to either renal insufficiency, a clinical condition suggesting intolerance to CAB, or CAB exposure within 90 days of admission. Nephrotoxicity was defined as a serum creatinine (SCr) level exceeding a 100% increase from baseline and an absolute level above 1.2 mg/dL. We used a hierarchical mixed-effect logistic regression model with nephrotoxicity as the outcome for the multivariate analysis. Results: The study included 327 LF-AMB and 81 CAB/LF-AMB patients with similar demographics and baseline SCr values. The mean pre-to-post percentage increase in SCr levels was greater for CAB/LF-AMB (122.9%) compared with LF-AMB (62.2%) (P < 0.001). The multivariate-adjusted odds ratio of nephrotoxicity was 5.93, for a 95% confidence interval of 2.92 to 12.05 (P < 0.001) for CAB/LF-AMB compared with LF-AMB. Hypokalemia, hypomagnesemia, and infusion-related reactions were more frequent with CAB/LF-AMB. Compared with the LF-AMB group, the CAB/LF-AMB patients had a longer post-amphotericin B LOS (24.1 days vs. 15.7 days, respectively; P < 0.001), with a marginal effect of 4.5 days longer for those receiving CAB/LF-AMB (P = 0.016). Conclusion: In this retrospective study, we noted a significantly longer post-amphotericin B LOS and a greater frequency of adverse events, including nephrotoxicity, for patients whose initial treatment was CAB and who were switched to LF-AMB, compared with patients who received LF-AMB only. PMID:23946621

Measuring teamwork and conflict among emergency medical technician personnel.

PubMed

Patterson, P Daniel; Weaver, Matthew D; Weaver, Sallie J; Rosen, Michael A; Todorova, Gergana; Weingart, Laurie R; Krackhardt, David; Lave, Judith R; Arnold, Robert M; Yealy, Donald M; Salas, Eduardo

2012-01-01

We sought to develop a reliable and valid tool for measuring teamwork among emergency medical technician (EMT) partnerships. We adapted existing scales and developed new items to measure components of teamwork. After recruiting a convenience sample of 39 agencies, we tested a 122-item draft survey tool (EMT-TEAMWORK). We performed a series of exploratory factor analyses (EFAs) and confirmatory factor analysis (CFA) to test reliability and construct validity, describing variation in domain and global scores using descriptive statistics. We received 687 completed surveys. The EFAs identified a nine-factor solution. We labeled these factors 1) Team Orientation, 2) Team Structure & Leadership, 3) Partner Communication, Team Support, & Monitoring, 4) Partner Trust and Shared Mental Models, 5) Partner Adaptability & Back-Up Behavior, 6) Process Conflict, 7) Strong Task Conflict, 8) Mild Task Conflict, and 9) Interpersonal Conflict. We tested a short-form (30-item SF) and long-form (45-item LF) version. The CFAs determined that both the SF and the LF possess positive psychometric properties of reliability and construct validity. The EMT-TEAMWORK-SF has positive internal consistency properties, with a mean Cronbach's alpha coefficient ≥0.70 across all nine factors (mean = 0.84; minimum = 0.78, maximum = 0.94). The mean Cronbach's alpha coefficient for the EMT-TEAMWORK-LF was 0.87 (minimum = 0.79, maximum = 0.94). There was wide variation in weighted scores across all nine factors and the global score for the SF and LF. Mean scores were lowest for the Team Orientation factor (48.1, standard deviation [SD] 21.5, SF; 49.3, SD 19.8, LF) and highest (more positive) for the Interpersonal Conflict factor (87.7, SD 18.1, for both SF and LF). We developed a reliable and valid survey to evaluate teamwork between EMT partners.

Influence of level and duration of feeding polysaccharide (laminarin and fucoidan) extracts from brown seaweed (Laminaria digitata) on quality indices of fresh pork.

PubMed

Moroney, N C; O'Grady, M N; Robertson, R C; Stanton, C; O'Doherty, J V; Kerry, J P

2015-01-01

The effect of level (450 or 900 mg laminarin (L) and fucoidan (F) /kg feed) and duration (3 or 6 wks) of feeding a seaweed (Laminaria digitata) extract containing L/F on the quality of pork (longissimus thoracis et lumborum (LTL)) stored in modified atmosphere packs and on organ lipid stability was examined. Mechanisms of L/F antioxidant activity in LTL were evaluated. Plasma total antioxidant status, LTL pH, colour, microbiology and 'eating quality' sensory analysis were unaffected by dietary L/F. 'Visual' sensory descriptors (purchasing appeal and overall visual acceptability) were enhanced (p<0.05) in L/F450-3 LTL. Lipid oxidation was lower (p<0.05) in L/F450-3 and L/F900-3 LTL and reduced in L/F900-6 kidney homogenates. In cooked minced pork, lipid oxidation was not reduced by dietary L/F. Saturated fatty acids were lower (p<0.05) in L/F900-6 LTL. Results indicated L/F in pig diets for 3 weeks enhanced pork quality. Copyright © 2014 Elsevier Ltd. All rights reserved.

Experimental Mouse Model of Lumbar Ligamentum Flavum Hypertrophy.

PubMed

Saito, Takeyuki; Yokota, Kazuya; Kobayakawa, Kazu; Hara, Masamitsu; Kubota, Kensuke; Harimaya, Katsumi; Kawaguchi, Kenichi; Hayashida, Mitsumasa; Matsumoto, Yoshihiro; Doi, Toshio; Shiba, Keiichiro; Nakashima, Yasuharu; Okada, Seiji

2017-01-01

Lumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in elderly people, with the number of LSCS patients increasing due to the aging of the population. The ligamentum flavum (LF) is a spinal ligament located in the interior of the vertebral canal, and hypertrophy of the LF, which causes the direct compression of the nerve roots and/or cauda equine, is a major cause of LSCS. Although there have been previous studies on LF hypertrophy, its pathomechanism remains unclear. The purpose of this study is to establish a relevant mouse model of LF hypertrophy and to examine disease-related factors. First, we focused on mechanical stress and developed a loading device for applying consecutive mechanical flexion-extension stress to the mouse LF. After 12 weeks of mechanical stress loading, we found that the LF thickness in the stress group was significantly increased in comparison to the control group. In addition, there were significant increases in the area of collagen fibers, the number of LF cells, and the gene expression of several fibrosis-related factors. However, in this mecnanical stress model, there was no macrophage infiltration, angiogenesis, or increase in the expression of transforming growth factor-β1 (TGF-β1), which are characteristic features of LF hypertrophy in LSCS patients. We therefore examined the influence of infiltrating macrophages on LF hypertrophy. After inducing macrophage infiltration by micro-injury to the mouse LF, we found excessive collagen synthesis in the injured site with the increased TGF-β1 expression at 2 weeks after injury, and further confirmed LF hypertrophy at 6 weeks after injury. Our findings demonstrate that mechanical stress is a causative factor for LF hypertrophy and strongly suggest the importance of macrophage infiltration in the progression of LF hypertrophy via the stimulation of collagen production.

Short Segment Spinal Instrumentation With Index Vertebra Pedicle Screw Placement for Pathologies Involving the Anterior and Middle Vertebral Column Is as Effective as Long Segment Stabilization With Cage Reconstruction: A Biomechanical Study.

PubMed

Bartanusz, Viktor; Harris, Jonathan; Moldavsky, Mark; Cai, Yiwei; Bucklen, Brandon

2015-11-01

An in vitro, cadaveric biomechanical study. The aim of the present study was to compare single-segment posterior instrumentation and fracture-level screws with single/multilevel posterior fixation and corpectomy in a simulated, unstable burst fracture model. The optimal extent of instrumentation for surgical cases of non-neoplastic vertebral body pathologies remains uncertain. Although several clinical studies demonstrate advantages of short segment instrumentation with index-level screws over more extensive corpectomy and anterior-posterior techniques, a comprehensive biomechanical comparison of these techniques is currently lacking. Six bovine spines (T11-L5) were tested in flexion, extension, lateral bending (LB), and axial rotation (AR) following simulated burst fracture at L2. Posterior instrumentation included 1 level above/below (1LF) and 2 levels above/below fracture level (2LF), intermediate or index screws at fracture level (FF), and cross-connectors above/below fracture level (CC). Anterior corpectomy devices included expandable corpectomy spacers with/without integrated screws, ACDi and ACD, respectively FORTIFY-Integrated/FORTIFY; Globus Medical, Inc., PA. Constructs were tested in the following order: (1) Intact; (2) 1LF; (3) 1LF and CC; (4) 1LF and FF; (5) 1LF, CC, and FF; (6) 2LF; (7) 2LF and CC; (8) 2LF and FF; (9) 2LF, CC, and FF; (10) 2LF and ACD; (11) 2LF, ACD, and CC; (12) 1LF and ACDi; (13) 1LF, ACDi, and CC. During flexion, all constructs except 1LF reduced motion relative to intact (P ≤ 0.05). Anterior support was most stable, but no differences were found between constructs (P ≥ 0.05). Every construct reduced motion in extension, though no differences were found between constructs and intact (P ≥ 0.05). During LB, all constructs reduced motion relative to intact (P ≤ 0.05); 2LF constructs further reduced motion (P ≤ 0.05). No construct returned AR motion to intact, with significant increases in 1LF and ACDi, 2LF and ACD, and 2LF, ACD, and CC (P ≤ 0.05). Cross-connectors and fracture screws reinforced each other in posterior-only constructs, providing maximum stability (P ≥ 0.05). This biomechanical comparison study found no significant superiority of combined anterior-posterior constructs over short segment fracture screw fixation, only multilevel posterior instrumentation with and without anterior support, providing increased stability in LB. Biomechanical equivalency suggests that short segment fracture screw intervention may provide appropriate stabilization for non-neoplastic pathologies involving the anterior and middle vertebral columns. 2.

Binding and Endocytosis of Bovine Hololactoferrin by the Parasite Entamoeba histolytica.

PubMed

Ortíz-Estrada, Guillermo; Calderón-Salinas, Víctor; Shibayama-Salas, Mineko; León-Sicairos, Nidia; de la Garza, Mireya

2015-01-01

Entamoeba histolytica is a human parasite that requires iron (Fe) for its metabolic function and virulence. Bovine lactoferrin (B-Lf) and its peptides can be found in the digestive tract after dairy products are ingested. The aim of this study was to compare virulent trophozoites recently isolated from hamster liver abscesses with nonvirulent trophozoites maintained for more than 30 years in cultures in vitro regarding their interaction with iron-charged B-Lf (B-holo-Lf). We performed growth kinetics analyses of trophozoites in B-holo-Lf and throughout several consecutive transfers. The virulent parasites showed higher growth and tolerance to iron than nonvirulent parasites. Both amoeba variants specifically bound B-holo-Lf with a similar K d . However, averages of 9.45 × 10(5) and 6.65 × 10(6) binding sites/cell were found for B-holo-Lf in nonvirulent and virulent amoebae, respectively. Virulent amoebae bound more efficiently to human and bovine holo-Lf, human holo-transferrin, and human and bovine hemoglobin than nonvirulent amoebae. Virulent amoebae showed two types of B-holo-Lf binding proteins. Although both amoebae endocytosed this glycoprotein through clathrin-coated vesicles, the virulent amoebae also endocytosed B-holo-Lf through a cholesterol-dependent mechanism. Both amoeba variants secreted cysteine proteases cleaving B-holo-Lf. These data demonstrate that the B-Lf endocytosis is more efficient in virulent amoebae.

Macrophage Infiltration Is a Causative Factor for Ligamentum Flavum Hypertrophy through the Activation of Collagen Production in Fibroblasts.

PubMed

Saito, Takeyuki; Hara, Masamitsu; Kumamaru, Hiromi; Kobayakawa, Kazu; Yokota, Kazuya; Kijima, Ken; Yoshizaki, Shingo; Harimaya, Katsumi; Matsumoto, Yoshihiro; Kawaguchi, Kenichi; Hayashida, Mitsumasa; Inagaki, Yutaka; Shiba, Keiichiro; Nakashima, Yasuharu; Okada, Seiji

2017-12-01

Ligamentum flavum (LF) hypertrophy causes lumbar spinal canal stenosis, leading to leg pain and disability in activities of daily living in elderly individuals. Although previous studies have been performed on LF hypertrophy, its pathomechanisms have not been fully elucidated. In this study, we demonstrated that infiltrating macrophages were a causative factor for LF hypertrophy. Induction of macrophages into the mouse LF by applying a microinjury resulted in LF hypertrophy along with collagen accumulation and fibroblasts proliferation at the injured site, which were very similar to the characteristics observed in the severely hypertrophied LF of human. However, we found that macrophage depletion by injecting clodronate-containing liposomes counteracted LF hypertrophy even with microinjury. For identification of fibroblasts in the LF, we used collagen type I α 2 linked to green fluorescent protein transgenic mice and selectively isolated green fluorescent protein-positive fibroblasts from the microinjured LF using laser microdissection. A quantitative RT-PCR on laser microdissection samples revealed that the gene expression of collagen markedly increased in the fibroblasts at the injured site with infiltrating macrophages compared with the uninjured location. These results suggested that macrophage infiltration was crucial for LF hypertrophy by stimulating collagen production in fibroblasts, providing better understanding of the pathophysiology of LF hypertrophy. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

A rapid and accurate quantification method for real-time dynamic analysis of cellular lipids during microalgal fermentation processes in Chlorella protothecoides with low field nuclear magnetic resonance.

PubMed

Wang, Tao; Liu, Tingting; Wang, Zejian; Tian, Xiwei; Yang, Yi; Guo, Meijin; Chu, Ju; Zhuang, Yingping

2016-05-01

The rapid and real-time lipid determination can provide valuable information on process regulation and optimization in the algal lipid mass production. In this study, a rapid, accurate and precise quantification method of in vivo cellular lipids of Chlorella protothecoides using low field nuclear magnetic resonance (LF-NMR) was newly developed. LF-NMR was extremely sensitive to the algal lipids with the limits of the detection (LOD) of 0.0026g and 0.32g/L in dry lipid samples and algal broth, respectively, as well as limits of quantification (LOQ) of 0.0093g and 1.18g/L. Moreover, the LF-NMR signal was specifically proportional to the cellular lipids of C. protothecoides, thus the superior regression curves existing in a wide detection range from 0.02 to 0.42g for dry lipids and from 1.12 to 8.97gL(-1) of lipid concentration for in vivo lipid quantification were obtained with all R(2) higher than 0.99, irrespective of the lipid content and fatty acids profile variations. The accuracy of this novel method was further verified to be reliable by comparing lipid quantification results to those obtained by GC-MS. And the relative standard deviation (RSD) of LF-NMR results were smaller than 2%, suggesting the precision of this method. Finally, this method was successfully used in the on-line lipid monitoring during the algal lipid fermentation processes, making it possible for better understanding of the lipid accumulation mechanism and dynamic bioprocess control. Copyright © 2016 Elsevier B.V. All rights reserved.

The faint-end of galaxy luminosity functions at the Epoch of Reionization

NASA Astrophysics Data System (ADS)

Yue, B.; Castellano, M.; Ferrara, A.; Fontana, A.; Merlin, E.; Amorín, R.; Grazian, A.; Mármol-Queralto, E.; Michałowski, M. J.; Mortlock, A.; Paris, D.; Parsa, S.; Pilo, S.; Santini, P.; Di Criscienzo, M.

2018-05-01

During the Epoch of Reionization (EoR), feedback effects reduce the efficiency of star formation process in small halos or even fully quench it. The galaxy luminosity function (LF) may then turn over at the faint-end. We analyze the number counts of z > 5 galaxies observed in the fields of four Frontier Fields (FFs) clusters and obtain constraints on the LF faint-end: for the turn-over magnitude at z ~ 6, MUVT >~-13.3 for the circular velocity threshold of quenching star formation process, vc* <~ 47 km s-1. We have not yet found significant evidence of the presence of feedback effects suppressing the star formation in small galaxies.

Mapping the epitopes of a neutralizing antibody fragment directed against the lethal factor of Bacillus anthracis and cross-reacting with the homologous edema factor.

PubMed

Thullier, Philippe; Avril, Arnaud; Mathieu, Jacques; Behrens, Christian K; Pellequer, Jean-Luc; Pelat, Thibaut

2013-01-01

The lethal toxin (LT) of Bacillus anthracis, composed of the protective antigen (PA) and the lethal factor (LF), plays an essential role in anthrax pathogenesis. PA also interacts with the edema factor (EF, 20% identity with LF) to form the edema toxin (ET), which has a lesser role in anthrax pathogenesis. The first recombinant antibody fragment directed against LF was scFv 2LF; it neutralizes LT by blocking the interaction between PA and LF. Here, we report that scFv 2LF cross-reacts with EF and cross-neutralizes ET, and we present an in silico method taking advantage of this cross-reactivity to map the epitope of scFv 2LF on both LF and EF. This method identified five epitope candidates on LF, constituted of a total of 32 residues, which were tested experimentally by mutating the residues to alanine. This combined approach precisely identified the epitope of scFv 2LF on LF as five residues (H229, R230, Q234, L235 and Y236), of which three were missed by the consensus epitope candidate identified by pre-existing in silico methods. The homolog of this epitope on EF (H253, R254, E258, L259 and Y260) was experimentally confirmed to constitute the epitope of scFv 2LF on EF. Other inhibitors, including synthetic molecules, could be used to target these epitopes for therapeutic purposes. The in silico method presented here may be of more general interest.

A novel heart rate control model provides insights linking LF-HRV behavior to the open-loop gain.

PubMed

Dvir, Hila; Bobrovsky, Ben Zion; Gabbay, Uri

2013-09-20

Low-frequency heart rate variability (LF-HRV) at rest has already been successfully modeled as self-sustained oscillations in a nonlinear control loop, but these models fail to simulate LF-HRV decreases either during aerobic exercise or in heart failure patients. Following control engineering practices, we assume the existence of a biological excitation (dither) within the heart rate control loop that softens the nonlinearity and studied LF-HRV behavior in a dither-embedded model. We adopted the Ottesen model with some revisions and induced a dither of high-frequency stochastic perturbations. We simulated scenarios of a healthy subject at rest and during aerobic exercise (by decreasing peripheral vascular resistance) and a heart failure patient (by decreasing stroke volume). The simulations resembled physiological LF-HRV behavior, i.e., LF-HRV decreased during aerobic exercise and in the heart failure patient. The simulations exhibited LF-HRV dependency on the open-loop gain, which is related to the product of the feedback gain and the feed forward gain. We are the first to demonstrate that LF-HRV may be dependent on the open-loop gain. Accordingly, reduced open-loop gain results in decreased LF-HRV, and vice versa. Our findings explain a well-known but unexplained observed phenomenon of reduced LF-HRV both in heart failure patients and in healthy subjects performing aerobic exercise. These findings have implications on how changes in LF-HRV can be interpreted physiologically, a necessary step towards the clinical utilization of LF-HRV. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Physicochemical properties of β-carotene emulsions stabilized by chlorogenic acid-lactoferrin-glucose/polydextrose conjugates.

PubMed

Liu, Fuguo; Wang, Di; Xu, Honggao; Sun, Cuixia; Gao, Yanxiang

2016-04-01

In this study, the influence of chlorogenic acid (CA)-lactoferrin (LF)-glucose (Glc) conjugate and CA-LF-polydextrose (PD) conjugate on the physicochemical characteristics of β-carotene emulsions was investigated. Novel emulsifiers were formed during Maillard reaction between CA-LF conjugate and Glc/PD. The physicochemical properties of β-carotene emulsions were characterized by droplet size, ζ-potential, rheological behavior, transmission changes during centrifugal sedimentation and β-carotene degradation. Results showed that the covalent attachment of Glc or PD to CA-LF conjugate effectively increased the hydrophilicity of the oil droplets surfaces and strengthened the steric repulsion between the oil droplets. Glucose was better than polydextrose for the conjugation with CA-LF conjugate to stabilize β-carotene emulsions. In comparison with LF and CA-LF-Glc/PD mixtures, CA-LF-Glc/PD ternary conjugates exhibited better emulsifying properties and improved physical stability of β-carotene emulsions during the freeze-thaw treatment. In addition, CA-LF-Glc/PD conjugates significantly enhanced chemical stability of β-carotene in the emulsions against ultraviolet light exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Development and comparative evaluation of up-converting phosphor technology based lateral flow assay for rapid detection of Yersinia pestis, Bacillus anthracis spore and Brucella spp].

PubMed

Li, Chunfeng; Zhang, Pingping; Wang, Xiaoying; Liu, Xiao; Zhao, Yong; Sun, Chongyun; Wang, Chengbin; Yang, Ruifu; Zhou, Lei

2015-01-01

To develop an up-converting phosphor technology based lateral flow (UPT-LF) assay for rapid and quantitative detection of Yersinia pestis, Bacillus anthracis spore and Brucella spp.and make the comparison with BioThreat Alert (BTA) test strips (Tetracore Inc., USA). Using up-converting phosphor nano-particles (UCP-NPs) as the bio-marker, three double-antibody-sandwich model based UPT-LF strips including Plague-UPT-LF, Anthrax-UPT-LF, Brucella-UPT-LF were prepared and its sensitivity, accuracy, linearity and specificity were determined by detecting 10(10), 10(9), 10(8), 10(7), 10(6), 10(5) and 0 CFU/ml series of concentrations of Y.pestis, B.anthracis, Brucella standards and other 27 kinds of 10(9) CFU/ml series of contrations of bacteria strains.Furthermore, the speed, sensitivity and accuracy of bacteria standards and simulated sample detection were compared between UPT-LF and BTA system. The detection limit of Plague-UPT-LF, Anthrax-UPT-LF and Brucella-LF was 10(5) CFU/ml. The CV of series of bacteria concentrations was ≤ 15%, and the r between lg (T/C-cut-off) and lg (concentration) was 0.996,0.998 and 0.999 (F values were 1 647.57, 743.51 and 1 822.17. All the P values were <0.001), respectively. The specificity of Plague-UPT-LF and Brucella-LF were excellent, while that of Anthrax-UPT-LF was a little bit regretful because of non-specific reaction with two isolates of B. subtilis and one B.cereus. On-site evaluation showed the detection time of UPT-LF for all Y.pestis, B.anthracis spore and Brucella spp.was 33, 36 and 37 min, while BTA was 115, 115 and 111 min, which revealed the higher detection speed and sensitivity of UPT-LF comparing with BTA. The negative rate of two methods for blank standard was both 5/5, the sensitivity of UPT-LF for Y.pestis,B.anthracis spore and Brucella spp. was all 10(5) CFU/ml, then BTA was 10(6), 10(6) and 10(5) CFU/ml, respectively. The detection rate of UPT-LF for all three bacteria analog positive samples was 16/16, while BTA for B.anthracis was 7/16 only. The good performance including rapidness, simplicity and high sensitivity will bring the bright future of UPT-LF to be broadly used on-site as first response to bio-terrorism.

Vertical Leaching of Allelochemicals Affecting Their Bioactivity and the Microbial Community of Soil.

PubMed

Xiao, Zhongxiang; Le, Chang; Xu, Zhenghao; Gu, Zhefeng; Lv, Junfei; Shamsi, Imran Haider

2017-09-13

Leaching of allelochemicals in soil is one of the fundamental processes that determines allelopathic activities but is often overlooked. In the present study, the vertical leaching of seven putative allelochemicals as well as one pesticide and one herbicide was investigated using polyvinyl chloride columns combined with a bioassay approach. The results indicated that the leachability of pretilachlor and imidacloprid were the best (Lf > 0.8), followed by vanillin and coumarin (Lf > 0.6). The leachability of daidzein, menthol, and m-tyrosine were medium (0.3 < Lf < 0.6). The lowest leachability has been observed on p-coumaric and p-hydroxybenzoic acids (Lf < 0.3). The chemicals were classified into three clusters according to the phospholipid fatty acid profile (i.e., vanillin in one cluster, coumarin and menthol in the second cluster, and the rest in the third cluster). Bioactivities of the chemicals changed dramatically. Germination of lettuce seeds was suppressed by imidacloprid and pretilachlor, and the suppression was concentration-dependent. The bioactivity of most of the allelochemicals were progressively decreased with the downward movement of chemicals. The results indicated that leaching mediated the microbial communities and the interactions of chemical-microorganism and modified the bioavailability of allelochemicals in soil.

Tractography of Association Fibers Associated with Language Processing.

PubMed

Egger, K; Yang, S; Reisert, M; Kaller, C; Mader, I; Beume, L; Weiller, C; Urbach, H

2015-10-01

Several major association fiber tracts are known to be part of the language processing system. There is evidence that high angular diffusion-based MRI is able to separate these fascicles in a constant way. In this study, we wanted to proof this thesis using a novel whole brain "global tracking" approach and to test for possible lateralization. Global tracking was performed in six healthy right-handed volunteers for the arcuate fascicle (AF), the medial longitudinal fascicle (MdLF), the inferior fronto-occipital fascicle (IFOF), and the inferior longitudinal fascicle (ILF). These fiber tracts were characterized quantitatively using the number of streamlines (SL) and the mean fractional anisotropy (FA). We were able to characterize the AF, the MdLF, the IFOF, and the ILF consistently in six healthy volunteers using global tracking. A left-sided dominance (LI > 0.2) for the AF was found in all participants. The MdLF showed a left-sided dominance in four participants (one female, three male). Regarding the FA, no lateralization (LI > 0.2) could be shown in any of the fascicles. Using a novel global tracking algorithm we confirmed that the courses of the primary language processing associated fascicles can consistently be differentiated. Additionally we were able to show a streamline-based left-sided lateralization in the AF of all right-handed healthy subjects.

On the faint-end of the high-z galaxy luminosity function

NASA Astrophysics Data System (ADS)

Yue, Bin; Ferrara, Andrea; Xu, Yidong

2016-12-01

Recent measurements of the luminosity function (LF) of galaxies in the Epoch of Reionization (EoR, z ≳ 6) indicate a very steep increase of the number density of low-mass galaxies populating the LF faint-end. However, as star formation in low-mass haloes can be easily depressed or even quenched by ionizing radiation, a turnover is expected at some faint UV magnitudes. Using a physically motivated analytical model, we quantify reionization feedback effects on the LF faint-end shape. We find that if reionization feedback is neglected, the power-law Schechter parametrization characterizing the LF faint-end remains valid up to absolute UV magnitude ˜-9. If instead radiative feedback is strong enough that quenches star formation in haloes with circular velocity smaller than 50 km s-1, the LF starts to drop at absolute UV magnitude ˜-15, I.e. slightly below the detection limits of current (unlensed) surveys at z ˜ 5. The LFs may rise again at higher absolute UV magnitude, where, as a result of interplay between reionization process and galaxy formation, most of the galaxy light is from relic stars formed before the EoR. We suggest that the galaxy number counts data, particularly in lensed fields, can put strong constraints on reionization feedback. In models with stronger reionization feedback, stars in galaxies with absolute UV magnitude higher than ˜-13 and smaller than ˜-8 are typically older. Hence, the stellar age-UV magnitude relation can be used as an alternative feedback probe.

Significant antibacterial activity and synergistic effects of camel lactoferrin with antibiotics against methicillin-resistant Staphylococcus aureus (MRSA).

PubMed

Redwan, Elrashdy M; El-Baky, Nawal Abd; Al-Hejin, Ahmed M; Baeshen, Mohammed N; Almehdar, Hussein A; Elsaway, Abdulrahman; Gomaa, Abu-Bakr M; Al-Masaudi, Saad Berki; Al-Fassi, Fahad A; AbuZeid, Isam Eldin; Uversky, Vladimir N

2016-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) causes major healthcare problems in many countries, as it is present as several hospital- and community-associated strains. Hospital-associated MRSA is one of the most prevalent nosocomial pathogens throughout the world and infections caused by community-acquired MRSA are rising. This emphasizes the need for new and efficient anti-MRSA agents. We evaluated the antibacterial effects of camel lactoferrin (cLf) and human lactoferrin (hLf) alone and in combination with several antibiotics against MRSA. Antimicrobials were tested against MRSA and an S. aureus control strain by the agar disc diffusion method. The minimum inhibitory concentration (MIC) was determined for antimicrobials by the broth microdilution method. Synergy between cLf or hLf and antibiotics was examined by checkerboard and time-kill assays. The agar disc diffusion assay showed that MRSA growth was inhibited by cLf at 0.25-3 mg/ml and hLf at 1-3 mg/ml. cLf demonstrated 3 times higher inhibitory activity against MRSA than hLf in terms of MIC values (250 vs. 750 μg/ml, respectively). Biotinylated cLf was recognized by two membrane proteins of MRSA, 66-67 KDa. Combinations of cLf or hLf and oxacillin or vancomycin at sub-MIC levels enhanced in vitro antibacterial activity against MRSA compared with each agent alone. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Human lactoferrin stimulates skin keratinocyte function and wound re-epithelialization.

PubMed

Tang, L; Wu, J J; Ma, Q; Cui, T; Andreopoulos, F M; Gil, J; Valdes, J; Davis, S C; Li, J

2010-07-01

Human lactoferrin (hLF), a member of the transferrin family, is known for its antimicrobial and anti-inflammatory effects. Recent studies on various nonskin cell lines indicate that hLF may have a stimulatory effect on cell proliferation. To study the potential role of hLF in wound re-epithelialization. The effects of hLF on cell growth, migration, attachment and survival were assessed, with a rice-derived recombinant hLF (holo-rhLF), using proliferation analysis, scratch migration assay, calcein-AM/propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method, respectively. The mechanisms of hLF on cell proliferation and migration were explored using specific pathway inhibitors. The involvement of lactoferrin receptor low-density lipoprotein receptor-related protein 1 (LRP1) was examined with RNA interference technique. An in vivo swine second-degree burn wound model was also used to assess wound re-epithelialization. Studies revealed that holo-rhLF significantly stimulated keratinocyte proliferation which could be blocked by mitogen-activated protein kinase (MAPK) kinase 1 inhibitor. Holo-rhLF also showed strong promoting effects on keratinocyte migration, which could be blocked by either inhibition of the MAPK, Src and Rho/ROCK pathways, or downregulation of the LRP1 receptor. With cells under starving or 12-O-tetradecanoylphorbol-13-acetate exposure, the addition of holo-rhLF was found greatly to increase cell viability and inhibit cell apoptosis. Additionally, holo-rhLF significantly increased the rate of wound re-epithelialization in swine second-degree burn wounds. Our studies demonstrate the direct effects of holo-rhLF on wound re-epithelialization including the enhancement of keratinocyte proliferation and migration as well as the protection of cells from apoptosis. The data strongly indicate its potential therapeutic applications in wound healing.

Effects of Recombinant Human Lactoferrin on Osteoblast Growth and Bone Status in Piglets.

PubMed

Li, Qiuling; Zhao, Jie; Hu, Wenping; Wang, Jianwu; Yu, Tian; Dai, Yunping; Li, Ning

2018-04-03

Lactoferrin (LF), an ~80 kDa iron-binding glycoprotein, modulates many biological effects, including antimicrobial and immunomodulatory activities. Recently, it was shown that LF also regulates bone cell activity, suggesting its therapeutic effect on postmenopausal bone loss. However, a minimal amount is known regarding the effects of recombinant human LF (rhLF) supplementation on bone status in young healthy infants. We found osteoblast cell differentiation was significantly promoted in vitro. Furthermore, treatment of human osteoblast cells with rhLF rapidly induced phosphorylation of p44/p42 mitogen-activated protein kinase (p44/p42 MAPK, ERK1/2). In order to investigate the effects of rhLF on bone status in vivo, we used a piglet model, which is a useful model for human infants. Piglets were supplemented with rhLF milk for 30 days. Bone formation markers, Serum calcium concentration, bone mineral density (BMD), bone mineral content (BMC), tibia bone strength, and the overall metabolite profile analysis showed that rhLF was advantageous to the bone growth in piglets. These findings suggest that rhLF supplementation benefits neonate bone health by modulating bone formation.

Antibacterial effects of lactoferricin B.

PubMed

Vorland, L H; Ulvatne, H; Andersen, J; Haukland, H H; Rekdal, O; Svendsen, J S; Gutteberg, T J

1999-01-01

The antimicrobial peptide, lactoferricin, can be generated upon gastric pepsin cleavage of lactoferrin. We have examined the inhibitory efficacy of lactoferricin of bovine origin (Lf-cin B) on Escherichia coli, Proteus mirabilis and Staphylococcus aureus with or without a cell wall. We found that spheroplasts and protoplasts had a lower MIC than their counterparts with a cell wall. We also compared the efficacies of Lf-cin B (17-31) made of all L-amino acids and all D-amino acids. The peptide made of all D-amino acids was more active than the corresponding L-enantiomer. Furthermore, we examined the influence of Lf-cin B on the motility of E. coli and the influence of temperature on the susceptibility of bacteria exposed to Lf-cin B. Bacteria exposed to sub-MIC of Lf-cin B lost their motility. Bacteria exposed to Lf-cin B at 20 degrees C were more sensitive to Lf-cin B than when exposed at 37 degrees C. These findings indicate that the cell envelope is a limiting step for Lf-cin B to exert its antibiotic effect. We cannot rule out a receptor-mediated first step for Lf-cin B (17-31).

Antibacterial and cell penetrating effects of LFcin17-30, LFampin265-284, and LF chimera on enteroaggregative Escherichia coli.

PubMed

Reyes-Cortes, Ruth; Acosta-Smith, Erika; Mondragón-Flores, Ricardo; Nazmi, Kamran; Bolscher, Jan G M; Canizalez-Roman, Adrian; Leon-Sicairos, Nidia

2017-02-01

Lactoferrin (LF) is a protein with antimicrobial activity, which is conferred in part by 2 regions contained in its N-terminal lobe. These regions have been used to develop the following synthetic peptides: lactoferricin17-30, lactoferrampin265-284, and LF chimera (a fusion of lactoferricin17-30 and lactoferrampin265-284). We have reported that these LF peptides have antibacterial activity against several pathogenic bacteria; however, the exact mechanism of action has not been established. Here, we report the effects of LF peptides on the viability of enteroaggregative Escherichia coli (EAEC) and the ability of these peptides to penetrate into the bacteria cytoplasm. The viability of EAEC treated with LF peptides was determined via enumeration of colony-forming units, and the binding and internalization of the LF peptides was followed via immunogold labeling and electron microscopy. Treatment of EAEC with 20 and 40 μmol/L LF peptides reduced bacterial growth compared with untreated bacteria. Initially the peptides associated with the plasma membrane, but after 5 to 30 min of incubation, the peptides were found in the cytoplasm. Remarkably, bacteria treated with LF chimera developed cytosolic electron-dense structures that contained the antimicrobial peptide. Our results suggest that the antibacterial mechanism of LF peptides on EAEC involves their interaction with and penetration into the bacteria.

Anthrax toxin.

PubMed

Bhatnagar, R; Batra, S

2001-01-01

Anthrax is primarily a disease of herbivores caused by gram-positive, aerobic, spore-forming Bacillus anthracis. Humans are accidental hosts through the food of animal origin and animal products. Anthrax is prevelant in most parts of the globe, and cases of anthrax have been reported from almost every country. Three forms of the disease have been recognized: cutaneous (through skin), gastrointestinal (through alimentary tract), and pulmonary (by inhalation of spores). The major virulence factors of Bacillus anthracis are a poly-D glutamic acid capsule and a three-component protein exotoxin. The genes coding for the toxin and the enzymes responsible for capsule production are carried on plasmid pXO1 and pXO2, respectively. The three proteins of the exotoxin are protective antigen (PA, 83 kDa), lethal factor (LF, 90 kDa), and edema factor (EF, 89 kDa). The toxins follow the A-B model with PA being the B moeity and LF/EF, the alternative A moeities. LF and EF are individually nontoxic, but in combination with PA form two toxins causing different pathogenic responses in animals and cultured cells. PA + LF forms the lethal toxin and PA + EF forms the edema toxin. During the process of intoxication, PA binds to the cell surface receptor and is cleaved at the sequence RKKR (167) by cell surface proteases such as furin generating a cell-bound, C-terminal 63 kDa protein (PA63). PA63 possesses a binding site to which LF or EF bind with high affinity. The complex is then internalized by receptor-mediated endocytosis. Acidification of the vesicle leads to instertion of PA63 into the endosomal membrane and translocation of LF/EF across the bilayer into the cytosol where they exert their toxic effects. EF has a calcium- and calmodulin-dependent adenylate cyclase activity. Recent reports indicate that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 (MAPKK1 and 2), and this cleavage inactivates MAPKK1 and thus inhibits the mitogen-activated protein kinase signal transduction pathway. We describe in detail the studies so far done on unraveling the molecular mechanisms of pathogenesis of Bacillus anthracis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kerby, Leslie Marie

Emission of light fragments (LF) from nuclear reactions is an open question. Different reaction mechanisms contribute to their production; the relative roles of each, and how they change with incident energy, mass number of the target, and the type and emission energy of the fragments is not completely understood. None of the available models are able to accurately predict emission of LF from arbitrary reactions. However, the ability to describe production of LF (especially at energies ≳ 30 MeV) from many reactions is important for different applications, such as cosmic-ray-induced Single Event Upsets (SEUs), radiation protection, and cancer therapy withmore » proton and heavy-ion beams, to name just a few. The Cascade-Exciton Model (CEM) version 03.03 and the Los Alamos version of the Quark-Gluon String Model (LAQGSM) version 03.03 event generators in Monte Carlo N-Particle Transport Code version 6 (MCNP6) describe quite well the spectra of fragments with sizes up to ⁴He across a broad range of target masses and incident energies (up to ~ 5 GeV for CEM and up to ~ 1 TeV/A for LAQGSM). However, they do not predict the high energy tails of LF spectra heavier than ⁴He well. Most LF with energies above several tens of MeV are emitted during the precompound stage of a reaction. The current versions of the CEM and LAQGSM event generators do not account for precompound emission of LF larger than ⁴He. The aim of our work is to extend the precompound model in them to include such processes, leading to an increase of predictive power of LF-production in MCNP6. This entails upgrading the Modified Exciton Model currently used at the preequilibrium stage in CEM and LAQGSM. It also includes expansion and examination of the coalescence and Fermi break-up models used in the precompound stages of spallation reactions within CEM and LAQGSM. Extending our models to include emission of fragments heavier than ⁴He at the precompound stage has indeed provided results that have much better agreement with experimental data.« less

Lassa fever-induced sensorineural hearing loss: A neglected public health and social burden.

PubMed

Mateer, Elizabeth J; Huang, Cheng; Shehu, Nathan Y; Paessler, Slobodan

2018-02-01

Although an association between Lassa fever (LF) and sudden-onset sensorineural hearing loss (SNHL) was confirmed clinically in 1990, the prevalence of LF-induced SNHL in endemic countries is still underestimated. LF, a viral hemorrhagic fever disease caused by Lassa virus (LASV), is endemic in West Africa, causing an estimated 500,000 cases and 5,000 deaths per year. Sudden-onset SNHL, one complication of LF, occurs in approximately one-third of survivors and constitutes a neglected public health and social burden. In the endemic countries, where access to hearing aids is limited, SNHL results in a decline of the quality of life for those affected. In addition, hearing loss costs Nigeria approximately 43 million dollars per year. The epidemiology of LF-induced SNHL has not been characterized well. The complication of LF induced by SNHL is also an important consideration for vaccine development and treatments. However, research into the mechanism has been hindered by the lack of autopsy samples and relevant small animal models. Recently, the first animal model that mimics the symptoms of SNHL associated with LF was developed. Preliminary data from the new animal model as well as the clinical case studies support the mechanism of immune-mediated injury that causes SNHL in LF patients. This article summarizes clinical findings of hearing loss in LF patients highlighting the association between LASV infection and SNHL as well as the potential mechanism(s) for LF-induced SNHL. Further research is necessary to identify the mechanism and the epidemiology of LF-induced SNHL.

Aftereffects of Intense Low-Frequency Sound on Spontaneous Otoacoustic Emissions: Effect of Frequency and Level.

PubMed

Jeanson, Lena; Wiegrebe, Lutz; Gürkov, Robert; Krause, Eike; Drexl, Markus

2017-02-01

The presentation of intense, low-frequency (LF) sound to the human ear can cause very slow, sinusoidal oscillations of cochlear sensitivity after LF sound offset, coined the "Bounce" phenomenon. Changes in level and frequency of spontaneous otoacoustic emissions (SOAEs) are a sensitive measure of the Bounce. Here, we investigated the effect of LF sound level and frequency on the Bounce. Specifically, the level of SOAEs was tracked for minutes before and after a 90-s LF sound exposure. Trials were carried out with several LF sound levels (93 to 108 dB SPL corresponding to 47 to 75 phons at a fixed frequency of 30 Hz) and different LF sound frequencies (30, 60, 120, 240 and 480 Hz at a fixed loudness level of 80 phons). At an LF sound frequency of 30 Hz, a minimal sound level of 102 dB SPL (64 phons) was sufficient to elicit a significant Bounce. In some subjects, however, 93 dB SPL (47 phons), the lowest level used, was sufficient to elicit the Bounce phenomenon and actual thresholds could have been even lower. Measurements with different LF sound frequencies showed a mild reduction of the Bounce phenomenon with increasing LF sound frequency. This indicates that the strength of the Bounce not only is a simple function of the spectral separation between SOAE and LF sound frequency but also depends on absolute LF sound frequency, possibly related to the magnitude of the AC component of the outer hair cell receptor potential.

Lactoferrin and necrotizing enterocolitis.

PubMed

Sherman, Michael P

2013-03-01

Lactoferrin (LF) is a multifunctional protein and a member of the transferrin family. LF and lysozyme in breast milk kill bacteria. In the stomach, pepsin digests and releases a potent peptide antibiotic called lactoferricin from native LF. The antimicrobial characteristics of LF may facilitate a healthy intestinal microbiome. LF is the major whey in human milk; its highest concentration is in colostrum. This fact highlights early feeding of colostrum and also fresh mature milk as a way to prevent necrotizing enterocolitis. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparative Evaluation of Pavement Crack Detection Using Kernel-Based Techniques in Asphalt Road Surfaces

NASA Astrophysics Data System (ADS)

Miraliakbari, A.; Sok, S.; Ouma, Y. O.; Hahn, M.

2016-06-01

With the increasing demand for the digital survey and acquisition of road pavement conditions, there is also the parallel growing need for the development of automated techniques for the analysis and evaluation of the actual road conditions. This is due in part to the resulting large volumes of road pavement data captured through digital surveys, and also to the requirements for rapid data processing and evaluations. In this study, the Canon 5D Mark II RGB camera with a resolution of 21 megapixels is used for the road pavement condition mapping. Even though many imaging and mapping sensors are available, the development of automated pavement distress detection, recognition and extraction systems for pavement condition is still a challenge. In order to detect and extract pavement cracks, a comparative evaluation of kernel-based segmentation methods comprising line filtering (LF), local binary pattern (LBP) and high-pass filtering (HPF) is carried out. While the LF and LBP methods are based on the principle of rotation-invariance for pattern matching, the HPF applies the same principle for filtering, but with a rotational invariant matrix. With respect to the processing speeds, HPF is fastest due to the fact that it is based on a single kernel, as compared to LF and LBP which are based on several kernels. Experiments with 20 sample images which contain linear, block and alligator cracks are carried out. On an average a completeness of distress extraction with values of 81.2%, 76.2% and 81.1% have been found for LF, HPF and LBP respectively.

A deterministic (non-stochastic) low frequency method for geoacoustic inversion.

PubMed

Tolstoy, A

2010-06-01

It is well known that multiple frequency sources are necessary for accurate geoacoustic inversion. This paper presents an inversion method which uses the low frequency (LF) spectrum only to estimate bottom properties even in the presence of expected errors in source location, phone depths, and ocean sound-speed profiles. Matched field processing (MFP) along a vertical array is used. The LF method first conducts an exhaustive search of the (five) parameter search space (sediment thickness, sound-speed at the top of the sediment layer, the sediment layer sound-speed gradient, the half-space sound-speed, and water depth) at 25 Hz and continues by retaining only the high MFP value parameter combinations. Next, frequency is slowly increased while again retaining only the high value combinations. At each stage of the process, only those parameter combinations which give high MFP values at all previous LF predictions are considered (an ever shrinking set). It is important to note that a complete search of each relevant parameter space seems to be necessary not only at multiple (sequential) frequencies but also at multiple ranges in order to eliminate sidelobes, i.e., false solutions. Even so, there are no mathematical guarantees that one final, unique "solution" will be found.

The development of the International Network for Frontier Research on Earthquake Precursors (INFREP) by designing new analysing software and by setting up new recording locations of radio VLF/LF signals in Romania

NASA Astrophysics Data System (ADS)

Moldovan, Iren-Adelina; Petruta Constantin, Angela; Emilian Toader, Victorin; Toma-Danila, Dragos; Biagi, Pier Francesco; Maggipinto, Tommaso; Dolea, Paul; Septimiu Moldovan, Adrian

2014-05-01

Based on scientific evidences supporting the causality between earthquake preparatory stages, space weather and solar activity and different types of electromagnetic (EM) disturbances together with the benefit of having full access at ground and space based EM data, INFREP proposes a complex and cross correlated investigation of phenomena that occur in the coupled system Lithosphere-Atmosphere-Ionsophere in order to identify possible causes responsible for anomalous effects observed in the propagation characteristics of radio waves, especially at low (LF) and very low frequency (VLF). INFREP, a network of VLF (20-60 kHz) and LF (150-300 kHz) radio receivers, was put into operation in Europe in 2009, having as principal goal, the study of disturbances produced by the earthquakes on the propagation properties of these signals. The Romanian NIEP VLF / LF monitoring system consisting in a radio receiver -made by Elettronika S.R.L. (Italy) and provided by the Bari University- and the infrastructure that is necessary to record and transmit the collected data, is a part of the international initiative INFREP. The NIEP VLF / LF receiver installed in Romania was put into operation in February 2009 in Bucharest and relocated to the Black-Sea shore (Dobruja Seismologic Observatory) in December 2009. The first development of the Romanian EM monitoring system was needed because after changing the receiving site from Bucharest to Eforie we obtained unsatisfactory monitoring data, characterized by large fluctuations of the received signals' intensities. Trying to understand this behavior has led to the conclusion that the electric component of the electromagnetic field was possibly influenced by the local conditions. Starting from this observation we have run some tests and changed the vertical antenna with a loop-type antenna that is more appropriate in highly electric-field polluted environments. Since the amount of recorded data is huge, for streamlining the research process we have realized the automation of the transfer, storage and initial processing of data using the LabView software platform. The special designed LabVIEW application, which accesses the VLF/LF receiver through internet, opens the receiver's web-page and automatically retrieves the list of data files to synchronize the user-side data with the receiver's data. Missing zipped files are also automatically downloaded. The application performs primary, statistical correlation and spectral analysis, appends daily files into monthly and annual files and performs 3D color-coded maps with graphic representations of VLF and LF signals' intensities versus the minute-of-the-day and the day-of-the-month, facilitating a near real-time observation of VLF and LF electromagnetic waves' propagation. Another feature of the software is the correlation of the daily recorded files for the studied frequencies by overlaying the 24 hours radio activity and taking into account the sunrise and sunset. The next step in developing the Romanian EM recording system is to enlarge the INFREP network with new VLF/LF receivers for a better coverage and separation of European seismogenic zones. This will be done in the future by using national resources. The unitary seismotectonic zoning of Romania and the whole Europe is a very important step for this goal.

Targeting delivery of etoposide to inhibit the growth of human glioblastoma multiforme using lactoferrin- and folic acid-grafted poly(lactide-co-glycolide) nanoparticles.

PubMed

Kuo, Yung-Chih; Chen, Yu-Chun

2015-02-01

Lactoferrin (Lf) and folic acid (FA) were crosslinked on poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) for transporting etoposide across the blood-brain barrier (BBB) and treating human brain malignant glioblastoma. Lf- and FA-grafted PLGA NPs (Lf/FA/PLGA NPs) were employed to permeate the monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes and to inhibit the multiplication of U87MG cells. Lf/FA/PLGA NPs showed a satisfactory entrapment efficiency of etoposide and characteristics of sustained drug release. When compared with PLGA NPs, the permeability coefficient for etoposide across the BBB using Lf/FA/PLGA NPs increased about twofold. The antiproliferative efficacy against the growth of U87MG cells was in the following order: Lf/FA/PLGA NPs>FA/PLGA NPs>PLGA NPs>free etoposide solution. In addition, the targeting ability of Lf/FA/PLGA NPs was evidenced by immunostaining of Lf receptor on HBMECs and folate receptor on U87MG cells during endocytosis. Lf/FA/PLGA NPs with loaded etoposide can be a promising anticancer pharmacotherapy to enhance the delivery of etoposide to malignant brain tumors for preclinical trials. Copyright © 2014 Elsevier B.V. All rights reserved.

Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma

PubMed Central

Wei, Minyan; Guo, Xiucai; Tu, Liuxiao; Zou, Qi; Li, Qi; Tang, Chenyi; Chen, Bao; Xu, Yuehong; Wu, Chuanbin

2015-01-01

Lactoferrin (Lf) is a potential-targeting ligand for hepatocellular carcinoma (HCC) cells because of its specific binding with asialoglycoprotein receptor (ASGPR). In this present work, a doxorubicin (DOX)-loaded, Lf-modified, polyethylene glycol (PEG)ylated liposome (Lf-PLS) system was developed, and its targeting effect and antitumor efficacy to HCC was also explored. The DOX-loaded Lf-PLS system had spherical or oval vesicles, with mean particle size approximately 100 nm, and had an encapsulation efficiency of 97%. The confocal microscopy and flow cytometry indicated that the cellular uptake of Lf-PLS was significantly higher than that of PEGylated liposome (PLS) in ASGPR-positive cells (P<0.05) but not in ASGPR-negative cells (P>0.05). Cytotoxicity assay by MTT demonstrated that DOX-loaded Lf-PLS showed significantly stronger antiproliferative effects on ASGPR-positive HCC cells than did PLS without the Lf modification (P<0.05). The in vivo antitumor studies on male BALB/c nude mice bearing HepG2 xenografts demonstrated that DOX-loaded Lf-PLS had significantly stronger antitumor efficacy compared with PLS (P<0.05) and free DOX (P<0.05). All these results demonstrated that a DOX-loaded Lf-PLS might have great potential application for HCC-targeting therapy. PMID:26316745

Effects of irrigation water salinity on evapotranspiration modified by leaching fractions in hot pepper plants.

PubMed

Qiu, Rangjian; Liu, Chunwei; Wang, Zhenchang; Yang, Zaiqiang; Jing, Yuanshu

2017-08-03

We investigated whether leaching fraction (LF) is able to modify the effects of irrigation water salinity (EC iw ) on evapotranspiration (ET). We conducted an experiment with a completely randomized block design using five levels of EC iw and two LFs. Results showed that the electrical conductivity of drainage water (EC dw ) in an LF of 0.29 was considerably higher during the 21-36 days after transplanting (DAT), and considerably lower after 50 DAT than in an LF of 0.17. The hourly, nighttime, daily, cumulative and seasonal ET all decreased considerably as a result of an increase in the EC iw . The daily ET started to be considerably higher in the LF of 0.29 than in the LF of 0.17 from 65 DAT. Compared with the LF of 0.17, the seasonal ET in the LF of 0.29 under various EC iw levels increased by 4.8%-8.7%. The Maas and Hoffman and van Genuchten and Hoffman models both corresponded well with the measured relative seasonal ET and the LF had no marked effects on these model parameters. Collectively, an increase in the level of EC iw always decreased the ET substantially. An increase in the LF increased the ET considerably, but there was a time lag.

Rapid identification of Lonicerae japonicae Flos and Lonicerae Flos by Fourier transform infrared (FT-IR) spectroscopy and two-dimensional correlation analysis

NASA Astrophysics Data System (ADS)

Yan, Rui; Chen, Jian-bo; Sun, Su-qin; Guo, Bao-lin

2016-11-01

Lonicerae japonicae Flos (LJF) and Lonicerae Flos (LF) are widely-used herbs derived from several plants of the genus Lonicera with similar appearances. LF are usually misused or counterfeited as LJF for economically motivated adulteration. However, the saponins in LF may cause serious side-effects. In this research, the infrared spectroscopic tri-step identification approach is used to develop a simple and rapid method to discriminate LJF and LF to ensure the safety and efficacy of these herbal drugs. In the primary identification by Fourier transform infrared spectra, LJF and LF show different peaks near 1534, 1404, and 781 cm-1. In the secondary identification by the second derivative infrared spectra, LJF and LF show more different peaks near 1078, 1050, 988, 923, 855, 815, and 781 cm-1. In the tertiary identification by the two-dimensional correlation infrared spectra, the differences between LJF and LF are shown more remarkably and convincingly. The results show the potential of the infrared spectroscopic tri-step identification approach in the rapid identification of LJF and LF when the samples are too few to build a statistical recognition rule. This should be very helpful to ensure the quality, safety, and efficacy of LJF and LF for clinical applications.

Effect of lactoferrin on osteogenic differentiation of human adipose stem cells.

PubMed

Ying, Xiaozhou; Cheng, Shaowen; Wang, Wei; Lin, Zhongqin; Chen, Qingyu; Zhang, Wei; Kou, Dongquan; Shen, Yue; Cheng, Xiaojie; Peng, Lei; Zi Xu, Hua; Zhu Lu, Chuan

2012-03-01

Many in vitro studies of the analysis of the lactoferrin (LF) effect on cells have been reported. However, no study has yet investigated the effect of LF on osteogenic differentiation of human adipose-derived stem cells (hADSCs). The aim of this study was to evaluate the effect of LF on osteogenic differentiation of human adipose stem cells. The hADSCs were cultured in an osteogenic medium with 0, 10, 50 and 100 μg/ml LF, respectively. hADSC proliferation was analysed by Cell Counting Kit-8 (CCK-8) assay, and cell osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, von Kossa staining and real-time polymerase chain reaction (RT-PCR). Cell proliferation was significantly increased by LF in a dose-dependent manner from days 4 to 14. Cells cultured with 100 μg/ml LF presented a higher activity compared with the control. The deposition of calcium was increased after the addition of LF. The mRNA expression of type I collagen (COL-I), ALP, osteocalcin (OCN) and RUNX2 increased markedly as a result of LF treatment. We have shown for the first time that LF could promote the proliferation and osteogenic differentiation of hADSCs, which could be a promising approach for enhancing osteogenic capacity of cell-based construction in bone tissue engineering.

Attenuation of massive cytokine response to the staphylococcal enterotoxin B superantigen by the innate immunomodulatory protein lactoferrin

PubMed Central

Hayworth, J L; Kasper, K J; Leon-Ponte, M; Herfst, C A; Yue, D; Brintnell, W C; Mazzuca, D M; Heinrichs, D E; Cairns, E; Madrenas, J; Hoskin, D W; McCormick, J K; Haeryfar, S M M

2009-01-01

Staphylococcal enterotoxin B (SEB) is a pyrogenic exotoxin and a potent superantigen which causes massive T cell activation and cytokine secretion, leading to profound immunosuppression and morbidity. The inhibition of SEB-induced responses is thus considered a goal in the management of certain types of staphylococcal infections. Lactoferrin (LF) is a multi-functional glycoprotein with both bacteriostatic and bactericidal activities. In addition, LF is known to have potent immunomodulatory properties. Given the anti-microbial and anti-inflammatory properties of this protein, we hypothesized that LF can modulate T cell responses to SEB. Here, we report that bovine LF (bLF) was indeed able to attenuate SEB-induced proliferation, interleukin-2 production and CD25 expression by human leucocyte antigen (HLA)-DR4 transgenic mouse T cells. This inhibition was not due to bLF's iron-binding capacity, and could be mimicked by the bLF-derived peptide lactoferricin. Cytokine secretion by an engineered SEB-responsive human Jurkat T cell line and by peripheral blood mononuclear cells from healthy donors was also inhibited by bLF. These findings reveal a previously unrecognized property of LF in modulation of SEB-triggered immune activation and suggest a therapeutic potential for this naturally occurring protein during toxic shock syndrome. PMID:19659771

[Isolation and purification of recombinant human lactoferrin (rhLF) from transgenic rice and its antibacterial activities].

PubMed

Wu, Jinghuan; Yang, Lichen; Liu, Gaige; Gong, Zhaolong; Liu, Jikai; Hu, Yujie; Guo, Yunchang; Piao, Jianhua; Shen, Zhicheng; Yang, Xiaoguang

2013-05-01

To study the isolation and purification of recombinant human lactoferrin (rhLF) from transgenic rice, and to check its antibacterial activities. After isolated rhLF from transgenic rice via saturated ammonium sulfate precipitation, then purified it through CM Sepharose FF-exchange chromatography and molecular sieve chromatography Sephadex G25. The inhibition effects under different concentrations of rhLF (0.25, 0.5, 1.0, 2.0, 4.0, and 5.0 mg/ml) against Salmonella typhimurium, Staphyloccocus aureus, Bacillus cereus, Listeria monocytogenes were observed, using broth microdilution method. The rhLF was obtained at a higher purity (about 90%) through successful isolation and purification. After Coomassie blue staining, Westernblot and mass spectrometer analysis, it was identified as the purpose protein with the molecular weight of approximately 79 kDa. The antibacterial experiments showed that 5 mg/ml and 4 mg/ml rhLF could inhibite Salmonella typhimurium and Staphylococcus aureus persistently, 2 mg/ml and 1 mg/ml rhLF showed a significant inhibitory effects in the later period; while 0.5 mg/ml or lower concentration, showed no inhibitory effects. As to Bacillus cereus, only 5 mg/ml and 4 mg/ml rhLF exhibited certain inhibitory effects within 18 hours. Listeria monocytogenes was inhibited within 18 hours just at 5 mg/ml rhLF. The rhLF could be successfully separated and purified from transgenic rice, and the purified protein still has significant antibacterial activities.

Bovine lactoferrin and lactoferricin exert antitumor activities on human colorectal cancer cells (HT-29) by activating various signaling pathways.

PubMed

Jiang, Rulan; Lönnerdal, Bo

2017-02-01

Lactoferrin (Lf) is an iron-binding glycoprotein that is present at high concentrations in milk. Bovine lactoferricin (LfcinB) is a peptide fragment generated by pepsin proteolysis of bovine lactoferrin (bLf). LfcinB consists of amino acid residues 17-41 proximal to the N-terminus of bLf and a disulfide bond between residues 19 and 36, forming a loop. Both bLf and LfcinB have been demonstrated to have antitumor activities. Colorectal cancer is the second most common cause of cancer death in developed countries. We hypothesized that bLf and LfcinB exert antitumor activities on colon cancer cells (HT-29) by triggering various signaling pathways. bLf and LfcinB significantly induced apoptosis in HT-29 cells but not in normal human intestinal epithelial cells, as revealed by the ApoTox-Glo Triplex Assay. The LIVE/DEAD cell viability assay showed that both bLf and LfcinB reduced the viability of HT-29 cells. Transcriptome analysis indicated that bLf, cyclic LfcinB, and linear LfcinB exerted antitumor activities by differentially activating diverse signaling pathways, including p53, apoptosis, and angiopoietin signaling. Immunoblotting results confirmed that both bLf and LfcinBs increased expression of caspase-8, p53, and p21, critical proteins in tumor suppression. These results provide valuable information regarding bLf and LfcinB for potential clinical applications in colon cancer therapy.

Lassa fever in post-conflict sierra leone.

PubMed

Shaffer, Jeffrey G; Grant, Donald S; Schieffelin, John S; Boisen, Matt L; Goba, Augustine; Hartnett, Jessica N; Levy, Danielle C; Yenni, Rachael E; Moses, Lina M; Fullah, Mohammed; Momoh, Mambo; Fonnie, Mbalu; Fonnie, Richard; Kanneh, Lansana; Koroma, Veronica J; Kargbo, Kandeh; Ottomassathien, Darin; Muncy, Ivana J; Jones, Abigail B; Illick, Megan M; Kulakosky, Peter C; Haislip, Allyson M; Bishop, Christopher M; Elliot, Deborah H; Brown, Bethany L; Zhu, Hu; Hastie, Kathryn M; Andersen, Kristian G; Gire, Stephen K; Tabrizi, Shervin; Tariyal, Ridhi; Stremlau, Mathew; Matschiner, Alex; Sampey, Darryl B; Spence, Jennifer S; Cross, Robert W; Geisbert, Joan B; Folarin, Onikepe A; Happi, Christian T; Pitts, Kelly R; Geske, F Jon; Geisbert, Thomas W; Saphire, Erica Ollmann; Robinson, James E; Wilson, Russell B; Sabeti, Pardis C; Henderson, Lee A; Khan, S Humarr; Bausch, Daniel G; Branco, Luis M; Garry, Robert F

2014-03-01

Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF.

In-situ single pass intestinal permeability and pharmacokinetic study of developed Lumefantrine loaded solid lipid nanoparticles.

PubMed

Garg, Anuj; Bhalala, Kripal; Tomar, Devendra Singh; Wahajuddin

2017-01-10

The present investigation aims to develop lumefantrine loaded binary solid lipid nanoparticles (LF-SLNs) to improve its poor and variable oral bioavailability. The oral bioavailability of LF is poor and variable due to its limited aqueous solubility and P-gp mediated efflux occurring in small intestine. LF-SLNs were prepared using binary lipid mixture of stearic acid and caprylic acid stabilized with TPGS (D-alpha tocopheryl polyethylene glycol 1000 succinate) and Poloxamer 188. Developed LF-SLNs were characterized for particle size distribution, zeta potential, entrapment efficiency, solid state properties and biopharmaceutical properties including in situ intestinal permeability and oral bioavailability. The particle size distribution, zeta potential and entrapment efficiency of optimized batch (LF-SLN7) was found to be 357.7±43.27nm, 25.29±1.15mV and 97.35±0.30%, respectively. DSC thermographs showed loss of crystalline nature of lumefantrine in LF-SLNs. In situ single pass intestinal permeability study (SPIP) study indicated significant enhancement in the effective intestinal permeability of LF from LF-SLN7 as compared to that of control. Pharmacokinetic study also showed significant increase in Cmax and area under curve (AUC0- ∞ ) from LF-SLN7 (3860±521ng/mL and 43181±2557h×ng/mL, respectively) as compared to that of LF-control suspension (1425±563ng/mL and 19586±1537h×ng/mL, respectively). Thus, developed LF-SLNs can be promising to overcome P-gp efflux pump and enhance the oral bioavailability of lumefantrine. Copyright © 2016 Elsevier B.V. All rights reserved.

Soluble Fermentable Dietary Fibre (Pectin) Decreases Caloric Intake, Adiposity and Lipidaemia in High-Fat Diet-Induced Obese Rats

PubMed Central

Adam, Clare L.; Thomson, Lynn M.; Williams, Patricia A.; Ross, Alexander W.

2015-01-01

Consumption of a high fat diet promotes obesity and poor metabolic health, both of which may be improved by decreasing caloric intake. Satiety-inducing ingredients such as dietary fibre may be beneficial and this study investigates in diet-induced obese (DIO) rats the effects of high or low fat diet with or without soluble fermentable fibre (pectin). In two independently replicated experiments, young adult male DIO rats that had been reared on high fat diet (HF; 45% energy from fat) were given HF, low fat diet (LF; 10% energy from fat), HF with 10% w/w pectin (HF+P), or LF with 10% w/w pectin (LF+P) ad libitum for 4 weeks (n = 8/group/experiment). Food intake, body weight, body composition (by magnetic resonance imaging), plasma hormones, and plasma and liver lipid concentrations were measured. Caloric intake and body weight gain were greatest in HF, lower in LF and HF+P, and lowest in the LF+P group. Body fat mass increased in HF, was maintained in LF, but decreased significantly in LF+P and HF+P groups. Final plasma leptin, insulin, total cholesterol and triglycerides were lower, and plasma satiety hormone PYY concentrations were higher, in LF+P and HF+P than in LF and HF groups, respectively. Total fat and triglyceride concentrations in liver were greatest in HF, lower in LF and HF+P, and lowest in the LF+P group. Therefore, the inclusion of soluble fibre in a high fat (or low fat) diet promoted increased satiety and decreased caloric intake, weight gain, adiposity, lipidaemia, leptinaemia and insulinaemia. These data support the potential of fermentable dietary fibre for weight loss and improving metabolic health in obesity. PMID:26447990

Bactericidal effect of bovine lactoferrin and synthetic peptide lactoferrin chimera in Streptococcus pneumoniae and the decrease in luxS gene expression by lactoferrin.

PubMed

León-Sicairos, Nidia; Angulo-Zamudio, Uriel A; Vidal, Jorge E; López-Torres, Cynthia A; Bolscher, Jan G M; Nazmi, Kamran; Reyes-Cortes, Ruth; Reyes-López, Magda; de la Garza, Mireya; Canizalez-Román, Adrian

2014-10-01

Streptococcus pneumoniae (pneumococcus) is responsible for nearly one million child deaths annually. Pneumococcus causes infections such as pneumonia, otitis media, meningitis, and sepsis. The human immune system includes antibacterial peptides and proteins such as lactoferrin (LF), but its activity against pneumococcus is not fully understood. The aim of this work was to evaluate the bactericidal effect of bovine lactoferrin (bLF) and the synthetic LF-peptides lactoferricin (LFcin17-30), lactoferrampin (LFampin265-284), and LFchimera against S. pneumoniae planktonic cells. The mechanism of damage was also investigated, as well as the impact of these peptides on the transcription levels of genes known to encode important virulence factors. S. pneumoniae planktonic cells were treated with bLF, LFcin17-30, LFampin265-284 and LFchimera at different time points. The viability of treated planktonic cells was assessed by dilution and plating (in CFU/ml). The interaction between LF and LF-peptides coupled to fluorescein was visualized using a confocal microscope and flow cytometry, whereas the damage at structural levels was observed by electron microscopy. Damage to bacterial membranes was further evaluated by membrane permeabilization by use of propidium iodide and flow cytometry, and finally, the expression of pneumococcal genes was evaluated by qRT-PCR. bLF and LFchimera were the best bactericidal agents. bLF and peptides interacted with bacteria causing changes in the shape and size of the cell and membrane permeabilization. Moreover, the luxS gene was down-regulated in bacteria treated with LF. In conclusion, LF and LFchimera have a bactericidal effect, and LF down-regulates genes involved in the pathogenicity of pneumococcus, thus demonstrating potential as new agents for the treatment of pneumococcal infections.

Inhibition of Candida albicans Biofilm Formation by the Synthetic Lactoferricin Derived Peptide hLF1-11

PubMed Central

Morici, Paola; Fais, Roberta; Rizzato, Cosmeri

2016-01-01

The aim of this study was to evaluate the in vitro activity of the synthetic peptide hLF1-11 against biofilm produced by clinical isolates of Candida albicans with different fluconazole susceptibility. The antibiofilm activity of the peptide hLF1-11 was assessed in terms of reduction of biofilm cellular density, metabolic activity and sessile cell viability. The extent of morphogenesis in hLF1-11 treated and untreated biofilms was also investigated microscopically. Transcription levels of genes related to cell adhesion, hyphal development and extracellular matrix production were analysed by qRT-PCR in hLF1-11 treated and untreated biofilms. Exogenous dibutyryl-cAMP (db-cAMP) was used to rescue morphogenesis in cells exposed to the peptide. The results revealed that hLF1-11 exhibited an inhibitory effect on biofilm formation by all C. albicans isolates tested in a dose-dependent manner, regardless of their fluconazole susceptibility. Visual inspection of treated or untreated biofilm cells with an inverted microscope revealed a significant reduction in hyphal formation by hLF1-11 treated cells, as early as 3 hours of incubation. Moreover, hLF1-11 showed a reduced activity on preadherent cells. hLF1-11 induced the down-regulation of biofilm and hyphal-associated genes, which were predominantly regulated via the Ras1-cAMP-Efg1 pathway. Indeed, exogenous db-cAMP restored morphogenesis in hLF1-11 treated cells. The hLF1-11 peptide significantly inhibited biofilm formation by C. albicans mainly at early stages, interfering with biofilm cellular density and metabolic activity, and affected morphogenesis through the Ras1-cAMP-Efg1 pathway. Our findings provide the first evidence that hLF1-11 could represent a potential candidate for the prevention of biofilm formation by C. albicans. PMID:27902776

Resolving Ambiguities in the LF/HF Ratio: LF-HF Scatter Plots for the Categorization of Mental and Physical Stress from HRV.

PubMed

von Rosenberg, Wilhelm; Chanwimalueang, Theerasak; Adjei, Tricia; Jaffer, Usman; Goverdovsky, Valentin; Mandic, Danilo P

2017-01-01

It is generally accepted that the activities of the autonomic nervous system (ANS), which consists of the sympathetic (SNS) and parasympathetic nervous systems (PNS), are reflected in the low- (LF) and high-frequency (HF) bands in heart rate variability (HRV)-while, not without some controversy, the ratio of the powers in those frequency bands, the so called LF-HF ratio (LF/HF), has been used to quantify the degree of sympathovagal balance. Indeed, recent studies demonstrate that, in general: (i) sympathovagal balance cannot be accurately measured via the ratio of the LF- and HF- power bands; and (ii) the correspondence between the LF/HF ratio and the psychological and physiological state of a person is not unique. Since the standard LF/HF ratio provides only a single degree of freedom for the analysis of this 2D phenomenon, we propose a joint treatment of the LF and HF powers in HRV within a two-dimensional representation framework, thus providing the required degrees of freedom. By virtue of the proposed 2D representation, the restrictive assumption of the linear dependence between the activity of the autonomic nervous system (ANS) and the LF-HF frequency band powers is demonstrated to become unnecessary. The proposed analysis framework also opens up completely new possibilities for a more comprehensive and rigorous examination of HRV in relation to physical and mental states of an individual, and makes possible the categorization of different stress states based on HRV. In addition, based on instantaneous amplitudes of Hilbert-transformed LF- and HF-bands, a novel approach to estimate the markers of stress in HRV is proposed and is shown to improve the robustness to artifacts and irregularities, critical issues in real-world recordings. The proposed approach for resolving the ambiguities in the standard LF/HF-ratio analyses is verified over a number of real-world stress-invoking scenarios.

Inhibition of Candida albicans Biofilm Formation by the Synthetic Lactoferricin Derived Peptide hLF1-11.

PubMed

Morici, Paola; Fais, Roberta; Rizzato, Cosmeri; Tavanti, Arianna; Lupetti, Antonella

2016-01-01

The aim of this study was to evaluate the in vitro activity of the synthetic peptide hLF1-11 against biofilm produced by clinical isolates of Candida albicans with different fluconazole susceptibility. The antibiofilm activity of the peptide hLF1-11 was assessed in terms of reduction of biofilm cellular density, metabolic activity and sessile cell viability. The extent of morphogenesis in hLF1-11 treated and untreated biofilms was also investigated microscopically. Transcription levels of genes related to cell adhesion, hyphal development and extracellular matrix production were analysed by qRT-PCR in hLF1-11 treated and untreated biofilms. Exogenous dibutyryl-cAMP (db-cAMP) was used to rescue morphogenesis in cells exposed to the peptide. The results revealed that hLF1-11 exhibited an inhibitory effect on biofilm formation by all C. albicans isolates tested in a dose-dependent manner, regardless of their fluconazole susceptibility. Visual inspection of treated or untreated biofilm cells with an inverted microscope revealed a significant reduction in hyphal formation by hLF1-11 treated cells, as early as 3 hours of incubation. Moreover, hLF1-11 showed a reduced activity on preadherent cells. hLF1-11 induced the down-regulation of biofilm and hyphal-associated genes, which were predominantly regulated via the Ras1-cAMP-Efg1 pathway. Indeed, exogenous db-cAMP restored morphogenesis in hLF1-11 treated cells. The hLF1-11 peptide significantly inhibited biofilm formation by C. albicans mainly at early stages, interfering with biofilm cellular density and metabolic activity, and affected morphogenesis through the Ras1-cAMP-Efg1 pathway. Our findings provide the first evidence that hLF1-11 could represent a potential candidate for the prevention of biofilm formation by C. albicans.

Lactoferrin inhibits dexamethasone-induced chondrocyte impairment from osteoarthritic cartilage through up-regulation of extracellular signal-regulated kinase 1/2 and suppression of FASL, FAS, and Caspase 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tu, Yihui; Xue, Huaming; Institute of Life Science, College of Medicine, Swansea University, Singleton Park

Highlights: •Dex exerts dose-dependant inhibition of HACs viability and induction of apoptosis. •Dex-induced impairment of chondrocytes was attenuated by rhLF. •ERK and FASL/FAS signaling are involved in the effects of rhLF. •OA patients with glucocorticoid-induced cartilage damage may benefit from treatment with rhLF. -- Abstract: Dexamethasone (Dex) is commonly used for osteoarthritis (OA) with excellent anti-inflammatory and analgesic effect. However, Dex also has many side effects following repeated use over prolonged periods mainly through increasing apoptosis and inhibiting proliferation. Lactoferrin (LF) exerts significantly anabolic effect on many cells and little is known about its effect on OA chondrocytes. Therefore, themore » aim of this study is to investigate whether LF can inhibit Dex-induced OA chondrocytes apoptosis and explore its possible molecular mechanism involved in. MTT assay was used to determine the optimal concentration of Dex and recombinant human LF (rhLF) on chondrocytes at different time and dose points. Chondrocytes were then stimulated with Dex in the absence or presence of optimal concentration of rhLF. Cell proliferation and viability were evaluated using MTT and LIVE/DEAD assay, respectively. Cell apoptosis was evaluated by multi-parameter apoptosis assay kit using both confocal microscopy and flow cytometry, respectively. The expression of extracellular signal-regulated kinase (ERK), FAS, FASL, and Caspase-3 (CASP3) at the mRNA and protein levels were examined by real-time polymerase chain reaction (PCR) and immunocytochemistry, respectively. The optimal concentration of Dex (25 μg/ml) and rhLF (200 μg/ml) were chosen for the following experiments. rhLF significantly reversed the detrimental effect of Dex on chondrocytes proliferation, viability, and apoptosis. In addition, rhLF significantly prevented Dex-induced down-regulation of ERK and up-regulation of FAS, FASL, and CASP3. These findings demonstrated that rhLF acts as an anabolic effect on chondrocytes through significantly reversing Dex-induced chondrocytes apoptosis. This study may contribute to further investigating the clinical application of LF on OA.« less

Lactobacillus fermentum Suo Attenuates HCl/Ethanol Induced Gastric Injury in Mice through Its Antioxidant Effects

PubMed Central

Suo, Huayi; Zhao, Xin; Qian, Yu; Sun, Peng; Zhu, Kai; Li, Jian; Sun, Baozhong

2016-01-01

The purpose of the study was to determine the inhibitory effects of Lactobacillus fermentum Suo (LF-Suo) on HCl/ethanol induced gastric injury in ICR (Institute for Cancer Research) mice and explain the mechanism of these effects through the molecular biology activities of LF-Suo. The studied mice were divided into four groups: healthy, injured, LF-Suo-L and LF-Suo-H group. After the LF-Suo intragastric administration, the gastric injury area was reduced compared to the injured group. The serum MOT (motilin), SP (substance P), ET (endothelin) levels of LF-Suo treated mice were lower, and SS (somatostatin), VIP (vasoactive intestinal peptide) levels were higher than the injured group mice. The cytokine IL-6 (interleukin 6), IL-12 (interleukin 12), TNF-α (tumor necrosis factor-α) and IFN-γ (interferon-γ) serum levels were decreased after the LF-Suo treatment. The gastric tissues SOD (superoxide dismutase), GSH-Px (glutathione peroxidase), NO (nitric oxide) and activities of LF-Suo treated mice were increased and MDA (malondialdehyde) activity was decreased compared to the injured group mice. By the RT-PCR assay, LF-Suo raised the occludin, EGF (epidermal growth factor), EGFR (epidermal growth factor receptor), VEGF (vascular endothelial growth factor), Fit-1 (fms-like tyrosine kinase-1), IκB-α (inhibitor kappaB-α), nNOS (neuronal nitric oxide synthase), eNOS (endothelial nitric oxide synthase), Mn-SOD, Cu/Zn-SOD, CAT (catalase) mRNA or protein expressions and reduced the COX-2, NF-κB (nuclear factor kappaB), and iNOS (inducible nitric oxide synthase) expressions in gastric tissues compared to the gastric injured group mice. A high concentration (1.0 × 109 CFU/kg b.w.) of LF-Suo treatment showed stronger anti-gastric injury effects compared to a low concentration of (0.5 × 109 CFU/kg b.w.) of LF-Suo treatment. LF-Suo also showed strong survival in pH 3.0 man-made gastric juice and hydrophobic properties. These results indicate that LF-Suo has potential use as probiotics for its gastric injury treatment effects. PMID:26978395

[The role of lactoferrin in the proper development of newborns].

PubMed

Artym, Jolanta; Zimecki, Michał

2005-01-01

Colostrum and milk contain, in addition to nutritional constituents, also proteins crucial for the normal development of the offspring. Lactoferrin (LF) belongs to the family of iron-binding proteins and exhibits a wide spectrum of antimicrobial and immunotropic properties. LF is particularly resistant to proteolytic degradation in alimentary tract, in contrast to other milk proteins, e.g. casein. In any case, LF-derived peptides also possess potent antibacterial activities. LF is absorbed from the intestine by means of specific receptors located on brush border cells. Administered orally, LF stimulates both local and systemic immune response. LF plays a role in the absorption of nutrients. The protein can deliver such metal ions as iron, manganese, and zinc and facilitate the absorption of sugars. LF stimulates the proliferation of gut endothelial cells and the growth of gut-associated lymphatic follicles. This property suggests the possibility of applying LF in premature infants and patients with damaged intestinal mucus. LF controls the proper composition of the gut microflora. It suppresses the growth of pathogenic bacteria while promoting the multiplication of nonpathogenic Lactobacillus and Bifidobacterium. Newborns fed an artificial diet develop harmful microflora (Enterococcus, Enterobacter, Bacteroides, Escherichia). The non-pathogenic microflora ensures low pH, produces some vitamins, increases the activity of NK cells, T lymphocytes, and macrophages, promotes the production of protective immunoglobulins, and lowers the risk of allergies. In studies on mice, LF was found to be protective in bacteremia and endotoxemia. The protein stimulates the activity of reticulo-endothelial system cells and elicits myelopoiesis, thus increasing the killing and clearance of bacteria. In the model of experimental endotoxemia, LF inhibits the activity of pro-inflammatory cytokines, nitric oxide, and reactive forms of oxygen. LF can also promote the differentiation of T and B cells from their immature precursors and increases the activity of NK and LAK cells. It also protects against the toxicity of reactive oxygen radicals. This property may be particularly relevant when baby food, based on modified cow's milk, contains mineral iron, which may be a source of harmful free radicals. In summary, it is obvious that natural human milk has the best value for newborns. Supplementation of artificial baby food with LF seems essential to improve the protective and immunoenhancing property of this kind of diet. It is clear that cow's milk is not appropriate for human newborns. Cow's milk contains 50 times less LF, only traces of lysozyme, and lower concentrations of other whey proteins and immunologically relevant immunoglobulins. Therefore commercially available baby foods (United States, Japan) are supplemented with LF.

Subionospheric VLF/LF radio waves propagation characteristics before, during and after the Sofia, Bulgaria Mw=5.6 earthquake occurred on 22 May 2012

NASA Astrophysics Data System (ADS)

Moldovan, Iren Adelina; Emilian Toader, Victorin; Nenovski, Petko; Biagi, Pier Francesco; Maggipinto, Tommaso; Septimiu Moldovan, Adrian; Ionescu, Constantin

2013-04-01

In 2009, INFREP, a network of VLF (20-60 kHz) and LF (150-300 kHz) radio receivers, was put into operation in Europe having as principal goal, the study of disturbances produced by the earthquakes on the propagation properties of these signals. On May 22nd, 2012 an earthquake with Mw=567 occurred in Bulgaria, near Sofia, inside the "sensitive" area of the INFREP VLF/LF electromagnetic network. The data collected on different frequencies, during April-May 2012 were studied using different methods of analysis: daily correlation methods, spectral approaches and terminator time techniques, in order to find out possible connections between the seismic activity and the subionospheric propagation properties of radio waves. The studies were performed with the help of a specially designed LabVIEW application, which accesses the VLF/LF receiver through internet. This program opens the receiver's web-page and automatically retrieves the list of data files to synchronize the user-side data with the receiver's data. Missing zipped files are also automatically downloaded. The application performs primary, statistical correlation and spectral analysis, appends daily files into monthly and annual files and performs 3D colour-coded maps with graphic representations of VLF and LF signals' intensities versus the minute-of-the-day and the day-of-the-month, facilitating a near real-time observation of VLF and LF electromagnetic waves' propagation. Another feature of the software is the correlation of the daily recorded files for the studied frequencies by overlaying the 24 hours radio activity and taking into account the sunrise and sunset. Data are individually processed (spectral power, correlations, differentiation, filtered using bandpass, lowpass, highpass). JTFA spectrograms (Cone-Shaped Distribution CSD, Gabor, Wavelet, short-time Fourier transform STFT, Wigner-Ville Distribution WVD, Choi-Williams Distribution CWD) are used, too.

Measuring teamwork and conflict among Emergency Medical Technician personnel

PubMed Central

Patterson, P. Daniel; Weaver, Matthew D.; Weaver, Sallie J.; Rosen, Michael A.; Todorova, Gergana; Weingart, Laurie R.; Krackhardt, David; Lave, Judith R.; Arnold, Robert M.; Yealy, Donald M.; Salas, Eduardo

2011-01-01

Objective We sought to develop a reliable and valid tool for measuring teamwork among Emergency Medical Technician (EMT) partnerships. Methods We adapted existing scales and developed new items to measure components of teamwork. After recruiting a convenience sample of 39 agencies, we tested a 122-item draft survey tool. We performed a series of Exploratory Factor Analyses (EFA) and Confirmatory Factor Analysis (CFA) to test reliability and construct validity, describing variation in domain and global scores using descriptive statistics. Results We received 687 completed surveys. The EFA analyses identified a 9-factor solution. We labeled these factors [1] Team Orientation, [2] Team Structure & Leadership, [3] Partner Communication, Team Support, & Monitoring, [4] Partner Trust and Shared Mental Models, [5] Partner Adaptability & Back-Up Behavior, [6] Process Conflict, [7] Strong Task Conflict, [8] Mild Task Conflict, and [9] Interpersonal Conflict. We tested a short form (30-item SF) and long form (45-item LF) version. The CFA analyses determined that both the SF and LF versions possess positive psychometric properties of reliability and construct validity. The EMT-TEAMWORK-SF has positive internal consistency properties with a mean Cronbach’s alpha coefficient ≥0.70 across all 9-factors (mean=0.84; min=0.78, max=0.94). The mean Cronbach’s alpha coefficient for the EMT-TEAMWORK-LF version was 0.87 (min=0.79, max=0.94). There was wide variation in weighted scores across all 9 factors and the global score for the SF and LF versions. Mean scores were lowest for the Team Orientation factor (48.1, SD 21.5 SF; 49.3 SD 19.8 LF) and highest (more positive) for the Interpersonal Conflict factor (87.7 SD 18.1 for both SF and LF). Conclusions We developed a reliable and valid survey to evaluate teamwork between EMT partners. PMID:22128909

A TALE OF DWARFS AND GIANTS: USING A z = 1.62 CLUSTER TO UNDERSTAND HOW THE RED SEQUENCE GREW OVER THE LAST 9.5 BILLION YEARS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rudnick, Gregory H.; Tran, Kim-Vy; Papovich, Casey

2012-08-10

We study the red sequence in a cluster of galaxies at z = 1.62 and follow its evolution over the intervening 9.5 Gyr to the present day. Using deep YJK{sub s} imaging with the HAWK-I instrument on the Very Large Telescope, we identify a tight red sequence and construct its rest-frame i-band luminosity function (LF). There is a marked deficit of faint red galaxies in the cluster that causes a turnover in the LF. We compare the red-sequence LF to that for clusters at z < 0.8, correcting the luminosities for passive evolution. The shape of the cluster red-sequence LFmore » does not evolve between z = 1.62 and z = 0.6 but at z < 0.6 the faint population builds up significantly. Meanwhile, between z = 1.62 and 0.6 the inferred total light on the red sequence grows by a factor of {approx}2 and the bright end of the LF becomes more populated. We construct a simple model for red-sequence evolution that grows the red sequence in total luminosity and matches the constant LF shape at z > 0.6. In this model the cluster accretes blue galaxies from the field whose star formation is quenched and who are subsequently allowed to merge. We find that three to four mergers among cluster galaxies during the 4 Gyr between z = 1.62 and z = 0.6 match the observed LF evolution between the two redshifts. The inferred merger rate is consistent with other studies of this cluster. Our result supports the picture that galaxy merging during the major growth phase of massive clusters is an important process in shaping the red-sequence population at all luminosities.« less

Laser fluorescence detection of subgingival calculus using the DIAGNOdent Classic versus periodontal probing.

PubMed

Shakibaie, Fardad; Walsh, Laurence J

2016-11-01

Deposits of subgingival calculus on the root surfaces of the teeth are difficult to detect with conventional methods such as tactile probing. This study compared the performance of a 655-nm wavelength laser fluorescence (LF) system (DIAGNOdent Classic with a periodontal tip) with conventional periodontal probing under defined conditions in a laboratory simulation, using an experienced examiner. Models with a total of 30 extracted teeth with varying levels of subgingival deposits scattered on their root surfaces were prepared, and silicone impression material applied to replicate periodontal soft tissues. The models were located in a phantom head, and the presence of subgingival calculus recorded at 8 points per tooth (240 sites), then the entire scoring process repeated after 1 and 2 weeks. The optimal LF threshold was determined as a fluorescence score of 7 using Receiver Operating Characteristic curves. When compared the gold standard of direct microscopic examination of roots, LF was more sensitive, specific, and accurate than tactile probing (68.3 vs. 51.7 %; 92.1 vs. 67.8; and 80.2 vs. 59.8 %, respectively), and was also more reproducible (Cohen kappa 0.60 vs. 0.39). These data support the concept of using LF as an adjunct to clinical diagnosis.

Remote sensing and modeling of lightning caused long recovery events within the lower ionosphere using VLF/LF radio wave propagation

NASA Astrophysics Data System (ADS)

Schmitter, E. D.

2014-11-01

On the 4 November 2012 at 3:04:27 UT a strong lightning in the midst of the North Sea affected the propagation conditions of VLF/LF transmitter radio signals from NRK (Iceland, 37.5 kHz) and GBZ (UK, 19.58 kHz) received at 5246° N 8° E (NW Germany). The amplitude and phase dips show a recovery time of 6-12 min pointing to a LOng Recovery Early VLF (LORE) event. Clear assignment of the causative return stroke in space and time was possible with data from the WWLLN (Worldwide Lightning Location Network). Based on a return stroke current model the electric field is calculated and an excess electron density distribution which decays over time in the lower ionosphere is derived. Ionization, attachment and recombination processes are modeled in detail. Entering the electron density distribution in VLF/LF radio wave propagation calculations using the LWPC (Long Wavelength Propagation Capability) code allows to model the VLF/LF amplitude and phase behavior by adjusting the return stroke current moment. The results endorse and quantify the conception of lower ionosphere EMP heating by strong - but not necessarily extremely strong - return strokes of both polarities.

Production and characterization of tearless and non-pungent onion.

PubMed

Kato, Masahiro; Masamura, Noriya; Shono, Jinji; Okamoto, Daisaku; Abe, Tomoko; Imai, Shinsuke

2016-04-06

The onion lachrymatory factor (LF) is produced from trans-S-1-propenyl-L-cysteine sulfoxide (PRENCSO) through successive reactions catalyzed by alliinase (EC 4.4.1.4) and lachrymatory factor synthase (LFS), and is responsible for the tear inducing-property and the pungency of fresh onions. We developed tearless, non-pungent onions non-transgenically by irradiating seeds with neon-ion at 20 Gy. The bulbs obtained from the irradiated seeds and their offspring bulbs produced by selfing were screened by organoleptic assessment of tear-inducing property or HPLC analysis of LF production. After repeated screening and seed production by selfing, two tearless, non-pungent bulbs were identified in the third generation (M3) bulbs. Twenty M4 bulbs obtained from each of them showed no tear-inducing property or pungency when evaluated by 20 sensory panelists. The LF production levels in these bulbs were approximately 7.5-fold lower than those of the normal onion. The low LF production levels were due to reduction in alliinase activity, which was a result of low alliinase mRNA expression (less than 1% of that in the normal onion) and consequent low amounts of the alliinase protein. These tearless, non-pungent onions should be welcomed by all who tear while chopping onions and those who work in facilities where fresh onions are processed.

Process Characterization of Electrical Discharge Machining of Highly Doped Silicon

DTIC Science & Technology

2012-06-01

EEE .! E# EEE @! E#EEEI! E#EEEJ! E# EE "! E# EE ".! E# EE "@! E# EE "I! E# EE "J! $L! $U! 07$(L<--B(L$B(F-O(D1$(ZL]\\(E[( GMU! GML! 64... EE ! LFE# EE ! L@F# EE ! L@E# EE ! L<F# EE ! L<E# EE ! L.F# EE ! &*6)! M! NDO! D! %A! DP! N5P! /G! G! LY > (Z B ; [( G&’=41416(D1ɟ$(H&%&C-$-%( IEFG(N.76=416(LY...roughing experiment. Surface roughness measurements ranged from just over 24

A new laboratory approach to shale analysis using NMR relaxometry

USGS Publications Warehouse

Washburn, Kathryn E.; Birdwell, Justin E.; Baez, Luis; Beeney, Ken; Sonnenberg, Steve

2013-01-01

Low-field nuclear magnetic resonance (LF-NMR) relaxometry is a non-invasive technique commonly used to assess hydrogen-bearing fluids in petroleum reservoir rocks. Measurements made using LF-NMR provide information on rock porosity, pore-size distributions, and in some cases, fluid types and saturations (Timur, 1967; Kenyon et al., 1986; Straley et al., 1994; Brown, 2001; Jackson, 2001; Kleinberg, 2001; Hurlimann et al., 2002). Recent improvements in LF-NMR instrument electronics have made it possible to apply methods used to measure pore fluids to assess highly viscous and even solid organic phases within reservoir rocks. T1 and T2 relaxation responses behave very differently in solids and liquids; therefore the relationship between these two modes of relaxation can be used to differentiate organic phases in rock samples or to characterize extracted organic materials. Using T1-T2 correlation data, organic components present in shales, such as kerogen and bitumen, can be examined in laboratory relaxometry measurements. In addition, implementation of a solid-echo pulse sequence to refocus T2 relaxation caused by homonuclear dipolar coupling during correlation measurements allows for improved resolution of solid-phase protons. LF-NMR measurements of T1 and T2 relaxation time distributions were carried out on raw oil shale samples from the Eocene Green River Formation and pyrolyzed samples of these shales processed by hydrous pyrolysis and techniques meant to mimic surface and in-situ retorting. Samples processed using the In Situ Simulator approach ranged from bitumen and early oil generation through to depletion of petroleum generating potential. The standard T1-T2 correlation plots revealed distinct peaks representative of solid- and liquid-like organic phases; results on the pyrolyzed shales reflect changes that occurred during thermal processing. The solid-echo T1 and T2 measurements were used to improve assessment of the solid organic phases, specifically kerogen, thermally degraded kerogen, and char. Integrated peak areas from the LF-NMR results representative of kerogen and bitumen were found to be well correlated with S1 and S2 parameters from Rock-Eval programmed pyrolysis. This study demonstrates that LFNMR relaxometry can provide a wide range of information on shales and other reservoir rocks that goes well beyond porosity and pore-fluid analysis.

The Impact of Lymphatic Filariasis Mass Drug Administration Scaling Down on Soil-Transmitted Helminth Control in School-Age Children. Present Situation and Expected Impact from 2016 to 2020.

PubMed

Mupfasoni, Denise; Montresor, Antonio; Mikhailov, Alexei; King, Jonathan

2016-12-01

Lymphatic filariasis (LF) and soil-transmitted-helminths (STH) are co-endemic in 58 countries which are mostly in Africa and Asia. Worldwide, 486 million school-age children are considered at risk of both diseases. In 2000, the World Health Organization (WHO) established the global programme to eliminate LF by 2020. Since then, the LF elimination programme has distributed ivermectin or diethylcarbamazine citrate (DEC) in combination with albendazole, thereby also treating STH. Consequently, many school-age children have been treated for STH through the LF programme. As treatment targets towards the 2020 LF elimination goal are achieved, many countries are implementing the transmission assessment survey (TAS) and, if the LF prevalence is estimated to be less than 1%, scaling down mass drug administration (MDA). We analysed the 2014 data on preventive chemotherapy (PC) reported from LF STH co-endemic countries and projected the year and location of TAS expected to be conducted between 2016 and 2020 to assess the impact of this scaling down on STH PC. Eighty percent of all co-endemic countries that have already stopped LF MDA nationally were able to establish STH PC through schools. It is estimated that 14% of the total number of children presently covered by the LF programme is at risk of not continuing to receive PC for STH. In order to achieve and maintain the WHO 2020 goal for STH control, there is an urgent need to establish and reinforce school-based deworming programmes in countries scaling-down national LF elimination programmes.

Quantum Field Theory in Two Dimensions: Light-front Versus Space-like Solutions

NASA Astrophysics Data System (ADS)

Martinovic̆, L'ubomír

2017-07-01

A few non-perturbative topics of quantum field theory in D=1+1 are studied in both the conventional (SL) and light-front (LF) versions. First, we give a concise review of the recently proposed quantization of the two-dimensional massless LF fields. The LF version of bosonization follows in a simple and natural way including the bosonized form of the Thirring model. As a further application, we demonstrate the closeness of the 2D massless LF quantum fields to conformal field theory (CFT). We calculate several correlation functions including those between the components of the LF energy-momentum tensor and derive the LF version of the Virasoro algebra. Using the Euclidean time variable, we can immediately transform calculated quantities to the (anti)holomorphic form. The results found are in agreement with those from CFT. Finally, we show that the proposed framework provides us with the elements needed for an independent LF study of exactly solvable models. We compute the non-perturbative correlation functions from the exact operator solution of the LF Thirring model and compare it to the analogous results in the SL theory. While the vacuum effects are automatically taken into account in the LF case, the non-trivial vacuum structure has to be incorported by an explicit diagonalization of the SL Hamiltonians, to obtain the equivalently complete solution.

Formulation for Oral Delivery of Lactoferrin Based on Bovine Serum Albumin and Tannic Acid Multilayer Microcapsules

NASA Astrophysics Data System (ADS)

Kilic, Ece; Novoselova, Marina V.; Lim, Su Hui; Pyataev, Nikolay A.; Pinyaev, Sergey I.; Kulikov, Oleg A.; Sindeeva, Olga A.; Mayorova, Oksana A.; Murney, Regan; Antipina, Maria N.; Haigh, Brendan; Sukhorukov, Gleb B.; Kiryukhin, Maxim V.

2017-03-01

Lactoferrin (Lf) has considerable potential as a functional ingredient in food, cosmetic and pharmaceutical applications. However, the bioavailability of Lf is limited as it is susceptible to digestive enzymes in gastrointestinal tract. The shells comprising alternate layers of bovine serum albumin (BSA) and tannic acid (TA) were tested as Lf encapsulation system for oral administration. Lf absorption by freshly prepared porous 3 μm CaCO3 particles followed by Layer-by-Layer assembly of the BSA-TA shells and dissolution of the CaCO3 cores was suggested as the most efficient and harmless Lf loading method. The microcapsules showed high stability in gastric conditions and effectively protected encapsulated proteins from digestion. Protective efficiency was found to be 76 ± 6% and 85 ± 2%, for (BSA-TA)4 and (BSA-TA)8 shells, respectively. The transit of Lf along the gastrointestinal tract (GIT) of mice was followed in vivo and ex vivo using NIR luminescence. We have demonstrated that microcapsules released Lf in small intestine allowing 6.5 times higher concentration than in control group dosed with the same amount of free Lf. Significant amounts of Lf released from microcapsules were then absorbed into bloodstream and accumulated in liver. Suggested encapsulation system has a great potential for functional foods providing lactoferrin.

Lactoferrin: A Natural Glycoprotein Involved in Iron and Inflammatory Homeostasis

PubMed Central

Cutone, Antimo; Lepanto, Maria Stefania; Paesano, Rosalba; Valenti, Piera

2017-01-01

Human lactoferrin (hLf), an iron-binding multifunctional cationic glycoprotein secreted by exocrine glands and by neutrophils, is a key element of host defenses. HLf and bovine Lf (bLf), possessing high sequence homology and identical functions, inhibit bacterial growth and biofilm dependently from iron binding ability while, independently, bacterial adhesion to and the entry into cells. In infected/inflamed host cells, bLf exerts an anti-inflammatory activity against interleukin-6 (IL-6), thus up-regulating ferroportin (Fpn) and transferrin receptor 1 (TfR1) and down-regulating ferritin (Ftn), pivotal actors of iron and inflammatory homeostasis (IIH). Consequently, bLf inhibits intracellular iron overload, an unsafe condition enhancing in vivo susceptibility to infections, as well as anemia of inflammation (AI), re-establishing IIH. In pregnant women, affected by AI, bLf oral administration decreases IL-6 and increases hematological parameters. This surprising effect is unrelated to iron supplementation by bLf (80 μg instead of 1–2 mg/day), but to its role on IIH. AI is unrelated to the lack of iron, but to iron delocalization: cellular/tissue overload and blood deficiency. BLf cures AI by restoring iron from cells to blood through Fpn up-expression. Indeed, anti-inflammatory activity of oral and intravaginal bLf prevents preterm delivery. Promising bLf treatments can prevent/cure transitory inflammation/anemia/oral pathologies in athletes. PMID:28914813

Factors Affecting Lactoferrin Concentration in Human Milk: How Much Do We Know?

PubMed Central

Villavicencio, Aasith; Rueda, Maria S.; Turin, Christie G.; Ochoa, Theresa J.

2017-01-01

Lactoferrin (LF) is a breast milk glycoprotein with antimicrobial and anti-inflammatory effects. Its beneficial properties in infants, especially in those born preterm, are currently being studied in clinical trials. However, the maternal and nursing infant factors that may affect the concentration of LF in breast milk are still not clear. We conducted a systematic review to investigate the factors that may affect LF concentration. We used a 2-step approach to identify the eligible studies according to inclusion/exclusion criteria and to determine which studies would be considered. We included 70 qualified articles from 29 countries with publication dates ranging from 1976 to 2015. We described the correlation between LF concentration in breast milk and lactation stage; 10 maternal factors, such as race, parity, among others; and 2 infant factors, infections and prematurity. Colostrum has the highest LF levels, but they decrease with days postpartum. No other factor has been consistently associated with LF concentration. A major limitation of the majority of the published studies is the small sample size and the different methods used to measure LF concentration. Therefore, there is a need for large, multicenter studies with standardized study design, sample collection, and LF measurement methods to identify clinically significant factors associated with LF expression in breast milk, which will help promote exclusive breastfeeding in preterm infants. PMID:28075610

78 FR 66945 - Proposed Collection; 60-Day Comment request: Gulf Long-Term Follow-Up Study (GuLF STUDY)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-07

... Comment request: Gulf Long-Term Follow-Up Study (GuLF STUDY) Summary: In compliance with the requirement... days of the date of this publication. Proposed Collection: Gulf Long-Term Follow-Up Study (GuLF STUDY... GuLF STUDY is to investigate potential short- and long-term health effects associated with oil spill...

Research and development on lactoferrin and its derivatives in China from 2011-2015.

PubMed

Wang, Xiao; Wang, Xiumin; Hao, Ya; Teng, Da; Wang, Jianhua

2017-02-01

Lactoferrin (Lf), a multifunctional glycoprotein, is an important antimicrobial and immune regulatory protein present in neutrophils and most exocrine secretions of mammals. Lactoferricin (Lfcin) is located in the N-terminal region of this protein. In this review, the current state of research into Lf and Lfcin in China is described. Searching with HistCite software in Web Sci located 118 papers published by Chinese researchers from 2011-2015, making China one of the top 3 producers of Lf research and development in the world. The biological functions of Lf and Lfcin are discussed, including antibacterial, antiviral, antifungal, anticarcinogenic, and anti-inflammatory activities; targeted drug delivery, induction of neurocyte, osteoblast, and tenocyte growth, and possible mechanisms of action. The preparation and heterologous expression of Lf in animals, bacteria, and yeast are discussed in detail. Five Lf-related food additive factories and 9 Lf-related health food production companies are certified by the China Food and Drug Administration (CFDA). The latest progress in the generation of transgenic livestock in China, the safety of the use of transgenic animals, and future prospects for the uses of Lf and Lfcin are also covered.

A novel protein tyrosine phosphatase like phytase from Lactobacillus fermentum NKN51: Cloning, characterization and application in mineral release for food technology applications.

PubMed

Sharma, Rekha; Kumar, Piyush; Kaushal, Vandana; Das, Rahul; Kumar Navani, Naveen

2018-02-01

A novel protein tyrosine phosphatase like phytase (PTPLP), designated as PhyLf from probiotic bacterium Lactobacillus fermentum NKN51 was identified, cloned, expressed and characterized. The recombinant PhyLf showed specific activity of 174.5 U/mg. PhyLf exhibited strict specificity towards phytate and optimum temperature at 60 °C, pH 5.0 and ionic strength of 100 mM. K m and K cat of PhyLf for phytate were 0.773 mM and 84.31 s -1 , respectively. PhyLf exhibited high resistance against oxidative inactivation. PhyLf shares no homology, sans the active site with reported PTLPs, warranting classification as a new subclass. Dephytinization of durum wheat and finger millet under in vitro gastrointestinal conditions using PhyLf enhanced the bioaccessibility of mineral ions. Probiotic origin, phytate specificity, resistance to oxidative environment and gastric milieu coupled with ability to release micronutrients are unique properties of PhyLf which present a strong case for its use in ameliorating nutritional value of cereals and animal feed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interference of the antimicrobial peptide lactoferricin B with the action of various antibiotics against Escherichia coli and Staphylococcus aureus.

PubMed

Vorland, L H; Osbakk, S A; Perstølen, T; Ulvatne, H; Rekdal, O; Svendsen, J S; Gutteberg, T J

1999-01-01

The antimicrobial peptide, lactoferricin, can be generated upon gastric pepsin cleavage of lactoferrin. We have examined the interaction of lactoferricin of bovine origin, Lf-cin B, with the antibiotics penicillin G, vancomycin, gentamicin, colistin, D-cycloserine and erythromycin against E. coli ATCC 25922 and Staphylococcus aureus ATCC 25923. We demonstrated synergism between Lf-cin B and erythromycin against E. coli, and partial synergism between Lf-cin B and penicillin G, vancomycin and gentamicin against E. coli. Only penicillin G acted in partial synergism with Lf-cin B against S. aureus. Lf-cin B antagonized vancomycin and gentamicin against S. aureus in low concentration. We conclude that Lf-cin B may facilitate the uptake of antibiotics across the cell envelope.

Fractionation and cellulase treatment for enhancing the properties of kraft-based dissolving pulp.

PubMed

Duan, Chao; Wang, Xinqi; Zhang, YanLing; Xu, Yongjian; Ni, Yonghao

2017-01-01

The aim of this study was to investigate a combined process involving pulp fractionation and cellulase treatment of each fraction for improving the molecular weight distribution (MWD) and reactivity of a kraft-based dissolving pulp. Three pulp fractions, namely long-fiber, mid-fiber and short-fiber fractions (LF, MF and SF, respectively), were used as the substrates. The results showed that the SF had the highest accessibility, lowest viscosity, and highest cellulase adsorption capacity, while the opposite was true for the LF. At a given viscosity, the combined process led to a lower polydispersity index (3.71 vs 4.98) and a higher Fock reactivity (85.6% vs 76.3%), in comparison to the conventional single-stage cellulase treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impacts of Electric Propulsion Systems on Submarine Design

DTIC Science & Technology

1989-06-01

in oersteds D = the density of the steel in grams per cubic centimeter p = the elec" .,; al resistivity of the steel in microohm-centimeters N = the...Condition Al (Sum W1-W7) 4138.64 144.09 15.24 Lead Ballast 413.86 142.50 13.70 Condition A 4552.50 143.95 15.1 Variable Load Weights 209.53 87.46 9.86...fscanf(fp, "%lf", &lr); fscanf(fp, *W%lf?, &vol); fscanf(fp, "%lf", &wt.); fac~ azif (f p, "%lf" &ph); fscant (fp, "%If, &pe); fscanf(fp, "%lf" &i2r

[Determination of LF-VD refining furnace slag by X ray fluorescence spectrometry].

PubMed

Kan, Bin; Cheng, Jian-ping; Song, Zu-feng

2004-10-01

Eight components, i.e. TFe, CaO, MgO, Al2O3, SiO2, TiO2, MnO and P2O5 in refining furnace slag were determined by X ray fluorescence spectrometer. Because the content of CaO was high, the authors selected 12 national and departmental grade slag standard samples and prepared a series of synthetic standard samples by adding spectrally pure reagents to them. The calibration curve is suitable to the sample analysis of CaO, MgO and SiO2 with widely varying range. Meanwhile, the points on the curve are even. The samples were prepared at high temperature by adding Li2B4O7 as flux. The experiments for the selection of the sample preparation conditions about strip reagents, melting temperature and dulition ratio were carried out. The matrix effects on absorption and enhancement were corrected by means of PH model and theoretical alpha coefficient. Moreover, the precision and accuracy experiments were performed. In comparison with chemical analysis method, the quantitative analytical results for each component are satisfactory. The method has proven rapid, precise and simple.

Erythropoietin and Nrf2: key factors in the neuroprotection provided by apo-lactoferrin.

PubMed

Zakharova, E T; Sokolov, A V; Pavlichenko, N N; Kostevich, V A; Abdurasulova, I N; Chechushkov, A V; Voynova, I V; Elizarova, A Yu; Kolmakov, N N; Bass, M G; Semak, I V; Budevich, A I; Kozhin, P M; Zenkov, N K; Klimenko, V M; Kirik, O V; Korzhevskii, D E; Menshchikova, E B; Vasilyev, V B

2018-05-10

Among the properties of lactoferrin (LF) are bactericidal, antianemic, immunomodulatory, antitumour, antiphlogistic effects. Previously we demonstrated its capacity to stabilize in vivo HIF-1-alpha and HIF-2-alpha, which are redox-sensitive multiaimed transcription factors. Various tissues of animals receiving recombinant human LF (rhLF) responded by expressing the HIF-1-alpha target genes, hence such proteins as erythropoietin (EPO), ceruloplasmin, etc. were synthesized in noticeable amounts. Among organs in which EPO synthesis occurred were brain, heart, spleen, liver, kidneys and lungs. Other researchers showed that EPO can act as a protectant against severe brain injury and status epilepticus in rats. Therefore, we tried rhLF as a protector against the severe neurologic disorders developed in rats, such as the rotenone-induced model of Parkinson's disease and experimental autoimmune encephalomyelitis as a model of multiple sclerosis, and observed its capacity to mitigate the grave symptoms. Moreover, an intraperitoneal injection of rhLF into mice 1 h after occlusion of the medial cerebral artery significantly diminished the necrosis area measured on the third day in the ischaemic brain. During this period EPO was synthesized in various murine tissues. It was known that EPO induces nuclear translocation of Nrf2, which, like HIF-1-alpha, is a transcription factor. In view that under conditions of hypoxia both factors demonstrate a synergistic protective effect, we suggested that LF activates the Keap1/Nrf2 signaling pathway, an important link in proliferation and differentiation of normal and malignant cells. J774 macrophages were cultured for 3 days without or in the presence of ferric and ferrous ions (RPMI-1640 and DMEM/F12, respectively). Then cells were incubated with rhLF or Deferiprone. Confocal microscopy revealed nuclear translocation of Nrf2 (the key event in Keap1/Nrf2 signaling) induced by apo-rhLF (iron-free, RPMI-1640). The reference compound Deferiprone (iron chelator) had the similar effect. Upon iron binding (in DMEM/F12) rhLF did not activate the Keap1/Nrf2 pathway. Added to J774, apo-rhLF enhanced transcription of Nrf2-dependent genes coding for glutathione S-transferase P and heme oxygenase-1. Western blotting revealed presence of Nrf2 in mice brain after 6 days of oral administration of apo-rhLF, but not Fe-rhLF or equivalent amount of PBS. Hence, apo-LF, but not holo-LF, induces the translocation of Nrf2 from cytoplasm to the nucleus, probably due to its capacity to induce EPO synthesis.

Conjugation Magnetic PAEEP-PLLA Nanoparticles with Lactoferrin as a Specific Targeting MRI Contrast Agent for Detection of Brain Glioma in Rats

NASA Astrophysics Data System (ADS)

Luo, Binhua; Wang, Siqi; Rao, Rong; Liu, Xuhan; Xu, Haibo; Wu, Yun; Yang, Xiangliang; Liu, Wei

2016-04-01

The diagnosis of malignant brain gliomas is largely based on magnetic resonance imaging (MRI) with contrast agents. In recent years, nano-sized contrast agents have been developed for improved MRI diagnosis. In this study, oleylamine-coated Fe3O4 magnetic nanoparticles (OAM-MNPs) were synthesized with thermal decomposition method and encapsulated in novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer nanoparticles. The OAM-MNP-loaded PAEEP-PLLA nanoparticles (M-PAEEP-PLLA-NPs) were further conjugated with lactoferrin (Lf) for glioma tumor targeting. The Lf-conjugated M-PAEEP-PLLA-NPs (Lf-M-PAEEP-PLLA-NPs) were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), thermo-gravimetric analysis (TGA), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). The average size of OAM-MNPs, M-PAEEP-PLLA-NPs, and Lf-M-PAEEP-PLLA-NPs were 8.6 ± 0.3, 165.7 ± 0.6, and 218.2 ± 0.4 nm, with polydispersity index (PDI) of 0.185 ± 0.023, 0.192 ± 0.021, and 0.224 ± 0.036, respectively. TEM imaging showed that OAM-MNPs were monodisperse and encapsulated in Lf-M-PAEEP-PLLA-NPs. TGA analysis showed that the content of iron oxide nanoparticles was 92.8 % in OAM-MNPs and 45.2 % in Lf-M-PAEEP-PLLA-NPs. VSM results indicated that both OAM-MNPs and Lf-M-PAEEP-PLLA-NPs were superparamagnetic, and the saturated magnetic intensity were 77.1 and 74.8 emu/g Fe. Lf-M-PAEEP-PLLA-NPs exhibited good biocompatibility in cytotoxicity assay. The high cellular uptake of Lf-M-PAEEP-PLLA-NPs in C6 cells indicated that Lf provided effective targeting for the brain tumor cells. The T 2 relaxation rate ( r 2) of M-PAEEP-PLLA-NPs and Lf-M-PAEEP-PLLA-NPs were calculated to be 167.2 and 151.3 mM-1 s-1. In MRI on Wistar rat-bearing glioma tumor, significant contrast enhancement could clearly appear at 4 h after injection and last 48 h. Prussian blue staining of the section clearly showed the retention of Lf-M-PAEEP-PLLA-NPs in tumor tissues. The results from the in vitro and in vivo MRI indicated that Lf-M-PAEEP-PLLA-NPs possessed strong, long-lasting, tumor targeting, and enhanced tumor MRI contrast ability. Lf-M-PAEEP-PLLA-NPs represent a promising nano-sized MRI contrast agent for brain glioma targeting MRI.

Beat-to-Beat Variability of Ventricular Action Potential Duration Oscillates at Low Frequency During Sympathetic Provocation in Humans

PubMed Central

Porter, Bradley; van Duijvenboden, Stefan; Bishop, Martin J.; Orini, Michele; Claridge, Simon; Gould, Justin; Sieniewicz, Benjamin J.; Sidhu, Baldeep; Razavi, Reza; Rinaldi, Christopher A.; Gill, Jaswinder S.; Taggart, Peter

2018-01-01

Background: The temporal pattern of ventricular repolarization is of critical importance in arrhythmogenesis. Enhanced beat-to-beat variability (BBV) of ventricular action potential duration (APD) is pro-arrhythmic and is increased during sympathetic provocation. Since sympathetic nerve activity characteristically exhibits burst patterning in the low frequency range, we hypothesized that physiologically enhanced sympathetic activity may not only increase BBV of left ventricular APD but also impose a low frequency oscillation which further increases repolarization instability in humans. Methods and Results: Heart failure patients with cardiac resynchronization therapy defibrillator devices (n = 11) had activation recovery intervals (ARI, surrogate for APD) recorded from left ventricular epicardial electrodes alongside simultaneous non-invasive blood pressure and respiratory recordings. Fixed cycle length was achieved by right ventricular pacing. Recordings took place during resting conditions and following an autonomic stimulus (Valsalva). The variability of ARI and the normalized variability of ARI showed significant increases post Valsalva when compared to control (p = 0.019 and p = 0.032, respectively). The oscillatory behavior was quantified by spectral analysis. Significant increases in low frequency (LF) power (p = 0.002) and normalized LF power (p = 0.019) of ARI were seen following Valsalva. The Valsalva did not induce changes in conduction variability nor the LF oscillatory behavior of conduction. However, increases in the LF power of ARI were accompanied by increases in the LF power of systolic blood pressure (SBP) and the rate of systolic pressure increase (dP/dtmax). Positive correlations were found between LF-SBP and LF-dP/dtmax (rs = 0.933, p < 0.001), LF-ARI and LF-SBP (rs = 0.681, p = 0.001) and between LF-ARI and LF-dP/dtmax (rs = 0.623, p = 0.004). There was a strong positive correlation between the variability of ARI and LF power of ARI (rs = 0.679, p < 0.001). Conclusions: In heart failure patients, physiological sympathetic provocation induced low frequency oscillation (~0.1 Hz) of left ventricular APD with a strong positive correlation between the LF power of APD and the BBV of APD. These findings may be of importance in mechanisms underlying stability/instability of repolarization and arrhythmogenesis in humans. PMID:29670531

Evolution of spatial and temporal correlations in the solar wind - Observations and interpretation

NASA Technical Reports Server (NTRS)

Klein, L. W.; Matthaeus, W. H.; Roberts, D. A.; Goldstein, M. L.

1992-01-01

Observations of solar wind magnetic field spectra from 1-22 AU indicate a distinctive structure in frequency which evolves with increasing heliocentric distance. At 1 AU extremely low frequency correlations are associated with temporal variations at the solar period and its first few harmonics. For periods of l2-96 hours, a l/f distribution is observed, which we interpret as an aggregate of uncorrelated coronal structures which have not dynamically interacted by 1 AU. At higher frequencies the familiar Kolmogorov-like power law is seen. Farther from the sun the frequency break point between the shallow l/f and the steeper Kolmogorov spectrum evolves systematically towards lower frequencies. We suggest that the Kolmogorov-like spectra emerge due to in situ turbulence that generates spatial correlations associated with the turbulent cascade and that the background l/f noise is a largely temporal phenomenon, not associated with in situ dynamical processes. In this paper we discuss these ideas from the standpoint of observations from several interplanetary spacecraft.

Mechanical role of the posterior column components in the cervical spine.

PubMed

Hartman, Robert A; Tisherman, Robert E; Wang, Cheng; Bell, Kevin M; Lee, Joon Y; Sowa, Gwendolyn A; Kang, James D

2016-07-01

To quantify the mechanical role of posterior column components in human cervical spine segments. Twelve C6-7 segments were subjected to resection of (1) suprasinous/interspinous ligaments (SSL/ISL), (2) ligamenta flavum (LF), (3) facet capsules, and (4) facets. A robot-based testing system performed repeated flexibility testing of flexion-extension (FE), axial rotation (AR), and lateral bending (LB) to 2.5Nm and replayed kinematics from intact flexibility tests for each state. Range-of-motion, stiffness, moment resistance and resultant forces were calculated. The LF contributes largely to moment resistance, particularly in flexion. Facet joints were primary contributors to AR and LB mechanics. Moment/force responses were more sensitive and precise than kinematic outcomes. The LF is mechanically important in the cervical spine; its injury could negatively impact load distribution. Damage to facets in a flexion injury could lead to AR or LB hypermobility. Quantifying the contribution of spinal structures to moment resistance is a sensitive, precise process for characterizing structural mechanics.

75 FR 77880 - Proposed Collection; Comment Request; GuLF Worker Study: Gulf Long-Term Follow-Up Study for Oil...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-14

... Request: New. Need and Use of Information Collection: The purpose of the GuLF Study is to investigate... Request; GuLF Worker Study: Gulf Long-Term Follow-Up Study for Oil Spill Clean-Up Workers and Volunteers... instruments display a currently valid OMB control number. Proposed Collection Title: GuLF Worker Study: Gulf...

Emerging trends in Lassa fever: redefining the role of immunoglobulin M and inflammation in diagnosing acute infection.

PubMed

Branco, Luis M; Grove, Jessica N; Boisen, Matt L; Shaffer, Jeffrey G; Goba, Augustine; Fullah, Mohammed; Momoh, Mambu; Grant, Donald S; Garry, Robert F

2011-10-24

Lassa fever (LF) is a devastating hemorrhagic viral disease that is endemic to West Africa and responsible for thousands of human deaths each year. Analysis of humoral immune responses (IgM and IgG) by antibody-capture ELISA (Ab-capture ELISA) and Lassa virus (LASV) viremia by antigen-capture ELISA (Ag-capture ELISA) in suspected patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW) in Sierra Leone over the past five years is reshaping our understanding of acute LF. Analyses in LF survivors indicated that LASV-specific IgM persists for months to years after initial infection. Furthermore, exposure to LASV appeared to be more prevalent in historically non-endemic areas of West Africa with significant percentages of reportedly healthy donors IgM and IgG positive in LASV-specific Ab-capture ELISA. We found that LF patients who were Ag positive were more likely to die than suspected cases who were only IgM positive. Analysis of metabolic and immunological parameters in Ag positive LF patients revealed a strong correlation between survival and low levels of IL-6, -8, -10, CD40L, BUN, ALP, ALT, and AST. Despite presenting to the hospital with fever and in some instances other symptoms consistent with LF, the profiles of Ag negative IgM positive individuals were similar to those of normal donors and nonfatal (NF) LF cases, suggesting that IgM status cannot necessarily be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. Only LASV viremia assessed by Ag-capture immunoassay, nucleic acid detection or virus isolation should be used to diagnose acute LASV infection in West Africans. LASV-specific IgM serostatus cannot be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. By applying these criteria, we identified a dysregulated metabolic and pro-inflammatory response profile conferring a poor prognosis in acute LF. In addition to suggesting that the current diagnostic paradigm for acute LF should be reconsidered, these studies present new opportunities for therapeutic interventions based on potential prognostic markers in LF.

Using Rasch Analysis to Validate the Motor Activity Log and the Lower Functioning Motor Activity Log in Patients With Stroke.

PubMed

Chuang, I-Ching; Lin, Keh-Chung; Wu, Ching-Yi; Hsieh, Yu-Wei; Liu, Chien-Ting; Chen, Chia-Ling

2017-10-01

The Motor Activity Log (MAL) and Lower-Functioning MAL (LF-MAL) are used to assess the amount of use of the more impaired arm and the quality of movement during activities in real-life situations for patients with stroke. This study used Rasch analysis to examine the psychometric properties of the MAL and LF-MAL in patients with stroke. This is a methodological study. The MAL and LF-MAL include 2 scales: the amount of use (AOU) and the quality of movement (QOM). Rasch analysis was used to examine the unidimensionality, item difficulty hierarchy, targeting, reliability, and differential item functioning (DIF) of the MAL and LF-MAL. A total of 403 patients with mild or moderate stroke completed the MAL, and 134 patients with moderate/severe stroke finished the LF-MAL. Evidence of disordered thresholds and poor model fit were found both in the MAL and LF-MAL. After the rating categories were collapsed and misfit items were deleted, all items of the revised MAL and LF-MAL exhibited ordering and constituted unidimensional constructs. The person-item map showed that these assessments were difficult for our participants. The person reliability coefficients of these assessments ranged from .79 to .87. No items in the revised MAL and LF-MAL exhibited bias related to patients' characteristics. One limitation is the recruited patients, who have relatively high-functioning ability in the LF-MAL. The revised MAL and LF-MAL are unidimensional scales and have good reliability. The categories function well, and responses to all items in these assessments are not biased by patients' characteristics. However, the revised MAL and LF-MAL both showed floor effect. Further study might add easy items for assessing the performance of activity in real-life situations for patients with stroke. © 2017 American Physical Therapy Association

Lassa Fever in Post-Conflict Sierra Leone

PubMed Central

Hartnett, Jessica N.; Levy, Danielle C.; Yenni, Rachael E.; Moses, Lina M.; Fullah, Mohammed; Momoh, Mambo; Fonnie, Mbalu; Fonnie, Richard; Kanneh, Lansana; Koroma, Veronica J.; Kargbo, Kandeh; Ottomassathien, Darin; Muncy, Ivana J.; Jones, Abigail B.; Illick, Megan M.; Kulakosky, Peter C.; Haislip, Allyson M.; Bishop, Christopher M.; Elliot, Deborah H.; Brown, Bethany L.; Zhu, Hu; Hastie, Kathryn M.; Andersen, Kristian G.; Gire, Stephen K.; Tabrizi, Shervin; Tariyal, Ridhi; Stremlau, Mathew; Matschiner, Alex; Sampey, Darryl B.; Spence, Jennifer S.; Cross, Robert W.; Geisbert, Joan B.; Folarin, Onikepe A.; Happi, Christian T.; Pitts, Kelly R.; Geske, F. Jon; Geisbert, Thomas W.; Saphire, Erica Ollmann; Robinson, James E.; Wilson, Russell B.; Sabeti, Pardis C.; Henderson, Lee A.; Khan, S. Humarr; Bausch, Daniel G.; Branco, Luis M.; Garry, Robert F.

2014-01-01

Background Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Methodology/Principal Findings Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Conclusions/Significance Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF. PMID:24651047

Relationships among low-frequency local field potentials, spiking activity, and three-dimensional reach and grasp kinematics in primary motor and ventral premotor cortices

PubMed Central

Vargas-Irwin, Carlos E.; Truccolo, Wilson; Donoghue, John P.

2011-01-01

A prominent feature of motor cortex field potentials during movement is a distinctive low-frequency local field potential (lf-LFP) (<4 Hz), referred to as the movement event-related potential (mEP). The lf-LFP appears to be a global signal related to regional synaptic input, but its relationship to nearby output signaled by single unit spiking activity (SUA) or to movement remains to be established. Previous studies comparing information in primary motor cortex (MI) lf-LFPs and SUA in the context of planar reaching tasks concluded that lf-LFPs have more information than spikes about movement. However, the relative performance of these signals was based on a small number of simultaneously recorded channels and units, or for data averaged across sessions, which could miss information of larger-scale spiking populations. Here, we simultaneously recorded LFPs and SUA from two 96-microelectrode arrays implanted in two major motor cortical areas, MI and ventral premotor (PMv), while monkeys freely reached for and grasped objects swinging in front of them. We compared arm end point and grip aperture kinematics′ decoding accuracy for lf-LFP and SUA ensembles. The results show that lf-LFPs provide enough information to reconstruct kinematics in both areas with little difference in decoding performance between MI and PMv. Individual lf-LFP channels often provided more accurate decoding of single kinematic variables than any one single unit. However, the decoding performance of the best single unit among the large population usually exceeded that of the best single lf-LFP channel. Furthermore, ensembles of SUA outperformed the pool of lf-LFP channels, in disagreement with the previously reported superiority of lf-LFP decoding. Decoding results suggest that information in lf-LFPs recorded from intracortical arrays may allow the reconstruction of reach and grasp for real-time neuroprosthetic applications, thus potentially supplementing the ability to decode these same features from spiking populations. PMID:21273313

Enhancement of endotoxin neutralization by coupling of a C12-alkyl chain to a lactoferricin-derived peptide

PubMed Central

2004-01-01

Antibacterial peptide acylation, which mimics the structure of the natural lipopeptide polymyxin B, increases antimicrobial and endotoxin-neutralizing activities. The interaction of the lactoferricin-derived peptide LF11 and its N-terminally acylated analogue, lauryl-LF11, with different chemotypes of bacterial lipopolysaccharide (LPS Re, Ra and smooth S form) was investigated by biophysical means and was related to the peptides' biological activities. Both peptides exhibit high antibacterial activity against the three strains of Salmonella enterica differing in the LPS chemotype. Lauryl-LF11 has one order of magnitude higher activity against Re-type, but activity against Ra- and S-type bacteria is comparable with that of LF11. The alkyl derivative peptide lauryl-LF11 shows a much stronger inhibition of the LPS-induced cytokine induction in human mononuclear cells than LF11. Although peptide–LPS interaction is essentially of electrostatic nature, the lauryl-modified peptide displays a strong hydrophobic component. Such a feature might then explain the fact that saturation of the peptide binding takes place at a much lower peptide/LPS ratio for LF11 than for lauryl-LF11, and that an overcompensation of the negative LPS backbone charges is observed for lauryl-LF11. The influence of LF11 on the gel-to-liquid-crystalline phase-transition of LPS is negligible for LPS Re, but clearly fluidizing for LPS Ra. In contrast, lauryl-LF11 causes a cholesterol-like effect in the two chemotypes, fluidizing in the gel and rigidifying of the hydrocarbon chains in the liquid-crystalline phase. Both peptides convert the mixed unilamellar/non-lamellar aggregate structure of lipid A, the ‘endotoxic principle’ of LPS, into a multilamellar one. These data contribute to the understanding of the mechanisms of the peptide-mediated neutralization of endotoxin and effect of lipid modification of peptides. PMID:15344905

Evaluation of the bioactivity of recombinant human lactoferrins toward murine osteoblast-like cells for bone tissue engineering.

PubMed

Amini, Ashley A; Nair, Lakshmi S

2013-05-01

Lactoferrin (LF), which belongs to the iron-binding transferrin family, is an important regulator of the levels of free iron in the body fluids. LF has raised significant interest as a bioactive protein due to its wide array of physiological effects on many different cell types, including osteoblasts and osteoclasts. The glycoprotein's degree of iron saturation has a pivotal influence on its physical structure. The objective of this study is to investigate the biological effects of apo (low iron saturation), pis (partially iron saturated), and holo (high iron saturation) recombinant human LF (rhLF) on MC3T3-E1 cells to identify the suitable candidate for bone tissue engineering application. Our studies demonstrated a dose-dependent mitogenic response of MC3T3 to rhLF treatment irrespective of the iron concentration. Furthermore, rhLF induced the cells to produce transcription factors, chemokines, and cytokines as determined by β-catenin activation, phosphorylation of Akt, vascular endothelial growth factor, and interleukin (IL-6) expression. The iron saturation of rhLF did not have any significant effect on these biological activities of MC3T3 cells. In addition, the overall pattern of gene regulation in MC3T3-E1 cells upon rhLF treatment was followed by a global microarray analysis. Among the 45,200 genes tested, only 251 genes were found to be regulated by rhLFs of different iron concentrations. Of these, the transferrin receptor (Tfrc) was the only gene differentially regulated by the iron saturated and iron depleted (apo) rhLFs. In conclusion, the study demonstrated that rhLF is a bioactive protein and that the iron saturation of rhLF may not play a significant role in modulating osteoblast functions.

Oral lactoferrin protects against experimental candidiasis in mice.

PubMed

Velliyagounder, K; Alsaedi, W; Alabdulmohsen, W; Markowitz, K; Fine, D H

2015-01-01

To determine the role of human lactoferrin (hLF) in protecting the oral cavities of mice against Candida albicans infection in lactoferrin knockout (LFKO(-/-)) mice was compared to wild-type (WT) mice. We also aim to determine the protective role of hLF in LFKO(-/-) mice. Antibiotic-treated immunosuppressed mice were inoculated with C. albicans (or sham infection) by oral swab and evaluated for the severity of infection after 7 days of infection. To determine the protective role of hLF, we added 0·3% solution of hLF to the drinking water given to some of the mice. CFU count, scoring of lesions and microscopic observations were carried out to determine the severity of infection. LFKO(-/-) I mice showed a 2 log (P = 0·001) higher CFUs of C. albicans in the oral cavity compared to the WT mice infected with C. albicans (WTI). LFKO(-/-) I mice given hLF had a 3 log (P = 0·001) reduction in CFUs in the oral cavity compared to untreated LFKO(-/-) I mice. The severity of infection, observed by light microscopy, revealed that the tongue of the LFKO(-/-) I mice showed more white patches compared to WTI and LFKO(-/-) I + hLF mice. Scanning electron microscopic observations revealed that more filiform papillae were destroyed in LFKO(-/-) I mice when compared to WTI or LFKO(-/-) I + hLF mice. Human LF is important in protecting mice from oral C. albicans infection. Administered hLF may be used to prevent C. albicans infection. Human LF, a multifunctional iron-binding glycoprotein can be used as a therapeutic active ingredient in oral healthcare products against C. albicans. © 2014 The Society for Applied Microbiology.

Prebiotic effects of bovine lactoferrin on specific probiotic bacteria.

PubMed

Chen, Po-Wen; Liu, Zhen-Shu; Kuo, Tai-Chen; Hsieh, Min-Chi; Li, Zhe-Wei

2017-04-01

Bovine lactoferrin (bLf) is a natural iron-binding protein and it has been suggested to be a prebiotic agent, but this finding remains inconclusive. This study explores the prebiotic potential of bLf in 14 probiotics. Initially, bLf (1-32 mg/mL) treatment showed occasional and slight prebiotic activity in several probiotics only during the late experimental period (48, 78 h) at 37 °C. We subsequently supposed that bLf exerts stronger prebiotic effects when probiotic growth has been temperately retarded. Therefore, we incubated the probiotics at different temperatures, namely 37 °C, 28 °C, room temperature (approximately 22-24 °C), and 22 °C, to retard or inhibit their growth. As expected, bLf showed more favorable prebiotic activity in several probiotics when their growth was partially retarded at room temperature. Furthermore, at 22 °C, the growth of Bifidobacterium breve, Lactobacillus coryniformis, L. delbrueckii, L. acidophilus, B. angulatum, B. catenulatum, and L. paraplantarum were completely blocked. Notably, these probiotics started regrowing in the presence of bLf (1-32 mg/mL) in a significant and dose-dependent manner. Accordingly, bLf significantly increased the growth of Pediococcus pentosaceus, L. rhamnosus, and L. paracasei (BCRC 17483; a locally isolated strain) when their growth was retarded by incubation at 22 °C. In conclusion, bLf showed inconsistent prebiotic activity in the 14 probiotics at 37 °C, but revealed strong prebiotic activity in 10 probiotic strains at 22 °C. Therefore, this study enables determining additional roles of Lf in probiotic strains, which can facilitate developing novel combinational approaches by simultaneously using Lf and specific probiotics.

Effect of bovine apo-lactoferrin on the growth and virulence of Actinobacillus pleuropneumoniae.

PubMed

Luna-Castro, Sarahí; Aguilar-Romero, Francisco; Samaniego-Barrón, Luisa; Godínez-Vargas, Delfino; de la Garza, Mireya

2014-10-01

Actinobacillus pleuropneumoniae (App) is a Gram-negative bacterium that causes porcine pleuropneumonia, leading to economic losses in the swine industry. Due to bacterial resistance to antibiotics, new treatments for this disease are currently being sought. Lactoferrin (Lf) is an innate immune system glycoprotein of mammals that is microbiostatic and microbicidal and affects several bacterial virulence factors. The aim of this study was to investigate whether bovine iron-free Lf (BapoLf) has an effect on the growth and virulence of App. Two serotype 1 strains (reference strain S4074 and the isolate BC52) and a serotype 7 reference strain (WF83) were analyzed. First, the ability of App to grow in iron-charged BLf was discarded because in vivo, BapoLf sequesters iron and could be a potential source of this element favoring the infection. The minimum inhibitory concentration of BapoLf was 14.62, 11.78 and 10.56 µM for the strain BC52, S4074 and WF83, respectively. A subinhibitory concentration (0.8 µM) was tested by assessing App adhesion to porcine buccal epithelial cells, biofilm production, and the secretion and function of toxins and proteases. Decrease in adhesion (24-42 %) was found in the serotype 1 strains. Biofilm production decreased (27 %) for only the strain 4074 of serotype 1. Interestingly, biofilm was decreased (60-70 %) in the three strains by BholoLf. Hemolysis of erythrocytes and toxicity towards HeLa cells were not affected by BapoLf. In contrast, proteolytic activity in all strains was suppressed in the presence of BapoLf. Finally, oxytetracycline produced synergistic effect with BapoLf against App. Our results suggest that BapoLf affects the growth and several of the virulence factors in App.

Lethal factor antibodies contribute to lethal toxin neutralization in recipients of anthrax vaccine precipitated.

PubMed

Dumas, Eric K; Garman, Lori; Cuthbertson, Hannah; Charlton, Sue; Hallis, Bassam; Engler, Renata J M; Choudhari, Shyamal; Picking, William D; James, Judith A; Farris, A Darise

2017-06-08

A major difference between two currently licensed anthrax vaccines is presence (United Kingdom Anthrax Vaccine Precipitated, AVP) or absence (United States Anthrax Vaccine Adsorbed, AVA) of quantifiable amounts of the Lethal Toxin (LT) component Lethal Factor (LF). The primary immunogen in both vaccine formulations is Protective Antigen (PA), and LT-neutralizing antibodies directed to PA are an accepted correlate of vaccine efficacy; however, vaccination studies in animal models have demonstrated that LF antibodies can be protective. In this report we compared humoral immune responses in cohorts of AVP (n=39) and AVA recipients (n=78) matched 1:2 for number of vaccinations and time post-vaccination, and evaluated whether the LF response contributes to LT neutralization in human recipients of AVP. PA response rates (≥95%) and PA IgG concentrations were similar in both groups; however, AVP recipients exhibited higher LT neutralization ED 50 values (AVP: 1464.0±214.7, AVA: 544.9±83.2, p<0.0001) and had higher rates of LF IgG positivity (95%) compared to matched AVA vaccinees (1%). Multiple regression analysis revealed that LF IgG makes an independent and additive contribution to the LT neutralization response in the AVP group. Affinity purified LF antibodies from two independent AVP recipients neutralized LT and bound to LF Domain 1, confirming contribution of LF antibodies to LT neutralization. This study documents the benefit of including an LF component to PA-based anthrax vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of lumbar fasciae on the stability of the lower lumbar spine.

PubMed

Choi, Hae Won; Kim, Young Eun

2017-10-01

The biomechanical effect of tensioning the lumbar fasciae (LF) on the stability of the spine during sagittal plane motion was analysed using a validated finite element model of the normal lumbosacral spine (L4-S1). To apply the tension in the LF along the direction of the fibres, a local coordinate was allocated using dummy rigid beam elements that originated from the spinous process. Up to 10 Nm of flexion and 7.5 Nm of extension moment was applied with and without 20 N of lateral tension in the LF. A follower load of 400 N was additionally applied along the curvature of the spine. To identify how the magnitude of LF tension related to the stability of the spine, the tensioning on the fasciae was increased up to 40 N with an interval of 10 N under 7.5 Nm of flexion/extension moment. A fascial tension of 20 N produced a 59% decrease in angular motion at 2.5 Nm of flexion moment while there was a 12.3% decrease at 10 Nm in the L5-S1 segment. Its decrement was 53 and 9.6% at 2.5 Nm and 10 Nm, respectively, in the L4-L5 segment. Anterior translation was reduced by 12.1 and 39.0% at the L4-L5 and L5-S1 segments under 10 Nm of flexion moment, respectively. The flexion stiffness shows an almost linear increment with the increase in fascial tension. The results of this study showed that the effect of the LF on the stability of the spine is significant.

[Diabetes mellitus and nonalcoholic fatty liver disease: The verges of contingency].

PubMed

Bakulin, I G; Sandler, Yu G; Vinnitskaya, E V; Keiyan, V A; Rodionova, S V; Rotin, D L

To estimate the incidence of hepatic steatosis (HS) and liver fibrosis (LF) in patients with diabetes mellitus (DM), by applying the noninvasive techniques of liver fibroelastometry (LFE) and a battery of fibrotests (FTs); to determine their diagnostic value and to identify factors influencing the development of LF. A comprehensive examination was made in 82 diabetic patients (mean age, 56.7±12.7 years; p=0.033). The data were statistically evaluated using ROC curve analysis, correlation and single-factor analyses of variance, and multiple logistic regression analysis. FTs and LFE revealed that the DM patients had liver cirrhosis (LC) (METAVIR F4) in 12 (14.6%) and 15 (18.2%) patients, respectively. Those showed clinically significant fibrosis (METAVIR fibrosis stages F2-3) in 19 (23.1%) and 23 (28%) patients, respectively. Varying degrees of HS were present in 79 (96.3%) patients. LFE and FTs demonstrated comparable results in detecting LC (the area under the receiver operating characteristics curve (AUROC), 0.83 and 0.81, respectively). The development of LF is influenced by factors, such as the degree of HS, obesity, the activity of an inflammatory process, and the level of alanine aminotransferase and α2-macroglobulin. Diabetic patients are at high risk for NAFLD to develop LF and LC. LFE and FTs showed a comparably high accuracy in the diagnosis of LC in patients with DM and these may be used for screening. With allowance made for the existing risk factors of LF and LC, it is necessary to identify groups of patients with DM for further examination and follow-up. Patients who are diagnosed with stage F4 should be examined carefully to evaluate concurrent diseases and to make liver biopsy.

77 FR 32009 - Airworthiness Directives; Honeywell International, Inc. Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-31

... Airworthiness Directives; Honeywell International, Inc. Turbofan Engines AGENCY: Federal Aviation Administration... Honeywell International, Inc. ALF502L-2C; ALF502R-3; ALF502R-3A; ALF502R-5; LF507-1F; and LF507-1H turbofan...; ALF502R-3A; ALF502R-5; LF507-1F; and LF507- 1H turbofan engines, installed on airplanes of U.S. registry...

Urban lymphatic filariasis.

PubMed

Simonsen, Paul E; Mwakitalu, Mbutolwe E

2013-01-01

Lymphatic filariasis (LF) is a disabling and disfiguring disease resulting from a mosquito-borne parasitic infection. It is a major public health problem in many countries with a warm climate. Research and control activities have mainly focused on LF in rural areas where it also has its major impact. However, with rapid and unplanned growth of cities in the developing world, there is a need also to consider LF transmission and control in urban settings. Here, we review currently available knowledge on urban LF and the environmental and socio-economic basis for its occurrence. Among the three parasite species causing LF in humans, only Wuchereria bancrofti has been documented to have a significant potential for urban transmission. This is primarily because one of its vectors, Culex quinquefasciatus, thrives and proliferates excessively in crowded city areas with poor sanitary, sewerage and drainage facilities. For this reason, urban LF also often shows a marked focality in distribution, with most cases clustered in areas inhabited by the less privileged city populations. More knowledge on urban LF is needed, in particular on its socio-economic and human behavioural context, on the potential for transmission in regions where other LF vector species predominate, and on rapid methods for identification and mapping of risk areas, to provide a strong evidence base for its control.

Lactoferrin and prematurity: a promising milk protein?

PubMed

Ochoa, Theresa J; Sizonenko, Stéphane V

2017-02-01

Lactoferrin (Lf) is the major whey protein in milk, with multiple beneficial health effects including direct antimicrobial activities, anti-inflammatory effects, and iron homeostasis. Oral Lf supplementation in human preterm infants has been shown to reduce the incidence of sepsis and necrotizing enterocolitis. In preclinical models of antenatal stress and perinatal brain injury, bovine Lf protected the developing brain from neuronal loss, improved connectivity, increased neurotrophic factors, and decreased inflammation. It also supported brain development and cognition. Further, Lf can prevent preterm delivery by reducing proinflammatory factors and inhibiting premature cervix maturation. We review here the latest research on Lf in the field of neonatology.

Neural activity induced by visual food stimuli presented out of awareness: a preliminary magnetoencephalography study.

PubMed

Takada, Katsuko; Ishii, Akira; Matsuo, Takashi; Nakamura, Chika; Uji, Masato; Yoshikawa, Takahiro

2018-02-15

Obesity is a major public health problem in modern society. Appetitive behavior has been proposed to be partially driven by unconscious decision-making processes and thus, targeting the unconscious cognitive processes related to eating behavior is essential to develop strategies for overweight individuals and obese patients. Here, we presented food pictures below the threshold of awareness to healthy male volunteers and examined neural activity related to appetitive behavior using magnetoencephalography. We found that, among participants who did not recognize food pictures during the experiment, an index of heart rate variability assessed by electrocardiography (low-frequency component power/high-frequency component power ratio, LF/HF) just after picture presentation was increased compared with that just before presentation, and the increase in LF/HF was negatively associated with the score for cognitive restraint of food intake. In addition, increased LF/HF was negatively associated with increased alpha band power in Brodmann area (BA) 47 caused by food pictures presented below the threshold of awareness, and level of cognitive restraint was positively associated with increased alpha band power in BA13. Our findings may provide valuable clues to the development of methods assessing unconscious regulation of appetite and offer avenues for further study of the neural mechanisms related to eating behavior.

77 FR 14312 - Airworthiness Directives; Honeywell International, Inc. Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... International, Inc. Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of... Honeywell International, Inc. ALF502L-2C; ALF502R-3; ALF502R-3A; ALF502R-5; LF507-1F; and LF507-1H turbofan...; ALF502R-3A; ALF502R-5; LF507-1F; and LF507-1H turbofan engines, installed on airplanes of U.S. registry...

Understanding the cryptic nature of Lassa fever in West Africa.

PubMed

Gibb, Rory; Moses, Lina M; Redding, David W; Jones, Kate E

2017-09-01

Lassa fever (LF) is increasingly recognized by global health institutions as an important rodent-borne disease with severe impacts on some of West Africa's poorest communities. However, our knowledge of LF ecology, epidemiology and distribution is limited, which presents barriers to both short-term disease forecasting and prediction of long-term impacts of environmental change on Lassa virus (LASV) zoonotic transmission dynamics. Here, we synthesize current knowledge to show that extrapolations from past research have produced an incomplete picture of the incidence and distribution of LF, with negative consequences for policy planning, medical treatment and management interventions. Although the recent increase in LF case reports is likely due to improved surveillance, recent studies suggest that future socio-ecological changes in West Africa may drive increases in LF burden. Future research should focus on the geographical distribution and disease burden of LF, in order to improve its integration into public policy and disease control strategies.

High-Level Expression of Recombinant Bovine Lactoferrin in Pichia pastoris with Antimicrobial Activity

PubMed Central

Iglesias-Figueroa, Blanca; Valdiviezo-Godina, Norberto; Siqueiros-Cendón, Tania; Sinagawa-García, Sugey; Arévalo-Gallegos, Sigifredo; Rascón-Cruz, Quintín

2016-01-01

In this study, bovine lactoferrin (bLf), an iron-binding glycoprotein considered an important nutraceutical protein because of its several properties, was expressed in Pichia pastoris KM71-H under AOX1 promoter control, using pJ902 as the recombinant plasmid. Dot blotting analysis revealed the expression of recombinant bovine lactoferrin (rbLf) in Pichia pastoris. After Bach fermentation and purification by molecular exclusion, we obtained an expression yield of 3.5 g/L of rbLf. rbLf and predominantly pepsin-digested rbLf (rbLfcin) demonstrated antibacterial activity against Escherichia coli (E. coli) BL21DE3, Staphylococcus aureus (S. aureus) FRI137, and, in a smaller percentage, Pseudomonas aeruginosa (Ps. Aeruginosa) ATCC 27833. The successful expression and characterization of functional rbLf expressed in Pichia pastoris opens a prospect for the development of natural antimicrobial agents produced recombinantly. PMID:27294912

Diet-driven microbiota dysbiosis is associated with vagal remodeling and obesity.

PubMed

Sen, Tanusree; Cawthon, Carolina R; Ihde, Benjamin Thomas; Hajnal, Andras; DiLorenzo, Patricia M; de La Serre, Claire B; Czaja, Krzysztof

2017-05-01

Obesity is one of the major health issues in the United States. Consumption of diets rich in energy, notably from fats and sugars (high-fat/high-sugar diet: HF/HSD) is linked to the development of obesity and a popular dietary approach for weight loss is to reduce fat intake. Obesity research traditionally uses low and high fat diets and there has been limited investigation of the potential detrimental effects of a low-fat/high-sugar diet (LF/HSD) on body fat accumulation and health. Therefore, in the present study, we investigated the effects of HF/HSD and LF/HSD on microbiota composition, gut inflammation, gut-brain vagal communication and body fat accumulation. Specifically, we tested the hypothesis that LF/HSD changes the gut microbiota, induces gut inflammation and alters vagal gut-brain communication, associated with increased body fat accumulation. Sprague-Dawley rats were fed an HF/HSD, LF/HSD or control low-fat/low-sugar diet (LF/LSD) for 4weeks. Body weight, caloric intake, and body composition were monitored daily and fecal samples were collected at baseline, 1, 6 and 27days after the dietary switch. After four weeks, blood and tissues (gut, brain, liver and nodose ganglia) were sampled. Both HF/HSD and LF/HSD-fed rats displayed significant increases in body weight and body fat compared to LF/LSD-fed rats. 16S rRNA sequencing showed that both HF/HSD and LF/HSD-fed animals exhibited gut microbiota dysbiosis characterized by an overall decrease in bacterial diversity and an increase in Firmicutes/Bacteriodetes ratio. Dysbiosis was typified by a bloom in Clostridia and Bacilli and a marked decrease in Lactobacillus spp. LF/HSD-fed animals showed a specific increase in Sutterella and Bilophila, both Proteobacteria, abundances of which have been associated with liver damage. Expression of pro-inflammatory cytokines, such as IL-6, IL-1β and TNFα, was upregulated in the cecum while levels of tight junction protein occludin were downregulated in both HF/HSD and LF/HSD fed rats. HF/HSD and LF/HSD-fed rats also exhibited an increase in cecum and serum levels of lipopolysaccharide (LPS), a pro-inflammatory bacterial product. Immunofluorescence revealed the withdrawal of vagal afferents from the gut and at their site of termination the nucleus of the solitary tract (NTS) in both the HF/HSD and LF/HSD rats. Moreover, there was significant microglia activation in the nodose ganglia, which contain the vagal afferent neuron cell bodies, of HF/HSD and LF/HSD rats. Taken together, these data indicate that, similar to HF/HSD, consumption of an LF/HSD induces dysbiosis of gut microbiota, increases gut inflammation and alters vagal gut-brain communication. These changes are associated with an increase in body fat accumulation. © 2016.

Production and characterization of tearless and non-pungent onion

PubMed Central

Kato, Masahiro; Masamura, Noriya; Shono, Jinji; Okamoto, Daisaku; Abe, Tomoko; Imai, Shinsuke

2016-01-01

The onion lachrymatory factor (LF) is produced from trans-S-1-propenyl-L-cysteine sulfoxide (PRENCSO) through successive reactions catalyzed by alliinase (EC 4.4.1.4) and lachrymatory factor synthase (LFS), and is responsible for the tear inducing-property and the pungency of fresh onions. We developed tearless, non-pungent onions non-transgenically by irradiating seeds with neon-ion at 20 Gy. The bulbs obtained from the irradiated seeds and their offspring bulbs produced by selfing were screened by organoleptic assessment of tear-inducing property or HPLC analysis of LF production. After repeated screening and seed production by selfing, two tearless, non-pungent bulbs were identified in the third generation (M3) bulbs. Twenty M4 bulbs obtained from each of them showed no tear-inducing property or pungency when evaluated by 20 sensory panelists. The LF production levels in these bulbs were approximately 7.5-fold lower than those of the normal onion. The low LF production levels were due to reduction in alliinase activity, which was a result of low alliinase mRNA expression (less than 1% of that in the normal onion) and consequent low amounts of the alliinase protein. These tearless, non-pungent onions should be welcomed by all who tear while chopping onions and those who work in facilities where fresh onions are processed. PMID:27048847

Effects of prefrontal rTMS on autonomic reactions to affective pictures.

PubMed

Berger, Christoph; Domes, Gregor; Balschat, Johannes; Thome, Johannes; Höppner, Jacqueline

2017-02-01

Repetitive transcranial magnetic stimulation (rTMS) can modulate the excitability of stimulated cortical areas, such as prefrontal areas involved in emotion regulation. Low frequency (LF) rTMS is expected to have inhibitory effects on prefrontal regions, and thereby should disinhibit limbic activity, resulting in enhanced emotional and autonomic reactions. For high frequency (HF) rTMS, the opposite pattern might be assumed. The objective of this study was to determine the effects of different rTMS frequencies applied to the right dlPFC on autonomic functions and on emotional perception. In a crossover design, two groups of 20 healthy young women were either stimulated with one session of LF rTMS (1 Hz) or one session of HF rTMS (10 Hz), compared to sham stimulation. We assessed phasic cardiac responses (PCR), skin conductance reactions (SCR), and emotional appraisal of emotional pictures as well as recognition memory after each rTMS application. After LF rTMS, PCR (heart rate deceleration) during presentation of pictures with negative and neutral valence was significantly increased compared to the presentation of positive pictures. In contrast, the modulatory effect of picture valence and arousal on the cardiac orienting response was absent after HF rTMS. Our results suggest that frontal LF rTMS indirectly activates the ANS via inhibition of the right dlPFC activity, likely by enhancing the sensory processing or attention to aversive and neutral stimuli.

Crosstalk between coagulation and inflammation in mastitis and metritis in dairy cows.

PubMed

Bobowiec, Ryszard; Wessely-Szponder, Joanna; Hola, Piotr

2009-06-01

Coagulation and inflammation are closely related as part of the mechanisms of host defence during a severe infection. The aim of this study was to investigate the relation between thrombin as a factor in both the coagulative and inflammatory processes and neutrophil secretory function on the basis of lactoferrin (LF), elastase and myeloperoxidase release in the course of mastitis and metritis in cows. Thrombin generation was measured on the basis of hydrolysis of SAR-PRO-ARG-pNA and lactoferrin concentration was estimated by an ELISA method. The greatest thrombin generation was observed in the metritis group (1.18 +/- 0.62 IU). The level of LF was the highest in the group of cows with mastitis (0.74 +/- 0.55 mg/ml) in the first phase of the disease. In the second phase of the diseases the level of serum LF in cows with mastitis diminished to the value of 0.41 +/- 0.16 mg/ml, whereas in cows with metritis the level of LF increased to 0.51 +/- 0.17 mg/ml. This study reveals that the excessive production of thrombin not only causes hypercoagulatory disorders but also exaggerates neutrophil function by the release of some enzymes which may play a destructive role during disseminated intravascular coagulation (DIC). These enzymes also inhibit anticoagulative systems, thus potentially worsening the course of the disease.

The Coma Cluster Luminosity Function from Ultraviolet to Near-Infrared

NASA Astrophysics Data System (ADS)

Andreon, S.; Cuillandre, J.-C.; Pello, R.

The Coma cluster luminosity function (LF) from ultraviolet (2000 AA ) to the near-infrared (H band) is summarized. In the UV the LF is very steep, much steeper than in the optical. The steep Coma UV LF implies that faint and bright galaxies give similar contributions to the total UV flux and to the total metal production rate. The ComaUV LF is dominated in number and luminosity by blue galaxies, which are often faint in the optical. Therefore the Coma UV LF is dominated by star forming galaxies, not by massive and large galaxies. The optical Coma LF is relatively steep (alpha=-1.4) over the 11 magnitudes sampled, but its slope and shape depend on considered filter and magnitude. We found a clear steeping of the FL going from B to R bands, indicative of the presence of a large number of red dwarfs, as faint as three bright globular clusters. Furthermore, using Hubble Space Telescope images, we discover that blends of globular clusters, not resolved in individual components due to seeing, look like dwarf galaxies when observed from the ground and are numerous and bright. The existence of these fake extended sources increases the steepness of the LF at faint magnitudes, if not deal on. This concern affects previous deep probing of the luminosity function, but not the present work. The near-infrared LF wa s computed on a near-infrared selected sample of galaxies which photometry is complete down to the typical dwarf (M* +5) luminosity. The Coma LF can be described by a Schechter function with intermediate slope (alpha sim-1.3), plus a dip at MH~-22 mag. The shape of the Coma LF in H band is quite similar to th e one found in the B band. The similarity of the LF in the optical and H bands implies that in the central region of Coma there is no new population of galaxies which is too faint to be observed in the optical band (because dust enshrouded, for instance), down to the magnitudes of dwarfs. The exponential cut of the LF at the bright end is in good agreement with the one derived from shallower near-infrared samples o f galaxies, both in clusters and in the field. The faint end of the LF, reaching MH~-19 mag (roughly MB~ -15), is steep, but less than previously suggested from shallower near-infrared observations of an adjacent region in the Coma cluster.

Growth and tolerance of formula with lactoferrin in infants through one year of age: double-blind, randomized, controlled trial.

PubMed

Johnston, William H; Ashley, Claude; Yeiser, Michael; Harris, Cheryl L; Stolz, Suzanne I; Wampler, Jennifer L; Wittke, Anja; Cooper, Timothy R

2015-11-07

Human milk provides necessary macronutrients (protein, carbohydrate, fat) required for infant nutrition. Lactoferrin (Lf), a multifunctional iron-binding protein predominant in human milk, shares similar protein sequence, structure, and bioactivity with bovine Lf (bLf). This large-scale pediatric nutrition study was designed to evaluate growth and tolerance in healthy infants who received study formulas with bLf at concentrations within the range of mature human milk. In this multi-center, double-blind, parallel-designed, gender-stratified prospective study 480 infants were randomized to receive a marketed routine cow's milk-based infant formula (Control; n = 155) or one of two investigational formulas with bLf at 0.6 g/L (LF-0.6; n = 165) or 1.0 g/L (LF-1.0; n = 160) from 14-365 days of age. Investigational formulas also had a prebiotic blend of polydextrose (PDX) and galactooligosaccharides (GOS) and adjusted arachidonic acid (ARA). The primary outcome was weight growth rate from 14-120 days of age. Anthropometric measurements were taken at 14, 30, 60, 90, 120, 180, 275, and 365 days of age. Parental recall of formula intake, tolerance, and stool characteristics was collected at each time point. Medically-confirmed adverse events were collected throughout the study period. There were no group differences in growth rate (g/day) from 14-120 days of age; 353 infants completed the study through 365 days of age ( 110; LF-0.6: 127; LF-1.0: 116). Few differences in growth, formula intake, and infant fussiness or gassiness were observed through 365 day of age. Group discontinuation rates and the overall group incidence of medically-confirmed adverse events were not significantly different. From 30 through 180 days of age, group differences in stool consistency (P < 0.005) were detected with softer stools for infants in the LF-0.6 and LF-1.0 groups versus CONTROL. Compared to the Control, infants who received investigational formulas with bLf and the prebiotic blend of PDX and GOS experienced a softer stooling pattern similar to that reported in breastfed infants. This study demonstrated routine infant formulas with bLf, a blend of PDX and GOS, and adjusted ARA were safe, well-tolerated, and associated with normal growth when fed to healthy term infants through 365 days of age. ClinicalTrials.gov NCT01122654 . Registered 10 May 2010.

Uptake of ingested bovine lactoferrin and its accumulation in adult mouse tissues.

PubMed

Fischer, Romy; Debbabi, Hajer; Blais, Anne; Dubarry, Michel; Rautureau, Michèle; Boyaka, Prosper N; Tome, Daniel

2007-10-01

Lactoferrin is a glycoprotein with antimicrobial and immunoregulatory properties, which is found in milk, other external secretions, and in the secondary granules of neutrophils. The present study examined the time course of uptake and the pattern of tissue accumulation of bovine lactoferrin (bLf) following intragastric intubation of a single dose to adult naïve mice or to mice daily fed bLf for 4 weeks. Following ingestion, bLf was transferred from the intestine into peripheral blood in a form with intact molecular weight (80 kDa) and localized within 10 to 20 min after oral administration in the liver, kidneys, gall bladder, spleen, and brain of both groups of mice. Immunoreactive bLf could also be detected in the luminal contents of the stomach, small intestine and colon 1 h after intragastric intubation. Interestingly, serum and tissue accumulation of bLf was approximately 50% lower in mice chronically fed this protein than in those given only the single oral dose. Furthermore, significant levels of bLf-specific IgA and IgG antibodies as well as bLf-containing IgA- and IgG immune complexes were detected in mice chronically fed bLf but not in those fed only once. Taken together, these results indicate that bLf resists major proteolytic degradation in the intestinal lumen and is readily absorbed in an antigenic form in blood and various mouse tissues. Chronic ingestion of lactoferrin reduces its uptake, probably through mechanisms such as immune exclusion, which minimize potential harmful reactions to food products.

Cost-effectiveness of novel algorithms for rapid diagnosis of tuberculosis in HIV-infected individuals in Uganda.

PubMed

Shah, Maunank; Dowdy, David; Joloba, Moses; Ssengooba, Willy; Manabe, Yukari C; Ellner, Jerrold; Dorman, Susan E

2013-11-28

Xpert MTB/RIF ('Xpert') and urinary lateral-flow lipoarabinomannan (LF-LAM) assays offer rapid tuberculosis (TB) diagnosis. This study evaluated the cost-effectiveness of novel diagnostic algorithms utilizing combinations of Xpert and LF-LAM for the detection of active TB among people living with HIV. Cost-effectiveness analysis using data from a comparative study of LF-LAM and Xpert, with a target population of HIV-infected individuals with signs/symptoms of TB in Uganda. A decision-analysis model compared multiple strategies for rapid TB diagnosis:sputum smear-microscopy; sputum Xpert; smear-microscopy combined with LF-LAM; and Xpert combined with LF-LAM. Primary outcomes were the costs and DALY's averted for each algorithm. Cost-effectiveness was represented using incremental cost-effectiveness ratios (ICER). Compared with an algorithm of Xpert testing alone, the combination of Xpert with LF-LAM was considered highly cost-effective (ICER $57/DALY-averted) at a willingness to pay threshold of Ugandan GDP per capita. Addition of urine LF-LAM testing to smear-microscopy was a less effective strategy than Xpert replacement of smear-microscopy, but was less costly and also considered highly cost-effective (ICER $33 per DALY-averted) compared with continued usage of smear-microscopy alone. Cost-effectiveness of the Xpert plus LF-LAM algorithm was most influenced by HIV/ART costs and life-expectancy of patients after TB treatment. The addition of urinary LF-LAM to TB diagnostic algorithms for HIV-infected individuals is highly cost-effective compared with usage of either sputum smear-microscopy or Xpert alone.

Systematic review: Laparoscopic fundoplication for gastroesophageal reflux disease in partial responders to proton pump inhibitors

PubMed Central

Lundell, Lars; Bell, Martin; Ruth, Magnus

2014-01-01

AIM: To assess laparoscopic fundoplication (LF) in partial responders to proton pump inhibitors (PPIs) for gastroesophageal reflux disease (GERD). METHODS: We systematically searched PubMed and Embase (1966-Dec 2011) for articles reporting data on LF efficacy in partial responders. Due to a lack of randomized controlled trials, observational studies were included. Of 558 articles screened, 17 were eligible for inclusion. Prevalence data for individual symptoms were collated across studies according to mutually compatible time points (before and/or after LF). Where suitable, prevalence data were presented as percentage of patients reporting symptoms of any frequency or severity. RESULTS: Due to a lack of standardized reporting of symptoms, the proportion of patients experiencing symptoms was recorded across studies where possible. After LF, the proportion of partial responders with heartburn was reduced from 93.1% (5 studies) to 3.8% (5 studies), with similar results observed for regurgitation [from 78.4% (4 studies) to 1.9% (4 studies)]. However, 10 years after LF, 35.8% (2 studies) of partial responders reported heartburn and 29.1% (1 study) reported regurgitation. The proportion using acid-suppressive medication also increased, from 8.8% (4 studies) in the year after LF to 18.2% (2 studies) at 10 years. In the only study comparing partial responders to PPI therapy with complete responders, higher symptom scores and more frequent acid-suppressive medication use were seen in partial responders after LF. CONCLUSION: GERD symptoms improve after LF, but subsequently recur, and acid-suppressive medication use increases. LF may be less effective in partial responders than in complete responders. PMID:24574753

Crowdsourcing a Spatial Temporal Study of Low Frequency (LF) Propagation Effects Due to a Total Solar Eclipse: Engaging Students and Citizens in STEM

NASA Astrophysics Data System (ADS)

Lumsden, N. A.; Lukes, L.; Nelson, J.; Liles, W. C.; Kerby, K. C.; Crowov, F.; Rockway, J.

2015-12-01

The first experiments to study the effects of a solar eclipse on radio wave propagation were done in 1912 utilizing Low Frequency (LF; 30 - 300 kHz) radio waves at a handful of sites across Europe before any theory of the ionosphere had been confirmed and even before the word "ionosphere" existed. In the 1920s, a large cooperative experiment was promoted in the U.S. by Scientific American magazine. They collected over 2000 reports of AM broadcast stations from throughout the U.S. Unfortunately, many of the submissions were unusable because they lacked critical information such as date, time or location. We propose to use the 2017 solar eclipse over the continental U.S. to conduct the first wide-area LF propagation study. To perform this study, we plan to crowdsource the collection of the data by engaging student groups, citizens, and the scientific community. The tools for the different collection stations will consist of a simple homemade antenna, a simple receiver to convert the radio frequency (RF) signals to audio frequencies and a smart phone app. By using the time, date and location features of the smart phone, the problems experienced in the Scientific American experiment will be minimized. By crowdsourcing the observation sites, a number of different short, medium and long-paths studies can be obtained as the total eclipse crosses the continental U.S. The transmitter for this experiment will be WWVB located near Fort Collins, Colorado on 60.000 kHz. This is a U.S. frequency standard that is operated by NIST and transmits time codes. A second frequency, 55.500 kHz transmitted by a LF station in Dixon, CA is also being considered for this experiment. We will present an overall strategy for recruiting participants/crowdsourcing the RF collections during the 2017 total solar eclipse. Preliminary coverage calculations will be presented for WWVB and Dixon, as well as path loss calculations that can be expected during the solar eclipse condition. We will also present the 2016 plan to pilot/refine the design of the RF collection system (e.g., antenna, app) with multiple teams to help ensure project success during the eclipse. Also, we wish to solicit input from AGU attendees on how to increase participation and improve the experiment. Lastly, we will announce social media, website, and standards-based curriculum resources.

Very High Frequency Radio Emissions Associated With the Production of Terrestrial Gamma-Ray Flashes

NASA Astrophysics Data System (ADS)

Lyu, Fanchao; Cummer, Steven A.; Krehbiel, Paul R.; Rison, William; Briggs, Michael S.; Cramer, Eric; Roberts, Oliver; Stanbro, Matthew

2018-02-01

Recent studies of the close association between terrestrial gamma-ray flashes (TGFs) production and simultaneous lightning processes have shown that many TGFs are produced during the initial leader of intracloud flashes and that some low-frequency (LF) radio emissions may directly come from TGF itself. Measurements of any simultaneous very high frequency (VHF) radio emissions would give important insight into any lightning leader dynamics that are associated with TGF generation, and thus, such measurements are needed. Here we report on coordinated observations of TGFs detected simultaneously by Fermi Gamma-ray Burst Monitor, two VHF lightning mapping arrays, and Duke ground-based LF radio sensors to investigate more on the close association between TGFs and LF and VHF radio emissions. Three TGFs are analyzed here and confirm previous findings on the close association between TGF generation and lightning processes and, for the first time, provide time-aligned measurements of the VHF radio signature within a few tens of microseconds of TGF generation. Strong VHF emissions were observed essentially simultaneously with two TGFs and within a few tens of microseconds of a third TGF. Equally importantly, the VHF measurement details indicate that the TGF-associated emissions are nonimpulsive and extended in time. We conclude that the TGF-producing process is at least sometimes closely associated with strong VHF emissions, and thus, there may be a link between the generation of TGFs and active lightning streamer dynamics.

Emerging trends in Lassa fever: redefining the role of immunoglobulin M and inflammation in diagnosing acute infection

PubMed Central

2011-01-01

Background Lassa fever (LF) is a devastating hemorrhagic viral disease that is endemic to West Africa and responsible for thousands of human deaths each year. Analysis of humoral immune responses (IgM and IgG) by antibody-capture ELISA (Ab-capture ELISA) and Lassa virus (LASV) viremia by antigen-capture ELISA (Ag-capture ELISA) in suspected patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW) in Sierra Leone over the past five years is reshaping our understanding of acute LF. Results Analyses in LF survivors indicated that LASV-specific IgM persists for months to years after initial infection. Furthermore, exposure to LASV appeared to be more prevalent in historically non-endemic areas of West Africa with significant percentages of reportedly healthy donors IgM and IgG positive in LASV-specific Ab-capture ELISA. We found that LF patients who were Ag positive were more likely to die than suspected cases who were only IgM positive. Analysis of metabolic and immunological parameters in Ag positive LF patients revealed a strong correlation between survival and low levels of IL-6, -8, -10, CD40L, BUN, ALP, ALT, and AST. Despite presenting to the hospital with fever and in some instances other symptoms consistent with LF, the profiles of Ag negative IgM positive individuals were similar to those of normal donors and nonfatal (NF) LF cases, suggesting that IgM status cannot necessarily be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. Conclusion Only LASV viremia assessed by Ag-capture immunoassay, nucleic acid detection or virus isolation should be used to diagnose acute LASV infection in West Africans. LASV-specific IgM serostatus cannot be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. By applying these criteria, we identified a dysregulated metabolic and pro-inflammatory response profile conferring a poor prognosis in acute LF. In addition to suggesting that the current diagnostic paradigm for acute LF should be reconsidered, these studies present new opportunities for therapeutic interventions based on potential prognostic markers in LF. PMID:22023795

Stored Radioactive Material Landfill Site no. 7 (LF-7), Massachusetts Military Reservation, Cape Cod, MA

DTIC Science & Technology

2013-03-07

Consultative Letter 3. DATES COVERED (From – To) July 2012 – January 2013 4. TITLE AND SUBTITLE Stored Radioactive Material Landfill Site #7 (LF-7...performed 9-13 Jul 2012 at the stored radioactive material landfill site (LF-7) on Camp Edwards, Massachusetts Military Reservation, Cape Cod, MA...Walkover surveillance and environmental sampling were used to characterize any radioactive material presence at the LF-7 site. No observable or

UNC-1 regulates gap junctions important to locomotion in C. elegans.

PubMed

Chen, Bojun; Liu, Qiang; Ge, Qian; Xie, Jia; Wang, Zhao-Wen

2007-08-07

In C. elegans, loss-of-function (lf) mutations of the stomatin-like protein (SLP) UNC-1 and the innexin UNC-9 inhibit locomotion [1, 2] and modulate sensitivity to volatile anesthetics [3, 4]. It was unknown why unc-1(lf) and unc-9(lf) mutants have similar phenotypes. We tested the hypothesis that UNC-1 is a regulator of gap junctions formed by UNC-9. Analyses of junctional currents between body-wall muscle cells showed that electrical coupling was inhibited to a similar degree in unc-1(lf), unc-9(lf), and unc-1(lf);unc-9(lf) double mutants, suggesting that UNC-1 and UNC-9 function together. Expression of Punc-1::DsRED2 and Punc-9::GFP transcriptional fusions suggests that unc-1 and unc-9 are coexpressed in neurons and body-wall muscle cells. Immunohistochemistry showed that UNC-1 and UNC-9 colocalized at intercellular junctions and that unc-1(lf) did not alter UNC-9 expression or subcellular localization. Bimolecular fluorescence complementation (BiFC) assays suggest that UNC-1 and UNC-9 are physically very close at intercellular junctions. Targeted rescue experiments suggest that UNC-9 and UNC-1 function predominantly in neurons to control locomotion. Thus, in addition to the recently reported function of regulating mechanosensitive ion channels [5, 6], SLPs might have a novel function of regulating gap junctions.

Neuroprotection against apoptosis of SK-N-MC cells using RMP-7- and lactoferrin-grafted liposomes carrying quercetin

PubMed Central

Kuo, Yung-Chih; Tsao, Chien-Wei

2017-01-01

A drug delivery system of quercetin (QU)-encapsulated liposomes (LS) grafted with RMP-7, a bradykinin analog, and lactoferrin (Lf) was developed to permeate the blood–brain barrier (BBB) and rescue degenerated neurons, acting as an Alzheimer’s disease (AD) pharmacotherapy. This colloidal formulation of QU-encapsulated LS grafted with RMP-7 and Lf (RMP-7-Lf-QU-LS) was used to traverse human brain microvascular endothelial cells (HBMECs) regulated by human astrocytes (HAs) and to treat SK-N-MC cells after an insult with cytotoxic β-amyloid (Aβ) fibrils. We found that surface RMP-7 and Lf enhanced the ability of QU to cross the BBB without inducing strong toxicity and damaging the tight junction. In addition, RMP-7-Lf-QU-LS significantly reduced Aβ-induced neurotoxicity and improved the viability of SK-N-MC cells. Compared with free QU, RMP-7-Lf-QU-LS could also significantly inhibit the expression of phosphorylated c-Jun N terminal kinase, phosphorylated p38, and phosphorylated tau protein at serine 202 by SK-N-MC cells, indicating an important role of RMP-7, Lf, and LS in protecting neurons against apoptosis. RMP-7-Lf-QU-LS is a promising carrier targeting the BBB to prevent Aβ-insulted neurodegeneration and may have potential in managing AD in future clinical applications. PMID:28435263

Ceruloplasmin: Macromolecular Assemblies with Iron-Containing Acute Phase Proteins

PubMed Central

Samygina, Valeriya R.; Sokolov, Alexey V.; Bourenkov, Gleb; Petoukhov, Maxim V.; Pulina, Maria O.; Zakharova, Elena T.; Vasilyev, Vadim B.; Bartunik, Hans; Svergun, Dmitri I.

2013-01-01

Copper-containing ferroxidase ceruloplasmin (Cp) forms binary and ternary complexes with cationic proteins lactoferrin (Lf) and myeloperoxidase (Mpo) during inflammation. We present an X-ray crystal structure of a 2Cp-Mpo complex at 4.7 Å resolution. This structure allows one to identify major protein–protein interaction areas and provides an explanation for a competitive inhibition of Mpo by Cp and for the activation of p-phenylenediamine oxidation by Mpo. Small angle X-ray scattering was employed to construct low-resolution models of the Cp-Lf complex and, for the first time, of the ternary 2Cp-2Lf-Mpo complex in solution. The SAXS-based model of Cp-Lf supports the predicted 1∶1 stoichiometry of the complex and demonstrates that both lobes of Lf contact domains 1 and 6 of Cp. The 2Cp-2Lf-Mpo SAXS model reveals the absence of interaction between Mpo and Lf in the ternary complex, so Cp can serve as a mediator of protein interactions in complex architecture. Mpo protects antioxidant properties of Cp by isolating its sensitive loop from proteases. The latter is important for incorporation of Fe3+ into Lf, which activates ferroxidase activity of Cp and precludes oxidation of Cp substrates. Our models provide the structural basis for possible regulatory role of these complexes in preventing iron-induced oxidative damage. PMID:23843990

Novel lactoferrin-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) copolymer nanobubbles for tumor-targeting ultrasonic imaging

PubMed Central

Luo, Binhua; Liang, Huageng; Zhang, Shengwei; Qin, Xiaojuan; Liu, Xuhan; Liu, Wei; Zeng, Fuqing; Wu, Yun; Yang, Xiangliang

2015-01-01

In the study reported here, a novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer was synthesized by ring-opening polymerization reaction. The perfluoropentane-filled PAEEP-PLLA nanobubbles (NBs) were prepared using the O1/O2/W double-emulsion and solvent-evaporation method, with the copolymer as the shell and liquid perfluoropentane as the core of NBs. The prepared NBs were further conjugated with lactoferrin (Lf) for tumor-cell targeting. The resulting Lf-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) nanobubbles (Lf-PAEEP-PLLA NBs) were characterized by photon correlation spectroscopy, polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy, and transmission electron microscopy. The average size of the Lf-PAEEP-PLLA NBs was 328.4±5.1 nm, with polydispersity index of 0.167±0.020, and zeta potential of −12.6±0.3 mV. Transmission electron microscopy imaging showed that the Lf-PAEEP-PLLA NBs had a near-spherical structure, were quite monodisperse, and there was a clear interface between the copolymer shell and the liquid core inside the NBs. The Lf-PAEEP-PLLA NBs also exhibited good biocompatibility in cytotoxicity and hemolysis studies and good stability during storage. The high cellular uptake of Lf-PAEEP-PLLA NBs in C6 cells (low-density lipoprotein receptor-related protein 1-positive cells) at concentrations of 0–20 µg/mL indicated that the Lf provided effective targeting for brain-tumor cells. The in vitro acoustic behavior of Lf-PAEEP-PLLA NBs was evaluated using a B-mode clinical ultrasound imaging system. In vivo ultrasound imaging was performed on tumor-bearing BALB/c nude mice, and compared with SonoVue® microbubbles, a commercial ultrasonic contrast agent. Both in vitro and in vivo ultrasound imaging indicated that the Lf-PAEEP-PLLA NBs possessed strong, long-lasting, and tumor-enhanced ultrasonic contrast ability. Taken together, these results indicate that Lf-PAEEP-PLLA NBs represent a promising nano-sized ultrasonic contrast agent for tumor-targeting ultrasonic imaging. PMID:26396514

Novel lactoferrin-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) copolymer nanobubbles for tumor-targeting ultrasonic imaging.

PubMed

Luo, Binhua; Liang, Huageng; Zhang, Shengwei; Qin, Xiaojuan; Liu, Xuhan; Liu, Wei; Zeng, Fuqing; Wu, Yun; Yang, Xiangliang

2015-01-01

In the study reported here, a novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer was synthesized by ring-opening polymerization reaction. The perfluoropentane-filled PAEEP-PLLA nanobubbles (NBs) were prepared using the O1/O2/W double-emulsion and solvent-evaporation method, with the copolymer as the shell and liquid perfluoropentane as the core of NBs. The prepared NBs were further conjugated with lactoferrin (Lf) for tumor-cell targeting. The resulting Lf-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) nanobubbles (Lf-PAEEP-PLLA NBs) were characterized by photon correlation spectroscopy, polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy, and transmission electron microscopy. The average size of the Lf-PAEEP-PLLA NBs was 328.4±5.1 nm, with polydispersity index of 0.167±0.020, and zeta potential of -12.6±0.3 mV. Transmission electron microscopy imaging showed that the Lf-PAEEP-PLLA NBs had a near-spherical structure, were quite monodisperse, and there was a clear interface between the copolymer shell and the liquid core inside the NBs. The Lf-PAEEP-PLLA NBs also exhibited good biocompatibility in cytotoxicity and hemolysis studies and good stability during storage. The high cellular uptake of Lf-PAEEP-PLLA NBs in C6 cells (low-density lipoprotein receptor-related protein 1-positive cells) at concentrations of 0-20 µg/mL indicated that the Lf provided effective targeting for brain-tumor cells. The in vitro acoustic behavior of Lf-PAEEP-PLLA NBs was evaluated using a B-mode clinical ultrasound imaging system. In vivo ultrasound imaging was performed on tumor-bearing BALB/c nude mice, and compared with SonoVue(®) microbubbles, a commercial ultrasonic contrast agent. Both in vitro and in vivo ultrasound imaging indicated that the Lf-PAEEP-PLLA NBs possessed strong, long-lasting, and tumor-enhanced ultrasonic contrast ability. Taken together, these results indicate that Lf-PAEEP-PLLA NBs represent a promising nano-sized ultrasonic contrast agent for tumor-targeting ultrasonic imaging.

A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumann, Brian C.; Guzzo, Thomas J.; He Jiwei

2013-01-01

Purpose: Local-regional failures (LF) following radical cystectomy (RC) plus pelvic lymph node dissection (PLND) with or without chemotherapy for invasive urothelial bladder carcinoma are more common than previously reported. Adjuvant radiation therapy (RT) could reduce LF but currently has no defined role because of previously reported morbidity. Modern techniques with improved normal tissue sparing have rekindled interest in RT. We assessed the risk of LF and determined those factors that predict recurrence to facilitate patient selection for future adjuvant RT trials. Methods and Materials: From 1990-2008, 442 patients with urothelial bladder carcinoma at University of Pennsylvania were prospectively followed aftermore » RC plus PLND with or without chemotherapy with routine pelvic computed tomography (CT) or magnetic resonance imaging (MRI). One hundred thirty (29%) patients received chemotherapy. LF was any pelvic failure detected before or within 3 months of distant failure. Competing risk analyses identified factors predicting increased LF risk. Results: On univariate analysis, pathologic stage {>=}pT3, <10 nodes removed, positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology significantly predicted LF; node density was marginally predictive, but use of chemotherapy, number of positive nodes, type of surgical diversion, age, gender, race, smoking history, and body mass index were not. On multivariate analysis, only stage {>=}pT3 and <10 nodes removed were significant independent LF predictors with hazard ratios of 3.17 and 2.37, respectively (P<.01). Analysis identified 3 patient subgroups with significantly different LF risks: low-risk ({<=}pT2), intermediate-risk ({>=}pT3 and {>=}10 nodes removed), and high-risk ({>=}pT3 and <10 nodes) with 5-year LF rates of 8%, 23%, and 42%, respectively (P<.01). Conclusions: This series using routine CT and MRI surveillance to detect LF confirms that such failures are relatively common in cases of locally advanced disease and provides a rubric based on pathological stage and number of nodes removed that stratifies patients into 3 groups with significantly different LF risks to simplify patient selection for future adjuvant radiation therapy trials.« less

Patterns of Failure After Radical Cystectomy for pT3-4 Bladder Cancer: Implications for Adjuvant Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reddy, Abhinav V.; Pariser, Joseph J.; Pearce, Shane M.

2016-04-01

Purpose: In patients with muscle-invasive bladder cancer, local-regional failure (LF) has been reported to occur in up to 20% of patients following radical cystectomy. The goals of this study were to describe patterns of LF, as well as assess factors associated with LF in a cohort of patients with pT3-4 bladder cancer. This information may have implications towards the use of adjuvant radiation therapy. Methods and Materials: Patients with pathologic T3-4 N0-1 bladder cancer were examined from an institutional radical cystectomy database. Preoperative demographics and pathologic characteristics were examined. Outcomes included overall survival and LF. Local-regional failures were defined usingmore » follow-up imaging reports and scans, and the locations of LF were characterized. Variables were tested by univariate and multivariate analysis for association with LF and overall survival. Results: A total of 334 patients had pT3-4 and N0-1 disease after radical cystectomy and bilateral pelvic lymph node dissection. Of these, 46% received perioperative chemotherapy. The median age was 71 years old, and median follow-up was 11 months. On univariate analysis, margin status, pT stage, and pN stage, were all associated with LF (P<.05), however, on multivariate analysis, only pT and pN stages were significantly associated with LF (P<.05). Three strata of risk were defined, including low-risk patients with pT3N0 disease, intermediate-risk patients with pT3N1 or pT4N0 disease, and high-risk patients with pT4N1 disease, who had a 2-year incidence of LF of 12%, 33%, and 72%, respectively. The most common sites of pelvic relapse included the external and internal iliac lymph nodes (LNs) and obturator LN regions. Notably, 34% of patients with LF had local-regional only disease at the time of recurrence. Conclusions: Patients with pT4 or N1 disease have a 2-year risk of LF that exceeds 30%. These patients may be the most likely to benefit from local adjuvant therapies.« less

Lymphatic filariasis in Peninsular Malaysia: a cross-sectional survey of the knowledge, attitudes, and practices of residents.

PubMed

Al-Abd, Nazeh M; Nor, Zurainee Mohamed; Ahmed, Abdulhamid; Al-Adhroey, Abdulelah H; Mansor, Marzida; Kassim, Mustafa

2014-11-27

Lymphatic filariasis (LF) is a major cause of permanent disability in many tropical and sub-tropical countries of the world. Malaysia is one of the countries in which LF is an endemic disease. Five rounds of the mass drug administration (MDA) program have been conducted in Malaysia as part of the Global Program to Eliminate Lymphatic Filariasis (GPELF) by year 2020. This study investigated the level of awareness of LF and the MDA program in a population living in an endemic area of the country. A descriptive cross-sectional survey that involved 230 respondents (≥15 years old) living in the LF endemic communities of Terengganu state in Peninsular Malaysia was performed. Demographic, socioeconomic, and knowledge, attitudes and practices (KAP) data of the respondents were obtained using pre-tested questionnaires and were analyzed using SPSS software version 13.0. More than 80% of the respondents were aware of LF and the common symptoms of the disease. Moreover, about 70% of the respondents that were aware of LF indicated that it is a problematic disease. Approximately 77% of the respondents indicated that filariasis is transmitted by mosquitoes. Two-thirds of respondents preferred hospital treatment for illness; however, only 12% had participated and/or received treatment for LF during an MDA program. Only 35% of the respondents that participated in this research were aware of the MDA program that had taken place in the area. None of the respondents had knowledge of the drug used in the treatment of LF. The findings from this research indicated that there was no significant association between LF awareness and with gender, age group, educational status, occupation, or socio-economic status of the respondents (P >0.05). A good proportion of the respondents are aware of LF, its mode of transmission and symptoms, however they demonstrated a poor knowledge of MDA which took place in the study area. For greater understanding of LF in the Malaysian population, there is a need for an enhancement in the delivery of health education and information programs and mass mobilization campaigns in endemic communities.

Assessing the feasibility of integration of self-care for filarial lymphoedema into existing community leprosy self-help groups in Nepal.

PubMed

Pryce, Joseph; Mableson, Hayley E; Choudhary, Ramesh; Pandey, Basu Dev; Aley, Dambar; Betts, Hannah; Mackenzie, Charles D; Kelly-Hope, Louise A; Cross, Hugh

2018-01-30

Lymphatic filariasis (LF) and leprosy are disabling infectious diseases endemic in Nepal. LF infection can lead to lymphoedema and hydrocoele, while secondary effects of leprosy infection include impairments to hands, eyes and feet. The disabling effects of both conditions can be managed through self-care and the supportive effects of self-help groups (SHGs). A network of SHGs exists for people affected by leprosy in four districts in Nepal's Central Development Region, however no such service exists for people affected by LF. The aim of this study was to determine the feasibility of integrating LF affected people into existing leprosy SHGs in this area. A survey was conducted using a semi-structured questionnaire to elicit information on: (i) participant characteristics, clinical manifestation and disease burden; (ii) participants' knowledge of management of their condition and access to services; and (iii) participants' knowledge and perceptions of the alternate condition (LF affected participants' knowledge of leprosy and vice versa) and attitudes towards integration. A total of 52 LF affected and 53 leprosy affected participants were interviewed from 14 SHGs. On average, leprosy affected participants were shown to have 1.8 times greater knowledge of self-care techniques, and practiced 2.5 times more frequently than LF affected participants. Only a quarter of LF affected participants had accessed a health service for their condition, compared with 94.3% of leprosy affected people accessing a service (including SHGs), at least once a week. High levels of stigma were perceived by both groups towards the alternate condition, however, the majority of LF (79%) and leprosy (94.3%) affected participants stated that they would consider attending an integrated SHG. LF affected participants need to increase their knowledge of self-care and access to health services. Despite stigma being a potential barrier, attitudes towards integration were positive, suggesting that the SHGs may be a good platform for LF affected people to start self-care in this area. This is not a registered trial.

A finer view of the conditional galaxy luminosity function and magnitude-gap statistics

NASA Astrophysics Data System (ADS)

Trevisan, M.; Mamon, G. A.

2017-10-01

The gap between first- and second-ranked galaxy magnitudes in groups is often considered a tracer of their merger histories, which in turn may affect galaxy properties, and also serves to test galaxy luminosity functions (LFs). We remeasure the conditional luminosity function (CLF) of the Main Galaxy Sample of the SDSS in an appropriately cleaned subsample of groups from the Yang catalogue. We find that, at low group masses, our best-fitting CLF has steeper satellite high ends, yet higher ratios of characteristic satellite to central luminosities in comparison with the CLF of Yang et al. The observed fractions of groups with large and small magnitude gaps as well as the Tremaine & Richstone statistics are not compatible with either a single Schechter LF or with a Schechter-like satellite plus lognormal central LF. These gap statistics, which naturally depend on the size of the subsamples, and also on the maximum projected radius, Rmax, for defining the second brightest galaxy, can only be reproduced with two-component CLFs if we allow small gap groups to preferentially have two central galaxies, as expected when groups merge. Finally, we find that the trend of higher gap for higher group velocity dispersion, σv, at a given richness, discovered by Hearin et al., is strongly reduced when we consider σv in bins of richness, and virtually disappears when we use group mass instead of σv. This limits the applicability of gaps in refining cosmographic studies based on cluster counts.

D-region Ionospheric Imaging Using VLF/LF Broadband Sferics, Forward Modeling, and Tomography

NASA Astrophysics Data System (ADS)

McCormick, J.; Cohen, M.

2017-12-01

The D-region of the ionosphere (60-90 km altitude) is highly variable on timescales from fractions of a second to many hours, and on spatial scales from 10 km to many hundreds of km. VLF and LF (3-30kHz, 30-300kHz) radio waves are guided to global distances by reflecting off of the ground and the D-region, making the Earth-ionosphere waveguide (EIWG). Therefore, information about the current state of the ionosphere is encoded in received VLF/LF radio waves since they act like probes of the D-region. The return stroke of lightning is an impulsive event that radiates powerful broadband radio emissions in VLF/LF bands known as `radio atmospherics' or `sferics'. Lightning flashes occur about 40-50 times per second throughout the Earth. An average of 2000 lightning storms occur each day with a mean duration of 30 minutes creating a broad spatial and temporal distribution of lightning VLF/LF sources. With careful processing, we can recover high fidelity measurements of amplitude and phase of both the radial and azimuthal magnetic field sferic components. By comparison to a theoretical EIWG propagation model such as the Long Wave Propagation Capability (LWPC) developed by the US Navy, with a standard forward modeling approach, we can infer information about the current state of the D-region. Typically, the ionosphere is parametrized to reduce the dimensionality of the problem which usually results in an electron density vs altitude profile. For large distances (Greater than 1000 km), these results can be interpreted as path-averaged information. In contrast to studies using navy transmitters to study the D-region, the full spectral information allows for more complete information and less ambiguous inferred ionospheric parameters. With the spatial breadth of lightning sources taken together with a broadly distributed VLF/LF receiver network, a dense set of measurements are acquired in a tomographic sense. Using the wealth of linear algebra and imaging techniques it is possible to produce a 2D image of the D-region electron density profile.

Validating a Local Failure Risk Stratification for Use in Prospective Studies of Adjuvant Radiation Therapy for Bladder Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumann, Brian C.; He, Jiwei; Hwang, Wei-Ting

Purpose: To inform prospective trials of adjuvant radiation therapy (adj-RT) for bladder cancer after radical cystectomy, a locoregional failure (LF) risk stratification was proposed. This stratification was developed and validated using surgical databases that may not reflect the outcomes expected in prospective trials. Our purpose was to assess sources of bias that may affect the stratification model's validity or alter the LF risk estimates for each subgroup: time bias due to evolving surgical techniques; trial accrual bias due to inclusion of patients who would be ineligible for adj-RT trials because of early disease progression, death, or loss to follow-up shortlymore » after cystectomy; bias due to different statistical methods to estimate LF; and subgrouping bias due to different definitions of the LF subgroups. Methods and Materials: The LF risk stratification was developed using a single-institution cohort (n=442, 1990-2008) and the multi-institutional SWOG 8710 cohort (n=264, 1987-1998) treated with radical cystectomy with or without chemotherapy. We evaluated the sensitivity of the stratification to sources of bias using Fine-Gray regression and Kaplan-Meier analyses. Results: Year of radical cystectomy was not associated with LF risk on univariate or multivariate analysis after controlling for risk group. By use of more stringent inclusion criteria, 26 SWOG patients (10%) and 60 patients from the single-institution cohort (14%) were excluded. Analysis of the remaining patients confirmed 3 subgroups with significantly different LF risks with 3-year rates of 7%, 17%, and 36%, respectively (P<.01), nearly identical to the rates without correcting for trial accrual bias. Kaplan-Meier techniques estimated higher subgroup LF rates than competing risk analysis. The subgroup definitions used in the NRG-GU001 adj-RT trial were validated. Conclusions: These sources of bias did not invalidate the LF risk stratification or substantially change the model's LF estimates.« less

Partnering for impact: Integrated transmission assessment surveys for lymphatic filariasis, soil transmitted helminths and malaria in Haiti.

PubMed

Knipes, Alaine Kathryn; Lemoine, Jean Frantz; Monestime, Franck; Fayette, Carl R; Direny, Abdel N; Desir, Luccene; Beau de Rochars, Valery E; Streit, Thomas G; Renneker, Kristen; Chu, Brian K; Chang, Michelle A; Mace, Kimberly E; Won, Kimberly Y; Lammie, Patrick J

2017-02-01

Since 2001, Haiti's National Program for the Elimination of Lymphatic Filariasis (NPELF) has worked to reduce the transmission of lymphatic filariasis (LF) through annual mass drug administration (MDA) with diethylcarbamazine and albendazole. The NPELF reached full national coverage with MDA for LF in 2012, and by 2014, a total of 14 evaluation units (48 communes) had met WHO eligibility criteria to conduct LF transmission assessment surveys (TAS) to determine whether prevalence had been reduced to below a threshold, such that transmission is assumed to be no longer sustainable. Haiti is also endemic for malaria and many communities suffer a high burden of soil transmitted helminths (STH). Heeding the call from WHO for integration of neglected tropical diseases (NTD) activities, Haiti's NPELF worked with the national malaria control program (NMCP) and with partners to develop an integrated TAS (LF-STH-malaria) to include assessments for malaria and STH. The aim of this study was to evaluate the feasibility of using TAS surveys for LF as a platform to collect information about STH and malaria. Between November 2014 and June 2015, TAS were conducted in 14 evaluation units (EUs) including 1 TAS (LF-only), 1 TAS-STH-malaria, and 12 TAS-malaria, with a total of 16,655 children tested for LF, 14,795 tested for malaria, and 298 tested for STH. In all, 12 of the 14 EUs passed the LF TAS, allowing the program to stop MDA for LF in 44 communes. The EU where children were also tested for STH will require annual school-based treatment with albendazole to maintain reduced STH levels. Finally, only 12 of 14,795 children tested positive for malaria by RDT in 38 communes. Haiti's 2014-2015 Integrated TAS surveys provide evidence of the feasibility of using the LF TAS as a platform for integration of assessments for STH and or malaria.

Lactoferrin-derived resistance against plant pathogens in transgenic plants.

PubMed

Lakshman, Dilip K; Natarajan, Savithiry; Mandal, Sudhamoy; Mitra, Amitava

2013-12-04

Lactoferrin (LF) is a ubiquitous cationic iron-binding milk glycoprotein that contributes to nutrition and exerts a broad-spectrum primary defense against bacteria, fungi, protozoa, and viruses in mammals. These qualities make lactoferrin protein and its antimicrobial motifs highly desirable candidates to be incorporated in plants to impart broad-based resistance against plant pathogens or to economically produce them in bulk quantities for pharmaceutical and nutritional purposes. This study introduced bovine LF (BLF) gene into tobacco ( Nicotiana tabacum var. Xanthi), Arabidopsis ( A. thaliana ) and wheat ( Triticum aestivum ) via Agrobacterium -mediated plant transformation. Transgenic plants or detached leaves exhibited high levels of resistance against the damping-off causing fungal pathogen Rhizoctonia solani and the head blight causing fungal pathogen Fusarium graminearum . LF also imparted resistance to tomato plants against a bacterial pathogen, Ralstonia solanacearum . Similarly, other researchers demonstrated expression of LF and LF-mediated high-quality resistance to several other aggressive fungal and bacterial plant pathogens in transgenic plants and against viral pathogens by foliar applications of LF or its derivatives. Taken together, these studies demonstrated the effectiveness of LF for improving crop quality and its biopharming potentials for pharmaceautical and nutritional applications.

Two splice variants of the bovine lactoferrin gene identified in Staphylococcus aureus isolated from mastitis in dairy cattle.

PubMed

Huang, J M; Wang, Z Y; Ju, Z H; Wang, C F; Li, Q L; Sun, T; Hou, Q L; Hang, S Q; Hou, M H; Zhong, J F

2011-12-21

Bovine lactoferrin (bLF) is a member of the transferrin family; it plays an important role in the innate immune response. We identified novel splice variants of the bLF gene in mastitis-infected and healthy cows. Reverse transcription-polymerase chain reaction (RT-PCR) and clone sequencing analysis were used to screen the splice variants of the bLF gene in the mammary gland, spleen and liver tissues. One main transcript corresponding to the bLF reference sequence was found in three tissues in both healthy and mastitis-infected cows. Quantitative real-time PCR analysis showed that the expression levels of the LF gene's main transcript were not significantly different in tissues from healthy versus mastitis-infected cows. However, the new splice variant, LF-AS2, which has the exon-skipping alternative splicing pattern, was only identified in mammary glands infected with Staphylococcus aureus. Sequencing analysis showed that the new splice variant was 251 bp in length, including exon 1, part of exon 2, part of exon 16, and exon 17. We conclude that bLF may play a role in resistance to mastitis through alternative splicing mechanisms.

Inhibition of HSV cell-to-cell spread by lactoferrin and lactoferricin.

PubMed

Jenssen, Håvard; Sandvik, Kjersti; Andersen, Jeanette H; Hancock, Robert E W; Gutteberg, Tore J

2008-09-01

The milk protein lactoferrin (Lf) has multiple functions, including immune stimulation and antiviral activity towards herpes simplex virus 1 and 2 (HSV-1 and HSV-2); antiviral activity has also been reported for the N-terminal pepsin-derived fragment lactoferricin (Lfcin). The anti-HSV mode of action of Lf and Lfcin is assumed to involve, in part, their interaction with the cell surface glycosaminoglycan heparan sulfate, thereby blocking of viral entry. In this study we investigated the ability of human and bovine Lf and Lfcin to inhibit viral cell-to-cell spread as well as the involvement of cell surface glycosaminoglycans during viral cell-to-cell spread. Lf and Lfcin from both human and bovine origin, inhibited cell-to-cell spread of both HSV-1 and HSV-2. Inhibition of cell-to-cell spread by bovine Lfcin involved cell surface chondroitin sulfate. Based on transmission electron microscopy studies, human Lfcin, like bovine Lfcin, was randomly distributed intracellularly, thus differences in their antiviral activity could not be explained by differences in their distribution. In contrast, the cellular localization of iron-saturated (holo)-Lf appeared to differ from that of apo-Lf, indicating that holo- and apo-Lf may exhibit different antiviral mechanisms.

Apoptotic effects of bovine apo-lactoferrin on HeLa tumor cells.

PubMed

Luzi, Carla; Brisdelli, Fabrizia; Iorio, Roberto; Bozzi, Argante; Carnicelli, Veronica; Di Giulio, Antonio; Lizzi, Anna Rita

2017-01-01

Lactoferrin (Lf), a cationic iron-binding glycoprotein of 80 kDa present in body secretions, is known as a compound with marked antimicrobial activity. In the present study, the apoptotic effect of iron-free bovine lactoferrin (apo-bLf) on human epithelial cancer (HeLa) cells was examined in association with reactive oxygen species and glutathione (GSH) levels. Apoptotic effect of iron-free bovine lactoferrin inhibited the growth of HeLa cells after 48 hours of treatment while the diferric-bLf was ineffective in the concentration range tested (from 1 to 12.5 μM). Western blot analysis showed that key apoptotic regulators including Bax, Bcl-2, Sirt1, Mcl-1, and PARP-1 were modulated by 1.25 μM of apo-bLf. In the same cell line, apo-bLf induced apoptosis together with poly (ADP-ribose) polymerase cleavage, caspase activation, and a significant drop of NAD + . In addition, apo-bLf-treated HeLa cells showed a marked increase of reactive oxygen species level and a significant GSH depletion. On the whole, apo-bLf triggered apoptosis of HeLa cells upon oxygen radicals burst and GSH decrease. Copyright © 2017 John Wiley & Sons, Ltd.

Therapeutic Effect of Activated Carbon-Induced Constipation Mice with Lactobacillus fermentum Suo on Treatment

PubMed Central

Suo, Huayi; Zhao, Xin; Qian, Yu; Li, Guijie; Liu, Zhenhu; Xie, Jie; Li, Jian

2014-01-01

The aim of this study was to investigate the effects of Lactobacillus fermentum Suo (LF-Suo) on activated carbon-induced constipation in ICR (Institute of Cancer Research) mice. ICR mice were orally administered with lactic acid bacteria for 9 days. Body weight, diet intake, drinking amount, defecation status, gastrointestinal transit and defecation time, and the serum levels of MTL (motilin), Gas (gastrin), ET (endothelin), SS (somatostatin), AChE (acetylcholinesterase), SP (substance P), VIP (vasoactive intestinal peptide) were used to evaluate the preventive effects of LF-Suo on constipation. Bisacodyl, a laxative drug, was used as a positive control. The normal, control, 100 mg/kg bisacodyl treatment, LB (Lactobacillus bulgaricus)-, LF-Suo (L)- and LF-Suo (H)-treated mice showed the time to the first black stool defecation at 90, 218, 117, 180, 155 and 137 min, respectively. By the oral administration of LB-, LF-Suo (L), LF-Suo (H) or bisacodyl (100 mg/kg), the gastrointestinal transit was reduced to 55.2%, 72.3%, 85.5% and 94.6%, respectively, of the transit in normal mice, respectively. In contrast to the control mice, the serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Suo (p < 0.05). By the RT-PCR (reverse transcription–polymerase chain reaction) and western blot assays, LF-Suo increased the c-Kit, SCF (stem cell factor), GDNF (glial cell line-derived neurotrophic factor) and decreased TRPV1 (transient receptor potential vanilloid 1), NOS (nitric oxide synthase) expressions of small intestine tissue in mice. These results demonstrate that lactic acid bacteria has preventive effects on mouse constipation and LF-Suo demonstrated the best functional activity. PMID:25464378

Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells

PubMed Central

Roy, Kislay; Patel, Yogesh S; Kanwar, Rupinder K; Rajkhowa, Rangam; Wang, Xungai; Kanwar, Jagat R

2016-01-01

This study used the Eri silk nanoparticles (NPs) for delivering apo-bovine lactoferrin (Apo-bLf) (~2% iron saturated) and Fe-bLf (100% iron saturated) in MDA-MB-231 and MCF-7 breast cancer cell lines. Apo-bLf and Fe-bLf-loaded Eri silk NPs with sizes between 200 and 300 nm (±10 nm) showed a significant internalization within 4 hours in MDA-MB-231 cells when compared to MCF-7 cells. The ex vivo loop assay with chitosan-coated Fe-bLf-loaded silk NPs was able to substantiate its future use in oral administration and showed the maximum absorption within 24 hours by ileum. Both Apo-bLf and Fe-bLf induced increase in expression of low-density lipoprotein receptor-related protein 1 and lactoferrin receptor in epidermal growth factor (EGFR)-positive MDA-MB-231 cells, while transferrin receptor (TfR) and TfR2 in MCF-7 cells facilitated the receptor-mediated endocytosis of NPs. Controlled and sustained release of both bLf from silk NPs was shown to induce more cancer-specific cytotoxicity in MDA-MB-231 and MCF-7 cells compared to normal MCF-10A cells. Due to higher degree of internalization, the extent of cytotoxicity and apoptosis was significantly higher in MDA-MB-231 (EGFR+) cells when compared to MCF-7 (EGFR−) cells. The expression of a prominent anticancer target, survivin, was found to be downregulated at both gene and protein levels. Taken together, all the observations suggest the potential use of Eri silk NPs as a delivery vehicle for an anti-cancer milk protein, and indicate bLf for the treatment of breast cancer. PMID:26730188

Novel recombinant human lactoferrin: differential activation of oxidative stress related gene expression.

PubMed

Kruzel, Marian L; Actor, Jeffrey K; Zimecki, Michał; Wise, Jasen; Płoszaj, Paulina; Mirza, Shaper; Kruzel, Mark; Hwang, Shen-An; Ba, Xueqing; Boldogh, Istvan

2013-12-01

Lactoferrin, an iron-binding protein found in high concentrations in mammalian exocrine secretions, is an important component of the host defense system. It is also a major protein of the secondary granules of neutrophils from which is released upon activation. Due to its potential clinical utility, recombinant human lactoferrin (rhLF) has been produced in various eukaryotic expression systems; however, none of these are fully compatible with humans. Most of the biopharmaceuticals approved by the FDA for use in humans are produced in mammalian expression systems. The Chinese hamster ovary cells (CHO) have become the system of choice for proteins that require post-translational modifications, such as glycoproteins. The aim of this study was to scale-up expression and purification of rhLF in a CHO expression system, verify its glycan primary structure, and assess its biological properties in cell culture models. A stable CHO cell line producing >200mg/L of rhLF was developed and established. rhLF was purified by a single-step cation-exchange chromatography procedure. The highly homogenous rhLF has a molecular weight of approximately 80 kDa. MALDI-TOF mass spectrometric analysis revealed N-linked, partially sialylated glycans at two glycosylation sites, typical for human milk LF. This novel rhLF showed a protective effect against oxidative stress in a similar manner to its natural counterpart. In addition, rhLF revealed a modulatory effect on cellular redox via upregulation of key antioxidant enzymes. These data imply that the CHO-derived rhLF is fully compatible with the native molecule, thus it has promise for human therapeutic applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Short term effects of energy restriction and dietary fat sub-type on weight loss and disease risk factors.

PubMed

Tapsell, L; Batterham, M; Huang, X F; Tan, S-Y; Teuss, G; Charlton, K; Oshea, J; Warensjö, E

2010-06-01

Decreasing energy intake relative to energy expenditure is the indisputable tenet of weight loss. In addition to caloric restriction modification of the type of dietary fat may provide further benefits. The aim of the present study was to examine the effect of energy restriction alone and with dietary fat modification on weight loss and adiposity, as well as on risk factors for obesity related disease. One-hundred and fifty overweight men and women were randomized into a 3month controlled trial with four low fat (30% energy) dietary arms: (1) isocaloric (LF); (2) isocaloric with 10% polyunsaturated fatty acids (LF-PUFA); (3) low calorie (LF-LC) (-2MJ); (4) low calorie with 10% PUFA (LF-PUFA-LC). Primary outcomes were changes in body weight and body fat and secondary outcomes were changes in fasting levels of leptin, insulin, glucose, lipids and erythrocyte fatty acids. Changes in dietary intake were assessed using 3day food records. One-hundred and twenty-two participants entered the study and 95 completed the study. All groups lost weight and body fat (P<0.0001 time effect for both), but the LC groups lost more weight (P=0.026 for diet effect). All groups reduced total cholesterol levels (P<0.0001 time effect and P=0.017 intervention effect), but the LC and PUFA groups were better at reducing triacylglycerol levels (P=0.056 diet effect). HDL increased with LF-LC and LF-PUFA but not with LF-PUFA-LC (0.042 diet effect). The LF and LF-LC groups reported greater dietary fat reductions than the two PUFA groups (P=0.043). Energy restriction has the most potent effect on weight loss and lipids, but fat modification is also beneficial when energy restriction is more modest.

Multicentre evaluations of two new rapid IgG4 tests (WB rapid and panLF rapid) for detection of lymphatic filariasis

PubMed Central

Noordin, Rahmah; Itoh, Makoto; Kimura, Eisaku; Abdul Rahman, Rohana; Ravindran, Balachandran; Mahmud, Rohela; Supali, Taniawati; Weerasooriya, Mirani

2007-01-01

In the global effort to eliminate lymphatic filariasis (LF), rapid field-applicable tests are useful tools that will allow on-site testing to be performed in remote places and the results to be obtained rapidly. Exclusive reliance on the few existing tests may jeopardize the progress of the LF elimination program, thus the introduction of other rapid tests would be useful to address this issue. Two new rapid immunochromatographic IgG4 cassette tests have been produced, namely WB rapid and panLF rapid, for detection of bancroftian filariasis and all three species of lymphatic filaria respectively. WB rapid was developed using BmSXP recombinant antigen, while PanLF rapid was developed using BmR1 and BmSXP recombinant antigens. A total of 165 WB rapid and 276 panLF rapid tests respectively were evaluated at USM and the rest were couriered to another university in Malaysia (98 WB rapid, 129 panLF rapid) and to universities in Indonesia (56 WB rapid, 62 panLF rapid), Japan (152 of each test) and India (18 of each test) where each of the tests underwent independent evaluations in a blinded manner. The average sensitivities of WB rapid and panLF rapid were found to be 97.6% (94%–100%) and 96.5% (94%–100%) respectively; while their average specificities were both 99.6% (99%–100%). Thus this study demonstrated that both the IgG4 rapid tests were highly sensitive and specific, and would be useful additional tests to facilitate the global drive to eliminate this disease. PMID:17961262

Passive vaccination with a human monoclonal antibody: generation of antibodies and studies for efficacy in Bacillus anthracis infections.

PubMed

vor dem Esche, Ulrich; Huber, Maria; Zgaga-Griesz, Andrea; Grunow, Roland; Beyer, Wolfgang; Hahn, Ulrike; Bessler, Wolfgang G

2011-07-01

A major difficulty in creating human monoclonal antibodies is the lack of a suitable myeloma cell line to be used for fusion experiments. In order to create fully human monoclonal antibodies for passive immunization, the human mouse heteromyeloma cell line CB-F7 was evaluated. Using this cell line, we generated human monoclonal antibodies against Bacillus anthracis toxin components. Antibodies against protective antigen (PA) and against lethal factor (LF) were obtained using peripheral blood lymphocytes (PBLs) from persons vaccinated with the UK anthrax vaccine. PBL were fused with the cell line CB-F7. We obtained several clones producing PA specific Ig and one clone (hLF1-SAN) producing a monoclonal antibody (hLF1) directed against LF. The LF binding antibody was able to neutralize Anthrax toxin activity in an in vitro neutralization assay, and preliminary in vivo studies in mice also indicated a trend towards protection. We mapped the epitope of the antibody binding to LF by dot blot analysis and ELIFA using 80 synthetic LF peptides of 20 amino acid lengths with an overlapping range of 10 amino acids. Our results suggest the binding of the monoclonal antibody to the peptide regions 121-150 or 451-470 of LF. The Fab-fragment of the antibody hLF1 was cloned in Escherichia coli and could be useful as part of a fully human monoclonal antibody for the treatment of Anthrax infections. In general, our studies show the applicability of the CB-F7 line to create fully human monoclonal antibodies for vaccination. Copyright © 2010 Elsevier GmbH. All rights reserved.

Theranostic multimodular potential of zinc-doped ferrite-saturated metal-binding protein-loaded novel nanocapsules in cancers

PubMed Central

Kamalapuram, Sishir K; Kanwar, Rupinder K; Roy, Kislay; Chaudhary, Rajneesh; Sehgal, Rakesh; Kanwar, Jagat R

2016-01-01

The present study successfully developed orally deliverable multimodular zinc (Zn) iron oxide (Fe3O4)-saturated bovine lactoferrin (bLf)-loaded polymeric nanocapsules (NCs), and evaluated their theranostic potential (antitumor efficacy, magnetophotothermal efficacy and imaging capability) in an in vivo human xenograft CpG-island methylator phenotype (CIMP)-1+/CIMP2−/chromosome instability-positive colonic adenocarcinoma (Caco2) and claudin-low, triple-negative (ER−/PR−/HER2−; MDA-MB-231) breast cancer model. Mice fed orally on the Zn-Fe-bLf NC diet showed downregulation in tumor volume and complete regression in tumor volume after 45 days of feeding. In human xenograft colon cancer, vehicle-control NC diet-group (n=5) mice showed a tumor volume of 52.28±11.55 mm3, and Zn-Fe-bLf NC diet (n=5)-treated mice had a tumor-volume of 0.10±0.073 mm3. In the human xenograft breast cancer model, Zn-Fe-bLf NC diet (n=5)-treated mice showed a tumor volume of 0.051±0.062 mm3 within 40 days of feeding. Live mouse imaging conducted by near-infrared fluorescence imaging of Zn-Fe-bLf NCs showed tumor site-specific localization and regression of colon and breast tumor volume. Ex vivo fluorescence-imaging analysis of the vital organs of mice exhibited sparse localization patterns of Zn-Fe-bLf NCs and also confirmed tumor-specific selective localization patterns of Zn-Fe-bLf NCs. Dual imaging using magnetic resonance imaging and computerized tomography scans revealed an unprecedented theranostic ability of the Zn-Fe-bLf NCs. These observations warrant consideration of multimodular Zn-Fe-bLf NCs for real-time cancer imaging and simultaneous cancer-targeted therapy. PMID:27099495

Effects of the major sudden stratospheric warming event of 2009 on the subionospheric very low frequency/low frequency radio signals

NASA Astrophysics Data System (ADS)

Pal, S.; Hobara, Y.; Chakrabarti, S. K.; Schnoor, P. W.

2017-07-01

This paper presents effects of the major sudden stratospheric warming (SSW) event of 2009 on the subionospheric very low frequency/low frequency (VLF/LF) radio signals propagating in the Earth-ionosphere waveguide. Signal amplitudes from four transmitters received by VLF/LF radio networks of Germany and Japan corresponding to the major SSW event are investigated for possible anomalies and atmospheric influence on the high- to middle-latitude ionosphere. Significant anomalous increase or decrease of nighttime and daytime amplitudes of VLF/LF signals by ˜3-5 dB during the SSW event have been found for all propagation paths associated with stratospheric temperature rise at 10 hPa level. Increase or decrease in VLF/LF amplitudes during daytime and nighttime is actually due to the modification of the lower ionospheric boundary conditions in terms of electron density and electron-neutral collision frequency profiles and associated modal interference effects between the different propagating waveguide modes during the SSW period. TIMED/SABER mission data are also used to investigate the upper mesospheric conditions over the VLF/LF propagation path during the same time period. We observe a decrease in neutral temperature and an increase in pressure at the height of 75-80 km around the peak time of the event. VLF/LF anomalies are correlated and in phase with the stratospheric temperature and mesospheric pressure variation, while minimum of mesospheric cooling shows a 2-3 day delay with maximum VLF/LF anomalies. Simulations of VLF/LF diurnal variation are performed using the well-known Long Wave Propagating Capability (LWPC) code within the Earth-ionosphere waveguide to explain the VLF/LF anomalies qualitatively.

Inhibition of Hyphal Growth of Azole-Resistant Strains of Candida albicans by Triazole Antifungal Agents in the Presence of Lactoferrin-Related Compounds

PubMed Central

Wakabayashi, Hiroyuki; Abe, Shigeru; Teraguchi, Susumu; Hayasawa, Hirotoshi; Yamaguchi, Hideyo

1998-01-01

The effects of bovine lactoferrin (LF) or the LF-derived antimicrobial peptide lactoferricin B (LFcin B) on the growth of Candida albicans hyphae, including those of three azole-resistant strains, were investigated by a crystal violet staining method. The hyphae of two highly azole-resistant strains were more susceptible to inhibition by LF or LFcin B than the azole-susceptible strains tested. One moderately azole-resistant strain was defective in the formation of hyphae and showed a susceptibility to LF greater than that of the susceptible strains but a susceptibility to LFcin B similar to that of the susceptible strains. The highly azole-resistant strain TIMM3317 showed trailing growth in the presence of fluconazole or itraconazole, while the extent of growth was reduced by the addition of LF or LFcin B at a sub-MIC. Thus, the addition of LF or LFcin B at a sub-MIC resulted in a substantial decrease in the MICs of fluconazole and itraconazole for two highly azole-resistant strains; e.g., the MIC of fluconazole for TIMM3317 was shifted from >256 to 0.25 μg/ml by LF, but the MICs were not decreased for the susceptible strains. The combination effects observed with triazoles and LF-related compounds in the case of the two highly azole-resistant strains were confirmed to be synergistic by the fractional inhibitory concentration index. These results demonstrate that for some azole-resistant C. albicans strains, LF-related compounds combined with triazoles can inhibit the growth of hyphae, an important form of this organism in pathogenesis. PMID:9660988

Studies of ferroelectric and dielectric properties of pure and doped barium titanate prepared by sol-gel method

NASA Astrophysics Data System (ADS)

Bisen, Supriya; Mishra, Ashutosh; Jarabana, Kanaka M.

2016-05-01

In this work, Barium Titanate (BaTiO3) powders were synthesized via Sol-Gel auto combustion method using citric acid as a chelating agent. We study the behavior of ferroelectric and dielectric properties of pure and doped BaTiO3 on different concentration. To understand the phase and structure of the powder calcined at 900°C were characterized by X-ray Diffraction shows that tetragonal phase is dominant for pure and doped BTO and data fitted by Rietveld Refinement. Electric and Dielectric properties were characterized by P-E Hysteresis and Dielectric measurement. In P-E measurement ferroelectric loop tracer applied for different voltage. The temperature dependant dielectric constant behavior was observed as a function of frequency recorded on hp-Hewlett Packard 4192A, LF impedance, 5Hz-13Hz analyzer.

Anthrax lethal factor inhibitors as potential countermeasure of the infection.

PubMed

Kumar, B V S Suneel; Malik, Siddharth; Grandhi, Pradeep; Dayam, Raveendra; Sarma, J A R P

2014-01-01

Anthrax Lethal Factor (LF) is a zinc-dependent metalloprotease, one of the virulence factor of anthrax infection. Three forms of the anthrax infection have been identified: cutaneous (through skin), gastrointestinal (through alimentary tract), and pulmonary (by inhalation of spores). Anthrax toxin is composed of protective antigen (PA), lethal factor (LF), and edema factor (EF). Protective antigen mediates the entry of Lethal Factor/Edema Factor into the cytosol of host cells. Lethal factor (LF) inactivates mitogen-activated protein kinase kinase inducing cell death, and EF is an adenylyl cyclase impairing host defenses. In the past few years, extensive studies are undertaken to design inhibitors targeting LF. The current review focuses on the small molecule inhibitors targeting LF activity and its structure activity relationships (SAR).

Production of human lactoferrin in animal milk.

PubMed

Goldman, I L; Georgieva, S G; Gurskiy, Ya G; Krasnov, A N; Deykin, A V; Popov, A N; Ermolkevich, T G; Budzevich, A I; Chernousov, A D; Sadchikova, E R

2012-06-01

Genetic constructs containing the human lactoferrin (hLf) gene were created within a joint program of Russian and Belorussian scientists. Using these constructs, transgenic mice were bred (the maximum hLf concentration in their milk was 160 g/L), and transgenic goats were also generated (up to 10 g/L hLf in their milk). Experimental goatherds that produced hLf in their milk were also bred, and the recombinant hLf was found to be identical to the natural protein in its physical and chemical properties. These properties included electrophoretic mobility, isoelectric point, recognition by polyclonal and monoclonal antibodies, circular dichroic spectra, interaction with natural ligands (DNA, lipopolysaccharides, and heparin), the binding of iron ions, the sequence of the 7 terminal amino acids, and its biological activity. The latter was assessed by the agglutination of Micrococcus luteus protoplasts, bactericidal activity against Escherichia coli and Listeria monocytogenes , and fungicidal activity against Candida albicans . We also demonstrated a significant increase in the activity of antibiotics when used in combination with Lf.

Implantable Cardiac Defibrillator Lead Failure and Management.

PubMed

Swerdlow, Charles D; Kalahasty, Gautham; Ellenbogen, Kenneth A

2016-03-22

The implantable-cardioverter defibrillator (ICD) lead is the most vulnerable component of the ICD system. Despite advanced engineering design, sophisticated manufacturing techniques, and extensive bench, pre-clinical, and clinical testing, lead failure (LF) remains the Achilles' heel of the ICD system. ICD LF has a broad range of adverse outcomes, ranging from intermittent inappropriate pacing to proarrhythmia leading to patient mortality. ICD LF is often considered in the context of design or construction defects, but is more appropriately considered in the context of the finite service life of a mechanical component placed in chemically stressful environment and subjected to continuous mechanical stresses. This clinical review summarizes LF mechanisms, assessment, and differential diagnosis of LF, including lead diagnostics, recent prominent lead recalls, and management of LF and functioning, but recalled leads. Despite recent advances in lead technology, physicians will likely continue to need to understand how to manage patients with transvenous ICD leads. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Systematic Evaluation of Low-Frequency Hiss and Energetic Electron Injections

DOE PAGES

Shi, Run; Li, Wen; Ma, Qianli; ...

2017-10-05

Here, the excitation of low-frequency (LF) plasmaspheric hiss, over the frequency range from 20 Hz to 100 Hz, is systematically investigated by comparing the hiss wave properties with electron injections at energies from tens of keV to several hundreds of keV. Both particle and wave data from the Van Allen Probes during the period from September 2012 to June 2016 are used in the present study. Our results demonstrate that the intensity of LF hiss has a clear day-night asymmetry, and increases with increasing geomagnetic activity, similar to the behavior of normal hiss (approximately hundred of hertz to several kilohertz).more » The occurrence rate of LF hiss in association with electron injections is up to 80% in the outer plasmasphere ( L > 4) on the dayside, and the strong correlation extends to lower L shells for more active times. In contrast, at lower L shells ( L < 3.5), LF hiss is seldom associated with electron injections. The LF hiss with Poynting flux directed away from the equator is dominant at higher magnetic latitudes and higher L shells, suggesting a local amplification of LF hiss in the outer plasmasphere. The averaged electron fluxes are larger at higher L shells, where significant LF hiss wave events are observed. Our study suggests the importance of electron injections and their drift trajectories toward the dayside plasmasphere in locally amplifying the LF hiss waves detected by the Van Allen Probes.« less

Systematic Evaluation of Low-Frequency Hiss and Energetic Electron Injections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Run; Li, Wen; Ma, Qianli

Here, the excitation of low-frequency (LF) plasmaspheric hiss, over the frequency range from 20 Hz to 100 Hz, is systematically investigated by comparing the hiss wave properties with electron injections at energies from tens of keV to several hundreds of keV. Both particle and wave data from the Van Allen Probes during the period from September 2012 to June 2016 are used in the present study. Our results demonstrate that the intensity of LF hiss has a clear day-night asymmetry, and increases with increasing geomagnetic activity, similar to the behavior of normal hiss (approximately hundred of hertz to several kilohertz).more » The occurrence rate of LF hiss in association with electron injections is up to 80% in the outer plasmasphere ( L > 4) on the dayside, and the strong correlation extends to lower L shells for more active times. In contrast, at lower L shells ( L < 3.5), LF hiss is seldom associated with electron injections. The LF hiss with Poynting flux directed away from the equator is dominant at higher magnetic latitudes and higher L shells, suggesting a local amplification of LF hiss in the outer plasmasphere. The averaged electron fluxes are larger at higher L shells, where significant LF hiss wave events are observed. Our study suggests the importance of electron injections and their drift trajectories toward the dayside plasmasphere in locally amplifying the LF hiss waves detected by the Van Allen Probes.« less

Release of endogenous opioids following transcutaneous electric nerve stimulation in an experimental model of acute inflammatory pain.

PubMed

Sabino, George S; Santos, Cristiane M F; Francischi, Janetti N; de Resende, Marcos Antônio

2008-02-01

Transcutaneous electric nerve stimulation (TENS) is a noninvasive treatment used in physiotherapy practice to promote analgesia in acute and chronic inflammatory conditions. The aim of the present study was to investigate the action mechanism of TENS at high (HF: 130 Hz) and low (LF: 10 Hz) frequencies in an inflammation model produced by the injection of carrageenan in rat paws (Cg; 250 microg). After carrageenan administration (0 time), either HF or LF TENS was applied to the inflamed paw of rats for 20 minutes, and hyperalgesia was assessed hourly using the modified Randall-Selitto method (1957). HF and LF TENS inhibited the carrageenan-induced hyperalgesia by 100%. Pretreatment of animals with intraplantar naltrexone (Nx; 50 microg) reversed the analgesic effect of the LF TENS but did not alter the effect of HF TENS. The application of HF and LF TENS to the contralateral paw reversed the hyperalgesia of the inflamed paw similar to that observed when TENS was applied to the inflamed paw. However, LF TENS presented a longer-lasting analgesic effect than HF TENS. Our data demonstrate that HF and LF TENS induced antihyperalgesia. We also report that the antihyperalgesia provoked by LF TENS is partially due to the local release of endogenous opioids. This study offers important information about physiotherapy practices aimed at pain relieving. TENS is a noninvasive treatment that promotes analgesia in acute and chronic inflammatory conditions. Scientists, patients, and the general population may benefit from this knowledge.

Measurement of liver function using hepatobiliary scintigraphy improves risk assessment in patients undergoing major liver resection.

PubMed

Cieslak, Kasia P; Bennink, Roelof J; de Graaf, Wilmar; van Lienden, Krijn P; Besselink, Marc G; Busch, Olivier R C; Gouma, Dirk J; van Gulik, Thomas M

2016-09-01

(99m)Tc-mebrofenin-hepatobiliary-scintigraphy (HBS) enables measurement of future remnant liver (FRL)-function and was implemented in our preoperative routine after calculation of the cut-off value for prediction of postoperative liver failure (LF). This study evaluates our results since the implementation of HBS. Additionally, CT-volumetric methods of FRL-assessment, standardized liver volumetry and FRL/body-weight ratio (FRL-BWR), were evaluated. 163 patients who underwent major liver resection were included. Insufficient FRL-volume and/or FRL-function <2.7%/min/m(2) were indications for portal vein embolization (PVE). Non-PVE patients were compared with a historical cohort (n = 55). Primary endpoints were postoperative LF and LF related mortality. Secondary endpoint was preoperative identification of patients at risk for LF using the CT-volumetric methods. 29/163 patients underwent PVE; 8/29 patients because of insufficient FRL-function despite sufficient FRL-volume. According to FRL-BWR and standardized liver volumetry, 16/29 and 11/29 patients, respectively, would not have undergone PVE. LF and LF related mortality were significantly reduced compared to the historical cohort. HBS appeared superior in the identification of patients with increased surgical risk compared to the CT-volumetric methods. Implementation of HBS in the preoperative work-up led to a function oriented use of PVE and was associated with a significant decrease in postoperative LF and LF related mortality. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Lactoferrin binding protein B – a bi-functional bacterial receptor protein

PubMed Central

Ostan, Nicholas K. H.; Yu, Rong-Hua; Ng, Dixon; Lai, Christine Chieh-Lin; Sarpe, Vladimir; Schriemer, David C.

2017-01-01

Lactoferrin binding protein B (LbpB) is a bi-lobed outer membrane-bound lipoprotein that comprises part of the lactoferrin (Lf) receptor complex in Neisseria meningitidis and other Gram-negative pathogens. Recent studies have demonstrated that LbpB plays a role in protecting the bacteria from cationic antimicrobial peptides due to large regions rich in anionic residues in the C-terminal lobe. Relative to its homolog, transferrin-binding protein B (TbpB), there currently is little evidence for its role in iron acquisition and relatively little structural and biophysical information on its interaction with Lf. In this study, a combination of crosslinking and deuterium exchange coupled to mass spectrometry, information-driven computational docking, bio-layer interferometry, and site-directed mutagenesis was used to probe LbpB:hLf complexes. The formation of a 1:1 complex of iron-loaded Lf and LbpB involves an interaction between the Lf C-lobe and LbpB N-lobe, comparable to TbpB, consistent with a potential role in iron acquisition. The Lf N-lobe is also capable of binding to negatively charged regions of the LbpB C-lobe and possibly other sites such that a variety of higher order complexes are formed. Our results are consistent with LbpB serving dual roles focused primarily on iron acquisition when exposed to limited levels of iron-loaded Lf on the mucosal surface and effectively binding apo Lf when exposed to high levels at sites of inflammation. PMID:28257520

Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects

PubMed Central

Bi, Chenchen; Duan, Dongyu; Chu, Liuxiang; Yu, Xin; Wu, Zimei; Wang, Aiping; Sun, Kaoxiang

2018-01-01

Introduction Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson’s disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD. Materials and methods The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs. Results Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference (P<0.05) in contralateral rotations between rats treated with Lf-R-NPs and those treated with R-NPs. Furthermore, Lf-R-NPs significantly alleviated nigrostriatal dopaminergic neurodegeneration in the rat model of 6-hydroxydopamine-induced PD. Conclusion Our findings show that Lf-R-NPs deliver rotigotine more efficiently to the brain, thereby enhancing efficacy. Therefore, Lf-R-NPs might have therapeutic potential for the treatment of PD. PMID:29391788

Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects.

PubMed

Yan, Xiuju; Xu, Lixiao; Bi, Chenchen; Duan, Dongyu; Chu, Liuxiang; Yu, Xin; Wu, Zimei; Wang, Aiping; Sun, Kaoxiang

2018-01-01

Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson's disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD. The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs. Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference ( P <0.05) in contralateral rotations between rats treated with Lf-R-NPs and those treated with R-NPs. Furthermore, Lf-R-NPs significantly alleviated nigrostriatal dopaminergic neurodegeneration in the rat model of 6-hydroxydopamine-induced PD. Our findings show that Lf-R-NPs deliver rotigotine more efficiently to the brain, thereby enhancing efficacy. Therefore, Lf-R-NPs might have therapeutic potential for the treatment of PD.

Lassa Fever Immune Plasma.

DTIC Science & Technology

1984-08-01

three instances, and one each for sickle cell crisis , severe anemia, pyelonephritis, cerebral malaria and tonsillitis. Treatment of LF with LFIP under...diagnosis of 46 LF and Presumptive LF patients treated at CLH April 1983 - March 1984. Clinical diagnosis No. Lassa fever 38 Typhoid fever 3 Sickle cell crisis 1

Accelerated Evolution of the Lyα Luminosity Function at z >~ 7 Revealed by the Subaru Ultra-deep Survey for Lyα Emitters at z = 7.3

NASA Astrophysics Data System (ADS)

Konno, Akira; Ouchi, Masami; Ono, Yoshiaki; Shimasaku, Kazuhiro; Shibuya, Takatoshi; Furusawa, Hisanori; Nakajima, Kimihiko; Naito, Yoshiaki; Momose, Rieko; Yuma, Suraphong; Iye, Masanori

2014-12-01

We present the ultra-deep Subaru narrowband imaging survey for Lyα emitters (LAEs) at z = 7.3 in the Subaru/XMM-Newton Deep Survey (SXDS) and Cosmic Evolution Survey (COSMOS) fields (~0.5 deg2) with a total integration time of 106 hr. Exploiting our new sharp bandwidth filter, NB101, installed on the Suprime-Cam, we have reached L(Lyα) = 2.4 × 1042 erg s-1 (5σ) for z = 7.3 LAEs, about four times deeper than previous Subaru z >~ 7 studies, which allows us to reliably investigate the evolution of the Lyα luminosity function (LF) for the first time down to the luminosity limit same as those of Subaru z = 3.1-6.6 LAE samples. Surprisingly, we only find three and four LAEs in the SXDS and COSMOS fields, respectively, while one expects a total of ~65 LAEs by our survey in the case of no Lyα LF evolution from z = 6.6 to 7.3. We identify a decrease of the Lyα LF from z = 6.6 to 7.3 at the >90% confidence level from our z = 7.3 Lyα LF with the best-fit Schechter parameters of L*{Lyα } = 2.7+8.0-1.2 × 1042 {erg} {s}-1 and φ * = 3.7+17.6-3.3 × 10-4 {Mpc}-3 for a fixed α = -1.5. Moreover, the evolution of the Lyα LF is clearly accelerated at z > 6.6 beyond the measurement uncertainties including cosmic variance. Because no such accelerated evolution of the UV-continuum LF or the cosmic star formation rate (SFR) is found at z ~ 7, but suggested only at z > 8, this accelerated Lyα LF evolution is explained by physical mechanisms different from a pure SFR decrease but related to the Lyα production and escape in the process of cosmic reionization. Because a simple accelerating increase of intergalactic medium neutral hydrogen absorbing Lyα cannot be reconciled with Thomson scattering of optical depth measurements from WMAP and Planck, our findings may support new physical pictures suggested by recent theoretical studies, such as the existence of HI clumpy clouds within cosmic ionized bubbles that are selectively absorbing Lyα and the large ionizing photon escape fraction of galaxies causing weak Lyα emission.

The opportunity of silicate product manufacturing with simultaneous pig iron reduction from slag technogenic formations

NASA Astrophysics Data System (ADS)

Sheshukov, O. Yu.; Lobanov, D. A.; Mikheenkov, M. A.; Nekrasov, I. V.; Egiazaryan, D. K.

2017-09-01

There are two main kinds of slag in modern steelmaking industry: the electric arc furnace slag (EAF slag) and ladle furnace slag (LF slag). The all known slag processing schemes provide the iron-containing component reduction while silicate component stays unprocessed. On the contrary, the silicate processing schemes doesn't provide the utilization of the iron-containing component. The present-day situation doesn't solve the problem of total slag utilization. The aim of this work is to investigate the opportunity of silicate product obtaining with simultaneous pig iron reduction from EAF and LF slags. The tests are conducted by the method of simplex-lattice design. The test samples are heated and melted under reductive conditions, slowly cooled and then analyzed by XRD methods. The experiment results prove the opportunity: the Portland clinker and pig iron can be simultaneously produced on the basis of these slags with a limestone addition.

Global transcriptome analysis of the maize (Zea mays L.) inbred line 08LF during leaf senescence initiated by pollination-prevention.

PubMed

Wu, Liancheng; Li, Mingna; Tian, Lei; Wang, Shunxi; Wu, Liuji; Ku, Lixia; Zhang, Jun; Song, Xiaoheng; Liu, Haiping; Chen, Yanhui

2017-01-01

In maize (Zea mays), leaf senescence acts as a nutrient recycling process involved in proteins, lipids, and nucleic acids degradation and transport to the developing sink. However, the molecular mechanisms of pre-maturation associated with pollination-prevention remain unclear in maize. To explore global gene expression changes during the onset and progression of senescence in maize, the inbred line 08LF, with severe early senescence caused by pollination prevention, was selected. Phenotypic observation showed that the onset of leaf senescence of 08LF plants occurred approximately 14 days after silking (DAS) by pollination prevention. Transcriptional profiling analysis of the leaf at six developmental stages during induced senescence revealed that a total of 5,432 differentially expressed genes (DEGs) were identified, including 2314 up-regulated genes and 1925 down-regulated genes. Functional annotation showed that the up-regulated genes were mainly enriched in multi-organism process and nitrogen compound transport, whereas down-regulated genes were involved in photosynthesis. Expression patterns and pathway enrichment analyses of early-senescence related genes indicated that these DEGs are involved in complex regulatory networks, especially in the jasmonic acid pathway. In addition, transcription factors from several families were detected, particularly the CO-like, NAC, ERF, GRAS, WRKY and ZF-HD families, suggesting that these transcription factors might play important roles in driving leaf senescence in maize as a result of pollination-prevention.

76 FR 67730 - Ocean Transportation Intermediary License Applicants

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-02

... Type: New OFF License LF Freight USA LLC dba LF Logistics dba LF Freight dba IDS Logistics USA, dba IDS Freight Services, dba AGI Logistics USA, dba AGI Logistics, 230-59 International Airport Center Blvd., 270... Individual), Caetano R. Lopes, Vice President, Application Type: Add NVO Service Eztrans Logistics Ltd. (NVO...

Protection of SK-N-MC cells against β-amyloid peptide-induced degeneration using neuron growth factor-loaded liposomes with surface lactoferrin.

PubMed

Kuo, Yung-Chih; Wang, Cheng-Ting

2014-07-01

A liposomal system with surface lactoferrin (Lf) was developed for delivering neuron growth factor (NGF) across the blood-brain barrier (BBB) and improving the viability of neuron-like SK-N-MC cells with deposited β-amyloid peptide (Aβ). The Lf-grafted liposomes carrying NGF (Lf/NGF-liposomes) were applied to a monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes (HAs) and to fibrillar Aβ1-42-insulted SK-N-MC cells. An increase in cholesterol mole percentage enhanced the particle size, absolute value of zeta potential, and physical stability, however, reduced the entrapment efficiency and release rate of NGF. In addition, an increase in Lf concentration increased the particle size, surface nitrogen percentage, NGF permeability across the BBB, and viability of HBMECs, HAs, and SK-N-MC cells, however, decreased the absolute value of zeta potential, surface phosphorus percentage, and loading efficiency of Lf. After treating with Lf/NGF-liposomes, a higher Aβ concentration yielded a lower survival of SK-N-MC cells. The current Lf/NGF-liposomes are efficacious drug carriers to target the BBB and inhibit the Aβ-induced neurotoxicity as potential pharmacotherapy for Alzheimer's disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Low-frequency components in harbor porpoise (Phocoena phocoena) clicks: communication signal, by-products, or artifacts?

PubMed

Hansen, M; Wahlberg, M; Madsen, P T

2008-12-01

Underwater sound signals for biosonar and communication normally have different source properties to serve the purposes of generating efficient acoustic backscatter from small objects or conveying information to conspecifics. Harbor porpoises (Phocoena phocoena) are nonwhistling toothed whales that produce directional, narrowband, high-frequency (HF) echolocation clicks. This study tests the hypothesis that their 130 kHz HF clicks also contain a low-frequency (LF) component more suited for communication. Clicks from three captive porpoises were analyzed to quantify the LF and HF source properties. The LF component is 59 (S.E.M=1.45 dB) dB lower than the HF component recorded on axis, and even at extreme off-axis angles of up to 135 degrees , the HF component is 9 dB higher than the LF component. Consequently, the active space of the HF component will always be larger than that of the LF component. It is concluded that the LF component is a by-product of the sound generator rather than a dedicated pulse produced to serve communication purposes. It is demonstrated that distortion and clipping in analog tape recorders can explain some of the prominent LF components reported in earlier studies, emphasizing the risk of erroneous classification of sound types based on recording artifacts.

Solitons of the coupled Schrödinger-Korteweg-de Vries system with arbitrary strengths of the nonlinearity and dispersion

NASA Astrophysics Data System (ADS)

Gromov, Evgeny; Malomed, Boris

2017-11-01

New two-component soliton solutions of the coupled high-frequency (HF)—low-frequency (LF) system, based on Schrödinger-Korteweg-de Vries (KdV) system with the Zakharov's coupling, are obtained for arbitrary relative strengths of the nonlinearity and dispersion in the LF component. The complex HF field is governed by the linear Schrödinger equation with a potential generated by the real LF component, which, in turn, is governed by the KdV equation including the ponderomotive coupling term, representing the feedback of the HF field onto the LF component. First, we study the evolution of pulse-shaped pulses by means of direct simulations. In the case when the dispersion of the LF component is weak in comparison to its nonlinearity, the input gives rise to several solitons in which the HF component is much broader than its LF counterpart. In the opposite case, the system creates a single soliton with approximately equal widths of both components. Collisions between stable solitons are studied too, with a conclusion that the collisions are inelastic, with a greater soliton getting still stronger, and the smaller one suffering further attenuation. Robust intrinsic modes are excited in the colliding solitons. A new family of approximate analytical two-component soliton solutions with two free parameters is found for an arbitrary relative strength of the nonlinearity and dispersion of the LF component, assuming weak feedback of the HF field onto the LF component. Further, a one-parameter (non-generic) family of exact bright-soliton solutions, with mutually proportional HF and LF components, is produced too. Intrinsic dynamics of the two-component solitons, induced by a shift of their HF component against the LF one, is also studied, by means of numerical simulations, demonstrating excitation of a robust intrinsic mode. In addition to the above-mentioned results for LF-dominated two-component solitons, which always run in one (positive) velocities, we produce HF-dominated soliton complexes, which travel in the opposite (negative) direction. They are obtained in a numerical form and by means of a quasi-adiabatic analytical approximation. The solutions with positive and negative velocities correspond, respectively, to super- and subsonic Davydov-Scott solitons.

Konjac gel as pork backfat replacer in dry fermented sausages: processing and quality characteristics.

PubMed

Ruiz-Capillas, C; Triki, M; Herrero, A M; Rodriguez-Salas, L; Jiménez-Colmenero, F

2012-10-01

The effect of replacing animal fat (0%, 50% and 80% of pork backfat) by an equal proportion of konjac gel, on processing and quality characteristics of reduced and low-fat dry fermented sausage was studied. Weight loss, pH, and water activity of the sausage were affected (P<0.05) by fat reduction and processing time. Low lipid oxidation levels were observed during processing time irrespective of the dry sausage formulation. The fat content for normal-fat (NF), reduced-fat (RF) and low-fat (LF) sausages was 29.96%, 19.69% and 13.79%, respectively. This means an energy reduction of about 14.8% for RF and 24.5% for LF. As the fat content decreases there is an increase (P<0.05) in hardness and chewiness and a decrease (P<0.05) in cohesiveness. No differences were appreciated (P>0.05) in the presence of microorganisms as a result of the reformulation. The sensory panel considered that NF and RF products had acceptable sensory characteristics. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Eyeball Pressure Stimulation Unveils Subtle Autonomic Cardiovascular Dysfunction in Persons with a History of Mild Traumatic Brain Injury.

PubMed

Hilz, Max J; Aurnhammer, Felix; Flanagan, Steven R; Intravooth, Tassanai; Wang, Ruihao; Hösl, Katharina M; Pauli, Elisabeth; Koehn, Julia

2015-11-15

After mild traumatic brain injury (mTBI), patients have increased long-term mortality rates, persisting even beyond 13 years. Pathophysiology is unclear. Yet, central autonomic network dysfunction may contribute to cardiovascular dysregulation and increased mortality. Purely parasympathetic cardiovascular challenge by eyeball pressure stimulation (EP), might unveil subtle autonomic dysfunction in post-mTBI patients. We investigated whether mild EP shows autonomic cardiovascular dysregulation in post-mTBI patients. In 24 patients (34 ± 12 years; 5-86 months post-injury) and 27 controls (30 ± 11 years), we monitored respiration, electrocardiographic RR intervals (RRI), systolic and diastolic blood pressure (BPsys, BPdia) before and during 2 min of 30 mm Hg EP, applied by an ophthalmologic ocular pressure device (Okulopressor(®)). We calculated spectral powers of RRI in the mainly sympathetic low frequency (LF; 0.04-0.15 Hz) and parasympathetic high frequency (HF; 0.15-0.5 Hz) ranges, and of BP in the sympathetic LF range, the RRI-LF/HF ratio as index of the sympathetic-parasympathetic balance, normalized (nu) RRI-LF- and HF-powers, and LF- and HF-powers after natural logarithmic transformation (ln). Parameters before and during EP in post-mTBI patients and controls were compared by repeated measurement analysis of variance with post hoc analysis (p < 0.05). During EP, BPsys and BPdia increased in post-mTBI patients. Only in controls but not in post-mTBI patients, EP increased RRI-HFnu-powers and decreased RRI-LF-powers, RRI-LFnu-powers, BPsys-LF-powers, BPsys-lnLF-powers and BPdia-lnLF-powers. RRI-LF/HF ratios slightly increased in post-mTBI patients but slightly decreased in controls upon EP. Even with only mild EP, our controls showed normal EP responses and shifted sympathetic-parasympathetic balance towards parasympathetic predominance. In contrast, our post-mTBI patients could not increase parasympathetic heart rate modulation but increased BP upon EP, indicating a paradox sympathetic activation. The findings support the hypothesis that central autonomic dysfunction might contribute to an increased cardiovascular risk, even years after mTBI.

Impact of dietary fiber coatings on behavior of protein-stabilized lipid droplets under simulated gastrointestinal conditions.

PubMed

Tokle, Tanushree; Lesmes, Uri; Decker, Eric Andrew; McClements, David Julian

2012-01-01

Multilayer emulsions containing lipid droplets coated by lactoferrin (LF) - anionic polysaccharide layers have improved resistance to environmental stresses (such as pH, salt, and temperature), but their behavior within the gastrointestinal tract (GIT) is currently unknown. The objective of this research was therefore to monitor changes in the physicochemical properties and digestibility of these systems under simulated GIT conditions. Primary emulsions (5% corn oil, 0.5% LF) were prepared using a high-pressure homogenizer. Secondary emulsions (5% corn oil, 0.5% LF, 0.5% polysaccharide) were prepared by incorporating alginate, low methoxyl pectin (LMP) or high methoxyl pectin (HMP) into primary emulsions. Emulsions were then subjected to simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) conditions in sequence. LF, LF-LMP and LF-HMP emulsions were stable to droplet aggregation in the stomach but aggregated in the small intestine, whereas LF-alginate emulsions aggregated in both the stomach and small intestine. The presence of a dietary fiber coating around the initial lipid droplets had little influence on the total extent of lipid digestion in SIF, but LF-alginate emulsions had a slower initial digestion rate than the other emulsions. These results suggest that the dietary fiber coatings may become detached in the small intestine, or that they were permeable to digestive enzymes. Pepsin was found to have little influence on the physical stability or digestibility of the emulsions. The knowledge obtained from this study is important for the design of delivery systems for encapsulation and release of lipophilic bioactive ingredients.

Bovine Lactoferrin and Lactoferrin-Derived Peptides Inhibit the Growth of Vibrio cholerae and Other Vibrio species.

PubMed

Acosta-Smith, Erika; Viveros-Jiménez, Karina; Canizalez-Román, Adrian; Reyes-Lopez, Magda; Bolscher, Jan G M; Nazmi, Kamran; Flores-Villaseñor, Hector; Alapizco-Castro, Gerardo; de la Garza, Mireya; Martínez-Garcia, Jesús J; Velazquez-Roman, Jorge; Leon-Sicairos, Nidia

2017-01-01

Vibrio is a genus of Gram-negative bacteria, some of which can cause serious infectious diseases. Vibrio infections are associated with the consumption of contaminated food and classified in Vibrio cholera infections and non-cholera Vibrio infections. In the present study, we investigate whether bovine lactoferrin (bLF) and several synthetic peptides corresponding to bLF sequences, are able to inhibit the growth or have bactericidal effect against V. cholerae and other Vibrio species. The antibacterial activity of LF and LF-peptides was assessed by kinetics of growth or determination of colony forming unit in bacteria treated with the peptides and antibiotics. To get insight in the mode of action, the interaction between bLF and bLF-peptides (coupled to FITC) and V. cholera was evaluated. The damage of effector-induced bacterial membrane permeability was measured by inclusion of the fluorescent dye propidium iodide using flow cytometry, whereas the bacterial ultrastructural damage in bacteria treated was observed by transmission electron microscopy. The results showed that bLF and LFchimera inhibited the growth of the V. cholerae strains; LFchimera permeabilized the bacteria which membranes were seriously damaged. Assays with a multidrug-resistant strain of Vibrio species indicated that combination of sub-lethal doses of LFchimera with ampicillin or tetracycline strongly reduced the concentration of the antibiotics to reach 95% growth inhibition. Furthermore, LFchimera were effective to inhibit the V. cholerae counts and damage due to this bacterium in a model mice. These data suggest that LFchimera and bLF are potential candidates to combat the V. cholerae and other multidrug resistant Vibrio species.

Effects of Static Stretching Exercise on Lumbar Flexibility and Central Arterial Stiffness.

PubMed

Logan, Jeongok G; Kim, Suk-Sun; Lee, Mijung; Byon, Ha Do; Yeo, SeonAe

Previous studies have demonstrated that arterial stiffness is associated with lumbar flexibility (LF). Stretching exercise targeted to improve LF may have a beneficial effect on reducing arterial stiffness. We examined the effects of a single bout of a structured, static stretching exercise on arterial stiffness, LF, peripheral and central blood pressure (BP), and heart rate (HR) and tested the association between LF and central arterial stiffness. The study had a pretest-posttest design without a control group. Thirty healthy women followed a video demonstration of a 30-minute whole-body stretching exercise. Carotid-femoral pulse wave velocity (cf-PWV), augmentation index, LF, peripheral and central BP, and HR were measured before and after the stretching exercise. One bout of a static stretching exercise significantly reduced cf-PWV (t29 = 2.708, P = .011) and HR (t29 = 7.160, P = .000) and increased LF (t29 = 12.248, P < .000). Augmentation index and peripheral and central BP also decreased but did not reach statistical significance. Despite no association found between cf-PWV and LF, the larger increase in LF the subjects had, the larger decrease in cf-PWV they had after exercise (r = 0.500, P = .005). Study findings highlight the potential benefit of a static stretching exercise on central arterial stiffness, an independent predictor of cardiovascular morbidity. Static stretching exercise conducted in the sitting position may be used as an effective intervention to reduce cardiovascular risk after a cardiac event or for patients whose sympathetic function should not be overly activated or whose gaits are not stable.

Functional relationships of landfill and landraise capacity with design and operation parameters.

PubMed

Aivaliotis, Vassilis; Dokas, Ioannis; Hatzigiannakou, Maria; Panagiotakopoulos, Demetrios

2004-08-01

Solid waste management presses for effective landfill design and operation. While planning and operating a landfill (LF) or a landraise (LR), choices need to be made regarding: (1) LF-LR morphology (base shape, side slopes, final cover thickness, LR/LF height/depth); (2) cell geometry (height, length, slopes); and (3) operation parameters (waste density, working face length, cover thicknesses). These parameters affect LF/LR capacity, operation lifespan and construction/ operation costs. In this paper, relationships are generated between capacity (C, space available for waste) and the above parameters. Incorporating real data into simulation kgamma A1.38, runs, two types of functions are developed: first, C = where A is the LF/LR base area size and kgamma a base shape-dependent coefficient; and second, C = alpha(p,gamma,A) + delta(p,gamma,A)Xp for every parameter p, where Xp is the value of p and alpha(p,gamma,A) and delta(p,gamma,A) are parameter- and base (shape/size)-specific coefficients. Moreover, the relationship between LF depth and LR height that balances excavation volume with cover material, is identified. Another result is that, for a symmetrical combination of LF/LR, with base surface area shape between square and 1:2 orthogonal, and final density between 500 and 800 kg m(-3), waste quantity placed ranges from 1.76A1.38 to 2.55A1.38 tons. The significance of such functions is obvious, as they allow the analyst to investigate alternative LF/LR schemes and make trade-off analyses.

Antioxidants in vegan diet and rheumatic disorders.

PubMed

Hänninen; Kaartinen, K; Rauma, A L; Nenonen, M; Törrönen, R; Häkkinen, A S; Adlercreutz, H; Laakso, J

2000-11-30

Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.

Effects of single and combined low frequency electromagnetic fields and simulated microgravity on gene expression of human mesenchymal stem cells during chondrogenesis

PubMed Central

Hammerschmid, Florian; Blum, Helmut; Krebs, Stefan; Redeker, Julia I.; Holzapfel, Boris M.; Jansson, Volkmar; Müller, Peter E.

2016-01-01

Introduction Low frequency electromagnetic fields (LF-EMF) and simulated microgravity (SMG) have been observed to affect chondrogenesis. A controlled bioreactor system was developed to apply LF-EMF and SMG singly or combined during chondrogenic differentiation of human mesenchymal stem cells (hMSCs) in 3D culture. Material and methods An external motor gear SMG bioreactor was combined with magnetic Helmholtz coils for EMF (5 mT; 15 Hz). Pellets of hMSCs (±TGF-β3) were cultured (P5) under SMG, LF-EMF, LF-EMF/SMG and control (1 g) conditions for 3 weeks. Sections were stained with safranin-O and collagen type II. Gene expression was evaluated by microarray and real-time polymerase chain reaction analysis. Results Simulated microgravity application significantly changed gene expression; specifically, COLXA1 but also COL2A1, which represents the chondrogenic potential, were reduced (p < 0.05). Low frequency electromagnetic fields application showed no gene expression changes on a microarray basis. LF-EMF/SMG application obtained significant different expression values from cultures obtained under SMG conditions with a re-increase of COL2A1, therefore rescuing the chondrogenic potential, which had been lowered by SMG. Conclusions Simulated microgravity lowered hypertrophy but also the chondrogenic potential of hMSCs. Combined LF-EMF/SMG provided a rescue effect of the chondrogenic potential of hMSCs although no LF-EMF effect was observed under optimal conditions. The study provides new insights into how LF-EMF and SMG affect chondrogenesis of hMSCs and how they generate interdependent effects. PMID:29765449

The effects of instruction and hand dominance on grip-to-load force coordination in manipulation tasks.

PubMed

Jin, Xin; Uygur, Mehmet; Getchell, Nancy; Hall, Susan J; Jaric, Slobodan

2011-10-31

The force applied upon a vertically oriented hand-held object could be decomposed into two orthogonal and highly coordinated components: the grip force (GF; the component perpendicular to the hand-object contact area that provides friction) and the load force (LF; the parallel component that can move the object or support the body). The aim of this study was to investigate the underexplored effects of task instruction and hand dominance on GF-LF coordination. Sixteen right-handed subjects performed bimanual manipulation against a horizontally oriented instrumented device under different sets of instructions. The tasks involved exertion of ramp-and-hold or oscillation patterns of LF performed symmetrically with two hands, while the instructions regarding individual actions were either similar (pull with both hands) or dissimilar (pull with one hand and hold with another). The results revealed that the instruction "to pull" leads to higher indices of GF-LF coordination than the instruction "to hold", as evidenced by a lower GF-LF ratio, higher GF-LF coupling, and higher GF modulation. The only effect of hand dominance was a moderate time lag of GF relative to LF changes observed in the non-dominant hand. We conclude that the instructions could play an important role in GF-LF coordination and, therefore, they should be taken into account when exploring or routinely testing hand function. Additionally, the results suggest that the neural control of GF of the non-dominant hand could involve some feedback mechanisms. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Experimental study on the human thermal comfort based on the heart rate variability (HRV) analysis under different environments.

PubMed

Zhu, Hui; Wang, Hanqing; Liu, Zhiqiang; Li, Duanru; Kou, Guangxiao; Li, Can

2018-03-01

In order to study the human thermal comfort under different environments, the electrocardiogram (ECG) data of 6 subjects were recorded continuously under 60 environments composed by different air temperature, relative humidity and air speed that were created by an environmental chamber. Based on the ECG data, the frequency-domain method was adopted to obtain the heart rate variability (HRV) results. Among the HRV indices, the ratio of the low frequency power and high frequency power of the HRV analysis results (LF/HF), which reflects the balance of the autonomic nervous system, was selected as an indicator of the thermal comfort in the study. And the effects of air temperature, relative humidity and air speed on LF/HF were scrutinized. Meanwhile, a questionnaire survey was conducted during the experiment to evaluate the thermal comfort of the subjects. And the relationships between mean LF/HF and thermal sensation, mean thermal comfort were established based on the survey. The results showed that different LF/HF was observed under different environments, and that the air temperature had the most significant effects on LF/HF. The changes in the air temperature could easily lead to the excitation of the sympathetic nerve that could promote the activities of the thermoregulatory effectors thus thermal discomfort. Additionally, the fitting curves illustrating the relationships between LF/HF and thermal sensation and thermal comfort showed that the higher LF/HF yielded thermal discomfort, while the low LF/HF indicated a thermally acceptable state. Copyright © 2017 Elsevier B.V. All rights reserved.

"Lactoferrin and Peptide-derivatives: Antimicrobial Agents with Potential Use in Nonspecific Immunity Modulation".

PubMed

Drago-Serrano, Maria Elisa; Campos-Rodriguez, Rafael; Carrero, Julio Cesar; de la Garza, Mireya

2018-03-27

Lactoferrin (Lf) is a conserved cationic non-heme glycoprotein that is part of the innate immune defense system of mammals. Lf is present in colostrum, milk and mucosal sites, and it is also produced by polymorphonuclear neutrophils and secreted at infection sites. Lf and Lf N-terminus peptide-derivatives named lactoferricins (Lfcins) are molecules with microbiostatic and microbicidal action in a wide array of pathogens. In addition, they display regulatory properties on components of nonspecific immunity, including toll-like receptors, pro- and anti-inflammatory cytokines, and reactive oxygen species. Mechanisms explaining the ability of Lf and Lfcins to display both up- and down-modulatory properties on cells are not fully understood but result, in part, from their interactions with membrane receptors that elicit biochemical signal pathways, whereas other receptors enable the nuclear translocation of these molecules for the modulation of target genes. The dual role of Lf and Lfcins as antimicrobials and immunomodulators is of biotechnological and pharmaceutical interest. Native Lf and its peptide-derivatives from human and bovine sources, the recombinant versions of the human protein, and their synthetic peptides have potential application as adjunctive agents in therapies to combat infections caused by multi-resistant bacteria and those caused by fungi, protozoa and viruses, as well as in the prevention and reduction of several types of cancer and response to LPS-shock, among other effects. In this review, we summarize the immunomodulatory properties of the unique multifunctional protein Lf and its N-terminus peptides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Lactoferrin promote primary rat osteoblast proliferation and differentiation via up-regulation of insulin-like growth factor-1 expression.

PubMed

Hou, Jian-ming; Wu, Man; Lin, Qing-ming; Lin, Fan; Xue, Ying; Lan, Xu-hua; Chen, En-yu; Wang, Mei-li; Yang, Hai-yan; Wang, Feng-xiong

2014-08-01

The aim of this study was to explore the effect of lactoferrin (LF) in primary fetal rat osteoblasts proliferation and differentiation and investigate the underlying molecular mechanisms. Primary rat osteoblasts were obtained from the calvarias of neonatal rats. Osteoblasts were treated with LF (0.1-1000 μg/mL), or OSI-906 [a selective inhibitor of insulin-like growth factor 1 (IGF-1) receptor and insulin receptor]. The IGF-1 was then knocked down by small hairpin RNA (shRNA) technology and then was treated with recombinant human IGF-1 or LF. Cell proliferation and differentiation were measured by MTT assay and alkaline phosphatase (ALP) assay, respectively. The expression of IGF-1 and IGF binding protein 2 (IGFBP2) mRNA were analyzed using real-time PCR. LF promotes the proliferation and differentiation of osteoblasts in a certain range (1-100 μg/mL) in time- and dose-dependent manner. The mRNA level of IGF-1 was significantly increased, while the expression of IGFBP2 was suppressed by LF treatment. Knockdown of IGF-1 by shRNA in primary rat osteoblast dramatically decreased the abilities of proliferation and differentiation of osteoblasts and blocked the proliferation and differentiation effect of LF in osteoblasts. OSI906 (5 μM) blocked the mitogenic and differentiation of LF in osteoblasts. Proliferation and differentiation of primary rat osteoblasts in response to LF are mediated in part by stimulating of IGF-1 gene expression and alterations in the gene expression of IGFBP2.

Interfacial engineering using mixed protein systems: emulsion-based delivery systems for encapsulation and stabilization of β-carotene.

PubMed

Mao, Yingyi; Dubot, Marie; Xiao, Hang; McClements, David Julian

2013-05-29

Emulsion-based delivery systems are needed to encapsulate, protect, and deliver lipophilic bioactive components in the food, personal care, and pharmaceutical industries. The functional performance of these systems can be controlled by engineering the composition and structure of the interfacial layer coating the lipid droplets. In this study, interfacial properties were controlled using two globular proteins with widely differing isoelectric points: lactoferrin (LF: pI ≈ 8.5) and β-lactoglobulin (BLG: pI ≈ 5). Oil-in-water emulsions were prepared with different interfacial properties: [LF]-only; [BLG]-only; [LF]-[BLG]-(laminated); [BLG]-[LF]-(laminated); and [BLG/LF]-(mixed). The influence of pH, ionic strength, and temperature on the physical stability of β-carotene-enriched emulsions was investigated. [LF]-emulsions were stable to droplet aggregation from pH 2 to 9 (0 mM NaCl), but all other emulsions aggregated at intermediate pH values. [BLG]-emulsions aggregated at high salt levels (≥50 mM NaCl), but all other emulsions were stable (0 to 300 mM NaCl). [BLG/LF]-emulsions were unstable to heating (≥60 °C), but all other emulsions were stable (30 to 90 °C). Color fading due to β-carotene degradation occurred relatively quickly in [BLG]-emulsions (37 °C) but was considerably lower in all other emulsions, which was attributed to the ability of LF to bind iron or interact with β-carotene. This study provides useful information for designing emulsion-based delivery systems to encapsulate and protect bioactive lipids, such as carotenoids.

Antibacterial activity in bovine lactoferrin-derived peptides.

PubMed Central

Hoek, K S; Milne, J M; Grieve, P A; Dionysius, D A; Smith, R

1997-01-01

Several peptides sharing high sequence homology with lactoferricin B (Lf-cin B) were generated from bovine lactoferrin (Lf) with recombinant chymosin. Two peptides were copurified, one identical to Lf-cin B and another differing from Lf-cin B by the inclusion of a C-terminal alanine (lactoferricin). Two other peptides were copurified from chymosin-hydrolyzed Lf, one differing from Lf-cin B by the inclusion of C-terminal alanyl-leucine and the other being a heterodimer linked by a disulfide bond. These peptides were isolated in a single step from chymosin-hydrolyzed Lf by membrane ion-exchange chromatography and were purified by reverse-phase high-pressure liquid chromatography (HPLC). They were characterized by N-terminal Edman sequencing, mass spectrometry, and antibacterial activity determination. Pure lactoferricin, prepared from pepsin-hydrolyzed Lf, was purified by standard chromatography techniques. This peptide was analyzed against a number of gram-positive and gram-negative bacteria before and after reduction of its disulfide bond or cleavage after its single methionine residue and was found to inhibit the growth of all the test bacteria at a concentration of 8 microM or less. Subfragments of lactoferricin were isolated from reduced and cleaved peptide by reverse-phase HPLC. Subfragment 1 (residues 1 to 10) was active against most of the test microorganisms at concentrations of 10 to 50 microM. Subfragment 2 (residues 11 to 26) was active against only a few microorganisms at concentrations up to 100 microM. These antibacterial studies indicate that the activity of lactoferricin is mainly, but not wholly, due to its N-terminal region. PMID:8980754

Purification and biophysical characterization of the core protease domain of anthrax lethal factor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gkazonis, Petros V.; Dalkas, Georgios A.; Chasapis, Christos T.

2010-06-04

Anthrax lethal toxin (LeTx) stands for the major virulence factor of the anthrax disease. It comprises a 90 kDa highly specific metalloprotease, the anthrax lethal factor (LF). LF possesses a catalytic Zn{sup 2+} binding site and is highly specific against MAPK kinases, thus representing the most potent native biomolecule to alter and inactivate MKK [MAPK (mitogen-activated protein kinase) kinases] signalling pathways. Given the importance of the interaction between LF and substrate for the development of anti-anthrax agents as well as the potential treatment of nascent tumours, the analysis of the structure and dynamic properties of the LF catalytic site aremore » essential to elucidate its enzymatic properties. Here we report the recombinant expression and purification of a C-terminal part of LF (LF{sub 672-776}) that harbours the enzyme's core protease domain. The biophysical characterization and backbone assignments ({sup 1}H, {sup 13}C, {sup 15}N) of the polypeptide revealed a stable, well folded structure even in the absence of Zn{sup 2+}, suitable for high resolution structural analysis by NMR.« less

Predicting fracture of mortar beams under three-point bending using non-extensive statistical modeling of electric emissions

NASA Astrophysics Data System (ADS)

Stergiopoulos, Ch.; Stavrakas, I.; Triantis, D.; Vallianatos, F.; Stonham, J.

2015-02-01

Weak electric signals termed as 'Pressure Stimulated Currents, PSC' are generated and detected while cement based materials are found under mechanical load, related to the creation of cracks and the consequent evolution of cracks' network in the bulk of the specimen. During the experiment a set of cement mortar beams of rectangular cross-section were subjected to Three-Point Bending (3PB). For each one of the specimens an abrupt mechanical load step was applied, increased from the low load level (Lo) to a high final value (Lh) , where Lh was different for each specimen and it was maintained constant for long time. The temporal behavior of the recorded PSC show that during the load increase a spike-like PSC emission was recorded and consequently a relaxation of the PSC, after reaching its final value, follows. The relaxation process of the PSC was studied using non-extensive statistical physics (NESP) based on Tsallis entropy equation. The behavior of the Tsallis q parameter was studied in relaxation PSCs in order to investigate its potential use as an index for monitoring the crack evolution process with a potential use in non-destructive laboratory testing of cement-based specimens of unknown internal damage level. The dependence of the q-parameter on the Lh (when Lh <0.8Lf), where Lf represents the 3PB strength of the specimen, shows an increase on the q value when the specimens are subjected to gradually higher bending loadings and reaches a maximum value close to 1.4 when the applied Lh becomes higher than 0.8Lf. While the applied Lh becomes higher than 0.9Lf the value of the q-parameter gradually decreases. This analysis of the experimental data manifests that the value of the entropic index q obtains a characteristic decrease while reaching the ultimate strength of the specimen, and thus could be used as a forerunner of the expected failure.

Complete genomic sequence of the Lactobacillus temperate phage LF1.

PubMed

Yoon, Bo Hyun; Chang, Hyo Ihl

2011-10-01

Bacteriophage LF1, a newly isolated temperate phage from a mitomycin-C-induced lysate of wild type Lactobacillus fermentum, was found to contain a double-strand DNA of 42,606 base pairs (bp) with a G+C content of 45%. Bioinformatic analysis of the phage genome revealed 57 putative open reading frames (ORFs). The predicted protein products of ORFs were determined and described. According to morphological analysis by transmission electron microscopy (TEM), LF1 has an isometric head and a non-contractile tail, indicating that it belongs to the family Siphoviridae. The temperate phage LF1 has a good genetic mosaic relationship with ΦPYB5 in the packaging module. To our knowledge, this is first report of genomic sequencing and characterization of temperate phage LF1 from wild-type L. fermentum isolated from Kimchi in Korea.

Brain-Derived Neurotrophic Factor in Patients with Primary Open-Angle Glaucoma and Age-related Cataract.

PubMed

Shpak, Alexander A; Guekht, Alla B; Druzhkova, Tatiana A; Kozlova, Ksenia I; Gulyaeva, Natalia V

2018-02-01

To study brain-derived neurotrophic factor (BDNF) content in aqueous humor (AH), lacrimal fluid (LF), and blood serum (BS) in patients with age-related cataract and primary open-angle glaucoma (POAG). BDNF was studied in 57 patients with age-related cataract, 55 patients with POAG combined with cataract, and 29 healthy controls (one eye in each person). AH was sampled during cataract surgery. The levels of BDNF in LF and BS did not differ in cataract patients and controls. The concentration of BDNF (pg/mL) in patients with POAG and cataract was lower than in cataract patients in AH (35.2 ± 14.2 vs. 54.6 ± 29.6, P < 0.001), LF (78.0 ± 25.1 vs. 116.2 ± 43.1, P < 0.001), and BS (19230 ± 5960 vs. 22440 ± 7580, P < 0.02), while the AH/LF ratio was similar (0.46 ± 0.18 vs. 0.48 ± 0.19). The AH level of BDNF declined in early POAG and relatively increased in the next stages of the disease, inversely correlating with visual field index (Pearson's correlation coefficient r = -0.404, P = 0.002) and average retinal nerve fiber layer thickness (r = -0.322, P = 0.018). BDNF contents in LF and BS were also the lowest in early POAG. BDNF in AH strongly correlated with its content in LF (r = 0.66, P < 0.000). A formula was suggested to calculate the AH concentration of BDNF basing on its content in LF. BDNF contents are decreased in AH, LF, and BS of patients with POAG demonstrating a significant decrease in the early POAG and relative increase in the next stages of the disease. A strong correlation exists between BDNF contents in AH and LF.

Lactoferrin-binding proteins in Shigella flexneri.

PubMed Central

Tigyi, Z; Kishore, A R; Maeland, J A; Forsgren, A; Naidu, A S

1992-01-01

The ability of Shigella flexneri to interact with lactoferrin (Lf) was examined with a 125I-labeled protein-binding assay. The percent binding of human lactoferrin (HLf) and bovine lactoferrin (BLf) to 45 S. flexneri strains was 19 +/- 3 and 21 +/- 3 (mean +/- standard error of the mean), respectively. 125I-labeled HLf and BLf binding to strain M90T reached an equilibrium within 2 h. Unlabeled HLf and BLf displaced the 125I-HLf-bacteria interaction in a dose-dependent manner. The Lf-bacterium complex was uncoupled by KSCN or urea, but not by NaCl. The interaction was specific, and approximately 4,800 HLf binding sites (affinity constant [Ka], 690 nM) or approximately 5,700 BLf binding sites (Ka, 104 nM) per cell were estimated in strain M90T by a Scatchard plot analysis. The native cell envelope (CE) and outer membrane (OM) did not reveal Lf-binding components in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. However, after being boiled, the CE and OM preparations showed three distinct horseradish peroxidase-Lf reactive bands of about 39, 22, and 16 kDa. The 39-kDa component was also reactive to a monoclonal antibody specific for porin (PoI) proteins of members of the family Enterobacteriaceae. The Lf-binding protein pattern was similar with BLf or HLf, for Crb+ and Crb- strains. The protein-Lf complex was dissociable by KSCN or urea and was stable after treatment with NaCl. Variation (loss) in the O chain of lipopolysaccharide (LPS) markedly enhanced the Lf-binding capacity in the isogenic rough strain SFL1070-15 compared with its smooth parent strain, SFL1070. These data establish that Lf binds to specific components in the bacterial OM; the heat-modifiable, anti-PoI-reactive, and LPS-associated properties suggested that the Lf-binding proteins are porins in S. flexneri. Images PMID:1319403

Bovine lactoferrin binds oleic acid to form an anti-tumor complex similar to HAMLET.

PubMed

Fang, Bing; Zhang, Ming; Tian, Mai; Jiang, Lu; Guo, Hui Yuan; Ren, Fa Zheng

2014-04-04

α-Lactalbumin (α-LA) can bind oleic acid (OA) to form HAMLET-like complexes, which exhibited highly selective anti-tumor activity in vitro and in vivo. Considering the structural similarity to α-LA, we conjectured that lactoferrin (LF) could also bind OA to obtain a complex with anti-tumor activity. In this study, LF-OA was prepared and its activity and structural changes were compared with α-LA-OA. The anti-tumor activity was evaluated by methylene blue assay, while the apoptosis mechanism was analyzed using flow cytometry and Western blot. Structural changes of LF-OA were measured by fluorescence spectroscopy and circular dichroism. The interactions of OA with LF and α-LA were evaluated by isothermal titration calorimetry (ITC). LF-OA was obtained by heat-treatment at pH8.0 with LD50 of 4.88, 4.95 and 4.62μM for HepG2, HT29, and MCF-7 cells, respectively, all of which were 10 times higher than those of α-LA-OA. Similar to HAMLET, LF-OA induced apoptosis in tumor cells through both death receptor- and mitochondrial-mediated pathways. Exposure of tryptophan residues and the hydrophobic regions as well as the loss of tertiary structure were observed in LF-OA. Besides these similarities, LF showed different secondary structure changes when compared with α-LA, with a decrease of α-helix and β-turn and an increase of β-sheet and random coil. ITC results showed that there was a higher binding number of OA to LF than to α-LA, while both of the proteins interacted with OA through van der Waals forces and hydrogen bonds. This study provides a theoretical basis for further exploration of protein-OA complexes. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Postexposure prophylaxis for Lassa fever: Experience from a recent outbreak in Nigeria.

PubMed

Isa, Samson E; Okwute, Attah; Iraoyah, Kelly O; Nathan, Shehu Y; Simji, Gomerep S; Okolo, Mark O; Anejo-Okopi, Joseph; Spicola, Daria; Isa, Daisy E

2016-01-01

Secondary transmission of Lassa fever (LF) occurs in the community and in health-care facilities, and is associated with high fatality in Nigeria. We investigated the role of oral ribavirin postexposure prophylaxis (orPEP) in preventing LF among the primary contacts of confirmed cases from December 2015 to March 2016. Epidemiological and clinical data of LF contacts were prospectively collected. However, information regarding ribavirin adverse effects (AEs) were collected retrospectively through a telephone interview. High-risk contacts were clinically monitored ΁ orPEP. Thirty-five (94.6%) out of the 37 individuals enrolled in the study were contacts of confirmed LF cases, and friends and family members (54%) constituted the largest group. However, only 29 (83%) individuals were classified as high-risk contacts. Twenty-one (60%) of contacts were prescribed ribavirin with 6 (28.6%) of them reporting AEs. Body weakness (33%) was the most frequent AE, but there was no incidence of treatment discontinuation due to AE. Furthermore, there were no reported cases of LF among all respondents (0%), whether they had orPEP or not. Secondary transmission of LF seems uncommon and the benefit of orPEP is uncertain. Although AEs of ribavirin may not be uncommon, they are rarely serious enough to cause treatment interruption. More emphasis should be on supporting persons looking after LF cases adopt measures that minimize the risks of exposure.

Lactoferrin denaturation induced by anionic surfactants: The role of the ferric ion in the protein stabilization.

PubMed

Ferreira, Gabriel Max Dias; Ferreira, Guilherme Max Dias; Agudelo, Álvaro Javier Patiño; Hudson, Eliara Acipreste; Dos Santos Pires, Ana Clarissa; da Silva, Luis Henrique Mendes

2018-05-11

Here, investigation was made of the interaction between Lactoferrin (Lf) and the anionic surfactants sodium dodecyl sulfate (SDS), sodium dodecylbenzene sulfonate (SDBS), and sodium decyl sulfate (DSS), using isothermal titration calorimetry, Nano differential scanning calorimetry (NanoDSC), and fluorescence spectroscopy. The Lf-surfactant interaction was enthalpically favorable (the integral enthalpy change ranged from -5.99 kJ mol -1 , for SDS at pH 3.0, to -0.61 kJ mol -1 , for DSS at pH 12.0) and promoted denaturation of the protein. The Lf denaturation efficiency followed the order DSS < SDS < SDBS. The extent of binding of the surfactants to Lf strongly depended on pH and the surfactant structure, reaching a maximum value of 505 SDBS molecules per gram of Lf at pH 3.0. The different efficiencies of the surfactants in denaturing Lf were attributed to the balance of hydrophobic and electrostatic interactions, which also depended on pH and the surfactant structure, highlighting the SDBS-tryptophan residue specific interaction, where SDBS acted as a quencher of fluorescence. Interestingly, the NanoDSC and fluorescence measurements showed that the ferric ion bound to Lf increased its stability against denaturation induced by the surfactants. The results have important implications for understanding the influence of surfactants on structural changes in metalloproteins. Copyright © 2017. Published by Elsevier B.V.

The Galactic HII Region Luminosity Function at Infrared and Radio Wavelengths

NASA Astrophysics Data System (ADS)

Mascoop, Joshua; Anderson, Loren; Sandor Makai, Zoltan; Armentrout, William Paul

2018-01-01

HII regions are the clearest indicators of ongoing high-mass star formation. The HII region luminosity function (LF) therefore probes present global star formation properties, and its shape has been related to HII region properties and galaxy Hubble types. Most HII region LF studies to date have been conducted in external galaxies; due to observational difficulties, there have been relatively few studies of the Milky Way HII region LF. Using ~600 HII regions from the WISE Catalog of Galactic HII Regions, we examine the Galactic LF in the first quadrant. Our high-resolution view of Galactic star formation regions allows us to separate nearby sources, and our sample is complete for all HII regions ionized by single O9.5 stars.We analyze the Galactic LF at six infrared wavelengths - where the emission is due to dust - and also at 20 cm, where the emission is from ionized gas. All LFs have a similar shape, showing that infrared LFs can be used in place of ionized gas tracers. All LFs can be described by a single power law with an index of approximately -2, in agreement with previous studes. We find no compelling evidence of a break or "knee" in the LF. Moreover, we see no significant variation in the form of the LF as a function of heliocentric distance, HII region size, or Galactocentric radius.

Competitive and double antibody sandwich ELISA for the quantification of lactoferrins by using monoclonal and chicken egg yolk IgY antibodies.

PubMed

Sunwoo, Hoon; Gujral, Naiyana; Suresh, Mavanur

2011-01-01

Two effective competitive and double antibody sandwich ELISA based on monoclonal (MAb) and chicken egg yolk IgY antibodies were developed to determine lactoferrin (LF) content in infant and milk formulas. Leghorn laying hens were immunized with purified bovine and human LFs to produce anti-bovine LF and anti-human LF IgY antibody in the egg yolk. After 5-8 weeks of the immunization, anti-LF IgY was extracted and analyzed by ELISA. Specific IgY antibodies against LFs cross reacted with human and bovine LFs, examined by ELISA and western-blot assay. Such cross-reactivity suggested the presence of common antigenic determinants between human and bovine LFs. An indirect competitive ELISA was preferred to quantify LF in milk and infant formulas, since the range of detection is 3.125-50 μg/mL, which is broader compared to the biotinylated ELISA system (5-50 ng/mL). As per the indirect competitive ELISA system, IgY at a concentration of the 150 μg/mL was incubated with various concentrations of bovine LF ranged from 0.003-100 μg/mL. The immunoassay was used to estimate the total bovine LF content in the milk samples and infant formulas, ranging from 49.28-80.96 μg/mL and 29.92-60.00 μg/mL, respectively.

Influence of human lactoferrin expression on iron homeostasis, flavonoids, and antioxidants in transgenic tobacco.

PubMed

Kumar, Vinay; Gill, Tejpal; Grover, Sunita; Ahuja, Paramvir Singh; Yadav, Sudesh Kumar

2013-02-01

This study was aimed at to check the influence of human lactoferrin (hLF) expression on iron homeostasis, flavonoids, and antioxidants in transgenic tobacco. Transgenic tobacco expressing hLF cDNA under the control of a CaMV 35S promoter was produced. The iron content as well as chlorophyll content of transgenic tobacco was lower compared to mock and untransformed wild plants. Interestingly, hLF transgenic tobacco showed higher level of transcript expression for genes related to iron content regulation like iron transporter and metal transporter. While expression of genes related to iron storage such as ferritin 1 and ferritin 2 was downregulated. The transcript expression of genes encoding antioxidant enzymes such as glutathione reductase, glutathione-S-transferase, ascorbate peroxidase, and catalase was downregulated in hLF transgenic tobacco compared to controls. Further, the transcript expression of two important genes encoding dihydroflavonol reductase (DFR) and phenylalanine ammonia lyase regulatory enzymes of flavonoid biosynthesis pathway was analyzed. The expression of DFR was found to be downregulated, while PAL expression was upregulated in hLF transgenic tobacco compared to mock and untransformed wild plant. Total phenolics, flavonoids, and proanthocyanidins contents were found to be higher in hLF transgenic tobacco than the mock and untransformed wild plant. Results suggest that hLF expression in transgenic tobacco leads to iron deficiency, downregulation of antioxidant enzymes, and increase in total flavonoids.

Removal of Escherichia coli via low frequency electromagnetic field in riverbank filtration system.

NASA Astrophysics Data System (ADS)

Selamat, Rossitah; Abustan, Ismail; Rizal Arshad, Mohd; Mokhtar Kamal, Nurul Hana

2018-04-01

The removal of Escherichia coli (E. coli) via low frequency of electromagnetic field (LF-EMF) with different magnetic field was studied. LF-EMF is known as a high magnetic susceptibility method, which could affect E. coli growth without the usage of chemicals. The aim of this study was to investigate the removal of E. coli by using LF-EMF in water abstraction for the riverbank filtration (RBF) application. The effect of LF-EMF with the intensity of 2 to 10mT and 50Hz on coiled column of 1mm copper wire at 1 to 6 hours was assessed. The removal of E. coli after exposing to LF-EMF on the column model was measured using most probable number (MPN/100mL) and colonies forming unit (CFU/100mL) methods. Water flows into the column were varied up to 6 hours and with flowrate of 100 mL/min. Experimental results demonstrate that 100% of E. coli was removed at 8mT after 6 hours exposure. The magnetic field at 10mT removed 100% of E. coli after 4 hours exposure. The results obtained in this study proved that the LF-EMF was efficient in E. coli removal from RBF system. These finding indicated that the LF-EMF intensities and time of exposure can affect the removal of E. coli.

The Effect of Massage Therapy on Autonomic Activity in Critically Ill Children

PubMed Central

Guan, Ling; Yuskiv, Nataliya; Skippen, Peter; Brant, Rollin; Kissoon, Niranjan

2014-01-01

Objectives. Our main objective was to describe the effect of foot and hand (F&H) massage on the autonomic nervous system (ANS) activity in children hospitalized in a pediatric intensive care unit (PICU); the secondary objectives were to assess the relationship between ANS function and the clinical severity and to explore the effects of repeated massage sessions on the ANS. Methods. Design was a descriptive experimental study. Intervention was single or six session(s) of F&H massage. ANS function was assessed through the frequency-domain analysis of heart rate variability. Main metrics included high and low frequency power (HF and LF), HF + LF, and LF/HF ratio. Results. Eighteen children participated in the study. A strong Spearman's correlation (ρ = −0.77) was observed between HF + LF and clinical severity. During massage, the parasympathetic activity (measured by HF) increased significantly from baseline (P = 0.04) with a mean percentage increase of 75% (95% CI: 20%∼130%). LF increased by 56% (95% CI: 20%∼92%) (P = 0.026). Repeated sessions were associated with a persistent effect on HF and LF which peaked at the second session and remained stable thereafter. Conclusions. HF + LF is positively correlated with clinical severity. F&H massage can improve the ANS activity and the effect persists when repeated sessions are offered. PMID:25587344

Recombinant lactoferrin (Lf) of Vechur cow, the critical breed of Bos indicus and the Lf gene variants.

PubMed

Anisha, Shashidharan; Bhasker, Salini; Mohankumar, Chinnamma

2012-03-01

Vechur cow, categorized as a critically maintained breed by the FAO, is a unique breed of Bos indicus due to its extremely small size, less fodder intake, adaptability, easy domestication and traditional medicinal property of the milk. Lactoferrin (Lf) is an iron-binding glycoprotein that is found predominantly in the milk of mammals. The full coding region of Lf gene of Vechur cow was cloned, sequenced and expressed in a prokaryotic system. Antibacterial activity of the recombinant Lf showed suppression of bacterial growth. To the best of our knowledge this is the first time that the full coding region of Lf gene of B. indicus Vechur breed is sequenced, successfully expressed in a prokaryotic system and characterized. Comparative analysis of Lf gene sequence of five Vechur cows with B. taurus revealed 15 SNPs in the exon region associated with 11 amino acid substitutions. The amino acid arginine was noticed as a pronounced substitution and the tertiary structure analysis of the BLfV protein confirmed the positions of arginine in the β sheet region, random coil and helix region 1. Based on the recent reports on the nutritional therapies of arginine supplementation for wound healing and for cardiovascular diseases, the higher level of arginine in the lactoferrin protein of Vechur cow milk provides enormous scope for further therapeutic studies. Copyright © 2011 Elsevier B.V. All rights reserved.

Optimization of tetanus toxoid ammonium sulfate precipitation process using response surface methodology.

PubMed

Brgles, Marija; Prebeg, Pero; Kurtović, Tihana; Ranić, Jelena; Marchetti-Deschmann, Martina; Allmaier, Günter; Halassy, Beata

2016-10-02

Tetanus toxoid (TTd) is a highly immunogenic, detoxified form of tetanus toxin, a causative agent of tetanus disease, produced by Clostridium tetani. Since tetanus disease cannot be eradicated but is easily prevented by vaccination, the need for the tetanus vaccine is permanent. The aim of this work was to investigate the possibility of optimizing TTd purification, i.e., ammonium sulfate precipitation process. The influence of the percentage of ammonium sulfate, starting amount of TTd, buffer type, pH, temperature, and starting purity of TTd on the purification process were investigated using optimal design for response surface models. Responses measured for evaluation of the ammonium sulfate precipitation process were TTd amount (Lf/mL) and total protein content. These two parameters were used to calculate purity (Lf/mgPN) and the yield of the process. Results indicate that citrate buffer, lower temperature, and lower starting amount of TTd result in higher purities of precipitates. Gel electrophoresis combined with matrix-assisted laser desorption ionization-mass spectrometric analysis of precipitates revealed that there are no inter-protein cross-links and that all contaminating proteins have pIs similar to TTd, so this is most probably the reason for the limited success of purification by precipitation.

Measurement fidelity of heart rate variability signal processing: The devil is in the details

PubMed Central

Jarrin, Denise C.; McGrath, Jennifer J.; Giovanniello, Sabrina; Poirier, Paul; Lambert, Marie

2017-01-01

Heart rate variability (HRV) is a particularly valuable quantitative marker of the flexibility and balance of the autonomic nervous system. Significant advances in software programs to automatically derive HRV have led to its extensive use in psychophysiological research. However, there is a lack of systematic comparisons across software programs used to derive HRV indices. Further, researchers report meager details on important signal processing decisions making synthesis across studies challenging. The aim of the present study was to evaluate the measurement fidelity of time- and frequency-domain HRV indices derived from three predominant signal processing software programs commonly used in clinical and research settings. Triplicate ECG recordings were derived from 20 participants using identical data acquisition hardware. Among the time-domain indices, there was strong to excellent correspondence (ICCavg =0.93) for SDNN, SDANN, SDNNi, rMSSD, and pNN50. The frequency-domain indices yielded excellent correspondence (ICCavg =0.91) for LF, HF, and LF/HF ratio, except for VLF which exhibited poor correspondence (ICCavg =0.19). Stringent user-decisions and technical specifications for nuanced HRV processing details are essential to ensure measurement fidelity across signal processing software programs. PMID:22820268

Atomic structure of the murine norovirus protruding domain and sCD300lf receptor complex.

PubMed

Kilic, Turgay; Koromyslova, Anna; Malak, Virginie; Hansman, Grant S

2018-03-21

Human noroviruses are the leading cause of acute gastroenteritis in human. Noroviruses also infect animals such as cow, mice, cat, and dog. How noroviruses bind and enter host cells is still incompletely understood. Recently, the type I transmembrane protein CD300lf was recently identified as the murine norovirus receptor, yet it is unclear how the virus capsid and receptor interact at the molecular level. In this study, we determined the X-ray crystal structure of the soluble CD300lf (sCD300lf) and murine norovirus capsid-protruding domain complex at 2.05 Å resolution. We found that the sCD300lf binding site is located on the topside of the protruding domain and involves a network of hydrophilic and hydrophobic interactions. The sCD300lf locked nicely into a complementary cavity on the protruding domain that is additionally coordinated with a positive surface charge on the sCD300lf and a negative surface charge on the protruding domain. Five of six protruding domain residues interacting with sCD300lf were maintained between different murine norovirus strains, suggesting that the sCD300lf was capable of binding to a highly conserved pocket. Moreover, a sequence alignment with other CD300 paralogs showed that the sCD300lf interacting residues were partially conserved in CD300ld, but variable in other CD300 family members, consistent with previously reported infection selectivity. Overall, these data provide insights into how a norovirus engages a protein receptor and will be important for a better understanding of selective recognition and norovirus attachment and entry mechanisms. IMPORTANCE Noroviruses exhibit exquisite host-range specificity due to species-specific interactions between the norovirus capsid protein and host molecules. Given this strict host-range restriction it has been unclear how the viruses are maintained within a species between relatively sporadic epidemics. While much data demonstrates that noroviruses can interact with carbohydrates, recent work has shown that expression of the protein CD300lf is both necessary and sufficient for murine norovirus infection of mice and binding of the virus to permissive cells. Importantly, the expression of this murine protein by human cells renders them fully permissive for murine norovirus infection, indicating that at least in this case host-range restriction is determined by molecular events that control receptor binding and entry. Defining the atomic-resolution interactions between the norovirus capsid protein and its cognate receptor is essential for a molecular understanding of host-range restriction and norovirus tropism. Copyright © 2018 American Society for Microbiology.

Immunization of pregnant cows with Shiga toxin-2 induces high levels of specific colostral antibodies and lactoferrin able to neutralize E. coli O157:H7 pathogenicity.

PubMed

Albanese, Adriana; Sacerdoti, Flavia; Seyahian, E Abril; Amaral, Maria Marta; Fiorentino, Gabriela; Fernandez Brando, Romina; Vilte, Daniel A; Mercado, Elsa C; Palermo, Marina S; Cataldi, Angel; Zotta, Elsa; Ibarra, Cristina

2018-03-20

E. coli O157:H7 is a foodborne pathogen responsible for bloody diarrhea, hemorrhagic colitis and hemolytic uremic syndrome (HUS). The objective of the present work was to evaluate the ability of colostral IgG obtained from Stx2-immunized cows to prevent against E. coli O157:H7 infection and Stx2 cytotoxicity. Hyperimmune colostrum (HC) was obtained from cows intramuscularly immunized with inactivated Stx2 or vehicle for controls. Colostral IgG was purified by affinity chromatography. Specific IgG antibodies against Stx2 and bovine lactoferrin (bLF) levels in HC and the corresponding IgG (HC-IgG/bLF) were determined by ELISA. The protective effects of HC-IgG/bLF against Stx2 cytotoxicity and adhesion of E. coli O157:H7 and its Stx2-negative mutant were analyzed in HCT-8 cells. HC-IgG/bLF prevention against E. coli O157:H7 was studied in human colon and rat colon loops. Protection against a lethal dose of E. coli O157:H7 was evaluated in a weaned mice model. HC-IgG/bLF showed high anti-Stx2 titers and high bLF levels that were able to neutralize the cytotoxic effects of Stx2 in vitro and in vivo. Furthermore, HC-IgG/bLF avoided the inhibition of water absorption induced by E. coli O157:H7 in human colon and also the pathogenicity of E. coli O157:H7 and E. coli O157:H7Δstx2 in rat colon loops. Finally, HC-IgG/bLF prevented in a 100% the lethality caused by E. coli O157:H7 in a weaned mice model. Our study suggests that HC-IgG/bLF have protective effects against E. coli O157:H7 infection. These beneficial effects may be due to specific anti-Stx2 neutralizing antibodies in combination with high bLF levels. These results allow us to consider HC-IgG/bLF as a nutraceutical tool which could be used in combination with balanced supportive diets to prevent HUS. However further studies are required before recommendations can be made for therapeutic and clinical applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Low-gradient aortic stenosis

PubMed Central

Clavel, Marie-Annick; Magne, Julien; Pibarot, Philippe

2016-01-01

Abstract An important proportion of patients with aortic stenosis (AS) have a ‘low-gradient’ AS, i.e. a small aortic valve area (AVA <1.0 cm2) consistent with severe AS but a low mean transvalvular gradient (<40 mmHg) consistent with non-severe AS. The management of this subset of patients is particularly challenging because the AVA-gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF-LG. Furthermore, a substantial proportion of patients with AS may have a normal-flow, low-gradient (NF-LG) AS: i.e. a small AVA—low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high-gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS. PMID:27190103

Responses of heart rate variability to acute pain after minor spinal surgery: optimal thresholds and correlation with the numeric rating scale.

PubMed

Sesay, Musa; Robin, Georges; Tauzin-Fin, Patrick; Sacko, Oumar; Gimbert, Edouard; Vignes, Jean-Rodolphe; Liguoro, Dominique; Nouette-Gaulain, Karine

2015-04-01

The autonomic nervous system is influenced by many stimuli including pain. Heart rate variability (HRV) is an indirect marker of the autonomic nervous system. Because of paucity of data, this study sought to determine the optimal thresholds of HRV above which the patients are in pain after minor spinal surgery (MSS). Secondly, we evaluated the correlation between HRV and the numeric rating scale (NRS). Following institutional review board approval, patients who underwent MSS were assessed in the postanesthesia care unit after extubation. A laptop containing the HRV software was connected to the ECG monitor. The low-frequency band (LF: 0.04 to 0.5 Hz) denoted both sympathetic and parasympathetic activities, whereas the high-frequency band (HF: 0.15 to 0.4 Hz) represented parasympathetic activity. LF/HF was the sympathovagal balance. Pain was quantified by the NRS ranging from 0 (no pain) to 10 (worst imaginable pain). Simultaneously, HRV parameters were noted. Optimal thresholds were calculated using receiver operating characteristic curves with NRS>3 as cutoff. The correlation between HRV and NRS was assessed using the Spearman rank test. We included 120 patients (64 men and 56 women), mean age 51±14 years. The optimal pain threshold values were 298 ms for LF and 3.12 for LF/HF, with no significant change in HF. NRS was correlated with LF (r=0.29, P<0.005) and LF/HF (r=0.31, P<0.001) but not with HF (r=0.09, NS). This study suggests that, after MSS, values of LF>298 m and LF/HF>3.1 denote acute pain (NRS>3). These HRV parameters are significantly correlated with NRS.

New methodology to assess activity status of occlusal caries in primary teeth using laser fluorescence device.

PubMed

Braga, Mariana Minatel; de Benedetto, Monique Saveriano; Imparato, Jose Carlos Pettorossi; Mendes, Fausto Medeiros

2010-01-01

An in vivo study was conducted to verify the ability of laser fluorescence (LF) to assess the activity status of occlusal caries in primary teeth, using different air-drying times. Occlusal sites (707) were examined using LF (DIAGNOdent) after air-drying for 3 s and 15 s, and the difference between readings (DIF15 s-3 s) was calculated. For concurrent validation of LF, visual criteria-Nyvad (NY) and Lesion Activity Assessment associated with the International Caries Detection and Assessment System (LAA-ICDAS)-were the reference standards for lesion activity. Histological exam using a pH-indicator dye (0.1% methyl red) was performed in 46 exfoliated/extracted teeth for criterion validation. LF readings and DIF15 s-3 s were compared using Kruskall-Wallis and Mann-Whitney tests. Receiver operating characteristic analyses were performed and validity parameters calculated, considering the caries activity assessment. Using NY, active lesions (3 s: 30.0+/-29.3; 15 s: 34.2+/-30.6) presented higher LF readings than inactive lesions (3 s: 17.0+/-16.3; 15 s: 19.2+/-17.3; p<0.05), different from LAA-ICDAS. Active cavitated caries resulted in higher LF readings (3 s: 50.3+/-3.5; 15 s: 54.7+/-30.2) than inactive cavitated caries (3 s: 19.9+/-16.3; 15 s: 22.8+/-16.8). Therefore, LF can distinguish cavitated active and inactive lesions classified by NY, but not by LAA-ICDAS; however, this difference might be related to the visual system rather than to LF. The air-drying time could be an alternative to improve the caries activity assessment; however, longer air-drying time is suggested to be tested subsequently.

Efficiency of the Lung Flute for sputum induction in patients with presumed pulmonary tuberculosis.

PubMed

Sakashita, Kentaro; Fujita, Akira; Takamori, Mikio; Nagai, Takayuki; Matsumoto, Tomoshige; Saito, Takefumi; Nakagawa, Taku; Ogawa, Kenji; Shigeto, Eriko; Nakatsumi, Yasuto; Goto, Hajime; Mitarai, Satoshi

2018-04-01

High quality sputum helps increase the sensitivity of the diagnosis of pulmonary tuberculosis. To evaluate the efficiency of the acoustic device (Lung Flute; LF) in sputum induction compared with the conventional method, hypertonic saline inhalation (HSI). In this crossover study, patients with presumed pulmonary tuberculosis submitted 3 consecutive sputa: the first sputum without induction and the second and third ones using LF and HSI. We compared the efficiency of the 2 induction methods. Sixty-four participants were eligible. Thirty-five (54.6%) patients had negative smears on the first sputum without induction. Among those patients, 25.7% and 22.9% patients were smear-positive after using LF and HSI, respectively (P = .001). The positive conversion rate was not significantly different between the methods. The first samples without induction yielded 65.7% positive cultures, whereas 71.4% and 77.1% of the samples from LF and HSI were positive, respectively (P = .284). Similar results were observed in the nucleic acid amplification test [no induction (60.0%), LF (72.0%) and HSI (60.0%); P = .341]. In 29 smear-positive patients on the first sputum without induction, we observed no significant increase in smear grade, culture yield and nucleic acid amplification test positivity with either method. LF tended to induce fewer adverse events; desaturation (3.1% vs 11.1%; P = .082) and throat pain (1.5% vs 9.5%; P = .057). LF showed significantly fewer total adverse events (15.8% vs 34.9%; P = .023). Our study showed LF had similar sputum induction efficiency to HSI with relatively fewer complications. © 2017 The Authors. The Clinical Respiratory Journal Published by John Wiley & Sons Ltd.

High- and low-frequency transcutaneous electrical nerve stimulation does not reduce experimental pain in elderly individuals

PubMed Central

Bergeron-Vézina, Kayla; Corriveau, Hélène; Martel, Marylie; Harvey, Marie-Philippe; Léonard, Guillaume

2015-01-01

Abstract Despite its widespread clinical use, the efficacy of transcutaneous electrical nerve stimulation (TENS) remains poorly documented in elderly individuals. In this randomized, double-blind crossover study, we compared the efficacy of high-frequency (HF), low-frequency (LF), and placebo (P) TENS in a group of 15 elderly adults (mean age: 67 ± 5 years). The effect of HF-, LF-, and P-TENS was also evaluated in a group of 15 young individuals (26 ± 5 years; same study design) to validate the effectiveness of the TENS protocols that were used in the elderly group. Each participant came to the laboratory on 3 separate occasions to receive, in random order, HF-, LF-, and P-TENS. Pain intensity and pain perception thresholds were assessed before, during, and after TENS, using an experimental heat pain paradigm. For the young group, there was a significant decrease in pain intensity during and after HF- and LF-TENS when compared with baseline, with both HF- and LF-TENS being superior to P-TENS. In the older group, HF- and LF-TENS did not reduce pain when compared with baseline and no difference was observed between the 2 active TENS sessions and P-TENS. High-frequency, LF-, and P-TENS all increased pain thresholds in young individuals, whereas in older individuals, only LF-TENS increased pain thresholds. Taken together, these results suggest that TENS is effective in young, but not in older, individuals. Future studies should be conducted to confirm these results in pain populations and to identify strategies that could enhance the effect of TENS in the elderly. PMID:26101836

Linear and nonlinear winter atmospheric responses to extreme phases of low frequency Pacific sea surface temperature variability

NASA Astrophysics Data System (ADS)

Cao, Dandan; Wu, Qigang; Hu, Aixue; Yao, Yonghong; Liu, Shizuo; Schroeder, Steven R.; Yang, Fucheng

2018-02-01

This study examines Northern Hemisphere winter (DJFM) atmospheric responses to opposite strong phases of interdecadal (low frequency, LF) Pacific sea surface temperature (SST) forcing, which resembles El Niño-Southern Oscillation (ENSO) on a longer time scale, in observations and GFDL and CAM4 model simulations. Over the Pacific-North America (PNA) sector, linear observed responses of 500-hPa height (Z500) anomalies resemble the PNA teleconnection pattern, but show a PNA-like nonlinear response because of a westward Z500 shift in the negative (LF-) relative to the positive LF (LF+) phase. Significant extratropical linear responses include a North Atlantic Oscillation (NAO)-like Z500 anomaly, a dipole-like Z500 anomaly over northern Eurasia associated with warming over mid-high latitude Eurasia, and a Southern Annular anomaly pattern associated with warming in southern land areas. Significant nonlinear Z500 responses also include a NAO-like anomaly pattern. Models forced by LF+ and LF- SST anomalies reproduce many aspects of observed linear and nonlinear responses over the Pacific-North America sector, and linear responses over southern land, but not in the North Atlantic-European sector and Eurasia. Both models simulate PNA-like linear responses in the North Pacific-North America region similar to observed, but show larger PNA-like LF+ responses, resulting in a PNA nonlinear response. The nonlinear PNA responses result from both nonlinear western tropical Pacific rainfall changes and extratropical transient eddy feedbacks. With LF tropical Pacific forcing only (LFTP+ and LFTP-, climatological SST elsewhere), CAM4 simulates a significant NAO response to LFTP-, including a linear negative and nonlinear positive NAO response.

Inhibition of intestinal polyp growth by oral ingestion of bovine lactoferrin and immune cells in the large intestine.

PubMed

Iigo, Masaaki; Alexander, David B; Xu, Jiegou; Futakuchi, Mitsuru; Suzui, Masumi; Kozu, Takahiro; Akasu, Takayuki; Saito, Daizo; Kakizoe, Tadao; Yamauchi, Koji; Abe, Fumiaki; Takase, Mitsunori; Sekine, Kazunori; Tsuda, Hiroyuki

2014-10-01

Studies using animal models have demonstrated that ingestion of bovine lactoferrin (bLF) inhibits carcinogenesis in the colon and other organs of experimental animals. As a result of these studies, a blinded, randomized, controlled clinical trial was conducted in the National Cancer Center Hospital, Tokyo, Japan to determine whether ingestion of bLF had an effect on the growth of colorectal polyps in humans. Patients with colorectal polyps ≤5 mm diameter and likely to be adenomas ingested 0, 1.5, or 3.0 g bLF daily for 1 year. Ingestion of 3.0 g bLF suppressed the growth of colorectal polyps and increased the level of serum human lactoferrin in trial participants 63 years old or younger. The purpose of the present study was to investigate correlations between immune parameters and changes in polyp size. Trial participants with regressing polyps had increased NK cell activity, increased serum hLF levels (indicating increased neutrophil activity), and increased numbers of CD4+ cells in the polyps. These findings are consistent with a correlation between higher immune activity and suppression of colorectal polyps. In addition, participants with regressing polyps had lower numbers of PMNs and increased numbers of S100A8+ cells in the polyps, consistent with a correlation between lower inflammatory potential in the colon and suppression of colorectal polyps. Trial participants ingesting bLF had increased serum hLF levels, a possible increase in systemic NK cell activity, and increased numbers of CD4+ and CD161+ cells in the polyps. Taken together, our findings suggest that bLF suppressed colorectal polyps by enhancing immune responsiveness.

Leptospermum flavescens Constituent-LF1 Causes Cell Death through the Induction of Cell Cycle Arrest and Apoptosis in Human Lung Carcinoma Cells

PubMed Central

Navanesan, Suerialoasan; Abdul Wahab, Norhanom; Manickam, Sugumaran; Sim, Kae Shin

2015-01-01

Leptospermum flavescens Sm. (Myrtaceae), locally known as ‘Senna makki’ is a smallish tree that is widespread and recorded to naturally occur in the montane regions above 900 m a.s.l from Burma to Australia. Although the species is recorded to be used traditionally to treat various ailments, there is limited data on biological and chemical investigations of L. flavescens. The aim of the present study was to investigate and understand the ability of L. flavescens in inducing cell death in lung cancer cells. The cytotoxic potentials of the extraction yields (methanol, hexane, ethyl acetate and water extracts as wells as a semi pure fraction, LF1) were evaluated against two human non-small cell lung carcinoma cell lines (A549 and NCI-H1299) using the MTT assay. LF1 showed the greatest cytotoxic effect against both cell lines with IC50 values of 7.12 ± 0.07 and 9.62 ± 0.50 μg/ml respectively. LF1 treated cells showed a sub-G1 region in the cell cycle analysis and also caused the presence of apoptotic morphologies in cells stained with acridine orange and ethidium bromide. Treatment with LF1 manifested an apoptotic population in cells that were evaluated using the Annexin V/ propidium iodide assay. Increasing dosage of LF1 caused a rise in the presence of activated caspase-3 enzymes in treated cells. Blockage of cell cycle progression was also observed in LF1-treated cells. These findings suggest that LF1 induces apoptosis and cell cycle arrest in treated lung cancer cells. Further studies are being conducted to isolate and identify the active compound as well to better understand the mechanism involved in inducing cell death. PMID:26287817

Bovine Lactoferrin and Lactoferrin-Derived Peptides Inhibit the Growth of Vibrio cholerae and Other Vibrio species

PubMed Central

Acosta-Smith, Erika; Viveros-Jiménez, Karina; Canizalez-Román, Adrian; Reyes-Lopez, Magda; Bolscher, Jan G. M.; Nazmi, Kamran; Flores-Villaseñor, Hector; Alapizco-Castro, Gerardo; de la Garza, Mireya; Martínez-Garcia, Jesús J.; Velazquez-Roman, Jorge; Leon-Sicairos, Nidia

2018-01-01

Vibrio is a genus of Gram-negative bacteria, some of which can cause serious infectious diseases. Vibrio infections are associated with the consumption of contaminated food and classified in Vibrio cholera infections and non-cholera Vibrio infections. In the present study, we investigate whether bovine lactoferrin (bLF) and several synthetic peptides corresponding to bLF sequences, are able to inhibit the growth or have bactericidal effect against V. cholerae and other Vibrio species. The antibacterial activity of LF and LF-peptides was assessed by kinetics of growth or determination of colony forming unit in bacteria treated with the peptides and antibiotics. To get insight in the mode of action, the interaction between bLF and bLF-peptides (coupled to FITC) and V. cholera was evaluated. The damage of effector-induced bacterial membrane permeability was measured by inclusion of the fluorescent dye propidium iodide using flow cytometry, whereas the bacterial ultrastructural damage in bacteria treated was observed by transmission electron microscopy. The results showed that bLF and LFchimera inhibited the growth of the V. cholerae strains; LFchimera permeabilized the bacteria which membranes were seriously damaged. Assays with a multidrug-resistant strain of Vibrio species indicated that combination of sub-lethal doses of LFchimera with ampicillin or tetracycline strongly reduced the concentration of the antibiotics to reach 95% growth inhibition. Furthermore, LFchimera were effective to inhibit the V. cholerae counts and damage due to this bacterium in a model mice. These data suggest that LFchimera and bLF are potential candidates to combat the V. cholerae and other multidrug resistant Vibrio species. PMID:29375503

Poincaré plot indexes of heart rate variability detect dynamic autonomic modulation during general anesthesia induction.

PubMed

Hsu, Che-Hao; Tsai, Ming-Ya; Huang, Go-Shine; Lin, Tso-Chou; Chen, Kuen-Pao; Ho, Shung-Tai; Shyu, Liang-Yu; Li, Chi-Yuan

2012-03-01

Beat-to-beat heart rate variability (HRV) is caused by the fluctuating balance of sympathetic and parasympathetic tone. The Poincaré plot has been used to evaluate HRV. In this study, we validate that this new method may qualitatively and quantitatively assess the sympathovagal fluctuation in patients during induction of anesthesia with sevoflurane. Twenty-eight young patients were allocated for the study. The patients received a tilt test and on the next day they sustained anesthesia induced with inhaled anesthetics. Electrocardiography signals from the patients were relayed to an analogue-digital converter. The Poincaré plot is quantified by measuring SD1, SD2, and SD1/SD2. Power spectral analyses were performed and LF, HF and HF/LF were calculated. The LF power and the SD2 of the Poincaré plot increased while subjects were tilt-up from the supine position. Additionally, a significant correlation were found between LF and SD2, HF and SD1 (p < 0.05), and LF/HF and SD2/SD1 (p < 0.01). Sevoflurane inhalation for 10 minutes had no effect on heart rate, but diminished LF, total power and SD1, SD2 of the Poincaré plot respectively. However, the LF, SD2 and LF/HF increased; the HF, SD1 and SD1/SD2 ratio decreased after intubation stimulation. Poincaré plot and power spectral analysis of HRV during tilt test and sevoflurane induction significantly correlate. Poincaré plot analysis is easier and more sensitive at evaluating the sympathovagal balance and observing the beat-to-beat HRV. Copyright © 2012. Published by Elsevier B.V.

[BLG gene knockout and hLF gene knock-in at BLG locus in goat by TALENs].

PubMed

Song, Shaozheng; Zhu, Mengmin; Yuan, Yuguo; Rong, Yao; Xu, Sheng; Chen, Si; Mei, Junyan; Cheng, Yong

2016-03-01

To knock out β-lactoglobulin (BLG) gene and insert human lactoferrin (hLF) coding sequence at BLG locus of goat, the transcription activator-like effector nucleases (TALEN) mediated recombination was used to edit the BLG gene of goat fetal fibroblast, then as donor cells for somatic cell nuclear transfer. We designed a pair of specific plasmid TALEN-3-L/R for goat BLG exon III recognition sites, and BLC14-TK vector containing a negative selection gene HSV-TK, was used for the knock in of hLF gene. TALENs plasmids were transfected into the goat fetal fibroblast cells, and the cells were screened three days by 2 μg/mL puromycin. DNA cleavage activities of cells were verified by PCR amplification and DNA production sequencing. Then, targeting vector BLC14-TK and plasmids TALEN-3-L/R were co-transfected into goat fetal fibroblasts, both 700 μg/mL G418 and 2 μg/mL GCV were simultaneously used to screen G418-resistant cells. Detections of integration and recombination were implemented to obtain cells with hLF gene site-specific integration. We chose targeting cells as donor cells for somatic cell nuclear transfer. The mutagenicity of TALEN-3-L/R was between 25% and 30%. A total of 335 reconstructed embryos with 6 BLG-/hLF+ targeting cell lines were transferred into 16 recipient goats. There were 9 pregnancies confirmed by ultrasound on day 30 to 35 (pregnancy rate of 39.1%), and one of 50-day-old fetus with BLG-/hLF+ was achieved. These results provide the basis for hLF gene knock-in at BLG locus of goat and cultivating transgenic goat of low allergens and rich hLF in the milk.

Recombinase polymerase amplification (RPA) combined with lateral flow (LF) strip for detection of Toxoplasma gondii in the environment.

PubMed

Wu, Y D; Xu, M J; Wang, Q Q; Zhou, C X; Wang, M; Zhu, X Q; Zhou, D H

2017-08-30

Toxoplasma gondii infects all warm-blooded vertebrates, resulting in a great threat to human health and significant economic loss to the livestock industry. Ingestion of infectious oocysts of T. gondii from the environment is the major source of transmission. Detection of T. gondii oocysts by existing methods is laborious, time-consuming and expensive. The objective of the present study was to develop a recombinase polymerase amplification (RPA) method combined with a lateral flow (LF) strip for detection of T. gondii oocysts in the soil and water. The DNA of T. gondii oocysts was amplified by a pair of specific primers based on the T. gondii B1 gene over 15min at a constant temperature ranging from 30°C to 45°C using RPA. The amplification product was visualized by the lateral flow (LF) strip within 5min using the specific probe added to the RPA reaction system. The sensitivity of the established assay was 10 times higher than that of nested PCR with a lower detection limit of 0.1 oocyst per reaction, and there was no cross-reactivity with other closely related protozoan species. Fifty environmental samples were further assessed for the detection validity of the LF-RPA assay (B1-LF-RPA) and compared with nested PCR based on the B1 gene sequence. The B1-LF-RPA and nested PCR both showed that 5 out of the 50 environmental samples were positive. The B1-LF-RPA method was also proven to be sufficiently tolerant of existing inhibitors in the environment. In addition, the advantages of simple operation, speediness and cost-effectiveness make B1-LF-RPA a promising molecular detection tool for T. gondii. Copyright © 2017 Elsevier B.V. All rights reserved.

Studies of ferroelectric and dielectric properties of pure and doped barium titanate prepared by sol-gel method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bisen, Supriya; Mishra, Ashutosh; Jarabana, Kanaka M.

2016-05-23

In this work, Barium Titanate (BaTiO{sub 3}) powders were synthesized via Sol-Gel auto combustion method using citric acid as a chelating agent. We study the behavior of ferroelectric and dielectric properties of pure and doped BaTiO{sub 3} on different concentration. To understand the phase and structure of the powder calcined at 900°C were characterized by X-ray Diffraction shows that tetragonal phase is dominant for pure and doped BTO and data fitted by Rietveld Refinement. Electric and Dielectric properties were characterized by P-E Hysteresis and Dielectric measurement. In P-E measurement ferroelectric loop tracer applied for different voltage. The temperature dependant dielectricmore » constant behavior was observed as a function of frequency recorded on hp-Hewlett Packard 4192A, LF impedance, 5Hz-13Hz analyzer.« less

A far wing line shape theory and its application to the water vibrational bands (II)

NASA Technical Reports Server (NTRS)

Ma, Q.; Tipping, R. H.

1992-01-01

Attention is given to a far wing line shape theory based on binary collision and quasi-static approximations. The theory is applicable for both the LF and HF wings of vibrational-rotational bands. It is used to calculate the frequency and temperature dependence of the continuous absorption coefficient for frequencies up to 10,000/cm for pure water vapor. The results are compared with existing laboratory data in the 2400-2700/cm window and in the 3000-4300/cm band center region, with field measurements in the 2000-2225/cm region and with a recent experimental measurement near 9466/cm. It is concluded that both the magnitude and temperature dependence of the water vapor continuum can be accounted for by the present theory without the introduction of any adjustable parameters. Refinements of the theory and extension to foreign-broadened absorption are also discussed.

Crystallographic evidence for noncoplanar catalytic aspartic acids in plasmepsin II resides in the Protein Data Bank.

PubMed

Robbins, Arthur H; Dunn, Ben M; Agbandje-McKenna, Mavis; McKenna, Robert

2009-03-01

The carboxylate atoms of the two catalytic aspartic acid residues in aspartic proteases are nearly coplanar and in the uncomplexed form share an in-plane nucleophilic water molecule that is central to the mechanism of these enzymes. This note reports that while reviewing the electron-density maps derived from the deposited data for uncomplexed plasmepsin II from Plasmodium falciparum [Asojo et al. (2003), J. Mol. Biol. 327, 173-181; PDB code 1lf4], it was discovered that the aspartic acid residues in this structure should in fact be distinctly noncoplanar. The crystallographic model from the deposited coordinates has been re-refined against the 1.9 A resolution published diffraction data to an R(cryst) of 21.2% and an R(free) of 22.2%. The catalytic water molecule is present, but the plane of the carboxylate group of Asp214 is rotated by 66 degrees from its original position.

Experimental investigation of standing wave effect in dual-frequency capacitively coupled argon discharges: role of a low-frequency source

NASA Astrophysics Data System (ADS)

Zhao, Kai; Liu, Yong-Xin; Kawamura, E.; Wen, De-Qi; Lieberman, M. A.; Wang, You-Nian

2018-05-01

It is well known that the plasma non-uniformity caused by the standing wave effect has brought about great challenges for plasma material processing. To improve the plasma uniformity, a low-frequency (LF) power source is introduced into a 100 MHz very-high-frequency (VHF) capacitively coupled argon plasma reactor. The effect of the LF parameters (LF voltage amplitude ϕ L and LF source f L) on the radial profile of plasma density has been investigated by utilizing a hairpin probe. The result at a low pressure (1 Pa) is compared to the one obtained by a 2D fluid-analytical capacitively coupled plasma model, showing good agreement in the plasma density radial profile. The experimental results show that the plasma density profile exhibits different dependences on ϕ L and f L at different gas pressures/electrode driven types (i.e., the two rf sources are applied on one electrode (case I) and separate electrodes (case II)). At low pressures (e.g., 8 Pa), the pronounced standing wave effect revealed in a VHF discharge can be suppressed at a relatively high ϕ L or a low f L in case I, because the HF sheath heating is largely weakened due to strong modulation by the LF source. By contrast, ϕ L and f L play insignificant roles in suppressing the standing wave effect in case II. At high pressures (e.g., 20 Pa), the opposite is true. The plasma density radial profile is more sensitive to ϕ L and f L in case II than in case I. In case II, the standing wave effect is surprisingly enhanced with increasing ϕ L at higher pressures; however, the center-high density profile caused by the standing wave effect can be compensated by increasing f L due to the enhanced electrostatic edge effect dominated by the LF source. In contrast, the density radial profile shows a much weaker dependence on ϕ L and f L in case I at higher pressures. To understand the different roles of ϕ L and f L, the electron excitation dynamics in each case are analyzed based on the measured spatio-temporal distributions of the electron-impact excitation rate by phase resolved optical emission spectroscopy.

Characteristics of dilatational infrasonic pulses accompanying low-frequency earthquakes at Miyakejima Volcano, Japan

NASA Astrophysics Data System (ADS)

Fujiwara, Yoshiaki; Yamasato, Hitoshi; Shimbori, Toshiki; Sakai, Takayuki

2014-12-01

Since the caldera-forming eruption of Miyakejima Volcano in 2000, low-frequency (LF) earthquakes have occurred frequently beneath the caldera. Some of these LF earthquakes are accompanied by emergent infrasonic pulses that start with dilatational phases and may be accompanied by the eruption of small amounts of ash. The estimated source locations of both the LF earthquakes and the infrasonic signals are within the vent at shallow depth. Moreover, the maximum seismic amplitude roughly correlates with the maximum amplitude of the infrasonic pulses. From these observations, we hypothesized that the infrasonic waves were excited by partial subsidence within the vent associated with the LF earthquakes. To verify our hypothesis, we used the infrasonic data to estimate the volumetric change due to the partial subsidence associated with each LF earthquake. The results showed that partial subsidence in the vent can well explain the generation of infrasonic waves.

VLF/LF Radio Sounding of Ionospheric Perturbations Associated with Earthquakes

PubMed Central

Hayakawa, Masashi

2007-01-01

It is recently recognized that the ionosphere is very sensitive to seismic effects, and the detection of ionospheric perturbations associated with earthquakes, seems to be very promising for short-term earthquake prediction. We have proposed a possible use of VLF/LF (very low frequency (3-30 kHz) /low frequency (30-300 kHz)) radio sounding of the seismo-ionospheric perturbations. A brief history of the use of subionospheric VLF/LF propagation for the short-term earthquake prediction is given, followed by a significant finding of ionospheric perturbation for the Kobe earthquake in 1995. After showing previous VLF/LF results, we present the latest VLF/LF findings; One is the statistical correlation of the ionospheric perturbation with earthquakes and the second is a case study for the Sumatra earthquake in December, 2004, indicating the spatical scale and dynamics of ionospheric perturbation for this earthquake.

Measured Early Lateral Energy Fractions in Concert Halls and Opera Houses

NASA Astrophysics Data System (ADS)

BARRON, M.

2000-04-01

In the 30 years since early lateral reflections were first suggested as important for concert halls, spatial impression and source broadening have become almost universally accepted as essential characteristics of halls with good acoustics. Two objective measures of source broadening have been proposed. Measured values of the best defined of these measures, the early lateral energy fraction (LF), are considered here. Results from two independent measurement surveys are discussed. Comparisons of LF values by hall show a significant link between hall mean LF and hall width. There is however considerable overlap between measured LF values in different halls so the relevance of describing halls by their mean early lateral energy fraction values is questionable. The behaviour of LF values within auditoria is discussed for different concert hall plan forms and within opera houses. A measure of source broadening including sound level is proposed and results considered in the context of auditorium design.

Synthesis, analysis and processing of novel materials in the yttrium oxide-aluminum oxide system

NASA Astrophysics Data System (ADS)

Marchal, Julien Claudius

In the current work, liquid feed flame spray pyrolysis (LF-FSP) was used to create three novel nanopowders in the Y2O3-Al 2O3 system: alpha-Al2O3, YAG (garnet Y3Al5O12) and hexagonal Y3Al 5O12. For example, LF-FSP combustion of metalloorganic yttrium and aluminum precursors in a 3/5 ratio forms hexagonal Y3Al5O 12, a newly discovered crystalline phase detailed in this work. The resulting 15-35 nm average particle size, single crystal nanopowders were characterized by TGA-DTA, XRD, HR-TEM, electron diffraction and FTIR. The data was used to establish a model for the crystal structure of this new phase (hexagonal, with crystal parameter of a = 0.736 nm, c = 1.052) consisting of a superlattice of substituted hexagonal YAlO3. YAG has been extensively investigated for its applications as scintillators, phosphors and as a laser host. Fully dispersible, unaggregated single crystal YAG nanopowders with average particle sizes of 35-50 nm were obtained from hexagonal Y3Al5O12 after annealing at 850°C-1200°C (for 2h-8d). The resulting YAG nanopowder was processed into green bodies using cold isostatic pressing after adding binders. 99%+ dense monoliths were obtained after sintering at 1400°C in vacuum (6-8 h), while maintaining grain sizes < 500 nm. The ability to sinter while keeping sub-micron grains differs from present techniques (where translucency is obtained through exaggerated grain growth to 5-10 microns) reported in the literature for sintering polycrystalline YAG, and is the first step for improving polycrystalline YAG laser host optical properties. LF-FSP processing of transition Al2O3 nanopowders converts them to single crystal alpha-Al2O3 nanopowders, previously thought impossible to obtain. The alpha-Al2O 3 nanopowders thus obtained, consist of unaggregated 30-40 nm single particles. These nanopowders were characterized by XRD, HR-TEM, SEM, DLS, FTIR. Green bodies of alpha-Al2O3 nanopowders were sintered to 99% density without sintering aids at 1400°C (6-8 h). After HIPing at 1400°C and 138 MPa, the pellets exhibited some transparency. LF-FSP thus allows synthesis of large quantities of previously unavailable alpha-Al 2O3 nanopowders necessary for developing nanograined alpha-Al 2O3 ceramic monoliths for transparent armors, polycrystalline laser hosts and prosthetic implants. Most importantly, it demonstrates the use of LF-FSP to modify the crystalline phase of nanopowders, without causing aggregation.

76 FR 73489 - Airworthiness Directives; Honeywell International Inc. Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-29

... Airworthiness Directives; Honeywell International Inc. Turbofan Engines AGENCY: Federal Aviation Administration...-1F, and LF507-IH turbofan engines. This AD requires removing from service certain second stage high... International Inc. ALF502L-2C, ALF502R-3, ALF502R-3A, ALF502R-5, LF507-1F, and LF507-IH turbofan engines, with...

Defense Environmental Restoration Program Annual Report to Congress for Fiscal Year 1986

DTIC Science & Technology

1987-03-16

LF 01 LANDFILL $3 AND HAROFILL RUFS C SITE LF 02 LANDFILL I RI C SITE LF 03 LANDFILL 2 RI C SITE LU 01 BLDG 2017 -BEA ABANDONED UST FS C SITE tU 02 BLDG...Army Amiunition Plant, Texarkana Hill Air force Base, Ogden Ogden Defense Depot, Ogden Toele Army Depot, Tooele VIFIOIA Defense General Supply Center

The effect of different fibre volume fraction on mechanical properties of banana/pineapple leaf (PaLF)/glass hybrid composite

NASA Astrophysics Data System (ADS)

Hanafee, Z. M.; Khalina, A.; Norkhairunnisa, M.; Syams, Z. Edi; Liew, K. E.

2017-09-01

This paper investigates the effect of fibre volume fraction on mechanical properties of banana-pineapple leaf (PaLF)-glass reinforced epoxy resin under tensile loading. Uniaxial tensile tests were carried out on specimens with different fibre contents (30%, 40%, 50% in weight). The composite specimens consists of 13 different combinations. The effect of hybridisation between synthetic and natural fibre onto tensile properties was determined and the optimum fibre volume fraction was obtained at 50% for both banana and PaLF composites. Additional 1 layer of woven glass fibre increased the tensile strength of banana-PaLF composite up to 85%.

Assessing Progress in Reducing the At-Risk Population after 13 Years of the Global Programme to Eliminate Lymphatic Filariasis

PubMed Central

Hooper, Pamela J.; Chu, Brian K.; Mikhailov, Alexei; Ottesen, Eric A.; Bradley, Mark

2014-01-01

Background In 1997, the World Health Assembly adopted Resolution 50.29, committing to the elimination of lymphatic filariasis (LF) as a public health problem, subsequently targeted for 2020. The initial estimates were that 1.2 billion people were at-risk for LF infection globally. Now, 13 years after the Global Programme to Eliminate Lymphatic Filariasis (GPELF) began implementing mass drug administration (MDA) against LF in 2000—during which over 4.4 billion treatments have been distributed in 56 endemic countries—it is most appropriate to estimate the impact that the MDA has had on reducing the population at risk of LF. Methodology/Principal Findings To assess GPELF progress in reducing the population at-risk for LF, we developed a model based on defining reductions in risk of infection among cohorts of treated populations following each round of MDA. The model estimates that the number of people currently at risk of infection decreased by 46% to 789 million through 2012. Conclusions/Significance Important progress has been made in the global efforts to eliminate LF, but significant scale-up is required over the next 8 years to reach the 2020 elimination goal. PMID:25411843

Can the individual calibration be modified when laser fluorescence method is used for caries detection?

PubMed

Reyes, Alessandra; Ferreira, Gisele E; Santos, Joyce; Mendes, Fausto M; Imparato, Jose C P; Braga, Mariana M

2013-03-01

Individual calibration (IC) for caries detection methods based on fluorescence is time-consuming, especially for paediatric dentists, if the calibration has to be performed tooth-by-tooth. However, it is not clear how this calibration actually interfere in laser fluorescence (LF) readings. This in vivo study was to verify the influence of different modes of IC on laser fluorescence (LF) readings. Ninety six occlusal and 95 buccal surfaces of 1st permanent molars were examined using LF device after IC performed on control (no IC), the examined teeth, a permanent incisor, a 1st primary molar or a 2nd primary molar. All modes of IC were performed in the same child. Wilcoxon test and Bland-Altman analysis were used to compare the readings. Intraclass correlation coefficients (ICC) were calculated. Laser fluorescence readings without prior calibration were higher than readings performed after any mode of IC and resulted in different values of ICC. After other IC modes, the LF readings were statistically similar. The absence of IC influences LF readings and LF reproducibility, but different IC methods can be considered in clinical practice. © 2012 The Authors. International Journal of Paediatric Dentistry © 2012 BSPD, IAPD and Blackwell Publishing Ltd.

Effects of Enteric-coated Lactoferrin Tablets Containing Lactobacillus brevis subsp. coagulans on Fecal Properties, Defecation Frequency and Intestinal Microbiota of Japanese Women with a Tendency for Constipation: a Randomized Placebo-controlled Crossover Study

PubMed Central

SUZUKI, Noriyuki; MURAKOSHI, Michiaki; ONO, Tomoji; MORISHITA, Satoru; KOIDE, Misao; BAE, Min Jung; TOTSUKA, Mamoru; SHIMIZU, Makoto; SUGIYAMA, Keikichi; NISHINO, Hoyoku; IIDA, Norio

2013-01-01

The effects of oral administration of enteric-coated tablets containing lactoferrin (LF; 100 mg/tablet) and heat-killed Lactobacillus brevis subsp. coagulans FREM BP-4693 (LB; 6×109 bacteria/tablet) on fecal properties were examined in 32 Japanese women (20–60 years of age) with a tendency for constipation (defecation frequency at equal to or less than 10 times/2 weeks) by a double-blind placebo-controlled crossover design. A significant increase in defecation days per week was obserbed in the subjects who ingested the tablets containing LF and LB compared with the placebo group. The number of bifidobacteria in feces also significantly increased compared with the placebo group. In an in vitro study, LF and tryptic hydrolysate of LF, but not peptic hydrolysate of LF, upregulated the growth of Bifidobacterium longum ATCC15707 when added to the culture. These results demonstrate the capability of the enteric-coated tablets containing LF and LB in improving intestinal function and suggest that they have a growth promoting function for bifidobacteria. PMID:24936358

Coacervates of lactotransferrin and β- or κ-casein: structure determined using SAXS.

PubMed

de Kruif, C G Kees; Pedersen, JanSkov; Huppertz, Thom; Anema, Skelte G

2013-08-20

Lactotransferrin (LF) is a large globular protein in milk with immune-regulatory and bactericidal properties. At pH 6.5, LF (M = 78 kDa) carries a net (calculated) charge of +21. β-Casein (BCN) and κ-casein (KCN) are part of the casein micelle complex in milk. Both BCN and KCN are amphiphillic proteins with a molar mass of 24 and 19 kDa and carry net charges of -14 and -4, respectively. Both BCN and KCN form soap-like micelles, with 40 and 65 monomers, respectively. The net negative charges are located in the corona of the micelles. On mixing LF with the caseins, coacervates are formed. We analyzed the structure of these coarcervates using SAXS. It was found that LF binds to the corona of the micellar structures, at the charge neutrality point. BCN/LF and KCN/LF ratios at the charge neutrality point were found to be ~1.2 and ~5, respectively. We think that the findings are relevant for the protection mechanism of globular proteins in bodily fluids where unstructured proteins are abundant (saliva). The complexes will prevent docking of enzymes on specific charged groups on the globular protein.

Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer's disease.

PubMed

Meng, Qingqing; Wang, Aiping; Hua, Hongchen; Jiang, Ying; Wang, Yiyun; Mu, Hongjie; Wu, Zimei; Sun, Kaoxiang

2018-01-01

Safe and effective delivery of therapeutic drugs to the brain is important for successful therapy of Alzheimer's disease (AD). To develop Huperzine A (HupA)-loaded, mucoadhesive and targeted polylactide-co-glycoside (PLGA) nanoparticles (NPs) with surface modification by lactoferrin (Lf)-conjugated N-trimethylated chitosan (TMC) (HupA Lf-TMC NPs) for efficient intranasal delivery of HupA to the brain for AD treatment. HupA Lf-TMC NPs were prepared using the emulsion-solvent evaporation method and optimized using the Box-Behnken design. The particle size, zeta potential, drug entrapment efficiency, adhesion and in vitro release behavior were investigated. The cellular uptake was investigated by fluorescence microscopy and flow cytometry. MTT assay was used to evaluate the cytotoxicity of the NPs. In vivo imaging system was used to investigate brain targeting effect of NPs after intranasal administration. The biodistribution of Hup-A NPs after intranasal administration was determined by liquid chromatography-tandem mass spectrometry. Optimized HupA Lf-TMC NPs had a particle size of 153.2±13.7 nm, polydispersity index of 0.229±0.078, zeta potential of +35.6±5.2 mV, drug entrapment efficiency of 73.8%±5.7%, and sustained release in vitro over a 48 h period. Adsorption of mucin onto Lf-TMC NPs was 86.9%±1.8%, which was significantly higher than that onto PLGA NPs (32.1%±2.5%). HupA Lf-TMC NPs showed lower toxicity in the 16HBE cell line compared with HupA solution. Qualitative and quantitative cellular uptake experiments indicated that accumulation of Lf-TMC NPs was higher than nontargeted analogs in 16HBE and SH-SY5Y cells. In vivo imaging results showed that Lf-TMC NPs exhibited a higher fluorescence intensity in the brain and a longer residence time than nontargeted NPs. After intranasal administration, Lf-TMC NPs facilitated the distribution of HupA in the brain, and the values of the drug targeting index in the mouse olfactory bulb, cerebrum (with hippocampus removal), cerebellum, and hippocampus were about 2.0, 1.6, 1.9, and 1.9, respectively. Lf-TMC NPs have good sustained-release effect, adhesion and targeting ability, and have a broad application prospect as a nasal drug delivery carrier.

The past matters: estimating intrinsic hookworm transmission intensity in areas with past mass drug administration to control lymphatic filariasis.

PubMed

Werkman, Marleen; Truscott, James E; Toor, Jaspreet; Wright, James E; Anderson, Roy M

2017-05-23

Current WHO guidelines for soil-transmitted helminth (STH) control focus on mass drug administration (MDA) targeting preschool-aged (pre-SAC) and school-aged children (SAC), with the goal of eliminating STH as a public health problem amongst children. Recently, attention and funding has turned towards the question whether MDA alone can result in the interruption of transmission for STH. The lymphatic filariasis (LF) elimination programme, have been successful in reaching whole communities. There is the possibility of building upon the infrastructure created for these LF-programmes to enhance the control of STH. Using hookworm as an example, we explore what further MDA coverage might be required to induce interruption of transmission for hookworm in the wake of a successful LF programme. Analyses based on the model of STH transmission and MDA impact predict the effects of previous LF control by MDA over five years, on a defined baseline prevalence of STH in an area with a defined transmission intensity (the basic reproductive number R 0 ). If the LF MDA programme achieved a high coverage (70, 70 and 60% for pre-SAC, SAC and adults, respectively) we expect that in communities with a hookworm prevalence of 15%, after 5 years of LF control, the intrinsic R 0 value in that setting is 2.47. By contrast, if lower LF coverages were achieved (40, 40 and 30% for pre-SAC, SAC and adults, respectively), with the same prevalence of 15% at baseline (after 5 years of LF MDA), the intrinsic hookworm R 0 value is predicted to be 1.67. The intrinsic R 0 value has a large effect on the expected successes of follow-up STH programmes post LF MDA. Consequently, the outcomes of identical programmes may differ between these communities. To design the optimal MDA intervention to eliminate STH infections, it is vital to have information on historical MDA programmes and baseline prevalence to estimate the intrinsic transmission intensity for the defined setting (R 0 ). The baseline prevalence alone is not sufficient to inform policy for the control of STH, post cessation of LF MDA, since this will be highly dependent on the intensity and effectiveness of past programmes and the intrinsic transmission intensity of the dominant STH species in any given setting.

Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export.

PubMed

White, Phillip J; Lapworth, Amanda L; An, Jie; Wang, Liping; McGarrah, Robert W; Stevens, Robert D; Ilkayeva, Olga; George, Tabitha; Muehlbauer, Michael J; Bain, James R; Trimmer, Jeff K; Brosnan, M Julia; Rolph, Timothy P; Newgard, Christopher B

2016-07-01

A branched-chain amino acid (BCAA)-related metabolic signature is strongly associated with insulin resistance and predictive of incident diabetes and intervention outcomes. To better understand the role that this metabolite cluster plays in obesity-related metabolic dysfunction, we studied the impact of BCAA restriction in a rodent model of obesity in which BCAA metabolism is perturbed in ways that mirror the human condition. Zucker-lean rats (ZLR) and Zucker-fatty rats (ZFR) were fed either a custom control, low fat (LF) diet, or an isonitrogenous, isocaloric LF diet in which all three BCAA (Leu, Ile, Val) were reduced by 45% (LF-RES). We performed comprehensive metabolic and physiologic profiling to characterize the effects of BCAA restriction on energy balance, insulin sensitivity, and glucose, lipid and amino acid metabolism. LF-fed ZFR had higher levels of circulating BCAA and lower levels of glycine compared to LF-fed ZLR. Feeding ZFR with the LF-RES diet lowered circulating BCAA to levels found in LF-fed ZLR. Activity of the rate limiting enzyme in the BCAA catabolic pathway, branched chain keto acid dehydrogenase (BCKDH), was lower in liver but higher in skeletal muscle of ZFR compared to ZLR and was not responsive to diet in either tissue. BCAA restriction had very little impact on metabolites studied in liver of ZFR where BCAA content was low, and BCKDH activity was suppressed. However, in skeletal muscle of LF-fed ZFR compared to LF-fed ZLR, where BCAA content and BCKDH activity were increased, accumulation of fatty acyl CoAs was completely normalized by dietary BCAA restriction. BCAA restriction also normalized skeletal muscle glycine content and increased urinary acetyl glycine excretion in ZFR. These effects were accompanied by lower RER and improved skeletal muscle insulin sensitivity in LF-RES fed ZFR as measured by hyperinsulinemic-isoglycemic clamp. Our data are consistent with a model wherein elevated circulating BCAA contribute to development of obesity-related insulin resistance by interfering with lipid oxidation in skeletal muscle. BCAA-dependent lowering of the skeletal muscle glycine pool appears to contribute to this effect by slowing acyl-glycine export to the urine.

The medical educator, the discourse analyst, and the phonetician: a collaborative feedback methodology for clinical communication.

PubMed

Woodward-Kron, Robyn; Stevens, Mary; Flynn, Eleanor

2011-05-01

Frameworks for clinical communication assist educators in making explicit the principles of good communication and providing feedback to medical trainees. However, existing frameworks rarely take into account the roles of culture and language in communication, which can be important for international medical graduates (IMGs) whose first language is not English. This article describes the collaboration by a medical educator, a discourse analyst, and a phonetician to develop a communication and language feedback methodology to assist IMG trainees at a Victorian hospital in Australia with developing their doctor-patient communication skills. The Communication and Language Feedback (CaLF) methodology incorporates a written tool and video recording of role-plays of doctor-patient interactions in a classroom setting or in an objective structured clinical examination (OSCE) practice session with a simulated patient. IMG trainees receive verbal feedback from their hospital-based medical clinical educator, the simulated patient, and linguists. The CaLF tool was informed by a model of language in context, observation of IMG communication training, and process evaluation by IMG participants during January to August 2009. The authors provided participants with a feedback package containing their practice video (which included verbal feedback) and the completed CaLF tool.The CaLF methodology provides a tool for medical educators and language practitioners to work collaboratively with IMGs to enhance communication and language skills. The ongoing interdisciplinary collaboration also provides much-needed applied research opportunities in intercultural health communication, an area the authors believe cannot be adequately addressed from the perspective of one discipline alone. Copyright © by the Association of American medical Colleges.

Cordyceps sinensis oral liquid prolongs the lifespan of the fruit fly, Drosophila melanogaster, by inhibiting oxidative stress.

PubMed

Zou, Yingxin; Liu, Yuxiang; Ruan, Minghua; Feng, Xu; Wang, Jiachun; Chu, Zhiyong; Zhang, Zesheng

2015-10-01

This study investigated the effect of Cordyceps sinensis oral liquid (CSOL) on the lifespan of Drosophila melanogaster (fruit fly). Following the lifelong treatment of fruit flies with CSOL, lifespan was examined. The activity of copper-zinc-containing superoxide dismutase 1 (SOD1), manganese-containing superoxide dismutase 2 (SOD2) and catalase (CAT), as well as the lipofuscin (LF) content were determined. The mRNA levels of SOD1, SOD2 and CAT were quantified by qPCR. Hydrogen peroxide (H2O2) and paraquat were used to mimic the effects of damage caused by acute oxidative stress. D-galactose was used to mimic chronic pathological aging. CSOL significantly prolonged the lifespan of the fruit flies under physiological conditions. The activity of SOD1 and CAT was upregulated, and LF accumulation was inhibited by CSOL. CSOL had no effect on the transcriptional levels (mRNA) of these enzymes. The survival time of the fruit flies which were negatively affected by exposure to H2O2 or paraquat was significantly prolonged by CSOL. In fruit flies pathologically aged by epxosure to D-galactose, CSOL also significantly prolonged their lifespan, upregulated the activity of SOD1 and CAT, and inhibited LF accumulation. The findings of our study indicate that CSOL prolongs the lifespan of fruit flies through an anti-oxidative stress pathway involving the upregulation of SOD1 and CAT activity and the inhibition of LF accumulation. CSOL may thus be explored as a novel agent for slowing the human aging process.

Cordyceps sinensis oral liquid prolongs the lifespan of the fruit fly, Drosophila melanogaster, by inhibiting oxidative stress

PubMed Central

ZOU, YINGXIN; LIU, YUXIANG; RUAN, MINGHUA; FENG, XU; WANG, JIACHUN; CHU, ZHIYONG; ZHANG, ZESHENG

2015-01-01

This study investigated the effect of Cordyceps sinensis oral liquid (CSOL) on the lifespan of Drosophila melanogaster (fruit fly). Following the lifelong treatment of fruit flies with CSOL, lifespan was examined. The activity of copper-zinc-containing superoxide dismutase 1 (SOD1), manganese-containing superoxide dismutase 2 (SOD2) and catalase (CAT), as well as the lipofuscin (LF) content were determined. The mRNA levels of SOD1, SOD2 and CAT were quantified by qPCR. Hydrogen peroxide (H2O2) and paraquat were used to mimic the effects of damage caused by acute oxidative stress. D-galactose was used to mimic chronic pathological aging. CSOL significantly prolonged the lifespan of the fruit flies under physiological conditions. The activity of SOD1 and CAT was upregulated, and LF accumulation was inhibited by CSOL. CSOL had no effect on the transcriptional levels (mRNA) of these enzymes. The survival time of the fruit flies which were negatively affected by exposure to H2O2 or paraquat was significantly prolonged by CSOL. In fruit flies pathologically aged by epxosure to D-galactose, CSOL also significantly prolonged their lifespan, upregulated the activity of SOD1 and CAT, and inhibited LF accumulation. The findings of our study indicate that CSOL prolongs the lifespan of fruit flies through an anti-oxidative stress pathway involving the upregulation of SOD1 and CAT activity and the inhibition of LF accumulation. CSOL may thus be explored as a novel agent for slowing the human aging process. PMID:26239097

Decreased microRNA levels lead to deleterious increases in neuronal M2 muscarinic receptors in Spinal Muscular Atrophy models

PubMed Central

O'Hern, Patrick J; do Carmo G. Gonçalves, Inês; Brecht, Johanna; López Soto, Eduardo Javier; Simon, Jonah; Chapkis, Natalie; Lipscombe, Diane; Kye, Min Jeong; Hart, Anne C

2017-01-01

Spinal Muscular Atrophy (SMA) is caused by diminished Survival of Motor Neuron (SMN) protein, leading to neuromuscular junction (NMJ) dysfunction and spinal motor neuron (MN) loss. Here, we report that reduced SMN function impacts the action of a pertinent microRNA and its mRNA target in MNs. Loss of the C. elegans SMN ortholog, SMN-1, causes NMJ defects. We found that increased levels of the C. elegans Gemin3 ortholog, MEL-46, ameliorates these defects. Increased MEL-46 levels also restored perturbed microRNA (miR-2) function in smn-1(lf) animals. We determined that miR-2 regulates expression of the C. elegans M2 muscarinic receptor (m2R) ortholog, GAR-2. GAR-2 loss ameliorated smn-1(lf) and mel-46(lf) synaptic defects. In an SMA mouse model, m2R levels were increased and pharmacological inhibition of m2R rescued MN process defects. Collectively, these results suggest decreased SMN leads to defective microRNA function via MEL-46 misregulation, followed by increased m2R expression, and neuronal dysfunction in SMA. DOI: http://dx.doi.org/10.7554/eLife.20752.001 PMID:28463115

Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

PubMed Central

Jiang, Xiaohong; Dalebout, Tim J.; Bredenbeek, Peter J.; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S.; Lukashevich, Igor S.

2010-01-01

Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV GP1 and GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and –GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF and LASV GP proteins in infected cells. YF17D/LASV-GP1&GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1&GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. PMID:21145373

Global transcriptome analysis of the maize (Zea mays L.) inbred line 08LF during leaf senescence initiated by pollination-prevention

PubMed Central

Wang, Shunxi; Wu, Liuji; Ku, Lixia; Zhang, Jun; Song, Xiaoheng; Liu, Haiping

2017-01-01

In maize (Zea mays), leaf senescence acts as a nutrient recycling process involved in proteins, lipids, and nucleic acids degradation and transport to the developing sink. However, the molecular mechanisms of pre-maturation associated with pollination-prevention remain unclear in maize. To explore global gene expression changes during the onset and progression of senescence in maize, the inbred line 08LF, with severe early senescence caused by pollination prevention, was selected. Phenotypic observation showed that the onset of leaf senescence of 08LF plants occurred approximately 14 days after silking (DAS) by pollination prevention. Transcriptional profiling analysis of the leaf at six developmental stages during induced senescence revealed that a total of 5,432 differentially expressed genes (DEGs) were identified, including 2314 up-regulated genes and 1925 down-regulated genes. Functional annotation showed that the up-regulated genes were mainly enriched in multi-organism process and nitrogen compound transport, whereas down-regulated genes were involved in photosynthesis. Expression patterns and pathway enrichment analyses of early-senescence related genes indicated that these DEGs are involved in complex regulatory networks, especially in the jasmonic acid pathway. In addition, transcription factors from several families were detected, particularly the CO-like, NAC, ERF, GRAS, WRKY and ZF-HD families, suggesting that these transcription factors might play important roles in driving leaf senescence in maize as a result of pollination-prevention. PMID:28973044

Accelerated evolution of the Lyα luminosity function at z ≳ 7 revealed by the Subaru ultra-deep survey for Lyα emitters at z = 7.3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konno, Akira; Ouchi, Masami; Ono, Yoshiaki

2014-12-10

We present the ultra-deep Subaru narrowband imaging survey for Lyα emitters (LAEs) at z = 7.3 in the Subaru/XMM-Newton Deep Survey (SXDS) and Cosmic Evolution Survey (COSMOS) fields (∼0.5 deg{sup 2}) with a total integration time of 106 hr. Exploiting our new sharp bandwidth filter, NB101, installed on the Suprime-Cam, we have reached L(Lyα) = 2.4 × 10{sup 42} erg s{sup –1} (5σ) for z = 7.3 LAEs, about four times deeper than previous Subaru z ≳ 7 studies, which allows us to reliably investigate the evolution of the Lyα luminosity function (LF) for the first time down to themore » luminosity limit same as those of Subaru z = 3.1-6.6 LAE samples. Surprisingly, we only find three and four LAEs in the SXDS and COSMOS fields, respectively, while one expects a total of ∼65 LAEs by our survey in the case of no Lyα LF evolution from z = 6.6 to 7.3. We identify a decrease of the Lyα LF from z = 6.6 to 7.3 at the >90% confidence level from our z = 7.3 Lyα LF with the best-fit Schechter parameters of L{sub Lyα}{sup ∗}=2.7{sub −1.2}{sup +8.0}×10{sup 42} erg s{sup −1} and ϕ{sup ∗}=3.7{sub −3.3}{sup +17.6}×10{sup −4} Mpc{sup −3} for a fixed α = –1.5. Moreover, the evolution of the Lyα LF is clearly accelerated at z > 6.6 beyond the measurement uncertainties including cosmic variance. Because no such accelerated evolution of the UV-continuum LF or the cosmic star formation rate (SFR) is found at z ∼ 7, but suggested only at z > 8, this accelerated Lyα LF evolution is explained by physical mechanisms different from a pure SFR decrease but related to the Lyα production and escape in the process of cosmic reionization. Because a simple accelerating increase of intergalactic medium neutral hydrogen absorbing Lyα cannot be reconciled with Thomson scattering of optical depth measurements from WMAP and Planck, our findings may support new physical pictures suggested by recent theoretical studies, such as the existence of HI clumpy clouds within cosmic ionized bubbles that are selectively absorbing Lyα and the large ionizing photon escape fraction of galaxies causing weak Lyα emission.« less

Optimization of Refining Craft for Vegetable Insulating Oil

NASA Astrophysics Data System (ADS)

Zhou, Zhu-Jun; Hu, Ting; Cheng, Lin; Tian, Kai; Wang, Xuan; Yang, Jun; Kong, Hai-Yang; Fang, Fu-Xin; Qian, Hang; Fu, Guang-Pan

2016-05-01

Vegetable insulating oil because of its environmental friendliness are considered as ideal material instead of mineral oil used for the insulation and the cooling of the transformer. The main steps of traditional refining process included alkali refining, bleaching and distillation. This kind of refining process used in small doses of insulating oil refining can get satisfactory effect, but can't be applied to the large capacity reaction kettle. This paper using rapeseed oil as crude oil, and the refining process has been optimized for large capacity reaction kettle. The optimized refining process increases the acid degumming process. The alkali compound adds the sodium silicate composition in the alkali refining process, and the ratio of each component is optimized. Add the amount of activated clay and activated carbon according to 10:1 proportion in the de-colorization process, which can effectively reduce the oil acid value and dielectric loss. Using vacuum pumping gas instead of distillation process can further reduce the acid value. Compared some part of the performance parameters of refined oil products with mineral insulating oil, the dielectric loss of vegetable insulating oil is still high and some measures are needed to take to further optimize in the future.

Development of a time-trend model for analyzing and predicting case-pattern of Lassa fever epidemics in Liberia, 2013-2017.

PubMed

Olugasa, Babasola O; Odigie, Eugene A; Lawani, Mike; Ojo, Johnson F

2015-01-01

The objective was to develop a case-pattern model for Lassa fever (LF) among humans and derive predictors of time-trend point distribution of LF cases in Liberia in view of the prevailing under-reporting and public health challenge posed by the disease in the country. A retrospective 5 years data of LF distribution countrywide among humans were used to train a time-trend model of the disease in Liberia. A time-trend quadratic model was selected due to its goodness-of-fit (R2 = 0.89, and P < 0.05) and best performance compared to linear and exponential models. Parameter predictors were run on least square method to predict LF cases for a prospective 5 years period, covering 2013-2017. The two-stage predictive model of LF case-pattern between 2013 and 2017 was characterized by a prospective decline within the South-coast County of Grand Bassa over the forecast period and an upward case-trend within the Northern County of Nimba. Case specific exponential increase was predicted for the first 2 years (2013-2014) with a geometric increase over the next 3 years (2015-2017) in Nimba County. This paper describes a translational application of the space-time distribution pattern of LF epidemics, 2008-2012 reported in Liberia, on which a predictive model was developed. We proposed a computationally feasible two-stage space-time permutation approach to estimate the time-trend parameters and conduct predictive inference on LF in Liberia.

Maturation of heart rate and blood pressure variability during sleep in term-born infants.

PubMed

Yiallourou, Stephanie R; Sands, Scott A; Walker, Adrian M; Horne, Rosemary S C

2012-02-01

Abnormal blood pressure control is implicated in the sudden infant death syndrome (SIDS). However, no data exist on normal development of blood pressure control during infancy. This study assessed maturation of autonomic control of blood pressure and heart rate during sleep within the first 6 months of life. Term infants (n = 31) were studied longitudinally at 2-4 weeks, 2-3 months, and 5-6 months postnatal age. Infants underwent daytime polysomnography at each age studied. Blood pressure and heart rate were recorded during quiet (QS) and active (AS) sleep in undisturbed baseline and head-up tilt conditions. Autonomic control was assessed using spectral indices of blood pressure and heart rate variability (BPV and HRV) in ranges of low frequency (LF, reflecting sympathetic + parasympathetic activity) and high frequency (HF, parasympathetic activity), total power (LF+HF), and LF/HF ratio (sympathovagal balance). With increasing postnatal age and predominantly during QS, HRV-LF, HRV-HF, and HRV total power increased, while HRV-LF/HF decreased. BPV-LF/HF also decreased with postnatal age. All changes were evident in both baseline and head-up tilt conditions. BPV-LF and BPV total power during tilts were markedly reduced in QS versus AS at each age. In sleeping infants, sympathetic vascular modulation of the circulation decreases with age, while parasympathetic control of heart rate is strengthened. These normative data will aid in the early identification of conditions where autonomic function is impaired, such as in SIDS.

Protective effects of lactoferrin against intestinal mucosal damage induced by lipopolysaccharide in human intestinal Caco-2 cells.

PubMed

Hirotani, Yoshihiko; Ikeda, Kenji; Kato, Ryuji; Myotoku, Michiaki; Umeda, Takashi; Ijiri, Yoshio; Tanaka, Kazuhiko

2008-09-01

Indirect evidence suggests that lactoferrin (Lf), a major iron-binding protein in human milk, induces enterocyte growth and proliferation, depending on its concentration and affects the function and permeability of the intestinal mucosa. The bacterial endotoxin (lipopolysaccharide, LPS) is known to cause mucosal hyperpermeability in vivo. However, protective effects of Lf against LPS-mediated intestinal mucosal damage and barrier function in epithelial cells are not yet fully clarified. The aim of this study was to investigate whether Lf can reduce the cellular injury and alter epithelial hyperpermeability caused by LPS in human intestinal Caco-2 cells. When cell viability was measured by a WST-1 assay (tetrazolium salt-based assay), the protective effects against LPS-induced damage to Caco-2 cells were observed at doses of 800 and 1000 microg/ml Lf. The barrier function of Caco-2 monolayer tight junctions was assessed by measuring transepithelial electrical resistance (TEER) and permeability of FITC-labeled dextran 4000 (FD-4). The treatment of Caco-2 cells with Lf at doses of 400 and 1000 microg/ml significantly increased TEER as compared to treatment with LPS alone for 2 h (p<0.05). Further, at doses of 400 and 1000 microg/ml, Lf inhibited the enhancement of LPS-mediated permeability in Caco-2 cell monolayer. The results of this study suggest that Lf may have protective effects against LPS-mediated intestinal mucosal damage and impairment of barrier function in intestinal epithelial cells.

Surface area and volume determination of subgingival calculus using laser fluorescence.

PubMed

Shakibaie, Fardad; Walsh, Laurence J

2014-03-01

Visible red (655 nm) laser fluorescence (LF) devices are currently used for identifying deposits of subgingival calculus on the root surfaces of teeth during dental examination and treatment; however, it is not known how the fluorescence readings produced by commercially available LF systems correlate to the nature of the deposits. This laboratory study explored the correlation between LF digital readings and the surface area and volume of subgingival calculus deposits on teeth. A collection of 30 extracted human posterior teeth with various levels of subgingival deposits of calculus across 240 sites were used in a clinical simulation, with silicone impression material used to replicate periodontal soft tissues. The teeth were scored by two examiners by using three commercial LF systems (DIAGNOdent, DIAGNOdent Pen and KEY3). The silicone was removed, and the teeth were removed for photography at × 20 magnification under white or ultraviolet light. The surface area, thickness, and volume were calculated, and both linear least squares regression and nonlinear (Spearman's rank method) correlation coefficients were determined. Visible red LF digital readings showed better correlation to calculus volume than to surface area. Overall, the best performance was found for the KEY3 system (Spearman coefficient 0.59), compared to the Classic DIAGNOdent (0.56) and the DIAGNOdent Pen (0.49). These results indicate that while visible red LF systems vary somewhat in performance, their LF readings provide a useful estimation of the volume of subgingival calculus deposits present on teeth.

Antimicrobial peptide hLF1-11 directs granulocyte-macrophage colony-stimulating factor-driven monocyte differentiation toward macrophages with enhanced recognition and clearance of pathogens.

PubMed

van der Does, Anne M; Bogaards, Sylvia J P; Ravensbergen, Bep; Beekhuizen, Henry; van Dissel, Jaap T; Nibbering, Peter H

2010-02-01

The human lactoferrin-derived peptide hLF1-11 displays antimicrobial activities in vitro and is effective against infections with antibiotic-resistant bacteria and fluconazole-resistant Candida albicans in animals. However, the mechanisms underlying these activities remain largely unclear. Since hLF1-11 is ineffective in vitro at physiological salt concentrations, we suggested modulation of the immune system as an additional mechanism of action of the peptide. We investigated whether hLF1-11 affects human monocyte-macrophage differentiation and determined the antimicrobial activities of the resulting macrophages. Monocytes were cultured for 7 days with GM-CSF in the presence of hLF1-11, control peptide, or saline for various intervals. At day 6, the cells were stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or heat-killed C. albicans for 24 h. Thereafter, the levels of cytokines in the culture supernatants, the expression of pathogen recognition receptors, and the antimicrobial activities of these macrophages were determined. The results showed that a short exposure of monocytes to hLF1-11 during GM-CSF-driven differentiation is sufficient to direct differentiation of monocytes toward a macrophage subset characterized by both pro- and anti-inflammatory cytokine production and increased responsiveness to microbial structures. Moreover, these macrophages are highly effective against C. albicans and Staphylococcus aureus. In conclusion, hLF1-11 directs GM-CSF-driven differentiation of monocytes toward macrophages with enhanced effector functions.

Identification of milk proteins enhancing the antimicrobial activity of lactoferrin and lactoferricin.

PubMed

Murata, M; Wakabayashi, H; Yamauchi, K; Abe, F

2013-08-01

Lactoferrin (LF) is known as an iron-binding antimicrobial protein present in exocrine secretions such as milk and releases the potent antimicrobial peptide lactoferricin (LFcin) by hydrolysis with pepsin. The antimicrobial activity of LF and LFcin has been studied well; however, their cooperative action with other milk proteins remains to be elucidated. In this study, we identified milk proteins enhancing the antimicrobial activity of bovine LF and LFcin against gram-negative bacteria, gram-positive bacteria, and fungi. As the target fraction, we isolated a minor milk protein fraction around 15 kDa, which was identified as bovine RNase 5 (angiogenin-1), RNase 4, and angiogenin-2 by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. As these proteins are collectively known as the RNase A family, we referred to the target protein fraction as milk RNase of 15 kDa (MR15). The number of colony-forming units of Escherichia coli and other pathogenic microorganisms with the addition of MR15 to LF (MR15:LF ratio=16:1,000) was dramatically lowered than that with LF alone. On the other hand, MR15 itself did not show any reductions in the number of colony-forming units at the concentrations tested. Similarly, the antimicrobial activities of LFcin against various microorganisms were significantly enhanced by the addition of MR15. These results suggest that LF and MR15 may be concomitantly acting antimicrobial agents in milk. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The analysis of soil characteristics near the animal feed and fertiliser mill using the Bartington

NASA Astrophysics Data System (ADS)

Azhari, Adinda Syifa; Agustine, Eleonora; Fitriani, Dini

2017-07-01

Industrial activities have the potential to make pollution in agricultural land, the waste contains poisonous material and it is dangerous for the environment. In general, waste from factory is dumped directly into the river, but in the current study an object that is going to be conscientious is soil on around mill. There are three sampling sites are around fertilizer plants, feed mills and original uncontaminated soil. This research has been conducted to assess the impact of pollution resulting from the two mills for the environment. Physical parameter that used is magnetic susceptibility. Sampling was conducted using the method of magnetic susceptibility of rock to see the value of low frequency (lf) and shows Frequency Dependent (fd%) using the MS2B Bartington. The results from this study is at a location close to the fertilizer plant at a depth of 0-5 cm has a value susceptibility low frequency ( lf)=187.1 - 494.8, fd (%)=1.37 - 2:46, at a depth of 6-10 cm susceptibility value of low frequency (lf)=211 - 832.7,fd (%)=1.04 - 5.37. Results in the area of animal feed mill at a depth of 0-5 cm value susceptibility low frequency (lf)=111.9 - 325.7, fd (%)=0.8 - 3.57, at a depth of 6-10 cm value susceptibility low frequency (lf)=189.2 to 386.8,fd (%)=0.33 - 3.7. Results in the original soil at a depth of 0-5 cm susceptibility value of low frequency (lf)=1188.7 - 2237.8,fd (%)=2.75 - 4.65, at a depth of 6-10 cm value susceptibility low frequency (lf)=977.7 - 2134.7,fd (%)=3.06 - 6.21. The highest value was in the arealf original, shows the area has a high mineral content andlf lows were in the area near the factory fodder it is caused by high pollution, resulting in lower mineral content in the soil.

A source migration of low frequency earthquakes during the 2000 activity of Miyake-jima volcano, Japan

NASA Astrophysics Data System (ADS)

Kobayashi, T.; Ohminato, T.; Fujita, E.; Ida, Y.

2002-12-01

The volcanic activity of Miyake-jima started at 18:30 (JST) on June 26, 2000 with large ground deformation and earthquake swarms. The seismic activity started at the southern part of the island. The hypocenter distribution migrated northwestward and slipped away out of the island by early in the morning, June 27. Low frequency (LF) earthquakes with dominant frequencies of 0.2 and 0.4 Hz were first observed in the afternoon of June 27. The LF activity lasted till the first summit eruption on July 8. Earthquake Research Institute of Tokyo University and National Research Institute for Earth Science and Disaster Prevention deployed 3 CMG-3T and 4 STS-2 broadband seismometers in the island. More than 300 LF earthquakes are detected during the period from June 27 to July 8. Most of the LF events whose dominant frequency is 0.2Hz occurred before July 1, while LF events with dominant frequency of 0.4Hz mainly occurred after July 2. We determine hypocenters of these LF events by using the following technique. For each LF event, we assume a source location on a grid point in a homogeneous half-space. A reference station is chosen among all the stations. The cross correlation coefficients are computed between the waveform of the reference station and those of other stations. Then, the coefficients for all the stations are summed. In the same manner, summations of the coefficients are computed grid by grid. A grid point that gives the maximum value of the sum of the coefficients is regarded as the best estimate of the source location of the LF event under consideration. The result shows that hypocenters of LF events are spread over the southern to western part of the island and they migrate from south to the west day by day. Hypocenter migrations associated with volcanic activity have been often reported but usually for short period events. This is one of remarkable cases in which a migration of earthquakes with dominant frequencies as low as 0.2 and 0.4Hz are clearly observed.

Amplitude and phase perturbations on VLF/LF signals at Belgrade due to X-ray flare intensity

NASA Astrophysics Data System (ADS)

Sulic, Desanka

2016-07-01

Narrowband very low frequency (VLF, 3-30 kHz) and low frequency (LF, 30-300 kHz) radio signals are powerful tool for long-range remote sensing of the ionospheric D-region electron density. Propagation of VLF/LF signals emitted by man-made transmitters takes place in the Earth-ionosphere waveguide and strongly depends on the electrical properties of the ionosphere. Changes in the D-region electron density cause changes in the received amplitude and phase on VLF/LF signals. Comparing the measured VLF/LF perturbations with LWPC simulations based on the predicted changes to the D-region, so as to infer the average D-region electron density profiles along the waveguide. The data were recorded at a Belgrade (44.85 ^{0} N, 20.38 ^{0} E) Serbia by AbsPAL and AWESOME receivers since 2003 and 2008 up to 2015, respectively. The first purpose of this paper is to give an account on the dropping amplitude phenomena on one long and three short VLF paths. The NAA-BEL path is sufficiently long, D = 6540 km and oriented west-east to show well-developed sunrise and sunset effects on amplitude and phase. Measured NAA/24.00 kHz signal at Belgrade shows three amplitude minima in time interval when sunrise reaches Belgrade and Maine, USA. Similar but less evident changes occur in time interval defined by sunsets at receiver and transmitter sites. The results show that at the times of amplitude minima the rate of change of phase becomes quite large. GQD/22.10 kHz, DHO/23.40 kHz and NSC/45.90 kHz signals propagate over short paths, D < 2000 km to Belgrade and reflect once on the middle of the paths. When an ionization process starts in the middle of the propagation path, the consequence is development of the first amplitude minimum and transition from phase level during night to phase level during daytime. On the basis of changing reflection characteristics of the D-region our numerical results show that a VLF propagation is a superposition of n _{n} ˜17 and n _{d} ˜7 discrete modes during nighttime and daytime condition, respectively. Propagation of LF radio signal is performed with n _{n} ˜34 (nighttime) and n _{d} ˜10 (daytime) discrete modes. The second purpose of this paper is to give an account of the narrowband VLF/LF perturbations induced by disturbances in the D-region to the event of solar X-ray flare. During occurrence of solar flare the altitude profile of ionospheric conductivity changes, a VLF/LF signal reflects from lower height and these changes result that VLF/LF propagation is performed with more discrete modes than in normal ionospheric condition. Amplitude and phase perturbations on different VLF/LF signals observed at Belgrade have sensitive dependence on: X-ray flare intensity, solar zenith angle, occurrence of solar flare under solar zenith angle which is close with timing of amplitude minimum in normal ionospheric condition and geophysical characteristics of path. The GQD-BEL path is short, D = 1982 km and oriented west-east. A solar flare X17.2 (I _{X} = 1.72 10 ^{-3} Wm ^{-2}) class occurred on 28 Oct 2003 with peak of intensity at 11:10 UT. This powerful solar flare induced amplitude and huge phase perturbation on GQD/22.10 kHz signal (Δ A=5.35 dB and Δ φ = 75 ^{0}). The NSC-BEL path is short, D = 953 km and oriented southwest-northeast. A solar flare M5.77 (I _{X} = 5.77 10 ^{-4} Wm ^{-2}) class occurred on 10 May 2012 with peak of intensity at 04:18 UT. Illumination of the D-region from east to west was under solar zenith angle 80.3 ^{0} < χ < 87.4 ^{0} and the consequence is very untypical LF perturbations. It is interesting to note that these two events are very rare.

Contribution of microbial carbon to soil fractions: significance of diverse microbial group biochemistry

NASA Astrophysics Data System (ADS)

Throckmorton, H.; Bird, J. A.; Dane, L.; Firestone, M. K.; Horwath, W. R.

2011-12-01

The importance of diverse microbial groups to soil C maintenance is still a matter of debate. This study follows the turnover of 13C labeled nonliving residues from diverse microbial groups into soil physical fractions in situ in a temperate forest in California (CA) and a tropical forest in Puerto Rico (PR), during 5 sampling points per site- over a 3 and 2 year period, respectively. Microbial groups include fungi, actinomycetes, Gm(+) bacteria, and Gm(-) bacteria, isolated from CA and PR soils to obtain temperate and tropical isolates composited of 3-4 species per group. The selected density fractionation approach isolated: a "light fraction" (LF), non-mineral aggregate "occluded fraction" (OF), and a "mineral bound fraction" (MF). Pyrolysis gas chromatography mass spectrometry (Py-GC-MS) was employed to characterize microbial group isolates, whole soils, and fractions. Microbial isolates contained unique biochemical fingerprints: temperate and tropical fungi and tropical Gm(-) were characterized by a low abundance of phenol, benzene, and N-compounds compared with other microbial group isolates. Py-GC-MS revealed compositional differences among soil fractions at both sites, likely attributed to differences in the decomposition stage and C source material (ie. plant vs. microbial). For both sites, benzene and N-compounds were greatest in the MF; lignin and phenol compounds were greatest in the LF; and lipids were greatest in the OF. The trend for polysaccharides differed between sites, with the greatest concentration in the CA OF; and for PR with the lowest concentration in the OF, and similar concentrations in the LF and MF. SOM chemistry was most similar between sites in the LF, compared with the OF and MF, suggesting that differences in SOM chemistry between sites may be more attributed to differential decomposition processes than unique litter quality inputs. A substantial portion of microbial C moved from the LF into the OF, and the MF by the first sampling point for both sites. Microbial C inputs were more stable in the OF and MF than the LF throughout the course of the study at both sites. There were no differences in 13C recovery among microbial isolates in any fractions in PR, despite minor differences in overall turnover rates. In CA, there were some differences among microbial isolates in 13C recovery in the LF and OF, which related to 13C recoveries in whole soils. In the CA MF, microbial 13C recoveries did not significantly differ, and in generally low variability among treatments was observed. Results support increased protection of microbial C via association with the MF; however, differential sorption of various microbial group isolates over others was not observed. Overall results suggest that inherent properties of microbial residues may be more important to determining its stability in CA soils when it is 1) unassociated with the mineral matrix (LF); or 2) physically occluded within aggregates; compared with that intimately associated with mineral surfaces (MF). Compound-specific recovery of microbial isolates with Py-GC-MS-IRMS will be discussed.

Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals

PubMed Central

Nocerino, Nunzia; Fulgione, Andrea; Iannaccone, Marco; Tomasetta, Laura; Ianniello, Flora; Martora, Francesca; Lelli, Marco; Roveri, Norberto; Capuano, Federico; Capparelli, Rosanna

2014-01-01

The emergence of bacterial strains resistant to antibiotics is a general public health problem. Progress in developing new molecules with antimicrobial properties has been made. In this study, we evaluated the biological activity of a hybrid nanocomposite composed of synthetic biomimetic hydroxyapatite surface-functionalized by lactoferrin (LF-HA). We evaluated the antimicrobial, anti-inflammatory, and antioxidant properties of LF-HA and found that the composite was active against both Gram-positive and Gram-negative bacteria, and that it modulated proinflammatory and anti-inflammatory responses and enhanced antioxidant properties as compared with LF alone. These results indicate the possibility of using LF-HA as an antimicrobial system and biomimetic hydroxyapatite as a candidate for innovative biomedical applications. PMID:24623976

Ablation of porcine ligamentum flavum with Ho:YAG, q-switched Ho:YAG, and quadrupled Nd:YAG lasers.

PubMed

Johnson, Matt R; Codd, Patrick J; Hill, Westin M; Boettcher, Tara

2015-12-01

Ligamentum flavum (LF) is a tough, rubbery connective tissue providing a portion of the ligamentous stability to the spinal column, and in its hypertrophied state forms a significant compressive pathology in degenerative spinal stenosis. The interaction of lasers and this biological tissue have not been thoroughly studied. Technological advances improving endoscopic surgical access to the spinal canal makes selective removal of LF using small, flexible tools such as laser-coupled fiber optics increasingly attractive for treatment of debilitating spinal stenosis. Testing was performed to assess the effect of Ho:YAG, Q-switched Ho:YAG, and frequency quadrupled Nd:YAG lasers on samples of porcine LF. The objective was to evaluate the suitability of these lasers for surgical removal of LF. LF was resected from porcine spine within 2 hours of sacrifice and stored in saline until immediately prior to laser irradiation, which occurred within an additional 2 hours. The optical absorbance of a sample was measured over the spectral band from 190 to 2,360 nm both before and after dehydration. For the experiments using the Ho:YAG (λ = 2,080 nm, tp  = 140 µs, FWHM) and Q-Switched Ho:YAG (λ = 2,080 nm, tp  = 260 ns, FWHM) lasers, energy was delivered to the LF through a laser-fiber optic with 600 µm core and NA = 0.39. For the experiment using the frequency quadrupled Nd:YAG laser (λ = 266 nm, tp  = 5 ns FWHM), rather than applying the laser energy through a laser-fiber, the energy was focused through an aperture and lens directly onto the LF. Five experiments were conducted to evaluate the effect of the given lasers on LF. First, using the Ho:YAG laser, the single-pulse laser-hole depth versus laser fluence was measured with the laser-fiber in direct contact with the LF (1 g force) and with a standoff distance of 1 mm between the laser-fiber face and the LF. Second, with the LF remaining in situ and the spine bisected along the coronal plane, the surface temperature of the LF was measured with an IR camera during irradiation with the Ho:YAG laser, with and without constant saline flush. Third, the mass loss was measured over the course of 450 Ho:YAG pulses. Fourth, hole depth and temperature were measured over 30 pulses of fixed fluence from the Ho:YAG and Q-Switched Ho:YAG lasers. Fifth, the ablation rate and surface temperature were measured as a function of fluence from the Nd:YAG laser. Several LF staining and hole-depth measurement techniques were also explored. Aside from the expected absorbance peaks corresponding to the water in the LF, the most significant peaks in absorbance were located in the spectral band from 190 to 290 nm and persisted after the tissue was dehydrated. In the first experiment, using the Ho:YAG laser and with the laser-fiber in direct contact with the LF, the lowest single-pulse fluence for which LF was visibly removed was 35 J/cm(2) . Testing was conducted at 6 fluences between 35 and 354 J/cm(2) . Over this range the single-pulse hole depth was shown to be near linear (R(2)  = 0.9374, M = 1.6), ranging from 40 to 639 µm (N = 3). For the case where the laser-fiber face was displaced 1 mm from the LF surface, the lowest single-pulse fluence for which tissue was visibly removed was 72 J/cm(2) . Testing was conducted at 4 energy densities between 72 and 180 J/cm(2) . Over this range the single-pulse hole depth was shown to be near linear (R(2)  = 0.8951, M = 1.4), ranging from 31 to 220 µm (N = 3). In the second experiment, with LF in situ, constant flushing with room temperature saline was shown to drastically reduce surface temperature during exposure to Ho:YAG at 5 Hz with the laser-fiber in direct contact with the LF. Without saline, over 1 minute of treatment with a per-pulse fluence of 141 mJ/cm(2) , the average maximum surface temperature measured 110°C. With 10 cc's of saline flushed over 1 minute and a per-pulse laser fluence of 212 mJ/cm(2) , the average maximum surface temperature was 35°C. In the third experiment, mass loss was shown to be linear over 450 pulses of 600 mJ from the Ho:YAG laser (212 J/cm(2) , direct contact, N = 4; 108 J/cm(2) , 1 mm standoff, N = 4). With the laser-fiber in direct contact, an average of 53 mg was removed (R(2)  = 0.996, M = 0.117) and with 1 mm laser-fiber standoff, an average of 44 mg was removed (R(2)  = 0.9988, M = 0.097). In the fourth experiment, 30 pulses of the Ho:YAG and Q-Switched Ho:YAG lasers at 1 mm standoff, and 5 Hz produced similar hole depths for the tested fluences of 9 J/cm(2) (151 and 154 µm, respectively) and 18 J/cm(2) (470 and 442 µm, respectively), though the Ho:YAG laser produced significantly more carbonization around the rim of the laser-hole. The increased carbonization was corroborated by higher measured LF temperature. In all tests with the Ho:YAG and Q-Switched Ho:YAG, an audible photo-acoustic affect coincided with the laser pulse. In the fifth experiment, with the frequency quadrupled Nd:YAG laser at 15 Hz for 450 pulses, ablation depth per pulse was shown to be linear for the fluence range of 0.18 - 0.73 J/cm(2) (R(2)  = 0.989, M = 2.4). There was no noticeable photo-acoustic effect nor charring around the rim of the laser-hole. The Ho:YAG, Q-Switched Ho:YAG, and frequency quadrupled Nd:YAG lasers were shown to remove ligamentum flavum (LF). A single pulse of the Ho:YAG laser was shown to cause tearing of the tissue and a large zone of necrosis surrounding the laser-hole. Multiple pulses of the Ho:YAG and Q-Switched Ho:YAG lasers caused charring around the rim of the laser-hole, though the extent of charring was more extensive with the Ho:YAG laser. Charring caused by the Ho:YAG laser was shown to be mitigated by continuously flushing the affected LF with saline during irradiation. The Nd:YAG laser was shown to ablate LF with no gross visible indication of thermal damage to surrounding LF. © 2015 Wiley Periodicals, Inc.

Effectiveness of Tai Chi on Cardiac Autonomic Function and Symptomatology in Women With Fibromyalgia: A Randomized Controlled Trial.

PubMed

Wong, Alexei; Figueroa, Arturo; Sanchez-Gonzalez, Marcos A; Son, Won-Mok; Chernykh, Oksana; Park, Song-Young

2018-04-01

The present study examined the effects of a 12-week Tai Chi (TC) training regimen on heart rate variability (HRV), symptomatology, muscle fitness and body composition in women with fibromyalgia. Participants were randomly assigned to either a TC training group (n = 18) or a control group (n = 19). HRV, symptomatology, muscle fitness and body composition were measured before and after 12 weeks. There were significant decreases (p < 0.05) in sympathovagal balance (LnLF/LnHF), sympathetic tone (LnLF, nLF), pain, and fatigue, and significant increases (p < 0.05) in parasympathetic tone (LnHF, nHF), strength and flexibility following TC compared with no changes after control. The changes in LnLF and LnLF/LnHF were correlated with changes in pain. There were no significant changes in HR, sleep quality and body composition after TC or control. TC may be an effective therapeutic intervention for improving sympathovagal balance, pain, fatigue, strength and flexibility in women with fibromyalgia.

Low trans structured fat from flaxseed oil improves plasma and hepatic lipid metabolism in apo E(-/-) mice.

PubMed

Cho, Yun-Young; Kwon, Eun-Young; Kim, Hye-Jin; Park, Yong-Bok; Lee, Ki-Teak; Park, Taesun; Choi, Myung-Sook

2009-07-01

The objective of this study was to explicate the effects of feeding low trans structured fat from flaxseed oil (LF) on plasma and hepatic lipid metabolism involved in apo E(-/-) mice. The animals were fed a commercial shortening (CS), commercial low trans fat (CL) and LF diet based on AIN-76 diet (10% fat) for 12 weeks. LF supplementation exerted a significant suppression in hepatic lipid accumulation with the concomitant decrease in liver weight. The LF significantly lowered plasma total cholesterol and free fatty acid whereas it significantly increased HDL-C concentration and the HDL-C/total-C ratio compared to the CS group. Reduction of hepatic lipid levels in the LF group was related with the suppression of hepatic enzyme activities for fatty acid and triglyceride synthesis, and cholesterol regulating enzyme activity compared to the CS and CL groups. Accordingly, low trans structured fat from flaxseed oil is highly effective for improving hyperlipidemia and hepatic lipid accumulation in apo E(-/-) mice.

Constraints in the diagnosis and treatment of Lassa Fever and the effect on mortality in hospitalized children and women with obstetric conditions in a rural district hospital in Sierra Leone.

PubMed

Dahmane, A; van Griensven, J; Van Herp, M; Van den Bergh, R; Nzomukunda, Y; Prior, J; Alders, P; Jambai, A; Zachariah, R

2014-03-01

Lassa fever (LF) is an acute viral haemorrhagic infection, endemic in West Africa. Confirmatory diagnosis and treatment (ribavirin) is difficult, expensive, and restricted to specialised hospitals. Among confirmed and suspected LF cases, we report on clinical and laboratory features, timing and administration of ribavirin and the relationship with case fatality. We conducted an audit of patient files of suspected LF cases admitted to a pediatric and obstetric referral hospital in rural Sierra Leone (April 2011 to February 2012). There were 84 suspected LF cases; 36 (43%) were laboratory-confirmed cases, of whom only 20 (56%) received ribavirin after a median duration of eight days (IQR 314 days) of hospital admission. Of 16 patients who did not receive ribavirin, 14 (87%) died before ribavirin treatment could be commenced. Starting ribavirin within six days of admission was associated with a case fatality of 29% (2/7), while starting ribavirin later than six days was associated with a case fatality of 50% (6/12). Among the 48 suspected LF cases without laboratory confirmation, there were 21 (44%) deaths. These findings highlight shortcomings in LF management, including diagnostic and treatment delays. More research and development efforts should be devoted to this 'neglected disease'.

Study on the Therapeutic Benefit on Lactoferrin in Patients with Colorectal Cancer Receiving Chemotherapy

PubMed Central

Moastafa, Tarek M.; El-Sissy, Alaa El-Din Elsayed; El-Saeed, Gehan K.; Koura, Mai Salah El-Din

2014-01-01

A double-blinded parallel randomized controlled clinical trial was conducted on two groups of colorectal cancer patients to study the therapeutic benefit of orally administered bovine lactoferrin (bLF) on colorectal cancer patients having age ranges from 20 to 71 years and who received 5-fluorouracil and leucovorin calcium. Test group (15 patients) received oral bLF 250 mg/day beside chemotherapy for three months. Control group (15 patients) received chemotherapy only. Serum lactoferrin (LF), serum glutathione-s-transferase enzyme (GST), interferon gamma (INF-γ), tumor marker carcinoembryonic antigen (CEA), renal function tests, hepatic function tests, and complete blood count were measured for both groups before and at the end of the trial. Although, there was a significant effect of oral bLF (250 mg/day) that indicated a significant improvement in mean percent of change of all parameters 3 months after treatment, there was no significant difference between results of patients in the test group and patients in the control group after treatment. This result suggests that oral bLF has significant therapeutic effect on colorectal cancer patients. Our study suggests that daily administration of bLF showed a clinically beneficial effect to colorectal cancer patients with better disease prognosis but that needs further looking into. PMID:27350986

Study on the Therapeutic Benefit on Lactoferrin in Patients with Colorectal Cancer Receiving Chemotherapy.

PubMed

Moastafa, Tarek M; El-Sissy, Alaa El-Din Elsayed; El-Saeed, Gehan K; Koura, Mai Salah El-Din

2014-01-01

A double-blinded parallel randomized controlled clinical trial was conducted on two groups of colorectal cancer patients to study the therapeutic benefit of orally administered bovine lactoferrin (bLF) on colorectal cancer patients having age ranges from 20 to 71 years and who received 5-fluorouracil and leucovorin calcium. Test group (15 patients) received oral bLF 250 mg/day beside chemotherapy for three months. Control group (15 patients) received chemotherapy only. Serum lactoferrin (LF), serum glutathione-s-transferase enzyme (GST), interferon gamma (INF-γ), tumor marker carcinoembryonic antigen (CEA), renal function tests, hepatic function tests, and complete blood count were measured for both groups before and at the end of the trial. Although, there was a significant effect of oral bLF (250 mg/day) that indicated a significant improvement in mean percent of change of all parameters 3 months after treatment, there was no significant difference between results of patients in the test group and patients in the control group after treatment. This result suggests that oral bLF has significant therapeutic effect on colorectal cancer patients. Our study suggests that daily administration of bLF showed a clinically beneficial effect to colorectal cancer patients with better disease prognosis but that needs further looking into.

Effect of exercise and caloric restriction on DMBA induced mammary tumorigenesis and plasma lipids in rats fed high fat diets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Magrane, D.

1991-03-15

Female Sprague-Dawley rats were given a single 10 mg dose of 7, 12-Dimethylbenz(a)anthracene (DMBA) and grouped as follows: (1) low fat-sedentary (LF-SED), (2) low fat-exercised (LF-EX), (3) high fat-sedentary (HF-SED), (4) high fat-exercised (HF-EX), (5) high fat-caloric restricted (HF-RES). Diets were isocaloric and contained 3.9% (LF) and 19.4% (HF) of corn oil. Group 5 was fed a 25% caloric restricted diet but with 24.6% fat content to equalize fat intake to HF-SED. After 12 weeks of diet or treadmill exercise, tumor data and plasma lipid profiles were determined. Results show that rats on HF-EX had more total tumors, % ofmore » tumors and tumors per tumor bearing rat than rats on HF-SED. The effect of exercise was also evident in LF-EX rats, when compared to LF-SED. Average tumor size and tumor volumes were not affected. The HF-RES group showed reduced tumor profiles compared to HF-SED. HDL, LDL, triglycerides and total cholesterol were unaffected by HF or LF diets or exercise. These data suggest that tumorigenesis is increased by moderate and constant exercise.« less

Activation of the classical pathway of complement by binding of bovine lactoferrin to unencapsulated Streptococcus agalactiae.

PubMed Central

Rainard, P

1993-01-01

The ability of lactoferrin (Lf) bound to Streptococcus agalactiae to interfere with the deposition of complement components on the bacterial surface was investigated by enzyme-linked immunosorbent assay (ELISA). By using a strain of S. agalactiae which activates the alternative pathway of complement in the absence of antibodies, it was found that pretreatment of bacteria with Lf shortened the lag phase preceding the deposition of C3 on bacteria. The kinetics of C3 deposition was comparable to that obtained by adding antibodies against S. agalactiae to agammaglobulinaemic precolostral calf serum (PCS) heated at 56 degrees for 3 min to inactivate the alternative pathway. Accelerated C3 deposition did not occur in the absence of Ca2+ ions. Deposition of C4 on bacteria occurred only when either antibodies or Lf were added to PCS. These results demonstrate that the interaction of lactoferrin with bacteria activated the classical pathway of complement in the absence of antibodies. The binding of purified C1q to bacteria was promoted in a dose-dependent manner by Lf, suggesting that recruitment of classical pathway of complement resulted from the interaction of C1q with Lf adsorbed to the bacterial surface. Phagocytosis of bacteria opsonized with heated PCS (at 56 degrees for 3 min) and Lf was comparable to that occurring in the presence of heated PCS and antibodies. In conclusion, Lf was able to substitute for antibodies in order to activate the classical pathway of complement and to opsonize unencapsulated S. agalactiae efficiently. PMID:8406591

Synergistic activity of synthetic N-terminal peptide of human lactoferrin in combination with various antibiotics against carbapenem-resistant Klebsiella pneumoniae strains.

PubMed

Morici, P; Florio, W; Rizzato, C; Ghelardi, E; Tavanti, A; Rossolini, G M; Lupetti, A

2017-10-01

The spread of multi-drug resistant (MDR) Klebsiella pneumoniae strains producing carbapenemases points to a pressing need for new antibacterial agents. To this end, the in-vitro antibacterial activity of a synthetic N-terminal peptide of human lactoferrin, further referred to as hLF1-11, was evaluated against K. pneumoniae strains harboring different carbapenemase genes (i.e. OXA-48, KPC-2, KPC-3, VIM-1), with different susceptibility to colistin and other antibiotics, alone or in combination with conventional antibiotics (gentamicin, tigecycline, rifampicin, clindamycin, and clarithromycin). An antimicrobial peptide susceptibility assay was used to assess the bactericidal activity of hLF1-11 against the different K. pneumoniae strains tested. The synergistic activity was evaluated by a checkerboard titration method, and the fractional inhibitory concentration (FIC) index was calculated for the various combinations. hLF1-11 was more efficient in killing a K. pneumoniae strain susceptible to most antimicrobials (including colistin) than a colistin-susceptible strain and a colistin-resistant MDR K. pneumoniae strain. In addition, hLF1-11 exhibited a synergistic effect with the tested antibiotics against MDR K. pneumoniae strains. The results of this study indicate that resistance to hLF1-11 and colistin are not strictly associated, and suggest an hLF1-11-induced sensitizing effect of K. pneumoniae to antibiotics, especially to hydrophobic antibiotics, which are normally not effective on Gram-negative bacteria. Altogether, these data indicate that hLF1-11 in combination with antibiotics is a promising candidate to treat infections caused by MDR-K. pneumoniae strains.

The use of subionospheric VLF/LF propagation for the study of lower ionospheric perturbations associated with earthquakes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayakawa, M.

It is recently recognized that the ionosphere is very sensitive to seismic effects, and the detection of ionospheric perturbations associated with earthquakes (EQs), attracts a lot of attention as a very promising candidate for short-term EQ prediction. In this review we propose a possible use of VLF/LF (very low frequency (3-30 kHz)/low frequency (30-300 kHz)) radio sounding of seismo-ionospheric perturbations. We first present the first convincing evidence on the presence of ionospheric perturbations for the disastrous Kobe EQ in 1995. The significant shift in terminator times in the VLF/LF diurnal variation, is successfully interpreted in terms of lowering of themore » lower ionosphere prior to the EQ, which is the confirmation of seismo-ionospheric perturbations. In order to avoid the overlapping with my own previous reviews [1, 2], we try to present the latest results including the statistical evidence on the correlation between the VLF/LF propagation anomalies (ionospheric perturbations) and EQs (especially with large magnitude and with shallow depth), a case study on the Indonesia Sumatra EQ (wavelike structures in the VLF/LF data), medium-distance (6{approx}8 Mm) propagation anomalies, the fluctuation spectra of subionospheric VLF/LF data (atmospheric gravity waves effect, the effect of Earth's tides etc.), and the mechanism of lithosphere - atmosphere - ionosphere coupling. Finally, we indicate the present situation of this kind of VLF/LF activities going on in different parts of the globe and we suggest the importance of international collaboration in this seismo-electromagnetics study.« less

Influence of bovine lactoferrin on the growth of selected probiotic bacteria under aerobic conditions.

PubMed

Chen, Po-Wen; Ku, Yu-We; Chu, Fang-Yi

2014-10-01

Bovine lactoferrin (bLf) is a natural glycoprotein, and it shows broad-spectrum antimicrobial activity. However, reports on the influences of bLf on probiotic bacteria have been mixed. We examined the effects of apo-bLf (between 0.25 and 128 mg/mL) on both aerobic and anaerobic cultures of probiotics. We found that bLf had similar effects on the growth of probiotics under aerobic or anaerobic conditions, and that it actively and significantly (at concentrations of >0.25 mg/mL) retarded the growth rate of Bifidobacterium bifidum (ATCC 29521), B. longum (ATCC 15707), B. lactis (BCRC 17394), B. infantis (ATCC 15697), Lactobacillus reuteri (ATCC 23272), L. rhamnosus (ATCC 53103), and L. coryniformis (ATCC 25602) in a dose-dependent manner. Otherwise, minimal inhibitory concentrations (MICs) were 128 or >128 mg/mL against B. bifidum, B. longum, B. lactis, L. reuteri, and L. rhamnosus (ATCC 53103). With regard to MICs, bLf showed at least four-fold lower inhibitory effect on probiotics than on pathogens. Intriguingly, bLf (>0.25 mg/mL) significantly enhanced the growth of Rhamnosus (ATCC 7469) and L. acidophilus (BCRC 14065) by approximately 40-200 %, during their late periods of growth. Supernatants produced from aerobic but not anaerobic cultures of L. acidophilus reduced the growth of Escherichia coli by about 20 %. Thus, bLf displayed a dose-dependent inhibitory effect on the growth of most probiotic strains under either aerobic or anaerobic conditions. An antibacterial supernatant prepared from the aerobic cultures may have significant practical use.

Testing the tripartite model in young adolescents: is hyperarousal specific for anxiety and not depression?

PubMed

Greaves-Lord, Kirstin; Ferdinand, Robert F; Sondeijker, Frouke E P L; Dietrich, Andrea; Oldehinkel, Albertine J; Rosmalen, Judith G M; Ormel, Johan; Verhulst, Frank C

2007-09-01

To clarify the distinction between anxiety and depression, the tripartite model was introduced. According to this model, physiological hyperarousal (PH, i.e. autonomic hyperactivity) is specific for anxiety and not depression. Research on the relation between anxiety, depression and physiological measures representing arousal is lacking. Parent- and self-reported anxiety and depressive problems were assessed using the CBCL and RCADS. Heart rate (HR), heart rate variability in the low frequency (HRV LF) and respiratory sinus arrythmia (RSA) were used as indices for autonomic arousal. Parent-reported anxiety was associated with low RSA in supine posture. This association was also found for self-reported anxiety problems, but only in boys. These findings point towards high arousal in anxiety. Self-reported depressive problems were associated with low HRV LF in standing posture and high RSA in supine posture in boys, pointing towards low arousal in depression. However, self-reported depressive problems were also associated with high HR in standing posture and with low HRV LF in supine posture in girls, suggesting high arousal in depression. Although HRV LF in standing posture is primarily sympathetically mediated, and HRV LF in supine posture is primarily vagally mediated, the association between HRV LF and sympathetic versus vagal function is not exclusive. Thus, HRV LF measures are merely approaches of high or low arousal. Some evidence was found for hyperarousal in anxiety, but also for hyperarousal in depression. Apparently, the idea of hyperarousal in anxiety and not in depression is too simple to reflect the more complex reality.

Impact of humic acid on the degradation of levofloxacin by aqueous permanganate: Kinetics and mechanism.

PubMed

Xu, Ke; Ben, Weiwei; Ling, Wencui; Zhang, Yu; Qu, Jiuhui; Qiang, Zhimin

2017-10-15

Levofloxacin (LF) is a frequently detected fluoroquinolone in surface water, and permanganate (MnO 4 - ) is a commonly used oxidant in drinking water treatment. This study investigated the impact of humic acid (HA) on LF degradation by aqueous MnO 4 - from both kinetic and mechanistic aspects. In the absence of HA, the second-order rate constant (k) of LF degradation by MnO 4 - was determined to be 3.9 M -1  s -1 at pH 7.5, which increased with decreasing pH. In the presence of HA, the pseudo-first-order rate constant (k obs ) of LF degradation at pH 7.5 was significantly increased by 3.8- and 2.8-fold at [HA] o :[KMnO 4 ] o (mass ratio) = 0.5 and 1, respectively. Secondary oxidant scavenging and electron paramagnetic resonance tests indicated that HA could form a complex with Mn(III), a strongly oxidative intermediate produced in the reaction of MnO 4 - with HA, to induce the successive formation of superoxide radicals (O 2 - ) and hydroxyl radicals (OH). The resulting OH primarily contributed to the accelerated LF degradation, and the complex [HA-Mn(III)] could account for the rest of acceleration. The degradation of LF and its byproducts during MnO 4 - oxidation was mainly through hydroxylation, dehydrogenation and carboxylation, and the presence of HA led to a stronger destruction of LF. This study helps better understand the degradation of organic micropollutants by MnO 4 - in drinking water treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enhancing physicochemical properties of emulsions by heteroaggregation of oppositely charged lactoferrin coated lutein droplets and whey protein isolate coated DHA droplets.

PubMed

Li, Xin; Wang, Xu; Xu, Duoxia; Cao, Yanping; Wang, Shaojia; Wang, Bei; Sun, Baoguo; Yuan, Fang; Gao, Yanxiang

2018-01-15

The formation and physicochemical stability of mixed functional components (lutein & DHA) emulsions through heteroaggregation were studied. It was formed by controlled heteroaggregation of oppositely charged lutein and DHA droplets coated by cationic lactoferrin (LF) and anionic whey protein isolate (WPI), respectively. Heteroaggregation was induced by mixing the oppositely charged LF-lutein and WPI-DHA emulsions together at pH 6.0. Droplet size, zeta-potential, transmission-physical stability, microrheological behavior and microstructure of the heteroaggregates formed were measured as a function of LF-lutein to WPI-DHA droplet ratio. Lutein degradation and DHA oxidation by measurement of lipid hydroperoxides and thiobarbituric acid reactive substances were determined. Upon mixing the two types of bioactive compounds droplets together, it was found that the largest aggregates and highest physical stability occurred at a droplet ratio of 40% LF-lutein droplets to 60% WPI-DHA droplets. Heteroaggregates formation altered the microrheological properties of the mixed emulsions mainly by the special network structure of the droplets. When LF-coated lutein droplets ratios were more than 30% and less than 60%, the mixed emulsions exhibited distinct decreases in the Mean Square Displacement, which indicated that their limited scope of Brownian motion and stable structure. Mixed emulsions with LF-lutein/WPI-DHA droplets ratio of 4:6 exhibited Macroscopic Viscosity Index with 13 times and Elasticity Index with 3 times of magnitudes higher than the individual emulsions from which they were prepared. Compared with the WPI-DHA emulsion or LF-lutein emulsion, the oxidative stability of the heteroaggregate of LF-lutein/WPI-DHA emulsions was improved. Heteroaggregates formed by oppositely charged bioactive compounds droplets may be useful for creating specific food structures that lead to desirable physicochemical properties, such as microrheological property, physical and chemical stabilities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Music induces different cardiac autonomic arousal effects in young and older persons.

PubMed

Hilz, Max J; Stadler, Peter; Gryc, Thomas; Nath, Juliane; Habib-Romstoeck, Leila; Stemper, Brigitte; Buechner, Susanne; Wong, Samuel; Koehn, Julia

2014-07-01

Autonomic arousal-responses to emotional stimuli change with age. Age-dependent autonomic responses to music-onset are undetermined. To determine whether cardiovascular-autonomic responses to "relaxing" or "aggressive" music differ between young and older healthy listeners. In ten young (22.8±1.7 years) and 10 older volunteers (61.7±7.7 years), we monitored respiration (RESP), RR-intervals (RRI), and systolic and diastolic blood pressure (BPsys, BPdia) during silence and 180second presentations of two "relaxing" and two "aggressive" classical-music excerpts. Between both groups, we compared RESP, RRI, BPs, spectral-powers of mainly sympathetic low-frequency (LF: 0.04-0.15Hz) and parasympathetic high-frequency (HF: 0.15-0.5Hz) RRI-oscillations, RRI-LF/HF-ratios, RRI-total-powers (TP-RRI), and BP-LF-powers during 30s of silence, 30s of music-onset, and the remaining 150s of music presentation (analysis-of-variance and post-hoc analysis; significance: p<0.05). During silence, both groups had similar RRI, LF/HF-ratios and LF-BPs; RESP, LF-RRI, HF-RRI, and TP-RRI were lower, but BPs were higher in older than younger participants. During music-onset, "relaxing" music decreased RRI in older and increased BPsys in younger participants, while "aggressive" music decreased RRI and increased BPsys, LF-RRI, LF/HF-ratios, and TP-RRI in older, but increased BPsys and RESP and decreased HF-RRI and TP-RRI in younger participants. Signals did not differ between groups during the last 150s of music presentation. During silence, autonomic modulation was lower - but showed sympathetic predominance - in older than younger persons. Responses to music-onset, particularly "aggressive" music, reflect more of an arousal- than an emotional-response to music valence, with age-specific shifts of sympathetic-parasympathetic balance mediated by parasympathetic withdrawal in younger and by sympathetic activation in older participants. Copyright © 2014 Elsevier B.V. All rights reserved.

Alternate day fasting (ADF) with a high-fat diet produces similar weight loss and cardio-protection as ADF with a low-fat diet.

PubMed

Klempel, Monica C; Kroeger, Cynthia M; Varady, Krista A

2013-01-01

Alternate day fasting (ADF) with a low-fat (LF) diet is effective for weight loss and cardio-protection. However, the applicability of these findings is questionable as the majority of Americans consume a high-fat (HF) diet. The goal of this study was to determine if these beneficial changes in body weight and coronary heart disease (CHD) risk can be reproduced if an HF background diet is used in place of an LF diet during ADF. Thirty-two obese subjects were randomized to an ADF-HF (45% fat) or ADF-LF diet (25% fat), which consisted of two phases: 1) a 2-week baseline weight maintenance period, and 2) an 8-week ADF weight loss period. All food was provided during the study. Body weight was reduced (P<0.0001) by ADF-HF (4.8%±1.1%) and by ADF-LF (4.2%±0.8%). Fat mass decreased (P<0.0001) by ADF-HF (5.4±1.5 kg) and ADF-LF (4.2±0.6 kg). Fat free mass remained unchanged. Waist circumference decreased (P<0.001) by ADF-HF (7.2±1.5 cm) and ADF-LF (7.3±0.9 cm). LDL cholesterol and triacylglycerol concentrations were reduced (P<0.001) by both interventions (ADF-HF: 18.3%±4.6%, 13.7%±4.8%; and ADF-LF: 24.8%±2.6%, 14.3%±4.4%). HDL cholesterol, blood pressure, and heart rate remained unchanged. There were no between-group differences for any parameter. These findings suggest that an ADF-HF diet is equally as effective as an ADF-LF diet in helping obese subjects lose weight and improve CHD risk factors. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of slow breathing rate on heart rate variability and arterial baroreflex sensitivity in essential hypertension.

PubMed

Li, Changjun; Chang, Qinghua; Zhang, Jia; Chai, Wenshu

2018-05-01

This study is to investigate the effects of slow breathing on heart rate variability (HRV) and arterial baroreflex sensitivity in essential hypertension.We studied 60 patients with essential hypertension and 60 healthy controls. All subjects underwent controlled breathing at 8 and 16 breaths per minute. Electrocardiogram, respiratory, and blood pressure signals were recorded simultaneously. We studied effects of slow breathing on heart rate, blood pressure and respiratory peak, high-frequency (HF) power, low-frequency (LF) power, and LF/HF ratio of HRV with traditional and corrected spectral analysis. Besides, we tested whether slow breathing was capable of modifying baroreflex sensitivity in hypertensive subjects.Slow breathing, compared with 16 breaths per minute, decreased the heart rate and blood pressure (all P < .05), and shifted respiratory peak toward left (P < .05). Compared to 16 breaths/minute, traditional spectral analysis showed increased LF power and LF/HF ratio, decreased HF power of HRV at 8 breaths per minute (P < .05). As breathing rate decreased, corrected spectral analysis showed increased HF power, decreased LF power, LF/HF ratio of HRV (P < .05). Compared to controls, resting baroreflex sensitivity decreased in hypertensive subjects. Slow breathing increased baroreflex sensitivity in hypertensive subjects (from 59.48 ± 6.39 to 78.93 ± 5.04 ms/mm Hg, P < .05) and controls (from 88.49 ± 6.01 to 112.91 ± 7.29 ms/mm Hg, P < .05).Slow breathing can increase HF power and decrease LF power and LF/HF ratio in essential hypertension. Besides, slow breathing increased baroreflex sensitivity in hypertensive subjects. These demonstrate slow breathing is indeed capable of shifting sympatho-vagal balance toward vagal activities and increasing baroreflex sensitivity, suggesting a safe, therapeutic approach for essential hypertension.

Low-gradient aortic stenosis.

PubMed

Clavel, Marie-Annick; Magne, Julien; Pibarot, Philippe

2016-09-07

An important proportion of patients with aortic stenosis (AS) have a 'low-gradient' AS, i.e. a small aortic valve area (AVA <1.0 cm(2)) consistent with severe AS but a low mean transvalvular gradient (<40 mmHg) consistent with non-severe AS. The management of this subset of patients is particularly challenging because the AVA-gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF-LG. Furthermore, a substantial proportion of patients with AS may have a normal-flow, low-gradient (NF-LG) AS: i.e. a small AVA-low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high-gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Differences in energy expenditure and substrate oxidation between habitual high fat and low fat consumers (phenotypes).

PubMed

Cooling, J; Blundell, J

1998-07-01

To investigate physiological differences between habitual high-fat (HF) and low-fat (LF) consumers, which could influence the balance between energy expenditure and energy intake, and the potential for weight gain. 16 young, lean males (eight HF and eight LF consumers; % energy from fat 44.3 and 32.0, respectively). Habitual dietary variables (from FFQ), body mass index (BMI), body fat % (measured by impedance), resting metabolic rate (RMR) (indirect calorimetry), substrate oxidation and basal heart rate, postprandial thermogenesis and heart rate in response to a high-fat (low carbohydrate (CHO)) and high-CHO (low fat) challenge. HF and LF (selected for their intake of fat) did not differ significantly in BMI or % body fat. HF had a significantly higher RMR (1624 vs 1455 kcal/d) and basal heart rate (66 vs 57 bpm) than LF. Differences in oxygen utilisation and heart rate were maintained over a 180 min period, following the high-fat and high-CHO challenge meals. HF had a significantly lower resting respiratory quotient (RQ) than LF and the differences in average RQ were significant over the 180 min examination period. HF had a significantly lower RQ response to the high fat (low CHO) than to the high CHO (low fat) challenge; this effect was not observed in LF. HF had higher total energy intake than LF and a higher absolute (but not %) intake of protein. Significant differences in basal energy expenditure and fat oxidation between habitual HF and LF consumers have been observed. The contributions of energy intake and protein intake (g not %) remain to be determined. In this particular group of subjects (young adult males) a high energy intake characterised by a large fat component is associated with metabolic adaptations which could offset the weight inducing properties of a high-fat diet. These physiological differences may be important when considering the relationship between dietary-fat and obesity.

Flow-gradient patterns in severe aortic stenosis with preserved ejection fraction: clinical characteristics and predictors of survival.

PubMed

Eleid, Mackram F; Sorajja, Paul; Michelena, Hector I; Malouf, Joseph F; Scott, Christopher G; Pellikka, Patricia A

2013-10-15

Among patients with severe aortic stenosis (AS) and preserved ejection fraction, those with low gradient (LG) and reduced stroke volume may have an adverse prognosis. We investigated the prognostic impact of stroke volume using the recently proposed flow-gradient classification. We examined 1704 consecutive patients with severe AS (aortic valve area <1.0 cm(2)) and preserved ejection fraction (≥50%) using 2-dimensional and Doppler echocardiography. Patients were stratified by stroke volume index (<35 mL/m(2) [low flow, LF] versus ≥35 mL/m(2) [normal flow, NF]) and aortic gradient (<40 mm Hg [LG] versus ≥40 mm Hg [high gradient, HG]) into 4 groups: NF/HG, NF/LG, LF/HG, and LF/LG. NF/LG (n=352, 21%), was associated with favorable survival with medical management (2-year estimate, 82% versus 67% in NF/HG; P<0.0001). LF/LG severe AS (n=53, 3%) was characterized by lower ejection fraction, more prevalent atrial fibrillation and heart failure, reduced arterial compliance, and reduced survival (2-year estimate, 60% versus 82% in NF/HG; P<0.001). In multivariable analysis, the LF/LG pattern was the strongest predictor of mortality (hazard ratio, 3.26; 95% confidence interval, 1.71-6.22; P<0.001 versus NF/LG). Aortic valve replacement was associated with a 69% mortality reduction (hazard ratio, 0.31; 95% confidence interval, 0.25-0.39; P<0.0001) in LF/LG and NF/HG, with no survival benefit associated with aortic valve replacement in NF/LG and LF/HG. NF/LG severe AS with preserved ejection fraction exhibits favorable survival with medical management, and the impact of aortic valve replacement on survival was neutral. LF/LG severe AS is characterized by a high prevalence of atrial fibrillation, heart failure, and reduced survival, and aortic valve replacement was associated with improved survival. These findings have implications for the evaluation and subsequent management of AS severity.

Increased sorbitol levels in the hypertrophic ligamentum flavum of diabetic patients with lumbar spinal canal stenosis.

PubMed

Luo, Jiaquan; Huang, Lu; Chen, Zhuo; Zeng, Zhaoxun; Miyamoto, Takeshi; Wu, Hao; Zhang, Zhongzu; Pan, Zhimin; Fujita, Nobuyuki; Hikata, Tomohiro; Iwanami, Akio; Tsuji, Takashi; Ishii, Ken; Nakamura, Masaya; Matsumoto, Morio; Watanabe, Kota; Cao, Kai

2017-05-01

The pathomechanism of the ligamentum flavum (LF) hypertrophy in diabetic patients with lumbar spinal canal stenosis (LSCS) remains unclear. A cross-sectional study was undertaken to investigate the mechanism of LF hypertrophy in these patients. Twenty-four diabetic and 20 normoglycemic patients with LSCS were enrolled in the study. The structure of the LF in the study subjects was evaluated using histological and immunohistochemical methods, and the levels of sorbitol, pro-inflammatory cytokines, and the fibrogenic factor, TGF-β1, in the LF were analyzed. In vitro experiments were performed using NIH3T3 fibroblasts to evaluate the effect of high-glucose conditions and an aldose reductase inhibitor on the cellular production of sorbitol, pro-inflammatory factors, and TGF-β1. We found that the LF of diabetic patients exhibited significantly higher levels of sorbitol and pro-inflammatory cytokines, TGF-β1 and of CD68-positive staining than that of the normoglycemic subjects. The diabetic LF was significantly thicker than that of the controls, and showed evidence of degeneration. The high glucose-cultured fibroblasts exhibited significantly higher levels of sorbitol, pro-inflammatory factors, and TGF-β1 compared to the low glucose-cultured cells, and these levels were dose-dependently reduced by treatment with the aldose reductase inhibitor. Taken together, our data suggests that increased sorbitol levels in the LF of diabetic patients results in increased production of pro-inflammatory and fibrogenic factor, which contribute to LF hypertrophy, and could increase the susceptibility of diabetic patients to LSCS. Furthermore, aldose reductase inhibition effectively reduced the levels of sorbitol and sorbitol-induced pro-inflammatory factor expression in high glucose-cultured fibroblasts. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1058-1066, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Limbal Fibroblasts Maintain Normal Phenotype in 3D RAFT Tissue Equivalents Suggesting Potential for Safe Clinical Use in Treatment of Ocular Surface Failure.

PubMed

Massie, Isobel; Dale, Sarah B; Daniels, Julie T

2015-06-01

Limbal epithelial stem cell deficiency can cause blindness, but transplantation of these cells on a carrier such as human amniotic membrane can restore vision. Unfortunately, clinical graft manufacture using amnion can be inconsistent. Therefore, we have developed an alternative substrate, Real Architecture for 3D Tissue (RAFT), which supports human limbal epithelial cells (hLE) expansion. Epithelial organization is improved when human limbal fibroblasts (hLF) are incorporated into RAFT tissue equivalent (TE). However, hLF have the potential to transdifferentiate into a pro-scarring cell type, which would be incompatible with therapeutic transplantation. The aim of this work was to assess the scarring phenotype of hLF in RAFT TEs in hLE+ and hLE- RAFT TEs and in nonairlifted and airlifted RAFT TEs. Diseased fibroblasts (dFib) isolated from the fibrotic conjunctivae of ocular mucous membrane pemphigoid (Oc-MMP) patients were used as a pro-scarring positive control against which hLF were compared using surrogate scarring parameters: matrix metalloproteinase (MMP) activity, de novo collagen synthesis, α-smooth muscle actin (α-SMA) expression, and transforming growth factor-β (TGF-β) secretion. Normal hLF and dFib maintained different phenotypes in RAFT TE. MMP-2 and -9 activity, de novo collagen synthesis, and α-SMA expression were all increased in dFib cf. normal hLF RAFT TEs, although TGF-β1 secretion did not differ between normal hLF and dFib RAFT TEs. Normal hLF do not progress toward a scarring-like phenotype during culture in RAFT TEs and, therefore, may be safe to include in therapeutic RAFT TE, where they can support hLE, although in vivo work is required to confirm this. dFib RAFT TEs (used in this study as a positive control) may be useful toward the development of an ex vivo disease model of Oc-MMP.

Limbal Fibroblasts Maintain Normal Phenotype in 3D RAFT Tissue Equivalents Suggesting Potential for Safe Clinical Use in Treatment of Ocular Surface Failure

PubMed Central

Dale, Sarah B.; Daniels, Julie T.

2015-01-01

Limbal epithelial stem cell deficiency can cause blindness, but transplantation of these cells on a carrier such as human amniotic membrane can restore vision. Unfortunately, clinical graft manufacture using amnion can be inconsistent. Therefore, we have developed an alternative substrate, Real Architecture for 3D Tissue (RAFT), which supports human limbal epithelial cells (hLE) expansion. Epithelial organization is improved when human limbal fibroblasts (hLF) are incorporated into RAFT tissue equivalent (TE). However, hLF have the potential to transdifferentiate into a pro-scarring cell type, which would be incompatible with therapeutic transplantation. The aim of this work was to assess the scarring phenotype of hLF in RAFT TEs in hLE+ and hLE− RAFT TEs and in nonairlifted and airlifted RAFT TEs. Diseased fibroblasts (dFib) isolated from the fibrotic conjunctivae of ocular mucous membrane pemphigoid (Oc-MMP) patients were used as a pro-scarring positive control against which hLF were compared using surrogate scarring parameters: matrix metalloproteinase (MMP) activity, de novo collagen synthesis, α-smooth muscle actin (α-SMA) expression, and transforming growth factor-β (TGF-β) secretion. Normal hLF and dFib maintained different phenotypes in RAFT TE. MMP-2 and -9 activity, de novo collagen synthesis, and α-SMA expression were all increased in dFib cf. normal hLF RAFT TEs, although TGF-β1 secretion did not differ between normal hLF and dFib RAFT TEs. Normal hLF do not progress toward a scarring-like phenotype during culture in RAFT TEs and, therefore, may be safe to include in therapeutic RAFT TE, where they can support hLE, although in vivo work is required to confirm this. dFib RAFT TEs (used in this study as a positive control) may be useful toward the development of an ex vivo disease model of Oc-MMP. PMID:25380529

Recombinase Polymerase Amplification Combined with Lateral Flow Strip for Listeria monocytogenes Detection in Food.

PubMed

Du, Xin-Jun; Zang, Yu-Xuan; Liu, Hai-Bin; Li, Ping; Wang, Shuo

2018-04-01

Listeria monocytogenes is an important food-borne pathogenic bacterium that causes human disease, resulting in economic losses worldwide. The current detection methods for L. monocytogenes are not well suited for direct field testing because they involve complicated, time-consuming operations. A simple, efficient method is vital for L. monocytogenes detection. In this study, we combined isothermal recombinase polymerase amplification (RPA) with a lateral flow (LF) strip to rapidly and reliably detect L. monocytogenes. In the presence of biotin- and digoxin-modified primers, RPA produced numerous digoxin- and biotin-attached duplex DNA products. These products were detected on an LF strip via dual immunoreactions (digoxin on the duplex DNA reacted with the anti-digoxin antibody on the gold nanoparticle (Au-NP) and the biotin on the duplex DNA captured by the streptavidin on the LF test zone). The accumulation of Au-NPs produced characteristic bands, enabling the visual detection of L. monocytogenes without instrumentation. This assay could be used to detect L. monocytogenes within 15 min, including DNA amplification with RPA for 10 min at 39 °C and visualization of the amplicons by LF strips for 5 min. Experiments confirmed a detection limit as low as 300 fg of DNA and 1.5 × 10 1 CFU in pure cultures. Furthermore, RPA-LF exhibited no cross-reactions with pathogens. Evaluation of the method with food samples indicated that the detection limit was substantially improved to 1.5 × 10° CFU for the original bacterial content in 25 g/mL samples after enrichment for 6 hr. RPA-LF can be used as a sensitive and rapid detection technique for L. monocytogenes. Recombinase polymerase amplification (RPA) can amplify target DNA at 37 to 42 °C without a thermal cycler. Lateral flow (LF) strips are portable, cheap and easy to operate. RPA combined with LF strips to detect Listeria monocytogenes can be widely used in remote areas. © 2018 Institute of Food Technologists®.

Assessment of lymphatic filariasis prior to re-starting mass drug administration campaigns in coastal Kenya.

PubMed

Njenga, Sammy M; Kanyi, Henry M; Mutungi, Faith M; Okoyo, Collins; Matendechero, Hadley S; Pullan, Rachel L; Halliday, Katherine E; Brooker, Simon J; Wamae, C Njeri; Onsongo, Joyce K; Won, Kimberly Y

2017-02-22

Lymphatic filariasis (LF) is a debilitating disease associated with extensive disfigurement and is one of a diverse group of diseases referred to as neglected tropical diseases (NTDs) which mainly occur among the poorest populations. In line with global recommendations to eliminate LF, Kenya launched its LF elimination programme in 2002 with the aim to implement annual mass drug administration (MDA) in order to interrupt LF transmission. However, the programme faced financial and administrative challenges over the years such that sustained annual MDA was not possible. Recently, there has been renewed interest to eliminate LF and the Kenyan Ministry of Health, through support from World Health Organization (WHO), restarted annual MDA in 2015. The objective of this study was to evaluate the current status of LF infection in the endemic coastal region of Kenya before MDA campaigns were restarted. Ten sentinel sites in Kwale, Kilifi, Tana River, Lamu, and Taita-Taveta counties in coastal Kenya were selected for participation in a cross-sectional survey of LF infection prevalence. At least 300 individuals in each sentinel village were sampled through random house-to-house visits. During the day, the point-of-care immunochromatographic test (ICT) was used to detect the presence of Wuchereria bancrofti circulating filarial antigen in finger prick blood samples collected from residents of the selected sentinel villages. Those individuals who tested positive with the ICT test were requested to provide a night-time blood sample for microfilariae (MF) examination. The overall prevalence of filarial antigenaemia was 1.3% (95% CI: 0.9-1.8%). Ndau Island in Lamu County had the highest prevalence (6.3%; 95% CI: 4.1-9.7%), whereas sites in Kilifi and Kwale counties had prevalences < 1.7%. Mean microfilarial density was also higher in Ndau Island (234 MF/ml) compared to sentinel sites in Kwale and Kilifi counties (< 25 MF/ml). No LF infection was detected in Tana River and Taita-Taveta counties. Overall, more than 88% of the study participants reported to have used a bed net the previous night. Prevalence of LF infection is generally very low in coastal Kenya, but there remain areas that require further rounds of MDA if the disease is to be eliminated as a public health problem in line with the ongoing global elimination efforts. However, areas where there was no evidence of LF transmission should be considered for WHO-recommended transmission assessment surveys in view of stopping MDA.

Comparison of the effect of daily consumption of probiotic compared with low-fat conventional yogurt on weight loss in healthy obese women following an energy-restricted diet: a randomized controlled trial.

PubMed

Madjd, Ameneh; Taylor, Moira A; Mousavi, Neda; Delavari, Alireza; Malekzadeh, Reza; Macdonald, Ian A; Farshchi, Hamid R

2016-02-01

Despite evidence for the beneficial effects of probiotics and low-fat dairy products, to our knowledge, no study has compared the beneficial effect on weight loss of consuming a probiotic yogurt (PY) compared with a standard low-fat yogurt (LF) during a hypoenergetic program. We compared the effect of the PY with LF yogurt consumption on body weight and cardiometabolic risk factors in women during a weight-loss program. Overweight and obese women [body mass index (in kg/m(2)): 27-40; age: 18-50 y) who usually consumed standard LFs were asked to consume either PY or LF every day with their main meals for 12 wk while following a weight-loss program. A total of 89 participants were randomly assigned to one of the 2 intervention groups. Baseline variables were not significantly different between groups. A statistically significant reduction in anthropometric measurements and significant improvements in cardiometabolic risk characteristics were observed over the 12 wk in both groups. However, no significant differences in weight loss and anthropometric measurements were seen between groups after the intervention. Compared with the LF group, the PY group had a greater (mean ± SD) decrease in total cholesterol (PY = -0.36 ± 0.10 mmol/L, LF = -0.31 ± 0.10 mmol/L; P = 0.024), low-density lipoprotein cholesterol (PY = -0.35 ± 0.10 mmol/L, LF = -0.31 ± 0.11 mmol/L; P = 0.018), homeostasis model assessment of insulin resistance (PY = -0.55 ± 0.32, LF = -0.42 ± 0.20; P = 0.002), 2-h postprandial glucose (PY = -0.61 ± 0.24 mmol/L, LF = -0.44 ± 0.19 mmol/L; P < 0.001), and fasting insulin concentration (PY = -1.76 ± 1.01 mU/mL, LF = -1.32 ± 0.62 mU/mL; P = 0.002), as secondary endpoints after the study. No significant differences were found for fasting plasma glucose, high-density lipoprotein cholesterol, or triglycerides within both groups after the 12 wk. Consumption of PY compared with LF with main meals showed no significant effects on weight loss. However, it may have positive effects on lipid profiles and insulin sensitivity during a weight-loss program. This trial was registered at http://www.irct.ir/ as IRCT201402177754N8. © 2016 American Society for Nutrition.

Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease

PubMed Central

Hua, Hongchen; Jiang, Ying; Wang, Yiyun; Mu, Hongjie; Wu, Zimei

2018-01-01

Background Safe and effective delivery of therapeutic drugs to the brain is important for successful therapy of Alzheimer’s disease (AD). Purpose To develop Huperzine A (HupA)-loaded, mucoadhesive and targeted polylactide-co-glycoside (PLGA) nanoparticles (NPs) with surface modification by lactoferrin (Lf)-conjugated N-trimethylated chitosan (TMC) (HupA Lf-TMC NPs) for efficient intranasal delivery of HupA to the brain for AD treatment. Methods HupA Lf-TMC NPs were prepared using the emulsion–solvent evaporation method and optimized using the Box–Behnken design. The particle size, zeta potential, drug entrapment efficiency, adhesion and in vitro release behavior were investigated. The cellular uptake was investigated by fluorescence microscopy and flow cytometry. MTT assay was used to evaluate the cytotoxicity of the NPs. In vivo imaging system was used to investigate brain targeting effect of NPs after intranasal administration. The biodistribution of Hup-A NPs after intranasal administration was determined by liquid chromatography–tandem mass spectrometry. Results Optimized HupA Lf-TMC NPs had a particle size of 153.2±13.7 nm, polydispersity index of 0.229±0.078, zeta potential of +35.6±5.2 mV, drug entrapment efficiency of 73.8%±5.7%, and sustained release in vitro over a 48 h period. Adsorption of mucin onto Lf-TMC NPs was 86.9%±1.8%, which was significantly higher than that onto PLGA NPs (32.1%±2.5%). HupA Lf-TMC NPs showed lower toxicity in the 16HBE cell line compared with HupA solution. Qualitative and quantitative cellular uptake experiments indicated that accumulation of Lf-TMC NPs was higher than nontargeted analogs in 16HBE and SH-SY5Y cells. In vivo imaging results showed that Lf-TMC NPs exhibited a higher fluorescence intensity in the brain and a longer residence time than nontargeted NPs. After intranasal administration, Lf-TMC NPs facilitated the distribution of HupA in the brain, and the values of the drug targeting index in the mouse olfactory bulb, cerebrum (with hippocampus removal), cerebellum, and hippocampus were about 2.0, 1.6, 1.9, and 1.9, respectively. Conclusion Lf-TMC NPs have good sustained-release effect, adhesion and targeting ability, and have a broad application prospect as a nasal drug delivery carrier. PMID:29440896

Life-Cycle Analysis of Greenhouse Gas Emissions and Water Consumption – Effects of Coal and Biomass Conversion to Liquid Fuels as Analyzed with the GREET Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Qianfeng; Cai, Hao; Han, Jeongwoo

The vast reserves of coal in the U.S. provide a significant incentive for the development of processes for coal conversion to liquid fuels (CTL). Also, CTL using domestic coal can help move the U.S. toward greater energy independence and security. However, current conversion technologies are less economically competitive and generate greater greenhouse gas (GHG) emissions than production of petroleum fuels. Altex Technologies Corporation (Altex, hereinafter) and Pennsylvania State University have developed a hybrid technology to produce jet fuel from a feedstock blend of coal and biomass. Collaborating with Altex, Argonne National Laboratory has expanded and used the Greenhouse gases, Regulatedmore » Emissions, and Energy use in Transportation (GREET®) model to assess the life-cycle GHG emissions and water consumption of this hybrid technology. Biomass feedstocks include corn stover, switchgrass, and wheat straw. The option of biomass densification (bales to pellets) is also evaluated in this study. The results show that the densification process generates additional GHG emissions as a result of additional biomass process energy demand. This process coproduces a large amount of char, and this study investigates two scenarios to treat char: landfill disposal (Char-LF) and combustion for combined heat and power (CHP). Since the CHP scenarios export excess heat and electricity as coproducts, two coproduct handling methods are used for well-to-wake (WTWa) analysis: displacement (Char-CHP-Disp) and energy allocation (Char-CHP-EnAllo). When the feedstock contains 15 wt% densified wheat straw and 85 wt% lignite coal, WTWa GHG emissions of the coal-and-biomass-to-liquid pathways are 116, 97, and 137 gCO2e per megajoule (MJ) under the Char-LF, Char-CHP-Disp, and Char-CHP-EnAllo scenarios, respectively, as compared to conventional jet fuel production at 84 gCO2e/MJ. WTWa water consumption values are 0.072, -0.046, and 0.044 gal/MJ for Char-LF, Char-CHP-Disp, and Char-CHP-EnAllo, respectively, as compared to conventional jet fuel production at 0.028 gal/MJ. To reach the break-even point of 84 gCO2e/MJ, under the assumptions of constant product yields and energy demands regardless of the share of biomass and coal feedstocks, 31 wt%, 23 wt%, and 53 wt% of the feedstock blend need to be biomass under the Char-LF, Char-CHP-Disp, and Char-CHP-EnAllo scenarios, respectively.« less

Online low-field NMR spectroscopy for process control of an industrial lithiation reaction-automated data analysis.

PubMed

Kern, Simon; Meyer, Klas; Guhl, Svetlana; Gräßer, Patrick; Paul, Andrea; King, Rudibert; Maiwald, Michael

2018-05-01

Monitoring specific chemical properties is the key to chemical process control. Today, mainly optical online methods are applied, which require time- and cost-intensive calibration effort. NMR spectroscopy, with its advantage being a direct comparison method without need for calibration, has a high potential for enabling closed-loop process control while exhibiting short set-up times. Compact NMR instruments make NMR spectroscopy accessible in industrial and rough environments for process monitoring and advanced process control strategies. We present a fully automated data analysis approach which is completely based on physically motivated spectral models as first principles information (indirect hard modeling-IHM) and applied it to a given pharmaceutical lithiation reaction in the framework of the European Union's Horizon 2020 project CONSENS. Online low-field NMR (LF NMR) data was analyzed by IHM with low calibration effort, compared to a multivariate PLS-R (partial least squares regression) approach, and both validated using online high-field NMR (HF NMR) spectroscopy. Graphical abstract NMR sensor module for monitoring of the aromatic coupling of 1-fluoro-2-nitrobenzene (FNB) with aniline to 2-nitrodiphenylamine (NDPA) using lithium-bis(trimethylsilyl) amide (Li-HMDS) in continuous operation. Online 43.5 MHz low-field NMR (LF) was compared to 500 MHz high-field NMR spectroscopy (HF) as reference method.

Sex-specific neuroanatomical correlates of fear expression in prefrontal-amygdala circuits.

PubMed

Gruene, Tina M; Roberts, Elian; Thomas, Virginia; Ronzio, Ashley; Shansky, Rebecca M

2015-08-01

The neural projections from the infralimbic region of the prefrontal cortex to the amygdala are important for the maintenance of conditioned fear extinction. Neurons in this pathway exhibit a unique pattern of structural plasticity that is sex-dependent, but the relationship between the morphologic characteristics of these neurons and successful extinction in male and female subjects is unknown. Using classic cued fear conditioning and an extinction paradigm in large cohorts of male and female rats, we identified subpopulations of both sexes that exhibited high (HF) or low (LF) levels of freezing on an extinction retrieval test, representing failed or successful extinction maintenance, respectively. We combined retrograde tracing with fluorescent intracellular microinjections to perform three-dimensional reconstructions of infralimbic neurons that project to the basolateral amygdala in these groups. The HF and LF male rats exhibited neuroanatomical distinctions that were not observed in HF or LF female rats. A retrospective analysis of behavior during fear conditioning and extinction revealed that despite no overall sex differences in freezing behavior, HF and LF phenotypes emerged in male rats during extinction and in female rats during fear conditioning, which does not involve infralimbic-basolateral amygdala neurons. Our results suggest that the neural processes underlying successful or failed extinction maintenance may be sex-specific. These findings are relevant not only to future basic research on sex differences in fear conditioning and extinction but also to exposure-based clinical therapies, which are similar in premise to fear extinction and which are primarily used to treat disorders that are more common in women than in men. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The combined study of the middle atmosphere meteorological parameters and lower ionosphere dynamics over Europe by means of remote VLF-LF measurements

NASA Astrophysics Data System (ADS)

Zetzer, J. I.; Lyakhov, A.; Yakymenko, K.

2012-12-01

The results of comprehensive analysis of long-term records of VLF-LF European transmitters by means of Mikhnevo geophysical observatory (Institute of Geospheres Dynamics), SID station A118 (France) and a number of AWESOM receivers are presented. In the previous study (A.A.Egoshin et al., Izvestiya, Physics of the Solid Earth, 2012, Vol. 48, No. 3, pp. 275-286) the results obtained under the minimum solar activity were presented that have shown the link between the lower ionosphere parameters and meteorological fields of the middle atmosphere. The current study expands the evidence to the increased solar activity level as well as the number of receivers, thus allowing more dense coverage of the Europe by the radio paths. Middle atmosphere data under study were provided by the EOS Aura Microwave Limb Sounder. These asynoptic data, in turn, were processed by the space-time spectral analysis on various pressure levels for various window lengths. The results are presented for the spatial structure of wave-like perturbations in the VLF-LF signal strength, which result from the lower ionosphere disturbances on various radio paths. Special short-windowed space-time study was evaluated for the periods of anomalous temporal behavior of the VLF-LF signals and the results of the altitude-latitude mode structures of the geopotential height, neutral temperature, water and ozone constituents are presented. It is shown that the spatial properties of the lower ionosphere can vary significantly at relatively small scale. Moreover, the altitude-latitude mode structures do not coincide in space as well as in time, thus, complicating the lower ionosphere response to the meteorological variations of the middle atmosphere. The analysis of all assembled data proves two main points. At first, it is possible to evaluate synoptic long-term monitoring of the middle atmosphere via the lower ionosphere perturbations as seen by VLF-LF receivers. At second, the theoretical models of the lower ionosphere must include the atmosphere dynamics. Otherwise, these models, which provide lower boundary conditions for the global self-consistent numerical ionosphere models, can set up wrong boundary conditions and lead to the unresolvable errors.

The influence of food quantity on metal bioaccumulation and reproduction in fathead minnows (Pimephales promelas) during chronic exposures to a metal mine effluent.

PubMed

Ouellet, Jacob D; Dubé, Monique G; Niyogi, Som

2013-05-01

Metal mine effluents can impact fish in the receiving environment via both direct effects from exposure as well as indirect effects via food web. The main objective of the present study was to assess whether an indirect effect such as reduced food (prey) availability could influence metal accumulation and reproductive capacity in fish during chronic exposure to a metal mine effluent. Breeding pairs of fathead minnows (Pimephales promelas) were exposed to either reference water (RW) or an environmentally relevant metal mine effluent [45 percent process water effluent (PWE)] for 21 days and fed either low food quantities [LF (a daily ration of 6-10 percent body weight)] or normal food quantities [NF (a daily ration of 20-30 percent body weight)] in artificial stream systems. Fish in RW treatments were fed Chironomus dilutus larvae cultured in RW (Treatments: RW-NF or RW-LF), while fish in PWE treatments were fed C. dilutus larvae cultured in PWE (Treatments: PWE-NF or PWE-LF). Tissue-specific (gill, liver, gonad and carcass) metal accumulation, egg production, and morphometric parameters in fish were analyzed. Fathead minnows that were exposed to LF rations had significantly smaller body, gonad and liver sizes, and were in a relatively poor condition compared to fathead minnows exposed to NF rations, regardless of the treatment water type (RW or PWE) (two-way ANOVA; p<0.05). Although elevated concentrations of copper, nickel, rubidium, selenium, and thallium were recorded in C. dilutus cultured in PWE, only the concentrations of rubidium, selenium and thallium increased in tissues of fish in PWE treatments. Interestingly though, despite the greater abundance of metal-contaminated food in the PWE-NF treatment, tissue metal accumulation pattern were almost similar between the PWE-NF and PWE-LF treatments, except for higher liver barium, cobalt and manganese concentrations in the latter treatment. This indicated that a higher food ration could help reduce the tissue burden of at least some metals and thereby ameliorate the toxicity of metal-mine effluents in fish. More importantly, cumulative egg production in fish was found to be lowest in the PWE-LF treatment, whereas fish egg production in the PWE-NF treatment was not impacted. Overall, these findings suggest that decreased food abundance could have a greater impact than metal accumulation in target tissues on the reproductive capacity of fish inhabiting metal-mine effluent receiving environments. Copyright © 2013 Elsevier Inc. All rights reserved.

[Effects of adiponectin gene SNP45T/G on changes of serum lipid ratios induced by high-carbohydrate/low-fat diet in healthy Chinese youth].

PubMed

Li, Yu-jia; Fang, Ding-zhi; Gong, Ren-rong; Du, Juan; Huang, Xin

2010-09-01

To investigate the effects of adiponectin gene (APM1) SNP45T/G on serum lipid ratios and their responses to high-carbohydrate/low-fat (HC/LF) diet in healthy young Chinese. Fifty-six healthy young subjects were given two consecutive diets. The first was control diet (54% carbohydrate, 15% protein, and 31% fat) for 7 days, and the second was HC/LF diet (70% carbohydrate, 15% protein, and 15% fat) for 6 days. Before and after each diet, serum lipids and SNP45T/G were analyzed. The ratios of TG/HDL-C, log (TG/HDL-C), TC/HDL-C, and LDL-C/HDL-C were calculated. There was no significant difference of baseline lipid ratios between subjects with TT genotype and subjects carrying G allele (G carriers) in the whole population or in the males and females separately. The G allele was associated with significantly higher TC/HDL-C after HC/LF diet in the males (P < 0.05); and the males with TT genotype had significant decreases of LDL-C/HDL-C (P < 0.05) and TC/HDL-C (P < 0.05) after HC/LF diet compared with those before the diet, while G carriers only experienced significant decrease of TC/HDL-C (P < 0.01). In the females, TT genotype was associated with significantly higher TG/HDL-C (P < 0.05) and log (TG/HDL-C) (P < 0.05) both before and after the HC/LF diet. When compared with those before HC/LF diet, elevated TG/HDL-C (P < 0.05) and log (TG/ HDL-C) (P < 0.05) and declined TC/HDL-C (P < 0.01) were observed in the subjects with TT genotype after the diet. In the female subjects of G carriers, LDL-C/HDL-C (P < 0.05) and TC/HDL-C (P < 0.01) decreased significantly after the HC/LF diet. G allele of APM1 45T/G could inhibit increase of TG/HDL-C and log (TG/HDL-C) and promote the decrease of LDL-C/HDL-C induced by HC/LF diet in healthy young females. But in the healthy young males, it might eliminate the decline of LDL-C/HDL-C induced by HC/LF diet and increase TC/HDL-C.

Interactions of surface-displayed glycolytic enzymes of Mycoplasma pneumoniae with components of the human extracellular matrix.

PubMed

Gründel, Anne; Jacobs, Enno; Dumke, Roger

2016-12-01

Mycoplasma pneumoniae is a major cause of community-acquired respiratory infections worldwide. Due to the strongly reduced genome, the number of virulence factors expressed by this cell wall-less pathogen is limited. To further understand the processes during host colonization, we investigated the interactions of the previously confirmed surface-located glycolytic enzymes of M. pneumoniae (pyruvate dehydrogenase A-C [PdhA-C], glyceraldehyde-3-phosphate dehydrogenase [GapA], lactate dehydrogenase [Ldh], phosphoglycerate mutase [Pgm], pyruvate kinase [Pyk] and transketolase [Tkt]) to the human extracellular matrix (ECM) proteins fibrinogen (Fn), fibronectin (Fc), lactoferrin (Lf), laminin (Ln) and vitronectin (Vc), respectively. Concentration-dependent interactions between Fn and Vc and all eight recombinant proteins derived from glycolytic enzymes, between Ln and PdhB-C, GapA, Ldh, Pgm, Pyk and Tkt, between Lf and PdhA-C, GapA and Pyk, and between Fc and PdhC and GapA were demonstrated. In most cases, these associations are significantly influenced by ionic forces and by polyclonal sera against recombinant proteins. In immunoblotting, the complex of human plasminogen, activator (tissue-type or urokinase plasminogen activator) and glycolytic enzyme was not able to degrade Fc, Lf and Ln, respectively. In contrast, degradation of Vc was confirmed in the presence of all eight enzymes tested. Our data suggest that the multifaceted associations of surface-localized glycolytic enzymes play a potential role in the adhesion and invasion processes during infection of human respiratory mucosa by M. pneumoniae. Copyright © 2016 Elsevier GmbH. All rights reserved.

Autonomic Recovery Is Delayed in Chinese Compared with Caucasian following Treadmill Exercise.

PubMed

Sun, Peng; Yan, Huimin; Ranadive, Sushant M; Lane, Abbi D; Kappus, Rebecca M; Bunsawat, Kanokwan; Baynard, Tracy; Hu, Min; Li, Shichang; Fernhall, Bo

2016-01-01

Caucasian populations have a higher prevalence of cardiovascular disease (CVD) when compared with their Chinese counterparts and CVD is associated with autonomic function. It is unknown whether autonomic function during exercise recovery differs between Caucasians and Chinese. The present study investigated autonomic recovery following an acute bout of treadmill exercise in healthy Caucasians and Chinese. Sixty-two participants (30 Caucasian and 32 Chinese, 50% male) performed an acute bout of treadmill exercise at 70% of heart rate reserve. Heart rate variability (HRV) and baroreflex sensitivity (BRS) were obtained during 5-min epochs at pre-exercise, 30-min, and 60-min post-exercise. HRV was assessed using frequency [natural logarithm of high (LnHF) and low frequency (LnLF) powers, normalized high (nHF) and low frequency (nLF) powers, and LF/HF ratio] and time domains [Root mean square of successive differences (RMSSD), natural logarithm of RMSSD (LnRMSSD) and R-R interval (RRI)]. Spontaneous BRS included both up-up and down-down sequences. At pre-exercise, no group differences were observed for any HR, HRV and BRS parameters. During exercise recovery, significant race-by-time interactions were observed for LnHF, nHF, nLF, LF/HF, LnRMSSD, RRI, HR, and BRS (up-up). The declines in LnHF, nHF, RMSSD, RRI and BRS (up-up) and the increases in LF/HF, nLF and HR were blunted in Chinese when compared to Caucasians from pre-exercise to 30-min to 60-min post-exercise. Chinese exhibited delayed autonomic recovery following an acute bout of treadmill exercise. This delayed autonomic recovery may result from greater sympathetic dominance and extended vagal withdrawal in Chinese. Chinese Clinical Trial Register ChiCTR-IPR-15006684.

Autonomic Recovery Is Delayed in Chinese Compared with Caucasian following Treadmill Exercise

PubMed Central

Sun, Peng; Yan, Huimin; Ranadive, Sushant M.; Lane, Abbi D.; Kappus, Rebecca M.; Bunsawat, Kanokwan; Baynard, Tracy; Hu, Min; Li, Shichang; Fernhall, Bo

2016-01-01

Caucasian populations have a higher prevalence of cardiovascular disease (CVD) when compared with their Chinese counterparts and CVD is associated with autonomic function. It is unknown whether autonomic function during exercise recovery differs between Caucasians and Chinese. The present study investigated autonomic recovery following an acute bout of treadmill exercise in healthy Caucasians and Chinese. Sixty-two participants (30 Caucasian and 32 Chinese, 50% male) performed an acute bout of treadmill exercise at 70% of heart rate reserve. Heart rate variability (HRV) and baroreflex sensitivity (BRS) were obtained during 5-min epochs at pre-exercise, 30-min, and 60-min post-exercise. HRV was assessed using frequency [natural logarithm of high (LnHF) and low frequency (LnLF) powers, normalized high (nHF) and low frequency (nLF) powers, and LF/HF ratio] and time domains [Root mean square of successive differences (RMSSD), natural logarithm of RMSSD (LnRMSSD) and R–R interval (RRI)]. Spontaneous BRS included both up-up and down-down sequences. At pre-exercise, no group differences were observed for any HR, HRV and BRS parameters. During exercise recovery, significant race-by-time interactions were observed for LnHF, nHF, nLF, LF/HF, LnRMSSD, RRI, HR, and BRS (up-up). The declines in LnHF, nHF, RMSSD, RRI and BRS (up-up) and the increases in LF/HF, nLF and HR were blunted in Chinese when compared to Caucasians from pre-exercise to 30-min to 60-min post-exercise. Chinese exhibited delayed autonomic recovery following an acute bout of treadmill exercise. This delayed autonomic recovery may result from greater sympathetic dominance and extended vagal withdrawal in Chinese. Trial Registration: Chinese Clinical Trial Register ChiCTR-IPR-15006684 PMID:26784109

Evaluation of autonomic functions of patients with multiple system atrophy and Parkinson's disease by head-up tilt test.

PubMed

Watano, Chikako; Shiota, Yuri; Onoda, Keiichi; Sheikh, Abdullah Md; Mishima, Seiji; Nitta, Eri; Yano, Shozo; Yamaguchi, Shuhei; Nagai, Atsushi

2018-02-01

The aim of this study was to evaluate the autonomic neural function in Parkinson's disease (PD) and multiple system atrophy (MSA) with head-up tilt test and spectral analysis of cardiovascular parameters. This study included 15 patients with MSA, 15 patients with PD, and 29 healthy control (HC) subjects. High frequency power of the RR interval (RR-HF), the ratio of low frequency power of RR interval to RR-HF (RR-LF/HF) and LF power of systolic BP were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively. Both patients with PD and MSA showed orthostatic hypotension and lower parasympathetic function (RR-HF) at tilt position as compared to HC subjects. Cardiac sympathetic function (RR-LF/HF) was significantly high in patients with PD than MSA at supine position. RR-LF/HF tended to increase in MSA and HC, but decreased in PD by tilting. Consequently, the change of the ratio due to tilting (ΔRR-LF/HF) was significantly lower in patients with PD than in HC subjects. Further analysis showed that compared to mild stage of PD, RR-LF/HF at the supine position was significantly higher in advanced stage. By tilting, it was increased in mild stage and decreased in the advanced stage of PD, causing ΔRR-LF/HF to decrease significantly in the advanced stage. Thus, we demonstrated that spectral analysis of cardiovascular parameters is useful to identify sympathetic and parasympathetic disorders in MSA and PD. High cardiac sympathetic function at the supine position, and its reduction by tilting might be a characteristic feature of PD, especially in the advanced stage.

Maturation of Heart Rate and Blood Pressure Variability during Sleep in Term-Born Infants

PubMed Central

Yiallourou, Stephanie R.; Sands, Scott A.; Walker, Adrian M.; Horne, Rosemary S.C.

2012-01-01

Study Objectives: Abnormal blood pressure control is implicated in the sudden infant death syndrome (SIDS). However, no data exist on normal development of blood pressure control during infancy. This study assessed maturation of autonomic control of blood pressure and heart rate during sleep within the first 6 months of life. Participants: Term infants (n = 31) were studied longitudinally at 2-4 weeks, 2-3 months, and 5-6 months postnatal age. Interventions: Infants underwent daytime polysomnography at each age studied. Blood pressure and heart rate were recorded during quiet (QS) and active (AS) sleep in undisturbed baseline and head-up tilt conditions. Measurements and Results: Autonomic control was assessed using spectral indices of blood pressure and heart rate variability (BPV and HRV) in ranges of low frequency (LF, reflecting sympathetic + parasympathetic activity) and high frequency (HF, parasympathetic activity), total power (LF+HF), and LF/HF ratio (sympathovagal balance). With increasing postnatal age and predominantly during QS, HRV-LF, HRV-HF, and HRV total power increased, while HRV-LF/HF decreased. BPV-LF/HF also decreased with postnatal age. All changes were evident in both baseline and head-up tilt conditions. BPV-LF and BPV total power during tilts were markedly reduced in QS versus AS at each age. Conclusions: In sleeping infants, sympathetic vascular modulation of the circulation decreases with age, while parasympathetic control of heart rate is strengthened. These normative data will aid in the early identification of conditions where autonomic function is impaired, such as in SIDS. Citation: Yiallourou SR; Sands SA; Walker AM; Horne RSC. Maturation of heart rate and blood pressure variability during sleep in term-born infants. SLEEP 2012;35(2):177-186. PMID:22294807

Preoperative depressed mood and perioperative heart rate variability in patients with hepatic cancer.

PubMed

Kim, Eun-Hee; Park, Jin-Hyoung; Lee, Sangmin M; Gwak, Mi-Sook; Kim, Gaab-Soo; Kim, Myung-Hee

2016-12-01

How perioperative heart rate variability (HRV) indices differ according to the anxiety or depressed mood of patients scheduled to undergo a major surgical procedure for cancer. Prospective observational study. Operating room. Forty-one male patients between 40 and 70 years of age with hepatocellular carcinoma were included in the final analysis. HRV was measured on the day before surgery (T1), impending anesthesia (T2), and after anesthetic induction (T3). Preoperative anxiety and depressed mood of all patients were evaluated using the State-Trait Anxiety Inventory and Self-Rating Depression Scale (SDS). HRV was significantly different among T1, T2, and T3. At T2, high frequency (HF) (normalized units of HF [nuHF]) was decreased and low frequency (LF) (normalized units of LF) and LF/HF were increased compared with those at T1 and T3. In the subgroup analysis between high and low SDS groups, high SDS group showed significantly decreased nuHF (P = .035), increased nuLF (P = .039), and increased LF/HF (P = .020) compared to low SDS group at T1. However, these values at T2 and T3 were not different between 2 groups. In analysis within the groups, low SDS group showed significant differences in nuHF, nuLF, and LF/HF among T1, T2, and T3 (P < .05, respectively), but no changes in these values were observed in high SDS group among the 3 different time points. HRV decreased significantly immediately before anesthesia and recovered to baseline with anesthetic induction. Preoperative, more depressed patients showed increased sympathetic tone at baseline and blunted response to impending anesthesia on the HRV measurements. Copyright © 2016 Elsevier Inc. All rights reserved.

Supplementing suckling rats with whey protein concentrate modulates the immune response and ameliorates rat rotavirus-induced diarrhea.

PubMed

Pérez-Cano, Francisco J; Marín-Gallén, Silvia; Castell, Margarida; Rodríguez-Palmero, María; Rivero, Montserrat; Castellote, Cristina; Franch, Angels

2008-12-01

Group A rotaviruses (RV) are the most common causative agents of acute gastroenteritis in children <2 y. The present study was designed to establish the effect of a bovine whey protein concentrate (WPC) in a RV infection model in suckling rats. From d 3 of life, suckling Lewis rats received daily supplements of WPC, WPC plus lactoferrin (LF), standard infant formula (SIF), or water (RV-infected group and an untreated, uninfected reference group). On d 8 of life, heterologous simian RV SA-11 was inoculated orally in the WPC-RV, WPC+LF-RV, SIF-RV, and RV groups. WPC and WPC+LF reduced diarrhea incidence from approximately 90% in RV group to approximately 60% in WPC-RV and WPC+LF-RV groups (P < 0.05), whereas the area under the curve (AUC) of severity along time diminished from approximately 10 AUC in the RV group to approximately 6 AUC in both supplemented groups (P < 0.05). Serum levels of anti-RV antibodies, splenocyte proliferation, and interferon-gamma secretion after specific stimulation were significantly lower in the WPC-RV and WPC+LF-RV groups than in the SIF-RV and RV groups. In the intraepithelial intestinal compartment, RV infection increased the proportion of typical mucosal T cells (IE-T CD8alphaalpha+); however, this modification was controlled by WPC and WPC+LF supplementation. In general, for most of the parameters studied, the SIF-RV and RV groups did not differ. In summary, daily supplementation with WPC or WPC+LF in early life considerably reduces the severity of RV-induced acute gastroenteritis and modulates the immune response against the pathogen.

Study on the Simultaneously Quantitative Detection for β-Lactoglobulin and Lactoferrin of Cow Milk by Using Protein Chip Technique.

PubMed

Yin, Ji Yong; Huo, Jun Sheng; Ma, Xin Xin; Sun, Jing; Huang, Jian

2017-12-01

To research a protein chip method which can simultaneously quantitative detect β-Lactoglobulin (β-L) and Lactoferrin (Lf) at one time. Protein chip printer was used to print both anti-β-L antibodies and anti-Lf antibodies on each block of protein chip. And then an improved sandwich detection method was applied while the other two detecting antibodies for the two antigens were added in the block after they were mixed. The detection conditions of the quantitative detection for simultaneous measurement of β-L and Lf with protein chip were optimized and evaluated. Based on these detected conditions, two standard curves of the two proteins were simultaneously established on one protein chip. Finally, the new detection method was evaluated by using the analysis of precision and accuracy. By comparison experiment, mouse monoclonal antibodies of the two antigens were chosen as the printing probe. The concentrations of β-L and Lf probes were 0.5 mg/mL and 0.5 mg/mL, respectively, while the titers of detection antibodies both of β-L and Lf were 1:2,000. Intra- and inter-assay variability was between 4.88% and 38.33% for all tests. The regression coefficients of protein chip comparing with ELISA for β-L and Lf were better than 0.734, and both of the two regression coefficients were statistically significant (r = 0.734, t = 2.644, P = 0.038; and r = 0.774, t = 2.998, P = 0.024). A protein chip method of simultaneously quantitative detection for β-L and Lf has been established and this method is worthy in further application. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Severe aortic stenosis patients with preserved ejection fraction according to flow and gradient classification: Prevalence and outcomes.

PubMed

González Gómez, Ariana; Fernández-Golfín, Covadonga; Monteagudo, Juan Manuel; Izurieta, Carlos; Hinojar, Rocío; García, Ana; Casas, Eduardo; Jiménez-Nacher, José Julio; Moya, José Luis; Ruiz, Soledad; Zamorano, José Luis

2017-12-01

Clinicians often encounter patients with apparently discordant echocardiographic findings, severe aortic stenosis (SAS) defined by aortic valve area (AVA) despite a low mean gradient. A new classification according to flow state and pressure gradient has been proposed. We sought to assess the prevalence, characteristics and outcomes of patients with asymptomatic SAS with preserved left-ventricular ejection fraction (LVEF) according to flow and gradient. In total 442 patients with SAS (AVAi<0.6 cm2/m2) and LVEF ≥50% (mean age 80+11years, 54,5% female) were included. Patients were classified according to flow state (≥ or <35ml/m 2 ) and mean pressure gradient (≥ or <40mmHg): Low Flow/Low Gradient (LF/LG): 21.3%(n=94); Normal Flow/Low Gradient (NF/LG): 32.1%(n=142); Low Flow/High Gradient (LF/HG): 6.8%(n=30); Normal Flow/High Gradient (NF/HG): 39,8%(n=176). Mean follow-up time was 20.5months (SD=10.3). Primary combined endpoint was cardiovascular mortality and hospital admission for SAS related symptom, secondary endpoint was aortic valve replacement (AVR), comparing HG group to LF/LG group. During follow-up 17 (18%) of LF/LG patients and 21 (10.2%) of HG patients met the primary endpoint. A lower free of event survival (cardiovascular mortality and hospital admission) was observed in patients with LF/LG AS (Breslow, p=0.002). Significant differences were noted between groups with a lower AVR free survival in the LF/LG group compared to HG groups (Breslow, p=0.002). Our study confirms the high prevalence and worse prognosis of LF/LG SAS. Clinicians must be aware of this entity to ensure appropriate patient management. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Local Failure in Parameningeal Rhabdomyosarcoma Correlates With Poor Response to Induction Chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ladra, Matthew M.; Mandeville, Henry C.; Niemierko, Andrzej

2015-06-01

Background: Local control remains a challenge in pediatric parameningeal rhabdomyosarcoma (PM-RMS), and survival after local failure (LF) is poor. Identifying patients with a high risk of LF is of great interest to clinicians. In this study, we examined whether tumor response to induction chemotherapy (CT) could predict LF in embryonal PM-RMS. Methods: We identified 24 patients with embryonal PM-RMS, age 2 to 18 years, with complete magnetic resonance imaging and gross residual disease after surgical resection. All patients received proton radiation therapy (RT), median dose 50.4 Gy{sub RBE} (50.4-55.8 Gy{sub RBE}). Tumor size was measured before initial CT and before RT. Results:more » With a median follow-up time of 4.1 years for survivors, LF was seen in 9 patients (37.5%). The median time from the initiation of CT to the start of RT was 4.8 weeks. Patients with LF had a similar initial (pre-CT) tumor volume compared with patients with local controlled (LC) (54 cm{sup 3} vs 43 cm{sup 3}, P=.9) but a greater median volume before RT (pre-RT) (40 cm{sup 3} vs 7 cm{sup 3}, P=.009) and a smaller median relative percent volume reduction (RPVR) in tumor size (0.4% vs 78%, P<.001). Older age (P=.05), larger pre-RT tumor volume (P=.03), and smaller RPVR (P=.003) were significantly associated with actuarial LF on univariate Cox analysis. Conclusions: Poor response to induction CT appears to be associated with an increased risk of LF in pediatric embryonal PM-RMS.« less

A Diverse Set of Single-domain Antibodies (VHHs) against the Anthrax Toxin Lethal and Edema Factors Provides a Basis for Construction of a Bispecific Agent That Protects against Anthrax Infection.

PubMed

Vrentas, Catherine E; Moayeri, Mahtab; Keefer, Andrea B; Greaney, Allison J; Tremblay, Jacqueline; O'Mard, Danielle; Leppla, Stephen H; Shoemaker, Charles B

2016-10-07

Infection with Bacillus anthracis, the causative agent of anthrax, can lead to persistence of lethal secreted toxins in the bloodstream, even after antibiotic treatment. VHH single-domain antibodies have been demonstrated to neutralize diverse bacterial toxins both in vitro and in vivo, with protein properties such as small size and high stability that make them attractive therapeutic candidates. Recently, we reported on VHHs with in vivo activity against the protective antigen component of the anthrax toxins. Here, we characterized a new set of 15 VHHs against the anthrax toxins that act by binding to the edema factor (EF) and/or lethal factor (LF) components. Six of these VHHs are cross-reactive against both EF and LF and recognize the N-terminal domain (LF N , EF N ) of their target(s) with subnanomolar affinity. The cross-reactive VHHs block binding of EF/LF to the protective antigen C-terminal binding interface, preventing toxin entry into the cell. Another VHH appears to recognize the LF C-terminal domain and exhibits a kinetic effect on substrate cleavage by LF. A subset of the VHHs neutralized against EF and/or LF in murine macrophage assays, and the neutralizing VHHs that were tested improved survival of mice in a spore model of anthrax infection. Finally, a bispecific VNA (VHH-based neutralizing agent) consisting of two linked toxin-neutralizing VHHs, JMN-D10 and JMO-G1, was fully protective against lethal anthrax spore infection in mice as a single dose. This set of VHHs should facilitate development of new therapeutic VNAs and/or diagnostic agents for anthrax. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Mechanisms of Autonomic Dysfunction Associated with Extreme Exertional Heat Stroke and Potential Efficacy of Novel Pharmacological Treatments

DTIC Science & Technology

2014-12-01

cardiovascular diseases. At higher doses, these medications have been prescribed to treat high blood pressure in humans and both may have relevance as...HR, and Tc. § Low frequency (LF) systolic blood pressure variability as an index of sympathetic modulation of vascular tone. § LF and high ... blood pressure variability (LFSYS), LF heart rate variability (LFHR), and high frequency heart rate variability (HFHR) in placebo-, clonidine-, and

Combined use of X-ray fluorescence microscopy, phase contrast imaging for high resolution quantitative iron mapping in inflamed cells

NASA Astrophysics Data System (ADS)

Gramaccioni, C.; Procopio, A.; Farruggia, G.; Malucelli, E.; Iotti, S.; Notargiacomo, A.; Fratini, M.; Yang, Y.; Pacureanu, A.; Cloetens, P.; Bohic, S.; Massimi, L.; Cutone, A.; Valenti, P.; Rosa, L.; Berlutti, F.; Lagomarsino, S.

2017-06-01

X-ray fluorescence microscopy (XRFM) is a powerful technique to detect and localize elements in cells. To derive information useful for biology and medicine, it is essential not only to localize, but also to map quantitatively the element concentration. Here we applied quantitative XRFM to iron in phagocytic cells. Iron, a primary component of living cells, can become toxic when present in excess. In human fluids, free iron is maintained at 10-18 M concentration thanks to iron binding proteins as lactoferrin (Lf). The iron homeostasis, involving the physiological ratio of iron between tissues/secretions and blood, is strictly regulated by ferroportin, the sole protein able to export iron from cells to blood. Inflammatory processes induced by lipopolysaccharide (LPS) or bacterial pathoge inhibit ferroportin synthesis in epithelial and phagocytic cells thus hindering iron export, increasing intracellular iron and bacterial multiplication. In this respect, Lf is emerging as an important regulator of both iron and inflammatory homeostasis. Here we studied phagocytic cells inflamed by bacterial LPS and untreated or treated with milk derived bovine Lf. Quantitative mapping of iron concentration and mass fraction at high spatial resolution is obtained combining X-ray fluorescence microscopy, atomic force microscopy and synchrotron phase contrast imaging.

Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.

PubMed

Jiang, Xiaohong; Dalebout, Tim J; Bredenbeek, Peter J; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S; Lukashevich, Igor S

2011-02-01

Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV-GP1 and -GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and -GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF proteins and LASV GP antigens in infected cells. YF17D/LASV-GP1 and -GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1 and -GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. Copyright © 2010 Elsevier Ltd. All rights reserved.

Constraints in the diagnosis and treatment of Lassa Fever and the effect on mortality in hospitalized children and women with obstetric conditions in a rural district hospital in Sierra Leone

PubMed Central

Dahmane, A.; van Griensven, J.; Van Herp, M.; Van den Bergh, R.; Nzomukunda, Y.; Prior, J.; Alders, P.; Jambai, A.; Zachariah, R.

2014-01-01

Background Lassa fever (LF) is an acute viral haemorrhagic infection, endemic in West Africa. Confirmatory diagnosis and treatment (ribavirin) is difficult, expensive, and restricted to specialised hospitals. Among confirmed and suspected LF cases, we report on clinical and laboratory features, timing and administration of ribavirin and the relationship with case fatality. Methods We conducted an audit of patient files of suspected LF cases admitted to a pediatric and obstetric referral hospital in rural Sierra Leone (April 2011 to February 2012). Results There were 84 suspected LF cases; 36 (43%) were laboratory-confirmed cases, of whom only 20 (56%) received ribavirin after a median duration of eight days (IQR 314 days) of hospital admission. Of 16 patients who did not receive ribavirin, 14 (87%) died before ribavirin treatment could be commenced. Starting ribavirin within six days of admission was associated with a case fatality of 29% (2/7), while starting ribavirin later than six days was associated with a case fatality of 50% (6/12). Among the 48 suspected LF cases without laboratory confirmation, there were 21 (44%) deaths. Conclusions These findings highlight shortcomings in LF management, including diagnostic and treatment delays. More research and development efforts should be devoted to this ‘neglected disease’. PMID:24535150

Fluorescence spectroscopic detection of virus-induced atherosclerosis

NASA Astrophysics Data System (ADS)

Yan, Wei-dong; Perk, Masis; Nation, Patric N.; Power, Robert F.; Liu, Liying; Jiang, Xiuyan; Lucas, Alexandra

1994-07-01

Laser-induced fluorescence (LF) has been developed as a diagnostic tool for the detection of atherosclerosis. We have examined the use of LF for the identification of accelerated atherosclerotic plaque growth induced by Marek's Disease Virus (MDV) infection in White Leghorn rooster chicks (R) as well as plaque regression after treatment. Twenty-eight newborn R were infected with 12,000 cfu of MDV. Twelve parallel control R had saline injection. LF spectra were recorded from the arteries in vitro with a CeramOptec laser angioplasty catheter during 308 nm XeCl excimer laser excitation. Significant differences were detected at 440 to 475, 525, 550, 600, and 650 nm in MDV-R (p<0.05). In a subsequent study, 60 R were infected with 5,000 cfu of MDV, and were then treated with either Pravastatin (PRV) or placebo at 3 months post infection. These PRV-R were followed for 6 months to detect changes in atherosclerotic plaque development. PRV reduced intimal proliferation produced by MDV infection on histological examination (PRV-R 128.0+/- 44.0 micrometers , placebo-R 412.2+/- 91.5 micrometers , pequals0.007). MDV infected, PRV treated R were examined for LF changes that correlated with decreased atherosclerosis. There was an associated significant increase in LF intensity in PRV-R at 405 to 425 nm (p<0.001). In conclusion, LF can detect intimal proliferation in virus- induced atherosclerosis and atherosclerotic plaque regression after PRV therapy.

Impact of a High-Fat or High-Fiber Diet on Intestinal Microbiota and Metabolic Markers in a Pig Model

PubMed Central

Heinritz, Sonja N.; Weiss, Eva; Eklund, Meike; Aumiller, Tobias; Heyer, Charlotte M.E.; Messner, Sabine; Rings, Andreas; Louis, Sandrine; Bischoff, Stephan C.; Mosenthin, Rainer

2016-01-01

To further elaborate interactions between nutrition, gut microbiota and host health, an animal model to simulate changes in microbial composition and activity due to dietary changes similar to those in humans is needed. Therefore, the impact of two different diets on cecal and colonic microbial gene copies and metabolic activity, organ development and biochemical parameters in blood serum was investigated using a pig model. Four pigs were either fed a low-fat/high-fiber (LF), or a high-fat/low-fiber (HF) diet for seven weeks, with both diets being isocaloric. A hypotrophic effect of the HF diet on digestive organs could be observed compared to the LF diet (p < 0.05). Higher gene copy numbers of Bacteroides (p < 0.05) and Enterobacteriaceae (p < 0.001) were present in intestinal contents of HF pigs, bifidobacteria were more abundant in LF pigs (p < 0.05). Concentrations of acetate and butyrate were higher in LF pigs (p < 0.05). Glucose was higher in HF pigs, while glutamic pyruvic transaminase (GPT) showed higher concentrations upon feeding the LF diet (p < 0.001). However, C-reactive protein (CRP) decreased with time in LF pigs (p < 0.05). In part, these findings correspond to those in humans, and are in support of the concept of using the pig as human model. PMID:27223303

Structural and magnetic properties of the products of the transformation of ferrihydrite: Effect of cobalt dications

NASA Astrophysics Data System (ADS)

Camacho, K. I.; Pariona, N.; Martinez, A. I.; Baggio-Saitovitch, E.; Herrera-Trejo, M.; Perry, Dale L.

2017-05-01

The effect of cobalt dications on the transformation of 2-line ferrihydrite (2LF) has been studied. The products of the transformation reaction were characterized by X-ray diffraction, Mössbauer spectroscopy (MS), transmission electron microscopy (TEM), magnetometry, and first-order reversal curve (FORC) diagrams. It was found that the concentration of cobalt dications plays an important role on the structural and magnetic properties of the products; i.e., for low cobalt concentrations, cobalt-substituted hematite is formed, while higher concentrations promote the formation of cobalt-substituted magnetite. Structural results revealed that formation of other iron oxide polymorphs is avoided and residual 2LF is always present in the final products. In this way, hematite/2LF and magnetite/2LF nanocomposites were formed. For all the samples, magnetic measurements yielded non-saturated hysteresis loops at a maximum field of 12 kOe. For cobalt-substituted hematite/2LF samples, FORC diagrams revealed the presence of multiple single-domain (SD) components which generate interaction coupling between SD with low and high coercivity. Moreover, for cobalt-substituted magnetite/2LF samples, the FORC diagrams revealed the components of wasp-waist hysteresis loops which consist of mixtures of SD and superparamagnetic particles. One of the goals of the present study is the rigorous, experimental documentation of ferrihydrite/hematite mixtures as a function of reaction conditions for use as analytical standards research.

Effect of deep pressure input on parasympathetic system in patients with wisdom tooth surgery.

PubMed

Chen, Hsin-Yung; Yang, Hsiang; Meng, Ling-Fu; Chan, Pei-Ying Sarah; Yang, Chia-Yen; Chen, Hsin-Ming

2016-10-01

Deep pressure input is used to normalize physiological arousal due to stress. Wisdom tooth surgery is an invasive dental procedure with high stress levels, and an alleviation strategy is rarely applied during extraction. In this study, we investigated the effects of deep pressure input on autonomic responses to wisdom tooth extraction in healthy adults. A randomized, controlled, crossover design was used for dental patients who were allocated to experimental and control groups that received treatment with or without deep pressure input, respectively. Autonomic indicators, namely the heart rate (HR), percentage of low-frequency (LF) HR variability (LF-HRV), percentage of high-frequency (HF) HRV (HF-HRV), and LF/HF HRV ratio (LF/HF-HRV), were assessed at the baseline, during wisdom tooth extraction, and in the posttreatment phase. Wisdom tooth extraction caused significant autonomic parameter changes in both groups; however, differential response patterns were observed between the two groups. In particular, deep pressure input in the experimental group was associated with higher HF-HRV and lower LF/HF-HRV during extraction compared with those in the control group. LF/HF-HRV measurement revealed balanced sympathovagal activation in response to deep pressure application. The results suggest that the application of deep pressure alters the response of HF-HRV and facilitates maintaining sympathovagal balance during wisdom tooth extraction. Copyright © 2016. Published by Elsevier B.V.

Impact of a High-Fat or High-Fiber Diet on Intestinal Microbiota and Metabolic Markers in a Pig Model.

PubMed

Heinritz, Sonja N; Weiss, Eva; Eklund, Meike; Aumiller, Tobias; Heyer, Charlotte M E; Messner, Sabine; Rings, Andreas; Louis, Sandrine; Bischoff, Stephan C; Mosenthin, Rainer

2016-05-23

To further elaborate interactions between nutrition, gut microbiota and host health, an animal model to simulate changes in microbial composition and activity due to dietary changes similar to those in humans is needed. Therefore, the impact of two different diets on cecal and colonic microbial gene copies and metabolic activity, organ development and biochemical parameters in blood serum was investigated using a pig model. Four pigs were either fed a low-fat/high-fiber (LF), or a high-fat/low-fiber (HF) diet for seven weeks, with both diets being isocaloric. A hypotrophic effect of the HF diet on digestive organs could be observed compared to the LF diet (p < 0.05). Higher gene copy numbers of Bacteroides (p < 0.05) and Enterobacteriaceae (p < 0.001) were present in intestinal contents of HF pigs, bifidobacteria were more abundant in LF pigs (p < 0.05). Concentrations of acetate and butyrate were higher in LF pigs (p < 0.05). Glucose was higher in HF pigs, while glutamic pyruvic transaminase (GPT) showed higher concentrations upon feeding the LF diet (p < 0.001). However, C-reactive protein (CRP) decreased with time in LF pigs (p < 0.05). In part, these findings correspond to those in humans, and are in support of the concept of using the pig as human model.

Bovine Mammary Nutrigenomics and Changes in the Milk Composition due to Rapeseed or Sunflower Oil Supplementation of High-Forage or High-Concentrate Diets.

PubMed

Leroux, Christine; Bernard, Laurence; Faulconnier, Yannick; Rouel, Jacques; de la Foye, Anne; Domagalski, Jordann; Chilliard, Yves

2016-01-01

Fatty acid (FA) composition plays a crucial role in milk nutritional quality. Despite the known nutritional regulation of ruminant milk composition, the overall mammary mechanisms underlying this regulation are far from being understood. The aim of our study was to determine nutritional regulation of mammary transcriptomes in relation to the cow milk composition. Twelve cows received diets differing in the forage-to-concentrate ratio [high forage (HF) and low forage (LF)] supplemented or not with lipids [HF with whole intact rapeseeds (RS) and LF sunflower oil (SO)] in a 4 × 4 Latin square design. Milk production and FA composition were determined. The gene expression profile was studied using RT-qPCR and a bovine microarray. Our results showed a higher amplitude of milk composition and mammary transcriptome responses to lipid supplementation with the LF-SO compared with the LF diet than with the HF-RS compared with the HF diet. Forty-nine differentially expressed genes, including genes involved in lipid metabolism, were identified with LF-SO versus LF, whereas RS supplementation to the HF diet did not affect the mammary transcriptome. This study highlights different responses to lipid supplementation of milk production and composition and mammary transcriptomes depending on the nature of lipid supplementation and the percentage of dietary concentrate. © 2016 S. Karger AG, Basel.

Elevated levels of triglyceride and triglyceride-rich lipoprotein triglyceride induced by a high-carbohydrate diet is associated with polymorphisms of APOA5-1131T>C and APOC3-482C>T in Chinese healthy young adults.

PubMed

Lin, Jia; Fang, Ding Zhi; Du, Juan; Shigdar, Sarah; Xiao, Li Ying; Zhou, Xue Dong; Duan, Wei

2011-01-01

Changes in lipid profiles have been shown to be associated with diet and apolipoprotein (APO) polymorphisms. Therefore, 2 polymorphisms, i.e. APOA5-1131T>C and APOC3-482C>T, and serum lipids were examined in a Chinese healthy young population with high-carbohydrate/low-fat (HC/LF) diet intervention. After a wash-out diet for 7 days, 56 young adults (22.89 ± 1.80 years) received the HC/LF diet for 6 days. Body mass index (BMI) and fasting serum lipid profiles at baseline, after the wash-out diet, and after the HC/LF diet were measured. APOA5-1131C carriers had higher triglyceride (TG) and TG-rich lipoprotein TG (TRL-TG) levels at baseline and after the HC/LF diet, though this mainly corresponded to the female cohort. APOC3-482T carriers had higher TRL-TG levels following the wash-out and HC/LF diets, but these were not directly attributable to a single gender. Both polymorphisms may play an important role in the elevated TG and TRL-TG levels induced by the HC/LF diet, especially in females, thus indicating a potential dietary prevention of coronary heart disease in this Chinese cohort. Copyright © 2011 S. Karger AG, Basel.

Rapid and automatic chemical identification of the medicinal flower buds of Lonicera plants by the benchtop and hand-held Fourier transform infrared spectroscopy

NASA Astrophysics Data System (ADS)

Chen, Jianbo; Guo, Baolin; Yan, Rui; Sun, Suqin; Zhou, Qun

2017-07-01

With the utilization of the hand-held equipment, Fourier transform infrared (FT-IR) spectroscopy is a promising analytical technique to minimize the time cost for the chemical identification of herbal materials. This research examines the feasibility of the hand-held FT-IR spectrometer for the on-site testing of herbal materials, using Lonicerae Japonicae Flos (LJF) and Lonicerae Flos (LF) as examples. Correlation-based linear discriminant models for LJF and LF are established based on the benchtop and hand-held FT-IR instruments. The benchtop FT-IR models can exactly recognize all articles of LJF and LF. Although a few LF articles are misjudged at the sub-class level, the hand-held FT-IR models are able to exactly discriminate LJF and LF. As a direct and label-free analytical technique, FT-IR spectroscopy has great potential in the rapid and automatic chemical identification of herbal materials either in laboratories or in fields. This is helpful to prevent the spread and use of adulterated herbal materials in time.

Effects of lactoferrin on the production of interferon-λ by the human intestinal epithelial cell line HT-29.

PubMed

Shin, Kouichirou; Oda, Hirotsugu; Wakabayashi, Hiroyuki; Yamauchi, Koji; Abe, Fumiaki

2017-02-01

We examined the in-vitro effects of bovine lactoferrin (LF) on the production of interferon-λ (IFN-λ), an antiviral cytokine important for the defense of enterocytes, using the human intestinal epithelial cell line HT-29. HT-29 cell cultures were treated with LF for 1 h, and the cultures were stimulated with polyinosinic-polycytidylic acid (poly I:C). LF increased the concentration of IFN-λ in the culture supernatant after stimulation in a dose-dependent manner. A similar increase in the concentration of IFN-λ was observed in the supernatant of cells washed between treatment with LF and stimulation with poly I:C. At 6 and 24 h after stimulation with poly I:C (early and late phases, respectively) treated cultures contained significantly higher concentrations of IFN-λ1 in the culture supernatant, and significantly higher IFN-λ1 and IFN-λ2 mRNA levels, than controls. These results suggest that LF activates the innate cellular immunity of the enterocytes to double-stranded RNA and increases the production of IFN-λ.

Seaweed polysaccharides (laminarin and fucoidan) as functional ingredients in pork meat: an evaluation of anti-oxidative potential, thermal stability and bioaccessibility.

PubMed

Moroney, Natasha C; O'Grady, Michael N; Lordan, Sinéad; Stanton, Catherine; Kerry, Joseph P

2015-04-20

The anti-oxidative potential of laminarin (L), fucoidan (F) and an L/F seaweed extract was measured using the DPPH free radical scavenging assay, in 25% pork (longissimus thoracis et lumborum (LTL)) homogenates (TBARS) (3 and 6 mg/mL) and in horse heart oxymyoglobin (OxyMb) (0.1 and 1 mg/mL). The DPPH activity of fresh and cooked minced LTL containing L (100 mg/g; L100), F100 and L/F100,300, and bioaccessibility post in vitro digestion (L/F300), was assessed. Theoretical cellular uptake of antioxidant compounds was measured in a transwell Caco-2 cell model. Laminarin displayed no activity and fucoidan reduced lipid oxidation but catalysed OxyMb oxidation. Fucoidan activity was lowered by cooking while the L/F extract displayed moderate thermal stability. A decrease in DPPH antioxidant activity of 44.15% and 36.63%, after 4 and 20 h respectively, indicated theoretical uptake of L/F antioxidant compounds. Results highlight the potential use of seaweed extracts as functional ingredients in pork.

Effect of Noradrenergic Neurotoxin DSP-4 and Maprotiline on Heart Rate Spectral Components in Stressed and Resting Rats.

PubMed

Kur'yanova, E V; Zhukova, Yu D; Teplyi, D L

2017-07-01

The effects of intraperitoneal DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, a noradrenergic neurotoxin) and maprotiline (an inhibitor of norepinephrine reuptake in synapses) on spectral components of heart rhythm variability were examined in outbred male and female rats treated with these agents in daily doses of 10 mg/kg for 3 days. At rest, DSP-4 elevated LF and VLF spectral components in male and female rats. Maprotiline elevated LF and VLF components in males at rest, increased HR and reduced all spectral components in resting females. Stress against the background of DSP-4 treatment sharply increased heart rate and reduced the powers of all spectral components (especially LF and VLF components). In maprotiline-treated rats, stress increased the powers of LF and VLF components. Thus, the central noradrenergic system participates in the formation of LF and VLF spectral components of heart rate variability at rest and especially during stressful stimulation, which can determine the phasic character of changes in the heart rate variability observed in stressed organism.

Cooking quality and starch digestibility of gluten free pasta using new bean flour.

PubMed

Giuberti, Gianluca; Gallo, Antonio; Cerioli, Carla; Fortunati, Paola; Masoero, Francesco

2015-05-15

The use of rice/leguminous blend may be nutritionally convenient in gluten free product manufacturing. Gluten free spaghetti was prepared with rice flour and different concentrations of bean flour (included at levels of 0%, 20% and 40%, w/w) derived from a new developed white-seeded low phytic acid and lectin free (ws+lpa+lf) bean cultivar. Protein, ash and dietary fibre contents increased linearly (P<0.05) while total starch decreased quadratically (P<0.05) with the inclusion of ws+lpa+lf bean flour. The colour of spaghetti was influenced (P<0.05) by ws+lpa+lf bean inclusion. With respect to 0% spaghetti, the inclusion of ws+lpa+lf bean increased linearly (P<0.05) the optimal cooking time and the water absorption capacity, without affecting cooking loss and texture properties. The ws+lpa+lf bean inclusion increases quadratically (P<0.05) the resistant starch content, while decreasing quadratically (P<0.05) the in vitro glycemic index. The partial replacement of rice flour with bean flour can favourably be used in gluten free spaghetti formulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adherence to a low-fat vs. low-carbohydrate diet differs by insulin resistance status.

PubMed

McClain, A D; Otten, J J; Hekler, E B; Gardner, C D

2013-01-01

Previous research shows diminished weight loss success in insulin-resistant (IR) women assigned to a low-fat (LF) diet compared to those assigned to a low-carbohydrate (LC) diet. These secondary analyses examined the relationship between insulin-resistance status and dietary adherence to either a LF-diet or LC-diet among 81 free-living, overweight/obese women [age = 41.9 ± 5.7 years; body mass index (BMI) = 32.6 ± 3.6 kg/m(2)]. This study found differential adherence by insulin-resistance status only to a LF-diet, not a LC-diet. IR participants were less likely to adhere and lose weight on a LF-diet compared to insulin-sensitive (IS) participants assigned to the same diet. There were no significant differences between IR and IS participants assigned to LC-diet in relative adherence or weight loss. These results suggest that insulin resistance status may affect dietary adherence to weight loss diets, resulting in higher recidivism and diminished weight loss success of IR participants advised to follow LF-diets for weight loss. © 2012 Blackwell Publishing Ltd.

Seaweed Polysaccharides (Laminarin and Fucoidan) as Functional Ingredients in Pork Meat: An Evaluation of Anti-Oxidative Potential, Thermal Stability and Bioaccessibility

PubMed Central

Moroney, Natasha C.; O’Grady, Michael N.; Lordan, Sinéad; Stanton, Catherine; Kerry, Joseph P.

2015-01-01

The anti-oxidative potential of laminarin (L), fucoidan (F) and an L/F seaweed extract was measured using the DPPH free radical scavenging assay, in 25% pork (longissimus thoracis et lumborum (LTL)) homogenates (TBARS) (3 and 6 mg/mL) and in horse heart oxymyoglobin (OxyMb) (0.1 and 1 mg/mL). The DPPH activity of fresh and cooked minced LTL containing L (100 mg/g; L100), F100 and L/F100,300, and bioaccessibility post in vitro digestion (L/F300), was assessed. Theoretical cellular uptake of antioxidant compounds was measured in a transwell Caco-2 cell model. Laminarin displayed no activity and fucoidan reduced lipid oxidation but catalysed OxyMb oxidation. Fucoidan activity was lowered by cooking while the L/F extract displayed moderate thermal stability. A decrease in DPPH antioxidant activity of 44.15% and 36.63%, after 4 and 20 h respectively, indicated theoretical uptake of L/F antioxidant compounds. Results highlight the potential use of seaweed extracts as functional ingredients in pork. PMID:25903283

Antimicrobial Activity of Lactoferrin-Related Peptides and Applications in Human and Veterinary Medicine.

PubMed

Bruni, Natascia; Capucchio, Maria Teresa; Biasibetti, Elena; Pessione, Enrica; Cirrincione, Simona; Giraudo, Leonardo; Corona, Antonio; Dosio, Franco

2016-06-11

Antimicrobial peptides (AMPs) represent a vast array of molecules produced by virtually all living organisms as natural barriers against infection. Among AMP sources, an interesting class regards the food-derived bioactive agents. The whey protein lactoferrin (Lf) is an iron-binding glycoprotein that plays a significant role in the innate immune system, and is considered as an important host defense molecule. In search for novel antimicrobial agents, Lf offers a new source with potential pharmaceutical applications. The Lf-derived peptides Lf(1-11), lactoferricin (Lfcin) and lactoferrampin exhibit interesting and more potent antimicrobial actions than intact protein. Particularly, Lfcin has demonstrated strong antibacterial, anti-fungal and antiparasitic activity with promising applications both in human and veterinary diseases (from ocular infections to osteo-articular, gastrointestinal and dermatological diseases).

The search for animal models for Lassa fever vaccine development

PubMed Central

Lukashevich, Igor S

2013-01-01

Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates. PMID:23256740

The search for animal models for Lassa fever vaccine development.

PubMed

Lukashevich, Igor S

2013-01-01

Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates.

[Nuclear transfer of goat somatic cells transgenic for human lactoferrin].

PubMed

Li, Lan; Shen, Wei; Pan, Qing-Yu; Min, Ling-Jiang; Sun, Yu-Jiang; Fang, Yong-Wei; Deng, Ji-Xian; Pan, Qing-Jie

2006-12-01

Transgenic animal mammary gland bioreactors are being used to produce recombinant proteins with appropriate post-translational modifications, and nuclear transfer of transgenic somatic cells is a more powerful method to produce mammary gland bioreactor. Here we describe efficient gene transfer and nuclear transfer in goat somatic cells. Gene targeting vector pGBC2LF was constructed by cloning human lactoferrin (LF) gene cDNA into exon 2 of the milk goat beta-casein gene, and the endogenous start condon was replaced by that of human LF gene. Goat fetal fibroblasts were transfected with linearized pGBC2LF and 14 cell lines were positive according to PCR and Southern blot. The transgenic cells were used as donor cells of nuclear transfer, and some of reconstructed embryos could develop to blastocyst in vitro.

Can Lymphatic Filariasis Be Eliminated by 2020?

PubMed

Rebollo, Maria P; Bockarie, Moses J

2017-02-01

Interventions against neglected tropical diseases (NTD), including lymphatic filariasis (LF), scaled up dramatically after the signing of the London Declaration (LD) in 2012. LF is targeted for elimination by 2020, but some countries are considered not on track to meet the 2020 target using the recommended preventive chemotherapy and morbidity management strategies. In this Opinion article we review the prospects for achieving LF elimination by 2020 in the light of the renewed global action against NTDs and the global efforts to achieve the sustainable development goals (SDGs) by 2030. We conclude that LF can be eliminated by 2020 using cross-sectoral and integrated approaches because of the compound effect of the other SDG activities related to poverty reduction and water and sanitation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enrichment of gluten-free cakes with lupin (Lupinus albus L.) or buckwheat (Fagopyrum esculentum M.) flours.

PubMed

Levent, Hacer; Bilgiçli, Nermin

2011-11-01

In the present study, the effect of debittered lupin flour (LF) and whole buckwheat flour (BF) on the nutritional and sensory quality of gluten-free cake was studied. LF (10, 20, 30 and 40%) and BF (5, 10, 15 and 20%) were partially replaced with corn starch and rice flour mixture (1:1 w/w) in the gluten-free cake recipe. LF increased the protein, calcium, iron, manganese, phosphorus and zinc contents of the cakes, while BF caused a significant increase (P < 0.05) especially in potassium and magnesium contents of the gluten-free cakes. According to the overall acceptability rating, it was concluded that gluten-free cake could be produced with satisfactory results by the addition of LF and BF up to 30% and 10%, respectively.

Aspects regarding the use of the INFREP network for identifying possible seismic precursors

NASA Astrophysics Data System (ADS)

Dolea, Paul; Cristea, Octavian; Dascal, Paul Vladut; Moldovan, Iren-Adelina; Biagi, Pier Francesco

In the last decades, one of the main research directions in identifying seismic precursors involved monitoring VLF (Very Low Frequency) and LF (Low Frequency) radio waves and analysing their propagation characteristics. Essentially this method consists of monitoring different available VLF and LF transmitters from long distance reception points. The received signal has two major components: the ground wave and the sky wave, where the sky wave propagates by reflection on the lower layers of the ionosphere. It is assumed that before and during major earthquakes, unusual changes may occur in the lower layers of the ionosphere, such as the modification of the charged particles number density and the altitude of the reflection zone. Therefore, these unusual changes in the ionosphere may generate unusual variations in the received signal level. The International Network for Frontier Research on Earthquake Precursors (INFREP) was developed starting with 2009 and consists of several dedicated VLF and LF radio receivers used for monitoring various radio transmitters located throughout Europe. The receivers' locations were chosen so that the propagation path from these VLF/LF stations would pass over high seismicity regions while others were chosen to obtain different control paths. The monitoring receivers are capable of continuously measuring the received signal amplitude from the VLF/LF stations of interest. The recorded data is then stored and sent to an INFREP database, which is available on the Internet for scientific researchers. By processing and analysing VLF and LF data samples, collected at different reception points and at different periods of the year, one may be able to identify some distinct patterns in the envelope of the received signal level over time. Significant deviations from these patterns may have local causes such as the electromagnetic pollution at the monitoring point, regional causes like existing electrical storms over the propagation path or even global causes generated by high-intensity solar flares. As a consequence, classifying these perturbations and minimizing them (when possible) would represent an important step towards identifying significant pattern deviations caused by seismic activities. Taken into consideration some of the issues mentioned above, this paper intends to present some aspects meant to improve the overall performance of the existing INFREP network. The signal-to-noise ratio improvement of the monitoring receiver may be achieved by relocating the antenna (or even the entire monitoring system if possible) in areas with less electromagnetic pollution within the VLF and LF bands. Other solution may involve replacing the existing electric ;whip; antennas with magnetic loop antennas. Regarding the measuring method, long-term averaging of the received signal to reduce the electromagnetic noise should be carefully applied. If the averaging time is too long, there is a risk that, during a seismic event, the details of the received signal envelope would be lost. Moreover, this may reduce the possibility of making correlations between the monitored stations and INFREP receivers in case of sudden ERP (Effective Radiated Power) variations of the VLF/LF stations. For the same reason, the time synchronization of the recorded data using (for instance) GPS technology is highly recommended. Other aspects related to the overall performance improvement of the INFREP network consist of monitoring other VLF/LF stations such as the Krasnodar station (south of Russia), part of the ALPHA/RSDN-20 VLF navigation system, or the 77.5 kHz DCF77 time signal transmitter (near Frankfurt am Main, Germany). Moreover, the installation of a new reception point in Romania (near Cluj-Napoca) for monitoring the Vrancea area (within the Carpathians Mountains) and the Adriatic region will provide complementary scientific data within the network.

Dual-frequency glow discharges in atmospheric helium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Xiaojiang; Guo, Ying; Magnetic Confinement Fusion Research Center, Ministry of Education of the People's Republic of China, Shanghai 201620

2015-10-15

In this paper, the dual-frequency (DF) glow discharges in atmospheric helium were experimented by electrical and optical measurements in terms of current voltage characteristics and optical emission intensity. It is shown that the waveforms of applied voltages or discharge currents are the results of low frequency (LF) waveforms added to high frequency (HF) waveforms. The HF mainly influences discharge currents, and the LF mainly influences applied voltages. The gas temperatures of DF discharges are mainly affected by HF power rather than LF power.

Urban lymphatic filariasis in the metropolis of Dar es Salaam, Tanzania

PubMed Central

2013-01-01

Background The last decades have seen a considerable increase in urbanization in Sub-Saharan Africa, and it is estimated that over 50% of the population will live in urban areas by 2040. Rapid growth of cities combined with limited economic resources often result in informal settlements and slums with favorable conditions for proliferation of vectors of lymphatic filariasis (LF). In Dar es Salaam, which has grown more than 30 times in population during the past 55 years (4.4 million inhabitants in 2012), previous surveys have indicated high prevalences of LF. This study investigated epidemiological aspects of LF in Dar es Salaam, as a background for planning and implementation of control. Methods Six sites with varying distance from the city center (3–30 km) and covering different population densities, socioeconomic characteristics, and water, sewerage and sanitary facilities were selected for the study. Pupils from one public primary school at each site were screened for circulating filarial antigen (CFA; marker of adult worm infection) and antibodies to Bm14 (marker of exposure to transmission). Community members were examined for CFA, microfilariae and chronic manifestations. Structured questionnaires were administered to pupils and heads of community households, and vector surveys were carried out in selected households. Results The study indicated that a tremendous decrease in the burden of LF infection had occurred, despite haphazard urbanisation. Contributing factors may be urban malaria control targeting Anopheles vectors, short survival time of the numerous Culex quinquefasciatus vectors in the urban environment, widespread use of bed nets and other mosquito proofing measures, and mass drug administration (MDA) in 2006 and 2007. Although the level of ongoing transmission was low, the burden of chronic LF disease was still high. Conclusions The development has so far been promising, but continued efforts are necessary to ensure elimination of LF as a public health problem. These will include improving the awareness of people about the role of mosquitoes in transmission of LF, more thorough implementation of environmental sanitation to reduce Cx. quinquefasciatus breeding, continued MDA to high-risk areas, and set-up of programmes for management of chronic LF disease. PMID:24289718

Effect of Body Composition on Physiological Responses to Cold-Water Immersion and the Recovery of Exercise Performance.

PubMed

Stephens, Jessica M; Halson, Shona L; Miller, Joanna; Slater, Gary J; Chapman, Dale W; Askew, Christopher D

2018-03-01

To explore the influence of body composition on thermal responses to cold-water immersion (CWI) and the recovery of exercise performance. Male subjects were stratified into 2 groups: low fat (LF; n = 10) or high fat (HF; n = 10). Subjects completed a high-intensity interval test (HIIT) on a cycle ergometer followed by a 15-min recovery intervention (control [CON] or CWI). Core temperature (T c ), skin temperature, and heart rate were recorded continuously. Performance was assessed at baseline, immediately post-HIIT, and 40 min postrecovery using a 4-min cycling time trial (TT), countermovement jump (CMJ), and isometric midthigh pull (IMTP). Perceptual measures (thermal sensation [TS], total quality of recovery [TQR], soreness, and fatigue) were also assessed. T c and TS were significantly lower in LF than in HF from 10 min (T c, LF 36.5°C ± 0.5°C, HF 37.2°C ± 0.6°C; TS, LF 2.3 ± 0.5 arbitrary units [a.u.], HF 3.0 ± 0.7 a.u.) to 40 min (T c , LF 36.1°C ± 0.6°C, HF 36.8°C ±0.7°C; TS, LF 2.3 ± 0.6 a.u., HF 3.2 ± 0.7 a.u.) after CWI (P < .05). Recovery of TT performance was significantly enhanced after CWI in HF (10.3 ± 6.1%) compared with LF (3.1 ± 5.6%, P = .01); however, no differences were observed between HF (6.9% ±5.7%) and LF (5.4% ± 5.2%) with CON. No significant differences were observed between groups for CMJ, IMTP, TQR, soreness, or fatigue in either condition. Body composition influences the magnitude of T c change during and after CWI. In addition, CWI enhanced performance recovery in the HF group only. Therefore, body composition should be considered when planning CWI protocols to avoid overcooling and maximize performance recovery.

α-Adrenergic effects on low-frequency oscillations in blood pressure and R-R intervals during sympathetic activation.

PubMed

Kiviniemi, Antti M; Frances, Maria F; Tiinanen, Suvi; Craen, Rosemary; Rachinsky, Maxim; Petrella, Robert J; Seppänen, Tapio; Huikuri, Heikki V; Tulppo, Mikko P; Shoemaker, J Kevin

2011-08-01

The present study was designed to address the contribution of α-adrenergic modulation to the genesis of low-frequency (LF; 0.04-0.15 Hz) oscillations in R-R interval (RRi), blood pressure (BP) and muscle sympathetic nerve activity (MSNA) during different sympathetic stimuli. Blood pressure and RRi were measured continuously in 12 healthy subjects during 5 min periods each of lower body negative pressure (LBNP; -40 mmHg), static handgrip exercise (HG; 20% of maximal force) and postexercise forearm circulatory occlusion (PECO) with and without α-adrenergic blockade by phentolamine. Muscle sympathetic nerve activity was recorded in five subjects during LBNP and in six subjects during HG and PECO. Low-frequency powers and median frequencies of BP, RRi and MSNA were calculated from power spectra. Low-frequency power during LBNP was lower with phentolamine versus without for both BP and RRi oscillations (1.6 ± 0.6 versus 1.2 ± 0.7 ln mmHg(2), P = 0.049; and 6.9 ± 0.8 versus 5.4 ± 0.9 ln ms(2), P = 0.001, respectively). In contrast, the LBNP with phentolamine increased the power of high-frequency oscillations (0.15-0.4 Hz) in BP and MSNA (P < 0.01 for both), which was not observed during saline infusion. Phentolamine also blunted the increases in the LBNP-induced increase in frequency of LF oscillations in BP and RRi. Phentolamine decreased the LF power of RRi during HG (P = 0.015) but induced no other changes in LF powers or frequencies during HG. Phentolamine resulted in decreased frequency of LF oscillations in RRi (P = 0.004) during PECO, and a similar tendency was observed in BP and MSNA. The power of LF oscillation in MSNA did not change during any intervention. We conclude that α-adrenergic modulation contributes to LF oscillations in BP and RRi during baroreceptor unloading (LBNP) but not during static exercise. Also, α-adrenergic modulation partly explains the shift to a higher frequency of LF oscillations during baroreceptor unloading and muscle metaboreflex activation.

Comparison of 2 weekly-equalized volume resistance-training routines using different frequencies on body composition and performance in trained males.

PubMed

Yue, Fu Leon; Karsten, Bettina; Larumbe-Zabala, Eneko; Seijo, Marcos; Naclerio, Fernando

2018-05-01

The present study compared the effects of 2 weekly-equalized volume and relative load interventions on body composition, strength, and power. Based on individual baseline maximal strength values, 18 recreationally trained men were pair-matched and consequently randomly assigned to one of the following experimental groups: a low volume per session with a high frequency (LV-HF, n = 9) group who trained for 4 days (Mondays, Tuesdays, Thursdays, and Fridays) or a high volume per session and low frequency (HV-LF, n = 9) group who trained for 2 days (Mondays and Thursdays). Both groups performed 2 different routines over 6 weeks. Participants were tested pre- and post- intervention for maximal strength, upper body power, fat-free mass, limb circumferences, and muscle thickness. Compared with baseline values, both groups increased their fat-free mass (HV-LF: +1.19 ± 1.94; LV-HF: +1.36 ± 1.06 kg, p < 0.05) and vastus medialis thickness (HV-LF: +2.18 ± 1.88, p < 0.01; LV-HF: +1.82 ± 2.43 mm, p < 0.05), but only the HV-LF group enhanced arm circumference (1.08 ± 1.47 cm, p < 0.05) and elbow flexors thickness (2.21 ± 2.81 mm, P < 0.01) values and decreased their fat mass (-2.41 ± 1.10, P < 0.01). Both groups improved (p < 0.01) the maximal loads lifted in the bench press (LV-HF: +0.14 ± 0.01; HV-LF: +0.14 ± 0.01 kg·body mass -1 ) and the squat (LV-HF: +0.14 ± 0.06; HV-LF: 0.17 ± 0.01 kg·body mass -1 ) exercises as well as in upper body power (LV-HF: +0.22 ± 0.25; HV-LF: +0.27 ± 0.22 W·body mass -1 ) Although both training strategies improved performance and lower body muscle mass, only the HV-LF protocol increased upper body hypertrophy and improved body composition.

Multifaceted Therapeutic Benefits of Factors Derived From Dental Pulp Stem Cells for Mouse Liver Fibrosis.

PubMed

Hirata, Marina; Ishigami, Masatoshi; Matsushita, Yoshihiro; Ito, Takanori; Hattori, Hisashi; Hibi, Hideharu; Goto, Hidemi; Ueda, Minoru; Yamamoto, Akihito

2016-10-01

: Chronic liver injury from various causes often results in liver fibrosis (LF). Although the liver possesses endogenous tissue-repairing activities, these can be overcome by sustained inflammation and excessive fibrotic scar formation. Advanced LF leads to irreversible cirrhosis and subsequent liver failure and/or hepatic cancer. Here, using the mouse carbon tetrachloride (CCl 4 )-induced LF model, we showed that a single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or of SHED-derived serum-free conditioned medium (SHED-CM) resulted in fibrotic scar resolution. SHED-CM suppressed the gene expression of proinflammatory mediators, such as TNF-α, IL-1β, and iNOS, and eliminated activated hepatic stellate cells by inducing their apoptosis, but protected parenchymal hepatocytes from undergoing apoptosis. In addition, SHED-CM induced tissue-repairing macrophages that expressed high levels of the profibrinolytic factor, matrix metalloproteinase 13. Furthermore, SHED-CM suppressed the CCl 4 -induced apoptosis of primary cultured hepatocytes. SHED-CM contained a high level of hepatocyte growth factor (HGF). Notably, HGF-depleted SHED-CM (dHGF-CM) did not suppress the proinflammatory response or resolve fibrotic scarring. Furthermore, SHED-CM, but not dHGF-CM, inhibited CCl 4 -induced hepatocyte apoptosis. These results suggest that HGF plays a central role in the SHED-CM-mediated resolution of LF. Taken together, our findings suggest that SHED-CM provides multifaceted therapeutic benefits for the treatment of LF. This study demonstrated that a single intravenous administration of stem cells from human exfoliated deciduous teeth (SHEDs) or of the serum-free conditioned medium (CM) derived from SHEDs markedly improved mouse liver fibrosis (LF). SHED-CM suppressed chronic inflammation, eliminated activated hepatic stellate cells by inducing their apoptosis, protected hepatocytes from undergoing apoptosis, and induced differentiation of tissue-repairing macrophages expressing high levels of the profibrinolytic factor matrix metalloproteinase 13. Furthermore, hepatocyte growth factor played a central role in the SHED-CM-mediated resolution of LF. This is the first report demonstrating the multifaceted therapeutic benefits of secreted factors derived from SHEDs for LF. ©AlphaMed Press.

Process for solvent refining of coal using a denitrogenated and dephenolated solvent

DOEpatents

Garg, Diwakar; Givens, Edwin N.; Schweighardt, Frank K.

1984-01-01

A process is disclosed for the solvent refining of non-anthracitic coal at elevated temperatures and pressure in a hydrogen atmosphere using a hydrocarbon solvent which before being recycled in the solvent refining process is subjected to chemical treatment to extract substantially all nitrogenous and phenolic constituents from the solvent so as to improve the conversion of coal and the production of oil in the solvent refining process. The solvent refining process can be either thermal or catalytic. The extraction of nitrogenous compounds can be performed by acid contact such as hydrogen chloride or fluoride treatment, while phenolic extraction can be performed by caustic contact or contact with a mixture of silica and alumina.

Optimization of palm oil physical refining process for reduction of 3-monochloropropane-1,2-diol (3-MCPD) ester formation.

PubMed

Zulkurnain, Musfirah; Lai, Oi Ming; Tan, Soo Choon; Abdul Latip, Razam; Tan, Chin Ping

2013-04-03

The reduction of 3-monochloropropane-1,2-diol (3-MCPD) ester formation in refined palm oil was achieved by incorporation of additional processing steps in the physical refining process to remove chloroester precursors prior to the deodorization step. The modified refining process was optimized for the least 3-MCPD ester formation and acceptable refined palm oil quality using response surface methodology (RSM) with five processing parameters: water dosage, phosphoric acid dosage, degumming temperature, activated clay dosage, and deodorization temperature. The removal of chloroester precursors was largely accomplished by increasing the water dosage, while the reduction of 3-MCPD esters was a compromise in oxidative stability and color of the refined palm oil because some factors such as acid dosage, degumming temperature, and deodorization temperature showed contradictory effects. The optimization resulted in 87.2% reduction of 3-MCPD esters from 2.9 mg/kg in the conventional refining process to 0.4 mg/kg, with color and oil stability index values of 2.4 R and 14.3 h, respectively.

Comparison of oil refining and biodiesel production process between screw press and n-hexane techniques from beauty leaf feedstock

NASA Astrophysics Data System (ADS)

Bhuiya, M. M. K.; Rasul, M. G.; Khan, M. M. K.; Ashwath, N.

2016-07-01

The Beauty Leaf Tree (Callophylum inophyllum) is regarded as an alternative source of energy to produce 2nd generation biodiesel due to its potentiality as well as high oil yield content in the seed kernels. The treating process is indispensable during the biodiesel production process because it can augment the yield as well as quality of the product. Oil extracted from both mechanical screw press and solvent extraction using n-hexane was refined. Five replications each of 25 gm of crude oil for screw press and five replications each of 25 gm of crude oil for n-hexane were selected for refining as well as biodiesel conversion processes. The oil refining processes consists of degumming, neutralization as well as dewaxing. The degumming, neutralization and dewaxing processes were performed to remove all the gums (phosphorous-based compounds), free fatty acids, and waxes from the fresh crude oil before the biodiesel conversion process carried out, respectively. The results indicated that up to 73% and 81% of mass conversion efficiency of the refined oil in the screw press and n-hexane refining processes were obtained, respectively. It was also found that up to 88% and 90% of biodiesel were yielded in terms of mass conversion efficiency in the transesterification process for the screw press and n-hexane techniques, respectively. While the entire processes (refining and transesterification) were considered, the conversion of beauty leaf tree (BLT) refined oil into biodiesel was yielded up to 65% and 73% of mass conversion efficiency for the screw press and n-hexane techniques, respectively. Physico-chemical properties of crude and refined oil, and biodiesel were characterized according to the ASTM standards. Overall, BLT has the potential to contribute as an alternative energy source because of high mass conversion efficiency.

The Lower Ionospheric VLF/LF Response to the 2017 Great American Solar Eclipse Observed Across the Continent

NASA Astrophysics Data System (ADS)

Cohen, M. B.; Gross, N. C.; Higginson-Rollins, M. A.; Marshall, R. A.; Gołkowski, M.; Liles, W.; Rodriguez, D.; Rockway, J.

2018-04-01

We present observations from 11 very low frequency (VLF)/low-frequency (LF) receivers across the continental United States during the 21 August 2017 "Great American Solar Eclipse." All receivers detected transmissions from VLF/LF beacons below 50 kHz, while seven also recorded LF beacons above 50 kHz, yielding dozens of individual transmitter-receiver radio links. Our observations show two separable superimposed signatures: (1) a gradual rise and fall in signal levels visible on almost all paths as the eclipse advances and then declines, as VLF attenuation is reduced by the changing ionosphere under an eclipsed Sun, and (2) direct reflective scattering off the narrow 100-km-wide totality spot, observed more uniquely when the transmitter or receiver, if not both, are relatively close to the totality spot.

DIAGNOdent Pen versus tactile sense for detection of subgingival calculus: an in vitro study.

PubMed

Shakibaie, Fardad; Walsh, Laurence J

2015-10-01

The objective of this study is to compare the performance of the DIAGNOdent laser fluorescence (LF) Pen to conventional periodontal probing for detection of subgingival calculus under defined laboratory conditions. Extracted teeth with various levels of subgingival deposits of calculus were mounted anatomically in stone casts, and an impression material was used to replicate periodontal soft tissues. The casts were examined for the presence of subgingival calculus at eight surfaces per tooth (240 sites) using LF and a periodontal probe. Sites were rescored after 1 and 3 weeks. Direct imaging of the root surfaces under magnification was the gold standard. As a result, for an experienced operator, LF was more accurate than tactile assessment (across all sites, 84.0% vs. 59.8%). The performance difference was greater for multi-rooted teeth (85.8% vs. 56.9%) than single-rooted teeth (77.2% vs. 66.7%). The performance of LF in this laboratory trial was influenced strongly by clinician skill and experience. When used by an experienced operator, LF was more sensitive (75.1% vs. 69.2%), specific (92.6% vs. 86.3%), and accurate (84% vs. 77.9%) than for an inexperienced operator. In conclusion, under the defined laboratory conditions used, LF had better performance than tactile examination, particularly for multi-rooted teeth. This method may have value clinically as an adjunct for detecting subgingival deposits of calculus in clinical practice. The usefulness of the method improves with operator experience.

Reception conditions of low frequency (LF) transmitter signals onboard DEMETER micro-satellite

NASA Astrophysics Data System (ADS)

Boudjada, M. Y.; Biagi, P. F.; Al-Haddad, E.; Galopeaud, P. H. M.; Besser, B.; Wolbang, D.; Prattes, G.; Eichelberger, H.; Stangle, G.; Parrot, M.; Schwingenschuh, K.

2017-12-01

We analyse the flux density variation associated to low frequency (LF) broadcasting transmitters observed by the ICE electric field experiment onboard DEMETER micro-satellite, observed from 01st Jan. to 09th Dec. 2010. We select five stations localized around the Mediterranean and the Black seas: Tipaza (252 kHz, 02°28'E, 36°33'N, Algeria), Roumoules (216 kHz, 06°08'E, 43°47'N, Monte Carlo), Polatli (180 kHz, 32°25'E, 39°45'N, Turkey), Nadour (171 kHz, 02°55'W, 35°02'N, Morocco) and Brasov (153 kHz, 25°36'E, 45°40', Romania). The detection of the LF transmitter signals by DEMETER micro-satellite is found to depend on the radiated power, the emitted frequency, and the orbit paths with regard to the location of the stations. This leads us to characterize the reception condition of the LF signals and to define time intervals where the detection probability is high. We show that LF signal are regularly recorded, each 12 days, when the satellite is above the broadcasting station. The signal intensity levels are principally significant during the solar activity. Hence we find that the solar and the geomagnetic activities are slightly correlated to the maxima of LF signal as recorded by DEMETER. Also we note a drop of the intensity level several days before the occurrence of earthquakes in/around the Mediterranean and Black seas.

Influence of lactoferrin in preventing preterm delivery: a pilot study.

PubMed

Giunta, Giuliana; Giuffrida, Lorena; Mangano, Katia; Fagone, Paolo; Cianci, Antonio

2012-01-01

Lactoferrin (Lf) is an approximately 80-kDa iron-binding glycoprotein, belonging to the transferrin family, with well-known bacteriostatic and bactericidal properties. It is produced and stored in specific (secondary) neutrophil granules and released during neutrophil activation and degranulation. Nowadays, Lf has a well-known therapeutic indication for combating iron deficiency anemia (IDA) in pregnant women. Studies suggest that Lf plays an important role against cervicovaginal infections by decreasing cytokines levels, such as interleukin (IL)-6, in cervicovaginal fluid. The aim of this preliminary trial was to evaluate the effectiveness of Lf in preventing preterm delivery caused by cervical infections and ripening. From November 2009 to August 2010, 21 pregnant women (26-32 weeks pregnant), aged between 22 and 36 years, suffering from IDA, at risk of preterm delivery, were prospectively enrolled in the study. One group (N=14) received 100 mg of recombinant human lactoferrin (bLf) [corrected] (lattoferrina; AG-pharma) twice a day before meals, for one month. The other group (N=7) received 520 mg of ferrous sulfate (Ferro-Grad; Abbott Laboratories, USA) once a day. The patients underwent transvaginal ultrasound to evaluate cervical length and funneling, and vaginal swabs were used to detect infections and cervicovaginal fluid sample collection to determine IL-6 levels. The results showed a correlation between the oral administration of 200 mg of bLf [corrected] with both the normalization of vaginal flora (vaginal infection disappearance) and the decrease in IL-6 cervicovaginal fluid levels in women at risk of preterm delivery.

Spectrum-Effect Relationships Between Chemical Fingerprints and Antibacterial Effects of Lonicerae Japonicae Flos and Lonicerae Flos Base on UPLC and Microcalorimetry

PubMed Central

Shi, Zhilong; Liu, Zhenjie; Liu, Chunsheng; Wu, Mingquan; Su, Haibin; Ma, Xiao; Zang, Yimei; Wang, Jiabo; Zhao, Yanling; Xiao, Xiaohe

2016-01-01

The traditional Chinese medicines Lonicerae Japonicae Flos (LJF, Jinyinhua in Chinese) and Lonicerae Flos (LF, Shanyinhua in Chinese) refer to the flower buds of five plants belonging to the Caprifoliaceae family. Until 2000, all of these were officially listed as a single item, LJF (Jinyinhua), in the Chinese Pharmacopoeia. However, there have recently been many academic controversies concerning the separation and combination of LJF and LF in administrative regulation. Till now there has been little work completed evaluating the relationships between biological activity and chemical properties among these drugs. Microcalorimetry and UPLC were used along with principal component analysis (PCA), hierarchical cluster analysis (HCA), and canonical correlation analysis (CCA) to investigate the relationships between the chemical ingredients and the antibacterial effects of LJF and LF. Using multivariate statistical analysis, LJF and LF could be initially separated according to their chemical fingerprints, and the antibacterial effects of the two herbal drugs were divided into two clusters. This result supports the disaggregation of LJF and LF by the Pharmacopoeia Committee. However, the sample of Lonicera fulvotomentosa Hsu et S. C. Cheng turned out to be an intermediate species, with similar antibacterial efficacy as LJF. The results of CCA indicated that chlorogenic acid and 3,4-Dicaffeoylquinic acid were the major components generating antibacterial effects. Furthermore, 3,4-Dicaffeoylquinic acid could be used as a new marker ingredient for quality control of LJF and LF. PMID:26869929

Low frequency noise and whole-body vibration cause increased levels of sister chromatid exchange in splenocytes of exposed mice.

PubMed

Silva, M J; Dias, A; Barreta, A; Nogueira, P J; Castelo-Branco, N A A; Boavida, M G

2002-01-01

Chronic exposure to low frequency (LF) noise and whole-body vibration (WBV) induces both physiological and psychological alterations in man. Recently, we have shown that long-term occupational exposure to LF noise and WBV produces genotoxic effects in man expressed as an increase in sister chromatid exchange (SCE) levels in lymphocytes. The objectives of the present study were to investigate whether the observed effect could be reproduced in a murine model and, if so, which of the agents, LF noise alone or in combination with WBV, would be instrumental in the SCE induction. SCEs were analyzed in spleen lymphocytes of mice exposed to LF noise alone and in combination with WBV for 300 and 600 hr. An effect at the cell cycle kinetics level was also investigated. The results revealed significant increases in the mean SCE number per cell and in the proportion of cells with high frequency of SCEs (HFCs) in lymphocytes of mice submitted to combined noise and WBV over controls. No significant differences were found between single noise-exposed and control mice. A cell cycle delay was observed exclusively in the noise and WBV exposure groups. In conclusion, we demonstrated that, as in exposed workers, prolonged exposure to the combination of LF noise and WBV determines an increase in SCE level in mice while LF noise alone is not effective in SCE induction. Copyright 2002 Wiley-Liss, Inc.

Is subcranial Le Fort III plus Le Fort I osteotomy stable?

PubMed

Boos Lima, Fernanda Brasil Daura Jorge; Hochuli Vieira, Eduardo; Juergens, Philipp; Lima Junior, Sergio Monteiro

2017-12-01

The purpose of this study was to test whether associated subcranial Le Fort III (sLF III) and Le Fort I (LF I) osteotomies are stable after large advancements of the middle third of the face and maxilla. The authors designed a retrospective study and enrolled a sample of consecutive patients with midface hypoplasia treated with associated sLF III and LF I osteotomies in this IRB-approved study between September 2013 and February 2015. To test whether the long-term stability was satisfactory, the authors compared cephalometric changes from immediately after surgery to 18 months after surgery taken from multi-slice computed tomography using two different third-party imaging software programs. Statistical significance was set as P ≤ 0.05. The sample comprised 11 patients (mean age 23.84 ± 4.17 yr; 54% men). The mean advancement of the upper incisor immediately after surgery was 10.03 ± 1.6 mm. After 18 months, the position of the upper incisor did not vary significantly (10.18 ± 2.35 mm). All other cephalometric landmarks did not present statistically significant differences between immediately after and 18 months after surgery, with horizontal and vertical variations of less than one millimetre. This study supports that sLF III and LF I osteotomies are effective in maintaining stable horizontal and vertical skeletal positioning after surgery. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Enzyme That Makes You Cry-Crystal Structure of Lachrymatory Factor Synthase from Allium cepa.

PubMed

Silvaroli, Josie A; Pleshinger, Matthew J; Banerjee, Surajit; Kiser, Philip D; Golczak, Marcin

2017-09-15

The biochemical pathway that gives onions their savor is part of the chemical warfare against microbes and animals. This defense mechanism involves formation of a volatile lachrymatory factor (LF) ((Z)-propanethial S-oxide) that causes familiar eye irritation associated with onion chopping. LF is produced in a reaction catalyzed by lachrymatory factor synthase (LFS). The principles by which LFS facilitates conversion of a sulfenic acid substrate into LF have been difficult to experimentally examine owing to the inherent substrate reactivity and lability of LF. To shed light on the mechanism of LF production in the onion, we solved crystal structures of LFS in an apo-form and in complex with a substrate analogue, crotyl alcohol. The enzyme closely resembles the helix-grip fold characteristic for plant representatives of the START (star-related lipid transfer) domain-containing protein superfamily. By comparing the structures of LFS to that of the abscisic acid receptor, PYL10, a representative of the START protein superfamily, we elucidated structural adaptations underlying the catalytic activity of LFS. We also delineated the architecture of the active site, and based on the orientation of the ligand, we propose a mechanism of catalysis that involves sequential proton transfer accompanied by formation of a carbanion intermediate. These findings reconcile chemical and biochemical information regarding thioaldehyde S-oxide formation and close a long-lasting gap in understanding of the mechanism responsible for LF production in the onion.

Enzyme That Makes You Cry–Crystal Structure of Lachrymatory Factor Synthase from Allium cepa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silvaroli, Josie A.; Pleshinger, Matthew J.; Banerjee, Surajit

The biochemical pathway that gives onions their savor is part of the chemical warfare against microbes and animals. This defense mechanism involves formation of a volatile lachrymatory factor (LF) ((Z)-propanethial S-oxide) that causes familiar eye irritation associated with onion chopping. LF is produced in a reaction catalyzed by lachrymatory factor synthase (LFS). The principles by which LFS facilitates conversion of a sulfenic acid substrate into LF have been difficult to experimentally examine owing to the inherent substrate reactivity and lability of LF. To shed light on the mechanism of LF production in the onion, we solved crystal structures of LFSmore » in an apo-form and in complex with a substrate analogue, crotyl alcohol. The enzyme closely resembles the helix-grip fold characteristic for plant representatives of the START (star-related lipid transfer) domain-containing protein superfamily. By comparing the structures of LFS to that of the abscisic acid receptor, PYL10, a representative of the START protein superfamily, we elucidated structural adaptations underlying the catalytic activity of LFS. We also delineated the architecture of the active site, and based on the orientation of the ligand, we propose a mechanism of catalysis that involves sequential proton transfer accompanied by formation of a carbanion intermediate. These findings reconcile chemical and biochemical information regarding thioaldehyde S-oxide formation and close a long-lasting gap in understanding of the mechanism responsible for LF production in the onion.« less

Laser fluorescence in monitoring the influence of targeted tooth brushing on remineralization of initial caries lesions on newly erupted molar teeth - RCT.

PubMed

Laitala, M-L; Jaanti, E; Vähänikkilä, H; Määttä, T; Heikka, H; Hausen, H; Anttonen, V

2017-11-01

This study aimed to monitor mineralization changes in initial caries lesions on newly erupted second molars using laser fluorescence (LF) scanning after a 1-month targeted tooth brushing intervention. Altogether, 124 13- to 14-year-old school children were invited to participate. Of those who fulfilled the clinical criteria (at least one initial lesion with LF value >10 in second molars), 51 gave their written consent to participate. Laser fluorescence values were registered at baseline and after 1-month follow-up period. All participants were individually taught targeted tooth brushing of their second molars and randomly provided tooth paste with 0 or 1500 ppm fluoride. Brushing frequency was investigated at baseline and after the follow-up. Change in LF values was compared considering the tooth, content of fluoride in the paste and brushing frequency. In lesions with LF values ≤30 at baseline, change in LF values demonstrated improvement. Improvement was detected especially in upper molars. In lesions with LF values >30 at baseline, improvement was least detected. Brushing frequency increased slightly during the intervention. Laser fluorescence is a simple method and useful in monitoring remineralization of incipient lesions even in weeks. Targeted tooth brushing seems to induce remineralization even in weeks. Laser fluorescence could be a valuable motivating tool in promoting patients' self-care. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Lymphatic filariasis in Papua New Guinea: distribution at district level and impact of mass drug administration, 1980 to 2011

PubMed Central

2013-01-01

Background Lymphatic filariasis (LF) caused by Wuchereria bancrofti is present at high prevalence in some parts of Papua New Guinea. However, there has been no rigorous data-based representative assessment of nationwide prevalence of LF. The LF programme has been daunted by the scope of the problem, and progress on mass drug administration (MDA) has been slow and lacking in resources. Methods A systematic literature review identified LF surveys in Papua New Guinea between 1980 and 2011. Results were extracted by location, time period and test used (blood slide, immunochromatographic test (ICT) or Og4C3 ELISA) and combined by district. Three criteria schemes based on the Global Programme to Eliminate Lymphatic Filariasis guidelines, with modifications, were developed to classify and prioritize districts by prevalence level. Results of repeated surveys in the same sites were used to investigate the impact of MDA on LF prevalence over the time period. Results There were 312 distinct survey sites identified in 80 of the 89 districts over the 31-year period. The overall LF prevalence in the sites tested was estimated at 18.5 to 27.5% by blood slide for microfilariae (Mf), 10.1% to 12.9% by ICT and 45.4% to 48.8% by Og4C3. Biases in site selection towards areas with LF, and change in type of assay used, affected the prevalence estimates, but overall decline in prevalence over the time period was observed. Depending on the criteria used, 34 to 36 districts (population 2.7 to 2.9 million) were classed as high endemic (≥5% prevalence), 15 to 25 districts (1.7 to 1.9 million) as low endemic (<5%) and 20 to 31 (1.3 to 2.2 million) as non-endemic. Nine districts (0.7 million) had no information. The strong impact of MDA, especially on microfilaria (Mf) prevalence, was noted in sites with repeat surveys. Conclusions This analytical review of past surveys of LF in Papua New Guinea enables better estimation of the national burden, identifies gaps in knowledge, quantifies and locates the population at risk, and can be used to predict the likely impact of MDA and/or vector control. Better targeting of districts by level of prevalence will strengthen the control programme, facilitate monitoring of the disease trend and increase the likelihood of reaching the target of LF elimination by 2020. PMID:23311302

Altered gut microbiota in female mice with persistent low body weights following removal of post-weaning chronic dietary restriction.

PubMed

Chen, Jun; Toyomasu, Yoshitaka; Hayashi, Yujiro; Linden, David R; Szurszewski, Joseph H; Nelson, Heidi; Farrugia, Gianrico; Kashyap, Purna C; Chia, Nicholas; Ordog, Tamas

2016-10-03

Nutritional interventions often fail to prevent growth failure in childhood and adolescent malnutrition and the mechanisms remain unclear. Recent studies revealed altered microbiota in malnourished children and anorexia nervosa. To facilitate mechanistic studies under physiologically relevant conditions, we established a mouse model of growth failure following chronic dietary restriction and examined microbiota in relation to age, diet, body weight, and anabolic treatment. Four-week-old female BALB/c mice (n = 12/group) were fed ad libitum (AL) or offered limited food to abolish weight gain (LF). A subset of restricted mice was treated with an insulin-like growth factor 1 (IGF1) analog. Food access was restored in a subset of untreated LF (LF-RF) and IGF1-treated LF mice (TLF-RF) on day 97. Gut microbiota were determined on days 69, 96-99 and 120 by next generation sequencing of the V3-5 region of the 16S rRNA gene. Microbiota-host factor associations were analyzed by distance-based PERMANOVA and quantified by the coefficient of determination R 2 for age, diet, and normalized body weight change (Δbwt). Microbial taxa on day 120 were compared following fitting with an overdispersed Poisson regression model. The machine learning algorithm Random Forests was used to predict age based on the microbiota. On day 120, Δbwt in AL, LF, LF-RF, and TLF-RF mice was 52 ± 3, -6 ± 1*, 40 ± 3*, and 46 ± 2 % (*, P < 0.05 versus AL). Age and diet, but not Δbwt, were associated with gut microbiota composition. Age explained a larger proportion of the microbiota variability than diet or Δbwt. Random Forests predicted chronological age based on the microbiota and indicated microbiota immaturity in the LF mice before, but not after, refeeding. However, on day 120, the microbiota community structure of LF-RF mice was significantly different from that of both AL and LF mice. IGF1 mitigated the difference from the AL group. Refed groups had a higher abundance of Bacteroidetes and Proteobacteria and a lower abundance of Firmicutes than AL mice. Persistent growth failure can be induced by 97-day dietary restriction in young female mice and is associated with microbiota changes seen in lean mice and individuals and anorexia nervosa. IGF1 facilitates recovery of body weights and microbiota.

Vegetation Influences on Long-Term Carbon Stabilization in Soils: a Coast Redwood-Prairie Comparison

NASA Astrophysics Data System (ADS)

Mambelli, S.; Burton, S. D.; McFarlane, K. J.; Torn, M. S.; Dawson, T. E.

2010-12-01

Complex interactions and feedbacks among soil, biota, climate, and parent material determine the long-term pathways and mechanisms of carbon persistence in soils. While it is well known that litter chemistry influences litter decay on annual-decadal timescales, its impact on long-term SOM storage is still under debate. We tested the role of the substrate available to decomposers in determining decomposition and sequestration of carbon by comparing two contrasting ecosystems representing end-members in terms of tissue lifespan and litter recalcitrance, an old-growth redwood forest and an adjacent tree-less prairie, at one site with identical climate, topography, and parent material. Solid-state CP MAS 13C NMR was applied to investigate the chemical structure of vegetation tissues (aboveground and belowground), and of soil fractions (particulate organic carbon free in the soil matrix and particulate organic carbon located inside soil aggregates, or free and occluded light fraction (LF), respectively) at different depths. In addition, the carbon stability of these soil density fractions was estimated based on radiocarbon modeling. Preliminary NMR results showed strong differences between redwood and prairie tissues, and between litters and surface soil fractions. On average, redwood litter contained more aromatic carbon (C and O substituted aryl C), more lipids (alkyl C) and fewer carbohydrates (O-alkyl C) than prairie litter. Under both vegetation types we found that the chemical structure changed consistently from litter to free LF, and from free LF to occluded LF. The alkyl C signal intensity increased, while the O-alkyl C fraction decreased, but more strongly at the redwood forest. The proportion of aromatic functional groups in the total organic matter (aromaticity) was always higher in the soil fractions compared with the original litters. Redwood soil fractions aromaticity was 0.32 (+80% from litter), while prairie soil fractions aromaticity varied from 0.17 (free LF) to 0.23 (occluded LF)(+40 and +90% from litter, respectively). The proportion of carbon in carbonyl groups (alkyl/O-alkyl ratio), an estimate of the degree of decomposition, increased from the free LF to the occluded LF at both ecosystems (0.30 to 0.75 in the redwood forest, 0.24 to 0.68 in the prairie, respectively). In summary, the similar decomposition stage of the redwood and prairie SOM and the higher aromaticity of the free LF in the redwood soil compared to the original litter suggest the preservation of recalcitrant redwood constituents but only in the free soil matrix. Further investigations at deeper soil depths are underway.

[The role of CD14 promoter - 159 C-> T polymorphism on changes of serum lipid ratios induced by high-carbohydrate/low-fat diets in healthy Chinese Han youth].

PubMed

Jiang, Zhe; Gong, Ren-rong; Li, Yuan-hao; Fan, Mei; Fang, Ding-zhi

2012-05-01

To investigate the role of CD14 promoter - 159 C-> T polymorphism on ratios of serum lipids and its interaction on the ratios with a high-carbohydrate/low-fat (HC/LF) diet in a young and healthy Chinese Han population. After a washout diet for seven days, fifty six healthy young subjects (22.89 +/- 1.80 years) were given the HC/LF diet for six days. Twelve-hour fasting venous blood samples were collected in the mornings of the first, the eighth and the fourteenth days. The serum lipid profiles and the CD14 -159 C->T polymorphism were analyzed. The ratios of triglyceride/high density lipoprotein-cholesterol (TG/HDL-c), log (TG/HDL-c), total cholesterol/high density lipoprotein-cholesterol (TC/HDL-c) and low density lipoprotein-cholesterol/high density lipoprotein-cholesterol (LDL-c/HDL-c) were calculated. The male carriers of the C allele had significantly higher TG/HDL-c and log (TG/HDL-c) than the female carriers at baseline, after the washout diet and after the HC/LF diet, higher TC/HDL-c at baseline and after the washout diet, and higher LDL-c/HDL-c only after the washout diet. The female subjects with the TT genotype had higher TG/HDL-c and log (TG/HDL-c) than the female carriers of the C allele at baseline, after the washout diet and after the HC/LF diet, higher LDL-c/HDL-c at baseline and after the HC/LF diet, and higher TC/HDL-c only after the washout diet. Compared with that before the HC/LF diet, TC/HDL-c was significantly decreased after the HC/LF diet regardless of gender and the genotype of the CD14 -159 polymorphism. LDL-c/HDL-c was significantly decreased in both the male and female carriers of the C allele. TG/HDL-c and log (TG/HDL-c) were significantly increased only in the female carriers of the C allele. In the subjects with C allele, the HC/LF diet is a minor factor and its effects on the lipid ratios can be masked by the effects of the C allele at CD14 -159. The interaction between the HC/LF diet and the C allele at CD14 -159 can decrease LDL-c/HDL-c in both males and females and increase TG/ HDL-c and log (TG/HDL-c) in the females.

Magnesium Recycling of Partially Oxidized, Mixed Magnesium-Aluminum Scrap through Combined Refining and Solid Oxide Membrane Electrolysis Processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiaofei Guan; Peter A. Zink; Uday B. Pal

2012-01-01

Pure magnesium (Mg) is recycled from 19g of partially oxidized 50.5wt.% Mg-Aluminum (Al) alloy. During the refining process, potentiodynamic scans (PDS) were performed to determine the electrorefining potential for magnesium. The PDS show that the electrorefining potential increases over time as the magnesium content inside the Mg-Al scrap decreases. Up to 100% percent of magnesium is refined from the Mg-Al scrap by a novel refining process of dissolving magnesium and its oxide into a flux followed by vapor phase removal of dissolved magnesium and subsequently condensing the magnesium vapor. The solid oxide membrane (SOM) electrolysis process is employed in themore » refining system to enable additional recycling of magnesium from magnesium oxide (MgO) in the partially oxidized Mg-Al scrap. The combination of the refining and SOM processes yields 7.4g of pure magnesium.« less

Shipborne LF-VLF oceanic lightning observations and modeling

NASA Astrophysics Data System (ADS)

Zoghzoghy, F. G.; Cohen, M. B.; Said, R. K.; Lehtinen, N. G.; Inan, U. S.

2015-10-01

Approximately 90% of natural lightning occurs over land, but recent observations, using Global Lightning Detection (GLD360) geolocation peak current estimates and satellite optical data, suggested that cloud-to-ground flashes are on average stronger over the ocean. We present initial statistics from a novel experiment using a Low Frequency (LF) magnetic field receiver system installed aboard the National Oceanic Atmospheric Agency (NOAA) Ronald W. Brown research vessel that allowed the detection of impulsive radio emissions from deep-oceanic discharges at short distances. Thousands of LF waveforms were recorded, facilitating the comparison of oceanic waveforms to their land counterparts. A computationally efficient electromagnetic radiation model that accounts for propagation over lossy and curved ground is constructed and compared with previously published models. We include the effects of Earth curvature on LF ground wave propagation and quantify the effects of channel-base current risetime, channel-base current falltime, and return stroke speed on the radiated LF waveforms observed at a given distance. We compare simulation results to data and conclude that previously reported larger GLD360 peak current estimates over the ocean are unlikely to fully result from differences in channel-base current risetime, falltime, or return stroke speed between ocean and land flashes.

Effect on HRV of archer athletes one day before competition after three different abdominal respiratory frequency.

PubMed

Zhang, Kai; Wei, Jun; Wang, Lin

2017-12-01

To study the effect on HRV of archer athletes one day before competition after three different abdominal respiratory frequencies. Eight elite archers performed three different respiratory frequency tests, HRV were recorded in pre-, during, and post-frequency control in frequency 16 (F16 group, n = 8), 8 (F8 group, n = 8), and 5 (F5 group, n = 8) times per minute, and hoped to find a respiratory adjust way to reduce stress. RMSSD, RR_triangular index, TP, VLF, LF, HF and LF/HF were analyzed to describe the effect of respiratory frequency. The average RR separate, RR_triangular index and HF showed no significant change in three respiratory frequency ( P  > 0.05); LF increased significantly in F16 group, but LP of F8 and F5 group increased first then reduced ( P  < .05); VLF rose in F8 and F5 group ( P  < .05, respectively), the LF/HF has the similar change as the LF in all the groups. The F16 group increased equilibrium of sympathetic and pneumogastric nerve system; F8 increase excitability of sympathetic nerve; mental fatigue remission in F5.

Isolation and in silico analysis of a novel H+-pyrophosphatase gene orthologue from the halophytic grass Leptochloa fusca

NASA Astrophysics Data System (ADS)

Rauf, Muhammad; Saeed, Nasir A.; Habib, Imran; Ahmed, Moddassir; Shahzad, Khurram; Mansoor, Shahid; Ali, Rashid

2017-02-01

Structure prediction can provide information about function and active sites of protein which helps to design new functional proteins. H+-pyrophosphatase is transmembrane protein involved in establishing proton motive force for active transport of Na+ across membrane by Na+/H+ antiporters. A full length novel H+-pyrophosphatase gene was isolated from halophytic grass Leptochloa fusca using RT-PCR and RACE method. Full length LfVP1 gene sequence of 2292 nucleotides encodes protein of 764 amino acids. DNA and protein sequences were used for characterization using bioinformatics tools. Various important potential sites were predicted by PROSITE webserver. Primary structural analysis showed LfVP1 as stable protein and Grand average hydropathy (GRAVY) indicated that LfVP1 protein has good hydrosolubility. Secondary structure analysis showed that LfVP1 protein sequence contains significant proportion of alpha helix and random coil. Protein membrane topology suggested the presence of 14 transmembrane domains and presence of catalytic domain in TM3. Three dimensional structure from LfVP1 protein sequence also indicated the presence of 14 transmembrane domains and hydrophobicity surface model showed amino acid hydrophobicity. Ramachandran plot showed that 98% amino acid residues were predicted in the favored region.

Stigma reduction and improved knowledge and attitudes towards filariasis using a comic book for children.

PubMed

el-Setouhy, Maged A; Rio, Francisco

2003-04-01

WHO has initiated a global program for lymphatic filariasis (LF) elimination by year 2020. A comic book was designed to improve knowledge and attitudes of Egyptian school children, which included messages on the acceptability of Mass Drug Administration (MDA) and stigma reduction. Comic book administration significantly reduced the fear of the studied children from LF as a killer disease. It helped in positively changing the attitudes of the children towards Elephantiasis patients (p-value <.001). The comic book also reduced the number of children who had earlier stated that they would avoid someone with LF. Knowledge about the ability of treating and preventing LF was also significantly increased among the children after reading the comic book. Moreover, comic book reading helped in raising the awareness towards MDA as the method of choice in preventing LF. Most of the children liked the comic book and its contents. Importantly, 96.2% found this book easy to understand. Many of relatives and friends read the comic book within 2 weeks after distribution. A well-accepted comic book for children is a proven way to reduce stigma and increase knowledge about disease prevention and treatment.

Cuckoo search via Levy flights applied to uncapacitated facility location problem

NASA Astrophysics Data System (ADS)

Mesa, Armacheska; Castromayor, Kris; Garillos-Manliguez, Cinmayii; Calag, Vicente

2017-11-01

Facility location problem (FLP) is a mathematical way to optimally locate facilities within a set of candidates to satisfy the requirements of a given set of clients. This study addressed the uncapacitated FLP as it assures that the capacity of every selected facility is finite. Thus, even if the demand is not known, which often is the case, in reality, organizations may still be able to take strategic decisions such as locating the facilities. There are different approaches relevant to the uncapacitated FLP. Here, the cuckoo search via Lévy flight (CS-LF) was used to solve the problem. Though hybrid methods produce better results, this study employed CS-LF to determine first its potential in finding solutions for the problem, particularly when applied to a real-world problem. The method was applied to the data set obtained from a department store in Davao City, Philippines. Results showed that applying CS-LF yielded better facility locations compared to particle swarm optimization and other existing algorithms. Although these results showed that CS-LF is a promising method to solve this particular problem, further studies on other FLP are recommended to establish a strong foundation of the capability of CS-LF in solving FLP.

Anxiety Level and Cardiac Autonomic Modulations in Coronary Artery Disease and Cardiac Syndrome X Patients.

PubMed

Lutfi, Mohamed Faisal

2017-01-01

Anxiety and cardiac autonomic modulations (CAM) were thoroughly investigated in coronary artery disease (CAD) and cardiac syndrome X (CSX) patients worldwide, but not among Sudanese with similar pathology. To compare levels of anxiety and CAM between Sudanese patients with CSX and CAD. Anxiety was evaluated in 51 CAD and 26 CSX patients using Taylor Manifest anxiety score (TMAS) questionnaire while heart rate variability derived indices were used to assess CAM, namely natural logarithm of low frequency (LnLF), high frequency (LnHF) and LF/HF ratio (LnLF/HF). Low anxiety levels were achieved by 6 (23.1%) and 9 (17.6%) patients with CSX and CAD respectively. High anxiety level was achieved by only one (3.8%) patient, who was suffering from CSX. TMAS was significantly higher in CSX (31.27 (21.97)) compared to CAD (21.86 (12.97), P = 0.021). However, abnormally increased anxiety was not associated with higher risk of CSX. LnLF, LnHF and LnLF/HF were comparable in CAD and CSX patients. CSX and CAD patients showed comparable CAM. Although anxiety levels were higher in CSX compared to CAD, TMAS ≥ 35 failed to show significant association with CSX.

The brain adjusts grip forces differently according to gravity and inertia: a parabolic flight experiment

PubMed Central

White, Olivier

2015-01-01

In everyday life, one of the most frequent activities involves accelerating and decelerating an object held in precision grip. In many contexts, humans scale and synchronize their grip force (GF), normal to the finger/object contact, in anticipation of the expected tangential load force (LF), resulting from the combination of the gravitational and the inertial forces. In many contexts, GF and LF are linearly coupled. A few studies have examined how we adjust the parameters–gain and offset–of this linear relationship. However, the question remains open as to how the brain adjusts GF regardless of whether LF is generated by different combinations of weight and inertia. Here, we designed conditions to generate equivalent magnitudes of LF by independently varying mass and movement frequency. In a control experiment, we directly manipulated gravity in parabolic flights, while other factors remained constant. We show with a simple computational approach that, to adjust GF, the brain is sensitive to how LFs are produced at the fingertips. This provides clear evidence that the analysis of the origin of LF is performed centrally, and not only at the periphery. PMID:25717293

Effects of lactoferrin derived peptides on simulants of biological warfare agents.

PubMed

Sijbrandij, Tjitske; Ligtenberg, Antoon J; Nazmi, Kamran; Veerman, Enno C I; Bolscher, Jan G M; Bikker, Floris J

2017-01-01

Lactoferrin (LF) is an important immune protein in neutrophils and secretory fluids of mammals. Bovine LF (bLF) harbours two antimicrobial stretches, lactoferricin and lactoferampin, situated in close proximity in the N1 domain. To mimic these antimicrobial domain parts a chimeric peptide (LFchimera) has been constructed comprising parts of both stretches (LFcin17-30 and LFampin265-284). To investigate the potency of this construct to combat a set of Gram positive and Gram negative bacteria which are regarded as simulants for biological warfare agents, the effect on bacterial killing, membrane permeability and membrane polarity were determined in comparison to the constituent peptides and the native bLF. Furthermore we aimed to increase the antimicrobial potency of the bLF derived peptides by cationic amino acid substitutions. Overall, the bactericidal activity of the peptides could be related to membrane disturbing effects, i.e. membrane permeabilization and depolarization. Those effects were most prominent for the LFchimera. Arginine residues were found to be crucial for displaying antimicrobial activity, as lysine to arginine substitutions resulted in an increased antimicrobial activity, affecting mostly LFampin265-284 whereas arginine to lysine substitutions resulted in a decreased bactericidal activity, predominantly in case of LFcin17-30.

Lactoferrin-derived peptides and Lactoferricin chimera inhibit virulence factor production and biofilm formation in Pseudomonas aeruginosa.

PubMed

Xu, G; Xiong, W; Hu, Q; Zuo, P; Shao, B; Lan, F; Lu, X; Xu, Y; Xiong, S

2010-10-01

To investigate the bactericidal activity of lactoferrin-derived peptides and a new LF-derived peptides chimera (LFchimera) against P. aeruginosa and the influence on virulence factors of P. aeruginosa. Lactoferricin (LFcin) and lactoferrampin (LFampin) are highly bioactive peptides isolated from the N-terminal region of lactoferrin (LF) by pepsin digestion. In this study, we designed LFchimera containing LFcin amino acids 17-30 and LFampin amino acids 268-284. Pseudomonas aeruginosa cells were incubated in medium with peptides at different concentrations, and then the assays of viability, pyocyanin, elastase activity and biofilm formation of P. aeruginosa were performed. We found that the concentration-dependent antibactericidal activity and down-regulating pyocyanin, elastase and biofilm formation of LFchimera were significantly stronger than those of LF, LFcin, LFampin or LFcin plus LFampin. Our results indicated that LF, LFcin, LFampin and LFchimera were potential candidates to combat P. aeruginosa, and LFchimera was the most effective in them. The new LFchimera has better activity against P. aeruginosa than LF, LFcin and LFampin and may be a promising new compound for treatment of P. aeruginosa infection. © 2010 The Authors. Journal compilation © 2010 The Society for Applied Microbiology.

76 FR 53480 - Prospective Grant of Exclusive License: Conjugate Vaccines Against B. anthracis

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-26

.... anthracis Protective Antigen (PA), Lethal Factor (LF) and Edema Factor (EF)'', U.S. Patent Application... catalytic proteins known as ``lethal factor'' (LF) and ``edema factor'' (EF). Although production of an...

Does disseminated nontuberculous mycobacterial disease cause false-positive Determine B-LAM lateral flow assay results? A retrospective review.

PubMed

Nel, Jeremy S; Lippincott, Christopher K; Berhanu, Rebecca; Spencer, David C; Sanne, Ian M; Ive, Prudence

2017-06-02

We retrospectively reviewed the Determine TB-LAM lateral flow assay (LF-LAM) results among HIV-infected patients with disseminated nontuberculous mycobacterial (NTM) disease. LF-LAM was positive in 19/21 patients without evidence of tuberculosis coinfection. Although tuberculosis-NTM coinfection may have been underdiagnosed, our results suggest that disseminated NTM disease may cause false-positive LF-LAM results. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

A study of the luminosity function for field galaxies. [non-rich-cluster galaxies

NASA Technical Reports Server (NTRS)

Felten, J. E.

1977-01-01

Nine determinations of the luminosity function (LF) for field galaxies are analyzed and compared. Corrections for differences in Hubble constants, magnitude systems, galactic absorption functions, and definitions of the LF are necessary prior to comparison. Errors in previous comparisons are pointed out. After these corrections, eight of the nine determinations are in fairly good agreement. The discrepancy in the ninth appears to be mainly an incompleteness effect. The LF data suggest that there is little if any distinction between field galaxies and those in small groups.

The Gulf Long-Term Follow-Up Study (GuLF STUDY): Biospecimen collection at enrollment.

PubMed

Engel, Lawrence S; Kwok, Richard K; Miller, Aubrey K; Blair, Aaron; Curry, Matthew D; McGrath, John A; Sandler, Dale P

2017-01-01

The 2010 Deepwater Horizon (DWH) explosion in the Gulf of Mexico led to the largest ever marine oil spill by volume. The GuLF STUDY is investigating possible adverse human health effects associated with oil spill activities. One objective of the study was to utilize biological specimens from study participants to examine spill-related adverse health effects. This study describes the methods for collecting, processing, shipping, and storing specimens during the enrollment phase of the study. GuLF STUDY participants living in Gulf States (Alabama, Florida, Louisiana, Mississippi, and eastern Texas) were eligible to complete a home visit at enrollment, one to three years after the DWH explosion. During this visit, blood, urine, toenail and hair clippings, and house dust samples were collected. Specimens were shipped overnight to a central processing laboratory in containers with cold and ambient temperature compartments. Most blood and urine specimens were then aliquoted and stored in liquid nitrogen vapor or at -80°C, with some samples stored at -20°C. A total of 11,193 participants completed a home visit, and over 99% provided at least one biospecimen. Most participants provided blood (93%), urine (99%), and toenail clippings (89%), and 40% provided hair. Nearly all participants (95%) provided house-dust samples. Most samples were received by the laboratory one (58%) or two (25%) days after collection. These biospecimens enable investigation of a range of biomarkers of spill-related adverse health effects, and possibly some biomarkers of spill-related exposures. The biospecimen collection, handling, and storage protocols were designed to maximize current and future scientific value within logistical and budgetary constraints and might serve as a template for future studies conducted in similar time-critical and geographically dispersed settings.

Fast quantification of proton magnetic resonance spectroscopic imaging with artificial neural networks

NASA Astrophysics Data System (ADS)

Bhat, Himanshu; Sajja, Balasrinivasa Rao; Narayana, Ponnada A.

2006-11-01

Accurate quantification of the MRSI-observed regional distribution of metabolites involves relatively long processing times. This is particularly true in dealing with large amount of data that is typically acquired in multi-center clinical studies. To significantly shorten the processing time, an artificial neural network (ANN)-based approach was explored for quantifying the phase corrected (as opposed to magnitude) spectra. Specifically, in these studies radial basis function neural network (RBFNN) was used. This method was tested on simulated and normal human brain data acquired at 3T. The N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, glutamate + glutamine (Glx)/Cr, and myo-inositol (mI)/Cr ratios in normal subjects were compared with the line fitting (LF) technique and jMRUI-AMARES analysis, and published values. The average NAA/Cr, Cho/Cr, Glx/Cr and mI/Cr ratios in normal controls were found to be 1.58 ± 0.13, 0.9 ± 0.08, 0.7 ± 0.17 and 0.42 ± 0.07, respectively. The corresponding ratios using the LF and jMRUI-AMARES methods were 1.6 ± 0.11, 0.95 ± 0.08, 0.78 ± 0.18, 0.49 ± 0.1 and 1.61 ± 0.15, 0.78 ± 0.07, 0.61 ± 0.18, 0.42 ± 0.13, respectively. These results agree with those published in literature. Bland-Altman analysis indicated an excellent agreement and minimal bias between the results obtained with RBFNN and other methods. The computational time for the current method was 15 s compared to approximately 10 min for the LF-based analysis.

The volcano-sedimentary succession of Upper Permian in Wuli area, central Qinghai-Tibetan Plateau: Sedimentology, geochemistry and paleogeography

NASA Astrophysics Data System (ADS)

Liu, Shengqian; Jiang, Zaixing; Gao, Yi

2017-04-01

Detailed observations on cores and thin sections well documented a volcano-sedimentary succession from Well TK2, which is located in Wuli area, central Qinghai-Tibetan Plateau. The TK2 volcano-sedimentary succession reflects an active sedimentary-tectonic setting in the north margin of North Qiangtang-Chamdo terrane in the late Permian epoch. Based on the observation and recognition on lithology and mineralogy, the components of TK2 succession are mainly volcanic and volcaniclastic rocks and four main lithofacies are recognized, including massive volcanic lithofacies (LF1), pyroclastic tuff lithofacies (LF2), tuffaceous sandstone lithofacies (LF3) and mudstone lithofacies (LF4). LF1 is characterized by felsic components, massive structure and porphyrotopic structure with local flow structure, which indicates submarine intrusive domes or extrusion-fed lavas that formed by magma ascents via faults or dykes. Meanwhile, its eruption style may reflect a relative high pressure compensation level (PCL) that mainly determined by water depth, which implies a deep-water environment. LF2 is composed of volcanic lapilli or ash and featured with massive structure, parallel bedding and various deformed laminations including convolve structure, slide deformation, ball-and-pillow structure, etc.. LF2 indicates the sedimentation of initial or reworked explosive products not far away from volcano centers, reflecting the proximal accumulation of volcano eruption-fed clasts or their resedimentation as debris flows. In addition, the submarine volcano eruptions may induced earthquakes that facilitate the resedimentation of unconsolidated sediments. LF3 contains abundant pyroclastic components and is commonly massive with rip-up mudstone clasts or usually interbedded with LF4. In addition, typical flute casts, scour structures and graded beddings in thin-interbedded layers of sandstone and mudstone are commonly observed, which also represents the sedimentation of debris flows or turbidity flows in a relative deep-water environment. LF4 indicates suspension deposits of distal turbidity sediments in deeper-water setting, which is mainly tuffaceous and ordinary mudstone, commonly interbedded with thin pyroclastic layers. Geochemically, the felsic volcanic rocks belong to tholeiitic to calc-alkaline series, exhibiting characteristics of right-leaning rare earth element (REE) patterns with conspicuous Eu negative anomalies, enrichments in large ion lithophile elements (LILEs) and depletions in high field-strength elements (HFSEs), which reflect an island arc environment that corresponds to the late-Permian subduction of slabs. The TK2 volcanic-sedimentary succession reveals a submarine volcano-dominated depositional model and proves the existence of a deeper water environment, at least in a restricted zone of Wuli area. However, the traditional sedimentary and paleogeographic knowledges are mostly about coal-forming transitional facies in stable environment. Therefore, the proposing of a deep-water volcano-sedimentary model will provide a further comprehension of paleogeography in southern Qinghai at late-Permian, which will also supplement the previous cognition of stable ocean-land transitional environments and provide a new sight to the paleogeographic framework of late-Permian in North Qiangtang-Chamdo terrane.

Augmenter of liver regeneration: substrate specificity of a flavin-dependent oxidoreductase from the mitochondrial intermembrane space.

PubMed

Daithankar, Vidyadhar N; Farrell, Scott R; Thorpe, Colin

2009-06-09

Augmenter of liver regeneration (ALR) is both a growth factor and a sulfhydryl oxidase that binds FAD in an unusual helix-rich domain containing a redox-active CxxC disulfide proximal to the flavin ring. In addition to the cytokine form of ALR (sfALR) that circulates in serum, a longer form, lfALR, is believed to participate in oxidative trapping of reduced proteins entering the mitochondrial intermembrane space (IMS). This longer form has an 80-residue N-terminal extension containing an additional, distal, CxxC motif. This work presents the first enzymological characterization of human lfALR. The N-terminal region conveys no catalytic advantage toward the oxidation of the model substrate dithiothreitol (DTT). In addition, a C71A or C74A mutation of the distal disulfide does not increase the turnover number toward DTT. Unlike Erv1p, the yeast homologue of lfALR, static spectrophotometric experiments with the human oxidase provide no evidence of communication between distal and proximal disulfides. An N-terminal His-tagged version of human Mia40, a resident oxidoreductase of the IMS and a putative physiological reductant of lfALR, was subcloned and expressed in Escherichia coli BL21 DE3 cells. Mia40, as isolated, shows a visible spectrum characteristic of an Fe-S center and contains 0.56 +/- 0.02 atom of iron per subunit. Treatment of Mia40 with guanidine hydrochloride and triscarboxyethylphosphine hydrochloride during purification removed this chromophore. The resulting protein, with a reduced CxC motif, was a good substrate of lfALR. However, neither sfALR nor lfALR mutants lacking the distal disulfide could oxidize reduced Mia40 efficiently. Thus, catalysis involves a flow of reducing equivalents from the reduced CxC motif of Mia40 to distal and then proximal CxxC motifs of lfALR to the flavin ring and, finally, to cytochrome c or molecular oxygen.

Augmenter of Liver Regeneration: Substrate Specificity of a Flavin-dependent Oxidoreductase from the Mitochondrial Intermembrane Space†

PubMed Central

Daithankar, Vidyadhar N.; Farrell, Scott R.; Thorpe, Colin

2009-01-01

Augmenter of liver regeneration (ALR) is both a growth factor and a sulfhydryl oxidase that binds FAD in an unusual helix-rich domain containing a redox-active CxxC disulfide proximal to the flavin ring. In addition to the cytokine form of ALR (sfALR) that circulates in serum, a longer form, lfALR, is believed to participate in oxidative trapping of reduced proteins entering the mitochondrial intermembrane space (IMS). This longer form has an 80-residue N-terminal extension containing an additional, distal, CxxC motif. This work presents the first enzymological characterization of human lfALR. The N-terminal region conveys no catalytic advantage towards the oxidation of the model substrate dithiothreitol (DTT). In addition, C71A or C74A mutations of the distal disulfide do not increase the turnover number towards DTT. Unlike Erv1p, the yeast homolog of lfALR, static spectrophotometric experiments of the human oxidase provide no evidence for communication between distal and proximal disulfides. An N-terminal his-tagged version of human Mia40, a resident oxidoreductase of the IMS and a putative physiological reductant of lfALR, was subcloned and expressed in Escherichia coli BL21 DE3 cells. Mia40, as isolated, shows a visible spectrum characteristic of an Fe/S center and contains 0.56 ± 0.02 atoms of iron per subunit. Treatment of Mia40 with guanidine hydrochloride and triscarboxyethylphosphine hydrochloride during purification removed this chromophore. The resulting protein, with a reduced CxC motif, was a good substrate of lfALR. However, neither sfALR, nor lfALR mutants lacking the distal disulfide, could oxidize reduced Mia40 efficiently. Thus, catalysis involves a flow of reducing equivalents from the reduced CxC motif of Mia40, to distal- and then proximal CxxC motifs of lfALR, to the flavin ring, and, finally, to cytochrome c or molecular oxygen. PMID:19397338

Multiple Circulating Infections Can Mimic the Early Stages of Viral Hemorrhagic Fevers and Possible Human Exposure to Filoviruses in Sierra Leone Prior to the 2014 Outbreak

PubMed Central

Boisen, Matthew L.; Schieffelin, John S.; Goba, Augustine; Oottamasathien, Darin; Jones, Abigail B.; Shaffer, Jeffrey G.; Hastie, Kathryn M.; Hartnett, Jessica N.; Momoh, Mambu; Fullah, Mohammed; Gabiki, Michael; Safa, Sidiki; Zandonatti, Michelle; Fusco, Marnie; Bornholdt, Zach; Abelson, Dafna; Gire, Stephen K.; Andersen, Kristian G.; Tariyal, Ridhi; Stremlau, Mathew; Cross, Robert W.; Geisbert, Joan B.; Pitts, Kelly R.; Geisbert, Thomas W.; Kulakoski, Peter; Wilson, Russell B.; Henderson, Lee; Sabeti, Pardis C.; Grant, Donald S.; Garry, Robert F.; Saphire, Erica O.; Khan, Sheik Humarr

2015-01-01

Abstract Lassa fever (LF) is a severe viral hemorrhagic fever caused by Lassa virus (LASV). The LF program at the Kenema Government Hospital (KGH) in Eastern Sierra Leone currently provides diagnostic services and clinical care for more than 500 suspected LF cases per year. Nearly two-thirds of suspected LF patients presenting to the LF Ward test negative for either LASV antigen or anti-LASV immunoglobulin M (IgM), and therefore are considered to have a non-Lassa febrile illness (NLFI). The NLFI patients in this study were generally severely ill, which accounts for their high case fatality rate of 36%. The current studies were aimed at determining possible causes of severe febrile illnesses in non-LF cases presenting to the KGH, including possible involvement of filoviruses. A seroprevalence survey employing commercial enzyme-linked immunosorbent assay tests revealed significant IgM and IgG reactivity against dengue virus, chikungunya virus, West Nile virus (WNV), Leptospira, and typhus. A polymerase chain reaction–based survey using sera from subjects with acute LF, evidence of prior LASV exposure, or NLFI revealed widespread infection with Plasmodium falciparum malaria in febrile patients. WNV RNA was detected in a subset of patients, and a 419 nt amplicon specific to filoviral L segment RNA was detected at low levels in a single patient. However, 22% of the patients presenting at the KGH between 2011 and 2014 who were included in this survey registered anti-Ebola virus (EBOV) IgG or IgM, suggesting prior exposure to this agent. The 2014 Ebola virus disease (EVD) outbreak is already the deadliest and most widely dispersed outbreak of its kind on record. Serological evidence reported here for possible human exposure to filoviruses in Sierra Leone prior to the current EVD outbreak supports genetic analysis that EBOV may have been present in West Africa for some time prior to the 2014 outbreak. PMID:25531344

Differential effects of low-fat and high-fat diets on fed-state hepatic triacylglycerol secretion, hepatic fatty acid profiles, and DGAT-1 protein expression in obese-prone Sprague-Dawley rats.

PubMed

Heden, Timothy D; Morris, E Matthew; Kearney, Monica L; Liu, Tzu-Wen; Park, Young-Min; Kanaley, Jill A; Thyfault, John P

2014-04-01

The purpose of this study was to compare the effects of short-term low-fat (LF) and high-fat (HF) diets on fed-state hepatic triacylglycerol (TAG) secretion, the content of proteins involved in TAG assembly and secretion, fatty acid oxidation (FAO), and the fatty acid profile of stored TAG. Using selectively bred obese-prone Sprague-Dawley rats, we directly measured fed-state hepatic TAG secretion, using Tyloxapol (a lipoprotein lipase inhibitor) and a standardized oral mixed meal (45% carbohydrate, 40% fat, 15% protein) bolus in animals fed a HF or LF diet for 2 weeks, after which the rats were maintained on their respective diet for 1 week (washout) prior to the liver being excised to measure protein content, FAO, and TAG fatty acid profiles. Hepatic DGAT-1 protein expression was ∼27% lower in HF- than in LF-fed animals (p < 0.05); the protein expression of all other molecules was similar in the 2 diets. The fed-state hepatic TAG secretion rate was ∼39% lower (p < 0.05) in HF- (4.62 ± 0.18 mmol·h(-1)) than in LF- (7.60 ± 0.57 mmol·h(-1)) fed animals. Hepatic TAG content was ∼2-fold higher (p < 0.05) in HF- (1.07 ± 0.15 nmol·g(-1) tissue) than in LF- (0.50 ± 0.16 nmol·g(-1) tissue) fed animals. In addition, the fatty acid profile of liver TAG in HF-fed animals closely resembled the diet, whereas in LF-fed animals, the fatty acid profile consisted of mostly de novo synthesized fatty acids. FAO was not altered by diet. LF and HF diets differentially alter fed-state hepatic TAG secretion, hepatic fatty acid profiles, and DGAT-1 protein expression.

Differential effects of low-fat and high-fat diets on fed-state hepatic triacylglycerol secretion, hepatic fatty acid profiles, and DGAT-1 protein expression in obese-prone Sprague–Dawley rats

PubMed Central

Heden, Timothy D.; Morris, E. Matthew; Kearney, Monica L.; Liu, Tzu-Wen; Park, Young-min; Kanaley, Jill A.; Thyfault, John P.

2015-01-01

The purpose of this study was to compare the effects of short-term low-fat (LF) and high-fat (HF) diets on fed-state hepatic triacylglycerol (TAG) secretion, the content of proteins involved in TAG assembly and secretion, fatty acid oxidation (FAO), and the fatty acid profile of stored TAG. Using selectively bred obese-prone Sprague–Dawley rats, we directly measured fed-state hepatic TAG secretion, using Tyloxapol (a lipoprotein lipase inhibitor) and a standardized oral mixed meal (45% carbohydrate, 40% fat, 15% protein) bolus in animals fed a HF or LF diet for 2 weeks, after which the rats were maintained on their respective diet for 1 week (washout) prior to the liver being excised to measure protein content, FAO, and TAG fatty acid profiles. Hepatic DGAT-1 protein expression was ~27% lower in HF- than in LF-fed animals (p < 0.05); the protein expression of all other molecules was similar in the 2 diets. The fed-state hepatic TAG secretion rate was ~39% lower (p < 0.05) in HF- (4.62 ± 0.18 mmol·h−1) than in LF- (7.60 ± 0.57 mmol·h−1) fed animals. Hepatic TAG content was ~2-fold higher (p < 0.05) in HF- (1.07 ± 0.15 nmol·g−1 tissue) than in LF- (0.50 ± 0.16 nmol·g−1 tissue) fed animals. In addition, the fatty acid profile of liver TAG in HF-fed animals closely resembled the diet, whereas in LF-fed animals, the fatty acid profile consisted of mostly de novo synthesized fatty acids. FAO was not altered by diet. LF and HF diets differentially alter fed-state hepatic TAG secretion, hepatic fatty acid profiles, and DGAT-1 protein expression. PMID:24669989

DETERMINATE and LATE FLOWERING are two TERMINAL FLOWER1/CENTRORADIALIS homologs that control two distinct phases of flowering initiation and development in pea.

PubMed

Foucher, Fabrice; Morin, Julie; Courtiade, Juliette; Cadioux, Sandrine; Ellis, Noel; Banfield, Mark J; Rameau, Catherine

2003-11-01

Genes in the TERMINAL FLOWER1 (TFL1)/CENTRORADIALIS family are important key regulatory genes involved in the control of flowering time and floral architecture in several different plant species. To understand the functions of TFL1 homologs in pea, we isolated three TFL1 homologs, which we have designated PsTFL1a, PsTFL1b, and PsTFL1c. By genetic mapping and sequencing of mutant alleles, we demonstrate that PsTFL1a corresponds to the DETERMINATE (DET) gene and PsTFL1c corresponds to the LATE FLOWERING (LF) gene. DET acts to maintain the indeterminacy of the apical meristem during flowering, and consistent with this role, DET expression is limited to the shoot apex after floral initiation. LF delays the induction of flowering by lengthening the vegetative phase, and allelic variation at the LF locus is an important component of natural variation for flowering time in pea. The most severe class of alleles flowers early and carries either a deletion of the entire PsTFL1c gene or an amino acid substitution. Other natural and induced alleles for LF, with an intermediate flowering time phenotype, present no changes in the PsTFL1c amino acid sequence but affect LF transcript level in the shoot apex: low LF transcript levels are correlated with early flowering, and high LF transcript levels are correlated with late flowering. Thus, different TFL1 homologs control two distinct aspects of plant development in pea, whereas a single gene, TFL1, performs both functions in Arabidopsis. These results show that different species have evolved different strategies to control key developmental transitions and also that the genetic basis for natural variation in flowering time may differ among plant species.

Novel Synthetic, Host-defense Peptide Protects Against Organ Injury/Dysfunction in a Rat Model of Severe Hemorrhagic Shock.

PubMed

Yamada, Noriaki; Martin, Lukas B; Zechendorf, Elisabeth; Purvis, Gareth S D; Chiazza, Fausto; Varrone, Barbara; Collino, Massimo; Shepherd, Joanna; Heinbockel, Lena; Gutsmann, Thomas; Correa, Wilmar; Brandenburg, Klaus; Marx, Gernot; Schuerholz, Tobias; Brohi, Karim; Thiemermann, Christoph

2017-03-10

To evaluate (1) levels of the host-defense/antimicrobial peptide LL-37 in patients with trauma and hemorrhagic shock (HS) and (2) the effects of a synthetic host-defense peptide; Pep19-4LF on multiple organ failure (MOF) associated with HS. HS is a common cause of death in severely injured patients. There is no specific therapy that reduces HS-associated MOF. (1) LL-37 was measured in 47 trauma/HS patients admitted to an urban major trauma center. (2) Male Wistar rats were submitted to HS (90 min, target mean arterial pressure: 27-32 mm Hg) or sham operation. Rats were treated with Pep19-4LF [66 (n = 8) or 333 μg/kg · h (n = 8)] or vehicle (n = 12) for 4 hours following resuscitation. Plasma LL-37 was 12-fold higher in patients with trauma/HS compared to healthy volunteers. HS rats treated with Pep19-4LF (high dose) had a higher mean arterial pressure at the end of the 4-hour resuscitation period (79 ± 4 vs 54 ± 5 mm Hg) and less renal dysfunction, liver injury, and lung inflammation than HS rats treated with vehicle. Pep19-4LF enhanced (kidney/liver) the phosphorylation of (1) protein kinase B and (2) endothelial nitric oxide synthase. Pep19-4LF attenuated the HS-induced (1) translocation of p65 from cytosol to nucleus, (2) phosphorylation of IκB kinase on Ser, and (3) phosphorylation of IκBα on Ser resulting in inhibition of nuclear factor kappa B and formation of proinflammatory cytokines. Pep19-4LF prevented the release of tumor necrosis factor alpha caused by heparan sulfate in human mononuclear cells by binding to this damage-associated molecular pattern. Trauma-associated HS results in release of LL-37. The synthetic host-defense/antimicrobial peptide Pep19-4LF attenuates the organ injury/dysfunction associated with HS.

Effect of variable soil texture, metal saturation of soil organic matter (SOM) and tree species composition on spatial distribution of SOM in forest soils in Poland.

PubMed

Gruba, Piotr; Socha, Jarosław; Błońska, Ewa; Lasota, Jarosław

2015-07-15

In this study we investigated the effect of fine (ϕ<0.05mm) fraction, i.e., silt+clay (FF) content in soils, site moisture, metal (Al and Fe) of soil organic matter (SOM) and forest species composition on the spatial distribution of carbon (C) pools in forest soils at the landscape scale. We established 275 plots in regular 200×200m grid in a forested area of 14.4km(2). Fieldwork included soil sampling of the organic horizon, mineral topsoil and subsoil down to 40cm deep. We analysed the vertical and horizontal distribution of soil organic carbon (SOC) stocks, as well as the quantity of physically separated fractions including the free light (fLF), occluded light (oLF) and mineral associated fractions (MAF) in the mineral topsoil (A, AE) horizons. Distribution of C in soils was predominantly affected by the variation in the FF content. In soils richer in the FF more SOC was accumulated in mineral horizons and less in the organic horizons. Accumulation of SOC in mineral soil was also positively affected by the degree of saturation of SOM with Al and Fe. The increasing share of beech influenced the distribution of C stock in soil profiles by reducing the depth of O horizon and increasing C stored in mineral soil. The content of FF was positively correlated with the content of C in MAF and fLF fractions. The content of oLF and MAF fractions was also positively influenced by a higher degree of metal saturation, particularly Al. Our results confirmed that Al plays an important role in the stabilization of SOM inside aggregates (CoLF) and as in CMAF fractions. We also found a significant, positive effect of beech on the CfLF and fir on the CoLF content. Copyright © 2015 Elsevier B.V. All rights reserved.

The very low-frequency band of heart rate variability represents the slow recovery component after a mental stress task.

PubMed

Usui, Harunobu; Nishida, Yusuke

2017-01-01

The very low-frequency (VLF) band of heart rate variability (HRV) has different characteristics compared with other HRV components. Here we investigated differences in HRV changes after a mental stress task. After the task, the high-frequency (HF) band and ratio of high- to low-frequency bands (LF/HF) immediately returned to baseline. We evaluated the characteristics of VLF band changes after a mental stress task. We hypothesized that the VLF band decreases during the Stroop color word task and there would be a delayed recovery for 2 h after the task (i.e., the VLF change would exhibit a "slow recovery"). Nineteen healthy, young subjects were instructed to rest for 10 min, followed by a Stroop color word task for 20 min. After the task, the subjects were instructed to rest for 120 min. For all subjects, R-R interval data were collected; analysis was performed for VLF, HF, and LF/HF ratio. HRV during the rest time and each 15-min interval of the recovery time were compared. An analysis of the covariance was performed to adjust for the HF band and LF/HF ratio as confounding variables of the VLF component. HF and VLF bands significantly decreased and the LF/HF ratio significantly increased during the task compared with those during rest time. During recovery, the VLF band was significantly decreased compared with the rest time. After the task, the HF band and LF/HF ratio immediately returned to baseline and were not significantly different from the resting values. After adjusting for HF and LF/HF ratio, the VLF band had significantly decreased compared with that during rest. The VLF band is the "slow recovery" component and the HF band and LF/HF ratio are the "quick recovery" components of HRV. This VLF characteristic may clarify the unexplained association of the VLF band in cardiovascular disease prevention.

Elimination of lymphatic filariasis as a public health problem from the Cook Islands.

PubMed

Ave, Charlie; Kapa, D Ramaiah; Ottesen, Eric

2018-01-01

The Cook Islands has a long history of high-endemicity lymphatic filariasis (LF) transmitted by Aedes vector mosquitoes. Though the infection prevalence had declined between 1975 and 1999 following episodic treatment activities, still infection was widespread with pockets of persistent infection. Beginning in 1999, the Cook Islands embarked on a national program, in partnership with Pacific Programme to Eliminate LF (PacELF), to eliminate LF as a public health problem. All 12 inhabited islands were identified as endemic, and six rounds of mass drug administration (MDA) with once-yearly, single-dose albendazole plus diethylcarbamazine (DEC) were implemented during 2000-2006 to interrupt transmission of LF. Surveys carried out at the baseline, mid-term, stop-MDA, and post-MDA periods assessed LF antigen (Ag) prevalence in children and adults. Historical data, health workers' observations, and hospital records were used to assess the trend and burden of chronic disease. The baseline Ag prevalence (1999) ranged from 2.0% in Manihiki to > 18.0% in Aitutaki, Mitiaro, and Pukapuka, and the national average Ag prevalence was 8.6%. MDA, carried out with a national treatment coverage over six annual rounds of MDA ranging from 63.5 to 96.7% in different years, was stopped in 2007. By then, the national Ag prevalence had declined to 0.27%. The post-MDA surveillance survey results (2013-2014) showed that Ag prevalence had fallen to 0% in 11/12 islands, and the national prevalence was only 0.03%. Chronic filarial disease had almost entirely disappeared. The Cook Islands met all the criteria required for the World Health Organization (WHO) to acknowledge elimination of LF as a public health problem, as it did officially in 2016. This success also confirms that LF, even when transmitted by Aedes mosquitoes that are recognized to be more efficient than other vector species, can be eliminated as a public health problem by six rounds of MDA.

The interruption of Onchocerca volvulus and Wuchereria bancrofti transmission by integrated chemotherapy in the Obongi focus, North Western Uganda

PubMed Central

Gabriel, Matwale; Tukahebwa, Edridah; Onapa, Ambrose Winston; Tinkitina, Benjamin; Tukesiga, Ephraim; Nyaraga, Michael; Auma, Anna Mary; Habomugisha, Peace; Byamukama, Edson; Oguttu, David; Katabarwa, Moses; Unnasch, Thomas Raymond

2017-01-01

Intervention Few studies have documented the interruption of onchocerciasis and Lymphatic Filariasis (LF) by integrated chemotherapy in Uganda. The study describes the interruption of transmission of the two diseases co-endemic in Obongi focus, north western Uganda. Base line data for Onchocerciasis and LF were collected in 1994 and 2006, respectively. Annual mass drug administration for onchocerciasis (Ivermectin) and Lymphatic Filariasis (Ivermectin + albendazole) was conducted for 20 and 6 years, respectively. Thereafter, assessments by skin snip, larval searches in rivers and human landing catches were performed. Children <10 years were screened for IgG4 antibodies using Ov16 ELISA technique in 2013. LF Pre-TAS and TAS1 were conducted in sentinel sites. ITN coverage and utilization for the implementation unit was also reported. Intervention coverage Onchocerciasis treatment coverage was <80% but improved with the introduction of CDTI in 1999. While for LF, effective coverage of >65% was achieved in the six treatment rounds. Household ownership of ITN’s and utilization was 96% and 72.4%., respectively. Impact Parasitological examinations conducted for onchocerciasis among 807 adults and children, revealed a reduction in mf prevalence from 58% in 1994 to 0% in 2012. Entomological monitoring conducted at the two sites had no single Simulium damnosum fly caught. Serological analysis using Ov16 ELISA for onchocerciasis revealed that out of the 3,308 children <10 years old screened in 2013, only 3/3308 (0.091%) positive cases were detected. All Ov16 positive children were negative when tested for patent infection by skin snip PCR. A reduction in LF microfilaria prevalence from 2.5% (n = 13/522) in 2006 to 0.0% (n = 602) in 2014 was observed. LF TAS1 conducted in 2015 among 1,532 children 6–7 years, all were negative for antigens of W. bancrofti. Conclusion The results concluded that interruption of onchocerciasis and LF has been achieved. PMID:29253862

Ad libitum Mediterranean and Low Fat Diets both Significantly Reduce Hepatic Steatosis: a Randomized Controlled Trial.

PubMed

Properzi, Catherine; O'Sullivan, Therese A; Sherriff, Jill L; Ching, Helena L; Jeffrey, Garry P; Buckley, Rachel F; Tibballs, Jonathan; MacQuillan, Gerry C; Garas, George; Adams, Leon A

2018-05-05

Although diet induced weight loss is first-line treatment for patients with non-alcoholic fatty liver disease (NAFLD), long-term maintenance is difficult. The optimal diet for either improvement in NAFLD or associated cardio-metabolic risk factors regardless of weight loss, is unknown. We examined the effect of two ad libitum isocaloric diets [Mediterranean (MD) or Low Fat (LF)] on hepatic steatosis and cardio-metabolic risk factors. Subjects with NAFLD were randomized to a 12-week blinded dietary intervention (MD vs LF). Hepatic steatosis was determined via magnetic resonance spectroscopy (MRS). From a total of 56 subjects enrolled, 49 subjects completed the intervention and 48 were included for analysis. During the intervention, subjects on the MD had significantly higher total and monounsaturated fat but lower carbohydrate and sodium intakes compared to LF subjects (p<0.01). At week 12, hepatic steatosis had reduced significantly in both groups (p<0.01) and there was no difference in liver fat reduction between the groups (p=0.32), with mean (SD) relative reductions of 25.0% (±25.3%) in LF and 32.4% (±25.5%) in MD. Liver enzymes also improved significantly in both groups. Weight loss was minimal and not different between groups [-1.6 (±2.1)kg in LF vs -2.1 (±2.5)kg in MD, (p=0.52)]. Within-group improvements in the Framingham risk score, total cholesterol, serum triglyceride, and HbA1c were observed in the MD (all p<0.05) but not with the LF diet. Adherence was higher for the MD compared to LF (88% vs. 64%, p=0.048). Ad libitum low fat and Mediterranean diets both improve hepatic steatosis to a similar degree. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Effects of dietary fat on muscle substrates, metabolism, and performance in athletes.

PubMed

Vogt, Michael; Puntschart, Adrian; Howald, Hans; Mueller, Bruno; Mannhart, Christoph; Gfeller-Tuescher, Liliane; Mullis, Primus; Hoppeler, Hans

2003-06-01

The present investigation aimed at identifying differences in muscle structural composition, substrate selection, and performance capacity in highly trained endurance athletes as a consequence of consuming a high-fat or a low-fat diet. Eleven duathletes ingested high-fat (53% fat; HF) or high-carbohydrate diets (17% fat; LF) for 5 wk in a randomized crossover design. In m. vastus lateralis, oxidative capacity estimated as volume of mitochondria per volume of muscle fiber (HF: 9.86 +/- 0.36 vs LF: 9.79 +/- 0.52%, mean +/- SE) was not different after the two diet periods. Intramyocellular lipid (IMCL) was significantly increased after HF compared with LF (1.54 +/- 0.27% vs 0.69 +/- 0.09%, P = 0.0076). Glycogen content was lower after HF than after LF, but this difference was not statistically significant (487.8 +/- 38.2 vs 534.4 +/- 32.6 mmol x kg-1 dry weight, P = 0.2454). Maximal power and [OV0312]O(2max) (63.6 +/- 0.9 vs 63.9 +/- 1.2 mL O(2) x min-1 x kg-1 on HF and LF) during an incremental exercise test to exhaustion were not different between the two diet periods. Total work output during a 20-min all-out time trial (298 +/- 6 vs 297 +/- 7 W) on a bicycle ergometer as well as half-marathon running time (80 min 12 s +/- 86 s vs 80 min 24 s +/- 82 s) were not different between HF and LF. Blood lactate concentrations and respiratory exchange ratios (RER) were significantly lower after HF than after LF at rest and during all submaximal exercise loads. Muscle glycogen stores were maintained after a 5-wk high-fat diet period whereas IMCL content was more than doubled. Endurance performance capacity was maintained at moderate to high-exercise intensities with a significantly larger contribution of lipids to total energy turnover.

Retinoids, retinoid analogs, and lactoferrin interact and differentially affect cell viability of 2 bovine mammary cell types in vitro.

PubMed

Wang, Y; Baumrucker, C R

2010-07-01

Two bovine mammary cell types (BME-UV1 and MeBo cells) were used to evaluate the effect of natural retinoids, retinoid analogs, and bovine lactoferrin (bLf) on cell viability in vitro. Experiments with Alamar Blue showed a linear relationship between fluorescence and cell viability index. The BME-UV1 cells exhibited twice the metabolic activity but required half the doubling time of the MeBo cells. The BME-UV1 cells were very sensitive to all-trans retinoic acid (atRA) inhibition of cell viability (P<0.05) and exhibited a dose-dependent inhibition with 9-cisRA (9cRA; P<0.05). The MeBo cells exhibited some inhibition with these natural ligands (P<0.05), but they were not as sensitive. The addition of bLf had similar inhibitory effects (P<0.05) on cell viability of the 2 mammary cell types. Applications of RA receptor (RAR) agonist indicated that the stimulation of the RAR in both mammary cell types was highly effective in inhibition of cell viability (P<0.05), whereas the application of an RAR antagonist stimulated MeBo cell viability (P<0.05) and inhibited BME-UV1 cell viability (P<0.05). Finally, the use of the RAR antagonist in conjunction with bLf indicated a rescue of the bLf effect in the MeBo cells, suggesting that bLf is acting through the RAR receptor. Conversely, bLf reverted inhibition of cell viability by 9cRA in the BME-UV1 cell type (P<0.05). We conclude that RAR interaction in bovine mammary cell types regulates cell viability in vitro; we hypothesize that the natural ligands mediate regulation of bovine mammary cell viability in vivo and that bLf can either enhance or reverse the retinoid-induced inhibition of cell viability, depending on the type of bovine mammary cell studied.

Discovery of a proteinaceous cellular receptor for a norovirus

PubMed Central

Orchard, Robert C.; Wilen, Craig B.; Doench, John G.; Baldridge, Megan T.; McCune, Broc T.; Lee, Ying-Chiang J.; Lee, Sanghyun; Pruett-Miller, Shondra M.; Nelson, Christopher A.; Fremont, Daved H.; Virgin, Herbert W.

2017-01-01

Human noroviruses (NoV) are a leading cause of gastroenteritis globally, yet host factors required for NoV infection are poorly understood. We identified host molecules essential for murine NoV (MNoV) induced cell death including CD300lf as a proteinaceous receptor. CD300lf is essential for MNoV binding and replication in cell lines and primary cells. Additionally, Cd300lf−/− mice are resistant to MNoV infection. Expression of CD300lf in human cells breaks the species barrier restricting MNoV replication. The crystal structure of the CD300lf ectodomain revealed a potential ligand binding cleft composed of residues critical for MNoV infection. Therefore, the presence of a proteinaceous receptor is the primary determinant of MNoV species tropism while other components of cellular machinery required for NoV replication are conserved between humans and mice. PMID:27540007

Structural basis for the unfolding of anthrax lethal factor by protective antigen oligomers

PubMed Central

Feld, Geoffrey K.; Thoren, Katie L.; Kintzer, Alexander F.; Sterling, Harry J.; Tang, Iok I.; Greenberg, Shoshana G.; Williams, Evan R.; Krantz, Bryan A.

2011-01-01

The protein transporter, anthrax lethal toxin, is comprised of protective antigen (PA), a transmembrane translocase, and lethal factor (LF), a cytotoxic enzyme. Following assembly into holotoxin complexes, PA forms an oligomeric channel that unfolds LF and translocates it into the host cell. We report the crystal structure of the core of a lethal toxin complex to 3.1-Å resolution; the structure contains a PA octamer bound to four LF PA-binding domains (LFN). The first α helix and β strand of each LFN unfold and dock into a deep amphipathic cleft on the surface of the PA octamer, which we call the α clamp. The α clamp possesses nonspecific polypeptide binding activity and is functionally relevant to efficient holotoxin assembly, PA octamer formation, and LF unfolding and translocation. This structure provides insight on the mechanism of translocation-coupled protein unfolding. PMID:21037566

Quality of low-fat meatballs containing Legume flours as extenders.

PubMed

Serdaroğlu, Meltem; Yıldız-Turp, Gülen; Abrodímov, Kiyalbek

2005-05-01

Meatballs were extended with blackeye bean flour (BBF), chickpea flour (CF), lentil flour (LF) and rusk (R) at level of 10%. Raw and cooked meatballs were analyzed for moisture, fat, protein and ash content. Cooking properties and colour parameters were evaluated. BBF and LF resulted in greater cooking yield, fat retention and moisture retention values. Meatballs extended with LF were lighter than other samples. Meatballs formulated with BBF had the lowest reduction in diameter. Meatballs with BBF and CF had higher water holding capacity (WHC) than other treatment groups. All meatballs incorporating legume flours were tougher (lower penetration values) than the R treatment. According to sensory evaluation results all meatball treatments had high acceptability and received high scores (6.8 and above). Meatballs with BBF and CF had lower TBA values than meatballs with LF and R at 3rd month of frozen storage at -18°C.

An improved asynchronous brain interface: making use of the temporal history of the LF-ASD feature vectors

NASA Astrophysics Data System (ADS)

Bashashati, Ali; Mason, Steve; Ward, Rabab K.; Birch, Gary E.

2006-06-01

The low-frequency asynchronous switch design (LF-ASD) has been introduced as a direct brain interface (BI) for asynchronous control applications. Asynchronous interfaces, as opposed to synchronous interfaces, have the advantage of being operational at all times and not only at specific system-defined periods. This paper modifies the LF-ASD design by incorporating into the system more knowledge about the attempted movements. Specifically, the history of feature values extracted from the EEG signal is used to detect a right index finger movement attempt. Using data collected from individuals with high-level spinal cord injuries and able-bodied subjects, it is shown that the error characteristics of the modified design are significantly better than the previous LF-ASD design. The true positive rate percentage increased by up to 15 which corresponds to 50% improvement when the system is operating with false positive rates in the 1-2% range.

Light Trapping with Silicon Light Funnel Arrays

PubMed Central

Nissan, Yuval; Gabay, Tamir; Shalev, Gil

2018-01-01

Silicon light funnels are three-dimensional subwavelength structures in the shape of inverted cones with respect to the incoming illumination. Light funnel (LF) arrays can serve as efficient absorbing layers on account of their light trapping capabilities, which are associated with the presence of high-density complex Mie modes. Specifically, light funnel arrays exhibit broadband absorption enhancement of the solar spectrum. In the current study, we numerically explore the optical coupling between surface light funnel arrays and the underlying substrates. We show that the absorption in the LF array-substrate complex is higher than the absorption in LF arrays of the same height (~10% increase). This, we suggest, implies that a LF array serves as an efficient surface element that imparts additional momentum components to the impinging illumination, and hence optically excites the substrate by near-field light concentration, excitation of traveling guided modes in the substrate, and mode hybridization. PMID:29562685

A preliminary study of the effects of an extract of Ligularia fischeri leaves on type II collagen-induced arthritis in DBA/1J mice.

PubMed

Choi, Eun Mi; Kim, Young Ho

2008-01-01

The present study was undertaken to determine whether Ligularia fischeri leaf extract (LF) is efficacious against collagen-induced arthritis (CIA) in mice. DBA/1J mice were immunized with bovine type II collagen and treated with LF (100 and 200 mg/kg) for 49 days. Mice were assessed regularly for signs of arthritis and the levels of rheumatoid factor, anti-type II collagen antibody, cytokines, AST, ALT, and creatinine in serum were also examined after the animals were killed. The arthritis score and paw edema were markedly suppressed in the groups treated with LF. Moreover, levels of rheumatoid factor, anti-type II collagen antibody, tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6 in sera were reduced by LF administration. These data suggest that L. fischeri might be effective for the treatment of inflammatory arthritis like human rheumatoid arthritis.

Bovine lactoferrin and lactoferricin interfere with intracellular trafficking of Herpes simplex virus-1.

PubMed

Marr, A K; Jenssen, H; Moniri, M Roshan; Hancock, R E W; Panté, N

2009-01-01

Although both lactoferrin (Lf), a component of the innate immune system of living organisms, and its N-terminal pepsin cleavage product lactoferricin (Lfcin) have anti-herpes activity, the precise mechanisms by which Lf and Lfcin bring about inhibition of herpes infections are not fully understood. In the present study, experiments were carried out to characterize the activity of bovine Lf and Lfcin (BLf and BLfcin) against the Herpes simplex virus-1 (HSV-1). HSV-1 cellular uptake and intracellular trafficking were studied by immunofluorescence microscopy. In comparison to the untreated infected control cells, both the BLf- and BLfcin-treated cells showed a significant reduction in HSV-1 cellular uptake. The few virus particles that were internalized appeared to have a delayed intracellular trafficking. Thus, in addition to their interference with the uptake of the virus into host cells, Lf and Lfcin also exert their antiviral effect intracellularly.

Moderate pressure massage elicits a parasympathetic nervous system response.

PubMed

Diego, Miguel A; Field, Tiffany

2009-01-01

Twenty healthy adults were randomly assigned to a moderate pressure or a light pressure massage therapy group, and EKGs were recorded during a 3-min baseline, during the 15-min massage period and during a 3-min postmassage period. EKG data were then used to derive the high frequency (HF), low frequency (LF) components of heart rate variability and the low to high frequency ratio (LF/HF) as noninvasive markers of autonomic nervous system activity. The participants who received the moderate pressure massage exhibited a parasympathetic nervous system response characterized by an increase in HF, suggesting increased vagal efferent activity and a decrease in the LF/HF ratio, suggesting a shift from sympathetic to parasympathetic activity that peaked during the first half of the massage period. On the other hand, those who received the light pressure massage exhibited a sympathetic nervous system response characterized by decreased HF and increased LF/HF.

CO luminosity function from Herschel-selected galaxies and the contribution of AGN

NASA Astrophysics Data System (ADS)

Vallini, L.; Gruppioni, C.; Pozzi, F.; Vignali, C.; Zamorani, G.

2016-02-01

We derive the carbon monoxide (CO) luminosity function (LF) for different rotational transitions [I.e. (1-0), (3-2), (5-4)] starting from the Herschel LF by Gruppioni et al. and using appropriate LCO-LIR conversions for different galaxy classes. Our predicted LFs fit the data so far available at z ≈ 0 and 2. We compare our results with those obtained by semi-analytical models (SAMs): while we find a good agreement over the whole range of luminosities at z ≈ 0, at z ≈ 1 and z ≈ 2, the tension between our LFs and SAMs in the faint and bright ends increases. We finally discuss the contribution of luminous active galactic nucleus (LX > 1044 erg s- 1) to the bright end of the CO LF concluding that they are too rare to reproduce the actual CO LF at z ≈ 2.

Ferrofluid-in-oil two-phase flow patterns in a flow-focusing microchannel

NASA Astrophysics Data System (ADS)

Sheu, T. S.; Chen, Y. T.; Lih, F. L.; Miao, J. M.

This study investigates the two-phase flow formation process of water-based Fe3O4 ferrofluid (dispersed phase) in a silicon oil (continuous phase) flow in the microfluidic flow-focusing microchannel under various operational conditions. With transparent PDMS chip and optical microscope, four main two-phase flow patterns as droplet flow, slug flow, ring flow and churn flow are observed. The droplet shape, size, and formation mechanism were also investigated under different Ca numbers and intended to find out the empirical relations. The paper marks an original flow pattern map of the ferrofluid-in-oil flows in the microfluidic flow-focusing microchannels. The flow pattern transiting from droplet flow to slug flow appears for an operational conditions of QR < 1 and Lf / W < 1. The power law index that related Lf / W to QR was 0.36 in present device.

The effects of burning and grazing on soil carbon dynamics in managed Peruvian tropical montane grasslands

NASA Astrophysics Data System (ADS)

Oliver, Viktoria; Oliveras, Imma; Kala, Jose; Lever, Rebecca; Arn Teh, Yit

2017-12-01

Montane tropical soils are a large carbon (C) reservoir, acting as both a source and a sink of CO2. Enhanced CO2 emissions originate, in large part, from the decomposition and losses of soil organic matter (SOM) following anthropogenic disturbances. Therefore, quantitative knowledge of the stabilization and decomposition of SOM is necessary in order to understand, assess and predict the impact of land management in the tropics. In particular, labile SOM is an early and sensitive indicator of how SOM responds to changes in land use and management practices, which could have major implications for long-term carbon storage and rising atmospheric CO2 concentrations. The aim of this study was to investigate the impacts of grazing and fire history on soil C dynamics in the Peruvian montane grasslands, an understudied ecosystem, which covers approximately a quarter of the land area in Peru. A density fractionation method was used to quantify the labile and stable organic matter pools, along with soil CO2 flux and decomposition measurements. Grazing and burning together significantly increased soil CO2 fluxes and decomposition rates and reduced temperature as a driver. Although there was no significant effect of land use on total soil C stocks, the combination of burning and grazing decreased the proportion of C in the free light fraction (LF), especially at the lower depths (10-20 and 20-30 cm). In the control soils, 20 % of the material recovered was in the free LF, which contained 30 % of the soil C content. In comparison, the burnt-grazed soil had the smallest recovery of the free LF (10 %) and a significantly lower C content (14 %). The burnt soils had a much higher proportion of C in the occluded LF (12 %) compared to the not-burnt soils (7 %) and there was no significant difference among the treatments in the heavy fraction (F) ( ˜ 70 %). The synergistic effect of burning and grazing caused changes to the soil C dynamics. CO2 fluxes were increased and the dominant temperature driver was obscured by some other process, such as changes in plant C and N allocation. In addition, the free LF was reduced when these two anthropogenic activities took place on the same site - most likely a result of reduced detritus being incorporated into the soil. A positive finding from this study is that the total soil C stocks were not significantly affected and the long-term (+10 years) C storage in the occluded LF and heavy F were not negatively impacted. Possibly this is because of low-intensity fire, fire-resilient grasses and because the grazing pressure is below the threshold necessary to cause severe degradation.

A 17-kDa Fragment of Lactoferrin Associates With the Termination of Inflammation and Peptides Within Promote Resolution

PubMed Central

Lutaty, Aviv; Soboh, Soaad; Schif-Zuck, Sagie; Zeituni-Timor, Orly; Rostoker, Ran; Podolska, Malgorzata J.; Schauer, Christine; Herrmann, Martin; Muñoz, Luis E.; Ariel, Amiram

2018-01-01

During the resolution of inflammation, macrophages engulf apoptotic polymorphonuclear cells (PMN) and can accumulate large numbers of their corpses. Here, we report that resolution phase macrophages acquire the neutrophil-derived glycoprotein lactoferrin (Lf) and fragments thereof in vivo and ex vivo. During the onset and resolving phases of inflammation in murine peritonitis and bovine mastitis, Lf fragments of 15 and 17 kDa occurred in various body fluids, and the murine fragmentation, accumulation, and release were mediated initially by neutrophils and later by efferocytic macrophages. The 17-kDa fragment contained two bioactive tripeptides, FKD and FKE that promoted resolution phase macrophage conversion to a pro-resolving phenotype. This resulted in a reduction in peritoneal macrophage numbers and an increase in the CD11blow subset of these cells. Moreover, FKE, but not FKD, peptides enhanced efferocytosis of apoptotic PMN, reduced TNFα and interleukin (IL)-6, and increased IL-10 secretion by lipopolysaccharide-stimulated macrophages ex vivo. In addition, FKE promoted neutrophil-mediated resolution at high concentrations (100 µM) by enhancing the formation of cytokine-scavenging aggregated NETs (tophi) at a low cellular density. Thus, PMN Lf is processed, acquired, and “recycled” by neutrophils and macrophages during inflammation resolution to generate fragments and peptides with paramount pro-resolving activities. PMID:29643857

Intermittency-induced criticality in the lower ionosphere prior to the 2016 Kumamoto earthquakes as embedded in the VLF propagation data observed at multiple stations

NASA Astrophysics Data System (ADS)

Potirakis, Stelios M.; Contoyiannis, Yiannis; Asano, Tomokazu; Hayakawa, Masashi

2018-01-01

A network of 8 VLF/LF receivers has recently been established across Japan, receiving subionospheric signals from different transmitters located both in the same and other countries. The primary purpose of this network is to study disturbances in the VLF/LF propagation through the lower ionosphere in possible relation to earthquake (EQ) preparation processes. Ionospheric perturbations of possible seismic origin have long been investigated and considered very promising for short-term EQ prediction. The raw amplitude data on reception of the above-mentioned network, after being appropriately filtered, were analyzed by means of the method of critical fluctuations (MCF) in analogy to thermal critical systems. The MCF analysis of the VLF/LF propagation revealed that intermittency-induced criticality was reached in the lower ionosphere from 1 week to 3 days prior to the catastrophic 2016 Kumamoto EQs. These fault-type EQs occurred within a two-day period (14 April: MW = 6.2 and MW = 6.0, 15 April: MW = 7.0) at shallow depths ( 10 km) and very close epicenters, while the main event was as huge as the former 1995 Kobe EQ. MCF analysis results are compared to those by the conventional nighttime fluctuation method as well as to those by natural time analysis method obtained for the same dataset, and are found to exhibit remarkable consistency.

Flexible Control of Safety Margins for Action Based on Environmental Variability.

PubMed

Hadjiosif, Alkis M; Smith, Maurice A

2015-06-17

To reduce the risk of slip, grip force (GF) control includes a safety margin above the force level ordinarily sufficient for the expected load force (LF) dynamics. The current view is that this safety margin is based on the expected LF dynamics, amounting to a static safety factor like that often used in engineering design. More efficient control could be achieved, however, if the motor system reduces the safety margin when LF variability is low and increases it when this variability is high. Here we show that this is indeed the case by demonstrating that the human motor system sizes the GF safety margin in proportion to an internal estimate of LF variability to maintain a fixed statistical confidence against slip. In contrast to current models of GF control that neglect the variability of LF dynamics, we demonstrate that GF is threefold more sensitive to the SD than the expected value of LF dynamics, in line with the maintenance of a 3-sigma confidence level. We then show that a computational model of GF control that includes a variability-driven safety margin predicts highly asymmetric GF adaptation between increases versus decreases in load. We find clear experimental evidence for this asymmetry and show that it explains previously reported differences in how rapidly GFs and manipulatory forces adapt. This model further predicts bizarre nonmonotonic shapes for GF learning curves, which are faithfully borne out in our experimental data. Our findings establish a new role for environmental variability in the control of action. Copyright © 2015 the authors 0270-6474/15/359106-16$15.00/0.

Consumption of a High-Fat Diet Induces Central Insulin Resistance Independent of Adiposity

PubMed Central

Clegg, Deborah J.; Gotoh, Koro; Kemp, Christopher; Wortman, Matthew D.; Benoit, Stephen C.; Brown, Lynda M.; D’Alessio, David; Tso, Patrick; Seeley, Randy J.; Woods, Stephen C.

2011-01-01

Plasma insulin enters the CNS where it interacts with insulin receptors in areas that are related to energy homeostasis and elicits a decrease of food intake and body weight. Here, we demonstrate that consumption of a high-fat (HF) diet impairs the central actions of insulin. Male Long-Evans rats were given chronic (70-day) or acute (3-day) ad libitum access to HF, low-fat (LF), or chow diets. Insulin administered into the 3rd-cerebral ventricle (i3vt) decreased food intake and body weight of LF and chow rats but had no effect on HF rats in either the chronic or the acute experiment. Rats chronically pair-fed the HF diet to match the caloric intake of LF rats, and with body weights and adiposity levels comparable to those of LF rats, were also unresponsive to i3vt insulin when returned to ad lib food whereas rats pair-fed the LF diet had reduced food intake and body weight when administered i3vt insulin. Insulin’s inability to reduce food intake in the presence of the high-fat diet was associated with a reduced ability of insulin to activate its signaling cascade, as measured by pAKT. Finally, i3vt administration of insulin increased hypothalamic expression of POMC mRNA in the LF-but not the HF-fed rats. We conclude that consumption of a HF diet leads to central insulin resistance following short exposure to the diet, and as demonstrated by reductions in insulin signaling and insulin-induced hypothalamic expression of POMC mRNA. PMID:21241723

Perspectives of Light-Front Quantized Field Theory: Some New Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, Prem P.

1999-08-13

A review of some basic topics in the light-front (LF) quantization of relativistic field theory is made. It is argued that the LF quantization is equally appropriate as the conventional one and that they lead, assuming the microcausality principle, to the same physical content. This is confirmed in the studies on the LF of the spontaneous symmetry breaking (SSB), of the degenerate vacua in Schwinger model (SM) and Chiral SM (CSM), of the chiral boson theory, and of the QCD in covariant gauges among others. The discussion on the LF is more economical and more transparent than that found inmore » the conventional equal-time quantized theory. The removal of the constraints on the LF phase space by following the Dirac method, in fact, results in a substantially reduced number of independent dynamical variables. Consequently, the descriptions of the physical Hilbert space and the vacuum structure, for example, become more tractable. In the context of the Dyson-Wick perturbation theory the relevant propagators in the front form theory are causal. The Wick rotation can then be performed to employ the Euclidean space integrals in momentum space. The lack of manifest covariance becomes tractable, and still more so if we employ, as discussed in the text, the Fourier transform of the fermionic field based on a special construction of the LF spinor. The fact that the hyperplanes x{sup {+-}} = 0 constitute characteristic surfaces of the hyperbolic partial differential equation is found irrelevant in the quantized theory; it seems sufficient to quantize the theory on one of the characteristic hyperplanes.« less

Effect of low-frequency electromagnetic fields on the Escherichia coli growth for application in riverbank filtration

NASA Astrophysics Data System (ADS)

Selamat, Rossitah; Abustan, Ismail; Arshad, Mohd Rizal; Kamal, Nurul Hana Mokhtar

2017-10-01

A 50 Hz low-frequency electromagnetic field (LF-EMF) could give removal effect on the growth of Escherichia coli (E. coli) in the riverbank filtration (RBF) was studied. The LF-EMF strengths were varied from 2 to 10 mT using coil column induce magnetic fields. For this study, two different columns with a diameter of 50 mm and 80 mm were applied; 1.5mm copper wires with the number of turns between 300 to 600 turns. Water samples were flowed into the column at flowrate of 50mL/min with temperature in range of 28-30°C. This study, it was found that the LF-EMF has significant removal effects on E. coli growth, where the removal of 100% of E. coli at 6 mT and 8 mT after 6 hrs exposed. Moreover, for shorter exposure period of 3 hrs exposed, 82% of E. coli removal were detected in 80 mm column for 8 mT and 10 mT magnetic field. These findings indicate that the application of LF-EMF is able to decrease the E. coli, can be and efficient in E. coli growth from river water intake. Thus, the results from this study proved that the utilization of LF-EMF is able to decrease the concentrations of E. coli, and contributes in slowing down their growth. Also, it can be indicated that the LF-EMF kill a part of E. coli exposed in the river water with the large magnetic field and long-time exposure.

Oscillatory patterns in sympathetic neural discharge and cardiovascular variables during orthostatic stimulus

NASA Technical Reports Server (NTRS)

Furlan, R.; Porta, A.; Costa, F.; Tank, J.; Baker, L.; Schiavi, R.; Robertson, D.; Malliani, A.; Mosqueda-Garcia, R.

2000-01-01

BACKGROUND: We tested the hypothesis that a common oscillatory pattern might characterize the rhythmic discharge of muscle sympathetic nerve activity (MSNA) and the spontaneous variability of heart rate and systolic arterial pressure (SAP) during a physiological increase of sympathetic activity induced by the head-up tilt maneuver. METHODS AND RESULTS: Ten healthy subjects underwent continuous recordings of ECG, intra-arterial pressure, respiratory activity, central venous pressure, and MSNA, both in the recumbent position and during 75 degrees head-up tilt. Venous samplings for catecholamine assessment were obtained at rest and during the fifth minute of tilt. Spectrum and cross-spectrum analyses of R-R interval, SAP, and MSNA variabilities and of respiratory activity provided the low (LF, 0.1 Hz) and high frequency (HF, 0.27 Hz) rhythmic components of each signal and assessed their linear relationships. Compared with the recumbent position, tilt reduced central venous pressure, but blood pressure was unchanged. Heart rate, MSNA, and plasma epinephrine and norepinephrine levels increased, suggesting a marked enhancement of overall sympathetic activity. During tilt, LF(MSNA) increased compared with the level in the supine position; this mirrored similar changes observed in the LF components of R-R interval and SAP variabilities. The increase of LF(MSNA) was proportional to the amount of the sympathetic discharge. The coupling between LF components of MSNA and R-R interval and SAP variabilities was enhanced during tilt compared with rest. CONCLUSIONS: During the sympathetic activation induced by tilt, a similar oscillatory pattern based on an increased LF rhythmicity characterized the spontaneous variability of neural sympathetic discharge, R-R interval, and arterial pressure.

Protein functionalized tramadol-loaded PLGA nanoparticles: preparation, optimization, stability and pharmacodynamic studies.

PubMed

Lalani, Jigar; Rathi, Mohan; Lalan, Manisha; Misra, Ambikanandan

2013-06-01

Poly (d,l-lactide-co-glycolide acid) (PLGA) Nanoparticles (NPs) with sustained drug release and enhanced circulation time presents widely explored non-invasive approach for drug delivery to brain. However, blood-brain barrier (BBB) limits the drug delivery to brain. This can be overcome by anchoring endogenous ligand like Transferrin (Tf) and Lactoferrin (Lf) on the surface of NPs, allowing efficient brain delivery via receptor-mediated endocytosis. The aim of the present investigation was preparation, optimization, characterization and comparative evaluation of targeting efficiency of Tf- vs. Lf-conjugated NPs. Tramadol-loaded PLGA NPs were prepared by nanoprecipitation techniques and optimized using 3(3) factorial design. The effect of polymer concentration, stabilizer concentration and organic:aqueous phase ratio were evaluated on particle size (PS) and entrapment efficiency (EE). The formulation was optimized based on desirability for lower PS (<150 nm) and higher EE (>70%). Optimized PLGA NPs were conjugated with Tf and Lf, characterized and evaluated for stability study. Pharmacodynamic study was performed in rat after intravenous administration. The optimized formulation had 100 mg of PLGA, 1% polyvinyl alcohol (PVA) and 1:2 acetone:water ratio. The Lf and Tf conjugation to PLGA NPs was estimated to 186 Tf and 185 Lf molecules per NPs. Lyophilization was optimized at 1:2 ratio of NPs:trehalose. The NPs were found stable for 6 months at refrigerated condition. Pharmacodynamic study demonstrated enhanced efficacy of ligand-conjugated NPs against unconjugated NPs. Conjugated NPs demonstrated significantly higher pharmacological effect over a period of 24 h. Furthermore Lf functionalized NPs exhibited better antinociceptive effect as compared to Tf functionalized NPs.

Single Session Low Frequency Left Dorsolateral Prefrontal Transcranial Magnetic Stimulation Changes Neurometabolite Relationships in Healthy Humans

PubMed Central

Bridges, Nathaniel R.; McKinley, Richard A.; Boeke, Danielle; Sherwood, Matthew S.; Parker, Jason G.; McIntire, Lindsey K.; Nelson, Justin M.; Fletchall, Catherine; Alexander, Natasha; McConnell, Amanda; Goodyear, Chuck; Nelson, Jeremy T.

2018-01-01

Background: Dorsolateral prefrontal cortex (DLPFC) low frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise as a treatment and investigative tool in the medical and research communities. Researchers have made significant progress elucidating DLPFC LF-rTMS effects—primarily in individuals with psychiatric disorders. However, more efforts investigating underlying molecular changes and establishing links to functional and behavioral outcomes in healthy humans are needed. Objective: We aimed to quantify neuromolecular changes and relate these to functional changes following a single session of DLPFC LF-rTMS in healthy participants. Methods: Eleven participants received sham-controlled neuronavigated 1 Hz rTMS to the region most activated by a 7-letter Sternberg working memory task (SWMT) within the left DLPFC. We quantified SWMT performance, functional magnetic resonance activation and proton Magnetic resonance spectroscopy (MRS) neurometabolite measure changes before and after stimulation. Results: A single LF-rTMS session was not sufficient to change DLPFC neurometabolite levels and these changes did not correlate with DLPFC activation changes. Real rTMS, however, significantly altered neurometabolite correlations (compared to sham rTMS), both with baseline levels and between the metabolites themselves. Additionally, real rTMS was associated with diminished reaction time (RT) performance improvements and increased activation within the motor, somatosensory and lateral occipital cortices. Conclusion: These results show that a single session of LF-rTMS is sufficient to influence metabolite relationships and causes widespread activation in healthy humans. Investigating correlational relationships may provide insight into mechanisms underlying LF-rTMS. PMID:29632477

Diet Modulation is an Effective Complementary Agent in Preventing and Treating Breast Cancer Lung Metastasis

PubMed Central

Zhao, Xiangmin; Rezonzew, Gabriel; Wang, Dezhi; Siegal, Gene P.; Hardy, Robert W.

2014-01-01

A significant percentage of breast cancer victims will suffer from metastases indicating that new approaches to preventing breast cancer metastasis are thus needed. Dietary stearate and chemotherapy have been shown to reduce breast cancer metastasis. We tested the complementary use of dietary stearate with a taxol-based chemotherapy which work through separate mechanisms to reduce breast cancer metastasis. We therefore carried out a prevention study in which diets were initiated prior to human MDA-MB-435 cancer cells being injected into the host and a treatment study in which diets were combined with paclitaxel (PTX). Using an orthotopic athymic nude mouse model and three diets (corn oil control diet/CO, low fat /LF or stearate/ST) the prevention study demonstrated that the ST diet decreased the incidence of lung metastasis by 50% compared to both the LF and CO diets. The ST diet also reduced the number and size of metastatic lung nodules compared to the LF diet. Results of the treatment study indicated that both the CO and ST diets decreased the number of mice with lung metastasis compared to the LF diet. Both CO and ST also decreased the number of lung metastases per mouse compared to the LF diet however only the ST diet cohort was significant. Histomorphometric analysis of the lung tumor tissue indicated that the ST diet plus PTX decreased angiogenesis compared to the LF diet plus PTX. In conclusion these results support combining diet with chemotherapy in both treatment and prevention settings. PMID:24832758

Inhibitory effect of hydroxypropyl methylcellulose acetate succinate on drug recrystallization from a supersaturated solution assessed using nuclear magnetic resonance measurements.

PubMed

Ueda, Keisuke; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

2013-10-07

We examined the inhibitory effect of hydroxypropyl methylcellulose acetate succinate (HPMC-AS) on drug recrystallization from a supersaturated solution using carbamazepine (CBZ) and phenytoin (PHT) as model drugs. HPMC-AS HF grade (HF) inhibited the recrystallization of CBZ more strongly than that by HPMC-AS LF grade (LF). 1D-1H NMR measurements showed that the molecular mobility of CBZ was clearly suppressed in the HF solution compared to that in the LF solution. Interaction between CBZ and HF in a supersaturated solution was directly detected using nuclear Overhauser effect spectroscopy (NOESY). The cross-peak intensity obtained using NOESY of HF protons with CBZ aromatic protons was greater than that with the amide proton, which indicated that CBZ had hydrophobic interactions with HF in a supersaturated solution. In contrast, no interaction was observed between CBZ and LF in the LF solution. Saturation transfer difference NMR measurement was used to determine the interaction sites between CBZ and HF. Strong interaction with CBZ was observed with the acetyl substituent of HPMC-AS although the interaction with the succinoyl substituent was quite small. The acetyl groups played an important role in the hydrophobic interaction between HF and CBZ. In addition, HF appeared to be more hydrophobic than LF because of the smaller ratio of the succinoyl substituent. This might be responsible for the strong hydrophobic interaction between HF and CBZ. The intermolecular interactions between CBZ and HPMC-AS shown by using NMR spectroscopy clearly explained the strength of inhibition of HPMC-AS on drug recrystallization.

Liquid-phase characterization of molecular interactions in polyunsaturated and n-fatty acid methyl esters by (1)H low-field nuclear magnetic resonance.

PubMed

Meiri, Nitzan; Berman, Paula; Colnago, Luiz Alberto; Moraes, Tiago Bueno; Linder, Charles; Wiesman, Zeev

2015-01-01

To identify and develop the best renewable and low carbon footprint biodiesel substitutes for petroleum diesel, the properties of different biodiesel candidates should be studied and characterized with respect to molecular structures versus biodiesel liquid property relationships. In our previous paper, (1)H low-field nuclear magnetic resonance (LF-NMR) relaxometry was investigated as a tool for studying the liquid-phase molecular packing interactions and morphology of fatty acid methyl esters (FAMEs). The technological potential was demonstrated with oleic acid and methyl oleate standards having similar alkyl chains but different head groups. In the present work, molecular organization versus segmental and translational movements of FAMEs in their pure liquid phase, with different alkyl chain lengths (10-20 carbons) and degrees of unsaturation (0-3 double bonds), were studied with (1)H LF-NMR relaxometry and X-ray, (1)H LF-NMR diffusiometry, and (13)C high-field NMR. Based on density values and X-ray measurements, it was proposed that FAMEs possess a liquid crystal-like order above their melting point, consisting of random liquid crystal aggregates with void spaces between them, whose morphological properties depend on chain length and degree of unsaturation. FAMEs were also found to exhibit different degrees of rotational and translational motions, which were rationalized by chain organization within the clusters, and the degree and type of molecular interactions and temperature effects. At equivalent fixed temperature differences from melting point, saturated FAME molecules were found to have similar translational motion regardless of chain length, expressed by viscosity, self-diffusion coefficients, and spin-spin (T 2) (1)H LF-NMR. T 2 distributions suggest increased alkyl chain rigidity, and reduced temperature response of the peaks' relative contribution with increasing unsaturation is a direct result of the alkyl chain's morphological packing and molecular interactions. Both the peaks' assignments for T 2 distributions of FAMEs and the model for their liquid crystal-like morphology in the liquid phase were confirmed. The study of morphological structures within liquids and their response to temperature changes by (1)H LF-NMR has a high value in the field of biodiesel and other research and applied disciplines in numerous physicochemical- and organizational-based properties, processes, and mechanisms of alkyl chains, molecular interactions, and morphologies.

Community-based field implementation scenarios of a short message service reporting tool for lymphatic filariasis case estimates in Africa and Asia.

PubMed

Mableson, Hayley E; Martindale, Sarah; Stanton, Michelle C; Mackenzie, Charles; Kelly-Hope, Louise A

2017-01-01

Lymphatic filariasis (LF) is a neglected tropical disease (NTD) targeted for global elimination by 2020. Currently there is considerable international effort to scale-up morbidity management activities in endemic countries, however there remains a need for rapid, cost-effective methods and adaptable tools for obtaining estimates of people presenting with clinical manifestations of LF, namely lymphoedema and hydrocele. The mHealth tool ' MeasureSMS-Morbidity ' allows health workers in endemic areas to use their own mobile phones to send clinical information in a simple format using short message service (SMS). The experience gained through programmatic use of the tool in five endemic countries across a diversity of settings in Africa and Asia is used here to present implementation scenarios that are suitable for adapting the tool for use in a range of different programmatic, endemic, demographic and health system settings. A checklist of five key factors and sub-questions was used to determine and define specific community-based field implementation scenarios for using the MeasureSMS-Morbidity tool in a range of settings. These factors included: (I) tool feasibility (acceptability; community access and ownership); (II) LF endemicity (high; low prevalence); (III) population demography (urban; rural); (IV) health system structure (human resources; community access); and (V) integration with other diseases (co-endemicity). Based on experiences in Bangladesh, Ethiopia, Malawi, Nepal and Tanzania, four implementation scenarios were identified as suitable for using the MeasureSMS-Morbidity tool for searching and reporting LF clinical case data across a range of programmatic, endemic, demographic and health system settings. These include: (I) urban, high endemic setting with two-tier reporting; (II) rural, high endemic setting with one-tier reporting; (III) rural, high endemic setting with two-tier reporting; and (IV) low-endemic, urban and rural setting with one-tier reporting. A decision-making framework built from the key factors and questions, and the resulting four implementation scenarios is proposed as a means of using the MeasureSMS-Morbidity tool. This framework will help national LF programmes consider appropriate methods to implement a survey using this tool to improve estimates of the clinical burden of LF. Obtaining LF case estimates is a vital step towards the elimination of LF as a public health problem in endemic countries.

The D-Region Ionospheric Response to the 2017 Solar Eclipse

NASA Astrophysics Data System (ADS)

Cohen, M.; McCormick, J.; Gross, N. C.; Higginson-Rollins, M. A.

2017-12-01

VLF/LF radio remote sensing (0.5-500 kHz) is an effective means for quantifying the D-region ionosphere (60-90 km altitude). Disturbances in the ionospheric electron density induce changes in the propagation of VLF/LF signals, so a network of transmitters and receivers can effectively "image" a disturbed region. VLF/LF signals can all be detected from 100s-1000s of km away. We utilize Georgia Tech's network of highly-sensitive VLF/LF receivers to quantify the lower ionospheric response to the "Great American Eclipse". Nine of these were deployed and operational across the Continental US, Alaska and Puerto Rico all operated successfully. Each receiver synchronously recorded the full radio spectrum between 0.5-470 kHz. The included figure shows the eclipse track at 80 km altitude with a green swath. The nine operational receivers are shown with blue stars, and operational VLF/LF transmitters in dark red. Gray lines are shown for each great-circle path linking a VLF/LF transmitter to a receiver. This constellation forms a dense spider's-web grid of radio links, with which we can effectively image the disturbed patch of the D-region ionosphere as it moves across the country. In addition, shown in yellow are NDGPS transmitters which lie between 285-325 kHz. The red dots are the 230,000 geolocated lightning strokes during the 90-mintue eclipse pass, each of which emitted an intense VLF/LF impulse. These are also detected by our receivers. We present our observations and comparison with a theoretical model, using a combination of three techniques established by a series of three 2017 journal papers: (1) Polarization measurements of VLF/LF transmitter signals, (2) Lightning-generated VLF sferics detected 1000s of km away, and (3) NDGPS beacons near 300 kHz for shorter-range sounding of a small patch of the ionosphere. We find evidence of large scale ionospheric changes which affect the D-region over the entire continental region with a slowly-varying signal perturbation. At some sites close to the totality zone, however, we have evidence of forward scattering from the shadow of the moon, which effectively is a patch of nighttime surrounded by daytime, that can only be observed in a narrower region around the totality zone. Implications of these results for D-region ionospheric dynamics are discussed.

Magnesium Recycling of Partially Oxidized, Mixed Magnesium-Aluminum Scrap Through Combined Refining and Solid Oxide Membrane (SOM) Electrolysis Processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guan, Xiaofei; Zink, Peter; Pal, Uday

2012-03-11

Pure magnesium (Mg) is recycled from 19g of partially oxidized 50.5wt.%Mg-Aluminum (Al) alloy. During the refining process, potentiodynamic scans (PDS) were performed to determine the electrorefining potential for magnesium. The PDS show that the electrorefining potential increases over time as the Mg content inside the Mg-Al scrap decreases. Up to 100% percent of magnesium is refined from the Mg-Al scrap by a novel refining process of dissolving magnesium and its oxide into a flux followed by vapor phase removal of dissolved magnesium and subsequently condensing the magnesium vapors in a separate condenser. The solid oxide membrane (SOM) electrolysis process ismore » employed in the refining system to enable additional recycling of magnesium from magnesium oxide (MgO) in the partially oxidized Mg-Al scrap. The combination of the refining and SOM processes yields 7.4g of pure magnesium; could not collect and weigh all of the magnesium recovered.« less

Relevant magnetic and soil parameters as potential indicators of soil conservation status of Mediterranean agroecosystems

NASA Astrophysics Data System (ADS)

Quijano, Laura; Chaparro, Marcos A. E.; Marié, Débora C.; Gaspar, Leticia; Navas, Ana

2014-09-01

The main sources of magnetic minerals in soils unaffected by anthropogenic pollution are iron oxides and hydroxides derived from parent materials through soil formation processes. Soil magnetic minerals can be used as indicators of environmental factors including soil forming processes, degree of pedogenesis, weathering processes and biological activities. In this study measurements of magnetic susceptibility are used to detect the presence and the concentration of soil magnetic minerals in topsoil and bulk samples in a small cultivated field, which forms a hydrological unit that can be considered to be representative of the rainfed agroecosystems of Mediterranean mountain environments. Additional magnetic studies such as isothermal remanent magnetization (IRM), anhysteretic remanent magnetization (ARM) and thermomagnetic measurements are used to identify and characterize the magnetic mineralogy of soil minerals. The objectives were to analyse the spatial variability of the magnetic parameters to assess whether topographic factors, soil redistribution processes, and soil properties such as soil texture, organic matter and carbonate contents analysed in this study, are related to the spatial distribution pattern of magnetic properties. The medians of mass specific magnetic susceptibility at low frequency (χlf) were 36.0 and 31.1 × 10-8 m3 kg-1 in bulk and topsoil samples respectively. High correlation coefficients were found between the χlf in topsoil and bulk core samples (r = 0.951, p < 0.01). In addition, volumetric magnetic susceptibility was measured in situ in the field (κis) and values varied from 13.3 to 64.0 × 10-5 SI. High correlation coefficients were found between χlf in topsoil measured in the laboratory and volumetric magnetic susceptibility field measurements (r = 0.894, p < 0.01). The results obtained from magnetic studies such as IRM, ARM and thermomagnetic measurements show the presence of magnetite, which is the predominant magnetic carrier, and hematite. The predominance of superparamagnetic minerals in upper soil layers suggests enrichment in pedogenic minerals. The finer soil particles, the organic matter content and the magnetic susceptibility values are statistically correlated and their spatial variability is related to similar physical processes. Runoff redistributes soil components including magnetic minerals and exports fine particles out the field. This research contributed to further knowledge on the application of soil magnetic properties to derive useful information on soil processes in Mediterranean cultivated soils.

Separation of Lead from Crude Antimony by Pyro-Refining Process with NaPO3 Addition

NASA Astrophysics Data System (ADS)

Ye, Longgang; Hu, Yuejie; Xia, Zhimei; Chen, Yongming

2016-06-01

The main purpose of this study was to separate lead from crude antimony through an oxidation pyro-refining process and by using sodium metaphosphate as a lead elimination reagent. The process parameters that will affect the refining results were optimized experimentally under controlled conditions, such as the sodium metaphosphate charging dosage, the refining temperature and duration, and the air flow rate, to determine their effect on the lead content in refined antimony and the lead removal rate. A minimum lead content of 0.0522 wt.% and a 98.6% lead removal rate were obtained under the following optimal conditions: W_{{{NaPO}_{{3}} }} = 15% W Sb (where W represents weight), a refining temperature of 800°C, a refining time of 30 min, and an air flow rate of 3 L/min. X-ray diffractometry and scanning electron microscopy showed that high-purity antimony was obtained. The smelting operation is free from smoke or ammonia pollution when using monobasic sodium phosphate or ammonium dihydrogen phosphate as the lead elimination reagent. However, this refining process can also remove a certain amount of sulfur, cobalt, and silicon simultaneously, and smelting results also suggest that sodium metaphosphate can be used as a potential lead elimination reagent for bismuth and copper refining.

Impact and Ballistic Response of Hybridized Thermoplastic Laminates

DTIC Science & Technology

2011-02-01

hybrid panels exhibit the lowest dynamic and residual deflection through all samples. Kevlar and [0/90] HB25 layup are similar in performance...HB25 + 2 Layer K705 Phenolic 1422.00 15.646 15.1638 Shot on Aramid Face 60/40 Mix HB25/LF1 1424.06 15.646 16.256 Shot on HB25 Face Dyneema HB80...Carbon 1420.46 16.764 16.3576 Shot on Carbon Face HB25 + 3-ply LF1 1427.38 16.866 18.4404 Shot on LF1 Face HB25 + 2 Layer K745 Phenolic 1418.00

Effects of age, education and gender on verbal fluency.

PubMed

Mathuranath, P S; George, A; Cherian, P J; Alexander, A; Sarma, S G; Sarma, P S

2003-12-01

The objective was to study the effects of age, education and gender on verbal fluency in cognitively unimpaired, older individuals. The methods used were as follows: cognitively unimpaired elderly (55-84 years) subjects (n=153), were administered category (animal) (CF) and letter (/pa/) (LF) fluency tasks, in their native language of Malayalam. Results and conclusions were (1) Level of education, but not age or gender, significantly influence LF. (2) Level of education (directly) and in the elderly subjects, age (inversely) affect CF. (3) Age, but not education, has a differential effect on the tasks of verbal fluency, influencing CF more than LF.

Nonlinear low frequency (LF) waves - Comets and foreshock phenomena

NASA Technical Reports Server (NTRS)

Tsurutani, Bruce T.

1991-01-01

A review is conducted of LF wave nonlinear properties at comets and in the earth's foreshock, engaging such compelling questions as why there are no cometary cyclotron waves, the physical mechanism responsible for 'dispersive whiskers', and the character of a general description of linear waves. Attention is given to the nonlinear properties of LF waves, whose development is illustrated by examples of waves and their features at different distances from the comet, as well as by computer simulation results. Also discussed is a curious wave mode detected from Comet Giacobini-Zinner, both at and upstream of the bow shock/wave.

Eye light flashes on the Mir space station.

PubMed

Avdeev, S; Bidoli, V; Casolino, M; De Grandis, E; Furano, G; Morselli, A; Narici, L; De Pascale, M P; Picozza, P; Reali, E; Sparvoli, R; Boezio, M; Carlson, P; Bonvicini, W; Vacchi, A; Zampa, N; Castellini, G; Fuglesang, C; Galper, A; Khodarovich, A; Ozerov, Yu; Popov, A; Vavilov, N; Mazzenga, G; Ricci, M; Sannita, W G; Spillantini, P

2002-04-01

The phenomenon of light flashes (LF) in eyes for people in space has been investigated onboard Mir. Data on particles hitting the eye have been collected with the SilEye detectors, and correlated with human observations. It is found that a nucleus in the radiation environment of Mir has roughly a 1% probability to cause an LF, whereas the proton probability is almost three orders of magnitude less. As a function of LET, the LF probability increases above 10 keV/micrometer, reaching about 5% at around 50 keV/micrometer. c 2002 Elsevier Science Ltd. All rights reserved.

Studies on anticancer activities of lactoferrin and lactoferricin.

PubMed

Yin, Cui Ming; Wong, Jack Ho; Xia, Jiang; Ng, Tzi Bun

2013-09-01

This review mainly summarizes results of recent studies on the anticancer activity of the multifunctional protein lactoferrin (Lf) and its derived peptide lactoferricin (Lfcin). The basic information on Lf and Lfcin, such as their sources, structures, and biological properties which favor their antitumor activity is introduced. The major anticancer mechanisms of Lf and Lfcin including cell cycle arrest, apoptosis, anti-angiogenesis, antimetastasis, immune modulation and necrosis are discussed. Other information from in vivo studies employing a mouse model is also provided. In addition, the roles of talatoferrin and delta lactoferrin, as well as improvement in drug delivery will be covered.

WRN conditioned media is sufficient for in vitro propagation of intestinal organoids from large farm and small companion animals.

PubMed

Powell, Robin H; Behnke, Michael S

2017-05-15

Recent years have seen significant developments in the ability to continuously propagate organoids derived from intestinal crypts. These advancements have been applied to mouse and human samples providing models for gastrointestinal tissue development and disease. We adapt these methods for the propagation of intestinal organoids (enteroids) from various large farm and small companion (LF/SC) animals, including cat, dog, cow, horse, pig, sheep and chicken. We show that LF/SC enteroids propagate and expand in L-WRN conditioned media containing signaling factors Wnt3a, R-spondin-3, and Noggin (WRN). Multiple successful isolations were achieved for each species, and the growth of LF/SC enteroids was maintained to high passage number. LF/SC enteroids expressed crypt stem cell marker LGR5 and low levels of mesenchymal marker VIM. Labeling with EdU also showed distinct regions of cell proliferation within the enteroids marking crypt-like regions. The ability to grow and maintain LF/SC enteroid cell lines provides additional models for the study of gastrointestinal developmental biology as well as platforms for the study of host-pathogen interactions between intestinal cells and zoonotic enteric pathogens of medical importance. © 2017. Published by The Company of Biologists Ltd.

Development of antibodies to protective antigen and lethal factor components of anthrax toxin in humans and guinea pigs and their relevance to protective immunity.

PubMed Central

Turnbull, P C; Broster, M G; Carman, J A; Manchee, R J; Melling, J

1986-01-01

A competitive inhibition enzyme-linked immunosorbent assay (ELISA) was developed to detect antibodies in serum to the protective antigen (PA) and lethal factor (LF) components of anthrax toxin. Current human vaccination schedules with an acellular vaccine induce predictable and lasting antibody titers to PA and, when present in the vaccine, to LF. Live spore vaccine administered to guinea pigs in a single dose conferred significantly better protection than the human vaccines (P less than 0.001), although they elicited significantly lower (P less than 0.0005) anti-PA and anti-LF titers at time of challenge with virulent Bacillus anthracis. Substantial anti-PA and anti-LF titers may not, therefore, indicate solid protective immunity against anthrax infection. The ELISA system was also shown to be capable of detecting anti-PA and anti-LF antibodies in the sera of individuals with histories of clinical anthrax. The advantage of ELISA over the Ouchterlony gel diffusion test and indirect microhemagglutination assay are demonstrated. There was a highly significant degree of correlation between ELISA and the indirect microhemagglutination assay (P less than 0.0005); but ELISA was markedly superior in terms of reproducibility, reliability, specificity, and simplicity in performance and stability of the bound antigen. PMID:3084381

The Comparative Effect of Carrot and Lemon Fiber as a Fat Replacer on Physico-chemical, Textural, and Organoleptic Quality of Low-fat Beef Hamburger.

PubMed

Soncu, Eda Demirok; Kolsarıcı, Nuray; Çiçek, Neslihan; Öztürk, Görsen Salman; Akoğlu, Ilker T; Arıcı, Yeliz Kaşko

2015-01-01

This study was designed to determine the usability of lemon fiber (LF-2%, 4%, 6%) and carrot fiber (CF-2%, 4%, 6%) to produce low-fat beef hamburgers. To that end, a certain amount of fat was replaced with each fiber. The proximate composition, pH value, cholesterol content, cooking characteristics, color, texture profile, and sensory properties of low-fat beef hamburgers were investigated. LF increased moisture content and cooking yield due to its better water binding properties, while CF caused higher fat and cholesterol contents owing to its higher fat absorption capacity (p<0.05). LF resulted in a lighter, redder, and more yellow color (p<0.05). Hardness, gumminess, springiness, and chewiness parameters decreased when the usage level of both fibers increased (p<0.05). However, more tender, gummy, springy, and smoother hamburgers were produced by the addition of CF in comparison with LF (p<0.05). Moreover, hamburgers including CF were rated with higher sensory scores (p<0.05). In conclusion, LF demonstrated better technological results in terms of cooking yield, shrinkage, moisture retention, and fat retention. However it is suggested that CF produces better low-fat hamburgers since up to 2% CF presented sensory and textural properties similar to those of regular hamburgers.

A novel surfactant-free lipid-based formulation for improving oral bioavailability of loratadine using colloidal silicon dioxide as emulsifier and solid carrier.

PubMed

Huang, Ri; Tan, Yonggang; Shen, Lao; Wang, Tao; Quan, Dongqin

2018-05-08

The purpose of this study was to develop an innovative surfactant-free lipid-based formulation (LF) for improving oral bioavailability of loratadine based on using solid particles colloidal silicon dioxide (CSD) as emulsifier and solid carrier. Loratadine was dissolved in oil solution with the aid of co-solvent and LF were prepared by a simple adsorption and milling technique. The LF Powder was evaluated in terms of angle of repose and X-ray powder diffraction. After dispersing and emulsifying in water, the particle size and morphology were also characterized. In vitro dissolution and pharmacokinetic behavior in vivo were also studied. Orthogonal design indicated that the amount of CSD in formulations had a major and significant influence on emulsification. The optimal formulation showed LF with good flowability and without crystallization or deposition of loratadine in it. After dispersing in water, an emulsion with mean droplet size of 1.2μm was obtained. Although the dissolution of drug from LF was slower in vitro in acidic aqueous solution, pharmacokinetic studies in vivo showed that the bioavailability of loratadine increased 2.49-fold by CF compared to commercial tablet. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Functional activities of acidic isoferritins and lactoferrin in vitro and in vivo.

PubMed

Broxmeyer, H E; Gentile, P; Cooper, S; Lu, L; Juliano, L; Piacibello, W; Meyers, P A; Cavanna, F

1984-01-01

The functional activities of acidic isoferritins (AIF) and lactoferin (LF) were evaluated. The inhibitory activity of AIF (AIFIA) was inactivated by preincubation with a monoclonal antibody (2A4) against AIF, but AIFIA was not inactivated by another monoclonal antibody against AIF (1C5), by a monoclonal antibody (3A5) against basic isoferritins, or by a heteroantiserum (LFT) against basic isoferritins. Monoclonal 2A4 also inactivated the inhibitory activity against colony formation by granulocyte-macrophage (CFU-GM) progenitor cells that was constitutively released by human monocytes or induced by human monocytes in the presence of OKT4+ lymphocytes. In addition to OKT4+ lymphocytes, the release of AIFIA from human monocytes was modulated by iron-saturated human LF and OKT8+ lymphocytes, both of which suppressed the release of AIFIA. Evidence for the physiologic relevance of AIF as a regulator of myelopoiesis was presented, in that human AIF suppressed the numbers of CFU-GM, BFU-E, and CFU-GEMM per femur and the cycling status of these cells in mice recovering from a sublethal dosage of Cytoxan. Abnormalities in LF and AIF interactions were found with cells from a pediatric patient with neutrophilia of unknown etiology that were consistent with the disease manifestations of neutrophilia. Polymorphonuclear neutrophils (PMN) from the patient contained low levels (1%-10% of control) of immunologically reactive LF and the LF found was ineffective as a suppressor molecule for the release of GM-CSF from normal mononuclear blood cells. In addition, the patient's GM-CSF releasing mononuclear blood cells were insensitive to the suppressive effects of purified LF, and colony formation by the patient's CFU-GM, but not BFU-E or CFU-GEMM, were insensitive to the suppressive effects of purified AIF. When the activity of purified AIF was assessed against mouse bone marrow cells under serum-free conditions, it was apparent that serum was not needed for the suppressive activity of AIF and that in some cases, serum actually masked the effects of AIF. Human monoblast cell line U937 was found to be a good model in vitro for the actions of LF and AIF; U937 cells induced for Ia-antigens by human gamma interferon were separated into populations of Ia-antigen+ and Ia-antigen- cells by fluorescence activated cell sorting (FACS), and LF and AIF suppressed colony formation only by the Ia-antigen+ U937 cells. A comparative analysis of bovine and human LF against release of GM-CSF from human mononuclear cells demonstrated that both were active in their iron-saturated form.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of Low- Versus High-Fidelity Simulations on the Cognitive Burden and Performance of Entry-Level Paramedicine Students: A Mixed-Methods Comparison Trial Using Eye-Tracking, Continuous Heart Rate, Difficulty Rating Scales, Video Observation and Interviews.

PubMed

Mills, Brennen W; Carter, Owen B-J; Rudd, Cobie J; Claxton, Louise A; Ross, Nathan P; Strobel, Natalie A

2016-02-01

High-fidelity simulation-based training is often avoided for early-stage students because of the assumption that while practicing newly learned skills, they are ill suited to processing multiple demands, which can lead to "cognitive overload" and poorer learning outcomes. We tested this assumption using a mixed-methods experimental design manipulating psychological immersion. Thirty-nine randomly assigned first-year paramedicine students completed low- or high-environmental fidelity simulations [low-environmental fidelity simulations (LF(en)S) vs. high-environmental fidelity simulation (HF(en)S)] involving a manikin with obstructed airway (SimMan3G). Psychological immersion and cognitive burden were determined via continuous heart rate, eye tracking, self-report questionnaire (National Aeronautics and Space Administration Task Load Index), independent observation, and postsimulation interviews. Performance was assessed by successful location of obstruction and time-to-termination. Eye tracking confirmed that students attended to multiple, concurrent stimuli in HF(en)S and interviews consistently suggested that they experienced greater psychological immersion and cognitive burden than their LF(en)S counterparts. This was confirmed by significantly higher mean heart rate (P < 0.001) and National Aeronautics and Space Administration Task Load Index mental demand (P < 0.05). Although group allocation did not influence the proportion of students who ultimately revived the patient (58% vs. 30%, P < 0.10), the HF(en)S students did so significantly more quickly (P < 0.01). The LF(en)S students had low immersion resulting in greater assessment anxiety. High-environmental fidelity simulation engendered immersion and a sense of urgency in students, whereas LF(en)S created assessment anxiety and slower performance. We conclude that once early-stage students have learned the basics of a clinical skill, throwing them in the "deep end" of high-fidelity simulation creates significant additional cognitive burden but this has considerable educational merit.

Bioremediation of a tropical clay soil contaminated with diesel oil.

PubMed

Chagas-Spinelli, Alessandra C O; Kato, Mario T; de Lima, Edmilson S; Gavazza, Savia

2012-12-30

The removal of polyaromatic hydrocarbons (PAH) in tropical clay soil contaminated with diesel oil was evaluated. Three bioremediation treatments were used: landfarming (LF), biostimulation (BS) and biostimulation with bioaugmentation (BSBA). The treatment removal efficiency for the total PAHs differed from the efficiencies for the removal of individual PAH compounds. In the case of total PAHs, the removal values obtained at the end of the 129-day experimental period were 87%, 89% and 87% for LF, BS and BSBA, respectively. Thus, the efficiency was not improved by the addition of nutrients and microorganisms. Typically, two distinct phases were observed. A higher removal rate occurred in the first 17 days (P-I) and a lower rate occurred in the last 112 days (P-II). In phase P-I, the zero-order kinetic parameter (μg PAH g(-1) soil d(-1)) values were similar (about 4.6) for all the three treatments. In P-II, values were also similar but much lower (about 0.14). P-I was characterized by a sharp pH decrease to less than 5.0 for the BS and BSBA treatments, while the pH remained near 6.5 for LF. Concerning the 16 individual priority PAH compounds, the results varied depending on the bioremediation treatment used and on the PAH species of interest. In general, compounds with fewer aromatic rings were better removed by BS or BSBA, while those with 4 or more rings were most effectively removed by LF. The biphasic removal behavior was observed only for some compounds. In the case of naphthalene, pyrene, chrysene, benzo[k]fluoranthene and benzo[a]pyrene, removal occurred mostly in the P-I phase. Therefore, the best degradation process for total or individual PAHs should be selected considering the target compounds and the local conditions, such as native microbiota and soil type. Copyright © 2012 Elsevier Ltd. All rights reserved.

YouTube as a Potential Training Resource for Laparoscopic Fundoplication.

PubMed

Frongia, Giovanni; Mehrabi, Arianeb; Fonouni, Hamidreza; Rennert, Helga; Golriz, Mohammad; Günther, Patrick

To analyze the surgical proficiency and educational quality of YouTube videos demonstrating laparoscopic fundoplication (LF). In this cross-sectional study, a search was performed on YouTube for videos demonstrating the LF procedure. The surgical and educational proficiency was evaluated using the objective component rating scale, the educational quality rating score, and total video quality score. Statistical significance was determined by analysis of variance, receiver operating characteristic curve, and odds ratio analysis. A total of 71 videos were included in the study; 28 (39.4%) videos were evaluated as good, 23 (32.4%) were moderate, and 20 (28.2%) were poor. Good-rated videos were significantly longer (good, 22.0 ± 5.2min; moderate, 7.8 ± 0.9min; poor, 8.5 ± 1.0min; p = 0.007) and video duration was predictive of good quality (AUC, 0.672 ± 0.067; 95% CI: 0.541-0.802; p = 0.015). For good quality, the cut-off video duration was 7:42 minute. This cut-off value had a sensitivity of 67.9%, a specificity of 60.5%, and an odds ratio of 3.23 (95% CI: 1.19-8.79; p = 0.022) in predicting good quality. Videos uploaded from industrial sources and with a higher views/days online ratio had a higher objective component rating scale and total video quality score. In contrast, the likes/dislikes ratio was not predictive of video quality. Many videos showing the LF procedure have been uploaded to YouTube with varying degrees of quality. A process for filtering LF videos with high surgical and educational quality is feasible by evaluating the video duration, uploading source, and the views/days online ratio. However, alternative videos platforms aimed at professionals should also be considered for educational purposes. Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Spectroscopic Diagnosis of Arsenic Contamination in Agricultural Soils

PubMed Central

Shi, Tiezhu; Liu, Huizeng; Chen, Yiyun; Fei, Teng; Wang, Junjie; Wu, Guofeng

2017-01-01

This study investigated the abilities of pre-processing, feature selection and machine-learning methods for the spectroscopic diagnosis of soil arsenic contamination. The spectral data were pre-processed by using Savitzky-Golay smoothing, first and second derivatives, multiplicative scatter correction, standard normal variate, and mean centering. Principle component analysis (PCA) and the RELIEF algorithm were used to extract spectral features. Machine-learning methods, including random forests (RF), artificial neural network (ANN), radial basis function- and linear function- based support vector machine (RBF- and LF-SVM) were employed for establishing diagnosis models. The model accuracies were evaluated and compared by using overall accuracies (OAs). The statistical significance of the difference between models was evaluated by using McNemar’s test (Z value). The results showed that the OAs varied with the different combinations of pre-processing, feature selection, and classification methods. Feature selection methods could improve the modeling efficiencies and diagnosis accuracies, and RELIEF often outperformed PCA. The optimal models established by RF (OA = 86%), ANN (OA = 89%), RBF- (OA = 89%) and LF-SVM (OA = 87%) had no statistical difference in diagnosis accuracies (Z < 1.96, p < 0.05). These results indicated that it was feasible to diagnose soil arsenic contamination using reflectance spectroscopy. The appropriate combination of multivariate methods was important to improve diagnosis accuracies. PMID:28471412

Integration of digital signal processing technologies with pulsed electron paramagnetic resonance imaging

PubMed Central

Pursley, Randall H.; Salem, Ghadi; Devasahayam, Nallathamby; Subramanian, Sankaran; Koscielniak, Janusz; Krishna, Murali C.; Pohida, Thomas J.

2006-01-01

The integration of modern data acquisition and digital signal processing (DSP) technologies with Fourier transform electron paramagnetic resonance (FT-EPR) imaging at radiofrequencies (RF) is described. The FT-EPR system operates at a Larmor frequency (Lf) of 300 MHz to facilitate in vivo studies. This relatively low frequency Lf, in conjunction with our ~10 MHz signal bandwidth, enables the use of direct free induction decay time-locked subsampling (TLSS). This particular technique provides advantages by eliminating the traditional analog intermediate frequency downconversion stage along with the corresponding noise sources. TLSS also results in manageable sample rates that facilitate the design of DSP-based data acquisition and image processing platforms. More specifically, we utilize a high-speed field programmable gate array (FPGA) and a DSP processor to perform advanced real-time signal and image processing. The migration to a DSP-based configuration offers the benefits of improved EPR system performance, as well as increased adaptability to various EPR system configurations (i.e., software configurable systems instead of hardware reconfigurations). The required modifications to the FT-EPR system design are described, with focus on the addition of DSP technologies including the application-specific hardware, software, and firmware developed for the FPGA and DSP processor. The first results of using real-time DSP technologies in conjunction with direct detection bandpass sampling to implement EPR imaging at RF frequencies are presented. PMID:16243552

Practical Advances in Petroleum Processing

NASA Astrophysics Data System (ADS)

Hsu, Chang S.; Robinson, Paul R.

"This comprehensive book by Robinson and Hsu will certainly become the standard text book for the oil refining business...[A] must read for all who are associated with oil refining." - Dr. Walter Fritsch, Senior Vice President Refining, OMV "This book covers a very advanced horizon of petroleum processing technology. For all refiners facing regional and global environmental concerns, and for those who seek a more sophisticated understanding of the refining of petroleum resources, this book has been long in coming." - Mr. Naomasa Kondo, Cosmo Oil Company, Ltd.

National Mass Drug Administration Costs for Lymphatic Filariasis Elimination

PubMed Central

Goldman, Ann S.; Guisinger, Victoria H.; Aikins, Moses; Amarillo, Maria Lourdes E.; Belizario, Vicente Y.; Garshong, Bertha; Gyapong, John; Kabali, Conrad; Kamal, Hussein A.; Kanjilal, Sanjat; Kyelem, Dominique; Lizardo, Jefrey; Malecela, Mwele; Mubyazi, Godfrey; Nitièma, P. Abdoulaye; Ramzy, Reda M. R.; Streit, Thomas G.; Wallace, Aaron; Brady, Molly A.; Rheingans, Richard; Ottesen, Eric A.; Haddix, Anne C.

2007-01-01

Background Because lymphatic filariasis (LF) elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA) programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin), a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk. Methodology/Principal Findings To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1) the total annual cost of the LF program, 2) the average cost per person treated, and 3) the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1) the age (newness) of the MDA program, 2) the use of volunteers, and 3) the size of the population treated. Substantial contributions by governments were documented – generally 60%–90% of program operation costs, excluding costs of donated medications. Conclusions/Significance MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones. PMID:17989784

Oral lactoferrin protects against experimental candidiasis in mice

PubMed Central

Velliyagounder, Kabilan; Alsaedi, Wijdan; Alabdulmohsen, Waad; Markowitz, Kenneth; Fine, Daniel H.

2015-01-01

Aims To determine the role of lactoferrin in protecting the oral cavities of mice against Candida albicans infection in lactoferrin knockout (LFKO−/−) mice were compared to wild-type (WT) mice. We also determine the protective role of human lactoferrin in the LFKO−/− mice. Methods and Results Antibiotic treated immunosuppressed mice were inoculated with C. albicans (or sham infection) by oral swab and evaluated for the severity of infection after 7 days of infection. To determine the protective role of hLF, we added 0.3% solution of hLF to the drinking water given to some of the mice. CFU count, scoring of lesions and microscopic observations were carried out to determine the severity of infection. LFKO−/−I mice showed a 2 log (P=0.001) higher CFUs of C. albicans in the oral cavity compared to the WTI mice. LFKO−/−I mice given hLF had a 3 log (P=0.001) reduction in CFUs in the oral cavity compared to untreated LFKO−/−I mice. The severity of infection, observed by light microscopy revealed that the tongue of the LFKO−/−I mice showed more white patches compared to WTI and LFKO−/−I+hLF mice. Scanning electron microscopic observation revealed that more filiform papillae were destroyed in LFKO−/−I mice when compared to WTI or LFKO−/−I +hLF mice. Conclusions Human lactoferrin is important in protecting mice from oral C. albicans infection. Administered hLF may be used to prevent C. albicans infection. Significance and Impact of the Study Human lactoferrin, a multifunctional iron-binding glycoprotein can be used as a therapeutic active ingredient in oral health care products against C. albicans. PMID:25319508

The genetic and developmental basis of an exaggerated craniofacial trait in East African cichlids.

PubMed

Concannon, Moira R; Albertson, R Craig

2015-12-01

The evolution of an exaggerated trait can lead to a novel morphology that allows organisms to exploit new niches. The molecular bases of such phenotypes can reveal insights into the evolution of unique traits. Here, we investigate a rare morphological innovation in modern haplochromine cichlids, a flap of fibrous tissue that causes a pronounced projection of the snout, which is limited to a single genus (Labeotropheus) of Lake Malawi cichlids. We compare flap size in our focal species L. fuelleborni (LF) to homologous landmarks in other closely related cichlid species that show a range of ecological overlap with LF, and demonstrate that variation in flap size is discontinuous among Malawi cichlid species. We demonstrate further that flap development in LF begins at early juvenile stages, and scales allometrically with body size. We then used an F2 hybrid mapping population, derived via crossing LF to a close ecological competitor that lacks this trait, Tropheops "red cheek" (TRC), to identify quantitative trait loci (QTL) that underlie flap development. In all, we identified four loci associated with variation in flap size, and for each the LF allele contributed to a larger flap. We next cross-referenced our QTL map with population genomic data, comparing natural populations of LF and TRC, to identify divergent polymorphisms within each QTL interval. Candidate genes for flap development are discussed. Together, these data indicate a relatively simple and tractable genetic basis for this morphological innovation, which is consistent with its apparently sudden and saltatory evolutionary history. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 662-670, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Effect of spontaneous saliva swallowing on short-term heart rate variability (HRV) and reliability of HRV analysis.

PubMed

Yildiz, Metin; Doma, Serian

2017-09-26

The effects of effortful swallowing and solid meal ingestions on heart rate variability (HRV) have been examined previously. The effects of spontaneous saliva swallowing on short-term HRV and reliability of HRV analysis have not been studied before. The effect of saliva swallowing on HRV analyses parameters [meanRRI, SDNN (standard deviation of normal-to-normal), LF (low frequency), HF (high frequency) powers, LH/HF] and the reliability of LF and HF powers were investigated by frequency, time-frequency and intraclass correlation coefficient (ICC) analyses. Electrocardiogram and swallowing signal that obtained from an electronic stethoscope placed on the necks of subjects were recorded simultaneously from 30 healthy and young volunteers in sitting position during 15 min. Spontaneous swallowing has been shown to significantly alter some HRV parameters (SDNN, LF power and LF/HF ratio). Time-frequency analysis results showed that the contribution of saliva swallowing to LF (1-58%) and HF (2-42%) powers could change significantly depending on the number of swallowing. The ICC of the LF and HF powers for the successive 5-min signal segments were found 0·89, 0·92, respectively. These values decreased to 0·73 and 0·90 in the subjects with more swallowing rate. When the analyses were made for 2-min signal periods, these values decreased to 0·63 and 0·67. We concluded that spontaneous saliva swallowing can change HRV parameters. We have also seen that changes in swallowing rate and use of short signal segments may reduce the reliability of HRV analyses. © 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

A Diverse Set of Single-domain Antibodies (VHHs) against the Anthrax Toxin Lethal and Edema Factors Provides a Basis for Construction of a Bispecific Agent That Protects against Anthrax Infection*

PubMed Central

Vrentas, Catherine E.; Moayeri, Mahtab; Keefer, Andrea B.; Greaney, Allison J.; Tremblay, Jacqueline; O'Mard, Danielle; Leppla, Stephen H.; Shoemaker, Charles B.

2016-01-01

Infection with Bacillus anthracis, the causative agent of anthrax, can lead to persistence of lethal secreted toxins in the bloodstream, even after antibiotic treatment. VHH single-domain antibodies have been demonstrated to neutralize diverse bacterial toxins both in vitro and in vivo, with protein properties such as small size and high stability that make them attractive therapeutic candidates. Recently, we reported on VHHs with in vivo activity against the protective antigen component of the anthrax toxins. Here, we characterized a new set of 15 VHHs against the anthrax toxins that act by binding to the edema factor (EF) and/or lethal factor (LF) components. Six of these VHHs are cross-reactive against both EF and LF and recognize the N-terminal domain (LFN, EFN) of their target(s) with subnanomolar affinity. The cross-reactive VHHs block binding of EF/LF to the protective antigen C-terminal binding interface, preventing toxin entry into the cell. Another VHH appears to recognize the LF C-terminal domain and exhibits a kinetic effect on substrate cleavage by LF. A subset of the VHHs neutralized against EF and/or LF in murine macrophage assays, and the neutralizing VHHs that were tested improved survival of mice in a spore model of anthrax infection. Finally, a bispecific VNA (VHH-based neutralizing agent) consisting of two linked toxin-neutralizing VHHs, JMN-D10 and JMO-G1, was fully protective against lethal anthrax spore infection in mice as a single dose. This set of VHHs should facilitate development of new therapeutic VNAs and/or diagnostic agents for anthrax. PMID:27539858

Early morning urine collection to improve urinary lateral flow LAM assay sensitivity in hospitalised patients with HIV-TB co-infection.

PubMed

Gina, Phindile; Randall, Philippa J; Muchinga, Tapuwa E; Pooran, Anil; Meldau, Richard; Peter, Jonny G; Dheda, Keertan

2017-05-12

Urine LAM testing has been approved by the WHO for use in hospitalised patients with advanced immunosuppression. However, sensitivity remains suboptimal. We therefore examined the incremental diagnostic sensitivity of early morning urine (EMU) versus random urine sampling using the Determine® lateral flow lipoarabinomannan assay (LF-LAM) in HIV-TB co-infected patients. Consenting HIV-infected inpatients, screened as part of a larger prospective randomized controlled trial, that were treated for TB, and could donate matched random and EMU samples were included. Thus paired sample were collected from the same patient, LF-LAM was graded using the pre-January 2014, with grade 1 and 2 manufacturer-designated cut-points (the latter designated grade 1 after January 2014). Single sputum Xpert-MTB/RIF and/or TB culture positivity served as the reference standard (definite TB). Those treated for TB but not meeting this standard were designated probable TB. 123 HIV-infected patients commenced anti-TB treatment and provided matched random and EMU samples. 33% (41/123) and 67% (82/123) had definite and probable TB, respectively. Amongst those with definite TB LF-LAM sensitivity (95%CI), using the grade 2 cut-point, increased from 12% (5-24; 5/43) to 39% (26-54; 16/41) with random versus EMU, respectively (p = 0.005). Similarly, amongst probable TB, LF-LAM sensitivity increased from 10% (5-17; 8/83) to 24% (16-34; 20/82) (p = 0.001). LF-LAM specificity was not determined. This proof of concept study indicates that EMU could improve the sensitivity of LF-LAM in hospitalised TB-HIV co-infected patients. These data have implications for clinical practice.