Expanding health insurance to increase health care utilization: will it have different effects in rural vs. urban areas?

PubMed

Erlyana, Erlyana; Damrongplasit, Kannika Kampanya; Melnick, Glenn

2011-05-01

This study investigates the importance of medical fee and distance to health care provider on individual's decision to seek care in developing countries. The estimation method used a mixed logit model applied to data from the third wave of the Indonesian family life survey (2000). The key variables of interest include medical fee and distance to different types of health care provider and individual characteristic variables. Urban dweller's decision to choose health care providers are sensitive to the monetary cost of medical care as measured by medical fee but they are not sensitive to distance. For those who reside in rural area, they are sensitive to the non-medical component cost of care as measured by travel distance but they are not sensitive to medical fee. As a result of those findings, policy makers should consider different sets of policy instruments when attempting to expand health service's usage in urban and rural areas of Indonesia. To increase access in urban areas, we recommend expansion of health insurance coverage in order to lower out-of-pocket medical expenditures. As for rural areas, expansion of medical infrastructures to reduce commuting distance and costs will be needed to increase utilization. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Twenty-five years of optical coherence tomography: the paradigm shift in sensitivity and speed provided by Fourier domain OCT [Invited

PubMed Central

de Boer, Johannes F.; Leitgeb, Rainer; Wojtkowski, Maciej

2017-01-01

Optical coherence tomography (OCT) has become one of the most successful optical technologies implemented in medicine and clinical practice mostly due to the possibility of non-invasive and non-contact imaging by detecting back-scattered light. OCT has gone through a tremendous development over the past 25 years. From its initial inception in 1991 [Science 254, 1178 (1991)1957169] it has become an indispensable medical imaging technology in ophthalmology. Also in fields like cardiology and gastro-enterology the technology is envisioned to become a standard of care. A key contributor to the success of OCT has been the sensitivity and speed advantage offered by Fourier domain OCT. In this review paper the development of FD-OCT will be revisited, providing a single comprehensive framework to derive the sensitivity advantage of both SD- and SS-OCT. We point out the key aspects of the physics and the technology that has enabled a more than 2 orders of magnitude increase in sensitivity, and as a consequence an increase in the imaging speed without loss of image quality. This speed increase provided a paradigm shift from point sampling to comprehensive 3D in vivo imaging, whose clinical impact is still actively explored by a large number of researchers worldwide. PMID:28717565

Mechanisms of thermal acclimation to exercise and heat

NASA Technical Reports Server (NTRS)

Nadel, E. R.; Pandolf, K. B.; Roberts, M. F.; Stolwijk, J. A. J.

1974-01-01

By plotting local sweating rate from a given area against the central sweating drive (which is analogous to esophageal temperature, when mean skin temperature is constant), it is possible to determine the characteristic gain constant of that area as well as its point of zero central drive. An increase in the gain constant as a result of acclimation would indicate an increased sensitivity of the sweating mechanism per unit of central sweating drive, i.e., enhanced peripheral sensitivity. A displacement of the point of zero central drive as a result of acclimation would indicate that central mechanisms are responsible for the heightened sweating response. The study was undertaken to provide information about whether central or peripheral physiological mechanisms provide for increased sweating capabilities during acclimation, and about whether the increased sweating capabilities in heat acclimation and physical training are provided for by the same mechanisms.

Transverse section radionuclide scanning system

DOEpatents

Kuhl, David E.; Edwards, Roy Q.

1976-01-01

This invention provides a transverse section radionuclide scanning system for high-sensitivity quantification of brain radioactivity in cross-section picture format in order to permit accurate assessment of regional brain function localized in three-dimensions. High sensitivity crucially depends on overcoming the heretofore known raster type scanning, which requires back and forth detector movement involving dead-time or partial enclosure of the scan field. Accordingly, this invention provides a detector array having no back and forth movement by interlaced detectors that enclose the scan field and rotate as an integral unit around one axis of rotation in a slip ring that continuously transmits the detector data by means of laser emitting diodes, with the advantages that increased amounts of data can be continuously collected, processed and displayed with increased sensitivity according to a suitable computer program.

Acoustic enhancement for photo detecting devices

DOEpatents

Thundat, Thomas G; Senesac, Lawrence R; Van Neste, Charles W

2013-02-19

Provided are improvements to photo detecting devices and methods for enhancing the sensitivity of photo detecting devices. A photo detecting device generates an electronic signal in response to a received light pulse. An electro-mechanical acoustic resonator, electrically coupled to the photo detecting device, damps the electronic signal and increases the signal noise ratio (SNR) of the electronic signal. Increased photo detector standoff distances and sensitivities will result.

Temperature Sensitivity as a Microbial Trait Using Parameters from Macromolecular Rate Theory

PubMed Central

Alster, Charlotte J.; Baas, Peter; Wallenstein, Matthew D.; Johnson, Nels G.; von Fischer, Joseph C.

2016-01-01

The activity of soil microbial extracellular enzymes is strongly controlled by temperature, yet the degree to which temperature sensitivity varies by microbe and enzyme type is unclear. Such information would allow soil microbial enzymes to be incorporated in a traits-based framework to improve prediction of ecosystem response to global change. If temperature sensitivity varies for specific soil enzymes, then determining the underlying causes of variation in temperature sensitivity of these enzymes will provide fundamental insights for predicting nutrient dynamics belowground. In this study, we characterized how both microbial taxonomic variation as well as substrate type affects temperature sensitivity. We measured β-glucosidase, leucine aminopeptidase, and phosphatase activities at six temperatures: 4, 11, 25, 35, 45, and 60°C, for seven different soil microbial isolates. To calculate temperature sensitivity, we employed two models, Arrhenius, which predicts an exponential increase in reaction rate with temperature, and Macromolecular Rate Theory (MMRT), which predicts rate to peak and then decline as temperature increases. We found MMRT provided a more accurate fit and allowed for more nuanced interpretation of temperature sensitivity in all of the enzyme × isolate combinations tested. Our results revealed that both the enzyme type and soil isolate type explain variation in parameters associated with temperature sensitivity. Because we found temperature sensitivity to be an inherent and variable property of an enzyme, we argue that it can be incorporated as a microbial functional trait, but only when using the MMRT definition of temperature sensitivity. We show that the Arrhenius metrics of temperature sensitivity are overly sensitive to test conditions, with activation energy changing depending on the temperature range it was calculated within. Thus, we propose the use of the MMRT definition of temperature sensitivity for accurate interpretation of temperature sensitivity of soil microbial enzymes. PMID:27909429

A novel photonic crystal fiber Mach-Zehnder interferometer for enhancing refractive index measurement sensitivity

NASA Astrophysics Data System (ADS)

Zhao, Yong; Xia, Feng; Hu, Hai-feng; Chen, Mao-qing

2017-11-01

A novel refractive index (RI) sensor based on photonic crystal fiber Mach-Zehnder interferometer (PCF-MZI) was proposed. It was realized by cascading a section of PCF with half-taper collapse regions (HTCRs) between two single mode fibers (SMFs). The relationship between RI sensitivity and interference length of the PCF-MZI was firstly investigated. Both simulation and experimental results showed that RI sensitivity increased with the increase of interference length. Afterwards, influence of HTCR parameters on RI sensitivity was experimentally investigated to further improve the sensitivity. With intensification of arc discharge intensity in HTCR fabrication process, HTCR with larger maximum taper diameter and longer collapsed region length was obtained, which enhanced evanescent field of the PCF-MZI and then generated higher RI sensitivity. Consequently, a high RI sensitivity of 181.96 nm/refractive index unit (RIU) was achieved in the RI range of 1.3333-1.3574. Increasing arc discharge intensity in HTCR fabrication process has the capacity to improve RI sensitivity of PCF-MZI and meanwhile provides higher mechanical strength and longer sensor life compared to the traditional method of tapering the fiber, which improves the RI sensitivity at the cost of reducing mechanical strength of the sensor. This PCF-MZI was characterized by high RI sensitivity, ease of fabrication, high mechanical strength, and robustness.

Adaptive controller for volumetric display of neuroimaging studies

NASA Astrophysics Data System (ADS)

Bleiberg, Ben; Senseney, Justin; Caban, Jesus

2014-03-01

Volumetric display of medical images is an increasingly relevant method for examining an imaging acquisition as the prevalence of thin-slice imaging increases in clinical studies. Current mouse and keyboard implementations for volumetric control provide neither the sensitivity nor specificity required to manipulate a volumetric display for efficient reading in a clinical setting. Solutions to efficient volumetric manipulation provide more sensitivity by removing the binary nature of actions controlled by keyboard clicks, but specificity is lost because a single action may change display in several directions. When specificity is then further addressed by re-implementing hardware binary functions through the introduction of mode control, the result is a cumbersome interface that fails to achieve the revolutionary benefit required for adoption of a new technology. We address the specificity versus sensitivity problem of volumetric interfaces by providing adaptive positional awareness to the volumetric control device by manipulating communication between hardware driver and existing software methods for volumetric display of medical images. This creates a tethered effect for volumetric display, providing a smooth interface that improves on existing hardware approaches to volumetric scene manipulation.

High fat diet and food restriction differentially modify the behavioral effects of quinpirole and raclopride in rats.

PubMed

Baladi, Michelle G; France, Charles P

2009-05-21

Nutritional status can impact dopamine systems in a manner that might be important to understanding possible common neurobiological mechanisms that mediate abnormal compulsive food (e.g., obesity) and drug taking. Limiting food intake, for example, can increase sensitivity to the behavioral effects of indirect-acting dopamine receptor agonists. Much less is known regarding possible diet-induced changes in sensitivity to direct-acting dopamine receptor drugs. The present study investigated the effects of a high fat diet and of food restriction on sensitivity of rats to the behavioral effects of a direct-acting dopamine receptor agonist and a dopamine receptor antagonist. Free access to high fat chow increased sensitivity to quinpirole-induced yawning without changing sensitivity to raclopride-induced catalepsy or quinpirole-induced hypothermia. Food restriction (10 g/day) decreased sensitivity to quinpirole-induced yawning and raclopride-induced catalepsy without affecting sensitivity to quinpirole-induced hypothermia. Free access to a standard chow restored sensitivity to the behavioral effects of both drugs in rats that were previously food-restricted but not in rats that previously ate a high fat diet. These data confirm that food restriction can decrease sensitivity to behavioral effects of direct-acting dopamine receptor drugs, they provide evidence (i.e., no change in hypothermic effects) indicating that these changes are not due to pharmacokinetic mechanisms, and they provide initial evidence showing enhanced sensitivity to behavioral effects of dopamine receptor drugs in rats eating a high fat diet. These changes in sensitivity of dopamine systems could be relevant to understanding the impact of nutrition on therapeutic and recreational drug use.

High fat diet and food restriction differentially modify the behavioral effects of quinpirole and raclopride in rats

PubMed Central

Baladi, Michelle G; France, Charles P

2009-01-01

Nutritional status can impact dopamine systems in a manner that might be important to understanding possible common neurobiological mechanisms that mediate abnormal compulsive food (e.g., obesity) and drug taking. Limiting food intake, for example, can increase sensitivity to the behavioral effects of indirect-acting dopamine receptor agonists. Much less is known regarding possible diet-induced changes in sensitivity to direct-acting dopamine receptor drugs. The present study investigated the effects of a high fat diet and of food restriction on sensitivity of rats to the behavioral effects of a direct-acting dopamine receptor agonist and a dopamine receptor antagonist. Free access to high fat chow increased sensitivity to quinpirole-induced yawning without changing sensitivity to raclopride-induced catalepsy or quinpirole-induced hypothermia. Food restriction (10 g/day) decreased sensitivity to quinpirole-induced yawning and raclopride-induced catalepsy without affecting sensitivity to quinpirole-induced hypothermia. Free access to a standard chow restored sensitivity to the behavioral effects of both drugs in rats that were previously food-restricted but not in rats that previously ate a high fat diet. These data confirm that food restriction can decrease sensitivity to behavioral effects of direct-acting dopamine receptor drugs, they provide evidence (i.e., no change in hypothermic effects) indicating that these changes are not due to pharmacokinetic mechanisms, and they provide initial evidence showing enhanced sensitivity to behavioral effects of dopamine receptor drugs in rats eating a high fat diet. These changes in sensitivity of dopamine systems could be relevant to understanding the impact of nutrition on therapeutic and recreational drug use. PMID:19327348

Pressure sensitivity of low permeability sandstones

USGS Publications Warehouse

Kilmer, N.H.; Morrow, N.R.; Pitman, Janet K.

1987-01-01

Detailed core analysis has been carried out on 32 tight sandstones with permeabilities ranging over four orders of magnitude (0.0002 to 4.8 mD at 5000 psi confining pressure). Relationships between gas permeability and net confining pressure were measured for cycles of loading and unloading. For some samples, permeabilities were measured both along and across bedding planes. Large variations in stress sensitivity of permeability were observed from one sample to another. The ratio of permeability at a nominal confining pressure of 500 psi to that at 5000 psi was used to define a stress sensitivity ratio. For a given sample, confining pressure vs permeability followed a linear log-log relationship, the slope of which provided an index of pressure sensitivity. This index, as obtained for first unloading data, was used in testing relationships between stress sensitivity and other measured rock properties. Pressure sensitivity tended to increase with increase in carbonate content and depth, and with decrease in porosity, permeability and sodium feldspar. However, scatter in these relationships increased as permeability decreased. Tests for correlations between pressure sensitivity and various linear combinations of variables are reported. Details of pore structure related to diagenetic changes appears to be of much greater significance to pressure sensitivity than mineral composition. ?? 1987.

PCR/LDR/universal array platforms for the diagnosis of infectious disease.

PubMed

Pingle, Maneesh; Rundell, Mark; Das, Sanchita; Golightly, Linnie M; Barany, Francis

2010-01-01

Infectious diseases account for between 14 and 17 million deaths worldwide each year. Accurate and rapid diagnosis of bacterial, fungal, viral, and parasitic infections is therefore essential to reduce the morbidity and mortality associated with these diseases. Classical microbiological and serological methods have long served as the gold standard for diagnosis but are increasingly being replaced by molecular diagnostic methods that demonstrate increased sensitivity and specificity and provide an identification of the etiologic agent in a shorter period of time. PCR/LDR coupled with universal array detection provides a highly sensitive and specific platform for the detection and identification of bacterial and viral infections.

PCR/LDR/Universal Array Platforms for the Diagnosis of Infectious Disease

PubMed Central

Pingle, Maneesh; Rundell, Mark; Das, Sanchita; Golightly, Linnie M.; Barany, Francis

2015-01-01

Infectious diseases account for between 14 and 17 million deaths worldwide each year. Accurate and rapid diagnosis of bacterial, fungal, viral, and parasitic infections is therefore essential to reduce the morbidity and mortality associated with these diseases. Classical microbiological and serological methods have long served as the gold standard for diagnosis but are increasingly being replaced by molecular diagnostic methods that demonstrate increased sensitivity and specificity and provide an identification of the etiologic agent in a shorter period of time. PCR/LDR coupled with universal array detection provides a highly sensitive and specific platform for the detection and identification of bacterial and viral infections. PMID:20217576

Significance of dual polarized long wavelength radar for terrain analysis

NASA Technical Reports Server (NTRS)

Macdonald, H. C.; Waite, W. P.

1978-01-01

Long wavelength systems with improved penetration capability have been considered to have the potential for minimizing the vegetation contribution and enhancing the surface return variations. L-band imagery of the Arkansas geologic test site provides confirmatory evidence of this effect. However, the increased wavelength increases the sensitivity to larger scale structure at relatively small incidence angles. The regularity of agricultural and urban scenes provides large components in the low frequency-large scale portion of the roughness spectrum that are highly sensitive to orientation. The addition of a cross polarized channel is shown to enable the interpreter to distinguish vegetation and orientational perturbations in the surface return.

Development of a 300,000-pixel ultrahigh-speed high-sensitivity CCD

NASA Astrophysics Data System (ADS)

Ohtake, H.; Hayashida, T.; Kitamura, K.; Arai, T.; Yonai, J.; Tanioka, K.; Maruyama, H.; Etoh, T. Goji; Poggemann, D.; Ruckelshausen, A.; van Kuijk, H.; Bosiers, Jan T.

2006-02-01

We are developing an ultrahigh-speed, high-sensitivity broadcast camera that is capable of capturing clear, smooth slow-motion videos even where lighting is limited, such as at professional baseball games played at night. In earlier work, we developed an ultrahigh-speed broadcast color camera1) using three 80,000-pixel ultrahigh-speed, highsensitivity CCDs2). This camera had about ten times the sensitivity of standard high-speed cameras, and enabled an entirely new style of presentation for sports broadcasts and science programs. Most notably, increasing the pixel count is crucially important for applying ultrahigh-speed, high-sensitivity CCDs to HDTV broadcasting. This paper provides a summary of our experimental development aimed at improving the resolution of CCD even further: a new ultrahigh-speed high-sensitivity CCD that increases the pixel count four-fold to 300,000 pixels.

Enhanced sensitivity for optical loss measurement in planar thin-films (Conference Presentation)

NASA Astrophysics Data System (ADS)

Yuan, Hua-Kang

2016-09-01

An organic-inorganic hybrid material benefits from processing advantages of organics and high refractive indices of inorganics. We focus on a titanium oxide hydrate system combined with common bulk polymers. In particular, we target thin-film structures of a few microns in thickness. Traditional Beer-Lambert approaches for measuring optical losses can only provide an upper limit estimate. This sensitivity is highly limited when considering the low-losses required for mid-range optical applications, on the order of 0.1 cm-1. For intensity based measurements, improving the sensitivity requires an increase in the optical path length. Instead, a new sensitive technique suitable for simple planar thin films is required. A number of systems were modelled to measure optical losses in films of 1 micron thick. The presented techniques utilise evanescent waves and total internal reflection to increase optical path length through the material. It was found that a new way of using prism coupling provides the greatest improvement in sensitivity. In keeping the requirements on the material simple, this method for measuring loss is well suited to any future developments of new materials in thin-film structures.

Protein detection system

DOEpatents

Fruetel, Julie A [Livermore, CA; Fiechtner, Gregory J [Bethesda, MD; Kliner, Dahv A. V. [San Ramon, CA; McIlroy, Andrew [Livermore, CA

2009-05-05

The present embodiment describes a miniature, microfluidic, absorption-based sensor to detect proteins at sensitivities comparable to LIF but without the need for tagging. This instrument utilizes fiber-based evanescent-field cavity-ringdown spectroscopy, in combination with faceted prism microchannels. The combination of these techniques will increase the effective absorption path length by a factor of 10.sup.3 to 10.sup.4 (to .about.1-m), thereby providing unprecedented sensitivity using direct absorption. The coupling of high-sensitivity absorption with high-performance microfluidic separation will enable real-time sensing of biological agents in aqueous samples (including aerosol collector fluids) and will provide a general method with spectral fingerprint capability for detecting specific bio-agents.

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

Ritter, Boyd

Insensitive high explosives (IHEs) based on 1,3,5-triamino 2,4,6-trinitro-benzene (TATB) are the IHEs of choice for use in nuclear warheads over conventional high explosives when safety is the only consideration, because they are very insensitive to thermal or mechanical initiation stimuli. It is this inherent insensitivity to high temperatures, shock, and impact, which provides detonation design challenges when designing TATB explosive systems while at the same time providing a significant level of protection against accidental initiation. Although classified as IHE, over the past few years the focus on explosive safety has demonstrated that the shock sensitivity of TATB is influenced withmore » respect to temperature. A number of studies have been performed on TATB and TATB formulations, plastic bonded explosives (PBX) 9502, and LX-17-01 (LX-17), which demonstrates the increase in shock sensitivity of the explosive after it has been preheated or thermally cycled over various temperature ranges. Many studies suggest the change in sensitivity is partly due to the decomposition rates of the temperature elevated TATB. Others point to the coefficient of thermal expansion, the crystalline structures of TATB and/or the combination of all factors, which create voids which can become active hot spots. During thermal cycling, TATB is known to undergo an irreversible increase in specific volume called ratchet growth. This increase in specific volume correlates to a decrease in density. This decrease in density and increase in volume, demonstrate the creations of additional void spaces which could serve as potential new initiation hot spots thus, increasing the overall sensitivity of the HE. This literature review evaluates the published works to understand why the shock sensitivity of TATB-based plastic bonded explosives (PBXs) changes with temperature.« less

Noninvasive and cost-effective trapping method for monitoring sensitive mammal populations

Treesearch

Stephanie E. Trapp; Elizabeth A. Flaherty

2017-01-01

Noninvasive sampling methods provide a means to monitor endangered, threatened, or sensitive species or populations while increasing the efficacy of personnel effort and time. We developed a monitoring protocol that utilizes single-capture hair snares and analysis of morphological features of hair for evaluating populations. During 2015, we used the West Virginia...

Understanding the Culture of Chinese Children and Families

ERIC Educational Resources Information Center

Cheung, Ruth; Nelson, Warren; Advincula, Luzelle; Cureton, Virginia Young; Canham, Daryl L.

2005-01-01

Providing appropriate health care to a client can be accomplished only in an environment that is sensitive to the cultural values and beliefs of the client. As the population of first-and second-generation Chinese immigrants increases in the United States, the need to develop culturally sensitive health care becomes significant. Chinese immigrants…

[Lethal anaphylactic shock model induced by human mixed serum in guinea pigs].

PubMed

Ren, Guang-Mu; Bai, Ji-Wei; Gao, Cai-Rong

2005-08-01

To establish an anaphylactic shock model induced by human mixed serum in guinea pigs. Eighteen guinea pigs were divided into two groups: sensitized and control, The sensitized group were immunized intracutaneously with human mixed serum and then induced by endocardiac injection after 3 weeks. Symptoms of anaphylactic shock appeared in the sensitized group. The level of serum IgE were increased in the sensitized group significantly. An animal model of anaphylactic shock wer established successfully. It provide a tool for both forensic study and anaphylactic shock therapy.

Fish wariness is a more sensitive indicator to changes in fishing pressure than abundance, length or biomass.

PubMed

Goetze, Jordan S; Januchowski-Hartley, Fraser A; Claudet, Joachim; Langlois, Tim J; Wilson, Shaun K; Jupiter, Stacy D

2017-06-01

Identifying the most sensitive indicators to changes in fishing pressure is important for accurately detecting impacts. Biomass is thought to be more sensitive than abundance and length, while the wariness of fishes is emerging as a new metric. Periodically harvested closures (PHCs) that involve the opening and closing of an area to fishing are the most common form of fisheries management in the western Pacific. The opening of PHCs to fishing provides a unique opportunity to compare the sensitivity of metrics, such as abundance, length, biomass and wariness, to changes in fishing pressure. Diver-operated stereo video (stereo-DOV) provides data on fish behavior (using a proxy for wariness, minimum approach distance) simultaneous to abundance and length estimates. We assessed the impact of PHC protection and harvesting on the abundance, length, biomass, and wariness of target species using stereo-DOVs. This allowed a comparison of the sensitivity of these metrics to changes in fishing pressure across four PHCs in Fiji, where spearfishing and fish drives are common. Before PHCs were opened to fishing they consistently decreased the wariness of targeted species but were less likely to increase abundance, length, or biomass. Pulse harvesting of PHCs resulted in a rapid increase in the wariness of fishes but inconsistent impacts across the other metrics. Our results suggest that fish wariness is the most sensitive indicator of fishing pressure, followed by biomass, length, and abundance. The collection of behavioral data simultaneously with abundance, length, and biomass estimates using stereo-DOVs offers a cost-effective indicator of protection or rapid increases in fishing pressure. Stereo-DOVs can rapidly provide large amounts of behavioral data from monitoring programs historically focused on estimating abundance and length of fishes, which is not feasible with visual methods. © 2017 by the Ecological Society of America.

Experimental Investigation of a Piezo-Optical Transducer for Highly Sensitive Strain Gauges

NASA Astrophysics Data System (ADS)

Paulish, A. G.; Zagubisalo, P. S.; Barakov, V. N.; Pavlov, M. A.

2018-03-01

The characteristics of a piezo-optical transducer of a new design with high strain sensitivity at compact size have been studied.The original form of the photoelastic element provides a considerable increase in the stress in its working area at a given external force, resulting in an increase in the sensitivity of the transducer. The main characteristics of the transducer were measured using a specially designed device. The strain at a given applied force was calculated using a developed mathematical model of the transducer. As a result, the sensitivity to the relative strain was Δ x/ x=3 · 10-10, the dynamic range was at least four orders of magnitude higher and the gauge factor three orders of magnitude higher than those of strain-resistive gauges.

Attenuation of soil microwave emissivity by corn and soybeans at 1.4 and 5 GHz

NASA Technical Reports Server (NTRS)

Jackson, Thomas J.; O'Neill, Peggy E.

1989-01-01

Theory and experiments have shown that passive microwave radiometers can be used to measure soil moisture. However, the presence of a vegetative cover alters the measurement that might be obtained under bare conditions. Deterministically accounting for the effect of vegetation and developing algorithms for extracting soil moisture from observations of a vegetable-soil complex present significant obstacles to the practical use of this approach. The presence of a vegetation canopy reduces the sensitivity of passive microwave instruments to soil moisture variations. The reduction in sensitivity, as compared to a bare-soil relationship, increases as microwave frequency increases, implying that the longest wavelength sensors should provide the most information. Sensitivity also decreases as the amount of vegetative wet biomass increases for a given type of vegetation.

An Interprofessional Education Project to Address Veterans' Healthcare Needs

ERIC Educational Resources Information Center

Peterson, Jane; Brommelsiek, Margaret; Amelung, Sarah Knopf

2017-01-01

Background/Objective: The number of veterans and their families seeking healthcare and support within civilian communities is increasing worldwide. There is a need for healthcare providers to provide sensitive, comprehensive care for veterans with both physical and behavioral health conditions. Many civilian providers are unfamiliar with veterans'…

Serine Protease Zymography: Low-Cost, Rapid, and Highly Sensitive RAMA Casein Zymography.

PubMed

Yasumitsu, Hidetaro

2017-01-01

To detect serine protease activity by zymography, casein and CBB stain have been used as a substrate and a detection procedure, respectively. Casein zymography has been using substrate concentration at 1 mg/mL and employing conventional CBB stain. Although ordinary casein zymography provides reproducible results, it has several disadvantages including time-consuming and relative low sensitivity. Improved casein zymography, RAMA casein zymography, is rapid and highly sensitive. RAMA casein zymography completes the detection process within 1 h after incubation and increases the sensitivity at least by tenfold. In addition to serine protease, the method also detects metalloprotease 7 (MMP7, Matrilysin) with high sensitivity.

Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides.

PubMed

Lázár, Viktória; Martins, Ana; Spohn, Réka; Daruka, Lejla; Grézal, Gábor; Fekete, Gergely; Számel, Mónika; Jangir, Pramod K; Kintses, Bálint; Csörgő, Bálint; Nyerges, Ákos; Györkei, Ádám; Kincses, András; Dér, András; Walter, Fruzsina R; Deli, Mária A; Urbán, Edit; Hegedűs, Zsófia; Olajos, Gábor; Méhi, Orsolya; Bálint, Balázs; Nagy, István; Martinek, Tamás A; Papp, Balázs; Pál, Csaba

2018-06-01

Antimicrobial peptides are promising alternative antimicrobial agents. However, little is known about whether resistance to small-molecule antibiotics leads to cross-resistance (decreased sensitivity) or collateral sensitivity (increased sensitivity) to antimicrobial peptides. We systematically addressed this question by studying the susceptibilities of a comprehensive set of 60 antibiotic-resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic-resistant bacteria show a high frequency of collateral sensitivity to antimicrobial peptides, whereas cross-resistance is relatively rare. We identify clinically relevant multidrug-resistance mutations that increase bacterial sensitivity to antimicrobial peptides. Collateral sensitivity in multidrug-resistant bacteria arises partly through regulatory changes shaping the lipopolysaccharide composition of the bacterial outer membrane. These advances allow the identification of antimicrobial peptide-antibiotic combinations that enhance antibiotic activity against multidrug-resistant bacteria and slow down de novo evolution of resistance. In particular, when co-administered as an adjuvant, the antimicrobial peptide glycine-leucine-amide caused up to 30-fold decrease in the antibiotic resistance level of resistant bacteria. Our work provides guidelines for the development of efficient peptide-based therapies of antibiotic-resistant infections.

Effects of inflammation on social processes and implications for health.

PubMed

Moieni, Mona; Eisenberger, Naomi I

2018-05-28

Although at first glance inflammation and social behavior may appear unrelated, research points to an important role for inflammation in shaping social processes. This review summarizes findings in this field, specifically highlighting work that provides support for the idea that inflammation can lead to (1) increases in sensitivity to negative, threatening social experiences and (2) increases in sensitivity to positive, socially rewarding experiences. These diverging sensitivities in response to inflammation may depend on context and be adaptive for recuperation and recovery from illness. This review also discusses the implications of these findings for health and future research, including implications for depression, loneliness, and inflammatory disorders. © 2018 New York Academy of Sciences.

Sensitivity of resonant tunneling diode photodetectors.

PubMed

Pfenning, Andreas; Hartmann, Fabian; Langer, Fabian; Kamp, Martin; Höfling, Sven; Worschech, Lukas

2016-09-02

We have studied the sensitivity of AlGaAs/GaAs double barrier resonant tunneling diode photodetectors with an integrated GaInNAs absorption layer for light sensing at the telecommunication wavelength of λ = 1.3 μm for illumination powers from pico- to microwatts. The sensitivity decreases nonlinearly with power. An illumination power increase of seven orders of magnitude leads to a reduction of the photocurrent sensitivity from S I  = 5.82 × 10(3) A W(-1) to 3.2 A W(-1). We attribute the nonlinear sensitivity-power dependence to an altered local electrostatic potential due to hole-accumulation that on the one hand tunes the tunneling current, but on the other hand affects the lifetime of photogenerated holes. In particular, the lifetime decreases exponentially with increasing hole population. The lifetime reduction results from an enhanced electrical field, a rise of the quasi-Fermi level, and an increased energy splitting within the triangular potential well. The non-constant sensitivity is a direct result of the non-constant lifetime. Based on these findings, we provide an expression that allows us to calculate the sensitivity as a function of illumination power and bias voltage, show a way to model the time-resolved photocurrent, and determine the critical power up to which the resonant tunneling diode photodetector sensitivity can be assumed constant.

O2 Plasma Etching and Antistatic Gun Surface Modifications for CNT Yarn Microelectrode Improve Sensitivity and Antifouling Properties.

PubMed

Yang, Cheng; Wang, Ying; Jacobs, Christopher B; Ivanov, Ilia N; Venton, B Jill

2017-05-16

Carbon nanotube (CNT) based microelectrodes exhibit rapid and selective detection of neurotransmitters. While different fabrication strategies and geometries of CNT microelectrodes have been characterized, relatively little research has investigated ways to selectively enhance their electrochemical properties. In this work, we introduce two simple, reproducible, low-cost, and efficient surface modification methods for carbon nanotube yarn microelectrodes (CNTYMEs): O 2 plasma etching and antistatic gun treatment. O 2 plasma etching was performed by a microwave plasma system with oxygen gas flow and the optimized time for treatment was 1 min. The antistatic gun treatment flows ions by the electrode surface; two triggers of the antistatic gun was the optimized number on the CNTYME surface. Current for dopamine at CNTYMEs increased 3-fold after O 2 plasma etching and 4-fold after antistatic gun treatment. When the two treatments were combined, the current increased 12-fold, showing the two effects are due to independent mechanisms that tune the surface properties. O 2 plasma etching increased the sensitivity due to increased surface oxygen content but did not affect surface roughness while the antistatic gun treatment increased surface roughness but not oxygen content. The effect of tissue fouling on CNT yarns was studied for the first time, and the relatively hydrophilic surface after O 2 plasma etching provided better resistance to fouling than unmodified or antistatic gun treated CNTYMEs. Overall, O 2 plasma etching and antistatic gun treatment improve the sensitivity of CNTYMEs by different mechanisms, providing the possibility to tune the CNTYME surface and enhance sensitivity.

On the Exploitation of Sensitivity Derivatives for Improving Sampling Methods

NASA Technical Reports Server (NTRS)

Cao, Yanzhao; Hussaini, M. Yousuff; Zang, Thomas A.

2003-01-01

Many application codes, such as finite-element structural analyses and computational fluid dynamics codes, are capable of producing many sensitivity derivatives at a small fraction of the cost of the underlying analysis. This paper describes a simple variance reduction method that exploits such inexpensive sensitivity derivatives to increase the accuracy of sampling methods. Three examples, including a finite-element structural analysis of an aircraft wing, are provided that illustrate an order of magnitude improvement in accuracy for both Monte Carlo and stratified sampling schemes.

Hydrogen Sulfide Treatment Promotes Glucose Uptake by Increasing Insulin Receptor Sensitivity and Ameliorates Kidney Lesions in Type 2 Diabetes

PubMed Central

Xue, Rong; Hao, Dan-Dan; Sun, Ji-Ping; Li, Wen-Wen; Zhao, Man-Man; Li, Xing-Hui; Chen, Ying; Zhu, Jian-Hua; Ding, Ying-Jiong; Liu, Jun

2013-01-01

Abstract Aims: To examine if hydrogen sulfide (H2S) can promote glucose uptake and provide amelioration in type 2 diabetes. Results: Treatment with sodium hydrosulfide (NaHS, an H2S donor) increased glucose uptake in both myotubes and adipocytes. The H2S gas solution showed similar effects. The NaHS effects were blocked by an siRNA-mediated knockdown of the insulin receptor (IR). NaHS also increased phosphorylation of the IR, PI3K, and Akt. In Goto-Kakizaki (GK) diabetic rats, chronic NaHS treatment (30 μmol·kg−1·day−1) decreased fasting blood glucose, increased insulin sensitivity, and increased glucose tolerance with increased phosphorylation of PI3K and Akt in muscles. Similar insulin-sensitizing effects of NaHS treatment were also observed in Wistar rats. Moreover, glucose uptake was reduced in the cells with siRNA-mediated knockdown of the H2S-generating enzyme cystathionine γ-lyase in the presence or absence of exogenous H2S. Moreover, chronic NaHS treatment reduced oxygen species and the number of crescentic glomeruli in the kidney of GK rats. Innovation and Conclusion: This study provides the first piece of evidence for the insulin-sensitizing effect of NaHS/H2S in the both in vitro and in vivo models of insulin resistance. Rebound Track: This work was rejected during a standard peer review and rescued by the Rebound Peer Review (Antoxid Redox Signal 16: 293–296, 2012) with the following serving as open reviewers: Jin-Song Bian, Samuel Dudley, Hideo Kimura, and Xian Wang. Antioxid. Redox Signal. 19, 5–23. PMID:23293908

Niacin Skin Sensitivity Is Increased in Adolescents at Ultra-High Risk for Psychosis

PubMed Central

Schäfer, Miriam R.; Milleit, Berko; Langbein, Kerstin; Hipler, Uta-Christina; Milleit, Christine; Klier, Claudia M.; Schlögelhofer, Monika; Holub, Magdalena; Holzer, Ingrid; Berk, Michael; McGorry, Patrick D.; Sauer, Heinrich; Amminger, G. Paul

2016-01-01

Background Most studies provide evidence that the skin flush response to nicotinic acid (niacin) stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR) phase of psychotic disorders. Methods We compared visual ratings of niacin sensitivity between adolescents at UHR for psychosis according to the one year transition outcome (UHR-T n = 11; UHR-NT n = 55) with healthy controls (HC n = 25) and first episode schizophrenia patients (FEP n = 25) treated with atypical antipsychotics. Results Contrary to our hypothesis niacin sensitivity of the entire UHR group was not attenuated, but significantly increased compared to the HC group, whereas no difference could be found between the UHR-T and UHR-NT groups. As expected, niacin sensitivity of FEP was attenuated compared to HC group. In UHR individuals niacin sensitivity was inversely correlated with omega-6 and -9 fatty acids (FA), but positively correlated with phospholipase A2 (inPLA2) activity, a marker of membrane lipid repair/remodelling. Conclusions Increased niacin sensitivity in UHR states likely indicates an impaired balance of eicosanoids and omega-6/-9 FA at a membrane level. Our findings suggest that the emergence of psychosis is associated with an increased mobilisation of eicosanoids prior to the transition to psychosis possibly reflecting a “pro-inflammatory state”, whereas thereafter eicosanoid mobilisation seems to be attenuated. Potential treatment implications for the UHR state should be further investigated. PMID:26894921

Salt-Sensitive Hypertension: Perspectives on Intrarenal Mechanisms

PubMed Central

Majid, Dewan S.A.; Prieto, Minolfa C.; Navar, L Gabriel

2015-01-01

Salt sensitive hypertension is characterized by increases in blood pressure in response to increases in dietary salt intake and is associated with an enhanced risk of cardiovascular and renal morbidity. Although researchers have sought for decades to understand how salt sensitivity develops in humans, the mechanisms responsible for the increases in blood pressure in response to high salt intake are complex and only partially understood. Until now, scientists have been unable to explain why some individuals are salt sensitive and others are salt resistant. Although a central role for the kidneys in the development of salt sensitivity and hypertension has been generally accepted, it is also recognized that hypertension is of multifactorial origin and a variety of factors can induce, or prevent, blood pressure responsiveness to the manipulation of salt intake. Excess salt intake in susceptible persons may also induce inappropriate central and sympathetic nervous system responses and increase the production of intrarenal angiotensin II, catecholamines and other factors such as oxidative stress and inflammatory cytokines. One key factor is the concomitant inappropriate or paradoxical activation of the intrarenal renin-angiotensin system, by high salt intake. This is reflected by the increases in urinary angiotensinogen during high salt intake in salt sensitive models. A complex interaction between neuroendocrine factors and the kidney may underlie the propensity for some individuals to retain salt and develop salt-dependent hypertension. In this review, we focus mainly on the renal contributions that provide the mechanistic link between chronic salt intake and the development of hypertension. PMID:26028244

Improving the Quality of Basic Education through the Use of Gender-Sensitive Student Councils: Experience of Six Selected Districts in Tanzania

ERIC Educational Resources Information Center

Mnubi, Godfrey Magoti

2017-01-01

This paper analyses whether the gender-sensitive and democratically elected student councils helped in strengthening school leadership and providing a platform for increased awareness and advocacy for male and female students to address their needs and rights in primary and secondary schools in Tanzania. The data were collected through qualitative…

Theoretical studies on effective metal-to-ligand charge transfer characteristics of novel ruthenium dyes for dye sensitized solar cells.

PubMed

Wang, Huei-Tang; Taufany, Fadlilatul; Nachimuthu, Santhanamoorthi; Jiang, Jyh-Chiang

2014-05-01

The development of ruthenium dye-sensitizers with highly effective metal-to-ligand charge transfer (MLCT) characteristics and narrowed transition energy gaps are essential for the new generation of dye-sensitized solar cells. Here, we designed a novel anchoring ligand by inserting the cyanovinyl-branches inside the anchoring ligands of selected highly efficient dye-sensitizers and studied their intrinsic optical properties using theoretical methods. Our calculated results show that the designed ruthenium dyes provide good performances as sensitizers compared to the selected efficient dyes, because of their red-shift in the UV-visible absorption spectra with an increase in the absorption intensity, smaller energy gaps and thereby enhancing MLCT transitions. We found that, the designed anchoring ligand acts as an efficient "electron-acceptor" which boosts electron-transfer from a -NCS ligand to this ligand via a Ru-bridge, thus providing a way to lower the transition energy gap and enhance the MLCT transitions.

The lethal interaction of x ray and penicillin induced lesions following x-irradiation of Escherichia coli B/r in the presence of hypoxic cell sensitizers

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

Gillies, N.E.; Obioha, F.I.

When Escherichia coli B/r were x-irradiated under anoxia in the presence of different electron-affinic sensitizers and then incubated in broth containing penicillin (at a concentration that did not kill unirradiated cells) additional killing of the bacteria occurred provided the sensitizers were of relatively high lipophilicity. The overall effect was to increase the efficiency of these sensitizers. It is concluded that sensitizer-dependent latent radiation lesions(s) are produced in membrane components of the cell envelope that interact with damage caused by penicillin in the peptidoglycan layer and this causes the additional lethality.

Influence of changing water sources and mineral chemistry on the everglades ecosystem

USGS Publications Warehouse

McCormick, P.V.; Harvey, J.W.; Crawford, E.S.

2011-01-01

Human influences during the previous century increased mineral inputs to the Florida Everglades by changing the sources and chemistry of surface inflows. Biogeochemical responses to this enrichment include changes in the availability of key limiting nutrients such as P, the potential for increased turnover of nutrient pools due to accelerated plant decomposition, and increased rates of mercury methylation associated with sulfate enrichment. Mineral enrichment has also been linked to the loss of sensitive macrophyte species, although dominant Everglades species appear tolerant of a broad range of mineral chemistry. Shifts in periphyton community composition and function provide an especially sensitive indicator of mineral enrichment. Understanding the influence of mineral chemistry on Everglades processes and biota may improve predictions of ecosystem responses to ongoing hydrologic restoration efforts and provide guidelines for protecting remaining mineral-poor areas of this peatland. Copyright ?? 2011 Taylor & Francis Group, LLC.

Pressure and cold pain threshold reference values in a large, young adult, pain-free population.

PubMed

Waller, Robert; Smith, Anne Julia; O'Sullivan, Peter Bruce; Slater, Helen; Sterling, Michele; McVeigh, Joanne Alexandra; Straker, Leon Melville

2016-10-01

Currently there is a lack of large population studies that have investigated pain sensitivity distributions in healthy pain free people. The aims of this study were: (1) to provide sex-specific reference values of pressure and cold pain thresholds in young pain-free adults; (2) to examine the association of potential correlates of pain sensitivity with pain threshold values. This study investigated sex specific pressure and cold pain threshold estimates for young pain free adults aged 21-24 years. A cross-sectional design was utilised using participants (n=617) from the Western Australian Pregnancy Cohort (Raine) Study at the 22-year follow-up. The association of site, sex, height, weight, smoking, health related quality of life, psychological measures and activity with pain threshold values was examined. Pressure pain threshold (lumbar spine, tibialis anterior, neck and dorsal wrist) and cold pain threshold (dorsal wrist) were assessed using standardised quantitative sensory testing protocols. Reference values for pressure pain threshold (four body sites) stratified by sex and site, and cold pain threshold (dorsal wrist) stratified by sex are provided. Statistically significant, independent correlates of increased pressure pain sensitivity measures were site (neck, dorsal wrist), sex (female), higher waist-hip ratio and poorer mental health. Statistically significant, independent correlates of increased cold pain sensitivity measures were, sex (female), poorer mental health and smoking. These data provide the most comprehensive and robust sex specific reference values for pressure pain threshold specific to four body sites and cold pain threshold at the dorsal wrist for young adults aged 21-24 years. Establishing normative values in this young age group is important given that the transition from adolescence to adulthood is a critical temporal period during which trajectories for persistent pain can be established. These data will provide an important research resource to enable more accurate profiling and interpretation of pain sensitivity in clinical pain disorders in young adults. The robust and comprehensive data can assist interpretation of future clinical pain studies and provide further insight into the complex associations of pain sensitivity that can be used in future research. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

High sensitive reflection type long period fiber grating biosensor for real time detection of thyroglobulin, a differentiated thyroid cancer biomarker: the Smart Health project

NASA Astrophysics Data System (ADS)

Quero, G.; Severino, R.; Vaiano, P.; Consales, M.; Ruvo, M.; Sandomenico, A.; Borriello, A.; Giordano, M.; Zuppolini, S.; Diodato, L.; Cutolo, A.; Cusano, A.

2015-09-01

We report the development of a reflection-type long period fiber grating (LPG) biosensor able to perform the real time detection of thyroid cancer markers in the needle washout of fine-needle aspiration biopsy. A standard LPG is first transformed in a practical probe working in reflection mode, then it is coated by an atactic-polystyrene overlay in order to increase its surrounding refractive index sensitivity and to provide, at the same time, the desired interfacial properties for a stable bioreceptor immobilization. The results provide a clear demonstration of the effectiveness and sensitivity of the developed biosensing platform, allowing the in vitro detection of human Thyroglobulin at sub-nanomolar concentrations.

Increased alignment sensitivity improves the usage of genome alignments for comparative gene annotation.

PubMed

Sharma, Virag; Hiller, Michael

2017-08-21

Genome alignments provide a powerful basis to transfer gene annotations from a well-annotated reference genome to many other aligned genomes. The completeness of these annotations crucially depends on the sensitivity of the underlying genome alignment. Here, we investigated the impact of the genome alignment parameters and found that parameters with a higher sensitivity allow the detection of thousands of novel alignments between orthologous exons that have been missed before. In particular, comparisons between species separated by an evolutionary distance of >0.75 substitutions per neutral site, like human and other non-placental vertebrates, benefit from increased sensitivity. To systematically test if increased sensitivity improves comparative gene annotations, we built a multiple alignment of 144 vertebrate genomes and used this alignment to map human genes to the other 143 vertebrates with CESAR. We found that higher alignment sensitivity substantially improves the completeness of comparative gene annotations by adding on average 2382 and 7440 novel exons and 117 and 317 novel genes for mammalian and non-mammalian species, respectively. Our results suggest a more sensitive alignment strategy that should generally be used for genome alignments between distantly-related species. Our 144-vertebrate genome alignment and the comparative gene annotations (https://bds.mpi-cbg.de/hillerlab/144VertebrateAlignment_CESAR/) are a valuable resource for comparative genomics. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Background odour induces adaptation and sensitization of olfactory receptors in the antennae of houseflies.

PubMed

Kelling, F J; Ialenti, F; Den Otter, C J

2002-06-01

The presence of background odour was found to have a small but significant effect on the sensitivity of the antennal olfactory system of houseflies, Musca domestica Linnaeus (Diptera: Muscidae), to new pulses of odour. We show that cross-adaptation and cross-sensitization between a background odour of (+/-)-1-octen-3-ol and pulses of (+/-)-1-octen-3-ol, 2-pentanone and R-(+)-limonene can occur, confirming that olfactory receptor cells are sensitive to different odours. Background odour can increase the responses to low concentration odour pulses and decrease the responses to higher concentration odour pulses. It is suggested that background odour has a larger effect on olfactory receptor cells that respond with a tonic increase of spike frequency, giving information about the level of odour concentration, i.e. the 'static' environment. Cells that respond in a phasic way only provide information on the dynamics of the olfactory environment.

The impact of cultural diversity forum on students' openness to diversity.

PubMed

Sanner, Susan; Baldwin, Dee; Cannella, Kathleen A S; Charles, Jennell; Parker, Lillian

2010-01-01

As the population demographics for the United States (U.S.) shift towards increasing diversity, it is essential that nurses provide culturally competent care. Cultural sensitivity has been identified as a major curricular element in the American Association of Colleges of Nursing's (AACN) The Essentials of Baccalaureate Education for Professional Nursing Practice. Thus it is imperative that nursing faculty use effective strategies to help nursing students develop cultural sensitivity and competence. Educational workshops focusing on cultural diversity are usually designed to increase people's cultural sensitivity. The purpose of this study was to assess the effectiveness of a cultural diversity forum on nursing students' cultural sensitivity as measured by their openness to diversity. A convenience sample of students was recruited from a public university in the southeastern United States. The workshop was designed as a forum that combined a keynote presentation, shared meal, and a small group interactional activity. Cultural sensitivity was measured using the Openness to Diversity/Challenge Scale (ODCS), and was administered to students before and after the forum. A convenience sample of 47 students agreed to participate and completed both the pretest and posttest. Following the workshop, the students had more cultural sensitivity as measured by their scores on the ODCS (Wilcoxin Signed-Rank test z= -3.286, p = 0.001). The findings suggested that an educational format like the cultural diversity forum can promote students' cultural sensitivity. Further research needs to continue to focus on the effectiveness of strategies to increase the cultural sensitivity of baccalaureate nursing students.

Basic design of MRM assays for peptide quantification.

PubMed

James, Andrew; Jorgensen, Claus

2010-01-01

With the recent availability and accessibility of mass spectrometry for basic and clinical research, the requirement for stable, sensitive, and reproducible assays to specifically detect proteins of interest has increased. Multiple reaction monitoring (MRM) or selective reaction monitoring (SRM) is a highly selective, sensitive, and robust assay to monitor the presence and amount of biomolecules. Until recently, MRM was typically used for the detection of drugs and other biomolecules from body fluids. With increased focus on biomarkers and systems biology approaches, researchers in the proteomics field have taken advantage of this approach. In this chapter, we will introduce the reader to the basic principle of designing and optimizing an MRM workflow. We provide examples of MRM workflows for standard proteomic samples and provide suggestions for the reader who is interested in using MRM for quantification.

Characterization of image heterogeneity using 2D Minkowski functionals increases the sensitivity of detection of a targeted MRI contrast agent.

PubMed

Canuto, Holly C; McLachlan, Charles; Kettunen, Mikko I; Velic, Marko; Krishnan, Anant S; Neves, Andre' A; de Backer, Maaike; Hu, D-E; Hobson, Michael P; Brindle, Kevin M

2009-05-01

A targeted Gd(3+)-based contrast agent has been developed that detects tumor cell death by binding to the phosphatidylserine (PS) exposed on the plasma membrane of dying cells. Although this agent has been used to detect tumor cell death in vivo, the differences in signal intensity between treated and untreated tumors was relatively small. As cell death is often spatially heterogeneous within tumors, we investigated whether an image analysis technique that parameterizes heterogeneity could be used to increase the sensitivity of detection of this targeted contrast agent. Two-dimensional (2D) Minkowski functionals (MFs) provided an automated and reliable method for parameterization of image heterogeneity, which does not require prior assumptions about the number of regions or features in the image, and were shown to increase the sensitivity of detection of the contrast agent as compared to simple signal intensity analysis. (c) 2009 Wiley-Liss, Inc.

Complement activation and liver impairment in trichloroethylene-sensitized BALB/c mice.

PubMed

Zhang, Jiaxiang; Zha, Wansheng; Wang, Feng; Jiang, Tao; Xu, Shuhai; Yu, Junfeng; Zhou, Chengfan; Shen, Tong; Wu, Changhao; Zhu, Qixing

2013-01-01

Our recent studies have shown that trichloroethylene (TCE) was able to induce multisystem injuries in the form of occupational medicamentosa-like dermatitis, including skin, kidney, and liver damages. However, the role of complement activation in the immune-mediated liver injury is not known. This study examined the role of complement activation in the liver injury in a mouse model of TCE-induced sensitization. Treatment of female BALB/c mice with TCE under specific dosing protocols resulted in skin inflammation and sensitization. Skin edema and erythema occurred in TCE-sensitized groups. Trichloroethylene sensitization produced liver histopathological lesions, increased serum alanine aminotransferase, aspartate transaminase activities, and the relative liver weight. The concentrations of serum complement components C3a-desArg, C5a-desArg, and C5b-9 were significantly increased in 24-hour, 48-hour, and 72-hour sensitization-positive groups treated with TCE and peaked in the 72-hour sensitization-positive group. Depositions of C3a, C5a, and C5b-9 into the liver tissue were also revealed by immunohistochemistry. Immunofluorescence further verified high C5b-9 expression in 24-hour, 48-hour, and 72-hour sensitization-positive groups in response to TCE treatment. Reverse transcription-polymerase chain reaction detected C3 messenger RNA expression in the liver, and this was significantly increased in 24-hour and 48-hour sensitization-positive groups with a transient reduction at 72 hours. These results provide the first experimental evidence that complement activation may play a key role in the generation and progression of immune-mediated hepatic injury by exposure to TCE.

An Initial Study of the Sensitivity of Aircraft Vortex Spacing System (AVOSS) Spacing Sensitivity to Weather and Configuration Input Parameters

NASA Technical Reports Server (NTRS)

Riddick, Stephen E.; Hinton, David A.

2000-01-01

A study has been performed on a computer code modeling an aircraft wake vortex spacing system during final approach. This code represents an initial engineering model of a system to calculate reduced approach separation criteria needed to increase airport productivity. This report evaluates model sensitivity toward various weather conditions (crosswind, crosswind variance, turbulent kinetic energy, and thermal gradient), code configurations (approach corridor option, and wake demise definition), and post-processing techniques (rounding of provided spacing values, and controller time variance).

Educating Gerontologists for Cultural Proficiency in End-of-Life Care Practice

ERIC Educational Resources Information Center

Stein, Gary L.; Sherman, Patricia A.; Bullock, Karen

2009-01-01

An educational program was developed to train practitioners to provide care for patients and families that are responsive to cultural concerns. The aim was to increase knowledge and improve attitudes toward providing culturally proficient and culturally sensitive care for patients and families facing life-threatening illnesses. The program…

Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans

PubMed Central

Stanhope, Kimber L.; Schwarz, Jean Marc; Keim, Nancy L.; Griffen, Steven C.; Bremer, Andrew A.; Graham, James L.; Hatcher, Bonnie; Cox, Chad L.; Dyachenko, Artem; Zhang, Wei; McGahan, John P.; Seibert, Anthony; Krauss, Ronald M.; Chiu, Sally; Schaefer, Ernst J.; Ai, Masumi; Otokozawa, Seiko; Nakajima, Katsuyuki; Nakano, Takamitsu; Beysen, Carine; Hellerstein, Marc K.; Berglund, Lars; Havel, Peter J.

2009-01-01

Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle–triglyceride and –cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults. PMID:19381015

The Gaussian atmospheric transport model and its sensitivity to the joint frequency distribution and parametric variability.

PubMed

Hamby, D M

2002-01-01

Reconstructed meteorological data are often used in some form of long-term wind trajectory models for estimating the historical impacts of atmospheric emissions. Meteorological data for the straight-line Gaussian plume model are put into a joint frequency distribution, a three-dimensional array describing atmospheric wind direction, speed, and stability. Methods using the Gaussian model and joint frequency distribution inputs provide reasonable estimates of downwind concentration and have been shown to be accurate to within a factor of four. We have used multiple joint frequency distributions and probabilistic techniques to assess the Gaussian plume model and determine concentration-estimate uncertainty and model sensitivity. We examine the straight-line Gaussian model while calculating both sector-averaged and annual-averaged relative concentrations at various downwind distances. The sector-average concentration model was found to be most sensitive to wind speed, followed by horizontal dispersion (sigmaZ), the importance of which increases as stability increases. The Gaussian model is not sensitive to stack height uncertainty. Precision of the frequency data appears to be most important to meteorological inputs when calculations are made for near-field receptors, increasing as stack height increases.

Bioengineering bacteriophages to enhance the sensitivity of phage amplification-based paper fluidic detection of bacteria.

PubMed

Alcaine, S D; Law, K; Ho, S; Kinchla, A J; Sela, D A; Nugen, S R

2016-08-15

Bacteriophage (phage) amplification is an attractive method for the detection of bacteria due to a narrow phage-host specificity, short amplification times, and the phages' ability to differentiate between viable and non-viable bacterial cells. The next step in phage-based bacteria detection is leveraging bioengineered phages to create low-cost, rapid, and easy-to-use detection platforms such as lateral flow assays. Our work establishes the proof-of-concept for the use of bioengineered T7 phage strains to increase the sensitivity of phage amplification-based lateral flow assays. We have demonstrated a greater than 10-fold increase in sensitivity using a phage-based protein reporter, maltose-binding protein, over the detection of replicated T7 phage viron itself, and a greater then 100-fold increase in sensitivity using a phage-based enzymatic reporter, alkaline phosphatase. This increase in sensitivity enabled us to detect 10(3)CFU/mL of Escherichia coli in broth after 7h, and by adding a filter concentration step, the ability to detect a regulatory relevant E. coli concentration of 100CFU/100mL in inoculated river water after 9h, where the current standard requires days for results. The combination of the paper fluidic format with phage-based detection provides a platform for the development of novel diagnostics that are sensitive, rapid, and easy to use. Copyright © 2016 Elsevier B.V. All rights reserved.

Cervical Cancer Screening in Low-Resource Settings: A Cost-Effectiveness Framework for Valuing Tradeoffs between Test Performance and Program Coverage

PubMed Central

Campos, Nicole G.; Castle, Philip E.; Wright, Thomas C.; Kim, Jane J.

2016-01-01

As cervical cancer screening programs are implemented in low-resource settings, protocols are needed to maximize health benefits under operational constraints. Our objective was to develop a framework for examining health and economic tradeoffs between screening test sensitivity, population coverage, and follow-up of screen-positive women, to help decision makers identify where program investments yield the greatest value. As an illustrative example, we used an individual-based Monte Carlo simulation model of the natural history of human papillomavirus (HPV) and cervical cancer calibrated to epidemiologic data from Uganda. We assumed once in a lifetime screening at age 35 with two-visit HPV DNA testing or one-visit visual inspection with acetic acid (VIA). We assessed the health and economic tradeoffs that arise between 1) test sensitivity and screening coverage; 2) test sensitivity and loss to follow-up (LTFU) of screen-positive women; and 3) test sensitivity, screening coverage, and LTFU simultaneously. The decline in health benefits associated with sacrificing HPV DNA test sensitivity by 20% (e.g., shifting from provider- to self-collection of specimens) could be offset by gains in coverage if coverage increased by at least 20%. When LTFU was 10%, two-visit HPV DNA testing with 80-90% sensitivity was more effective and more cost-effective than one-visit VIA with 40% sensitivity, and yielded greater health benefits than VIA even as VIA sensitivity increased to 60% and HPV test sensitivity declined to 70%. As LTFU increased, two-visit HPV DNA testing became more costly and less effective than one-visit VIA. Setting-specific data on achievable test sensitivity, coverage, follow-up rates, and programmatic costs are needed to guide programmatic decision making for cervical cancer screening. PMID:25943074

Photoacoustic imaging with planoconcave optical microresonator sensors: feasibility studies based on phantom imaging

NASA Astrophysics Data System (ADS)

Guggenheim, James A.; Zhang, Edward Z.; Beard, Paul C.

2017-03-01

The planar Fabry-Pérot (FP) sensor provides high quality photoacoustic (PA) images but beam walk-off limits sensitivity and thus penetration depth to ≍1 cm. Planoconcave microresonator sensors eliminate beam walk-off enabling sensitivity to be increased by an order-of-magnitude whilst retaining the highly favourable frequency response and directional characteristics of the FP sensor. The first tomographic PA images obtained in a tissue-realistic phantom using the new sensors are described. These show that the microresonator sensors provide near identical image quality as the planar FP sensor but with significantly greater penetration depth (e.g. 2-3cm) due to their higher sensitivity. This offers the prospect of whole body small animal imaging and clinical imaging to depths previously unattainable using the FP planar sensor.

Loss-of-function myostatin mutation increases insulin sensitivity and browning of white fat in Meishan pigs.

PubMed

Cai, Chunbo; Qian, Lili; Jiang, Shengwang; Sun, Youde; Wang, Qingqing; Ma, Dezun; Xiao, Gaojun; Li, Biao; Xie, Shanshan; Gao, Ting; Chen, Yaoxing; Liu, Jie; An, Xiaorong; Cui, Wentao; Li, Kui

2017-05-23

Myostatin-deficient mice showed a remarkable hypertrophy of skeletal muscle, with a decreased fat mass and enhanced insulin sensitivity. Currently, it is unclear if the inhibition of myostatin could be used as an approach to treat human obesity and insulin resistance. In this study, we investigated if the inhibition of porcine myostatin has any effect on fat deposition and insulin sensitivity using genetically engineered Meishan pigs containing a myostatin loss-of-function mutation (Mstn -/- ). Our results indicated that, when compared with wild-type pigs, the amount of subcutaneous fat and leaf fat of Mstn -/- pigs were significantly decreased mainly due to the browning of subcutaneous adipose tissue. Additionally, the serum insulin level decreased and the insulin sensitivity increased significantly in Mstn -/- pigs. Moreover, we found a significant increase in levels of insulin receptor and insulin receptor substrate proteins in skeletal muscle of Mstn -/- pigs, which then activating the insulin signaling pathway. Irisin-mediated regulation is not the only pathway for the activation of insulin signal in Mstn -/- skeletal muscle. This study provides valuable insight for the treatment of human obesity and diabetes mellitus.

SAFARI new and improved: extending the capabilities of SPICA's imaging spectrometer

NASA Astrophysics Data System (ADS)

Roelfsema, Peter; Giard, Martin; Najarro, Francisco; Wafelbakker, Kees; Jellema, Willem; Jackson, Brian; Sibthorpe, Bruce; Audard, Marc; Doi, Yasuo; di Giorgio, Anna; Griffin, Matthew; Helmich, Frank; Kamp, Inga; Kerschbaum, Franz; Meyer, Michael; Naylor, David; Onaka, Takashi; Poglitch, Albrecht; Spinoglio, Luigi; van der Tak, Floris; Vandenbussche, Bart

2014-08-01

The Japanese SPace Infrared telescope for Cosmology and Astrophysics, SPICA, aims to provide astronomers with a truly new window on the universe. With a large -3 meter class- cold -6K- telescope, the mission provides a unique low background environment optimally suited for highly sensitive instruments limited only by the cosmic background itself. SAFARI, the SpicA FAR infrared Instrument SAFARI, is a Fourier Transform imaging spectrometer designed to fully exploit this extremely low far infrared background environment. The SAFARI consortium, comprised of European and Canadian institutes, has established an instrument reference design based on a Mach-Zehnder interferometer stage with outputs directed to three extremely sensitive Transition Edge Sensor arrays covering the 35 to 210 μm domain. The baseline instrument provides R > 1000 spectroscopic imaging capabilities over a 2' by 2' field of view. A number of modifications to the instrument to extend its capabilities are under investigation. With the reference design SAFARI's sensitivity for many objects is limited not only by the detector NEP but also by the level of broad band background radiation - the zodiacal light for the shorter wavelengths and satellite baffle structures for the longer wavelengths. Options to reduce this background are dedicated masks or dispersive elements which can be inserted in the optics as required. The resulting increase in sensitivity can directly enhance the prime science goals of SAFARI; with the expected enhanced sensitivity astronomers would be in a better position to study thousands of galaxies out to redshift 3 and even many hundreds out to redshifts of 5 or 6. Possibilities to increase the wavelength resolution, at least for the shorter wavelength bands, are investigated as this would significantly enhance SAFARI's capabilities to study star and planet formation in our own galaxy.

Spatial patterns of stream temperatures and electric conductivity in a mesoscale catchment

NASA Astrophysics Data System (ADS)

Lieder, Ernestine; Weiler, Markus; Blume, Theresa

2017-04-01

Stream temperature and electric conductivity (EC) are both relatively easily measured and can provide valuable information on runoff generation processes and catchment storage.This study investigates the spatial variability of stream temperature and EC in a mesoscale basin. We focus on the mesoscale (sub-catchments and reach scale), and long term (seasonal / annual) stream temperature and EC patterns. Our study basin is the Attert catchment in Luxembourg (288km2), which contains multiple sub-catchments of different geology, topography and land use patterns. We installed 90 stream temperature and EC sensors at sites across the basin in summer 2015. The collected data is complemented by land use and discharge data and an extensive climate data set. Thermal sensitivity was calculated as the slope of daily air temperature-water-temperature regression line and describes the sensitivity of stream temperature to long term environmental change. Amplitude sensitivity was calculated as slope of the daily air and water temperature amplitude regression and describes the short term warming capacity of the stream. We found that groups with similar long term thermal and EC patterns are strongly related to different geological units. The sandstone reaches show the coldest temperatures and lowest annual thermal sensitivity to air temperature. The slate reaches are characterized by comparably low EC and high daily temperature amplitudes and amplitude sensitivity. Furthermore, mean annual temperatures and thermal sensitivities increase exponentially with drainage area, which can be attributed to the accumulation of heat throughout the system. On the reach scale, daily stream temperature fluctuations or sensitivities were strongly influenced by land cover distribution, stream shading and runoff volume. Daily thermal sensitivities were low for headwater streams; peaked for intermediate reaches in the middle of the catchment and then decreased again further downstream with increasing drainage area. Combining spatially distributed time series of stream temperatures and EC with information about geology, landscape and climate provides insight into the underlying hydrological processes and allows for the identification of thermally sensitive regions and reaches.

Novel Escherichia coli RF1 mutants with decreased translation termination activity and increased sensitivity to the cytotoxic effect of the bacterial toxins Kid and RelE.

PubMed

Diago-Navarro, Elizabeth; Mora, Liliana; Buckingham, Richard H; Díaz-Orejas, Ramón; Lemonnier, Marc

2009-01-01

Novel mutations in prfA, the gene for the polypeptide release factor RF1 of Escherichia coli, were isolated using a positive genetic screen based on the parD (kis, kid) toxin-antitoxin system. This original approach allowed the direct selection of mutants with altered translational termination efficiency at UAG codons. The isolated prfA mutants displayed a approximately 10-fold decrease in UAG termination efficiency with no significant changes in RF1 stability in vivo. All three mutations, G121S, G301S and R303H, were situated close to the nonsense codon recognition site in RF1:ribosome complexes. The prfA mutants displayed increased sensitivity to the RelE toxin encoded by the relBE system of E. coli, thus providing in vivo support for the functional interaction between RF1 and RelE. The prfA mutants also showed increased sensitivity to the Kid toxin. Since this toxin can cleave RNA in a ribosome-independent manner, this result was not anticipated and provided first evidence for the involvement of RF1 in the pathway of Kid toxicity. The sensitivity of the prfA mutants to RelE and Kid was restored to normal levels upon overproduction of the wild-type RF1 protein. We discuss these results and their utility for the design of novel antibacterial strategies in the light of the recently reported structure of ribosome-bound RF1.

Single input state, single–mode fiber–based polarization sensitive optical frequency domain imaging by eigenpolarization referencing

PubMed Central

Lippok, Norman; Villiger, Martin; Jun, Chang–Su; Bouma, Brett E.

2015-01-01

Fiber–based polarization sensitive OFDI is more challenging than free–space implementations. Using multiple input states, fiber–based systems provide sample birefringence information with the benefit of a flexible sample arm but come at the cost of increased system and acquisition complexity, and either reduce acquisition speed or require increased acquisition bandwidth. Here we show that with the calibration of a single polarization state, fiber–based configurations can approach the conceptual simplicity of traditional free–space configurations. We remotely control the polarization state of the light incident at the sample using the eigenpolarization states of a wave plate as a reference, and determine the Jones matrix of the output fiber. We demonstrate this method for polarization sensitive imaging of biological samples. PMID:25927775

What constitutes food variety? Stimulus specificity of food.

PubMed

Epstein, Leonard H; Robinson, Jodie L; Roemmich, James N; Marusewski, Angela L; Roba, Lora G

2010-02-01

Variety is a major influence of energy intake, but it is not known how much foods have to vary to influence eating. Using a stimulus specificity habituation paradigm we assessed the influence of varying the texture and appearance of nutritionally identical foods on responding for food and energy intake, and whether sensitization, or an increase in responding prior to habituation, was related to the rate of habituation or recovery of responding. Children responded for elbow macaroni and cheese until they habituated, then were provided either more elbow macaroni and cheese, spiral macaroni and cheese, or chicken nuggets. Children provided chicken nuggets or spiral macaroni and cheese recovered responding in comparison to more elbow macaroni and cheese. Children who sensitized showed slower habituation and consumed more food and more energy than those who did not sensitize, but did not differ in recovery of responding to the chicken nuggets or spiral macaroni and cheese. Results show small variations in food characteristics lead to recovery of responding and increased intake after children have habituated. 2009 Elsevier Ltd. All rights reserved.

Constitutive Lck Activity Drives Sensitivity Differences between CD8+ Memory T Cell Subsets.

PubMed

Moogk, Duane; Zhong, Shi; Yu, Zhiya; Liadi, Ivan; Rittase, William; Fang, Victoria; Dougherty, Janna; Perez-Garcia, Arianne; Osman, Iman; Zhu, Cheng; Varadarajan, Navin; Restifo, Nicholas P; Frey, Alan B; Krogsgaard, Michelle

2016-07-15

CD8(+) T cells develop increased sensitivity following Ag experience, and differences in sensitivity exist between T cell memory subsets. How differential TCR signaling between memory subsets contributes to sensitivity differences is unclear. We show in mouse effector memory T cells (TEM) that >50% of lymphocyte-specific protein tyrosine kinase (Lck) exists in a constitutively active conformation, compared with <20% in central memory T cells (TCM). Immediately proximal to Lck signaling, we observed enhanced Zap-70 phosphorylation in TEM following TCR ligation compared with TCM Furthermore, we observed superior cytotoxic effector function in TEM compared with TCM, and we provide evidence that this results from a lower probability of TCM reaching threshold signaling owing to the decreased magnitude of TCR-proximal signaling. We provide evidence that the differences in Lck constitutive activity between CD8(+) TCM and TEM are due to differential regulation by SH2 domain-containing phosphatase-1 (Shp-1) and C-terminal Src kinase, and we use modeling of early TCR signaling to reveal the significance of these differences. We show that inhibition of Shp-1 results in increased constitutive Lck activity in TCM to levels similar to TEM, as well as increased cytotoxic effector function in TCM Collectively, this work demonstrates a role for constitutive Lck activity in controlling Ag sensitivity, and it suggests that differential activities of TCR-proximal signaling components may contribute to establishing the divergent effector properties of TCM and TEM. This work also identifies Shp-1 as a potential target to improve the cytotoxic effector functions of TCM for adoptive cell therapy applications. Copyright © 2016 by The American Association of Immunologists, Inc.

Cultural Diversity Training: The Necessity of Cultural Competence for Health Care Providers and in Nursing Practice.

PubMed

Young, Susan; Guo, Kristina L

2016-01-01

The purpose of this article is to discuss the need to provide culturally sensitive care to the growing number of diverse health care consumers. A literature review of national standards and research on cultural competency was conducted and specifically focused on the field of nursing. This study supports the theory that cultural competence is learned over time and is a process of inner reflection and awareness. The domains of awareness, skill, and knowledge are essential competencies that must be gained by health care providers and especially for nurses. Although barriers to providing culturally sensitive care exist, gaining a better understanding of cultural competence is essential to developing realistic education and training techniques, which will lead to quality professional nursing practice for increasingly diverse populations.

Sharing and Reuse of Sensitive Data and Samples: Supporting Researchers in Identifying Ethical and Legal Requirements

PubMed Central

Schluender, Irene; Smee, Carol; Suhr, Stephanie

2015-01-01

Availability of and access to data and biosamples are essential in medical and translational research, where their reuse and repurposing by the wider research community can maximize their value and accelerate discovery. However, sharing human-related data or samples is complicated by ethical, legal, and social sensitivities. The specific ethical and legal requirements linked to sensitive data are often unfamiliar to life science researchers who, faced with vast amounts of complex, fragmented, and sometimes even contradictory information, may not feel competent to navigate through it. In this case, the impulse may be not to share the data in order to safeguard against unintentional misuse. Consequently, helping data providers to identify relevant ethical and legal requirements and how they might address them is an essential and frequently neglected step in removing possible hurdles to data and sample sharing in the life sciences. Here, we describe the complex regulatory context and discuss relevant online tools—one which the authors co-developed—targeted at assisting providers of sensitive data or biosamples with ethical and legal questions. The main results are (1) that the different approaches of the tools assume different user needs and prior knowledge of ethical and legal requirements, affecting how a service is designed and its usefulness, (2) that there is much potential for collaboration between tool providers, and (3) that enriched annotations of services (e.g., update status, completeness of information, and disclaimers) would increase their value and facilitate quick assessment by users. Further, there is still work to do with respect to providing researchers using sensitive data or samples with truly ‘useful’ tools that do not require pre-existing, in-depth knowledge of legal and ethical requirements or time to delve into the details. Ultimately, separate resources, maintained by experts familiar with the respective fields of research, may be needed while—in the longer term—harmonization and increase in ease of use will be very desirable. PMID:26186169

Specific down-regulation of XIAP with RNA interference enhances the sensitivity of canine tumor cell-lines to TRAIL and doxorubicin

PubMed Central

Spee, Bart; Jonkers, Martijn DB; Arends, Brigitte; Rutteman, Gerard R; Rothuizen, Jan; Penning, Louis C

2006-01-01

Background Apoptosis resistance occurs in various tumors. The anti-apoptotic XIAP protein is responsible for inhibiting apoptosis by reducing caspase-3 activation. Our aim is to evaluate whether RNA inhibition against XIAP increases the sensitivity of canine cell-lines for chemotherapeutics such as TRAIL and doxorubicin. We used small interfering RNA's (siRNA) directed against XIAP in three cell-lines derived from bile-duct epithelia (BDE), mammary carcinoma (P114), and osteosarcoma (D17). These cell-lines represent frequently occurring canine cancers and are highly comparable to their human counterparts. XIAP down-regulation was measured by means of quantitative PCR (Q-PCR) and Western blotting. The XIAP depleted cells were treated with a serial dilution of TRAIL or doxorubicin and compared to mock- and nonsense-treated controls. Viability was measured with a MTT assay. Results All XIAP siRNA treated cell-lines showed a mRNA down-regulation over 80 percent. Western blot analysis confirmed mRNA measurements. No compensatory effect of IAP family members was seen in XIAP depleted cells. The sensitivity of XIAP depleted cells for TRAIL was highest in BDE cells with an increase in the ED50 of 14-fold, compared to mock- and nonsense-treated controls. The sensitivity of P114 and D17 cell-lines increased six- and five-fold, respectively. Doxorubicin treatment in XIAP depleted cells increased sensitivity in BDE cells more than eight-fold, whereas P114 and D17 cell-lines showed an increase in sensitivity of three- and five-fold, respectively. Conclusion XIAP directed siRNA's have a strong sensitizing effect on TRAIL-reduced cell-viability and a smaller but significant effect with the DNA damaging drug doxorubicin. The increase in efficacy of chemotherapeutics with XIAP depletion provides the rationale for the use of XIAP siRNA's in insensitive canine tumors. PMID:16953886

Lyapunov exponents, covariant vectors and shadowing sensitivity analysis of 3D wakes: from laminar to chaotic regimes

NASA Astrophysics Data System (ADS)

Wang, Qiqi; Rigas, Georgios; Esclapez, Lucas; Magri, Luca; Blonigan, Patrick

2016-11-01

Bluff body flows are of fundamental importance to many engineering applications involving massive flow separation and in particular the transport industry. Coherent flow structures emanating in the wake of three-dimensional bluff bodies, such as cars, trucks and lorries, are directly linked to increased aerodynamic drag, noise and structural fatigue. For low Reynolds laminar and transitional regimes, hydrodynamic stability theory has aided the understanding and prediction of the unstable dynamics. In the same framework, sensitivity analysis provides the means for efficient and optimal control, provided the unstable modes can be accurately predicted. However, these methodologies are limited to laminar regimes where only a few unstable modes manifest. Here we extend the stability analysis to low-dimensional chaotic regimes by computing the Lyapunov covariant vectors and their associated Lyapunov exponents. We compare them to eigenvectors and eigenvalues computed in traditional hydrodynamic stability analysis. Computing Lyapunov covariant vectors and Lyapunov exponents also enables the extension of sensitivity analysis to chaotic flows via the shadowing method. We compare the computed shadowing sensitivities to traditional sensitivity analysis. These Lyapunov based methodologies do not rely on mean flow assumptions, and are mathematically rigorous for calculating sensitivities of fully unsteady flow simulations.

Redox Signaling and Bioenergetics Influence Lung Cancer Cell Line Sensitivity to the Isoflavone ME-344

PubMed Central

Manevich, Yefim; Reyes, Leticia; Britten, Carolyn D.; Townsend, Danyelle M.

2016-01-01

ME-344 [(3R,4S)-3,4-bis(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H-chromen-7-ol] is a second-generation derivative natural product isoflavone presently under clinical development. ME-344 effects were compared in lung cancer cell lines that are either intrinsically sensitive or resistant to the drug and in primary immortalized human lung embryonic fibroblasts (IHLEF). Cytotoxicity at low micromolar concentrations occurred only in sensitive cell lines, causing redox stress, decreased mitochondrial ATP production, and subsequent disruption of mitochondrial function. In a dose-dependent manner the drug caused instantaneous and pronounced inhibition of oxygen consumption rates (OCR) in drug-sensitive cells (quantitatively significantly less in drug-resistant cells). This was consistent with targeting of mitochondria by ME-344, with specific effects on the respiratory chain (resistance correlated with higher glycolytic indexes). OCR inhibition did not occur in primary IHLEF. ME-344 increased extracellular acidification rates in drug-resistant cells (significantly less in drug-sensitive cells), implying that ME-344 targets mitochondrial proton pumps. Only in drug-sensitive cells did ME-344 dose-dependently increase the intracellular generation of reactive oxygen species and cause oxidation of total (mainly glutathione) and protein thiols and the concomitant immediate increases in NADPH levels. We conclude that ME-344 causes complex, redox-specific, and mitochondria-targeted effects in lung cancer cells, which differ in extent from normal cells, correlate with drug sensitivity, and provide indications of a beneficial in vitro therapeutic index. PMID:27255112

Developing graduate student competency in providing culturally sensitive end of life care in critical care environments - a pilot study of a teaching innovation.

PubMed

Northam, Holly L; Hercelinskyj, Gylo; Grealish, Laurie; Mak, Anita S

2015-11-01

Australia's immigration policy has generated a rich diverse cultural community of staff and patients in critical care environments. Many different cultural perspectives inform individual actions in the context of critical care, including the highly sensitive area of end of life care, with nurses feeling poorly prepared to provide culturally sensitive end of life care. This article describes and evaluates the effectiveness of an educational innovation designed to develop graduate-level critical care nurses' capacity for effective interpersonal communication, as members of a multi-disciplinary team in providing culturally sensitive end-of-life care. A mixed method pilot study was conducted using a curriculum innovation intervention informed by The Excellence in Cultural Experiential Learning and Leadership Program (EXCELL),(1) which is a higher education intervention which was applied to develop the nurses' intercultural communication skills. 12 graduate nursing students studying critical care nursing participated in the study. 42% (n=5) of the participants were from an international background. Information about students' cultural learning was recorded before and after the intervention, using a cultural learning development scale. Student discussions of end of life care were recorded at Week 2 and 14 of the curriculum. The quantitative data was analysed using descriptive statistical analysis and qualitative data was thematically analysed. Students demonstrated an increase in cultural learning in a range of areas in the pre-post surveys including understandings of cultural diversity, interpersonal skills, cross cultural interactions and participating in multicultural groups. Thematic analysis of the end of life discussions revealed an increase in the levels of nurse confidence in approaching end of life care in critical care environments. The EXCELL program provides an effective and supportive educational framework to increase graduate nurses' cultural learning development and competence to manage culturally complex clinical issues such as end of life care, and is recommended as a framework for health care students to learn the skills required to provide culturally competent care in a range of culturally complex health care settings. Copyright © 2015 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

Herceptin conjugated PLGA-PHis-PEG pH sensitive nanoparticles for targeted and controlled drug delivery.

PubMed

Zhou, Zilan; Badkas, Apurva; Stevenson, Max; Lee, Joo-Youp; Leung, Yuet-Kin

2015-06-20

A dual functional nano-scaled drug carrier, comprising of a targeting ligand and pH sensitivity, has been made in order to increase the specificity and efficacy of the drug delivery system. The nanoparticles are made of a tri-block copolymer, poly(d,l lactide-co-glycolide) (PLGA)-b-poly(l-histidine) (PHis)-b-polyethylene glycol (PEG), via nano-precipitation. To provide the nanoparticle feature of endolysosomal escape and pH sensitivity, poly(l-histidine) was chosen as a proton sponge polymer. Herceptin, which specifically binds to HER2 antigen, was conjugated to the nanoparticles through click chemistry. The nanoparticles were characterized via dynamic light scattering (DLS) and transmission electron microscopy (TEM). Both methods showed the sizes of about 100nm with a uniform size distribution. The pH sensitivity was assessed by drug releases and size changes at different pH conditions. As pH decreased from 7.4 to 5.2, the drug release rate accelerated and the size significantly increased. During in vitro tests against human breast cancer cell lines, MCF-7 and SK-BR-3 showed significantly increased uptake for Herceptin-conjugated nanoparticles, as compared to non-targeted nanoparticles. Herceptin-conjugated pH-sensitive nanoparticles showed the highest therapeutic effect, and thus validated the efficacy of a combined approach of pH sensitivity and active targeting. Copyright © 2015 Elsevier B.V. All rights reserved.

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

PubMed Central

dos Santos, Marcelo R.; Sayegh, Ana L.C.; Armani, Rafael; Costa-Hong, Valéria; de Souza, Francis R.; Toschi-Dias, Edgar; Bortolotto, Luiz A.; Yonamine, Mauricio; Negrão, Carlos E.; Alves, Maria-Janieire N.N.

2018-01-01

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population. PMID:29791601

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users.

PubMed

Santos, Marcelo R Dos; Sayegh, Ana L C; Armani, Rafael; Costa-Hong, Valéria; Souza, Francis R de; Toschi-Dias, Edgar; Bortolotto, Luiz A; Yonamine, Mauricio; Negrão, Carlos E; Alves, Maria-Janieire N N

2018-05-21

Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population.

A conceptualisation framework for building consensus on environmental sensitivity.

PubMed

González Del Campo, Ainhoa

2017-09-15

Examination of the intrinsic attributes of a system that render it more or less sensitive to potential stressors provides further insight into the baseline environment. In impact assessment, sensitivity of environmental receptors can be conceptualised on the basis of their: a) quality status according to statutory indicators and associated thresholds or targets; b) statutory protection; or c) inherent risk. Where none of these considerations are pertinent, subjective value judgments can be applied to determine sensitivity. This pragmatic conceptual framework formed the basis of a stakeholder consultation process for harmonising degrees of sensitivity of a number of environmental criteria. Harmonisation was sought to facilitate their comparative and combined analysis. Overall, full or wide agreement was reached on relative sensitivity values for the large majority of the reviewed criteria. Consensus was easier to reach on some themes (e.g. biodiversity, water and cultural heritage) than others (e.g. population and soils). As anticipated, existing statutory measures shaped the outcomes but, ultimately, knowledge-based values prevailed. The agreed relative sensitivities warrant extensive consultation but the conceptual framework provides a basis for increasing stakeholder consensus and objectivity of baseline assessments. This, in turn, can contribute to improving the evidence-base for characterising the significance of potential impacts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optimizing Ionic Electrolytes for Dye-Sensitized Solar Cells

NASA Astrophysics Data System (ADS)

Fan, Xiaojuan; Hall, Sarah

2009-03-01

Dye-sensitized solar cells DSSCs provide next generation, low cost, and easy fabrication photovoltaic devices based on organic sensitizing molecules, polymer gel electrolyte, and metal oxide semiconductors. One of the key components is the solvent-free ionic liquid electrolyte that has low volatility and high stability. We report a rapid and low cost method to fabricate ionic polymer electrolyte used in DSSCs. Poly(ethylene oxide) (PEO) is blended with imidazolinium salt without any chemical solvent to form a gel electrolyte. Uniform and crack-free porous TiO2 thin films are sensitized by porphrine dye covered by the synthesized gel electrolyte. The fabricated DSSCs are more stable and potentially increase the photo-electricity conversion efficiency.

Collection of ions

DOEpatents

Orr, Christopher Henry; Luff, Craig Janson; Dockray, Thomas; Macarthur, Duncan Whittemore; Bounds, John Alan; Koster, James E.

2001-01-01

The apparatus and method provide an improved technique for detecting ions as the area from which ions are attracted to a detector is increased, consequently increasing the number of ions detected. This is achieved by providing the outer electrodes of the detector connected to the electrical potential, together with alternate intermediate electrodes. The other intermediate electrodes and preferably the housing are grounded. The technique renders such detection techniques more sensitive and gives them a lower threshold at which they can function.

An evidence-based framework for predicting the impact of differing autotroph-heterotroph thermal sensitivities on consumer–prey dynamics

PubMed Central

Yang, Zhou; Zhang, Lu; Zhu, Xuexia; Wang, Jun; Montagnes, David J S

2016-01-01

Increased temperature accelerates vital rates, influencing microbial population and wider ecosystem dynamics, for example, the predicted increases in cyanobacterial blooms associated with global warming. However, heterotrophic and mixotrophic protists, which are dominant grazers of microalgae, may be more thermally sensitive than autotrophs, and thus prey could be suppressed as temperature rises. Theoretical and meta-analyses have begun to address this issue, but an appropriate framework linking experimental data with theory is lacking. Using ecophysiological data to develop a novel model structure, we provide the first validation of this thermal sensitivity hypothesis: increased temperature improves the consumer's ability to control the autotrophic prey. Specifically, the model accounts for temperature effects on auto- and mixotrophs and ingestion, growth and mortality rates, using an ecologically and economically important system (cyanobacteria grazed by a mixotrophic flagellate). Once established, we show the model to be a good predictor of temperature impacts on consumer–prey dynamics by comparing simulations with microcosm observations. Then, through simulations, we indicate our conclusions remain valid, even with large changes in bottom-up factors (prey growth and carrying capacity). In conclusion, we show that rising temperature could, counterintuitively, reduce the propensity for microalgal blooms to occur and, critically, provide a novel model framework for needed, continued assessment. PMID:26684731

High hunger state increases olfactory sensitivity to neutral but not food odors.

PubMed

Stafford, Lorenzo D; Welbeck, Kimberley

2011-01-01

Understanding how hunger state relates to olfactory sensitivity has become more urgent due to their possible role in obesity. In 2 studies (within-subjects: n = 24, between-subjects: n = 40), participants were provided with lunch before (satiated state) or after (nonsatiated state) testing and completed a standardized olfactory threshold test to a neutral odor (Experiments 1 and 2) and discrimination test to a food odor (Experiment 2). Experiment 1 revealed that olfactory sensitivity was greater in the nonsatiated versus satiated state, with additionally increased sensitivity for the low body mass index (BMI) compared with high BMI group. Experiment 2 replicated this effect for neutral odors, but in the case of food odors, those in a satiated state had greater acuity. Additionally, whereas the high BMI group had higher acuity to food odors in the satiated versus nonsatiated state, no such differences were found for the low BMI group. The research here is the first to demonstrate how olfactory acuity changes as a function of hunger state and relatedness of odor to food and that BMI can predict differences in olfactory sensitivity.

The development of cortical sensitivity to visual word forms.

PubMed

Ben-Shachar, Michal; Dougherty, Robert F; Deutsch, Gayle K; Wandell, Brian A

2011-09-01

The ability to extract visual word forms quickly and efficiently is essential for using reading as a tool for learning. We describe the first longitudinal fMRI study to chart individual changes in cortical sensitivity to written words as reading develops. We conducted four annual measurements of brain function and reading skills in a heterogeneous group of children, initially 7-12 years old. The results show age-related increase in children's cortical sensitivity to word visibility in posterior left occipito-temporal sulcus (LOTS), nearby the anatomical location of the visual word form area. Moreover, the rate of increase in LOTS word sensitivity specifically correlates with the rate of improvement in sight word efficiency, a measure of speeded overt word reading. Other cortical regions, including V1, posterior parietal cortex, and the right homologue of LOTS, did not demonstrate such developmental changes. These results provide developmental support for the hypothesis that LOTS is part of the cortical circuitry that extracts visual word forms quickly and efficiently and highlight the importance of developing cortical sensitivity to word visibility in reading acquisition.

Experimental study on the influence of chemical sensitizer on pressure resistance in deep water of emulsion explosives

NASA Astrophysics Data System (ADS)

Liu, Lei; zhang, Zhihua; Wang, Ya; Qin, hao

2018-03-01

The study on the pressure resistance performance of emulsion explosives in deep water can provide theoretical basis for underwater blasting, deep-hole blasting and emulsion explosives development. The sensitizer is an important component of emulsion explosives. By using reusable experimental devices to simulate the charge environment in deep water, the influence of the content of chemical sensitizer on the deep-water pressure resistance performance of emulsion explosives was studied. The experimental results show that with the increasing of the content of chemical sensitizer, the deep-water pressure resistance performance of emulsion explosives gradually improves, and when the pressure is fairly large, the effect is particularly pronounced; in a certain range, with the increase of the content of chemical sensitizer, that emulsion explosives’ explosion performance also gradually improve, but when the content reaches a certain value, the explosion properties declined instead; under the same emulsion matrix condition, when the content of NANO2 is 0.2%, that the emulsion explosives has good resistance to water pressure and good explosion properties. The correctness of the results above was testified in model blasting.

CD8+ T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension.

PubMed

Liu, Yunmeng; Rafferty, Tonya M; Rhee, Sung W; Webber, Jessica S; Song, Li; Ko, Benjamin; Hoover, Robert S; He, Beixiang; Mu, Shengyu

2017-01-09

Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8 + T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8 + T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8 + T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K + channel Kir4.1, and stimulation of the Cl - channel ClC-K. The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension.

CD8+ T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension

PubMed Central

Liu, Yunmeng; Rafferty, Tonya M.; Rhee, Sung W.; Webber, Jessica S.; Song, Li; Ko, Benjamin; Hoover, Robert S.; He, Beixiang; Mu, Shengyu

2017-01-01

Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8+ T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8+ T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8+ T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K+ channel Kir4.1, and stimulation of the Cl− channel ClC-K. The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension. PMID:28067240

The Development of Cortical Sensitivity to Visual Word Forms

PubMed Central

Ben-Shachar, Michal; Dougherty, Robert F.; Deutsch, Gayle K.; Wandell, Brian A.

2011-01-01

The ability to extract visual word forms quickly and efficiently is essential for using reading as a tool for learning. We describe the first longitudinal fMRI study to chart individual changes in cortical sensitivity to written words as reading develops. We conducted four annual measurements of brain function and reading skills in a heterogeneous group of children, initially 7–12 years old. The results show age-related increase in children's cortical sensitivity to word visibility in posterior left occipito-temporal sulcus (LOTS), nearby the anatomical location of the visual word form area. Moreover, the rate of increase in LOTS word sensitivity specifically correlates with the rate of improvement in sight word efficiency, a measure of speeded overt word reading. Other cortical regions, including V1, posterior parietal cortex, and the right homologue of LOTS, did not demonstrate such developmental changes. These results provide developmental support for the hypothesis that LOTS is part of the cortical circuitry that extracts visual word forms quickly and efficiently and highlight the importance of developing cortical sensitivity to word visibility in reading acquisition. PMID:21261451

Increased sensitivity of prolonged P-wave during exercise stress test in detection of angiographically documented coronary artery disease.

PubMed

Wsol, Agnieszka; Wydra, Wioletta; Chmielewski, Marek; Swiatowiec, Andrzej; Kuch, Marek

2017-01-01

A retrospective study was designed to investigate P-wave duration changes in exercise stress test (EST) for the prediction of angiographically documented substantial coronary artery disease (CAD). We analyzed 265 cases of patients, who underwent EST and subsequently coronary angiography. Analysis of P-wave duration was performed in leads II, V5 at rest, and in the recovery period. The sensitivity and specificity for the isolated ST-segment depression were only 31% and 76%, respectively. The combination of ST-depression with other exercise-induced clinical and electrocardio-graphic abnormalities (chest pain, ventricular arrhythmia, hypotension, left bundle branch block) was characterized by 41% sensitivity and 69% specificity. The combination of abnormal recovery P-wave duration (≥ 120 ms) with ST-depression and other exercise-induced abnormalities had 83% sensitivity but only 20% specificity. Combined analysis of increased delta P-wave duration, ST-depression and other exercise-induced abnormalities had 69% sensitivity and 42% specificity. Sensitivity and specificity of the increase in delta P-wave duration for left CAD was 69% and 47%, respectively, and for 3-vessel CAD 70% and 50%, respectively. The presence of arterial hypertension negatively influenced the prog-nostic value of P-wave changes in the stress test. The results of the study show that an addition of P-wave duration changes assessment to ST-depression analysis and other exercise-induced abnormalities increase sensitivity of EST, especially for left CAD and 3-vessel coronary disease. We have also provided evidence for the negative influence of the presence of arterial hypertension on the predictive value of P-wave changes in the stress test. (Cardiol J 2017; 24, 2: 159-166).

Cell Wall Pectin and its Methyl-esterification in Transition Zone Determine Al Resistance in Cultivars of Pea (Pisum sativum)

PubMed Central

Li, Xuewen; Li, Yalin; Qu, Mei; Xiao, Hongdong; Feng, Yingming; Liu, Jiayou; Wu, Lishu; Yu, Min

2016-01-01

The initial response of plants to aluminum (Al) is the inhibition of root elongation, while the transition zone is the most Al sensitive zone in the root apex, which may sense the presence of Al and regulate the responses of root to Al toxicity. In the present study, the effect of Al treatment (30 μM, 24 h) on root growth, Al accumulation, and properties of cell wall of two pea (Pisum sativum L.) cultivars, cv Onward (Al-resistant) and cv Sima (Al-sensitive), were studied to disclose whether the response of root transition zone to Al toxicity determines Al resistance in pea cultivars. The lower relative root elongation (RRE) and higher Al content were founded in cv Sima compared with cv Onward, which were related to Al-induced the increase of pectin in root segments of both cultivars. The increase of pectin is more prominent in Al-sensitive cultivar than in Al-resistant cultivar. Aluminum toxicity also induced the increase of pectin methylesterases (PME), which is 2.2 times in root transition zone in Al-sensitive cv Sima to that of Al resistant cv Onward, thus led to higher demethylesterified pectin content in root transition zone of Al-sensitive cv Sima. The higher demethylesterified pectin content in root transition zone resulted in more Al accumulation in the cell wall and cytosol in Al-sensitive cv Sima. Our results provide evidence that the increase of pectin content and PME activity under Al toxicity cooperates to determine Al sensitivity in root transition zone that confers Al resistance in cultivars of pea (Pisum sativum). PMID:26870060

A generalized matching law analysis of cocaine vs. food choice in rhesus monkeys: effects of candidate 'agonist-based' medications on sensitivity to reinforcement.

PubMed

Hutsell, Blake A; Negus, S Stevens; Banks, Matthew L

2015-01-01

We have previously demonstrated reductions in cocaine choice produced by either continuous 14-day phendimetrazine and d-amphetamine treatment or removing cocaine availability under a cocaine vs. food choice procedure in rhesus monkeys. The aim of the present investigation was to apply the concatenated generalized matching law (GML) to cocaine vs. food choice dose-effect functions incorporating sensitivity to both the relative magnitude and price of each reinforcer. Our goal was to determine potential behavioral mechanisms underlying pharmacological treatment efficacy to decrease cocaine choice. A multi-model comparison approach was used to characterize dose- and time-course effects of both pharmacological and environmental manipulations on sensitivity to reinforcement. GML models provided an excellent fit of the cocaine choice dose-effect functions in individual monkeys. Reductions in cocaine choice by both pharmacological and environmental manipulations were principally produced by systematic decreases in sensitivity to reinforcer price and non-systematic changes in sensitivity to reinforcer magnitude. The modeling approach used provides a theoretical link between the experimental analysis of choice and pharmacological treatments being evaluated as candidate 'agonist-based' medications for cocaine addiction. The analysis suggests that monoamine releaser treatment efficacy to decrease cocaine choice was mediated by selectively increasing the relative price of cocaine. Overall, the net behavioral effect of these pharmacological treatments was to increase substitutability of food pellets, a nondrug reinforcer, for cocaine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Meta-analysis of diagnostic accuracy studies in mental health

PubMed Central

Takwoingi, Yemisi; Riley, Richard D; Deeks, Jonathan J

2015-01-01

Objectives To explain methods for data synthesis of evidence from diagnostic test accuracy (DTA) studies, and to illustrate different types of analyses that may be performed in a DTA systematic review. Methods We described properties of meta-analytic methods for quantitative synthesis of evidence. We used a DTA review comparing the accuracy of three screening questionnaires for bipolar disorder to illustrate application of the methods for each type of analysis. Results The discriminatory ability of a test is commonly expressed in terms of sensitivity (proportion of those with the condition who test positive) and specificity (proportion of those without the condition who test negative). There is a trade-off between sensitivity and specificity, as an increasing threshold for defining test positivity will decrease sensitivity and increase specificity. Methods recommended for meta-analysis of DTA studies --such as the bivariate or hierarchical summary receiver operating characteristic (HSROC) model --jointly summarise sensitivity and specificity while taking into account this threshold effect, as well as allowing for between study differences in test performance beyond what would be expected by chance. The bivariate model focuses on estimation of a summary sensitivity and specificity at a common threshold while the HSROC model focuses on the estimation of a summary curve from studies that have used different thresholds. Conclusions Meta-analyses of diagnostic accuracy studies can provide answers to important clinical questions. We hope this article will provide clinicians with sufficient understanding of the terminology and methods to aid interpretation of systematic reviews and facilitate better patient care. PMID:26446042

Improvement in the light sensitivity of the ultrahigh-speed high-sensitivity CCD with a microlens array

NASA Astrophysics Data System (ADS)

Hayashida, T.,; Yonai, J.; Kitamura, K.; Arai, T.; Kurita, T.; Tanioka, K.; Maruyama, H.; Etoh, T. Goji; Kitagawa, S.; Hatade, K.; Yamaguchi, T.; Takeuchi, H.; Iida, K.

2008-02-01

We are advancing the development of ultrahigh-speed, high-sensitivity CCDs for broadcast use that are capable of capturing smooth slow-motion videos in vivid colors even where lighting is limited, such as at professional baseball games played at night. We have already developed a 300,000 pixel, ultrahigh-speed CCD, and a single CCD color camera that has been used for sports broadcasts and science programs using this CCD. However, there are cases where even higher sensitivity is required, such as when using a telephoto lens during a baseball broadcast or a high-magnification microscope during science programs. This paper provides a summary of our experimental development aimed at further increasing the sensitivity of CCDs using the light-collecting effects of a microlens array.

Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle.

PubMed

Sung, Nayoung; Kwak-Kim, Joanne; Koo, H S; Yang, K M

2016-09-01

To investigate hCG-β level on postovulatory day (POD) 12 and its fold increase as predictors for pregnancy outcome after in vitro fertilization (IVF) cycles. A retrospective cohort study was performed in total 1408 fresh and 598 frozen cycles between November 2008 and October 2011, which resulted in biochemical pregnancy, early pregnancy loss, or live birth of singleton pregnancy. The serum hCG-β levels of POD 12 and 14 were compared among biochemical pregnancy, early pregnancy loss, and live birth groups. The cutoff values of POD 12 and 14 hCG-β levels and the degree of hCG-β increase from POD 12 to 14 were determined for each pregnancy outcome. POD 12 and 14 hCG-β levels stratified based on pregnancy outcomes were significantly different among the biochemical pregnancy, early pregnancy loss, and live birth in both fresh and frozen cycles. Serum hCG-β levels of POD 12 and 14 and the fold increase of hCG-β levels from POD 12 to 14 significantly predict pregnancy outcomes after fresh and frozen cycles. Among these, the cutoff value of POD 14 hCG-β had the highest sensitivity and positive predictive value (PPV). In fresh cycles, the cutoff values of POD 12 and 14 serum hCG-β levels for clinical pregnancies were 30.2 mIU/mL (sensitivity 81.3 %, specificity 79.6 %, and PPV 92.3 %) and 70.5 mIU/mL (sensitivity 88.4 %, specificity 85.2 %, and PPV 94.7 %). In pregnancies with POD 12 serum hCG-β levels ≥30.2 mIU/mL, the cutoff level of increase of hCG-β for clinical pregnancy was 2.56 (sensitivity 73.6 %, specificity 72.4 %, and PPV 97.8 %). Sequential application of cutoff values such as POD 12 hCG-β and fold increase of hCG-β improved predictability of pregnancy outcome as compared with that of POD 12 hCG-β alone. The cutoff values of POD 12 and 14 serum hCG-β levels for live birth were 40.5 mIU/mL (sensitivity 75.2 %, specificity 72.6 %, PPV 78.9 %) and 104.5 mIU/mL (sensitivity 80.3 %, specificity 74.1 %, PPV 80.8 %). In the frozen cycles, the cutoff values of POD 12 and 14 serum hCG-β level for clinical pregnancy were 31.5 IU/L (sensitivity 80.4 %, specificity 71.1 % and PPV 90 %) and 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %). In pregnancies with POD 12 serum hCG-β level ≥31.5 mIU/mL, the cutoff value for fold increase of hCG-β was 2.38 for clinical pregnancy (sensitivity 81.6 %, specificity 71.4 % and PPV 87.9 %). The cutoff values of POD 12 and 14 for live birth were 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %) and 101.6 mIU/mL (sensitivity 79.6 %, specificity 71.1 %, PPV 78.4 %). Sequential application of cutoff values for POD 12 hCG-β level and fold increase of hCG-β significantly increased PPV for live birth but not clinical pregnancy in frozen cycles. Early prediction of pregnancy outcome by using POD 12 and 14 cutoff levels and sequential application of cutoff value of fold increase could provide appropriate reference to health care providers to initiate earlier management of high-risk pregnancies and precise follow-up of abnormal pregnancies.

Dynamical Model of Drug Accumulation in Bacteria: Sensitivity Analysis and Experimentally Testable Predictions

DOE PAGES

Vesselinova, Neda; Alexandrov, Boian; Wall, Michael E.

2016-11-08

We present a dynamical model of drug accumulation in bacteria. The model captures key features in experimental time courses on ofloxacin accumulation: initial uptake; two-phase response; and long-term acclimation. In combination with experimental data, the model provides estimates of import and export rates in each phase, the time of entry into the second phase, and the decrease of internal drug during acclimation. Global sensitivity analysis, local sensitivity analysis, and Bayesian sensitivity analysis of the model provide information about the robustness of these estimates, and about the relative importance of different parameters in determining the features of the accumulation time coursesmore » in three different bacterial species: Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The results lead to experimentally testable predictions of the effects of membrane permeability, drug efflux and trapping (e.g., by DNA binding) on drug accumulation. A key prediction is that a sudden increase in ofloxacin accumulation in both E. coli and S. aureus is accompanied by a decrease in membrane permeability.« less

Dynamical Model of Drug Accumulation in Bacteria: Sensitivity Analysis and Experimentally Testable Predictions

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

Vesselinova, Neda; Alexandrov, Boian; Wall, Michael E.

We present a dynamical model of drug accumulation in bacteria. The model captures key features in experimental time courses on ofloxacin accumulation: initial uptake; two-phase response; and long-term acclimation. In combination with experimental data, the model provides estimates of import and export rates in each phase, the time of entry into the second phase, and the decrease of internal drug during acclimation. Global sensitivity analysis, local sensitivity analysis, and Bayesian sensitivity analysis of the model provide information about the robustness of these estimates, and about the relative importance of different parameters in determining the features of the accumulation time coursesmore » in three different bacterial species: Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The results lead to experimentally testable predictions of the effects of membrane permeability, drug efflux and trapping (e.g., by DNA binding) on drug accumulation. A key prediction is that a sudden increase in ofloxacin accumulation in both E. coli and S. aureus is accompanied by a decrease in membrane permeability.« less

Quantitative mass spectrometry methods for pharmaceutical analysis

PubMed Central

Loos, Glenn; Van Schepdael, Ann

2016-01-01

Quantitative pharmaceutical analysis is nowadays frequently executed using mass spectrometry. Electrospray ionization coupled to a (hybrid) triple quadrupole mass spectrometer is generally used in combination with solid-phase extraction and liquid chromatography. Furthermore, isotopically labelled standards are often used to correct for ion suppression. The challenges in producing sensitive but reliable quantitative data depend on the instrumentation, sample preparation and hyphenated techniques. In this contribution, different approaches to enhance the ionization efficiencies using modified source geometries and improved ion guidance are provided. Furthermore, possibilities to minimize, assess and correct for matrix interferences caused by co-eluting substances are described. With the focus on pharmaceuticals in the environment and bioanalysis, different separation techniques, trends in liquid chromatography and sample preparation methods to minimize matrix effects and increase sensitivity are discussed. Although highly sensitive methods are generally aimed for to provide automated multi-residue analysis, (less sensitive) miniaturized set-ups have a great potential due to their ability for in-field usage. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644982

Sensitization of human carcinoma cells to alkylating agents by small interfering RNA suppression of 3-alkyladenine-DNA glycosylase.

PubMed

Paik, Johanna; Duncan, Tod; Lindahl, Tomas; Sedgwick, Barbara

2005-11-15

One of the major cytotoxic lesions generated by alkylating agents is DNA 3-alkyladenine, which can be excised by 3-alkyladenine DNA glycosylase (AAG). Inhibition of AAG may therefore result in increased cellular sensitivity to chemotherapeutic alkylating agents. To investigate this possibility, we have examined the role of AAG in protecting human tumor cells against such agents. Plasmids that express small interfering RNAs targeted to two different regions of AAG mRNA were transfected into HeLa cervical carcinoma cells and A2780-SCA ovarian carcinoma cells. Stable derivatives of both cell types with low AAG protein levels were sensitized to alkylating agents. Two HeLa cell lines with AAG protein levels reduced by at least 80% to 90% displayed a 5- to 10-fold increase in sensitivity to methyl methanesulfonate, N-methyl-N-nitrosourea, and the chemotherapeutic drugs temozolomide and 1,3-bis(2-chloroethyl)-1-nitrosourea. These cells showed no increase in sensitivity to UV light or ionizing radiation. After treatment with methyl methanesulfonate, AAG knockdown HeLa cells were delayed in S phase but accumulated in G2-M. Our data support the hypothesis that ablation of AAG activity in human tumor cells may provide a useful strategy to enhance the efficacy of current chemotherapeutic regimens that include alkylating agents.

Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?

PubMed

Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica

2011-05-01

Central sensitization accounts for chronic 'unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that - theoretically - desensitize the CNS in humans. To provide a comprehensive treatment for 'unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization. © 2011 Informa UK, Ltd

Getting the Big Picture: Design Considerations for a ngVLA Short Spacing Array

NASA Astrophysics Data System (ADS)

Mason, Brian Scott; Cotton, William; Condon, James; Kepley, Amanda; Selina, Rob; Murphy, Eric Joseph

2018-01-01

The Next Generation VLA (ngVLA) aims to provide a revolutionary increase in cm-wavelength collecting area and sensitivity while at the same time providing excellent image fidelity for a broad spectrum of science cases. Likely ngVLA configurations currently envisioned provide sensitivity over a very wide range of spatial scales. The antenna diameter (notionally 18 meters) fundamentally limits the largest angular scales that can be reached. One simple and powerful way to image larger angular scales is to build a complementary interferometer comprising a smaller number of smaller-diameter dishes.We have investigated the requirements that such an array would need to meet in order to usefully scientifically complement the ngVLA; this poster presents the results of our investigation.

A novel, non-invasive transdermal fluid sampling methodology: IGF-I measurement following exercise

USDA-ARS?s Scientific Manuscript database

This study tested the hypothesis that transdermal fluid (TDF) provides a more sensitive and accurate measure of exercise-induced increases in insulin-like growth factor-I (IGF-I) than serum, and that these increases are detectable proximal, but not distal, to the exercising muscle. A novel, noninvas...

Metallized polymeric foam material

NASA Technical Reports Server (NTRS)

Birnbaum, B. A.; Bilow, N.

1974-01-01

Open-celled polyurethane foams can be coated uniformly with thin film of metal by vapor deposition of aluminum or by sensitization of foam followed by electroless deposition of nickel or copper. Foam can be further processed to increase thickness of metal overcoat to impart rigidity or to provide inert surface with only modest increase in weight.

Effects of Gain Changes on RPM Performance

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

Lousteau, Angela L; York, Robbie Lynn; Livesay, Jake

2012-03-01

The mission of the U.S. Department of Energy/National Nuclear Security Administration's (DOE/NNSA's) Office of the Second Line of Defense (SLD) is to strengthen the capability of foreign governments to deter, detect, and interdict the illicit trafficking of special nuclear and other radioactive materials across international borders and through the global maritime shipping system. The goal of this mission is to reduce the probability of these materials being fashioned into a weapon of mass destruction or radiological dispersal device that could be used against the United States or its international partners. This goal is achieved primarily through the installation and operationmore » of radiation detection equipment at border crossings, airports, seaports, and other strategic locations around the world. In order to effectively detect the movement of radioactive material, the response of these radiation detectors to various materials in various configurations must be well characterized. Oak Ridge National Laboratory (ORNL) investigated two aspects of Radiation Portal Monitor (RPM) settings, based on a preliminary investigation done by the Los Alamos National Laboratory (LANL): source-to-detector distance effect on amplifier gain and optimized discriminator settings. This report discusses this investigation. A number of conclusions can be drawn from the ORNL testing. First, for increased distance between the source and the detector, thus illuminating the entire detector rather than just the center of the detector (as is done during detector alignments), an increase in gain may provide a 5-15% increase in sensitivity (Fig. 4). However, increasing the gain without adjusting the discriminator settings is not recommended as this makes the monitor more sensitive to electronic noise and temperature-induced fluctuations. Furthermore, if the discriminators are adjusted in relation to the increase in gain, thus appropriately discriminating against electronic noise, the sensitivity gains are less than 5% (Fig. 6). ORNL does not consider this slight increase in sensitivity to be a worthwhile pursuit. Second, increasing the ULD will increase sensitivity a few percent (Fig. 7); however, it is not clear that the slight increase in sensitivity is worth the effort required to make the change (e.g., reliability, cost, etc.). Additionally, while the monitor would be more sensitive to HEU, it would also be more sensitive to NORM. Third, the sensitivity of the system remains approximately the same whether it is calibrated to a small source on contact or a large source far away (Fig. 6). This affirms that no changes to the existing calibration procedure are necessary.« less

Sensitivity Analysis in Sequential Decision Models.

PubMed

Chen, Qiushi; Ayer, Turgay; Chhatwal, Jagpreet

2017-02-01

Sequential decision problems are frequently encountered in medical decision making, which are commonly solved using Markov decision processes (MDPs). Modeling guidelines recommend conducting sensitivity analyses in decision-analytic models to assess the robustness of the model results against the uncertainty in model parameters. However, standard methods of conducting sensitivity analyses cannot be directly applied to sequential decision problems because this would require evaluating all possible decision sequences, typically in the order of trillions, which is not practically feasible. As a result, most MDP-based modeling studies do not examine confidence in their recommended policies. In this study, we provide an approach to estimate uncertainty and confidence in the results of sequential decision models. First, we provide a probabilistic univariate method to identify the most sensitive parameters in MDPs. Second, we present a probabilistic multivariate approach to estimate the overall confidence in the recommended optimal policy considering joint uncertainty in the model parameters. We provide a graphical representation, which we call a policy acceptability curve, to summarize the confidence in the optimal policy by incorporating stakeholders' willingness to accept the base case policy. For a cost-effectiveness analysis, we provide an approach to construct a cost-effectiveness acceptability frontier, which shows the most cost-effective policy as well as the confidence in that for a given willingness to pay threshold. We demonstrate our approach using a simple MDP case study. We developed a method to conduct sensitivity analysis in sequential decision models, which could increase the credibility of these models among stakeholders.

Population level differences in thermal sensitivity of energy assimilation in terrestrial salamanders.

PubMed

Clay, Timothy A; Gifford, Matthew E

2017-02-01

Thermal adaptation predicts that thermal sensitivity of physiological traits should be optimized to thermal conditions most frequently experienced. Furthermore, thermodynamic constraints predict that species with higher thermal optima should have higher performance maxima and narrower performance breadths. We tested these predictions by examining the thermal sensitivity of energy assimilation between populations within two species of terrestrial-lungless salamanders, Plethodon albagula and P. montanus. Within P. albagula, we examined populations that were latitudinally separated by >450km. Within P. montanus, we examined populations that were elevationally separated by >900m. Thermal sensitivity of energy assimilation varied substantially between populations of P. albagula separated latitudinally, but did not vary between populations of P. montanus separated elevationally. Specifically, in P. albagula, the lower latitude population had a higher thermal optimum, higher maximal performance, and narrower performance breadth compared to the higher latitude population. Furthermore, across all individuals as thermal optima increased, performance maxima also increased, providing support for the theory that "hotter is better". Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of a rapid immunochromatographic ODK-0901 test for detection of pneumococcal antigen in middle ear fluids and nasopharyngeal secretions.

PubMed

Hotomi, Muneki; Togawa, Akihisa; Takei, Shin; Sugita, Gen; Sugita, Rinya; Kono, Masamitsu; Fujimaki, Yutaka; Kamide, Yosuke; Uchizono, Akihiro; Kanesada, Keiko; Sawada, Shoichi; Okitsu, Naohiro; Tanaka, Yumi; Saijo, Yoko; Yamanaka, Noboru

2012-01-01

Since the incidence of penicillin-resistant Streptococcus pneumoniae has been increasing at an astonishing rate throughout the world, the need for accurate and rapid identification of pneumococci has become increasingly important to determine the appropriate antimicrobial treatment. We have evaluated an immunochromatographic test (ODK-0901) that detects pneumococcal antigens using 264 middle ear fluids (MEFs) and 268 nasopharyngeal secretions (NPSs). A sample was defined to contain S. pneumoniae when optochin and bile sensitive alpha hemolytic streptococcal colonies were isolated by culture. The sensitivity and specificity of the ODK-0901 test were 81.4% and 80.5%, respectively, for MEFs from patients with acute otitis media (AOM). In addition, the sensitivity and specificity were 75.2% and 88.8%, respectively, for NPSs from patients with acute rhinosinusitis. The ODK-0901 test may provide a rapid and highly sensitive evaluation of the presence of S. pneumoniae and thus may be a promising method of identifying pneumococci in MEFs and NPSs.

Evaluation of a Rapid Immunochromatographic ODK-0901 Test for Detection of Pneumococcal Antigen in Middle Ear Fluids and Nasopharyngeal Secretions

PubMed Central

Hotomi, Muneki; Togawa, Akihisa; Takei, Shin; Sugita, Gen; Sugita, Rinya; Kono, Masamitsu; Fujimaki, Yutaka; Kamide, Yosuke; Uchizono, Akihiro; Kanesada, Keiko; Sawada, Shoichi; Okitsu, Naohiro; Tanaka, Yumi; Saijo, Yoko; Yamanaka, Noboru

2012-01-01

Since the incidence of penicillin-resistant Streptococcus pneumoniae has been increasing at an astonishing rate throughout the world, the need for accurate and rapid identification of pneumococci has become increasingly important to determine the appropriate antimicrobial treatment. We have evaluated an immunochromatographic test (ODK-0901) that detects pneumococcal antigens using 264 middle ear fluids (MEFs) and 268 nasopharyngeal secretions (NPSs). A sample was defined to contain S. pneumoniae when optochin and bile sensitive alpha hemolytic streptococcal colonies were isolated by culture. The sensitivity and specificity of the ODK-0901 test were 81.4% and 80.5%, respectively, for MEFs from patients with acute otitis media (AOM). In addition, the sensitivity and specificity were 75.2% and 88.8%, respectively, for NPSs from patients with acute rhinosinusitis. The ODK-0901 test may provide a rapid and highly sensitive evaluation of the presence of S. pneumoniae and thus may be a promising method of identifying pneumococci in MEFs and NPSs. PMID:22448257

Adult attachment status predicts the developmental trajectory of maternal sensitivity in new motherhood among Chinese mothers.

PubMed

Liang, X; Wang, Z-Y; Liu, H-Y; Lin, Q; Wang, Z; Liu, Y

2015-01-01

to investigate adult attachment status in first-time mothers, and stability and/or changes in maternal sensitivity during infancy. longitudinal study using quantitative and qualitative methods, and statistical modelling. Three home visits were undertaken when the infant was approximately six, nine and 14 months old. The Adult-to-Parental Attachment Experience Survey was used, and scores for three dimensions were obtained: secure-autonomous, preoccupied and dismissive. Maternal sensitivity was assessed at each time point using the Maternal Behaviour Q-Sort by observing interaction between the mother and infant at home. homes and community settings in greater metropolitan Beijing, North China. 83 mothers and infants born in 2010 enrolled in this study. Data were missing for one or more time points in 20 cases. the mean score for maternal sensitivity tended to increase from six to 14 months. Post-hoc analyses of one-way repeated-measures analysis of variance revealed that maternal sensitivity was significantly higher at 14 months than at six or nine months. An unconditional latent growth model (LGM) of maternal sensitivity, estimated using the Bayesian approach, provided a good fit for the data. Using three attachment-related variables as predictors in the conditional LGM, the model fitting indices were found to be sufficient, and the results suggested that the secure score positively predicted the intercept of the growth model, and the dismissive score negatively predicted both the intercept and slope of the growth model. maternal sensitivity increased over time during infancy. Furthermore, individual differences existed in the developmental trajectory, which was influenced by maternal attachment status. knowledge about attachment-related differences in the trajectory of first-time mothers' sensitivity to infants may help midwives and doctors to provide individualised information and support, with special attention given to mothers with a dismissive attachment status. Copyright © 2014 Elsevier Ltd. All rights reserved.

A statewide evaluation of services provided to rape survivors.

PubMed

Wasco, Sharon M; Campbell, Rebecca; Howard, April; Mason, Gillian E; Staggs, Susan L; Schewe, Paul A; Riger, Stephanie

2004-02-01

This article presents the descriptive results of a statewide evaluation of hotline, advocacy, and counseling services provided to sexual assault victims in Illinois. Collaborative efforts of a multidisciplinary research team and sexual assault service providers resulted in victim-sensitive evaluation measures and data that reflect, for the first time, the collective impact of services on rape victims across the state of Illinois. Results of the evaluation suggest that, overall, services provided to rape victims provided support, increased information and knowledge, and helped victims to understand options and make decisions. The evaluation approach is notable for its collaborative nature and its sensitivity to rape victims during help-seeking and delivery; however, due to the high levels of distress common among rape survivors, some evaluation methods may not be appropriate for crisis intervention services such as hotline or advocacy. Implications for future evaluation research and policy are noted.

Dual Brushless Resolver Rate Sensor

NASA Technical Reports Server (NTRS)

Howard, David E. (Inventor)

1997-01-01

A resolver rate sensor is disclosed in which dual brushless resolvers are mechanically coupled to the same output shaft. Diverse inputs are provided to each resolver by providing the first resolver with a DC input and the second resolver with an AC sinusoidal input. A trigonometric identity in which the sum of the squares of the sin and cosine components equal one is used to advantage in providing a sensor of increased accuracy. The first resolver may have a fixed or variable DC input to permit dynamic adjustment of resolver sensitivity thus permitting a wide range of coverage. In one embodiment of the invention the outputs of the first resolver are directly inputted into two separate multipliers and the outputs of the second resolver are inputted into the two separate multipliers, after being demodulated in a pair of demodulator circuits. The multiplied signals are then added in an adder circuit to provide a directional sensitive output. In another embodiment the outputs from the first resolver is modulated in separate modulator circuits and the output from the modulator circuits are used to excite the second resolver. The outputs from the second resolver are demodulated in separate demodulator circuit and added in an adder circuit to provide a direction sensitive rate output.

Optimization of silver-dielectric-silver nanoshell for sensing applications

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

Shirzaditabar, Farzad; Saliminasab, Maryam

2013-08-15

In this paper, resonance light scattering (RLS) properties of a silver-dielectric-silver nanoshell, based on quasi-static approach and plasmon hybridization theory, are investigated. Scattering spectrum of silver-dielectric-silver nanoshell has two intense and clearly separated RLS peaks and provides a potential for biosensing based on surface plasmon resonance and surface-enhanced Raman scattering. The two RLS peaks in silver-dielectric-silver nanoshell are optimized by tuning the geometrical dimensions. In addition, the optimal geometry is discussed to obtain the high sensitivity of silver-dielectric-silver nanoshell. As the silver core radius increases, the sensitivity of silver-dielectric-silver nanoshell decreases whereas increasing the middle dielectric thickness increases the sensitivitymore » of silver-dielectric-silver nanoshell.« less

Method of making biocompatible electrodes

DOEpatents

Wollam, John S.

1992-01-01

A process of improving the sensing function of biocompatible electrodes and the product so made are disclosed. The process is designed to alter the surfaces of the electrodes at their tips to provide increased surface area and therefore decreased contact resistance at the electrode-tissue interface for increased sensitivity and essentially includes rendering the tips atomically clean by exposing them to bombardment by ions of an inert gas, depositing an adhesion layer on the cleaned tips, forming a hillocked layer on the adhesion layer by increasing the temperature of the tips, and applying a biocompatible coating on the hillocked layer. The resultant biocompatible electrode is characterized by improved sensitivity, minimum voltage requirement for organ stimulation and a longer battery life for the device in which it is employed.

Suppression of Reserve MCM Complexes Chemosensitizes to Gemcitabine and 5-Fluorouracil

PubMed Central

Bryant, Victoria L.; Elias, Roy M.; McCarthy, Susan M.; Yeatman, Timothy J.; Alexandrow, Mark G.

2015-01-01

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and is very difficult to treat with conventional chemotherapeutic regimens. Gemcitabine and 5-fluorouracil (5-FU) are used in the management of PDAC and act by indirectly blocking replicative forks. However, these drugs are not highly effective at suppressing disease progression, indicating a need for the development of innovative therapeutic approaches. Recent studies indicate that suppression of the MCM helicase may provide a novel means to sensitize cancer cells to chemotherapeutic agents that inhibit replicative fork progression. Mammalian cells assemble more MCM complexes on DNA than are required to start S-phase. The excess MCM complexes function as back-up initiation sites under conditions of replicative stress. The current study provides definitive evidence that co-suppression of the excess/back-up MCM complexes sensitizes PDAC tumor lines to both gemcitabine and 5-FU, leading to increased loss of proliferative capacity compared to drugs alone. This occurs because reduced MCM levels prevent efficient recovery of DNA replication in tumor cells exposed to drug. PDAC tumor cells are more sensitive to MCM loss in the presence of gemcitabine than are non-tumor, immortalized epithelial cells. Similarly, colon tumor cells are rendered less viable when co-suppression of MCM complexes occurs during exposure to the crosslinking agent oxaliplatin or topoisomerase inhibitor etoposide. Implications These studies demonstrate that suppressing the back-up complement of MCM complexes provides an effective sensitizing approach with the potential to increase the therapeutic index of drugs used in the clinical management of PDAC and other cancers. PMID:26063742

Suppression of Reserve MCM Complexes Chemosensitizes to Gemcitabine and 5-Fluorouracil.

PubMed

Bryant, Victoria L; Elias, Roy M; McCarthy, Susan M; Yeatman, Timothy J; Alexandrow, Mark G

2015-09-01

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and is very difficult to treat with conventional chemotherapeutic regimens. Gemcitabine and 5-fluorouracil are used in the management of PDAC and act by indirectly blocking replicative forks. However, these drugs are not highly effective at suppressing disease progression, indicating a need for the development of innovative therapeutic approaches. Recent studies indicate that suppression of the MCM helicase may provide a novel means to sensitize cancer cells to chemotherapeutic agents that inhibit replicative fork progression. Mammalian cells assemble more MCM complexes on DNA than are required to start S-phase. The excess MCM complexes function as backup initiation sites under conditions of replicative stress. The current study provides definitive evidence that cosuppression of the excess/backup MCM complexes sensitizes PDAC tumor lines to both gemcitabine and 5-FU, leading to increased loss of proliferative capacity compared with drugs alone. This occurs because reduced MCM levels prevent efficient recovery of DNA replication in tumor cells exposed to drug. PDAC tumor cells are more sensitive to MCM loss in the presence of gemcitabine than are nontumor, immortalized epithelial cells. Similarly, colon tumor cells are rendered less viable when cosuppression of MCM complexes occurs during exposure to the crosslinking agent oxaliplatin or topoisomerase inhibitor etoposide. These studies demonstrate that suppressing the backup complement of MCM complexes provides an effective sensitizing approach with the potential to increase the therapeutic index of drugs used in the clinical management of PDAC and other cancers. ©2015 American Association for Cancer Research.

Eating high fat chow increases the sensitivity of rats to 8-OH-DPAT-induced lower lip retraction.

PubMed

Li, Jun-Xu; Ju, Shutian; Baladi, Michelle G; Koek, Wouter; France, Charles P

2011-12-01

Eating high fat food can alter sensitivity to drugs acting on dopamine systems; this study examined whether eating high fat food alters sensitivity to a drug acting on serotonin (5-HT) systems. Sensitivity to (+)-8-hydroxy-2-(dipropylamino) tetralin hydrobromide (8-OH-DPAT; 5-HT1A receptor agonist)-induced lower lip retraction was examined in separate groups (n=8-9) of rats with free access to standard (5.7% fat) or high fat (34.3% fat) chow; sensitivity to quinpirole (dopamine D3/D2 receptor agonist)-induced yawning was also examined. Rats eating high fat chow gained more body weight than rats eating standard chow and, after 6 weeks of eating high fat chow, they were more sensitive to 8-OH-DPAT (0.01-0.1 mg/kg)-induced lower lip retraction and quinpirole (0.0032-0.32 mg/kg)-induced yawning. These changes were not reversed when rats that previously ate high fat chow were switched to eating standard chow and sensitivity to 8-OH-DPAT and quinpirole increased when rats that previously ate standard chow ate high fat chow. These data extend previous results showing changes in sensitivity to drugs acting on dopamine systems in animals eating high fat chow to a drug acting at 5-HT1A receptors and they provide support for the notion that eating certain foods impacts sensitivity to drugs acting on monoamine systems.

Eating high fat chow increases the sensitivity of rats to 8-OH-DPAT-induced lower lip retraction

PubMed Central

Li, Jun-Xu; Ju, Shutian; Baladi, Michelle G; Koek, Wouter; France, Charles P

2011-01-01

Eating high fat food can alter sensitivity to drugs acting on dopamine systems; this study examined whether eating high fat food alters sensitivity to a drug acting on serotonin (5-HT) systems. Sensitivity to (+)-8-hydroxy-2-(dipropylamino) tetralin hydrobromide (8-OH-DPAT; 5-HT1A receptor agonist)-induced lower lip retraction was examined in separate groups (n=8-9) of rats with free access to standard (5.7% fat) or high fat (34.3% fat) chow; sensitivity to quinpirole (dopamine D3/D2 receptor agonist)-induced yawning was also examined. Rats eating high fat chow gained more body weight than rats eating standard chow and, after 6 weeks of eating high fat chow, they were more sensitive to 8-OH-DPAT (0.01-0.1 mg/kg)-induced lower lip retraction and quinpirole (0.0032-0.32 mg/kg)-induced yawning. These changes were not reversed when rats that previously ate high fat chow were switched to eating standard chow and sensitivity to 8-OH-DPAT and quinpirole increased when rats that previously ate standard chow ate high fat chow. These data extend previous results showing changes in sensitivity to drugs acting on dopamine systems in animals eating high fat chow to a drug acting at 5-HT1A receptors and they provide support for the notion that eating certain foods impacts sensitivity to drugs acting on monoamine systems. PMID:21979831

How typical are 'typical' tremor characteristics? Sensitivity and specificity of five tremor phenomena.

PubMed

van der Stouwe, A M M; Elting, J W; van der Hoeven, J H; van Laar, T; Leenders, K L; Maurits, N M; Tijssen, M A J

2016-09-01

Distinguishing between different tremor disorders can be challenging. Some tremor disorders are thought to have typical tremor characteristics: the current study aims to provide sensitivity and specificity for five 'typical' tremor phenomena. Retrospectively, we examined 210 tremor patients referred for electrophysiological recordings between January 2008 and January 2014. The final clinical diagnosis was used as the gold standard. The first step was to determine whether patients met neurophysiological criteria for their type of tremor. Once established, we focused on 'typical' characteristics: tremor frequency decrease upon loading (enhanced physiological tremor (EPT)), amplitude increase upon loading, distractibility and entrainment (functional tremor (FT)), and intention tremor (essential tremor (ET)). The prevalence of these phenomena in the 'typical' group was compared to the whole group. Most patients (87%) concurred with all core clinical neurophysiological criteria for their tremor type. We found a frequency decrease upon loading to be a specific (95%), but not a sensitive (42%) test for EPT. Distractibility and entrainment both scored high on sensitivity (92%, 91%) and specificity (94%, 91%) in FT, whereas a tremor amplitude increase was specific (92%), but not sensitive (22%). Intention tremor was a specific finding in ET (85%), but not a sensitive test (45%). Combination of characteristics improved sensitivity. In this study, we retrospectively determined sensitivity and specificity for five 'typical' tremor characteristics. Characteristics proved specific, but few were sensitive. These data on tremor phenomenology will help practicing neurologists to improve distinction between different tremor disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Climate Sensitivity, Sea Level, and Atmospheric Carbon Dioxide

NASA Technical Reports Server (NTRS)

Hansen, James; Sato, Makiko; Russell, Gary; Kharecha, Pushker

2013-01-01

Cenozoic temperature, sea level and CO2 covariations provide insights into climate sensitivity to external forcings and sea-level sensitivity to climate change. Climate sensitivity depends on the initial climate state, but potentially can be accurately inferred from precise palaeoclimate data. Pleistocene climate oscillations yield a fast-feedback climate sensitivity of 3+/-1deg C for a 4 W/sq m CO2 forcing if Holocene warming relative to the Last Glacial Maximum (LGM) is used as calibration, but the error (uncertainty) is substantial and partly subjective because of poorly defined LGM global temperature and possible human influences in the Holocene. Glacial-to-interglacial climate change leading to the prior (Eemian) interglacial is less ambiguous and implies a sensitivity in the upper part of the above range, i.e. 3-4deg C for a 4 W/sq m CO2 forcing. Slow feedbacks, especially change of ice sheet size and atmospheric CO2, amplify the total Earth system sensitivity by an amount that depends on the time scale considered. Ice sheet response time is poorly defined, but we show that the slow response and hysteresis in prevailing ice sheet models are exaggerated. We use a global model, simplified to essential processes, to investigate state dependence of climate sensitivity, finding an increased sensitivity towards warmer climates, as low cloud cover is diminished and increased water vapour elevates the tropopause. Burning all fossil fuels, we conclude, would make most of the planet uninhabitable by humans, thus calling into question strategies that emphasize adaptation to climate change.

Ultrasonic Leak Detection System

NASA Technical Reports Server (NTRS)

Youngquist, Robert C. (Inventor); Moerk, J. Steven (Inventor)

1998-01-01

A system for detecting ultrasonic vibrations. such as those generated by a small leak in a pressurized container. vessel. pipe. or the like. comprises an ultrasonic transducer assembly and a processing circuit for converting transducer signals into an audio frequency range signal. The audio frequency range signal can be used to drive a pair of headphones worn by an operator. A diode rectifier based mixing circuit provides a simple, inexpensive way to mix the transducer signal with a square wave signal generated by an oscillator, and thereby generate the audio frequency signal. The sensitivity of the system is greatly increased through proper selection and matching of the system components. and the use of noise rejection filters and elements. In addition, a parabolic collecting horn is preferably employed which is mounted on the transducer assembly housing. The collecting horn increases sensitivity of the system by amplifying the received signals. and provides directionality which facilitates easier location of an ultrasonic vibration source.

Novel Escherichia coli RF1 mutants with decreased translation termination activity and increased sensitivity to the cytotoxic effect of the bacterial toxins Kid and RelE

PubMed Central

Diago-Navarro, Elizabeth; Mora, Liliana; Buckingham, Richard H; Díaz-Orejas, Ramón; Lemonnier, Marc

2008-01-01

Novel mutations in prfA, the gene for the polypeptide release factor RF1 of Escherichia coli, were isolated using a positive genetic screen based on the parD (kis, kid) toxin–antitoxin system. This original approach allowed the direct selection of mutants with altered translational termination efficiency at UAG codons. The isolated prfA mutants displayed a ∼10-fold decrease in UAG termination efficiency with no significant changes in RF1 stability in vivo. All three mutations, G121S, G301S and R303H, were situated close to the nonsense codon recognition site in RF1:ribosome complexes. The prfA mutants displayed increased sensitivity to the RelE toxin encoded by the relBE system of E. coli, thus providing in vivo support for the functional interaction between RF1 and RelE. The prfA mutants also showed increased sensitivity to the Kid toxin. Since this toxin can cleave RNA in a ribosome-independent manner, this result was not anticipated and provided first evidence for the involvement of RF1 in the pathway of Kid toxicity. The sensitivity of the prfA mutants to RelE and Kid was restored to normal levels upon overproduction of the wild-type RF1 protein. We discuss these results and their utility for the design of novel antibacterial strategies in the light of the recently reported structure of ribosome-bound RF1. PMID:19019162

Redox Signaling and Bioenergetics Influence Lung Cancer Cell Line Sensitivity to the Isoflavone ME-344.

PubMed

Manevich, Yefim; Reyes, Leticia; Britten, Carolyn D; Townsend, Danyelle M; Tew, Kenneth D

2016-08-01

ME-344 [(3R,4S)-3,4-bis(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H-chromen-7-ol] is a second-generation derivative natural product isoflavone presently under clinical development. ME-344 effects were compared in lung cancer cell lines that are either intrinsically sensitive or resistant to the drug and in primary immortalized human lung embryonic fibroblasts (IHLEF). Cytotoxicity at low micromolar concentrations occurred only in sensitive cell lines, causing redox stress, decreased mitochondrial ATP production, and subsequent disruption of mitochondrial function. In a dose-dependent manner the drug caused instantaneous and pronounced inhibition of oxygen consumption rates (OCR) in drug-sensitive cells (quantitatively significantly less in drug-resistant cells). This was consistent with targeting of mitochondria by ME-344, with specific effects on the respiratory chain (resistance correlated with higher glycolytic indexes). OCR inhibition did not occur in primary IHLEF. ME-344 increased extracellular acidification rates in drug-resistant cells (significantly less in drug-sensitive cells), implying that ME-344 targets mitochondrial proton pumps. Only in drug-sensitive cells did ME-344 dose-dependently increase the intracellular generation of reactive oxygen species and cause oxidation of total (mainly glutathione) and protein thiols and the concomitant immediate increases in NADPH levels. We conclude that ME-344 causes complex, redox-specific, and mitochondria-targeted effects in lung cancer cells, which differ in extent from normal cells, correlate with drug sensitivity, and provide indications of a beneficial in vitro therapeutic index. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Differential housing and novelty response: Protection and risk from locomotor sensitization

PubMed Central

Garcia, Erik J.; Haddon, Tara N.; Saucier, Donald A.; Cain, Mary E.

2017-01-01

High novelty seeking increases the risk for drug experimentation and locomotor sensitization. Locomotor sensitization to psychostimulants is thought to reflect neurological adaptations that promote the transition to compulsive drug taking. Rats reared in enrichment (EC) show less locomotor sensitization when compared to rats reared in isolation (IC) or standard conditions (SC). The current research study was designed to test if novelty response contributed locomotor sensitization and more importantly, if the different housing environments could change the novelty response to protect against the development of locomotor sensitization in both adolescence and adulthood. Experiment 1: rats were tested for their response to novelty using the inescapable novelty test (IEN) and pseudorandomly assigned to enriched (EC), isolated (IC), or standard (SC) housing conditions for 30 days. After housing, they were tested with IEN. Rats were then administered amphetamine (0.5 mg/kg) or saline and locomotor activity was measured followed by a sensitization test 14 days later. Experiment 2: rats were tested in the IEN test early adulthood and given five administrations of amphetamine (0.3 mg/kg) or saline and then either stayed in or switched housing environments for 30 days. Rats were then re-tested in the IEN test in late adulthood and administered five more injections of their respective treatments and tested for locomotor sensitization. Results indicate that IC and SC increased the response to novelty. EC housing decreased locomotor response to amphetamine and saline, and SC housing increased the locomotor response to amphetamine. Mediation results indicated that the late adult novelty response fully mediates the locomotor response to amphetamine and saline, while the early adulthood novelty response did not. Conclusions Differential housing changes novelty and amphetamine locomotor response. Novelty response is altered into adulthood and provides evidence that enrichment can be used to reduce drug vulnerability. PMID:28108176

Responses of Male C57BL/6N Mice to Observing the Euthanasia of Other Mice.

PubMed

Boivin, Gregory P; Bottomley, Michael A; Grobe, Nadja

2016-01-01

The AVMA Panel on Euthanasia recommends that sensitive animals should not be present during the euthanasia of others, especially of their own species, but does not provide guidelines on how to identify a sensitive species. To determine if mice are a sensitive species we reviewed literature on empathy in mice, and measured the cardiovascular and activity response of mice observing euthanasia of conspecifics. We studied male 16-wk-old C57BL/6N mice and found no increase in cardiovascular parameters or activity in the response of the mice to observing CO2 euthanasia. Mice observing decapitation had an increase in all values, but this was paralleled by a similar increase during mock decapitations in which no animals were handled or euthanized. We conclude that CO2 euthanasia of mice does not have an impact on other mice in the room, and that euthanasia by decapitation likely only has an effect due to the noise of the guillotine. We support the conceptual idea that mice are both a sensitive species and display empathy, but under the controlled circumstances of the euthanasia procedures used in this study there was no signaling of stress to witnessing inhabitants in the room.

Biguanides sensitize leukemia cells to ABT-737-induced apoptosis by inhibiting mitochondrial electron transport

PubMed Central

Velez, Juliana; Pan, Rongqing; Lee, Jason T.C.; Enciso, Leonardo; Suarez, Marta; Duque, Jorge Eduardo; Jaramillo, Daniel; Lopez, Catalina; Morales, Ludis; Bornmann, William; Konopleva, Marina; Krystal, Gerald; Andreeff, Michael; Samudio, Ismael

2016-01-01

Metformin displays antileukemic effects partly due to activation of AMPK and subsequent inhibition of mTOR signaling. Nevertheless, Metformin also inhibits mitochondrial electron transport at complex I in an AMPK-independent manner, Here we report that Metformin and rotenone inhibit mitochondrial electron transport and increase triglyceride levels in leukemia cell lines, suggesting impairment of fatty acid oxidation (FAO). We also report that, like other FAO inhibitors, both agents and the related biguanide, Phenformin, increase sensitivity to apoptosis induction by the bcl-2 inhibitor ABT-737 supporting the notion that electron transport antagonizes activation of the intrinsic apoptosis pathway in leukemia cells. Both biguanides and rotenone induce superoxide generation in leukemia cells, indicating that oxidative damage may sensitize toABT-737 induced apoptosis. In addition, we demonstrate that Metformin sensitizes leukemia cells to the oligomerization of Bak, suggesting that the observed synergy with ABT-737 is mediated, at least in part, by enhanced outer mitochondrial membrane permeabilization. Notably, Phenformin was at least 10-fold more potent than Metformin in abrogating electron transport and increasing sensitivity to ABT-737, suggesting that this agent may be better suited for targeting hematological malignancies. Taken together, our results suggest that inhibition of mitochondrial metabolism by Metformin or Phenformin is associated with increased leukemia cell susceptibility to induction of intrinsic apoptosis, and provide a rationale for clinical studies exploring the efficacy of combining biguanides with the orally bioavailable derivative of ABT-737, Venetoclax. PMID:27283492

Biguanides sensitize leukemia cells to ABT-737-induced apoptosis by inhibiting mitochondrial electron transport.

PubMed

Velez, Juliana; Pan, Rongqing; Lee, Jason T C; Enciso, Leonardo; Suarez, Marta; Duque, Jorge Eduardo; Jaramillo, Daniel; Lopez, Catalina; Morales, Ludis; Bornmann, William; Konopleva, Marina; Krystal, Gerald; Andreeff, Michael; Samudio, Ismael

2016-08-09

Metformin displays antileukemic effects partly due to activation of AMPK and subsequent inhibition of mTOR signaling. Nevertheless, Metformin also inhibits mitochondrial electron transport at complex I in an AMPK-independent manner, Here we report that Metformin and rotenone inhibit mitochondrial electron transport and increase triglyceride levels in leukemia cell lines, suggesting impairment of fatty acid oxidation (FAO). We also report that, like other FAO inhibitors, both agents and the related biguanide, Phenformin, increase sensitivity to apoptosis induction by the bcl-2 inhibitor ABT-737 supporting the notion that electron transport antagonizes activation of the intrinsic apoptosis pathway in leukemia cells. Both biguanides and rotenone induce superoxide generation in leukemia cells, indicating that oxidative damage may sensitize toABT-737 induced apoptosis. In addition, we demonstrate that Metformin sensitizes leukemia cells to the oligomerization of Bak, suggesting that the observed synergy with ABT-737 is mediated, at least in part, by enhanced outer mitochondrial membrane permeabilization. Notably, Phenformin was at least 10-fold more potent than Metformin in abrogating electron transport and increasing sensitivity to ABT-737, suggesting that this agent may be better suited for targeting hematological malignancies. Taken together, our results suggest that inhibition of mitochondrial metabolism by Metformin or Phenformin is associated with increased leukemia cell susceptibility to induction of intrinsic apoptosis, and provide a rationale for clinical studies exploring the efficacy of combining biguanides with the orally bioavailable derivative of ABT-737, Venetoclax.

[Advances of tumor targeting peptides drug delivery system with pH-sensitive activities].

PubMed

Ma, Yin-yun; Li, Li; Huang, Hai-feng; Gou, San-hu; Ni, Jing-man

2016-05-01

The pH-sensitive peptides drug delivery systems, which target to acidic extracellular environment of tumor tissue, have many advantages in drug delivery. They exhibit a high specificity to tumor and low cytotoxicity, which significantly increase the efficacy of traditional anti-cancer drugs. In recent years the systems have received a great attention. The pH-sensitive peptides drug delivery systems can be divided into five types according to the difference in pH-responsive mechanism,type of peptides and carrier materials. This paper summarizes the recent progresses in the field with a focus on the five types of pH-sensitive peptides in drug delivery systems. This may provide a guideline to design and application of tumor targeting drugs.

DELAYED HYPERSENSITIVITY

PubMed Central

Uhr, Jonathan W.; Salvin, S. B.; Pappenheimer, A. M.

1957-01-01

A general method for induction of the delayed hypersensitive state directed against single protein antigens is described. The method consists of intradermal injection of minute amounts of washed immune precipitates containing the antigen in question. Provided the specific precipitates are formed in the region of antibody excess, maximal sensitivity develops at least 2 to 3 weeks before detectable circulating antibody is formed in guinea pigs against the sensitizing antigen. Neither adjuvant nor killed acid-fast bacteria are required for induction of the delayed hypersensitive state although the degree of sensitization is considerably increased when the sensitizing material is incorporated in Freund's complete adjuvant. Characteristics of the "delayed" as opposed to the "immediate" hypersensitive states in the guinea pig are described and implications of the findings are discussed. PMID:13385403

Modeling the Sensitivity of Field Surveys for Detection of Environmental DNA (eDNA)

PubMed Central

Schultz, Martin T.; Lance, Richard F.

2015-01-01

The environmental DNA (eDNA) method is the practice of collecting environmental samples and analyzing them for the presence of a genetic marker specific to a target species. Little is known about the sensitivity of the eDNA method. Sensitivity is the probability that the target marker will be detected if it is present in the water body. Methods and tools are needed to assess the sensitivity of sampling protocols, design eDNA surveys, and interpret survey results. In this study, the sensitivity of the eDNA method is modeled as a function of ambient target marker concentration. The model accounts for five steps of sample collection and analysis, including: 1) collection of a filtered water sample from the source; 2) extraction of DNA from the filter and isolation in a purified elution; 3) removal of aliquots from the elution for use in the polymerase chain reaction (PCR) assay; 4) PCR; and 5) genetic sequencing. The model is applicable to any target species. For demonstration purposes, the model is parameterized for bighead carp (Hypophthalmichthys nobilis) and silver carp (H. molitrix) assuming sampling protocols used in the Chicago Area Waterway System (CAWS). Simulation results show that eDNA surveys have a high false negative rate at low concentrations of the genetic marker. This is attributed to processing of water samples and division of the extraction elution in preparation for the PCR assay. Increases in field survey sensitivity can be achieved by increasing sample volume, sample number, and PCR replicates. Increasing sample volume yields the greatest increase in sensitivity. It is recommended that investigators estimate and communicate the sensitivity of eDNA surveys to help facilitate interpretation of eDNA survey results. In the absence of such information, it is difficult to evaluate the results of surveys in which no water samples test positive for the target marker. It is also recommended that invasive species managers articulate concentration-based sensitivity objectives for eDNA surveys. In the absence of such information, it is difficult to design appropriate sampling protocols. The model provides insights into how sampling protocols can be designed or modified to achieve these sensitivity objectives. PMID:26509674

Modeling the Sensitivity of Field Surveys for Detection of Environmental DNA (eDNA).

PubMed

Schultz, Martin T; Lance, Richard F

2015-01-01

The environmental DNA (eDNA) method is the practice of collecting environmental samples and analyzing them for the presence of a genetic marker specific to a target species. Little is known about the sensitivity of the eDNA method. Sensitivity is the probability that the target marker will be detected if it is present in the water body. Methods and tools are needed to assess the sensitivity of sampling protocols, design eDNA surveys, and interpret survey results. In this study, the sensitivity of the eDNA method is modeled as a function of ambient target marker concentration. The model accounts for five steps of sample collection and analysis, including: 1) collection of a filtered water sample from the source; 2) extraction of DNA from the filter and isolation in a purified elution; 3) removal of aliquots from the elution for use in the polymerase chain reaction (PCR) assay; 4) PCR; and 5) genetic sequencing. The model is applicable to any target species. For demonstration purposes, the model is parameterized for bighead carp (Hypophthalmichthys nobilis) and silver carp (H. molitrix) assuming sampling protocols used in the Chicago Area Waterway System (CAWS). Simulation results show that eDNA surveys have a high false negative rate at low concentrations of the genetic marker. This is attributed to processing of water samples and division of the extraction elution in preparation for the PCR assay. Increases in field survey sensitivity can be achieved by increasing sample volume, sample number, and PCR replicates. Increasing sample volume yields the greatest increase in sensitivity. It is recommended that investigators estimate and communicate the sensitivity of eDNA surveys to help facilitate interpretation of eDNA survey results. In the absence of such information, it is difficult to evaluate the results of surveys in which no water samples test positive for the target marker. It is also recommended that invasive species managers articulate concentration-based sensitivity objectives for eDNA surveys. In the absence of such information, it is difficult to design appropriate sampling protocols. The model provides insights into how sampling protocols can be designed or modified to achieve these sensitivity objectives.

Teaching Preschool Children about Nature: A Project to Provide Soil Education for Children in Turkey

ERIC Educational Resources Information Center

Ogelman, Hulya Gulay

2012-01-01

In terms of gaining environmental awareness and sensitivity, preschool is the most important period in an individual's life. Preschool education enables lasting steps to be taken towards sustainable development, which has become widespread issue of increasing importance in recent years, and whose importance continues to increase. There is a need…

Permanent-magnet flowmeter having improved output-terminal means

DOEpatents

August, C.; Myers, H.J.

1981-10-26

Disclosed is an improved permanent magnet flowmeter capable of withstanding bending stresses in the direction of induced emf signals. The flowmeter includes a unique terminal arrangement integrally formed with the flowmeter by trepanning opposing wall sections of the flowmeter body. The terminal arrangement provides increased flowmeter sensitivity by increasing the strength of the induced emf signals.

The reinforcing value of vegetables does not increase with repeated exposure during a randomized controlled provided vegetable intervention among overweight and obese adults

USDA-ARS?s Scientific Manuscript database

Objective: The primary aim of this randomized controlled trial is to determine whether the relative reinforcing value (RRV) of vegetables compared to a snack food can be increased through repeated exposure (incentive sensitization) to amounts of vegetables recommended by the Dietary Guidelines for A...

Permanent magnet flowmeter having improved output terminal means

DOEpatents

August, Charles; Myers, Harry J.

1984-01-01

Disclosed is an improved permanent magnet flowmeter capable of withstanding bending stresses in the direction of induced emf signals. The flowmeter includes a unique terminal arrangement integrally formed with the flowmeter by trepanning opposing wall sections of the flowmeter body. The terminal arrangement provides increased flowmeter sensitivity by increasing the strength of the induced emf signals.

MEK5/ERK5 signaling inhibition increases colon cancer cell sensitivity to 5-fluorouracil through a p53-dependent mechanism

PubMed Central

Pereira, Diane M.; Simões, André E. S.; Gomes, Sofia E.; Castro, Rui E.; Carvalho, Tânia; Rodrigues, Cecília M. P.; Borralho, Pedro M.

2016-01-01

The MEK5/ERK5 signaling pathway is emerging as an important contributor to colon cancer onset, progression and metastasis; however, its relevance to chemotherapy resistance remains unknown. Here, we evaluated the impact of the MEK5/ERK5 cascade in colon cancer cell sensitivity to 5-fluorouracil (5-FU). Increased ERK5 expression was correlated with poor overall survival in colon cancer patients. In colon cancer cells, 5-FU exposure impaired endogenous KRAS/MEK5/ERK5 expression and/or activation. In turn, MEK5 constitutive activation reduced 5-FU-induced cytotoxicity. Using genetic and pharmacological approaches, we showed that ERK5 inhibition increased caspase-3/7 activity and apoptosis following 5-FU exposure. Mechanistically, this was further associated with increased p53 transcriptional activation of p21 and PUMA. In addition, ERK5 inhibition increased the response of HCT116 p53+/+ cells to 5-FU, but failed to sensitize HCT116 p53−/− cells to the cytotoxic effects of this chemotherapeutic agent, suggesting a p53-dependent axis mediating 5-FU sensitization. Finally, ERK5 inhibition using XMD8-92 was shown to increase the antitumor effects of 5-FU in a murine subcutaneous xenograft model, enhancing apoptosis while markedly reducing tumor growth. Collectively, our results suggest that ERK5-targeted in hibition provides a promising therapeutic approach to overcome resistance to 5-FU-based chemotherapy and improve colon cancer treatment. PMID:27144434

The Usefulness of Selected Physicochemical Indices, Cell Membrane Integrity and Sperm Chromatin Structure in Assessments of Boar Semen Sensitivity

PubMed Central

Wysokińska, A.; Kondracki, S.; Iwanina, M.

2015-01-01

The present work describes experiments undertaken to evaluate the usefulness of selected physicochemical indices of semen, cell membrane integrity and sperm chromatin structure for the assessment of boar semen sensitivity to processes connected with pre-insemination procedures. The experiments were carried out on 30 boars: including 15 regarded as providers of sensitive semen and 15 regarded as providers of semen that is little sensitive to laboratory processing. The selection of boars for both groups was based on sperm morphology analyses, assuming secondary morphological change incidence in spermatozoa as the criterion. Two ejaculates were manually collected from each boar at an interval of 3 to 4 months. The following analyses were carried out for each ejaculate: sperm motility assessment, sperm pH measurement, sperm morphology assessment, sperm chromatin structure evaluation and cell membrane integrity assessment. The analyses were performed three times. Semen storage did not cause an increase in the incidence of secondary morphological changes in the group of boars considered to provide sperm of low sensitivity. On the other hand, with continued storage there was a marked increase in the incidence of spermatozoa with secondary morphological changes in the group of boars regarded as producing more sensitive semen. Ejaculates of group I boars evaluated directly after collection had an approximately 6% smaller share of spermatozoa with undamaged cell membranes than the ejaculates of boars in group II (p≤0.05). In the process of time the percentage of spermatozoa with undamaged cell membranes decreased. The sperm of group I boars was characterised with a lower sperm motility than the semen of group II boars. After 1 hour of storing diluted semen, the sperm motility of boars producing highly sensitive semen was already 4% lower (p≤0.05), and after 24 hours of storage it was 6.33% lower than that of the boars that produced semen with a low sensitivity. Factors that confirm the accuracy of insemination male selection can include a low rate of sperm motility decrease during the storage of diluted semen, low and contained incidence of secondary morphological changes in spermatozoa during semen storage and a high frequency of spermatozoa with undamaged cell membranes. PMID:26580438

Differential sensitivity of the Response Bias Scale (RBS) and MMPI-2 validity scales to memory complaints.

PubMed

Gervais, Roger O; Ben-Porath, Yossef S; Wygant, Dustin B; Green, Paul

2008-12-01

The MMPI-2 Response Bias Scale (RBS) is designed to detect response bias in forensic neuropsychological and disability assessment settings. Validation studies have demonstrated that the scale is sensitive to cognitive response bias as determined by failure on the Word Memory Test (WMT) and other symptom validity tests. Exaggerated memory complaints are a common feature of cognitive response bias. The present study was undertaken to determine the extent to which the RBS is sensitive to memory complaints and how it compares in this regard to other MMPI-2 validity scales and indices. This archival study used MMPI-2 and Memory Complaints Inventory (MCI) data from 1550 consecutive non-head-injury disability-related referrals to the first author's private practice. ANOVA results indicated significant increases in memory complaints across increasing RBS score ranges with large effect sizes. Regression analyses indicated that the RBS was a better predictor of the mean memory complaints score than the F, F(B), and F(P) validity scales and the FBS. There was no correlation between the RBS and the CVLT, an objective measure of verbal memory. These findings suggest that elevated scores on the RBS are associated with over-reporting of memory problems, which provides further external validation of the RBS as a sensitive measure of cognitive response bias. Interpretive guidelines for the RBS are provided.

What makes a chemical an allergen?

PubMed

Kimber, Ian; Dearman, Rebecca J

2003-05-01

To consider the factors that confer on chemicals the ability to cause allergic sensitization, with particular emphasis on the induction of skin sensitization. Original and review articles available in the scientific literature. The expert opinion of the authors was used to select studies for inclusion in this review. A number of requirements must be met if a chemical is to induce skin sensitization. The most important requirements are access to the viable epidermis, the formation of stable conjugates with proteins, elicitation of cytokine production by skin cells, and the initiation of T-lymphocyte responses. In addition, qualitative aspects of induced immune responses influence the form of allergic sensitization. An increasingly sophisticated understanding of the factors required for the development of skin sensitization and other forms of chemical-induced allergy provides new opportunities for toxicological investigation and clinical management.

Experimental study on the sensitive depth of backwards detected light in turbid media.

PubMed

Zhang, Yunyao; Huang, Liqing; Zhang, Ning; Tian, Heng; Zhu, Jingping

2018-05-28

In the recent past, optical spectroscopy and imaging methods for biomedical diagnosis and target enhancing have been widely researched. The challenge to improve the performance of these methods is to know the sensitive depth of the backwards detected light well. Former research mainly employed a Monte Carlo method to run simulations to statistically describe the light sensitive depth. An experimental method for investigating the sensitive depth was developed and is presented here. An absorption plate was employed to remove all the light that may have travelled deeper than the plate, leaving only the light which cannot reach the plate. By measuring the received backwards light intensity and the depth between the probe and the plate, the light intensity distribution along the depth dimension can be achieved. The depth with the maximum light intensity was recorded as the sensitive depth. The experimental results showed that the maximum light intensity was nearly the same in a short depth range. It could be deduced that the sensitive depth was a range, rather than a single depth. This sensitive depth range as well as its central depth increased consistently with the increasing source-detection distance. Relationships between sensitive depth and optical properties were also investigated. It also showed that the reduced scattering coefficient affects the central sensitive depth and the range of the sensitive depth more than the absorption coefficient, so they cannot be simply added as reduced distinct coefficients to describe the sensitive depth. This study provides an efficient method for investigation of sensitive depth. It may facilitate the development of spectroscopy and imaging techniques for biomedical diagnosis and underwater imaging.

Targeted disruption of FANCC and FANCG in human cancer provides a preclinical model for specific therapeutic options.

PubMed

Gallmeier, Eike; Calhoun, Eric S; Rago, Carlo; Brody, Jonathan R; Cunningham, Steven C; Hucl, Tomas; Gorospe, Myriam; Kohli, Manu; Lengauer, Christoph; Kern, Scott E

2006-06-01

How specifically to treat pancreatic and other cancers harboring Fanconi anemia gene mutations has raised great interest recently, yet preclinical studies have been hampered by the lack of well-controlled human cancer models. We endogenously disrupted FANCC and FANCG in a human adenocarcinoma cell line and determined the impact of these genes on drug sensitivity, irradiation sensitivity, and genome maintenance. FANCC and FANCG disruption abrogated FANCD2 monoubiquitination, confirming an impaired Fanconi anemia pathway function. On treatment with DNA interstrand-cross-linking agents, FANCC and FANCG disruption caused increased clastogenic damage, G2/M arrest, and decreased proliferation. The extent of hypersensitivity varied among agents, with ratios of inhibitory concentration 50% ranging from 2-fold for oxaliplatin to 14-fold for melphalan, a drug infrequently used in solid tumors. No hypersensitivity was observed on gemcitabine, etoposide, 3-aminobenzamide, NU1025, or hydrogen peroxide. FANCC and FANCG disruption also resulted in increased clastogenic damage on irradiation, but only FANCG disruption caused a subsequent decrease in relative survival. Finally, FANCC and FANCG disruption increased spontaneous chromosomal breakage, supporting the role of these genes in genome maintenance and likely explaining why they are mutated in sporadic cancer. Our human cancer cell model provides optimal controls to elucidate fundamental biologic features of individual Fanconi anemia gene defects and facilitates preclinical studies of therapeutic options. The impact of Fanconi gene defects on drug and irradiation sensitivity renders these genes promising targets for a specific, genotype-based therapy for individual cancer patients, providing a strong rationale for clinical trials.

Why sensitive bacteria are resistant to hospital infection control

PubMed Central

van Kleef, Esther; Luangasanatip, Nantasit; Bonten, Marc J; Cooper, Ben S

2017-01-01

Background: Large reductions in the incidence of antibiotic-resistant strains of Staphylococcus aureus and Clostridium difficile have been observed in response to multifaceted hospital-based interventions. Reductions in antibiotic-sensitive strains have been smaller or non-existent. It has been argued that since infection control measures, such as hand hygiene, should affect resistant and sensitive strains equally, observed changes must have largely resulted from other factors, including changes in antibiotic use. We used a mathematical model to test the validity of this reasoning. Methods: We developed a mechanistic model of resistant and sensitive strains in a hospital and its catchment area. We assumed the resistant strain had a competitive advantage in the hospital and the sensitive strain an advantage in the community. We simulated a hospital hand hygiene intervention that directly affected resistant and sensitive strains equally. The annual incidence rate ratio ( IRR) associated with the intervention was calculated for hospital- and community-acquired infections of both strains. Results: For the resistant strain, there were large reductions in hospital-acquired infections (0.1 ≤ IRR ≤ 0.6) and smaller reductions in community-acquired infections (0.2 ≤ IRR ≤  0.9). These reductions increased in line with increasing importance of nosocomial transmission of the strain. For the sensitive strain, reductions in hospital acquisitions were much smaller (0.6 ≤ IRR ≤ 0.9), while communityacquisitions could increase or decrease (0.9 ≤ IRR ≤ 1.2). The greater the importance of the community environment for the transmission of the sensitive strain, the smaller the reductions. Conclusions: Counter-intuitively, infection control interventions, including hand hygiene, can have strikingly discordant effects on resistant and sensitive strains even though they target them equally, following differences in their adaptation to hospital and community-based transmission. Observed lack of effectiveness of control measures for sensitive strains does not provide evidence that infection control interventions have been ineffective in reducing resistant strains. PMID:29260003

Why sensitive bacteria are resistant to hospital infection control.

PubMed

van Kleef, Esther; Luangasanatip, Nantasit; Bonten, Marc J; Cooper, Ben S

2017-01-01

Large reductions in the incidence of antibiotic-resistant strains of Staphylococcus aureus and Clostridium difficile have been observed in response to multifaceted hospital-based interventions. Reductions in antibiotic-sensitive strains have been smaller or non-existent. It has been argued that since infection control measures, such as hand hygiene, should affect resistant and sensitive strains equally, observed changes must have largely resulted from other factors, including changes in antibiotic use. We used a mathematical model to test the validity of this reasoning. We developed a mechanistic model of resistant and sensitive strains in a hospital and its catchment area. We assumed the resistant strain had a competitive advantage in the hospital and the sensitive strain an advantage in the community. We simulated a hospital hand hygiene intervention that directly affected resistant and sensitive strains equally. The annual incidence rate ratio (IRR) associated with the intervention was calculated for hospital- and community-acquired infections of both strains. For the resistant strain, there were large reductions in hospital-acquired infections (0.1 ≤ IRR ≤ 0.6) and smaller reductions in community-acquired infections (0.2 ≤ IRR ≤ 0.9). These reductions increased in line with increasing importance of nosocomial transmission of the strain. For the sensitive strain, reductions in hospital acquisitions were much smaller (0.6 ≤ IRR ≤ 0.9), while community acquisitions could increase or decrease (0.9 ≤ IRR ≤ 1.2). The greater the importance of the community environment for the transmission of the sensitive strain, the smaller the reductions. Counter-intuitively, infection control interventions, including hand hygiene, can have strikingly discordant effects on resistant and sensitive strains even though they target them equally. This follows from differences in their adaptation to hospital- and community-based transmission. Observed lack of effectiveness of control measures for sensitive strains does not provide evidence that infection control interventions have been ineffective in reducing resistant strains.

The pilosebaceous unit—a phthalate-induced pathway to skin sensitization

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

Simonsson, Carl, E-mail: carl.simonsson@chem.gu.se; Stenfeldt, Anna-Lena; Karlberg, Ann-Therese

2012-10-01

Allergic contact dermatitis (ACD) is caused by low-molecular weight compounds called haptens. It has been shown that the potency of haptens can depend on the formulation in which they are applied on the skin. Specifically the sensitization potency of isothiocyanates, a group of haptens which can be released from e.g. adhesive tapes and neoprene materials, increases with the presence of phthalates; however, the underlying mechanisms are not clear. A better understanding of the mechanisms governing the potency of haptens is important, e.g. to improve the risk assessment and the formulation of chemicals in consumer products. In this study we havemore » explored phthalate-induced effects on the sensitization potency, skin distribution, and reactivity of fluorescent model isothiocyanate haptens using non-invasive two-photon microscopy to provide new insights regarding vehicle effects in ACD. The data presented in this paper indicate that the sensitization potency of isothiocyanates increases when applied in combination with dibutylphthalate due to a specific uptake via the pilosebaceous units. The results highlight the importance of shunt pathways when evaluating the bioavailability of skin sensitizers. The findings also indicate that vehicle-dependent hapten reactivity towards stratum corneum proteins regulates the bioavailability, and thus the potency, of skin sensitizers. -- Highlights: ► Vehicle effects on sensitization potency were investigated in the LLNA. ► In vivo cutaneous absorption of contact sensitizers was visualized using TPM. ► Sensitizing potency of isothiocyanates depends on the presence of a phthalate. ► Phthalate induced cutaneous absorption via the pilosebaceous units. ► Vehicle-dependent reactivity regulates sensitization potency.« less

High-sensitivity detection of triacetone triperoxide (TATP) and its precursor acetone

NASA Astrophysics Data System (ADS)

Dunayevskiy, Ilya; Tsekoun, Alexei; Prasanna, Manu; Go, Rowel; Patel, C. Kumar N.

2007-09-01

Triacetone triperoxide (C9H18O6, molecular mass of 222.24 g/mol) (TATP) is a powerful explosive that is easy to synthesize using commonly available household chemicals, acetone, and hydrogen peroxide 1 2. Because of the simplicity of its synthesis, TATP is often the explosive of choice for terrorists, including suicide bombers. For providing safety to the population, early detection of TATP and isolation of such individuals are essential. We report unambiguous, high-sensitivity detection of TATP and its precursor, acetone, using room-temperature quantum cascade laser photoacoustic spectroscopy (QCL-PAS). The available sensitivity is such that TATP, carried on a person (at a nominal body temperature of 37 °C), should be detectable at some distance. The combination of demonstrated detection of TATP and acetone should be ideal for screening at airports and other public places for providing increased public safety.

A community effort to assess and improve drug sensitivity prediction algorithms

PubMed Central

Costello, James C; Heiser, Laura M; Georgii, Elisabeth; Gönen, Mehmet; Menden, Michael P; Wang, Nicholas J; Bansal, Mukesh; Ammad-ud-din, Muhammad; Hintsanen, Petteri; Khan, Suleiman A; Mpindi, John-Patrick; Kallioniemi, Olli; Honkela, Antti; Aittokallio, Tero; Wennerberg, Krister; Collins, James J; Gallahan, Dan; Singer, Dinah; Saez-Rodriguez, Julio; Kaski, Samuel; Gray, Joe W; Stolovitzky, Gustavo

2015-01-01

Predicting the best treatment strategy from genomic information is a core goal of precision medicine. Here we focus on predicting drug response based on a cohort of genomic, epigenomic and proteomic profiling data sets measured in human breast cancer cell lines. Through a collaborative effort between the National Cancer Institute (NCI) and the Dialogue on Reverse Engineering Assessment and Methods (DREAM) project, we analyzed a total of 44 drug sensitivity prediction algorithms. The top-performing approaches modeled nonlinear relationships and incorporated biological pathway information. We found that gene expression microarrays consistently provided the best predictive power of the individual profiling data sets; however, performance was increased by including multiple, independent data sets. We discuss the innovations underlying the top-performing methodology, Bayesian multitask MKL, and we provide detailed descriptions of all methods. This study establishes benchmarks for drug sensitivity prediction and identifies approaches that can be leveraged for the development of new methods. PMID:24880487

A community effort to assess and improve drug sensitivity prediction algorithms.

PubMed

Costello, James C; Heiser, Laura M; Georgii, Elisabeth; Gönen, Mehmet; Menden, Michael P; Wang, Nicholas J; Bansal, Mukesh; Ammad-ud-din, Muhammad; Hintsanen, Petteri; Khan, Suleiman A; Mpindi, John-Patrick; Kallioniemi, Olli; Honkela, Antti; Aittokallio, Tero; Wennerberg, Krister; Collins, James J; Gallahan, Dan; Singer, Dinah; Saez-Rodriguez, Julio; Kaski, Samuel; Gray, Joe W; Stolovitzky, Gustavo

2014-12-01

Predicting the best treatment strategy from genomic information is a core goal of precision medicine. Here we focus on predicting drug response based on a cohort of genomic, epigenomic and proteomic profiling data sets measured in human breast cancer cell lines. Through a collaborative effort between the National Cancer Institute (NCI) and the Dialogue on Reverse Engineering Assessment and Methods (DREAM) project, we analyzed a total of 44 drug sensitivity prediction algorithms. The top-performing approaches modeled nonlinear relationships and incorporated biological pathway information. We found that gene expression microarrays consistently provided the best predictive power of the individual profiling data sets; however, performance was increased by including multiple, independent data sets. We discuss the innovations underlying the top-performing methodology, Bayesian multitask MKL, and we provide detailed descriptions of all methods. This study establishes benchmarks for drug sensitivity prediction and identifies approaches that can be leveraged for the development of new methods.

Practical considerations for a second-order directional hearing aid microphone system

NASA Astrophysics Data System (ADS)

Thompson, Stephen C.

2003-04-01

First-order directional microphone systems for hearing aids have been available for several years. Such a system uses two microphones and has a theoretical maximum free-field directivity index (DI) of 6.0 dB. A second-order microphone system using three microphones could provide a theoretical increase in free-field DI to 9.5 dB. These theoretical maximum DI values assume that the microphones have exactly matched sensitivities at all frequencies of interest. In practice, the individual microphones in the hearing aid always have slightly different sensitivities. For the small microphone separation necessary to fit in a hearing aid, these sensitivity matching errors degrade the directivity from the theoretical values, especially at low frequencies. This paper shows that, for first-order systems the directivity degradation due to sensitivity errors is relatively small. However, for second-order systems with practical microphone sensitivity matching specifications, the directivity degradation below 1 kHz is not tolerable. A hybrid order directive system is proposed that uses first-order processing at low frequencies and second-order directive processing at higher frequencies. This hybrid system is suggested as an alternative that could provide improved directivity index in the frequency regions that are important to speech intelligibility.

A new framework for comprehensive, robust, and efficient global sensitivity analysis: 1. Theory

NASA Astrophysics Data System (ADS)

Razavi, Saman; Gupta, Hoshin V.

2016-01-01

Computer simulation models are continually growing in complexity with increasingly more factors to be identified. Sensitivity Analysis (SA) provides an essential means for understanding the role and importance of these factors in producing model responses. However, conventional approaches to SA suffer from (1) an ambiguous characterization of sensitivity, and (2) poor computational efficiency, particularly as the problem dimension grows. Here, we present a new and general sensitivity analysis framework (called VARS), based on an analogy to "variogram analysis," that provides an intuitive and comprehensive characterization of sensitivity across the full spectrum of scales in the factor space. We prove, theoretically, that Morris (derivative-based) and Sobol (variance-based) methods and their extensions are special cases of VARS, and that their SA indices can be computed as by-products of the VARS framework. Synthetic functions that resemble actual model response surfaces are used to illustrate the concepts, and show VARS to be as much as two orders of magnitude more computationally efficient than the state-of-the-art Sobol approach. In a companion paper, we propose a practical implementation strategy, and demonstrate the effectiveness, efficiency, and reliability (robustness) of the VARS framework on real-data case studies.

Blacks against Korean Merchants: An Interpretation of Contributory Factors.

ERIC Educational Resources Information Center

Kim, K. Hugh

1990-01-01

Examines the 1990 boycott of Korean-owned food stores in Brooklyn by African Americans. Provides background on ethnic conflicts in America, especially those involving Asian Americans. Calls for increased racial and cultural sensitivity in communities and schools. (DM)

Assessment of the impact of increased solar ultraviolet radiation upon marine ecosystems

NASA Technical Reports Server (NTRS)

Vandyke, H.; Worrest, R. C.

1976-01-01

Data was provided to assess the potential impact upon marine ecosystems if space shuttle operations contribute to a reduction of the stratospheric ozone layer. The potential for irreversible damage to the productivity, structure and/or functioning of a model estuarine ecosystem by increased UV-B radiation was established. The sensitivity of key community components (the primary producers) to increased UV-B radiation was delineated.

Simplified and Efficient Quantification of Low-abundance Proteins at Very High Multiplex via Targeted Mass Spectrometry*

PubMed Central

Burgess, Michael W.; Keshishian, Hasmik; Mani, D. R.; Gillette, Michael A.; Carr, Steven A.

2014-01-01

Liquid chromatography–multiple reaction monitoring mass spectrometry (LC-MRM-MS) of plasma that has been depleted of abundant proteins and fractionated at the peptide level into six to eight fractions is a proven method for quantifying proteins present at low nanogram-per-milliliter levels. A drawback of fraction-MRM is the increased analysis time due to the generation of multiple fractions per biological sample. We now report that the use of heated, long, fused silica columns (>30 cm) packed with 1.9 μm of packing material can reduce or eliminate the need for fractionation prior to LC-MRM-MS without a significant loss of sensitivity or precision relative to fraction-MRM. We empirically determined the optimal column length, temperature, gradient duration, and sample load for such assays and used these conditions to study detection sensitivity and assay precision. In addition to increased peak capacity, longer columns packed with smaller beads tolerated a 4- to 6-fold increase in analyte load without a loss of robustness or reproducibility. The longer columns also provided a 4-fold improvement in median limit-of-quantitation values with increased assay precision relative to the standard 12 cm columns packed with 3 μm material. Overall, the optimized chromatography provided an approximately 3-fold increase in analysis throughput with excellent robustness and less than a 2-fold reduction in quantitative sensitivity relative to fraction-MRM. The value of the system for increased multiplexing was demonstrated by the ability to configure an 800-plex MRM-MS assay, run in a single analysis, comprising 2400 transitions with retention time scheduling to monitor 400 unlabeled and heavy labeled peptide pairs. PMID:24522978

Comparison of two cash transfer strategies to prevent catastrophic costs for poor tuberculosis-affected households in low- and middle-income countries: An economic modelling study.

PubMed

Rudgard, William E; Evans, Carlton A; Sweeney, Sedona; Wingfield, Tom; Lönnroth, Knut; Barreira, Draurio; Boccia, Delia

2017-11-01

Illness-related costs for patients with tuberculosis (TB) ≥20% of pre-illness annual household income predict adverse treatment outcomes and have been termed "catastrophic." Social protection initiatives, including cash transfers, are endorsed to help prevent catastrophic costs. With this aim, cash transfers may either be provided to defray TB-related costs of households with a confirmed TB diagnosis (termed a "TB-specific" approach); or to increase income of households with high TB risk to strengthen their economic resilience (termed a "TB-sensitive" approach). The impact of cash transfers provided with each of these approaches might vary. We undertook an economic modelling study from the patient perspective to compare the potential of these 2 cash transfer approaches to prevent catastrophic costs. Model inputs for 7 low- and middle-income countries (Brazil, Colombia, Ecuador, Ghana, Mexico, Tanzania, and Yemen) were retrieved by literature review and included countries' mean patient TB-related costs, mean household income, mean cash transfers, and estimated TB-specific and TB-sensitive target populations. Analyses were completed for drug-susceptible (DS) TB-related costs in all 7 out of 7 countries, and additionally for drug-resistant (DR) TB-related costs in 1 of the 7 countries with available data. All cost data were reported in 2013 international dollars ($). The target population for TB-specific cash transfers was poor households with a confirmed TB diagnosis, and for TB-sensitive cash transfers was poor households already targeted by countries' established poverty-reduction cash transfer programme. Cash transfers offered in countries, unrelated to TB, ranged from $217 to $1,091/year/household. Before cash transfers, DS TB-related costs were catastrophic in 6 out of 7 countries. If cash transfers were provided with a TB-specific approach, alone they would be insufficient to prevent DS TB catastrophic costs in 4 out of 6 countries, and when increased enough to prevent DS TB catastrophic costs would require a budget between $3.8 million (95% CI: $3.8 million-$3.8 million) and $75 million (95% CI: $50 million-$100 million) per country. If instead cash transfers were provided with a TB-sensitive approach, alone they would be insufficient to prevent DS TB-related catastrophic costs in any of the 6 countries, and when increased enough to prevent DS TB catastrophic costs would require a budget between $298 million (95% CI: $219 million-$378 million) and $165,367 million (95% CI: $134,085 million-$196,425 million) per country. DR TB-related costs were catastrophic before and after TB-specific or TB-sensitive cash transfers in 1 out of 1 countries. Sensitivity analyses showed our findings to be robust to imputation of missing TB-related cost components, and use of 10% or 30% instead of 20% as the threshold for measuring catastrophic costs. Key limitations were using national average data and not considering other health and social benefits of cash transfers. A TB-sensitive cash transfer approach to increase all poor households' income may have broad benefits by reducing poverty, but is unlikely to be as effective or affordable for preventing TB catastrophic costs as a TB-specific cash transfer approach to defray TB-related costs only in poor households with a confirmed TB diagnosis. Preventing DR TB-related catastrophic costs will require considerable additional investment whether a TB-sensitive or a TB-specific cash transfer approach is used.

Methionine Deprivation Induces a Targetable Vulnerability in Triple-negative Breast Cancer Cells by Enhancing TRAIL Receptor-2 Expression

PubMed Central

Strekalova, Elena; Malin, Dmitry; Good, David M.; Cryns, Vincent L.

2015-01-01

Purpose Many neoplasms are vulnerable to methionine deficiency by mechanisms that are poorly understood. Because gene profiling studies have revealed that methionine depletion increases TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) mRNA, we postulated that methionine stress sensitizes breast cancer cells to proapoptotic TRAIL-R2 agonists. Experimental Design Human triple (ER/PR/HER2)-negative breast carcinoma cell lines were cultured in control or methionine-free media. The effects of methionine depletion on TRAIL receptor expression and sensitivity to chemotherapy or a humanized agonistic TRAIL-R2 monoclonal antibody (lexatumumab) were determined. The melanoma-associated antigen MAGED2 was silenced to delineate its functional role in sensitizing TNBC cells to methionine stress. An orthotopic TNBC model was utilized to evaluate the effects of dietary methionine deficiency, lexatumumab or the combination. Results Methionine depletion sensitized TNBC cells to lexatumumab-induced caspase activation and apoptosis by increasing TRAIL-R2 mRNA and cell surface expression. MCF-10A cells transformed by oncogenic H-Ras, but not untransformed cells, and matrix-detached TNBC cells were highly sensitive to the combination of lexatumumab and methionine depletion. Proteomics analyses revealed that MAGED2, which has been reported to reduce TRAIL-R2 expression, was suppressed by methionine stress. Silencing MAGED2 recapitulated features of methionine deprivation, including enhanced mRNA and cell surface expression of TRAIL receptors and increased sensitivity to TRAIL receptor agonists. Dietary methionine deprivation enhanced the antitumor effects of lexatumumab in an orthotopic metastatic TNBC model. Conclusion Methionine depletion exposes a targetable defect in TNBC cells by increasing TRAIL-R2 expression. Our findings provide the foundation for a clinical trial combining dietary methionine restriction and TRAIL-R2 agonists. PMID:25724522

AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin

PubMed Central

2011-01-01

Background The transient receptor potential vanilloid type1 (TRPV1) is expressed in nociceptive sensory neurons and is sensitive to phosphorylation. A-Kinase Anchoring Protein 79/150 (AKAP150) mediates phosphorylation of TRPV1 by Protein Kinases A and C, modulating channel activity. However, few studies have focused on the regulatory mechanisms that control AKAP150 association with TRPV1. In the present study, we identify a role for calcium/calmodulin in controlling AKAP150 association with, and sensitization of, TRPV1. Results In trigeminal neurons, intracellular accumulation of calcium reduced AKAP150 association with TRPV1 in a manner sensitive to calmodulin antagonism. This was also observed in transfected Chinese hamster ovary (CHO) cells, providing a model for conducting molecular analysis of the association. In CHO cells, the deletion of the C-terminal calmodulin-binding site of TRPV1 resulted in greater association with AKAP150, and increased channel activity. Furthermore, the co-expression of wild-type calmodulin in CHOs significantly reduced TRPV1 association with AKAP150, as evidenced by total internal reflective fluorescence-fluorescence resonance energy transfer (TIRF-FRET) analysis and electrophysiology. Finally, dominant-negative calmodulin co-expression increased TRPV1 association with AKAP150 and increased basal and PKA-sensitized channel activity. Conclusions the results from these studies indicate that calcium/calmodulin interferes with the association of AKAP150 with TRPV1, potentially extending resensitization of the channel. PMID:21569553

AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin.

PubMed

Chaudhury, Sraboni; Bal, Manjot; Belugin, Sergei; Shapiro, Mark S; Jeske, Nathaniel A

2011-05-14

The transient receptor potential vanilloid type1 (TRPV1) is expressed in nociceptive sensory neurons and is sensitive to phosphorylation. A-Kinase Anchoring Protein 79/150 (AKAP150) mediates phosphorylation of TRPV1 by Protein Kinases A and C, modulating channel activity. However, few studies have focused on the regulatory mechanisms that control AKAP150 association with TRPV1. In the present study, we identify a role for calcium/calmodulin in controlling AKAP150 association with, and sensitization of, TRPV1. In trigeminal neurons, intracellular accumulation of calcium reduced AKAP150 association with TRPV1 in a manner sensitive to calmodulin antagonism. This was also observed in transfected Chinese hamster ovary (CHO) cells, providing a model for conducting molecular analysis of the association. In CHO cells, the deletion of the C-terminal calmodulin-binding site of TRPV1 resulted in greater association with AKAP150, and increased channel activity. Furthermore, the co-expression of wild-type calmodulin in CHOs significantly reduced TRPV1 association with AKAP150, as evidenced by total internal reflective fluorescence-fluorescence resonance energy transfer (TIRF-FRET) analysis and electrophysiology. Finally, dominant-negative calmodulin co-expression increased TRPV1 association with AKAP150 and increased basal and PKA-sensitized channel activity. the results from these studies indicate that calcium/calmodulin interferes with the association of AKAP150 with TRPV1, potentially extending resensitization of the channel.

Alteration in lipid composition of plasma membranes of sensitive and resistant Guerin carcinoma cells due to the action of free and liposomal form of cisplatin.

PubMed

Naleskina, L A; Todor, I N; Nosko, M M; Lukianova, N Y; Pivnyuk, V M; Chekhun, V F

2013-09-01

To study in vivo changes of lipid composition of plasma membranes of sensitive and resistant to cisplatin Guerin carcinoma cells under influence of free and liposomal cisplatin forms. The isolation of plasma membranes from parental (sensitive) and resistant to cisplatin Guerin carcinoma cells was by differential ultracentrifugation in sucrose density gradient. Lipids were detected by method of thin-layer chromatography. It was determined that more effective action of cisplatin liposomal form on resistant cells is associated with essential abnormalities of conformation of plasma membrane due to change of lipid components and architectonics of rafts. It results in the increase of membrane fluidity. Reconstructions in lipid composition of plasma membranes of cisplatin-resistant Guerin carcinoma cells provide more intensive delivery of drug into the cells, increase of its concentration and more effective interaction with cellular structural elements.

Molecular recognition using receptor-free nanomechanical infrared spectroscopy based on a quantum cascade laser

PubMed Central

Kim, Seonghwan; Lee, Dongkyu; Liu, Xunchen; Van Neste, Charles; Jeon, Sangmin; Thundat, Thomas

2013-01-01

Speciation of complex mixtures of trace explosives presents a formidable challenge for sensors that rely on chemoselective interfaces due to the unspecific nature of weak intermolecular interactions. Nanomechanical infrared (IR) spectroscopy provides higher selectivity in molecular detection without using chemoselective interfaces by measuring the photothermal effect of adsorbed molecules on a thermally sensitive microcantilever. In addition, unlike conventional IR spectroscopy, the detection sensitivity is drastically enhanced by increasing the IR laser power, since the photothermal signal comes from the absorption of IR photons and nonradiative decay processes. By using a broadly tunable quantum cascade laser for the resonant excitation of molecules, we increased the detection sensitivity by one order of magnitude compared to the use of a conventional IR monochromator. Here, we demonstrate the successful speciation and quantification of picogram levels of ternary mixtures of similar explosives (trinitrotoluene (TNT), cyclotrimethylene trinitramine (RDX), and pentaerythritol tetranitrate (PETN)) using nanomechanical IR spectroscopy. PMID:23346368

Radiation sensitivity of poliovirus, a model for norovirus, inoculated in oyster ( Crassostrea gigas) and culture broth under different conditions

NASA Astrophysics Data System (ADS)

Jung, Pil-Mun; Park, Jae Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Song, Beom-Seok; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Baek, Min; Chung, Young-Jin; Lee, Ju-Woon

2009-07-01

Poliovirus is a recognized surrogate for norovirus, pathogen in water and food, due to the structural and genetic similarity. Although radiation sensitivity of poliovirus in water or media had been reported, there has been no research in food model such as shellfish. In this study, oyster ( Crassostrea gigas) was incubated in artificial seawater contaminated with poliovirus, and thus radiation sensitivity of poliovirus was determined in inoculated oyster. The effects of ionizing radiation on the sensitivity of poliovirus were also evaluated under different conditions such as pH (4-7) and salt concentration (1-15%) in culture broth, and temperature during irradiation. The D10 value of poliovirus in PBS buffer, virus culture broth and oyster was determined to 0.46, 2.84 and 2.94 kGy, respectively. The initial plaque forming unit (PFU) of poliovirus in culture broth was slightly decreased as the decrease of pH and the increase of salt concentration, but radiation sensitivity was not affected by pH and salt contents. However, radiation resistance of poliovirus was increased at frozen state. These results provide the basic information for the inactivation of pathogenic virus in foods by using irradiation.

Face processing regions are sensitive to distinct aspects of temporal sequence in facial dynamics.

PubMed

Reinl, Maren; Bartels, Andreas

2014-11-15

Facial movement conveys important information for social interactions, yet its neural processing is poorly understood. Computational models propose that shape- and temporal sequence sensitive mechanisms interact in processing dynamic faces. While face processing regions are known to respond to facial movement, their sensitivity to particular temporal sequences has barely been studied. Here we used fMRI to examine the sensitivity of human face-processing regions to two aspects of directionality in facial movement trajectories. We presented genuine movie recordings of increasing and decreasing fear expressions, each of which were played in natural or reversed frame order. This two-by-two factorial design matched low-level visual properties, static content and motion energy within each factor, emotion-direction (increasing or decreasing emotion) and timeline (natural versus artificial). The results showed sensitivity for emotion-direction in FFA, which was timeline-dependent as it only occurred within the natural frame order, and sensitivity to timeline in the STS, which was emotion-direction-dependent as it only occurred for decreased fear. The occipital face area (OFA) was sensitive to the factor timeline. These findings reveal interacting temporal sequence sensitive mechanisms that are responsive to both ecological meaning and to prototypical unfolding of facial dynamics. These mechanisms are temporally directional, provide socially relevant information regarding emotional state or naturalness of behavior, and agree with predictions from modeling and predictive coding theory. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

[Diagnostics of acute myocardial infarction in elderly patients].

PubMed

Bahrmann, P; Heppner, H J; Bahrmann, A; Christ, M; Bertsch, T; Sieber, C C

2011-06-01

The early diagnosis of an acute myocardial infarction (MI) is improved by the introduction of novel high-sensitivity troponin assays. These assays can measure low level myocardial injury not detectable by standard troponin assays. Especially in older patients who appear to have a higher basal troponin level, the results must always be judged in the context of the medical history, physical examination, electrocardiogram (ECG) and any further findings. Even small increases in high-sensitivity troponin indicate increased risk for death or MI during follow-up. In the case of MI an invasive strategy results in better survival rates compared with conservative therapy but at the expense of an increased risk of bleeding in elderly patients. This article provides an overview on the diagnosis of MI in elderly patients.

Sensitivity, Specificity, PPV, and NPV for Predictive Biomarkers

PubMed Central

2015-01-01

Molecularly targeted cancer drugs are often developed with companion diagnostics that attempt to identify which patients will have better outcome on the new drug than the control regimen. Such predictive biomarkers are playing an increasingly important role in precision oncology. For diagnostic tests, sensitivity, specificity, positive predictive value, and negative predictive are usually used as performance measures. This paper discusses these indices for predictive biomarkers, provides methods for their calculation with survival or response endpoints, and describes assumptions involved in their use. PMID:26109105

Cirrus and Future Space Based Astronomy

NASA Technical Reports Server (NTRS)

Gautier, T. N.

1993-01-01

Astronomical observations from space make possible observations of sensitivity and spatial resolution impossible in the past. This increase in sensitivity will both make possible the observation of new phenomena and will bring observations against limitations not encountered before. This paper discusses the effects that infrared cirrus and diffuse interstellar clouds will have on space based observations. Some special opportunities provided by space observations of cirrus are presented and a partial list of currently planned observations of cirrus by space telescopes is given.

Can we calibrate simultaneously groundwater recharge and aquifer hydrodynamic parameters ?

NASA Astrophysics Data System (ADS)

Hassane Maina, Fadji; Ackerer, Philippe; Bildstein, Olivier

2017-04-01

By groundwater model calibration, we consider here fitting the measured piezometric heads by estimating the hydrodynamic parameters (storage term and hydraulic conductivity) and the recharge. It is traditionally recommended to avoid simultaneous calibration of groundwater recharge and flow parameters because of correlation between recharge and the flow parameters. From a physical point of view, little recharge associated with low hydraulic conductivity can provide very similar piezometric changes than higher recharge and higher hydraulic conductivity. If this correlation is true under steady state conditions, we assume that this correlation is much weaker under transient conditions because recharge varies in time and the parameters do not. Moreover, the recharge is negligible during summer time for many climatic conditions due to reduced precipitation, increased evaporation and transpiration by vegetation cover. We analyze our hypothesis through global sensitivity analysis (GSA) in conjunction with the polynomial chaos expansion (PCE) methodology. We perform GSA by calculating the Sobol indices, which provide a variance-based 'measure' of the effects of uncertain parameters (storage and hydraulic conductivity) and recharge on the piezometric heads computed by the flow model. The choice of PCE has the following two benefits: (i) it provides the global sensitivity indices in a straightforward manner, and (ii) PCE can serve as a surrogate model for the calibration of parameters. The coefficients of the PCE are computed by probabilistic collocation. We perform the GSA on simplified real conditions coming from an already built groundwater model dedicated to a subdomain of the Upper-Rhine aquifer (geometry, boundary conditions, climatic data). GSA shows that the simultaneous calibration of recharge and flow parameters is possible if the calibration is performed over at least one year. It provides also the valuable information of the sensitivity versus time, depending on the aquifer inertia and climatic conditions. The groundwater levels variations during recharge (increase) are sensitive to the storage coefficient whereas the groundwater levels variations after recharge (decrease) are sensitive to the hydraulic conductivity. The performed model calibration on synthetic data sets shows that the parameters and recharge are estimated quite accurately.

Measuring Atmospheric Carbon Dioxide from Space: The GOSAT and OCO-2 Missions

NASA Technical Reports Server (NTRS)

Crisp, David

2011-01-01

The Japanese Greenhouse gases Observing Satellite (GOSAT) is providing new insight into atmospheric carbon dioxide trends. The NASA Orbiting Carbon Observatory-2 (OCO-2)Mission will build on this record with increased sensitivity resolution, and coverage.

Enhanced inductance in laminated multilayer magnetic planar inductor for sensitive magnetic field detection

NASA Astrophysics Data System (ADS)

Wang, Yao; Wen, Yumei; Song, Fapeng; Li, Ping; Yu, Shumin

2018-04-01

The authors reported laminated multilayer magnetic planar inductors for sensitive magnetic field detection, which consist of two serially connected sandwich planar inductors (i.e., FeCuNbSiB/micro planar coil/FeCuNbSiB/micro planar coil/FeCuNbSiB). When ac current is applied to coils, the greatly increased inductance by the incorporated high permeability magnetic material and enlarged mutual-inductance among coils significantly improve the sensor sensitivity to the dc magnetic field. The demagnetizing field is also found to affect the performance severely when the shape and the number of magnetic layers vary. The investigation indicates that the proposed laminate can provide an inductance ratio of 665% at the frequency of 1 kHz. By connecting the sensor with a capacitor, the sensor output with varying dc magnetic fields is obtained by tuning the resonant frequency shift. The study indicates that the proposed sensor can provide a sensitivity of about 3.57 kHz/Oe with a resolution of 28 nT between 2 Oe and 60 Oe, which outperforms most of the magnetic sensors with frequency shifting output.

Quantifying serum antibody in bird fanciers' hypersensitivity pneumonitis.

PubMed

McSharry, Charles; Dye, George M; Ismail, Tengku; Anderson, Kenneth; Spiers, Elizabeth M; Boyd, Gavin

2006-06-26

Detecting serum antibody against inhaled antigens is an important diagnostic adjunct for hypersensitivity pneumonitis (HP). We sought to validate a quantitative fluorimetric assay testing serum from bird fanciers. Antibody activity was assessed in bird fanciers and control subjects using various avian antigens and serological methods, and the titer was compared with symptoms of HP. IgG antibody against pigeon serum antigens, quantified by fluorimetry, provided a good discriminator of disease. Levels below 10 mg/L were insignificant, and increasing titers were associated with disease. The assay was unaffected by total IgG, autoantibodies and antibody to dietary hen's egg antigens. Antigens from pigeon serum seem sufficient to recognize immune sensitivity to most common pet avian species. Decreasing antibody titers confirmed antigen avoidance. Increasing antibody titer reflected the likelihood of HP, and decreasing titers confirmed antigen avoidance. Quantifying antibody was rapid and the increased sensitivity will improve the rate of false-negative reporting and obviate the need for invasive diagnostic procedures. Automated fluorimetry provides a method for the international standardization of HP serology thereby improving quality control and improving its suitability as a diagnostic adjunct.

The ExaVolt Antenna: Concept and Development Updates

NASA Astrophysics Data System (ADS)

Pfendner, Carl

2017-03-01

A flux of ultrahigh energy neutrinos is expected both directly from sources and from interactions between ultrahigh energy cosmic rays and the cosmic microwave background. Using the cost-effective radio Cherenkov technique to search for these neutrinos, the ExaVolt Antenna (EVA) is a mission concept that aims to build on the capabilities of earlier radio-based balloon-borne neutrino detectors and increase the sensitivity to lower energies and fluxes. The novel EVA design exploits the surface of the balloon to provide a focusing reflector that aims to provide a signal gain of 30 dBi (compared to 10 dBi on ANITA). This increase in gain when combined with a large instantaneous viewing angle will yield a 10-fold increase in sensitivity and will allow this balloon-borne experiment to probe the expected low neutrino fluxes even at energies greater than 1019 eV. This contribution will present an overview of the mission concept, recent technology developments, and the results of a hang test of a 1:20-scale model which demonstrates the effectiveness of the design.

An Animal Model of Trichloroethylene-Induced Skin Sensitization in BALB/c Mice.

PubMed

Wang, Hui; Zhang, Jia-xiang; Li, Shu-long; Wang, Feng; Zha, Wan-sheng; Shen, Tong; Wu, Changhao; Zhu, Qi-xing

2015-01-01

Trichloroethylene (TCE) is a major occupational hazard and environmental contaminant that can cause multisystem disorders in the form of occupational medicamentosa-like dermatitis. Development of dermatitis involves several proinflammatory cytokines, but their role in TCE-mediated dermatitis has not been examined in a well-defined experimental model. In addition, few animal models of TCE sensitization are available, and the current guinea pig model has apparent limitations. This study aimed to establish a model of TCE-induced skin sensitization in BALB/c mice and to examine the role of several key inflammatory cytokines on TCE sensitization. The sensitization rate of dorsal painted group was 38.3%. Skin edema and erythema occurred in TCE-sensitized groups, as seen in 2,4-dinitrochlorobenzene (DNCB) positive control. Trichloroethylene sensitization-positive (dermatitis [+]) group exhibited increased thickness of epidermis, inflammatory cell infiltration, swelling, and necrosis in dermis and around hair follicle, but ear painted group did not show these histological changes. The concentrations of serum proinflammatory cytokines including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2 were significantly increased in 24, 48, and 72 hours dermatitis [+] groups treated with TCE and peaked at 72 hours. Deposition of TNF-α, IFN-γ, and IL-2 into the skin tissue was also revealed by immunohistochemistry. We have established a new animal model of skin sensitization induced by repeated TCE stimulations, and we provide the first evidence that key proinflammatory cytokines including TNF-α, IFN-γ, and IL-2 play an important role in the process of TCE sensitization. © The Author(s) 2015.

Climate sensitivity, sea level and atmospheric carbon dioxide

PubMed Central

Hansen, James; Sato, Makiko; Russell, Gary; Kharecha, Pushker

2013-01-01

Cenozoic temperature, sea level and CO2 covariations provide insights into climate sensitivity to external forcings and sea-level sensitivity to climate change. Climate sensitivity depends on the initial climate state, but potentially can be accurately inferred from precise palaeoclimate data. Pleistocene climate oscillations yield a fast-feedback climate sensitivity of 3±1°C for a 4 W m−2 CO2 forcing if Holocene warming relative to the Last Glacial Maximum (LGM) is used as calibration, but the error (uncertainty) is substantial and partly subjective because of poorly defined LGM global temperature and possible human influences in the Holocene. Glacial-to-interglacial climate change leading to the prior (Eemian) interglacial is less ambiguous and implies a sensitivity in the upper part of the above range, i.e. 3–4°C for a 4 W m−2 CO2 forcing. Slow feedbacks, especially change of ice sheet size and atmospheric CO2, amplify the total Earth system sensitivity by an amount that depends on the time scale considered. Ice sheet response time is poorly defined, but we show that the slow response and hysteresis in prevailing ice sheet models are exaggerated. We use a global model, simplified to essential processes, to investigate state dependence of climate sensitivity, finding an increased sensitivity towards warmer climates, as low cloud cover is diminished and increased water vapour elevates the tropopause. Burning all fossil fuels, we conclude, would make most of the planet uninhabitable by humans, thus calling into question strategies that emphasize adaptation to climate change. PMID:24043864

Climate sensitivity, sea level and atmospheric carbon dioxide.

PubMed

Hansen, James; Sato, Makiko; Russell, Gary; Kharecha, Pushker

2013-10-28

Cenozoic temperature, sea level and CO2 covariations provide insights into climate sensitivity to external forcings and sea-level sensitivity to climate change. Climate sensitivity depends on the initial climate state, but potentially can be accurately inferred from precise palaeoclimate data. Pleistocene climate oscillations yield a fast-feedback climate sensitivity of 3±1(°)C for a 4 W m(-2) CO2 forcing if Holocene warming relative to the Last Glacial Maximum (LGM) is used as calibration, but the error (uncertainty) is substantial and partly subjective because of poorly defined LGM global temperature and possible human influences in the Holocene. Glacial-to-interglacial climate change leading to the prior (Eemian) interglacial is less ambiguous and implies a sensitivity in the upper part of the above range, i.e. 3-4(°)C for a 4 W m(-2) CO2 forcing. Slow feedbacks, especially change of ice sheet size and atmospheric CO2, amplify the total Earth system sensitivity by an amount that depends on the time scale considered. Ice sheet response time is poorly defined, but we show that the slow response and hysteresis in prevailing ice sheet models are exaggerated. We use a global model, simplified to essential processes, to investigate state dependence of climate sensitivity, finding an increased sensitivity towards warmer climates, as low cloud cover is diminished and increased water vapour elevates the tropopause. Burning all fossil fuels, we conclude, would make most of the planet uninhabitable by humans, thus calling into question strategies that emphasize adaptation to climate change.

Desensitization: Overcoming the Immunologic Barriers to Transplantation

PubMed Central

Choi, Jua; Vo, Ashley; Peng, Alice; Jordan, Stanley C.

2017-01-01

HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection. PMID:28127571

Salt tolerance at single cell level in giant-celled Characeae

PubMed Central

Beilby, Mary J.

2015-01-01

Characean plants provide an excellent experimental system for electrophysiology and physiology due to: (i) very large cell size, (ii) position on phylogenetic tree near the origin of land plants and (iii) continuous spectrum from very salt sensitive to very salt tolerant species. A range of experimental techniques is described, some unique to characean plants. Application of these methods provided electrical characteristics of membrane transporters, which dominate the membrane conductance under different outside conditions. With this considerable background knowledge the electrophysiology of salt sensitive and salt tolerant genera can be compared under salt and/or osmotic stress. Both salt tolerant and salt sensitive Characeae show a rise in membrane conductance and simultaneous increase in Na+ influx upon exposure to saline medium. Salt tolerant Chara longifolia and Lamprothamnium sp. exhibit proton pump stimulation upon both turgor decrease and salinity increase, allowing the membrane PD to remain negative. The turgor is regulated through the inward K+ rectifier and 2H+/Cl- symporter. Lamprothamnium plants can survive in hypersaline media up to twice seawater strength and withstand large sudden changes in salinity. Salt sensitive C. australis succumbs to 50–100 mM NaCl in few days. Cells exhibit no pump stimulation upon turgor decrease and at best transient pump stimulation upon salinity increase. Turgor is not regulated. The membrane PD exhibits characteristic noise upon exposure to salinity. Depolarization of membrane PD to excitation threshold sets off trains of action potentials, leading to further loses of K+ and Cl-. In final stages of salt damage the H+/OH- channels are thought to become the dominant transporter, dissipating the proton gradient and bringing the cell PD close to 0. The differences in transporter electrophysiology and their synergy under osmotic and/or saline stress in salt sensitive and salt tolerant characean cells are discussed in detail. PMID:25972875

Comparison of winter wheat yield sensitivity to climate variables under irrigated and rain-fed conditions

NASA Astrophysics Data System (ADS)

Xiao, Dengpan; Shen, Yanjun; Zhang, He; Moiwo, Juana P.; Qi, Yongqing; Wang, Rende; Pei, Hongwei; Zhang, Yucui; Shen, Huitao

2016-09-01

Crop simulation models provide alternative, less time-consuming, and cost-effective means of determining the sensitivity of crop yield to climate change. In this study, two dynamic mechanistic models, CERES (Crop Environment Resource Synthesis) and APSIM (Agricultural Production Systems Simulator), were used to simulate the yield of wheat ( Triticum aestivum L.) under well irrigated (CFG) and rain-fed (YY) conditions in relation to different climate variables in the North China Plain (NCP). The study tested winter wheat yield sensitivity to different levels of temperature, radiation, precipitation, and atmospheric carbon dioxide (CO2) concentration under CFG and YY conditions at Luancheng Agro-ecosystem Experimental Stations in the NCP. The results from the CERES and APSIM wheat crop models were largely consistent and suggested that changes in climate variables influenced wheat grain yield in the NCP. There was also significant variation in the sensitivity of winter wheat yield to climate variables under different water (CFG and YY) conditions. While a temperature increase of 2°C was the threshold beyond which temperature negatively influenced wheat yield under CFG, a temperature rise exceeding 1°C decreased winter wheat grain yield under YY. A decrease in solar radiation decreased wheat grain yield under both CFG and YY conditions. Although the sensitivity of winter wheat yield to precipitation was small under the CFG, yield decreased significantly with decreasing precipitation under the rainfed YY treatment. The results also suggest that wheat yield under CFG linearly increased by ≈3.5% per 60 ppm (parts per million) increase in CO2 concentration from 380 to 560 ppm, and yield under YY increased linearly by ≈7.0% for the same increase in CO2 concentration.

Effects of Detector Thickness on Geometric Sensitivity and Event Positioning Errors in the Rectangular PET/X Scanner

NASA Astrophysics Data System (ADS)

MacDonald, Lawrence R.; Hunter, William C. J.; Kinahan, Paul E.; Miyaoka, Robert S.

2013-10-01

We used simulations to investigate the relationship between sensitivity and spatial resolution as a function of crystal thickness in a rectangular PET scanner intended for quantitative assessment of breast cancers. The system had two 20 × 15-cm2 and two 10 × 15-cm2 flat detectors forming a box, with the larger detectors separated by 4 or 8 cm. Depth-of-interaction (DOI) resolution was modeled as a function of crystal thickness based on prior measurements. Spatial resolution was evaluated independent of image reconstruction by deriving and validating a surrogate metric from list-mode data ( dFWHM). When increasing crystal thickness from 5 to 40 mm, and without using DOI information, the dFWHM for a centered point source increased from 0.72 to 1.6 mm. Including DOI information improved dFWHM by 12% and 27% for 5- and 40-mm-thick crystals, respectively. For a point source in the corner of the FOV, use of DOI information improved dFWHM by 20% (5-mm crystal) and 44% (40-mm crystal). Sensitivity was 7.7% for 10-mm-thick crystals (8-cm object). Increasing crystal thickness on the smaller side detectors from 10 to 20 mm (keeping 10-mm crystals on the larger detectors) boosted sensitivity by 24% (relative) and degraded dFWHM by only 3%/8% with/without DOI information. The benefits of measuring DOI must be evaluated in terms of the intended clinical task of assessing tracer uptake in small lesions. Increasing crystal thickness on the smaller side detectors provides substantial sensitivity increase with minimal accompanying loss in resolution.

Highly sensitive detection of dipicolinic acid with a water-dispersible terbium-metal organic framework.

PubMed

Bhardwaj, Neha; Bhardwaj, Sanjeev; Mehta, Jyotsana; Kim, Ki-Hyun; Deep, Akash

2016-12-15

The sensitive detection of dipicolinic acid (DPA) is strongly associated with the sensing of bacterial organisms in food and many types of environmental samples. To date, the demand for a sensitive detection method for bacterial toxicity has increased remarkably. Herein, we investigated the DPA detection potential of a water-dispersible terbium-metal organic framework (Tb-MOF) based on the fluorescence quenching mechanism. The Tb-MOF showed a highly sensitive ability to detect DPA at a limit of detection of 0.04nM (linear range of detection: 1nM to 5µM) and also offered enhanced selectivity from other commonly associated organic molecules. The present study provides a basis for the application of Tb-MOF for direct, convenient, highly sensitive, and specific detection of DPA in the actual samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Crisis of conscience: reconciling religious health care providers' beliefs and patients' rights.

PubMed

White, K A

1999-07-01

In this note, Katherine A. White explores the conflict between religious health care providers who provide care in accordance with their religious beliefs and the patients who want access to medical care that these religious providers find objectionable. Specifically, she examines Roman Catholic health care institutions and HMOs that follow the Ethical and Religious Directives for Catholic Health Care Services and considers other religious providers with similar beliefs. In accordance with the Directives, these institutions maintain policies that restrict access to "sensitive" services like abortion, family planning, HIV counseling, infertility treatment, and termination of life-support. White explains how most state laws protecting providers' right to refuse treatments in conflict with religious principles do not cover this wide range of services. Furthermore, many state and federal laws and some court decisions guarantee patients the right to receive this care. The constitutional complication inherent in this provider-patient conflict emerges in White's analysis of the interaction of the Free Exercise and Establishment Clauses of the First Amendment and patients' right to privacy. White concludes her note by exploring the success of both provider-initiated and legislatively mandated compromise strategies. She first describes the strategies adopted by four different religious HMOs which vary in how they increase or restrict access to sensitive services. She then turns her focus to state and federal "bypass" legislation, ultimately concluding that increased state supervision might help these laws become more viable solutions to provider-patient conflicts.

Money illusion among health care providers: should we adjust for inflation in analyses of provider behavior?

PubMed

Mayer, M L; Rozier, R G

2000-08-01

This analysis questions the appropriateness of inflation adjustment in analyses of provider behavior by comparing results from estimations using adjusted financial variables with those from estimations using unadjusted financial variables. Using Medicaid claims from 1984-1991, we explored the effects of Medicaid reimbursement increases on dentists' participation. Using results from inflation adjusted analyses, we would conclude that a 23% nominal increase in Medicaid reimbursement rates yields no increase in the number of Medicaid children seen by dentists. In contrast, estimations based on unadjusted reimbursement rates suggest that this same 23% nominal increase in reimbursement leads to an expected 16-person (15.4%) increase in the number of Medicaid patients seen per provider per year. These analyses demonstrate that results are sensitive to adjustment for inflation. While adjusting for inflation is a generally accepted practice in health services research, doing so without evidence that providers respond to adjusted reimbursement may be unjustified. More research is needed to determine the appropriateness of inflation adjustment in analyses of provider behavior, and the circumstances under which it should or should not be done.

Recommendations on Model Fidelity for Wind Turbine Gearbox Simulations; NREL (National Renewable Energy Laboratory)

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

Keller, J.; Lacava, W.; Austin, J.

2015-02-01

This work investigates the minimum level of fidelity required to accurately simulate wind turbine gearboxes using state-of-the-art design tools. Excessive model fidelity including drivetrain complexity, gearbox complexity, excitation sources, and imperfections, significantly increases computational time, but may not provide a commensurate increase in the value of the results. Essential designparameters are evaluated, including the planetary load-sharing factor, gear tooth load distribution, and sun orbit motion. Based on the sensitivity study results, recommendations for the minimum model fidelities are provided.

Development of a contactless DC current sensor with high linearity and sensitivity based on the magnetoelectric effect

NASA Astrophysics Data System (ADS)

Castro, N.; Reis, S.; Silva, M. P.; Correia, V.; Lanceros-Mendez, S.; Martins, P.

2018-06-01

The magnetoelectric (ME) effect is increasingly being considered an attractive alternative for magnetic field and smart current sensing, being able to sense static and dynamic magnetic fields. This work reports on a contactless DC current sensor device based on a ME PVDF/Metglas composite, a solenoid and the corresponding electronic instrumentation. The ME sample shows a maximum resonant ME coefficient (α 33) of 34.48 V cm‑1 Oe‑1, a linear response (R 2 = 0.998) and a sensitivity of 6.7 mV A‑1. With the incorporation of a charge amplifier, an AC-RMS converter and a microcontroller the linearity is maintained (R 2 = 0.997), the ME output voltage increases to a maximum of 2320 mV and the sensitivity rises to 476.5 mV A‑1. Such features allied to the highest sensitivity reported in the literature on polymer-based ME composites provide to the reported ME sensing device suitable characteristics to be used in non-contact electric current measurement, motor operational status checking, and condition monitoring of rechargeable batteries, among others.

Electrically responsive materials based on polycarbazole/sodium alginate hydrogel blend for soft and flexible actuator application.

PubMed

Sangwan, Watchara; Petcharoen, Karat; Paradee, Nophawan; Lerdwijitjarud, Wanchai; Sirivat, Anuvat

2016-10-20

The electromechanical properties, namely the storage modulus sensitivity and bending, of sodium alginate (SA) hydrogels and polycarbazole/sodium alginate (PCB/SA) hydrogel blends under applied electric field was investigated. The electromechanical properties of the pristine SA were studied under effects of crosslinking types and SA molecular weights, whereas the PCB/SA hydrogel blends were studied under the effect of PCB concentrations. The storage modulus sensitivity and bending of the pristine SA as crosslinked by the ionic crosslinking agent were found to be higher than those of the covalent crosslinking. The storage modulus sensitivity and deflection of the SA increased monotonically with increasing molecular weight. The highest electromechanical response of the PCB/SA hydrogel blends was obtained from the blend with 0.10% v/v PCB as it provided surprisingly the highest ever storage modulus sensitivity, (G'-G'0)/G'0 where G'0 and G' are the storage modulus without and with applied electric field, respectively, at 18.5 under applied electric field strength of 800V/mm. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of reward sensitivity and regional brain volumes on substance use initiation in adolescence

PubMed Central

Collins, Paul; Muetzel, Ryan; Schissel, Ann; Lim, Kelvin O.; Luciana, Monica

2015-01-01

This longitudinal study examines associations between baseline individual differences and developmental changes in reward [i.e. behavioral approach system (BAS)] sensitivity and relevant brain structures’ volumes to prospective substance use initiation during adolescence. A community sample of adolescents ages 15–18 with no prior substance use was assessed for substance use initiation (i.e. initiation of regular alcohol use and/or any use of other substances) during a 2-year follow-up period and for alcohol use frequency in the last year of the follow-up. Longitudinal ‘increases’ in BAS sensitivity were associated with substance use initiation and increased alcohol use frequency during the follow-up. Moreover, adolescents with smaller left nucleus accumbens at baseline were more likely to initiate substance use during the follow-up period. This study provides support for the link between developmental increases in reward sensitivity and substance use initiation in adolescence. The study also emphasizes the potential importance of individual differences in volumes of subcortical regions and their structural development for substance use initiation during adolescence. PMID:24526186

The role of interpersonal sensitivity, social support, and quality of life in rural older adults.

PubMed

Wedgeworth, Monika; LaRocca, Michael A; Chaplin, William F; Scogin, Forrest

The mental health of elderly individuals in rural areas is increasingly relevant as populations age and social structures change. While social support satisfaction is a well-established predictor of quality of life, interpersonal sensitivity symptoms may diminish this relation. The current study extends the findings of Scogin et al by investigating the relationship among interpersonal sensitivity, social support satisfaction, and quality of life among rural older adults and exploring the mediating role of social support in the relation between interpersonal sensitivity and quality of life (N = 128). Hierarchical regression revealed that interpersonal sensitivity and social support satisfaction predicted quality of life. In addition, bootstrapping resampling supported the role of social support satisfaction as a mediator between interpersonal sensitivity symptoms and quality of life. These results underscore the importance of nurses and allied health providers in assessing and attending to negative self-perceptions of clients, as well as the perceived quality of their social networks. Copyright © 2016 Elsevier Inc. All rights reserved.

Flexible three-dimensional electrochemical glucose sensor with improved sensitivity realized in hybrid polymer microelectromechanical systems technique.

PubMed

Patel, Jasbir N; Gray, Bonnie L; Kaminska, Bozena; Gates, Byron D

2011-09-01

Continuous glucose monitoring for patients with diabetes is of paramount importance to avoid severe health conditions resulting from hypoglycemia or hyperglycemia. Most available methods require an invasive setup and a health care professional. Handheld devices available on the market also require finger pricking for every measurement and do not provide continuous monitoring. Hence, continuous glucose monitoring from human tears using a glucose sensor embedded in a contact lens has been considered as a suitable option. However, the glucose concentration in human tears is very low in comparison with the blood glucose level (1/10-1/40 concentration). We propose a sensor that solves the sensitivity problem in a new way, is flexible, and is constructed onto the oxygen permeable contact lens material. To achieve such sensitivity while maintaining a small sensor footprint suitable for placement in a contact lens, we increased the active electrode area by using three-dimensional (3-D) electrode micropatterning. Fully flexible 3-D electrodes were realized utilizing ordered arrays of pillars with different shapes and heights. We successfully fabricated square and cylindrical pillars with different height (50, 100, and 200 μm) and uniform metal coverage to realize sensor electrodes. The increased surface area produces high amperometric current that increases sensor sensitivity up to 300% using 200 μm tall square pillars. The sensitivity improvement closely follows the improvement in the surface area of the electrode. The proposed flexible glucose sensors with 3-D microstructure electrodes are more sensitive to lower glucose concentrations and generate higher current signal than conventional glucose sensors. © 2011 Diabetes Technology Society.

Dual Brushless Resolver Rate Sensor

NASA Technical Reports Server (NTRS)

Howard, David E. (Inventor)

1996-01-01

This invention relates to dual analog angular rate sensors which are implemented without the use of mechanical brushes. A resolver rate sensor which includes two brushless resolvers which are mechanically coupled to the same output shaft is provided with inputs which are provided to each resolver by providing the first resolver with a DC input and the second resolver with an AC sinusoidal input. A trigonometric identity in which the sum of the squares of the sin and cosine components equal one is used to advantage in providing a sensor of increased accuracy. The first resolver may have a fixed or variable DC input to permit dynamic adjustment of resolver sensitivity thus permitting a wide range of coverage. Novelty and advantages of the invention reside in the excitation of a resolver with a DC signal and in the utilization of two resolvers and the trigonometric identity of cos(exp 2)(theta) + sin(exp 2)(theta) = 1 to provide an accurate rate sensor which is sensitive to direction and accurate through zero rate.

Responses of Male C57BL/6N Mice to Observing the Euthanasia of Other Mice

PubMed Central

Boivin, Gregory P; Bottomley, Michael A; Grobe, Nadja

2016-01-01

The AVMA Panel on Euthanasia recommends that sensitive animals should not be present during the euthanasia of others, especially of their own species, but does not provide guidelines on how to identify a sensitive species. To determine if mice are a sensitive species we reviewed literature on empathy in mice, and measured the cardiovascular and activity response of mice observing euthanasia of conspecifics. We studied male 16-wk-old C57BL/6N mice and found no increase in cardiovascular parameters or activity in the response of the mice to observing CO2 euthanasia. Mice observing decapitation had an increase in all values, but this was paralleled by a similar increase during mock decapitations in which no animals were handled or euthanized. We conclude that CO2 euthanasia of mice does not have an impact on other mice in the room, and that euthanasia by decapitation likely only has an effect due to the noise of the guillotine. We support the conceptual idea that mice are both a sensitive species and display empathy, but under the controlled circumstances of the euthanasia procedures used in this study there was no signaling of stress to witnessing inhabitants in the room. PMID:27423146

Decreased alertness due to sleep loss increases pain sensitivity in mice

PubMed Central

Alexandre, Chloe; Latremoliere, Alban; Ferreira, Ashley; Miracca, Giulia; Yamamoto, Mihoko; Scammell, Thomas E; Woolf, Clifford J

2018-01-01

Extended daytime and nighttime activities are major contributors to the growing sleep deficiency epidemic1,2, as is the high prevalence of sleep disorders like insomnia. The consequences of chronic insufficient sleep for health remain uncertain3. Sleep quality and duration predict presence of pain the next day in healthy subjects4–7, suggesting that sleep disturbances alone may worsen pain, and experimental sleep deprivation in humans supports this claim8,9. We demonstrate that sleep loss, but not sleep fragmentation, in healthy mice increases sensitivity to noxious stimuli (referred to as ‘pain’) without general sensory hyper-responsiveness. Moderate daily repeated sleep loss leads to a progressive accumulation of sleep debt and also to exaggerated pain responses, both of which are rescued after restoration of normal sleep. Caffeine and modafinil, two wake-promoting agents that have no analgesic activity in rested mice, immediately normalize pain sensitivity in sleep-deprived animals, without affecting sleep debt. The reversibility of mild sleep-loss-induced pain by wake-promoting agents reveals an unsuspected role for alertness in setting pain sensitivity. Clinically, insufficient or poor-quality sleep may worsen pain and this enhanced pain may be reduced not by analgesics, whose effectiveness is reduced, but by increasing alertness or providing better sleep. PMID:28481358

Increasing the sensitivity of LXe TPCs to dark matter by doping with helium or neon

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

Lippincott, W. Hugh; Alexander, Thomas R.; Hime, Andrew

Next generation liquid xenon TPCs are poised to increase our sensitivity to dark matter by two orders of magnitude over a wide range of possible dark matter candidates. This proceedings describes an idea to expand the reach and flexibility of such detectors even further, by adding helium and neon to the xenon to enable searches for very light dark matter and combining high and low Z targets in the same detector. Adding helium or neon to LXe-TPCs has many advantages. First, the helium or neon target benefits from the excellent self-shielding provided by a large liquid xenon detector. Second, themore » same instrumentation, PMTs, and data acquisition can be used. Third, light nuclei are more robust to the systematic uncertainties that affect light WIMP searches. Fourth, helium and neon recoils will likely produce larger signals in liquid xenon than xenon recoils, achieving lower energy thresholds, and further increasing the sensitivity to light WIMPs. Finally, by adding He/Ne in sequence after a Xe-only run, the source of any observed signal can be isolated.« less

Increasing the sensitivity of LXe TPCs to dark matter by doping with helium or neon

DOE PAGES

Lippincott, W. Hugh; Alexander, Thomas R.; Hime, Andrew

2017-02-03

Next generation liquid xenon TPCs are poised to increase our sensitivity to dark matter by two orders of magnitude over a wide range of possible dark matter candidates. This proceedings describes an idea to expand the reach and flexibility of such detectors even further, by adding helium and neon to the xenon to enable searches for very light dark matter and combining high and low Z targets in the same detector. Adding helium or neon to LXe-TPCs has many advantages. First, the helium or neon target benefits from the excellent self-shielding provided by a large liquid xenon detector. Second, themore » same instrumentation, PMTs, and data acquisition can be used. Third, light nuclei are more robust to the systematic uncertainties that affect light WIMP searches. Fourth, helium and neon recoils will likely produce larger signals in liquid xenon than xenon recoils, achieving lower energy thresholds, and further increasing the sensitivity to light WIMPs. Finally, by adding He/Ne in sequence after a Xe-only run, the source of any observed signal can be isolated.« less

Comparing the effects of food restriction and overeating on brain reward systems

PubMed Central

Avena, Nicole M.; Murray, Susan; Gold, Mark S.

2014-01-01

Both caloric restriction and overeating have been shown to affect neural processes associated with reinforcement. Both preclinical and some clinical studies have provided evidence that food restriction may increase reward sensitivity, and while there are mixed findings regarding the effects of overeating on reward sensitivity, there is strong evidence linking this behavior with changes in reward-related brain regions. Evidence of these changes comes in part from findings that show that such eating patterns are associated with increased drug use. The data discussed here regarding the differential effects of various eating patterns on reward systems may be particularly relevant to the aging population, as this population has been shown to exhibit altered reward sensitivity and decreased caloric consumption. Moreover, members of this population appear to be increasingly affected by the current obesity epidemic. Food, like alcohol or drugs, can stimulate its own consumption and produce similar neurochemical changes in the brain. Age-related loss of appetite, decreased eating, and caloric restriction are hypothesized to be associated with changes in the prevalence of substance misuse, abuse, and dependence seen in this cohort. PMID:23535488

The effects of antiepileptic inducers in neuropsychopharmacology, a neglected issue. Part II: Pharmacological issues and further understanding.

PubMed

de Leon, Jose

2015-01-01

The literature on inducers in epilepsy and bipolar disorder is seriously contaminated by false negative findings. Part II of this comprehensive review on antiepileptic drug (AED) inducers provides clinicians with further educational material about the complexity of interpreting AED drug-drug interactions. The basic pharmacology of induction is reviewed including the cytochrome P450 (CYP) isoenzymes, the Uridine Diphosphate Glucuronosyltransferases (UGTs), and P-glycoprotein (P-gp). CYP2B6 and CYP3A4 are very sensitive to induction. CYP1A2 is moderately sensitive while CYP2C9 and CYP2C19 are only mildly sensitive. CYP2D6 cannot be induced by medications. Induction of UGT and P-gp are poorly understood. The induction of metabolic enzymes such as CYPs and UGTs, and transporters such as P-gp, implies that the amount of these proteins increases when they are induced; this is almost always explained by increasing synthesis mediated by the so-called nuclear receptors (constitutive androstane, estrogen, glucocorticoid receptors and pregnaneX receptors). Although parti provides correction factors for AEDs, extrapolation from an average to an individual patient may be influenced by administration route, absence of metabolic enzyme for genetic reasons, and presence of inhibitors or other inducers. AED pharmacodynamic DDIs may also be important. Six patients with extreme sensitivity to AED inductive effects are described. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

Experiment on search for neutron-antineutron oscillations using a projected UCN source at the WWR-M reactor

NASA Astrophysics Data System (ADS)

Fomin, A. K.; Serebrov, A. P.; Zherebtsov, O. M.; Leonova, E. N.; Chaikovskii, M. E.

2017-01-01

We propose an experiment on search for neutron-antineutron oscillations based on the storage of ultracold neutrons (UCN) in a material trap. The sensitivity of the experiment mostly depends on the trap size and the amount of UCN in it. In Petersburg Nuclear Physics Institute (PNPI) a high-intensity UCN source is projected at the WWR-M reactor, which must provide UCN density 2-3 orders of magnitude higher than existing sources. The results of simulations of the designed experimental scheme show that the sensitivity can be increased by ˜ 10-40 times compared to sensitivity of previous experiment depending on the model of neutron reflection from walls.

Investigation of Ion Transmission Effects on Intact Protein Quantification in a Triple Quadrupole Mass Spectrometer

NASA Astrophysics Data System (ADS)

Wang, Evelyn H.; Appulage, Dananjaya Kalu; McAllister, Erin A.; Schug, Kevin A.

2017-09-01

Recently, direct intact protein quantitation using triple quadrupole mass spectrometry (QqQ-MS) and multiple reaction monitoring (MRM) was demonstrated (J. Am. Soc. Mass Spectrom. 27, 886-896 (2016)). Even though QqQ-MS is known to provide extraordinary detection sensitivity for quantitative analysis, we found that intact proteins exhibited a less than 5% ion transmission from the first quadrupole to the third quadrupole mass analyzer in the presence of zero collision energy (ZCE). With the goal to enhance intact protein quantitation sensitivity, ion scattering effects, proton transfer effects, and mass filter resolution widths were examined for their contributions to the lost signal. Protein standards myoglobin and ubiquitin along with small molecules reserpine and vancomycin were analyzed together with various collision induced dissociation (CID) gases (N2, He, and Ar) at different gas pressures. Mass resolution settings played a significant role in reducing ion transmission signal. By narrowing the mass resolution window by 0.35 m/z on each side, roughly 75%-90% of the ion signal was lost. The multiply charged proteins experienced additional proton transfer effects, corresponding to 10-fold signal reduction. A study of increased sensitivity of the method was also conducted with various MRM summation techniques. Although the degree of enhancement was analyte-dependent, an up to 17-fold increase in sensitivity was observed for ubiquitin using a summation of multiple MRM transitions. Biological matrix, human urine, and equine plasma were spiked with proteins to demonstrate the specificity of the method. This study provides additional insight into optimizing the use and sensitivity of QqQ-MS for intact protein quantification. [Figure not available: see fulltext.

Knockdown of ventral tegmental area mu-opioid receptors in rats prevents effects of social defeat stress: Implications for amphetamine cross-sensitization, social avoidance, weight regulation and expression of brain-derived neurotrophic factor

PubMed Central

Johnston, Caitlin E.; Herschel, Daniel; Lasek, Amy W.; Hammer, Ronald P.; Nikulina, Ella M.

2014-01-01

Social defeat stress causes social avoidance and long-lasting cross-sensitization to psychostimulants, both of which are associated with increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area (VTA). Moreover, social stress upregulates VTA mu-opioid receptor (MOR) mRNA. In the VTA, MOR activation inhibits GABA neurons to disinhibit VTA dopamine neurons, thus providing a role for VTA MORs in the regulation of psychostimulant sensitization. The present study determined the effect of lentivirus-mediated MOR knockdown in the VTA on the consequences of intermittent social defeat stress, a salient and profound stressor in humans and rodents. Social stress exposure induced social avoidance and attenuated weight gain in animals with non-manipulated VTA MORs, but both these effects were prevented by VTA MOR knockdown. Rats with non-manipulated VTA MOR expression exhibited cross-sensitization to amphetamine challenge (1.0 mg/kg, i.p.), evidenced by a significant augmentation of locomotion. By contrast, knockdown of VTA MORs prevented stress-induced cross-sensitization without blunting the locomotor-activating effects of amphetamine. At the time point corresponding to amphetamine challenge, immunohistochemical analysis was performed to examine the effect of stress on VTA BDNF expression. Prior stress exposure increased VTA BDNF expression in rats with non-manipulated VTA MOR expression, while VTA MOR knockdown prevented stress-induced expression of VTA BDNF. Taken together, these results suggest that upregulation of VTA MOR is necessary for the behavioral and biochemical changes induced by social defeat stress. Elucidating VTA MOR regulation of stress effects on the mesolimbic system may provide new therapeutic targets for treating stress-induced vulnerability to substance abuse. PMID:25446676

Solar cycle predicts folate-sensitive neonatal genotypes at discrete phases of the first trimester of pregnancy: a novel folate-related human embryo loss hypothesis.

PubMed

Lucock, Mark; Glanville, Tracey; Yates, Zoë; Walker, James; Furst, John; Simpson, Nigel

2012-08-01

Folate, a key periconceptional nutrient, is ultraviolet light (UV-R) sensitive. We therefore hypothesise that a relationship exists between sunspot activity, a proxy for total solar irradiance (particularly UV-R) reaching Earth, and the occurrence of folate-sensitive, epigenomic-related neonatal genotypes during the first trimester of pregnancy. Limited data is provided to support the hypothesis that the solar cycle predicts folate-related human embryo loss: 379 neonates born at latitude 54°N between 1998 and 2000 were examined for three folate-sensitive, epigenome-related polymorphisms, with solar activity for trimester one accessed via the Royal Greenwich Observatory-US Air force/National Oceanic and Atmospheric Administration Sunspot Database (34,110 total observation days). Logistic regression showed solar activity predicts C677T-methylenetetrahydrofolate reductase (C677T-MTHFR) and A66G-methionine synthase reductase (A66G-MSR) genotype at discrete phases of trimester one. Total and maximal sunspot activity predicts C677T-MTHFR genotype for days 31-60 of trimester one (p=0.0181 and 0.0366, respectively) and A66G-MSR genotype for days 61-90 of trimester one (p=0.0072 and 0.0105, respectively). Loss of UV-R sensitive folate associated with the sunspot cycle might therefore interact with variant folate genes to perturb DNA methylation and/or elaboration of the primary base sequence (thymidylate synthesis), as well as increase embryo-toxic homocysteine. We hypothesise that this may influence embryo viability leading to 677CC-MTHFR and 66GG-MSR embryo loss at times of increased solar activity. This provides an interesting and plausible link between well recognised 'folate gene originated developmental disorders' and 'solar activity/seasonality modulated developmental disorders'. Copyright © 2012 Elsevier Ltd. All rights reserved.

Improved Fiber-Optic-Coupled Pressure And Vibration Sensors

NASA Technical Reports Server (NTRS)

Zuckerwar, Allan J.; Cuomo, Frank W.

1994-01-01

Improved fiber-optic coupler enables use of single optical fiber to carry light to and from sensor head. Eliminates problem of alignment of multiple fibers in sensor head and simplifies calibration by making performance both more predictable and more stable. Sensitivities increased, sizes reduced. Provides increased margin for design of compact sensor heads not required to contain amplifier circuits and withstand high operating temperatures.

Diagnostic Accuracy of Memory Measures in Alzheimer’s Dementia and Mild Cognitive Impairment: a Systematic Review and Meta-Analysis

PubMed Central

Weissberger, Gali H.; Strong, Jessica V.; Stefanidis, Kayla B.; Summers, Mathew J.; Bondi, Mark W.; Stricker, Nikki H.

2018-01-01

With an increasing focus on biomarkers in dementia research, illustrating the role of neuropsychological assessment in detecting mild cognitive impairment (MCI) and Alzheimer’s dementia (AD) is important. This systematic review and meta-analysis, conducted in accordance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) standards, summarizes the sensitivity and specificity of memory measures in individuals with MCI and AD. Both meta-analytic and qualitative examination of AD versus healthy control (HC) studies (n = 47) revealed generally high sensitivity and specificity (≥ 80% for AD comparisons) for measures of immediate (sensitivity = 87%, specificity = 88%) and delayed memory (sensitivity = 89%, specificity = 89%), especially those involving word-list recall. Examination of MCI versus HC studies (n = 38) revealed generally lower diagnostic accuracy for both immediate (sensitivity = 72%, specificity = 81%) and delayed memory (sensitivity = 75%, specificity = 81%). Measures that differentiated AD from other conditions (n = 10 studies) yielded mixed results, with generally high sensitivity in the context of low or variable specificity. Results confirm that memory measures have high diagnostic accuracy for identification of AD, are promising but require further refinement for identification of MCI, and provide support for ongoing investigation of neuropsychological assessment as a cognitive biomarker of preclinical AD. Emphasizing diagnostic test accuracy statistics over null hypothesis testing in future studies will promote the ongoing use of neuropsychological tests as Alzheimer’s disease research and clinical criteria increasingly rely upon cerebrospinal fluid (CSF) and neuroimaging biomarkers. PMID:28940127

Common oxytocin receptor gene variant interacts with rejection sensitivity to influence cortisol reactivity during negative evaluation.

PubMed

Auer, Brandon J; Byrd-Craven, Jennifer; Grant, DeMond M; Granger, Douglas A

2015-09-01

The study tested the hypothesis that variation in the oxytocin receptor gene (OXTR rs53576) and self-report of rejection sensitivity are associated with adrenocortical reactivity to social stress. Participants (N=94; 36.17% male; Mage=20.18yrs; 62.8% Caucasian) completed a writing task on a salient problem in society, provided self-report via questionnaire of rejection sensitivity, and were then informed that a committee of peers would evaluate their written comments. Participants received either scripted praise or criticism as a way to induce social evaluative threat. Saliva was collected before and after the stress task and assayed for cortisol. Results revealed that cortisol levels increased in participants with moderate levels of social rejection sensitivity-inferred by rs53576 genotype and reported rejection sensitivity-while cortisol levels decreased in participants with high and low levels of social rejection sensitivity. Our findings suggest a curvilinear relationship between social rejection sensitivity and cortisol reactivity in the context of social rejection, warranting further consideration in future studies. Copyright © 2015. Published by Elsevier Inc.

Chemical Sensing Sensitivity of Long-Period Grating Sensor Enhanced by Colloidal Gold Nanoparticles

PubMed Central

Tang, Jaw-Luen; Wang, Jien-Neng

2008-01-01

A simple and effective method is proposed to improve spectral sensitivity and detection limit of long period gratings for refractive index or chemical sensing, where the grating surface is modified by a monolayer of colloidal gold nanoparticles. The transmission spectra and optical properties of gold nanospheres vary with the different refractive index of the environment near the surface of gold nanospheres. The sensor response of gold colloids increases linearly with solvents of increasing refractive index. The results for the measurement of sucrose and sodium chloride solutions are reported, which show that this type of sensor can provide a limiting resolution of ∼10-3 to ∼10-4 for refractive indices in the range of 1.34 to 1.39 and a noticeable increase in detection limit of refractive index to external medium. PMID:27879701

Quality and Cultural Sensitivity of Linguistically Appropriate Cardiovascular Disease Information for Chinese Immigrants: A Review of Online Resources From Heart Foundations.

PubMed

Li, Jialin; Lowres, Nicole; Jin, Kai; Zhang, Ling; Neubeck, Lis; Gallagher, Robyn

Chinese immigrants are at an increased risk for cardiovascular diseases (CVDs) compared with Chinese nationals partly because of lifestyle changes and knowledge deficits. Translated patient resources are available on the Internet and are often provided by health professionals; however, the quality and cultural sensitivity of these resources have not been reported. The aim of this study was to assess the availability, quality, and cultural sensitivity of Chinese-language information available from national "Heart Foundations" (cardiac research bodies, nongovernmental organisations) of the 5 most popular destinations of Chinese immigration. This study is a descriptive research in which national "Heart Foundation" websites were systematically searched for Chinese-language CVD patient education resources. Quality (content, identification, structure) was assessed using the Ensuring Quality Information for Patients instrument. Cultural sensitivity was evaluated using the Cultural Sensitivity Assessment Tool. From 107 identified resources, 33 were CVD specific: coronary heart disease (n = 20), arrhythmias (n = 7), and heart failure (n = 6). Quality of resources was adequate (mean Ensuring Quality Information for Patients score, 69%), but scores varied significantly (min, 60%; max, 85%). Although all resources were classified as culturally sensitive (Cultural Sensitivity Assessment Tool score ≥ 2.5), 2 resources scored low (≤2.5) for visual impact, and across all resources, written and visual domains were assessed as least culturally sensitive. Most resources lacked culturally specific references. Chinese-language CVD resources were inconsistent in the supply of key information. Quality and level of cultural sensitivity were adequate, but most resources lacked culturally specific references. Comprehensive, high-quality CVD resources powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation tailored for Chinese immigrants are urgently needed for healthcare providers to support CVD education and care of patients belonging to this population.

Investigating the Group-Level Impact of Advanced Dual-Echo fMRI Combinations

PubMed Central

Kettinger, Ádám; Hill, Christopher; Vidnyánszky, Zoltán; Windischberger, Christian; Nagy, Zoltán

2016-01-01

Multi-echo fMRI data acquisition has been widely investigated and suggested to optimize sensitivity for detecting the BOLD signal. Several methods have also been proposed for the combination of data with different echo times. The aim of the present study was to investigate whether these advanced echo combination methods provide advantages over the simple averaging of echoes when state-of-the-art group-level random-effect analyses are performed. Both resting-state and task-based dual-echo fMRI data were collected from 27 healthy adult individuals (14 male, mean age = 25.75 years) using standard echo-planar acquisition methods at 3T. Both resting-state and task-based data were subjected to a standard image pre-processing pipeline. Subsequently the two echoes were combined as a weighted average, using four different strategies for calculating the weights: (1) simple arithmetic averaging, (2) BOLD sensitivity weighting, (3) temporal-signal-to-noise ratio weighting and (4) temporal BOLD sensitivity weighting. Our results clearly show that the simple averaging of data with the different echoes is sufficient. Advanced echo combination methods may provide advantages on a single-subject level but when considering random-effects group level statistics they provide no benefit regarding sensitivity (i.e., group-level t-values) compared to the simple echo-averaging approach. One possible reason for the lack of clear advantages may be that apart from increasing the average BOLD sensitivity at the single-subject level, the advanced weighted averaging methods also inflate the inter-subject variance. As the echo combination methods provide very similar results, the recommendation is to choose between them depending on the availability of time for collecting additional resting-state data or whether subject-level or group-level analyses are planned. PMID:28018165

Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors.

PubMed

Lehrner, Amy; Bierer, Linda M; Passarelli, Vincent; Pratchett, Laura C; Flory, Janine D; Bader, Heather N; Harris, Iris R; Bedi, Aarti; Daskalakis, Nikolaos P; Makotkine, Iouri; Yehuda, Rachel

2014-02-01

Intergenerational effects of trauma have been observed clinically in a wide range of populations, and parental PTSD has been associated with an increased risk for psychopathology in offspring. In studies of Holocaust survivor offspring, parental PTSD, and particularly maternal PTSD, has been associated with increased risk for PTSD, low basal urinary cortisol excretion and enhanced cortisol suppression in response to dexamethasone. Such findings implicate maternally derived glucocorticoid programming in the intergenerational transmission of trauma-related consequences, potentially resulting from in utero influences or early life experiences. This study investigated the relative influence of Holocaust exposure and PTSD in mothers and fathers on glucocorticoid sensitivity in offspring. Eighty Holocaust offspring and 15 offspring of non-exposed Jewish parents completed evaluations and provided blood and urine samples. Glucocorticoid sensitivity was evaluated using the lysozyme suppression test (LST), an in vitro measure of glucocorticoid receptor sensitivity in a peripheral tissue, the dexamethasone suppression test (DST), and 24-h urinary cortisol excretion. Maternal PTSD was associated with greater glucocorticoid sensitivity in offspring across all three measures of glucocorticoid function. An interaction of maternal and paternal PTSD on the DST and 24-h urinary cortisol showed an effect of decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD. Although indirect, these findings are consistent with the hypothesis that epigenetic programming may be involved in the intergenerational transmission of trauma-related effects on glucocorticoid regulation. Published by Elsevier Ltd.

Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors

PubMed Central

Lehrner, Amy; Bierer, Linda M.; Passarelli, Vincent; Pratchett, Laura C.; Flory, Janine D.; Bader, Heather; Harris, Iris R.; Bedi, Aarti; Daskalakis, Nikolaos P.; Makotkine, Iouri; Yehuda, Rachel

2014-01-01

Intergenerational effects of trauma have been observed clinically in a wide range of populations, and parental PTSD has been associated with an increased risk for psychopathology in offspring. In studies of Holocaust survivor offspring, parental PTSD, and particularly maternal PTSD, has been associated with increased risk for PTSD, low basal urinary cortisol excretion and enhanced cortisol suppression in response to dexamethasone. Such findings implicate maternally derived glucocorticoid programming in the intergenerational transmission of trauma-related consequences, potentially resulting from in utero influences or early life experiences. This study investigated the relative influence of Holocaust exposure and PTSD in mothers and fathers on glucocorticoid sensitivity in offspring. Eighty Holocaust offspring and 15 offspring of non-exposed Jewish parents completed evaluations and provided blood and urine samples. Glucocorticoid sensitivity was evaluated using the lysozyme suppression test (LST), an in vitro measure of glucocorticoid receptor sensitivity in a peripheral tissue, the dexamethasone suppression test (DST), and 24 hour urinary cortisol excretion. Maternal PTSD was associated with greater glucocorticoid sensitivity in offspring across all three measures of glucocorticoid function. An interaction of maternal and paternal PTSD on the DST and 24-hr urinary cortisol showed an effect of decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD. Although indirect, these findings are consistent with the hypothesis that epigenetic programming may be involved in the intergenerational transmission of trauma-related effects on glucocorticoid regulation. PMID:24485493

WATER LEVEL AND OXYGEN DELIVERY/UTILIZATION IN POROUS SALT MARSH SEDIMENTS

EPA Science Inventory

Increasing terrestrial nutrient inputs to coastal waters is a global water quality issue worldwide, and salt marshes may provide a valuable nutrient buffer, either by direct removal or by smoothing out pulse inputs between sources and sensitive estuarine habitats. A major challen...

Study on turbulence characteristics and sensitivity of quadrant analysis to threshold level in Lake Taihu.

PubMed

Weng, Shenglin; Li, Yiping; Wei, Jin; Du, Wei; Gao, Xiaomeng; Wang, Wencai; Wang, Jianwei; Acharya, Kumud; Luo, Liancong

2018-05-01

The identification of coherent structures is very important in investigating the sediment transport mechanism and controlling the eutrophication in shallow lakes. This study analyzed the turbulence characteristics and the sensitivity of quadrant analysis to threshold level. Simultaneous in situ measurements of velocities and suspended sediment concentration (SSC) were conducted in Lake Taihu with acoustic Doppler velocimeter (ADV) and optical backscatter sensor (OBS) instruments. The results show that the increase in hole size makes the difference between dominant and non-dominant events more distinct. Wind velocity determines the frequency of occurrence of sweep and ejection events, which provide dominant contributions to the Reynolds stress. The increase of wind velocity enlarges the magnitude of coherent events but has little impact on the events frequency with the same hole size. The events occurring within short periods provide large contributions to the momentum flux. Transportation and diffusion of sediment are in control of the intermittent coherent events to a large extent.

Vulnerability of island tropical montane cloud forests to climate change, with special reference to East Maui, Hawaii

USGS Publications Warehouse

Loope, Lloyd L.; Giambelluca, Thomas W.

1998-01-01

Island tropical montane cloud forests may be among the most sensitive of the world's ecosystems to global climate change. Measurements in and above a montane cloud forest on East Maui, Hawaii, document steep microclimatic gradients. Relatively small climate-driven shifts in patterns of atmospheric circulation are likely to trigger major local changes in rainfall, cloud cover, and humidity. Increased interannual variability in precipitation and hurricane incidence would provide additional stresses on island biota that are highly vulnerable to disturbance-related invasion of non-native species. Because of the exceptional sensitivity of these microclimates and forests to change, they may provide valuable ‘listening posts’ for detecting the onset of human-induced global climate change.

Acute spinal cord injury (SCI) transforms how GABA affects nociceptive sensitization.

PubMed

Huang, Yung-Jen; Lee, Kuan H; Murphy, Lauren; Garraway, Sandra M; Grau, James W

2016-11-01

Noxious input can sensitize pain (nociceptive) circuits within the spinal cord, inducing a lasting increase in spinal cord neural excitability (central sensitization) that is thought to contribute to chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. The current study provides evidence that spinal cord injury (SCI) transforms how GABA affects nociceptive transmission within the spinal cord, recapitulating an earlier developmental state wherein GABA has an excitatory effect. In spinally transected rats, noxious electrical stimulation and inflammation induce enhanced mechanical reactivity (EMR), a behavioral index of nociceptive sensitization. Pretreatment with the GABA A receptor antagonist bicuculline blocked these effects. Peripheral application of an irritant (capsaicin) also induced EMR. Both the induction and maintenance of this effect were blocked by bicuculline. Cellular indices of central sensitization [c-fos expression and ERK phosphorylation (pERK)] were also attenuated. In intact (sham operated) rats, bicuculline had the opposite effect. Pretreatment with a GABA agonist (muscimol) attenuated nociceptive sensitization in intact, but not spinally injured, rats. The effect of SCI on GABA function was linked to a reduction in the Cl - transporter, KCC2, leading to a reduction in intracellular Cl - that would attenuate GABA-mediated inhibition. Pharmacologically blocking the KCC2 channel (with i.t. DIOA) in intact rats mimicked the effect of SCI. Conversely, a pharmacological treatment (bumetanide) that should increase intracellular Cl - levels blocked the effect of SCI. The results suggest that GABAergic neurons drive, rather than inhibit, the development of nociceptive sensitization after spinal injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Downregulation of hPMC2 imparts chemotherapeutic sensitivity to alkylating agents in breast cancer cells.

PubMed

Krishnamurthy, Nirmala; Liu, Lili; Xiong, Xiahui; Zhang, Junran; Montano, Monica M

2015-01-01

Triple negative breast cancer cell lines have been reported to be resistant to the cyotoxic effects of temozolomide (TMZ). We have shown previously that a novel protein, human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2) has a role in the repair of estrogen-induced abasic sites. Our present study provides evidence that downregulation of hPMC2 in MDA-MB-231 and MDA-MB-468 breast cancer cells treated with temozolomide (TMZ) decreases cell survival. This increased sensitivity to TMZ is associated with an increase in number of apurinic/apyrimidinic (AP) sites in the DNA. We also show that treatment with another alkylating agent, BCNU, results in an increase in AP sites and decrease in cell survival. Quantification of western blot analyses and immunofluorescence experiments reveal that treatment of hPMC2 downregulated cells with TMZ results in an increase in γ-H2AX levels, suggesting an increase in double strand DNA breaks. The enhancement of DNA double strand breaks in TMZ treated cells upon downregulation of hPCM2 is also revealed by the comet assay. Overall, we provide evidence that downregulation of hPMC2 in breast cancer cells increases cytotoxicity of alkylating agents, representing a novel mechanism of treatment for breast cancer. Our data thus has important clinical implications in the management of breast cancer and brings forth potentially new therapeutic strategies.

Comparison of algorithms of testing for use in automated evaluation of sensation.

PubMed

Dyck, P J; Karnes, J L; Gillen, D A; O'Brien, P C; Zimmerman, I R; Johnson, D M

1990-10-01

Estimates of vibratory detection threshold may be used to detect, characterize, and follow the course of sensory abnormality in neurologic disease. The approach is especially useful in epidemiologic and controlled clinical trials. We studied which algorithm of testing and finding threshold should be used in automatic systems by comparing among algorithms and stimulus conditions for the index finger of healthy subjects and for the great toe of patients with mild neuropathy. Appearance thresholds obtained by linear ramps increasing at a rate less than 4.15 microns/sec provided accurate and repeatable thresholds compared with thresholds obtained by forced-choice testing. These rates would be acceptable if only sensitive sites were studied, but they were too slow for use in automatic testing of insensitive parts. Appearance thresholds obtained by fast linear rates (4.15 or 16.6 microns/sec) overestimated threshold, especially for sensitive parts. Use of the mean of appearance and disappearance thresholds, with the stimulus increasing exponentially at rates of 0.5 or 1.0 just noticeable difference (JND) units per second, and interspersion of null stimuli, Békésy with null stimuli, provided accurate, repeatable, and fast estimates of threshold for sensitive parts. Despite the good performance of Békésy testing, we prefer forced choice for evaluation of the sensation of patients with neuropathy.

Critical loads of atmospheric deposition to Adirondack lake watersheds: A guide for policymakers

USGS Publications Warehouse

Burns, Douglas A.; Sullivan, Timothy J.

2015-01-01

Acid deposition is sometimes referred to as “acid rain,” although part of the acid load reaches the surface by means other than rainfall. In the eastern U.S., acid deposition consists of several forms of sulfur and nitrogen that largely originate as emissions to the atmosphere from sources such as electricity-generating facilities (coal, oil, and natural gas), diesel- and gasoline-burning vehicles, some agricultural activities, and smokestack industries. Acid deposition is known to cause deleterious effects to sensitive ecosystems of which the Adirondack region of New York State provides several well-known and well-studied examples. This largely forested region includes abundant lakes, streams, and wetlands and possesses several landscape features that result in high ecosystem sensitivity to acid deposition. These features include bedrock that weathers slowly, steep slopes, and thin, naturally acidic soils. An ecosystem is described as sensitive to, or affected by, acid deposition if prolonged exposure to acid deposition has resulted in detrimental ecosystem effects. Soils, streams, and lakes that are less sensitive are better able to buffer acid deposition. A principal reason that acidification is a concern for resource managers is because of the changes induced in native biota and their habitat on land and in water. As the chemistry of soils and surface waters in sensitive landscapes changes in response to prolonged exposure to acid deposition, organisms that cannot tolerate high acidity, such as sugar maple trees and many species of fish and aquatic insects, may be gradually eliminated from the ecosystem. Other biota such as red spruce may experience increased stress and reduced growth rates as a result of acidification, exposing these species to increased susceptibility to disease and other natural stressors and perhaps increased mortality. The ecological effects of acid deposition have been documented by extensive research that began in the U.S. in the 1970s and continues today. This report does not provide a detailed discussion of these ecological effects, but interested readers can refer to four publications that provide good summaries of current scientific knowledge of these effects, including extensive reference to previous research in the Adirondacks (Driscoll et al. 2001, Jenkins et al. 2007, Burns et al. 2011, Sullivan 2015).

Reinforcement Sensitivity and Risk for Psychopathology Following Exposure to Violence: A Vulnerability-Specificity Model in Latino Youth

PubMed Central

Gudiño, Omar G.; Nadeem, Erum; Kataoka, Sheryl H.; Lau, Anna S.

2013-01-01

Urban Latino youth are exposed to high rates of violence, which increases risk for diverse forms of psychopathology. To current study aims to increase specificity in predicting responses by testing the hypothesis that youths’ reinforcement sensitivity–behavioral inhibition (BIS) and behavioral approach (BAS)–is associated with specific clinical outcomes and increases risk for the development of such problems following exposure to violence. Utilizing a short-term longitudinal design, Latino youth (N=168) provided reports of BIS/BAS and emotional/behavioral problems at Time 1, exposure to violence between Time 1 and Time 2, and clinical symptoms at Time 2. Results suggested that reinforcement sensitivity moderated the relation between violence exposure and psychopathology, such that increasing levels of BIS were associated with elevated risk for internalizing and posttraumatic stress symptoms following exposure to violence whereas BAS increased risk for externalizing problems. The importance of building on existing knowledge to understand minority youth psychopathology is discussed. PMID:22080366

Spatial and spectral characterization of acid rain stress in Canadian Shield lakes

NASA Technical Reports Server (NTRS)

Marshall, Elizabeth J.; Tanis, Frederick J.

1989-01-01

Results from this study demonstrate that a remote sensor can discriminate lake clarity based upon reflection. The basic hypothesis was that seasonal and multiyear changes in lake optical transparency are indicative of sensitivity to acidic deposition. In many acid-sensitive lakes optical transparency is controlled by the amount of dissolved organic carbon (DOC) present. DOC is a strong absorbing, nonscattering material which has the greatest impact at short visible wavelengths, including Thematic Mapper band 1. Acid-sensitive lakes have high concentrations of aluminum which have been mobilized by acidic components contained in the runoff. Aluminum complexing with DOC is considered to be the primary mechanism to account for observed increases in lake transparency in acid-sensitive lakes. Thus seasonal changes in the optical transparency of lakes should provide an indication of the stress due to acid deposition and loading.

Comparison of two cash transfer strategies to prevent catastrophic costs for poor tuberculosis-affected households in low- and middle-income countries: An economic modelling study

PubMed Central

Lönnroth, Knut; Boccia, Delia

2017-01-01

Background Illness-related costs for patients with tuberculosis (TB) ≥20% of pre-illness annual household income predict adverse treatment outcomes and have been termed “catastrophic.” Social protection initiatives, including cash transfers, are endorsed to help prevent catastrophic costs. With this aim, cash transfers may either be provided to defray TB-related costs of households with a confirmed TB diagnosis (termed a “TB-specific” approach); or to increase income of households with high TB risk to strengthen their economic resilience (termed a “TB-sensitive” approach). The impact of cash transfers provided with each of these approaches might vary. We undertook an economic modelling study from the patient perspective to compare the potential of these 2 cash transfer approaches to prevent catastrophic costs. Methods and findings Model inputs for 7 low- and middle-income countries (Brazil, Colombia, Ecuador, Ghana, Mexico, Tanzania, and Yemen) were retrieved by literature review and included countries' mean patient TB-related costs, mean household income, mean cash transfers, and estimated TB-specific and TB-sensitive target populations. Analyses were completed for drug-susceptible (DS) TB-related costs in all 7 out of 7 countries, and additionally for drug-resistant (DR) TB-related costs in 1 of the 7 countries with available data. All cost data were reported in 2013 international dollars ($). The target population for TB-specific cash transfers was poor households with a confirmed TB diagnosis, and for TB-sensitive cash transfers was poor households already targeted by countries’ established poverty-reduction cash transfer programme. Cash transfers offered in countries, unrelated to TB, ranged from $217 to $1,091/year/household. Before cash transfers, DS TB-related costs were catastrophic in 6 out of 7 countries. If cash transfers were provided with a TB-specific approach, alone they would be insufficient to prevent DS TB catastrophic costs in 4 out of 6 countries, and when increased enough to prevent DS TB catastrophic costs would require a budget between $3.8 million (95% CI: $3.8 million–$3.8 million) and $75 million (95% CI: $50 million–$100 million) per country. If instead cash transfers were provided with a TB-sensitive approach, alone they would be insufficient to prevent DS TB-related catastrophic costs in any of the 6 countries, and when increased enough to prevent DS TB catastrophic costs would require a budget between $298 million (95% CI: $219 million–$378 million) and $165,367 million (95% CI: $134,085 million–$196,425 million) per country. DR TB-related costs were catastrophic before and after TB-specific or TB-sensitive cash transfers in 1 out of 1 countries. Sensitivity analyses showed our findings to be robust to imputation of missing TB-related cost components, and use of 10% or 30% instead of 20% as the threshold for measuring catastrophic costs. Key limitations were using national average data and not considering other health and social benefits of cash transfers. Conclusions A TB-sensitive cash transfer approach to increase all poor households’ income may have broad benefits by reducing poverty, but is unlikely to be as effective or affordable for preventing TB catastrophic costs as a TB-specific cash transfer approach to defray TB-related costs only in poor households with a confirmed TB diagnosis. Preventing DR TB-related catastrophic costs will require considerable additional investment whether a TB-sensitive or a TB-specific cash transfer approach is used. PMID:29112693

Differential housing and novelty response: Protection and risk from locomotor sensitization.

PubMed

Garcia, Erik J; Haddon, Tara N; Saucier, Donald A; Cain, Mary E

2017-03-01

High novelty seeking increases the risk for drug experimentation and locomotor sensitization. Locomotor sensitization to psychostimulants is thought to reflect neurological adaptations that promote the transition to compulsive drug taking. Rats reared in enrichment (EC) show less locomotor sensitization when compared to rats reared in isolation (IC) or standard conditions (SC). The current research study was designed to test if novelty response contributed locomotor sensitization and more importantly, if the different housing environments could change the novelty response to protect against the development of locomotor sensitization in both adolescence and adulthood. Experiment 1: rats were tested for their response to novelty using the inescapable novelty test (IEN) and pseudorandomly assigned to enriched (EC), isolated (IC), or standard (SC) housing conditions for 30days. After housing, they were tested with IEN. Rats were then administered amphetamine (0.5mg/kg) or saline and locomotor activity was measured followed by a sensitization test 14days later. Experiment 2: rats were tested in the IEN test early adulthood and given five administrations of amphetamine (0.3mg/kg) or saline and then either stayed in or switched housing environments for 30days. Rats were then re-tested in the IEN test in late adulthood and administered five more injections of their respective treatments and tested for locomotor sensitization. Results indicate that IC and SC increased the response to novelty. EC housing decreased locomotor response to amphetamine and saline, and SC housing increased the locomotor response to amphetamine. Mediation results indicated that the late adult novelty response fully mediates the locomotor response to amphetamine and saline, while the early adulthood novelty response did not. Differential housing changes novelty and amphetamine locomotor response. Novelty response is altered into adulthood and provides evidence that enrichment can be used to reduce drug vulnerability. Copyright © 2017 Elsevier Inc. All rights reserved.

Sensitivity analysis of a multilayer, finite-difference model of the Southeastern Coastal Plain regional aquifer system; Mississippi, Alabama, Georgia, and South Carolina

USGS Publications Warehouse

Pernik, Meribeth

1987-01-01

The sensitivity of a multilayer finite-difference regional flow model was tested by changing the calibrated values for five parameters in the steady-state model and one in the transient-state model. The parameters that changed under the steady-state condition were those that had been routinely adjusted during the calibration process as part of the effort to match pre-development potentiometric surfaces, and elements of the water budget. The tested steady-state parameters include: recharge, riverbed conductance, transmissivity, confining unit leakance, and boundary location. In the transient-state model, the storage coefficient was adjusted. The sensitivity of the model to changes in the calibrated values of these parameters was evaluated with respect to the simulated response of net base flow to the rivers, and the mean value of the absolute head residual. To provide a standard measurement of sensitivity from one parameter to another, the standard deviation of the absolute head residual was calculated. The steady-state model was shown to be most sensitive to changes in rates of recharge. When the recharge rate was held constant, the model was more sensitive to variations in transmissivity. Near the rivers, the riverbed conductance becomes the dominant parameter in controlling the heads. Changes in confining unit leakance had little effect on simulated base flow, but greatly affected head residuals. The model was relatively insensitive to changes in the location of no-flow boundaries and to moderate changes in the altitude of constant head boundaries. The storage coefficient was adjusted under transient conditions to illustrate the model 's sensitivity to changes in storativity. The model is less sensitive to an increase in storage coefficient than it is to a decrease in storage coefficient. As the storage coefficient decreased, the aquifer drawdown increases, the base flow decreased. The opposite response occurred when the storage coefficient was increased. (Author 's abstract)

Interventional MRI: tapering improves the distal sensitivity of the loopless antenna.

PubMed

Qian, Di; El-Sharkawy, AbdEl-Monem M; Atalar, Ergin; Bottomley, Paul A

2010-03-01

The "loopless antenna" is an interventional MRI detector consisting of a tuned coaxial cable and an extended inner conductor or "whip". A limitation is the poor sensitivity afforded at, and immediately proximal to, its distal end, which is exacerbated by the extended whip length when the whip is uniformly insulated. It is shown here that tapered insulation dramatically improves the distal sensitivity of the loopless antenna by pushing the current sensitivity toward the tip. The absolute signal-to-noise ratio is numerically computed by the electromagnetic method-of-moments for three resonant 3-T antennae with no insulation, uniform insulation, and with linearly tapered insulation. The analysis shows that tapered insulation provides an approximately 400% increase in signal-to-noise ratio in trans-axial planes 1 cm from the tip and a 16-fold increase in the sensitive area as compared to an equivalent, uniformly insulated antenna. These findings are directly confirmed by phantom experiments and by MRI of an aorta specimen. The results demonstrate that numerical electromagnetic signal-to-noise ratio analysis can accurately predict the loopless detector's signal-to-noise ratio and play a central role in optimizing its design. The manifold improvement in distal signal-to-noise ratio afforded by redistributing the insulation should improve the loopless antenna's utility for interventional MRI. (c) 2010 Wiley-Liss, Inc.

Salience network response to changes in emotional expressions of others is heightened during early adolescence: relevance for social functioning.

PubMed

Rosen, Maya L; Sheridan, Margaret A; Sambrook, Kelly A; Dennison, Meg J; Jenness, Jessica L; Askren, Mary K; Meltzoff, Andrew N; McLaughlin, Katie A

2018-05-01

Adolescence is a unique developmental period when the salience of social and emotional information becomes particularly pronounced. Although this increased sensitivity to social and emotional information has frequently been considered with respect to risk behaviors and psychopathology, evidence suggests that increased adolescent sensitivity to social and emotional cues may confer advantages. For example, greater sensitivity to shifts in the emotions of others is likely to promote flexible and adaptive social behavior. In this study, a sample of 54 children and adolescents (age 8-19 years) performed a delayed match-to-sample task for emotional faces while undergoing fMRI scanning. Recruitment of the anterior cingulate and anterior insula when the emotion of the probe face did not match the emotion held in memory followed a quadratic developmental pattern that peaked during early adolescence. These findings indicate meaningful developmental variation in the neural mechanisms underlying sensitivity to changes in the emotional expressions. Across all participants, greater activation of this network for changes in emotional expression was associated with less social anxiety and fewer social problems. These results suggest that the heightened salience of social and emotional information during adolescence may confer important advantages for social behavior, providing sensitivity to others' emotions that facilitates flexible social responding. © 2017 John Wiley & Sons Ltd.

Improving LC-MS sensitivity through increases in chromatographic performance: comparisons of UPLC-ES/MS/MS to HPLC-ES/MS/MS.

PubMed

Churchwell, Mona I; Twaddle, Nathan C; Meeker, Larry R; Doerge, Daniel R

2005-10-25

Recent technological advances have made available reverse phase chromatographic media with a 1.7 microm particle size along with a liquid handling system that can operate such columns at much higher pressures. This technology, termed ultra performance liquid chromatography (UPLC), offers significant theoretical advantages in resolution, speed, and sensitivity for analytical determinations, particularly when coupled with mass spectrometers capable of high-speed acquisitions. This paper explores the differences in LC-MS performance by conducting a side-by-side comparison of UPLC for several methods previously optimized for HPLC-based separation and quantification of multiple analytes with maximum throughput. In general, UPLC produced significant improvements in method sensitivity, speed, and resolution. Sensitivity increases with UPLC, which were found to be analyte-dependent, were as large as 10-fold and improvements in method speed were as large as 5-fold under conditions of comparable peak separations. Improvements in chromatographic resolution with UPLC were apparent from generally narrower peak widths and from a separation of diastereomers not possible using HPLC. Overall, the improvements in LC-MS method sensitivity, speed, and resolution provided by UPLC show that further advances can be made in analytical methodology to add significant value to hypothesis-driven research.

A blood biomarker for monitoring response to anti-EGFR therapy.

PubMed

Hughes, Nicholas P; Xu, Lingyun; Nielsen, Carsten H; Chang, Edwin; Hori, Sharon S; Natarajan, Arutselvan; Lee, Samantha; Kjær, Andreas; Kani, Kian; Wang, Shan X; Mallick, Parag; Gambhir, Sanjiv Sam

2018-04-13

To monitor therapies targeted to epidermal growth factor receptors (EGFR) in non-small cell lung cancer (NSCLC), we investigated Peroxiredoxin 6 (PRDX6) as a biomarker of response to anti-EGFR agents. We studied cells that are sensitive (H3255, HCC827) or resistant (H1975, H460) to gefitinib. PRDX6 was examined with either gefitinib or vehicle treatment using enzyme-linked immunosorbent assays. We created xenograft models from one sensitive (HCC827) and one resistant cell line (H1975) and monitored serum PRDX6 levels during treatment. PRDX6 levels in cell media from sensitive cell lines increased significantly after gefitinib treatment vs. vehicle, whereas there was no significant difference for resistant lines. PRDX6 accumulation over time correlated positively with gefitinib sensitivity. Serum PRDX6 levels in gefitinib-sensitive xenograft models increased markedly during the first 24 hours of treatment and then decreased dramatically during the following 48 hours. Differences in serum PRDX6 levels between vehicle and gefitinib-treated animals could not be explained by differences in tumor burden. Our results show that changes in serum PRDX6 during the course of gefitinib treatment of xenograft models provide insight into tumor response and such an approach offers several advantages over imaging-based strategies for monitoring response to anti-EGFR agents.

Increased conspicuousness can explain the match between visual sensitivities and blue plumage colours in fairy-wrens.

PubMed

Delhey, Kaspar; Hall, Michelle; Kingma, Sjouke A; Peters, Anne

2013-01-07

Colour signals are expected to match visual sensitivities of intended receivers. In birds, evolutionary shifts from violet-sensitive (V-type) to ultraviolet-sensitive (U-type) vision have been linked to increased prevalence of colours rich in shortwave reflectance (ultraviolet/blue), presumably due to better perception of such colours by U-type vision. Here we provide the first test of this widespread idea using fairy-wrens and allies (Family Maluridae) as a model, a family where shifts in visual sensitivities from V- to U-type eyes are associated with male nuptial plumage rich in ultraviolet/blue colours. Using psychophysical visual models, we compared the performance of both types of visual systems at two tasks: (i) detecting contrast between male plumage colours and natural backgrounds, and (ii) perceiving intraspecific chromatic variation in male plumage. While U-type outperforms V-type vision at both tasks, the crucial test here is whether U-type vision performs better at detecting and discriminating ultraviolet/blue colours when compared with other colours. This was true for detecting contrast between plumage colours and natural backgrounds (i), but not for discriminating intraspecific variability (ii). Our data indicate that selection to maximize conspicuousness to conspecifics may have led to the correlation between ultraviolet/blue colours and U-type vision in this clade of birds.

Sensitive Indicators of Zonal Stipa Species to Changing Temperature and Precipitation in Inner Mongolia Grassland, China

PubMed Central

Lv, Xiaomin; Zhou, Guangsheng; Wang, Yuhui; Song, Xiliang

2016-01-01

Climate change often induces shifts in plant functional traits. However, knowledge related to sensitivity of different functional traits and sensitive indicator representing plant growth under hydrothermal change remains unclear. Inner Mongolia grassland is predicted to be one of the terrestrial ecosystems which are most vulnerable to climate change. In this study, we analyzed the response of four zonal Stipa species (S. baicalensis, S. grandis, S. breviflora, and S. bungeana) from Inner Mongolia grassland to changing temperature (control, increased 1.5, 2, 4, and 6°C), precipitation (decreased 30 and 15%, control, increased 15 and 30%) and their combined effects via climate control chambers. The relative change of functional traits in the unit of temperature and precipitation change was regarded as sensitivity coefficient and sensitive indicators were examined by pathway analysis. We found that sensitivity of the four Stipa species to changing temperature and precipitation could be ranked as follows: S. bungeana > S. grandis > S. breviflora > S. baicalensis. In particular, changes in leaf area, specific leaf area and root/shoot ratio could account for 86% of the changes in plant biomass in the four Stipa species. Also these three measurements were more sensitive to hydrothermal changes than the other functional traits. These three functional indicators reflected the combination of plant production capacity (leaf area), adaptive strategy (root/shoot ratio), instantaneous environmental effects (specific leaf area), and cumulative environmental effects (leaf area and root/shoot ratio). Thus, leaf area, specific leaf area and root/shoot ratio were chosen as sensitive indicators in response to changing temperature and precipitation for Stipa species. These results could provide the basis for predicting the influence of climate change on Inner Mongolia grassland based on the magnitude of changes in sensitive indicators. PMID:26904048

The Relationship Between Cultural Sensitivity and Assertiveness in Nursing Students from Turkey.

PubMed

Kılıç, Serap Parlar; Sevinç, Sibel

2018-07-01

As foreigners live in and visit Turkey for various reasons, it is essential to provide culturally appropriate health care. This study was conducted to determine the relationship between cultural sensitivity and assertiveness in university nursing students. This descriptive, cross-sectional study was conducted at two universities in the cities of Kilis and Elazığ, Turkey. The study sample consisted of 444 nursing students. Data collection tools included a questionnaire about participant sociodemographic characteristics, Chen and Starosta's Intercultural Sensitivity Scale, and the Rathus Assertiveness Scale. The mean age of participants was 21.09 years. Most students (71.6%) were female and 34.7% of the students stayed at the hostel. Of the students, 44.4%, 27.5%, and 28.2% attended were the second-, third-, and fourth-year students, respectively. Participants were asked about problems related to caring for patients who speak different languages. The mean score for the Intercultural Sensitivity Scale was 89.42 ± 13.55 and the total score for all students for the Assertiveness Scale was 112.64 ± 15.61. We identified a positive relationship between total scores for the Intercultural Sensitivity Scale and the Assertiveness Scale ( p < .001). There was relationship between cultural sensitivity and gender and want to work overseas; assertiveness and year of nursing education and want to work overseas. Nursing students at both schools had a moderate level of cultural sensitivity and assertiveness. It has been determined that as assertiveness level of the students increased, intercultural sensitivity of them also increased. Consequently, it is concluded that training as assertive and self-confident individuals during the nursing education of students has a contribution to making patient-specific and culture-sensitive care.

Higher-eigenmode piezoresponse force microscopy: a path towards increased sensitivity and the elimination of electrostatic artifacts

NASA Astrophysics Data System (ADS)

MacDonald, Gordon A.; DelRio, Frank W.; Killgore, Jason P.

2018-03-01

Piezoresponse force microscopy (PFM) and related bias-induced strain sensing atomic force microscopy techniques provide unique characterization of material-functionality at the nanoscale. However, these techniques are prone to unwanted artifact signals that influence the vibration amplitude of the detecting cantilever. Here, we show that higher-order contact resonance eigenmodes can be readily excited in PFM. The benefits of using the higher-order eigenmodes include absolute sensitivity enhancement, electrostatic artifact reduction, and lateral versus normal strain decoupling. This approach can significantly increase the proportion of total signal arising from desired strain (as opposed to non-strain artifacts) in measurements with cantilevers exhibiting typical, few N m‑1 spring constants to cantilevers up to 1000× softer than typically used.

Re-thinking the role of motor cortex: Context-sensitive motor outputs?

PubMed Central

Gandolla, Marta; Ferrante, Simona; Molteni, Franco; Guanziroli, Eleonora; Frattini, Tiziano; Martegani, Alberto; Ferrigno, Giancarlo; Friston, Karl; Pedrocchi, Alessandra; Ward, Nick S.

2014-01-01

The standard account of motor control considers descending outputs from primary motor cortex (M1) as motor commands and efference copy. This account has been challenged recently by an alternative formulation in terms of active inference: M1 is considered as part of a sensorimotor hierarchy providing top–down proprioceptive predictions. The key difference between these accounts is that predictions are sensitive to the current proprioceptive context, whereas efference copy is not. Using functional electric stimulation to experimentally manipulate proprioception during voluntary movement in healthy human subjects, we assessed the evidence for context sensitive output from M1. Dynamic causal modeling of functional magnetic resonance imaging responses showed that FES altered proprioception increased the influence of M1 on primary somatosensory cortex (S1). These results disambiguate competing accounts of motor control, provide some insight into the synaptic mechanisms of sensory attenuation and may speak to potential mechanisms of action of FES in promoting motor learning in neurorehabilitation. PMID:24440530

Re-thinking the role of motor cortex: context-sensitive motor outputs?

PubMed

Gandolla, Marta; Ferrante, Simona; Molteni, Franco; Guanziroli, Eleonora; Frattini, Tiziano; Martegani, Alberto; Ferrigno, Giancarlo; Friston, Karl; Pedrocchi, Alessandra; Ward, Nick S

2014-05-01

The standard account of motor control considers descending outputs from primary motor cortex (M1) as motor commands and efference copy. This account has been challenged recently by an alternative formulation in terms of active inference: M1 is considered as part of a sensorimotor hierarchy providing top-down proprioceptive predictions. The key difference between these accounts is that predictions are sensitive to the current proprioceptive context, whereas efference copy is not. Using functional electric stimulation to experimentally manipulate proprioception during voluntary movement in healthy human subjects, we assessed the evidence for context sensitive output from M1. Dynamic causal modeling of functional magnetic resonance imaging responses showed that FES altered proprioception increased the influence of M1 on primary somatosensory cortex (S1). These results disambiguate competing accounts of motor control, provide some insight into the synaptic mechanisms of sensory attenuation and may speak to potential mechanisms of action of FES in promoting motor learning in neurorehabilitation. Copyright © 2014 unknown. Published by Elsevier Inc. All rights reserved.

Manual versus Automated Rodent Behavioral Assessment: Comparing Efficacy and Ease of Bederson and Garcia Neurological Deficit Scores to an Open Field Video-Tracking System.

PubMed

Desland, Fiona A; Afzal, Aqeela; Warraich, Zuha; Mocco, J

2014-01-01

Animal models of stroke have been crucial in advancing our understanding of the pathophysiology of cerebral ischemia. Currently, the standards for determining neurological deficit in rodents are the Bederson and Garcia scales, manual assessments scoring animals based on parameters ranked on a narrow scale of severity. Automated open field analysis of a live-video tracking system that analyzes animal behavior may provide a more sensitive test. Results obtained from the manual Bederson and Garcia scales did not show significant differences between pre- and post-stroke animals in a small cohort. When using the same cohort, however, post-stroke data obtained from automated open field analysis showed significant differences in several parameters. Furthermore, large cohort analysis also demonstrated increased sensitivity with automated open field analysis versus the Bederson and Garcia scales. These early data indicate use of automated open field analysis software may provide a more sensitive assessment when compared to traditional Bederson and Garcia scales.

Hyperspectral data analysis procedures with reduced sensitivity to noise

NASA Technical Reports Server (NTRS)

Landgrebe, David A.

1993-01-01

Multispectral sensor systems have become steadily improved over the years in their ability to deliver increased spectral detail. With the advent of hyperspectral sensors, including imaging spectrometers, this technology is in the process of taking a large leap forward, thus providing the possibility of enabling delivery of much more detailed information. However, this direction of development has drawn even more attention to the matter of noise and other deleterious effects in the data, because reducing the fundamental limitations of spectral detail on information collection raises the limitations presented by noise to even greater importance. Much current effort in remote sensing research is thus being devoted to adjusting the data to mitigate the effects of noise and other deleterious effects. A parallel approach to the problem is to look for analysis approaches and procedures which have reduced sensitivity to such effects. We discuss some of the fundamental principles which define analysis algorithm characteristics providing such reduced sensitivity. One such analysis procedure including an example analysis of a data set is described, illustrating this effect.

Optimal replenishment and credit policy in supply chain inventory model under two levels of trade credit with time- and credit-sensitive demand involving default risk

NASA Astrophysics Data System (ADS)

Mahata, Puspita; Mahata, Gour Chandra; Kumar De, Sujit

2018-03-01

Traditional supply chain inventory modes with trade credit usually only assumed that the up-stream suppliers offered the down-stream retailers a fixed credit period. However, in practice the retailers will also provide a credit period to customers to promote the market competition. In this paper, we formulate an optimal supply chain inventory model under two levels of trade credit policy with default risk consideration. Here, the demand is assumed to be credit-sensitive and increasing function of time. The major objective is to determine the retailer's optimal credit period and cycle time such that the total profit per unit time is maximized. The existence and uniqueness of the optimal solution to the presented model are examined, and an easy method is also shown to find the optimal inventory policies of the considered problem. Finally, numerical examples and sensitive analysis are presented to illustrate the developed model and to provide some managerial insights.

Orbiting passive microwave sensor simulation applied to soil moisture estimation

NASA Technical Reports Server (NTRS)

Newton, R. W. (Principal Investigator); Clark, B. V.; Pitchford, W. M.; Paris, J. F.

1979-01-01

A sensor/scene simulation program was developed and used to determine the effects of scene heterogeneity, resolution, frequency, look angle, and surface and temperature relations on the performance of a spaceborne passive microwave system designed to estimate soil water information. The ground scene is based on classified LANDSAT images which provide realistic ground classes, as well as geometries. It was determined that the average sensitivity of antenna temperature to soil moisture improves as the antenna footprint size increased. Also, the precision (or variability) of the sensitivity changes as a function of resolution.

Afferent thermosensory function in relapsing-remitting multiple sclerosis following exercise-induced increases in body temperature.

PubMed

Filingeri, Davide; Chaseling, Georgia; Hoang, Phu; Barnett, Michael; Davis, Scott L; Jay, Ollie

2017-08-01

What is the central question of this study? Between 60 and 80% of multiple sclerosis (MS) patients experience transient worsening of symptoms with increased body temperature (heat sensitivity). As sensory abnormalities are common in MS, we asked whether afferent thermosensory function is altered in MS following exercise-induced increases in body temperature. What is the main finding and its importance? Increases in body temperature of as little as ∼0.4°C were sufficient to decrease cold, but not warm, skin thermosensitivity (∼10%) in MS, across a wider temperature range than in age-matched healthy individuals. These findings provide new evidence on the impact of heat sensitivity on afferent function in MS, which could be useful for clinical evaluation of this neurological disease. In multiple sclerosis (MS), increases in body temperature result in transient worsening of clinical symptoms (heat sensitivity or Uhthoff's phenomenon). Although the impact of heat sensitivity on efferent physiological function has been investigated, the effects of heat stress on afferent sensory function in MS are unknown. Hence, we quantified afferent thermosensory function in MS following exercise-induced increases in body temperature with a new quantitative sensory test. Eight relapsing-remitting MS patients (three men and five women; 51.4 ± 9.1 years of age; Expanded Disability Status Scale score 2.8 ± 1.1) and eight age-matched control (CTR) subjects (five men and three women; 47.4 ± 9.1 years of age) rated the perceived magnitude of two cold (26 and 22°C) and two warm stimuli (34 and 38°C) applied to the dorsum of the hand before and after 30 min cycling in the heat (30°C air; 30% relative humidity). Exercise produced similar increases in mean body temperature in MS [+0.39°C (95% CI: +0.21, +0.53) P = 0.001] and CTR subjects [+0.41°C (95% CI: +0.25, +0.58) P = 0.001]. These changes were sufficient to decrease thermosensitivity significantly to all cold [26°C stimulus, -9.1% (95% CI: -17.0, -1.5), P = 0.006; 22°C stimulus, -10.6% (95% CI: -17.3, -3.7), P = 0.027], but not warm, stimuli in MS. Contrariwise, CTR subjects showed sensitivity reductions to colder stimuli only [22°C stimulus, -9.7% (95% CI: -16.4, -3.1), P = 0.011]. The observation that reductions in thermal sensitivity in MS were confined to the myelinated cold-sensitive pathway and extended across a wider (including milder and colder) temperature range than what is observed in CTR subjects provides new evidence on the impact of rising body temperature on afferent neural function in MS. Also, our findings support the use of our new approach to investigate afferent sensory function in MS during heat stress. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

SIGNIFICANCE OF INCORPORATING MEASURES OF SPERM PRODUCTION AND FUNCTION INTO RAT TOXICOLOGY STUDIES

EPA Science Inventory

The rat is the preferred species for reproductive toxicity testing. The inclusion of measures of rat sperm quality, such as motility and morphology, into reproductive test protocols often increases the sensitivity of the test to detect effects, and provides the toxicologist and ...

Light-controlled resistors provide quadrature signal rejection for high-gain servo systems

NASA Technical Reports Server (NTRS)

Mc Cauley, D. D.

1967-01-01

Servo amplifier feedback system, in which the phase sensitive detection, low pass filtering, and multiplication functions required for quadrature rejection, are preformed by light-controlled photoresistors, eliminates complex circuitry. System increases gain, improves signal-to-noise ratio, and eliminates the necessity for compensation.

Machine learning for classifying tuberculosis drug-resistance from DNA sequencing data.

PubMed

Yang, Yang; Niehaus, Katherine E; Walker, Timothy M; Iqbal, Zamin; Walker, A Sarah; Wilson, Daniel J; Peto, Tim E A; Crook, Derrick W; Smith, E Grace; Zhu, Tingting; Clifton, David A

2018-05-15

Correct and rapid determination of Mycobacterium tuberculosis (MTB) resistance against available tuberculosis (TB) drugs is essential for the control and management of TB. Conventional molecular diagnostic test assumes that the presence of any well-studied single nucleotide polymorphisms is sufficient to cause resistance, which yields low sensitivity for resistance classification. Given the availability of DNA sequencing data from MTB, we developed machine learning models for a cohort of 1839 UK bacterial isolates to classify MTB resistance against eight anti-TB drugs (isoniazid, rifampicin, ethambutol, pyrazinamide, ciprofloxacin, moxifloxacin, ofloxacin, streptomycin) and to classify multi-drug resistance. Compared to previous rules-based approach, the sensitivities from the best-performing models increased by 2-4% for isoniazid, rifampicin and ethambutol to 97% (P < 0.01), respectively; for ciprofloxacin and multi-drug resistant TB, they increased to 96%. For moxifloxacin and ofloxacin, sensitivities increased by 12 and 15% from 83 and 81% based on existing known resistance alleles to 95% and 96% (P < 0.01), respectively. Particularly, our models improved sensitivities compared to the previous rules-based approach by 15 and 24% to 84 and 87% for pyrazinamide and streptomycin (P < 0.01), respectively. The best-performing models increase the area-under-the-ROC curve by 10% for pyrazinamide and streptomycin (P < 0.01), and 4-8% for other drugs (P < 0.01). The details of source code are provided at http://www.robots.ox.ac.uk/~davidc/code.php. david.clifton@eng.ox.ac.uk. Supplementary data are available at Bioinformatics online.

Improving sensitivity of gold nanoparticle based fluorescence quenching and colorimetric aptasensor by using water resuspended gold nanoparticle.

PubMed

Liu, Jinchuan; Guan, Zheng; Lv, Zhenzhen; Jiang, Xiaoling; Yang, Shuming; Chen, Ailiang

2014-02-15

Gold nanoparticles (AuNPs) based fluorescence quenching or colorimetric aptasensor have been developed for many analytes recently largely because of the ease of detection, high sensitivity, and potential for high-throughput analysis. However, the effects of remnant non-AuNPs components in the colloid gold solution on these assays performance remain unclear. For the first time, we demonstrated that the remnant sodium citrate and the reaction products of three acids play counteractive roles in AuNPs based fluorescence quenching and colorimetric aptasensor in three ways in this study. First, the remnant sodium citrate in the colloid gold solution could increase the fluorescence intensity of FAM labeled on the aptamer that reduce the efficiency of AuNPs fluorescent quenching. Second, the reaction products of citric acid, HCl and ketoglutaric acid reduce the fluorescence recovery by quenching the fluorescence of FAM labeled on the aptamer dissociated from the surface of AuNPs upon addition of target. Lastly, the reaction products of three acids reduce the pH value of the colloid gold solution that reduce the sensitivity of AuNPs based colorimetric aptasensor by increasing the adsorption of aptamer to surface of AuNPs. With sulfadimethoxine and thrombin as model analytes, we found that water resuspended AuNPs can significantly increase the sensitivity by more than 10-fold for AuNPs based fluorescence quenching aptasensor. In the AuNPs based colorimetric aptasensor for sulfadimethoxine using the water resuspended AuNPs, the sensitivity also was increased by 10-fold compared with that of original AuNPs. The findings in this study provide theoretical guidance for further improving AuNPs based fluorescent quenching and colorimetric aptasensor by adjusting the composition of AuNPs solution. © 2013 Elsevier B.V. All rights reserved.

On the origin of increased sensitivity and mass resolution using silicon masks in MALDI.

PubMed

Diologent, Laurent; Franck, Julien; Wisztorski, Maxence; Treizebre, Anthony; Focsa, Cristian; Fournier, Isabelle; Ziskind, Michael

2014-02-04

Since its development, MALDI has proved its performance in the analysis of intact biomolecules up to high molecular weights, regardless of their polarity. Sensitivity of MALDI instruments is a key point for breaking the limits of observing biomolecules of lower abundances. Instrumentation is one way to improve sensitivity by increasing ion transmission and using more sensitive detection systems. On the other side, improving MALDI ion production yields would have important outcomes. MALDI ion production is still not well-controlled and, indeed, the amount of ions produced per laser shot with respect to the total volume of desorbed material is very low. This has particular implications for certain applications, such as MALDI MS imaging where laser beam focusing as fine as possible (5-10 μm) is searched in order to reach higher spatial resolution images. However, various studies point out an intrinsic decrease in signal intensity for strong focusing. We have therefore been interested in developing silicon mask systems to decrease an irradiated area by cutting rather than focusing the laser beam and to study the parameters affecting sensitivity using such systems. For this, we systematically examined variation with laser fluence of intensity and spectral resolution in MALDI of standard peptides when using silicon-etched masks of various aperture sizes. These studies demonstrate a simultaneous increase in spectral resolution and signal intensity. Origin of this effect is discussed in the frame of the two-step ionization model. Experimental data in the low fluence range are fitted with an increase of the primary ionization through matrix-silicon edge contact provided by the masks. On the other hand, behavior at higher fluence could be explained by an effect on the secondary ionization via changes in the plume dynamics.

Enhancing the sensitivity of needle-implantable electrochemical glucose sensors via surface rebuilding.

PubMed

Vaddiraju, Santhisagar; Legassey, Allen; Qiang, Liangliang; Wang, Yan; Burgess, Diane J; Papadimitrakopoulos, Fotios

2013-03-01

Needle-implantable sensors have shown to provide reliable continuous glucose monitoring for diabetes management. In order to reduce tissue injury during sensor implantation, there is a constant need for device size reduction, which imposes challenges in terms of sensitivity and reliability, as part of decreasing signal-to-noise and increasing layer complexity. Herein, we report sensitivity enhancement via electrochemical surface rebuilding of the working electrode (WE), which creates a three-dimensional nanoporous configuration with increased surface area. The gold WE was electrochemically rebuilt to render its surface nanoporous followed by decoration with platinum nanoparticles. The efficacy of such process was studied using sensor sensitivity against hydrogen peroxide (H2O2). For glucose detection, the WE was further coated with five layers, namely, (1) polyphenol, (2) glucose oxidase, (3) polyurethane, (4) catalase, and (5) dexamethasone-releasing poly(vinyl alcohol)/poly(lactic-co-glycolic acid) composite. The amperometric response of the glucose sensor was noted in vitro and in vivo. Scanning electron microscopy revealed that electrochemical rebuilding of the WE produced a nanoporous morphology that resulted in a 20-fold enhancement in H2O2 sensitivity, while retaining >98% selectivity. This afforded a 4-5-fold increase in overall glucose response of the glucose sensor when compared with a control sensor with no surface rebuilding and fittable only within an 18 G needle. The sensor was able to reproducibly track in vivo glycemic events, despite the large background currents typically encountered during animal testing. Enhanced sensor performance in terms of sensitivity and large signal-to-noise ratio has been attained via electrochemical rebuilding of the WE. This approach also bypasses the need for conventional and nanostructured mediators currently employed to enhance sensor performance. © 2013 Diabetes Technology Society.

A two-fold increase of carbon cycle sensitivity to tropical temperature variations.

PubMed

Wang, Xuhui; Piao, Shilong; Ciais, Philippe; Friedlingstein, Pierre; Myneni, Ranga B; Cox, Peter; Heimann, Martin; Miller, John; Peng, Shushi; Wang, Tao; Yang, Hui; Chen, Anping

2014-02-13

Earth system models project that the tropical land carbon sink will decrease in size in response to an increase in warming and drought during this century, probably causing a positive climate feedback. But available data are too limited at present to test the predicted changes in the tropical carbon balance in response to climate change. Long-term atmospheric carbon dioxide data provide a global record that integrates the interannual variability of the global carbon balance. Multiple lines of evidence demonstrate that most of this variability originates in the terrestrial biosphere. In particular, the year-to-year variations in the atmospheric carbon dioxide growth rate (CGR) are thought to be the result of fluctuations in the carbon fluxes of tropical land areas. Recently, the response of CGR to tropical climate interannual variability was used to put a constraint on the sensitivity of tropical land carbon to climate change. Here we use the long-term CGR record from Mauna Loa and the South Pole to show that the sensitivity of CGR to tropical temperature interannual variability has increased by a factor of 1.9 ± 0.3 in the past five decades. We find that this sensitivity was greater when tropical land regions experienced drier conditions. This suggests that the sensitivity of CGR to interannual temperature variations is regulated by moisture conditions, even though the direct correlation between CGR and tropical precipitation is weak. We also find that present terrestrial carbon cycle models do not capture the observed enhancement in CGR sensitivity in the past five decades. More realistic model predictions of future carbon cycle and climate feedbacks require a better understanding of the processes driving the response of tropical ecosystems to drought and warming.

Shock Initiation of Thermally Expanded TATB

NASA Astrophysics Data System (ADS)

Mulford, Roberta; Swift, Damian

2011-06-01

The plastic-bonded explosive PBX-9502 undergoes unusual hysteretic thermal expansion, or ``ratchet growth'' as a consequence of the uniaxial thermal expansion of the graphitic structure of the major component, TATB explosive. Upon thermal cycling, the density of the material can be reduced by as much as 9%, resulting in a distinct increase in the shock sensitivity of the solid. Run distances to detonation have been measured in thermally expanded samples of PBX-9502, using embedded particle velocity gauges and shock tracker gauges. Uniaxial shocks were generated using a light gas gun, to provide a repeatable stimulus for initiation of detonation. We have applied a porosity model to adjust standard Pop plot data to the reduced density of our samples, to investigate whether the sensitivity of the PBX 9502 increases ideally with the decreasing density, or whether the microscopically non-uniform expansion that occurs during ``ratchet growth'' leads to abnormal sensitivity, possibly as a result of cracking or debonding from the binder, as observed in micrographs of the sample.

Does the Concept of “Sensitization” Provide a Plausible Mechanism for the Putative Link Between the Environment and Schizophrenia?

PubMed Central

Collip, Dina; Myin-Germeys, Inez; Van Os, Jim

2008-01-01

Previous evidence reviewed in Schizophrenia Bulletin suggests the importance of a range of different environmental factors in the development of psychotic illness. It is unlikely, however, that the diversity of environmental influences associated with schizophrenia can be linked to as many different underlying mechanisms. There is evidence that environmental exposures may induce, in interaction with (epi)genetic factors, psychological or physiological alterations that can be traced to a final common pathway of cognitive biases and/or altered dopamine neurotransmission, broadly referred to as “sensitization,” facilitating the onset and persistence of psychotic symptoms. At the population level, the behavioral phenotype for sensitization may be examined by quantifying, in populations exposed to environmental risk factors associated with stress or dopamine-agonist drugs, (1) the increased rate of persistence (indicating lasting sensitization) of normally transient developmental expressions of subclinical psychotic experiences and (2) the subsequent increased rate of transition to clinical psychotic disorder. PMID:18203757

Constitutive and Treatment-Induced CXCL8-Signalling Selectively Modulates the Efficacy of Anti-Metabolite Therapeutics in Metastatic Prostate Cancer

PubMed Central

Longley, Daniel B.; Wilson, Richard H.; Johnston, Patrick G.; Waugh, David J. J.

2012-01-01

Background The current study was undertaken to characterize the effect of anti-metabolites on inducing CXCL8 signaling and determining whether the constitutive and/or drug-induced CXCL8 signaling in metastatic prostate cancer (CaP) cells modulates their sensitivity to this class of agent. Methods The response of metastatic CaP cells to 5-Fluorouracil (5-FU), Pemetrexed or Tomudex was determined using cell count assays, flow cytometry and PARP cleavage analysis. Quantitative-PCR, ELISA and immunoblots were employed to determine effects of drugs or CXCL8 administration on target gene/protein expression. Results Administration of 5-FU but not pemetrexed potentiated CXCL8 secretion and increased CXCR1 and CXCR2 gene expression in metastatic PC3 cells. Consistent with this, the inhibition of CXCL8 signaling using a CXCR2 antagonist, AZ10397767, increased the cytotoxicity of 5-FU by 4-fold (P<0.001), and increased 5-FU-induced apoptosis in PC3 cells (P<0.01). In contrast, while administration of AZ10397767 had no effect on the sensitivity of pemetrexed, the CXCR2 antagonist exerted the greatest effect in increasing the sensitivity of PC3 cells to Tomudex, a directed thymidylate synthase (TS) inhibitor. Subsequent experiments confirmed that administration of recombinant human CXCL8 increased TS expression, a response mediated in part by the CXCR2 receptor. Moreover, siRNA-mediated knockdown of the CXCL8-target gene Bcl-2 increased the sensitivity of PC3 cells to 5-FU. Conclusions CXCL8 signaling provides a selective resistance of metastatic prostate cancer cells to specific anti-metabolites by promoting a target-associated resistance, in addition to underpinning an evasion of treatment-induced apoptosis. PMID:22590561

System and process for pulsed multiple reaction monitoring

DOEpatents

Belov, Mikhail E

2013-05-17

A new pulsed multiple reaction monitoring process and system are disclosed that uses a pulsed ion injection mode for use in conjunction with triple-quadrupole instruments. The pulsed injection mode approach reduces background ion noise at the detector, increases amplitude of the ion signal, and includes a unity duty cycle that provides a significant sensitivity increase for reliable quantitation of proteins/peptides present at attomole levels in highly complex biological mixtures.

Accuracy of un-supervised versus provider-supervised self-administered HIV testing in Uganda: A randomized implementation trial.

PubMed

Asiimwe, Stephen; Oloya, James; Song, Xiao; Whalen, Christopher C

2014-12-01

Unsupervised HIV self-testing (HST) has potential to increase knowledge of HIV status; however, its accuracy is unknown. To estimate the accuracy of unsupervised HST in field settings in Uganda, we performed a non-blinded, randomized controlled, non-inferiority trial of unsupervised compared with supervised HST among selected high HIV risk fisherfolk (22.1 % HIV Prevalence) in three fishing villages in Uganda between July and September 2013. The study enrolled 246 participants and randomized them in a 1:1 ratio to unsupervised HST or provider-supervised HST. In an intent-to-treat analysis, the HST sensitivity was 90 % in the unsupervised arm and 100 % among the provider-supervised, yielding a difference 0f -10 % (90 % CI -21, 1 %); non-inferiority was not shown. In a per protocol analysis, the difference in sensitivity was -5.6 % (90 % CI -14.4, 3.3 %) and did show non-inferiority. We conclude that unsupervised HST is feasible in rural Africa and may be non-inferior to provider-supervised HST.

Sensitivities of Greenland ice sheet volume inferred from an ice sheet adjoint model

NASA Astrophysics Data System (ADS)

Heimbach, P.; Bugnion, V.

2009-04-01

We present a new and original approach to understanding the sensitivity of the Greenland ice sheet to key model parameters and environmental conditions. At the heart of this approach is the use of an adjoint ice sheet model. Since its introduction by MacAyeal (1992), the adjoint method has become widespread to fit ice stream models to the increasing number and diversity of satellite observations, and to estimate uncertain model parameters such as basal conditions. However, no attempt has been made to extend this method to comprehensive ice sheet models. As a first step toward the use of adjoints of comprehensive three-dimensional ice sheet models we have generated an adjoint of the ice sheet model SICOPOLIS of Greve (1997). The adjoint was generated by means of the automatic differentiation (AD) tool TAF. The AD tool generates exact source code representing the tangent linear and adjoint model of the nonlinear parent model provided. Model sensitivities are given by the partial derivatives of a scalar-valued model diagnostic with respect to the controls, and can be efficiently calculated via the adjoint. By way of example, we determine the sensitivity of the total Greenland ice volume to various control variables, such as spatial fields of basal flow parameters, surface and basal forcings, and initial conditions. Reliability of the adjoint was tested through finite-difference perturbation calculations for various control variables and perturbation regions. Besides confirming qualitative aspects of ice sheet sensitivities, such as expected regional variations, we detect regions where model sensitivities are seemingly unexpected or counter-intuitive, albeit ``real'' in the sense of actual model behavior. An example is inferred regions where sensitivities of ice sheet volume to basal sliding coefficient are positive, i.e. where a local increase in basal sliding parameter increases the ice sheet volume. Similarly, positive ice temperature sensitivities in certain parts of the ice sheet are found (in most regions it is negativ, i.e. an increase in temperature decreases ice sheet volume), the detection of which seems highly unlikely if only conventional perturbation experiments had been used. An effort to generate an efficient adjoint with the newly developed open-source AD tool OpenAD is also under way. Available adjoint code generation tools now open up a variety of novel model applications, notably with regard to sensitivity and uncertainty analyses and ice sheet state estimation or data assimilation.

Graphene-interfaced electrical biosensor for label-free and sensitive detection of foodborne pathogenic E. coli O157:H7.

PubMed

Pandey, Ashish; Gurbuz, Yasar; Ozguz, Volkan; Niazi, Javed H; Qureshi, Anjum

2017-05-15

E. coli O157:H7 is an enterohemorrhagic bacteria responsible for serious foodborne outbreaks that causes diarrhoea, fever and vomiting in humans. Recent foodborne E. coli outbreaks has left a serious concern to public health. Therefore, there is an increasing demand for a simple, rapid and sensitive method for pathogen detection in contaminated foods. In this study, we developed a label-free electrical biosensor interfaced with graphene for sensitive detection of pathogenic bacteria. This biosensor was fabricated by interfacing graphene with interdigitated microelectrodes of capacitors that were biofunctionalized with E. coli O157:H7 specific antibodies for sensitive pathogenic bacteria detection. Here, graphene nanostructures on the sensor surface provided superior chemical properties such as high carrier mobility and biocompatibility with antibodies and bacteria. The sensors transduced the signal based on changes in dielectric properties (capacitance) through (i) polarization of captured cell-surface charges, (ii) cells' internal bioactivity, (iii) cell-wall's electronegativity or dipole moment and their relaxation and (iv) charge carrier mobility of graphene that modulated the electrical properties once the pathogenic E. coli O157:H7 captured on the sensor surface. Sensitive capacitance changes thus observed with graphene based capacitors were specific to E. coli O157:H7 strain with a sensitivity as low as 10-100 cells/ml. The proposed graphene based electrical biosensor provided advantages of speed, sensitivity, specificity and in-situ bacterial detection with no chemical mediators, represents a versatile approach for detection of a wide variety of other pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

Methionine Deprivation Induces a Targetable Vulnerability in Triple-Negative Breast Cancer Cells by Enhancing TRAIL Receptor-2 Expression.

PubMed

Strekalova, Elena; Malin, Dmitry; Good, David M; Cryns, Vincent L

2015-06-15

Many neoplasms are vulnerable to methionine deficiency by mechanisms that are poorly understood. Because gene profiling studies have revealed that methionine depletion increases TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) mRNA, we postulated that methionine stress sensitizes breast cancer cells to proapoptotic TRAIL-R2 agonists. Human triple (ER/PR/HER2)-negative breast carcinoma cell lines were cultured in control or methionine-free media. The effects of methionine depletion on TRAIL receptor expression and sensitivity to chemotherapy or a humanized agonistic TRAIL-R2 monoclonal antibody (lexatumumab) were determined. The melanoma-associated antigen MAGED2 was silenced to delineate its functional role in sensitizing TNBC cells to methionine stress. An orthotopic TNBC model was utilized to evaluate the effects of dietary methionine deficiency, lexatumumab, or the combination. Methionine depletion sensitized TNBC cells to lexatumumab-induced caspase activation and apoptosis by increasing TRAIL-R2 mRNA and cell surface expression. MCF-10A cells transformed by oncogenic H-Ras, but not untransformed cells, and matrix-detached TNBC cells were highly sensitive to the combination of lexatumumab and methionine depletion. Proteomics analyses revealed that MAGED2, which has been reported to reduce TRAIL-R2 expression, was suppressed by methionine stress. Silencing MAGED2 recapitulated features of methionine deprivation, including enhanced mRNA and cell surface expression of TRAIL receptors and increased sensitivity to TRAIL receptor agonists. Dietary methionine deprivation enhanced the antitumor effects of lexatumumab in an orthotopic metastatic TNBC model. Methionine depletion exposes a targetable defect in TNBC cells by increasing TRAIL-R2 expression. Our findings provide the foundation for a clinical trial combining dietary methionine restriction and TRAIL-R2 agonists. Clin Cancer Res; 21(12); 2780-91. ©2015 AACR. ©2015 American Association for Cancer Research.

Wheat production in Bangladesh: its future in the light of global warming.

PubMed

Hossain, Akbar; Teixeira da Silva, Jaime A

2013-01-01

The most fundamental activity of the people of Bangladesh is agriculture. Modelling projections for Bangladesh indicate that warmer temperatures linked to climate change will severely reduce the growth of various winter crops (wheat, boro rice, potato and winter vegetables) in the north and central parts. In summer, crops in south-eastern parts of the country are at risk from increased flooding as sea levels increase. Wheat is one of the most important winter crops and is temperature sensitive and the second most important grain crop after rice. In this review, we provide an up-to-date and detailed account of wheat research of Bangladesh and the impact that global warming may have on agriculture, especially wheat production. Although flooding is not of major importance or consequence to the wheat crop at present, some perspectives are provided on this stress since wheat is flood sensitive and the incidence of flooding is likely to increase. This information and projections will allow wheat breeders to devise new breeding programmes to attempt to mitigate future global warming. We discuss what this implies for food security in the broader context of South Asia.

Wheat production in Bangladesh: its future in the light of global warming

PubMed Central

Hossain, Akbar; Teixeira da Silva, Jaime A.

2012-01-01

Background and aims The most fundamental activity of the people of Bangladesh is agriculture. Modelling projections for Bangladesh indicate that warmer temperatures linked to climate change will severely reduce the growth of various winter crops (wheat, boro rice, potato and winter vegetables) in the north and central parts. In summer, crops in south-eastern parts of the country are at risk from increased flooding as sea levels increase. Key facts Wheat is one of the most important winter crops and is temperature sensitive and the second most important grain crop after rice. In this review, we provide an up-to-date and detailed account of wheat research of Bangladesh and the impact that global warming may have on agriculture, especially wheat production. Although flooding is not of major importance or consequence to the wheat crop at present, some perspectives are provided on this stress since wheat is flood sensitive and the incidence of flooding is likely to increase. Projections This information and projections will allow wheat breeders to devise new breeding programmes to attempt to mitigate future global warming. We discuss what this implies for food security in the broader context of South Asia. PMID:23304431

Refugee health and medical student training.

PubMed

Griswold, Kim S

2003-10-01

Cultural awareness training is an increasingly important priority within medical curricula. This article describes an academic family practice-community partnership focusing on health care needs of refugees that became the model for a medical school selective on cultural sensitivity training. The monthly Refugee Health Night program featured dinner with preceptors and patients, international sessions on special medical needs of refugees, and actual clinical encounters with patients. Students were not expected to become culturally competent experts but, rather, health care providers sensitive to and appreciative of cultural context, experience, and expectations. We worked with students to develop sensitive methods of inquiry about mental health, especially around issues of war and torture. We used problem-based cases to emphasize primary care continuity and the benefit of establishing trust over time. Over 2 years, 50 students and nearly 300 refugees (more than 73 families) participated. Students reported that their interactions with the refugees provided positive learning experiences, including expanded knowledge of diverse cultures and enhanced skills for overcoming communication barriers. Patients of refugee status were able to have emergent health care needs met in a timely fashion. Providing health care for refugee individuals and families presents many challenges as well as extraordinary opportunities for patients and practitioners to learn from one another.

Real-time polarization-sensitive optical coherence tomography data processing with parallel computing

PubMed Central

Liu, Gangjun; Zhang, Jun; Yu, Lingfeng; Xie, Tuqiang; Chen, Zhongping

2010-01-01

With the increase of the A-line speed of optical coherence tomography (OCT) systems, real-time processing of acquired data has become a bottleneck. The shared-memory parallel computing technique is used to process OCT data in real time. The real-time processing power of a quad-core personal computer (PC) is analyzed. It is shown that the quad-core PC could provide real-time OCT data processing ability of more than 80K A-lines per second. A real-time, fiber-based, swept source polarization-sensitive OCT system with 20K A-line speed is demonstrated with this technique. The real-time 2D and 3D polarization-sensitive imaging of chicken muscle and pig tendon is also demonstrated. PMID:19904337

Prediction of skin sensitizers using alternative methods to animal experimentation.

PubMed

Johansson, Henrik; Lindstedt, Malin

2014-07-01

Regulatory frameworks within the European Union demand that chemical substances are investigated for their ability to induce sensitization, an adverse health effect caused by the human immune system in response to chemical exposure. A recent ban on the use of animal tests within the cosmetics industry has led to an urgent need for alternative animal-free test methods that can be used for assessment of chemical sensitizers. To date, no such alternative assay has yet completed formal validation. However, a number of assays are in development and the understanding of the biological mechanisms of chemical sensitization has greatly increased during the last decade. In this MiniReview, we aim to summarize and give our view on the recent progress of method development for alternative assessment of chemical sensitizers. We propose that integrated testing strategies should comprise complementary assays, providing measurements of a wide range of mechanistic events, to perform well-educated risk assessments based on weight of evidence. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Global sensitivity analysis of a dynamic agroecosystem model under different irrigation treatments

USDA-ARS?s Scientific Manuscript database

Savings in consumptive use through limited or deficit irrigation in agriculture has become an increasingly viable source of additional water for places with high population growth such as the Colorado Front Range, USA. Crop models provide a mechanism to evaluate various management methods without pe...

The Accessible School: Universal Design for Educational Settings.

ERIC Educational Resources Information Center

Bar, Laurel; Galluzzo, Judith

This book provides practical reasons for the Americans with Disabilities Act requirements for accessibility of school sites, buildings, and educational rooms as well as clear illustrations to aid in the explanation of the guidelines. It addresses practical matters such as safety and cost-effectiveness while increasing sensitivity to different…

The altitude of alpine treeline: a bellwether of climate change effects

Treesearch

William K. Smith; Matthew J. Germino; Daniel M. Johnson; Keith Reinhardt

2009-01-01

Because of the characteristically low temperatures and ambient CO2 concentrations associated with greater altitudes, mountain forests may be particularly sensitive to global warming and increased atmospheric CO2. Moreover, the upper treeline is probably the most stressful location within these forests, possibly providing an...

ASCA Ethical Standards and the Relevance of Eastern Ethical Theories

ERIC Educational Resources Information Center

Cook, Amy L.; Houser, Rick A.

2009-01-01

As schools become increasingly diverse through immigration and growth of minority groups, it is important that school counselors incorporate culturally sensitive ethical decision-making in their practice. The use of Western ethical theories in the application of professional codes of ethics provides a specific perspective in ethical…

Exploring Information Security Awareness Training to Reduce Unauthorized Disclosure of Information in Public Schools

ERIC Educational Resources Information Center

Fleming, Antoine

2017-01-01

Advances in technological uses within public schools provide increased methods to collect and store non-public personal information (NPI) or personally identifiable information (PII) from both students and employees. Consequently, the sensitive information collected is susceptible to unauthorized disclosure, as various public school employees are…

Integrating Cultural Humility into Health Care Professional Education and Training

ERIC Educational Resources Information Center

Chang, E-shien; Simon, Melissa; Dong, XinQi

2012-01-01

As US populations become increasing diverse, healthcare professionals are facing a heightened challenge to provide cross-cultural care. To date, medical education around the world has developed specific curricula on cultural competence training in acknowledgement of the importance of culturally sensitive and grounded services. This article…

Down-regulation of lipoprotein lipase increases glucose uptake in L6 muscle cells

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

Lopez, Veronica; Saraff, Kumuda; Medh, Jheem D., E-mail: jheem.medh@csun.edu

2009-11-06

Thiazolidinediones (TZDs) are synthetic hypoglycemic agents used to treat type 2 diabetes. TZDs target the peroxisome proliferator activated receptor-gamma (PPAR-{gamma}) and improve systemic insulin sensitivity. The contributions of specific tissues to TZD action, or the downstream effects of PPAR-{gamma} activation, are not very clear. We have used a rat skeletal muscle cell line (L6 cells) to demonstrate that TZDs directly target PPAR-{gamma} in muscle cells. TZD treatment resulted in a significant repression of lipoprotein lipase (LPL) expression in L6 cells. This repression correlated with an increase in glucose uptake. Down-regulation of LPL message and protein levels using siRNA resulted inmore » a similar increase in insulin-dependent glucose uptake. Thus, LPL down-regulation improved insulin sensitivity independent of TZDs. This finding provides a novel method for the management of insulin resistance.« less

Changing Me, Changing Us: Relationship Quality and Collective Efficacy as Major Outcomes in Systemic Couple Therapy.

PubMed

Aguilar-Raab, Corina; Grevenstein, Dennis; Gotthardt, Linda; Jarczok, Marc N; Hunger, Christina; Ditzen, Beate; Schweitzer, Jochen

2018-06-01

We examine the sensitivity to change in the Evaluation of Social Systems (EVOS) scale, which assesses relationship quality and collective efficacy. In Study 1 we conducted a waitlist-control, short-term couple therapy RCT study (N = 43 couples) with five systemic therapy sessions treating communication and partnership problems; our intent was to provide high external validity. Construct validity of EVOS was assessed by comparison with additionally applied scales (Family Scales; Outcome Questionnaire, OQ-45.2). In Study 2, N = 332 individuals completed an experiment with high internal validity in order to verify sensitivity to change in three different social contexts. Results from Study 1 revealed a significant increase in relationship quality in the treatment group directly after treatment, as compared to the control group. Sensitivity to change was slightly better for EVOS than for other measures. While this positive change could not be fully sustained between posttreatment and a 4-week follow-up, EVOS score did not fall below baseline and pretreatment levels, supporting moderate-to-large sensitivity to change. Study 2 supported high sensitivity to change in EVOS for couple relations, family relations, and work-team relationships. Therefore, EVOS can be used as an outcome measure to monitor the process of systemic interventions focusing on relationship quality and collective efficacy. Due to its sensitivity to change, EVOS can provide evidence for treatment success with regard to relationship aspects. © 2017 Family Process Institute.

Assessment of regional management strategies for controlling seawater intrusion

USGS Publications Warehouse

Reichard, E.G.; Johnson, T.A.

2005-01-01

Simulation-optimization methods, applied with adequate sensitivity tests, can provide useful quantitative guidance for controlling seawater intrusion. This is demonstrated in an application to the West Coast Basin of coastal Los Angeles that considers two management options for improving hydraulic control of seawater intrusion: increased injection into barrier wells and in lieu delivery of surface water to replace current pumpage. For the base-case optimization analysis, assuming constant groundwater demand, in lieu delivery was determined to be most cost effective. Reduced-cost information from the optimization provided guidance for prioritizing locations for in lieu delivery. Model sensitivity to a suite of hydrologic, economic, and policy factors was tested. Raising the imposed average water-level constraint at the hydraulic-control locations resulted in nonlinear increases in cost. Systematic varying of the relative costs of injection and in lieu water yielded a trade-off curve between relative costs and injection/in lieu amounts. Changing the assumed future scenario to one of increasing pumpage in the adjacent Central Basin caused a small increase in the computed costs of seawater intrusion control. Changing the assumed boundary condition representing interaction with an adjacent basin did not affect the optimization results. Reducing the assumed hydraulic conductivity of the main productive aquifer resulted in a large increase in the model-computed cost. Journal of Water Resources Planning and Management ?? ASCE.

Protective Effect of Antenatal Antioxidant on Nicotine-Induced Heart Ischemia-Sensitive Phenotype in Rat Offspring.

PubMed

Xiao, DaLiao; Wang, Lei; Huang, Xiaohui; Li, Yong; Dasgupta, Chiranjib; Zhang, Lubo

2016-01-01

Fetal nicotine exposure increased risk of developing cardiovascular disease later in life. The present study tested the hypothesis that perinatal nicotine-induced programming of heart ischemia-sensitive phenotype is mediated by enhanced reactive oxygen species (ROS) in offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth, in the absence or presence of a ROS inhibitor, N-acetyl-cysteine (NAC) in drinking water. Experiments were conducted in 8 month old age male offspring. Isolated hearts were perfused in a Langendorff preparation. Perinatal nicotine treatment significantly increased ischemia and reperfusion-induced left ventricular injury, and decreased post-ischemic recovery of left ventricular function and coronary flow rate. In addition, nicotine enhanced cardiac ROS production and significantly attenuated protein kinase Cε (PKCε) protein abundance in the heart. Although nicotine had no effect on total cardiac glycogen synthase kinase-3β (GSK3β) protein expression, it significantly increased the phosphorylation of GSK3β at serine 9 residue in the heart. NAC inhibited nicotine-mediated increase in ROS production, recovered PKCε gene expression and abrogated increased phosphorylation of GSK3β. Of importance, NAC blocked perinatal nicotine-induced increase in ischemia and reperfusion injury in the heart. These findings provide novel evidence that increased oxidative stress plays a causal role in perinatal nicotine-induced developmental programming of ischemic sensitive phenotype in the heart, and suggest potential therapeutic targets of anti-oxidative stress in the treatment of ischemic heart disease.

Exploring the Relationship between Reward and Punishment Sensitivity and Gambling Disorder in a Clinical Sample: A Path Modeling Analysis.

PubMed

Jiménez-Murcia, Susana; Fernández-Aranda, Fernando; Mestre-Bach, Gemma; Granero, Roser; Tárrega, Salomé; Torrubia, Rafael; Aymamí, Neus; Gómez-Peña, Mónica; Soriano-Mas, Carles; Steward, Trevor; Moragas, Laura; Baño, Marta; Del Pino-Gutiérrez, Amparo; Menchón, José M

2017-06-01

Most individuals will gamble during their lifetime, yet only a select few will develop gambling disorder. Gray's Reinforcement Sensitivity Theory holds promise for providing insight into gambling disorder etiology and symptomatology as it ascertains that neurobiological differences in reward and punishment sensitivity play a crucial role in determining an individual's affect and motives. The aim of the study was to assess a mediational pathway, which included patients' sex, personality traits, reward and punishment sensitivity, and gambling-severity variables. The Sensitivity to Punishment and Sensitivity to Reward Questionnaire, the South Oaks Gambling Screen, the Symptom Checklist-Revised, and the Temperament and Character Inventory-Revised were administered to a sample of gambling disorder outpatients (N = 831), diagnosed according to DSM-5 criteria, attending a specialized outpatient unit. Sociodemographic variables were also recorded. A structural equation model found that both reward and punishment sensitivity were positively and directly associated with increased gambling severity, sociodemographic variables, and certain personality traits while also revealing a complex mediational role for these dimensions. To this end, our findings suggest that the Sensitivity to Punishment and Sensitivity to Reward Questionnaire could be a useful tool for gaining a better understanding of different gambling disorder phenotypes and developing tailored interventions.

MACC1 regulates Fas mediated apoptosis through STAT1/3 - Mcl-1 signaling in solid cancers.

PubMed

Radhakrishnan, Harikrishnan; Ilm, Katharina; Walther, Wolfgang; Shirasawa, Senji; Sasazuki, Takehiko; Daniel, Peter T; Gillissen, Bernhard; Stein, Ulrike

2017-09-10

MACC1 was identified as a novel player in cancer progression and metastasis, but its role in death receptor-mediated apoptosis is still unexplored. We show that MACC1 knockdown sensitizes cancer cells to death receptor-mediated apoptosis. For the first time, we provide evidence for STAT signaling as a MACC1 target. MACC1 knockdown drastically reduced STAT1/3 activating phosphorylation, thereby regulating the expression of its apoptosis targets Mcl-1 and Fas. STAT signaling inhibition by the JAK1/2 inhibitor ruxolitinib mimicked MACC1 knockdown-mediated molecular signatures and apoptosis sensitization to Fas activation. Despite the increased Fas expression, the reduced Mcl-1 expression was instrumental in apoptosis sensitization. This reduced Mcl-1-mediated apoptosis sensitization was Bax and Bak dependent. MACC1 knockdown also increased TRAIL-induced apoptosis. MACC1 overexpression enhanced STAT1/3 phosphorylation and increased Mcl-1 expression, which was abrogated by ruxolitinib. The central role of Mcl-1 was strengthened by the resistance of Mcl-1 overexpressing cells to apoptosis induction. The clinical relevance of Mcl-1 regulation by MACC1 was supported by their positive expression correlation in patient-derived tumors. Altogether, we reveal a novel death receptor-mediated apoptosis regulatory mechanism by MACC1 in solid cancers through modulation of the STAT1/3-Mcl-1 axis. Copyright © 2017 Elsevier B.V. All rights reserved.

Atypical antipsychotics, insulin resistance and weight; a meta-analysis of healthy volunteer studies.

PubMed

Burghardt, Kyle J; Seyoum, Berhane; Mallisho, Abdullah; Burghardt, Paul R; Kowluru, Renu A; Yi, Zhengping

2018-04-20

Atypical antipsychotics increase the risk of diabetes and cardiovascular disease through their side effects of insulin resistance and weight gain. The populations for which atypical antipsychotics are used carry a baseline risk of metabolic dysregulation prior to medication which has made it difficult to fully understand whether atypical antipsychotics cause insulin resistance and weight gain directly. The purpose of this work was to conduct a systematic review and meta-analysis of atypical antipsychotic trials in healthy volunteers to better understand their effects on insulin sensitivity and weight gain. Furthermore, we aimed to evaluate the occurrence of insulin resistance with or without weight gain and with treatment length by using subgroup and meta-regression techniques. Overall, the meta-analysis provides evidence that atypical antipsychotics decrease insulin sensitivity (standardized mean difference=-0.437, p<0.001) and increase weight (standardized mean difference=0.591, p<0.001) in healthy volunteers. It was found that decreases in insulin sensitivity were potentially dependent on treatment length but not weight gain. Decreases in insulin sensitivity occurred in multi-dose studies <13days while weight gain occurred in studies 14days and longer (max 28days). These findings provide preliminary evidence that atypical antipsychotics cause insulin resistance and weight gain directly, independent of psychiatric disease and may be associated with length of treatment. Further, well-designed studies to assess the co-occurrence of insulin resistance and weight gain and to understand the mechanisms and sequence by which they occur are required. Copyright © 2018 Elsevier Inc. All rights reserved.

The water sensitive city: principles for practice.

PubMed

Wong, T H F; Brown, R R

2009-01-01

With the widespread realisation of the significance of climate change, urban communities are increasingly seeking to ensure resilience to future uncertainties in urban water supplies, yet change seems slow with many cities facing ongoing investment in the conventional approach. This is because transforming cities to more sustainable urban water cities, or to Water Sensitive Cities, requires a major overhaul of the hydro-social contract that underpins conventional approaches. This paper provides an overview of the emerging research and practice focused on system resilience and principles of sustainable urban water management Three key pillars that need to underpin the development and practice of a Water Sensitive City are proposed: (i) access to a diversity of water sources underpinned by a diversity of centralised and decentralised infrastructure; (ii) provision of ecosystem services for the built and natural environment; and (iii) socio-political capital for sustainability and water sensitive behaviours. While there is not one example in the world of a Water Sensitive City, there are cities that lead on distinct and varying attributes of the water sensitive approach and examples from Australia and Singapore are presented.

Apigenin sensitizes hepatocellular carcinoma cells to doxorubic through regulating miR-520b/ATG7 axis.

PubMed

Gao, Ai-Mei; Zhang, Xiao-Yu; Hu, Juan-Ni; Ke, Zun-Ping

2018-01-25

Chemo-resistance is a serious obstacle for successful treatment of cancer. Apigenin, a dietary flavonoid, has been reported as an anticancer drug in various malignant cancers. This study aimed to investigate the potential chemo-sensitization effect of apigenin in doxorubicin-resistant hepatocellular carcinoma cell line BEL-7402/ADM. We observed that apigenin significantly enhanced doxorubicin sensitivity, induced miR-520b expression and inhibited ATG7-dependent autophagy in BEL-7402/ADM cells. In addition, we also showed that miR-520b mimics increased doxorubicin sensitivity and inhibited ATG7-dependent autophagy. Meanwhile, we indicated that ATG7 was a potential target of miR-520b. Furthermore, APG inhibited the growth of hepatocellar carcinoma xenografts in nude mice by up-regulating miR-520b and inhibiting ATG7. Our finding provides evidence that apigenin sensitizes BEL-7402/ADM cells to doxorubicin through miR-520b/ATG7 pathway, which furtherly supports apigenin as a potential chemo-sensitizer for hepatocellular carcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a highly sensitive immunochromatographic detection kit for H5 influenza virus hemagglutinin using silver amplification.

PubMed

Wada, Atsuhiko; Sakoda, Yoshihiro; Oyamada, Takayoshi; Kida, Hiroshi

2011-12-01

H5N1, a highly pathogenic avian influenza virus (HPAIV), has become a serious epizootic threat to the poultry population in Asia. In addition, significant numbers of human cases of HPAIV infection have been reported to date. To prevent the spread of HPAIV among humans and to allow for timely medical intervention, a rapid and high sensitive method is needed to detect and subtype the causative HPAIVs. In the present study, a silver amplification technique used in photographic development was combined with immunochromatography technologies and a highly sensitive and rapid diagnostic test to detect the hemagglutinin of H5 influenza viruses was developed. The sensitivity of the test kit was increased 500 times by silver amplification. The sensitivity of the method was more than 10 times higher than those of conventional rapid influenza diagnostic tests, which detect viral nucleoproteins. The diagnostic system developed in the present study can therefore provide rapid and highly sensitive results and will be useful for diagnosis of H5 HPAIV infection in humans and animals. Copyright © 2011 Elsevier B.V. All rights reserved.

Polydimethylsiloxane microfluidic chemiluminescence immunodevice with the signal amplification strategy for sensitive detection of human immunoglobin G.

PubMed

Li, Huifang; Zhao, Mei; Liu, Wei; Chu, Weiru; Guo, Yumei

2016-01-15

A polydimethylsiloxane (PDMS) microfluidic chemiluminescence (CL) immunodevice for sensitive detection of human immunoglobin G (IgG) with the signal amplification strategy was developed in this work. The immunodevice was prepared by covalently immobilizing capture antibodies (Abs) on the silanized microchannel of microfluidic chip. Gold nanoparticles (AuNPs) functionalized with a high molar ratio of horseradish peroxidase (HRP) were used as an Ab label for signal amplification. Using a sandwich immunoassay, the multi-HRP conjugated AuNPs can catalyze the luminol-H2O2 CL system to achieve the high sensitivity. In addition, the double spiral flow-channel was adopted here, which can still contribute to the high sensitivity. Based on signal amplification strategy, the performance of human IgG tests revealed a lower detection limit (DL) of 0.03ng/mL and showed an increase of 7.4-fold in detection sensitivity compared to a commercial Ab-HRP conjugation. This microfluidic immunodevice can provide an alternative approach for sensitive detection of human IgG in the field of clinic diagnostic and therapeutic. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Vallis, Geoffrey K.

The project had two main components. The first concerns estimating the climate sensitivity in the presence of forcing uncertainty and natural variability. Climate sensitivity is the increase in the average surface temperature for a given increase in greenhouse gases, for example a doubling of carbon dioxide. We have provided new, probabilistic estimates of climate sensitivity using a simple climate model an the observed warming in the 20th century, in conjunction with ideas in data assimilation and parameter estimation developed in the engineering community. The estimates combine the uncertainty in the anthropogenic aerosols with the uncertainty arising because of natural variability.more » The second component concerns how the atmospheric circulation itself might change with anthropogenic global warming. We have shown that GCMs robustly predict an increase in the length scale of eddies, and we have also explored the dynamical mechanisms whereby there might be a shift in the latitude of the jet stream associated with anthropogenic warming. Such shifts in the jet might cause large changes in regional climate, potentially larger than the globally-averaged signal itself. We have also shown that the tropopause robustly increases in height with global warming, and that the Hadley Cell expands, and that the expansion of the Hadley Cell is correlated with the polewards movement of the mid-latitude jet.« less

Developmental programming: insulin sensitizer treatment improves reproductive function in prenatal testosterone-treated female sheep.

PubMed

Veiga-Lopez, Almudena; Lee, James S; Padmanabhan, Vasantha

2010-08-01

Prenatal testosterone (T) excess causes reproductive and metabolic disruptions including insulin resistance, attributes of women with polycystic ovary syndrome. This study tested the hypothesis that insulin resistance contributes toward severity of reproductive disruptions in prenatally T-treated females. Pregnant sheep were injected im with 100 mg of T-propionate semiweekly from d 30-90 of gestation. Immediately after the first breeding season, a subset of controls and prenatal T-treated (TR) sheep were administered an insulin sensitizer (rosiglitazone; 8 mg/d) orally for 8 months. Untreated control and prenatal T-treated females (T group) were studied in parallel. Biochemical analyses revealed rosiglitazone to be safe for use in sheep. Glucose tolerance tests performed before and after the insulin sensitizer treatment found that insulin sensitizer decreased cumulative insulin, cumulative insulin/glucose ratio, and insulin area under the curve by about 50% and increased the insulin sensitivity index by about 70% in the TR compared with the T group. Twenty percent of TR females showed a reduced number of cycles in the second relative to first breeding season as opposed to 80% of T group females showing such deterioration. Insulin sensitizer treatment also decreased the number of aberrant cycles (>/=18 d) during the second breeding season in the TR group relative to the first as opposed to the T group females showing an increase in the second breeding season relative to the first. These findings provide evidence that insulin sensitizer treatment prevents further deterioration of the reproductive axis in prenatal T-treated sheep, a finding of translational relevance to women with polycystic ovary syndrome.

Diagnostic Accuracy of Memory Measures in Alzheimer's Dementia and Mild Cognitive Impairment: a Systematic Review and Meta-Analysis.

PubMed

Weissberger, Gali H; Strong, Jessica V; Stefanidis, Kayla B; Summers, Mathew J; Bondi, Mark W; Stricker, Nikki H

2017-12-01

With an increasing focus on biomarkers in dementia research, illustrating the role of neuropsychological assessment in detecting mild cognitive impairment (MCI) and Alzheimer's dementia (AD) is important. This systematic review and meta-analysis, conducted in accordance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) standards, summarizes the sensitivity and specificity of memory measures in individuals with MCI and AD. Both meta-analytic and qualitative examination of AD versus healthy control (HC) studies (n = 47) revealed generally high sensitivity and specificity (≥ 80% for AD comparisons) for measures of immediate (sensitivity = 87%, specificity = 88%) and delayed memory (sensitivity = 89%, specificity = 89%), especially those involving word-list recall. Examination of MCI versus HC studies (n = 38) revealed generally lower diagnostic accuracy for both immediate (sensitivity = 72%, specificity = 81%) and delayed memory (sensitivity = 75%, specificity = 81%). Measures that differentiated AD from other conditions (n = 10 studies) yielded mixed results, with generally high sensitivity in the context of low or variable specificity. Results confirm that memory measures have high diagnostic accuracy for identification of AD, are promising but require further refinement for identification of MCI, and provide support for ongoing investigation of neuropsychological assessment as a cognitive biomarker of preclinical AD. Emphasizing diagnostic test accuracy statistics over null hypothesis testing in future studies will promote the ongoing use of neuropsychological tests as Alzheimer's disease research and clinical criteria increasingly rely upon cerebrospinal fluid (CSF) and neuroimaging biomarkers.

Enhancing Bottom-up and Top-down Proteomic Measurements with Ion Mobility Separations

DOE PAGES

Baker, Erin Shammel; Burnum-Johnson, Kristin E.; Ibrahim, Yehia M.; ...

2015-07-03

Proteomic measurements with greater throughput, sensitivity and additional structural information enhance the in-depth characterization of complex mixtures and targeted studies with additional information and higher confidence. While liquid chromatography separation coupled with mass spectrometry (LC-MS) measurements have provided information on thousands of proteins in different sample types, the additional of another rapid separation stage providing structural information has many benefits for analyses. Technical advances in ion funnels and multiplexing have enabled ion mobility separations to be easily and effectively coupled with LC-MS proteomics to enhance the information content of measurements. Finally, herein, we report on applications illustrating increased sensitivity, throughput,more » and structural information by utilizing IMS-MS and LC-IMS-MS measurements for both bottom-up and top-down proteomics measurements.« less

A stochastic model to determine the economic value of changing diagnostic test characteristics for identification of cattle for treatment of bovine respiratory disease.

PubMed

Theurer, M E; White, B J; Larson, R L; Schroeder, T C

2015-03-01

Bovine respiratory disease is an economically important syndrome in the beef industry, and diagnostic accuracy is important for optimal disease management. The objective of this study was to determine whether improving diagnostic sensitivity or specificity was of greater economic value at varied levels of respiratory disease prevalence by using Monte Carlo simulation. Existing literature was used to populate model distributions of published sensitivity, specificity, and performance (ADG, carcass weight, yield grade, quality grade, and mortality risk) differences among calves based on clinical respiratory disease status. Data from multiple cattle feeding operations were used to generate true ranges of respiratory disease prevalence and associated mortality. Input variables were combined into a single model that calculated estimated net returns for animals by diagnostic category (true positive, false positive, false negative, and true negative) based on the prevalence, sensitivity, and specificity for each iteration. Net returns for each diagnostic category were multiplied by the proportion of animals in each diagnostic category to determine group profitability. Apparent prevalence was categorized into low (<15%) and high (≥15%) groups. For both apparent prevalence categories, increasing specificity created more rapid, positive change in net returns than increasing sensitivity. Improvement of diagnostic specificity, perhaps through a confirmatory test interpreted in series or pen-level diagnostics, can increase diagnostic value more than improving sensitivity. Mortality risk was the primary driver for net returns. The results from this study are important for determining future research priorities to analyze diagnostic techniques for bovine respiratory disease and provide a novel way for modeling diagnostic tests.

Sensitivity analysis of a model of CO2 exchange in tundra ecosystems by the adjoint method

NASA Technical Reports Server (NTRS)

Waelbroek, C.; Louis, J.-F.

1995-01-01

A model of net primary production (NPP), decomposition, and nitrogen cycling in tundra ecosystems has been developed. The adjoint technique is used to study the sensitivity of the computed annual net CO2 flux to perturbation in initial conditions, climatic inputs, and model's main parameters describing current seasonal CO2 exchange in wet sedge tundra at Barrow, Alaska. The results show that net CO2 flux is most sensitive to parameters characterizing litter chemical composition and more sensitive to decomposition parameters than to NPP parameters. This underlines the fact that in nutrient-limited ecosystems, decomposition drives net CO2 exchange by controlling mineralization of main nutrients. The results also indicate that the short-term (1 year) response of wet sedge tundra to CO2-induced warming is a significant increase in CO2 emission, creating a positive feedback to atmosphreic CO2 accumulation. However, a cloudiness increase during the same year can severely alter this response and lead to either a slight decrease or a strong increase in emitted CO2, depending on its exact timing. These results demonstrate that the adjoint method is well suited to study systems encountering regime changes, as a single run of the adjoint model provides sensitivities of the net CO2 flux to perturbations in all parameters and variables at any time of the year. Moreover, it is shown that large errors due to the presence of thresholds can be avoided by first delimiting the range of applicability of the adjoint results.

Electromechanical response of silk fibroin hydrogel and conductive polycarbazole/silk fibroin hydrogel composites as actuator material.

PubMed

Srisawasdi, Thanida; Petcharoen, Karat; Sirivat, Anuvat; Jamieson, Alexander M

2015-11-01

Pure silk fibroin (SF) hydrogel and polycarbazole/silk fibroin (SF/PCZ) hydrogels were fabricated by solvent casting technique to evaluate electromechanical responses, dielectric properties, and cantilever deflection properties as functions of electric field strength, SF concentration, glutaraldehyde concentration, and PCZ concentration in the blends. Electromechanical properties were characterized in oscillatory shear mode at electric field strengths ranging from 0 to 600V/mm and at a temperature of 27°C. For both the pristine SF and SF/PCZ hydrogels, the storage modulus response (ΔG') and the storage modulus sensitivity (ΔG'/G'0) increased dramatically with increasing electric field strength. The pristine hydrogel possessed the highest storage modulus sensitivity value of 5.87, a relatively high value when compared with other previously studied electroactive polymers. With the addition of conductive PCZ in SF hydrogel, the storage modulus sensitivity and the relative dielectric constant decreased; the conductive polymer thus provided the softening effect under electric field. In the deflection response, the dielectrophoresis force and deflection distance increased monotonically with electric field strength, where the pure SF hydrogel showed the highest deflection distance and dielectrophoresis force. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparing the effects of food restriction and overeating on brain reward systems.

PubMed

Avena, Nicole M; Murray, Susan; Gold, Mark S

2013-10-01

Both caloric restriction and overeating have been shown to affect neural processes associated with reinforcement. Both preclinical and some clinical studies have provided evidence that food restriction may increase reward sensitivity, and while there are mixed findings regarding the effects of overeating on reward sensitivity, there is strong evidence linking this behavior with changes in reward-related brain regions. Evidence of these changes comes in part from findings that show that such eating patterns are associated with increased drug use. The data discussed here regarding the differential effects of various eating patterns on reward systems may be particularly relevant to the aging population, as this population has been shown to exhibit altered reward sensitivity and decreased caloric consumption. Moreover, members of this population appear to be increasingly affected by the current obesity epidemic. Food, like alcohol or drugs, can stimulate its own consumption and produce similar neurochemical changes in the brain. Age-related loss of appetite, decreased eating, and caloric restriction are hypothesized to be associated with changes in the prevalence of substance misuse, abuse, and dependence seen in this cohort. Copyright © 2013 Elsevier Inc. All rights reserved.

Testing the incentive-sensitization theory with at-risk drinkers: wanting, liking, and alcohol consumption.

PubMed

Ostafin, Brian D; Marlatt, G Alan; Troop-Gordon, Wendy

2010-03-01

Motivational models of addiction typically propose that alcohol and drugs are desired because of their hedonic effects (i.e., increasing pleasure or reducing distress). In contrast, the incentive-sensitization theory proposes that wanting motivation and liking motivation are separable and that after repeated substance use, motivation shifts from liking to wanting. Using a sample of 85 at-risk drinkers (as defined by the National Institute on Alcohol Abuse and Alcoholism), in the current study we examined the separability of liking motivation and wanting motivation for alcohol and whether years of drinking experience was associated with an increased role for wanting motivation and a decreased role for liking motivation. Consumption was measured with a free-drinking task. Wanting motivation was assessed immediately before drinking, and liking was assessed immediately after drinking had begun. The results indicated that (a) wanting motivation predicted variance of consumption unique from that accounted for by liking motivation, (b) longer drinking experience was associated with a decreased relation between liking motivation and consumption, and (c) longer drinking experience was not associated with an increased relation between wanting motivation and consumption. The results provide partial support for the incentive-sensitization theory.

Temperature sensitivity of methanogenesis in a thermokarst lake sediment core

NASA Astrophysics Data System (ADS)

Heslop, J. K.; Walter Anthony, K. M.; Grosse, G.; Anthony, P.; Bondurant, A.

2016-12-01

Little is known about temperature sensitivity of permafrost organic carbon (OC) mineralization over time scales of years to centuries following thaw. Due to their formation and thaw histories, taliks (thaw bulbs) beneath thermokarst lakes provide a unique natural laboratory from which to examine how permafrost thawed in saturated anaerobic conditions responds to changes in temperature following long periods of time since thaw. We anaerobically incubated samples from a 590 cm thermokarst lake sediment core near Fairbanks, Alaska at four temperatures (0, 3, 10, and 25 ºC) bracketing observed talik temperatures. We show that since initial thaw 400 yr BP CH4 production shifts from being most sensitive to at lower (0-3 ºC; Q10-EC=1.15E7) temperatures to being most sensitive at higher (10-25 ºC; Q10-EC=67) temperatures. Frozen sediments collected from beneath the talik, thawed at the commencement of the incubation, had significant (p ≤ 0.05) increases in CH4 production rates at lower temperatures but did not show significant CH4 production rate increases at higher temperatures (10-25 ºC). We hypothesize the thawing of sediments removed a major barrier to C mineralization, leading to rapid initial permafrost C mineralization and preferential mineralization of the most biolabile OC compounds. In contrast, sediments which had been thawed beneath the lake for longer periods of time did not experience statistically significant increases in CH4 production at lower temperatures (0-10 ºC), but had high temperature sensitivities at higher temperatures (10-25 ºC). We believe these rate increases are due to warmer temperatures in the experimental incubations crossing activation energy thresholds, allowing previously recalcitrant fractions of OC to be utilized, and/or the presence of different microbial communities adapted to thawed sediments. Recently-deposited sediments at shallow depths in the lake core experienced increases in CH4 production across all incubation temperatures (Q10-ST=4.4).

Diagnostic accuracy of functional, imaging and biochemical tests for patients presenting with chest pain to the emergency department: A systematic review and meta-analysis.

PubMed

Iannaccone, Mario; Gili, Sebastiano; De Filippo, Ovidio; D'Amico, Salvatore; Gagliardi, Marco; Bertaina, Maurizio; Mazzilli, Silvia; Rettegno, Sara; Bongiovanni, Federica; Gatti, Paolo; Ugo, Fabrizio; Boccuzzi, Giacomo G; Colangelo, Salvatore; Prato, Silvia; Moretti, Claudio; D'Amico, Maurizio; Noussan, Patrizia; Garbo, Roberto; Hildick-Smith, David; Gaita, Fiorenzo; D'Ascenzo, Fabrizio

2018-01-01

Non-invasive ischaemia tests and biomarkers are widely adopted to rule out acute coronary syndrome in the emergency department. Their diagnostic accuracy has yet to be precisely defined. Medline, Cochrane Library CENTRAL, EMBASE and Biomed Central were systematically screened (start date 1 September 2016, end date 1 December 2016). Prospective studies (observational or randomised controlled trial) comparing functional/imaging or biochemical tests for patients presenting with chest pain to the emergency department were included. Overall, 77 studies were included, for a total of 49,541 patients (mean age 59.9 years). Fast and six-hour highly sensitive troponin T protocols did not show significant differences in their ability to detect acute coronary syndromes, as they reported a sensitivity and specificity of 0.89 (95% confidence interval 0.79-0.94) and 0.84 (0.74-0.9) vs 0.89 (0.78-0.94) and 0.83 (0.70-0.92), respectively. The addition of copeptin to troponin increased sensitivity and reduced specificity, without improving diagnostic accuracy. The diagnostic value of non-invasive tests for patients without troponin increase was tested. Coronary computed tomography showed the highest level of diagnostic accuracy (sensitivity 0.93 (0.81-0.98) and specificity 0.90 (0.93-0.94)), along with myocardial perfusion scintigraphy (sensitivity 0.85 (0.77-0.91) and specificity 0.92 (0.83-0.96)). Stress echography was inferior to coronary computed tomography but non-inferior to myocardial perfusion scintigraphy, while exercise testing showed the lower level of diagnostic accuracy. Fast and six-hour highly sensitive troponin T protocols provide an overall similar level of diagnostic accuracy to detect acute coronary syndrome. Among the non-invasive ischaemia tests for patients without troponin increase, coronary computed tomography and myocardial perfusion scintigraphy showed the highest sensitivity and specificity.

Particle sensor array

NASA Technical Reports Server (NTRS)

Buehler, Martin G. (Inventor); Blaes, Brent R. (Inventor); Lieneweg, Udo (Inventor)

1994-01-01

A particle sensor array which in a preferred embodiment comprises a static random access memory having a plurality of ion-sensitive memory cells, each such cell comprising at least one pull-down field effect transistor having a sensitive drain surface area (such as by bloating) and at least one pull-up field effect transistor having a source connected to an offset voltage. The sensitive drain surface area and the offset voltage are selected for memory cell upset by incident ions such as alpha-particles. The static random access memory of the present invention provides a means for selectively biasing the memory cells into the same state in which each of the sensitive drain surface areas is reverse biased and then selectively reducing the reversed bias on these sensitive drain surface areas for increasing the upset sensitivity of the cells to ions. The resulting selectively sensitive memory cells can be used in a number of applications. By way of example, the present invention can be used for measuring the linear energy transfer of ion particles, as well as a device for assessing the resistance of CMOS latches to Cosmic Ray induced single event upsets. The sensor of the present invention can also be used to determine the uniformity of an ion beam.

Thermal effects on nonlinear vibration of a carbon nanotube-based mass sensor using finite element analysis

NASA Astrophysics Data System (ADS)

Kang, Dong-Keun; Kim, Chang-Wan; Yang, Hyun-Ik

2017-01-01

In the present study we carried out a dynamic analysis of a CNT-based mass sensor by using a finite element method (FEM)-based nonlinear analysis model of the CNT resonator to elucidate the combined effects of thermal effects and nonlinear oscillation behavior upon the overall mass detection sensitivity. Mass sensors using carbon nanotube (CNT) resonators provide very high sensing performance. Because CNT-based resonators can have high aspect ratios, they can easily exhibit nonlinear oscillation behavior due to large displacements. Also, CNT-based devices may experience high temperatures during their manufacture and operation. These geometrical nonlinearities and temperature changes affect the sensing performance of CNT-based mass sensors. However, it is very hard to find previous literature addressing the detection sensitivity of CNT-based mass sensors including considerations of both these nonlinear behaviors and thermal effects. We modeled the nonlinear equation of motion by using the von Karman nonlinear strain-displacement relation, taking into account the additional axial force associated with the thermal effect. The FEM was employed to solve the nonlinear equation of motion because it can effortlessly handle the more complex geometries and boundary conditions. A doubly clamped CNT resonator actuated by distributed electrostatic force was the configuration subjected to the numerical experiments. Thermal effects upon the fundamental resonance behavior and the shift of resonance frequency due to attached mass, i.e., the mass detection sensitivity, were examined in environments of both high and low (or room) temperature. The fundamental resonance frequency increased with decreasing temperature in the high temperature environment, and increased with increasing temperature in the low temperature environment. The magnitude of the shift in resonance frequency caused by an attached mass represents the sensing performance of a mass sensor, i.e., its mass detection sensitivity, and it can be seen that this shift is affected by the temperature change and the amount of electrostatic force. The thermal effects on the mass detection sensitivity are intensified in the linear oscillation regime and increase with increasing CNT length; this intensification can either improve or worsen the detection sensitivity.

Forest disturbances under climate change

NASA Astrophysics Data System (ADS)

Seidl, Rupert; Thom, Dominik; Kautz, Markus; Martin-Benito, Dario; Peltoniemi, Mikko; Vacchiano, Giorgio; Wild, Jan; Ascoli, Davide; Petr, Michal; Honkaniemi, Juha; Lexer, Manfred J.; Trotsiuk, Volodymyr; Mairota, Paola; Svoboda, Miroslav; Fabrika, Marek; Nagel, Thomas A.; Reyer, Christopher P. O.

2017-06-01

Forest disturbances are sensitive to climate. However, our understanding of disturbance dynamics in response to climatic changes remains incomplete, particularly regarding large-scale patterns, interaction effects and dampening feedbacks. Here we provide a global synthesis of climate change effects on important abiotic (fire, drought, wind, snow and ice) and biotic (insects and pathogens) disturbance agents. Warmer and drier conditions particularly facilitate fire, drought and insect disturbances, while warmer and wetter conditions increase disturbances from wind and pathogens. Widespread interactions between agents are likely to amplify disturbances, while indirect climate effects such as vegetation changes can dampen long-term disturbance sensitivities to climate. Future changes in disturbance are likely to be most pronounced in coniferous forests and the boreal biome. We conclude that both ecosystems and society should be prepared for an increasingly disturbed future of forests.

Forest disturbances under climate change

PubMed Central

Seidl, Rupert; Thom, Dominik; Kautz, Markus; Martin-Benito, Dario; Peltoniemi, Mikko; Vacchiano, Giorgio; Wild, Jan; Ascoli, Davide; Petr, Michal; Honkaniemi, Juha; Lexer, Manfred J.; Trotsiuk, Volodymyr; Mairota, Paola; Svoboda, Miroslav; Fabrika, Marek; Nagel, Thomas A.; Reyer, Christopher P. O.

2017-01-01

Forest disturbances are sensitive to climate. However, our understanding of disturbance dynamics in response to climatic changes remains incomplete, particularly regarding large-scale patterns, interaction effects and dampening feedbacks. Here we provide a global synthesis of climate change effects on important abiotic (fire, drought, wind, snow and ice) and biotic (insects and pathogens) disturbance agents. Warmer and drier conditions particularly facilitate fire, drought and insect disturbances, while warmer and wetter conditions increase disturbances from wind and pathogens. Widespread interactions between agents are likely to amplify disturbances, while indirect climate effects such as vegetation changes can dampen long-term disturbance sensitivities to climate. Future changes in disturbance are likely to be most pronounced in coniferous forests and the boreal biome. We conclude that both ecosystems and society should be prepared for an increasingly disturbed future of forests. PMID:28861124

Postnatal Developmental Trajectories of Neural Circuits in the Primate Prefrontal Cortex: Identifying Sensitive Periods for Vulnerability to Schizophrenia

PubMed Central

Hoftman, Gil D.; Lewis, David A.

2011-01-01

Schizophrenia is a disorder of cognitive neurodevelopment with characteristic abnormalities in working memory attributed, at least in part, to alterations in the circuitry of the dorsolateral prefrontal cortex. Various environmental exposures from conception through adolescence increase risk for the illness, possibly by altering the developmental trajectories of prefrontal cortical circuits. Macaque monkeys provide an excellent model system for studying the maturation of prefrontal cortical circuits. Here, we review the development of glutamatergic and γ-aminobutyric acid (GABA)-ergic circuits in macaque monkey prefrontal cortex and discuss how these trajectories may help to identify sensitive periods during which environmental exposures, such as those associated with increased risk for schizophrenia, might lead to the types of abnormalities in prefrontal cortical function present in schizophrenia. PMID:21505116

An improved method of chemical analysis for low levels of nitrogen in forest streams or in rainwater.

Treesearch

Elly E. Holcombe; Duane G. Moore; Richard L. Fredriksen

1986-01-01

A modification of the macro-Kjeldahl method that provides increased sensitivity was developed for determining very low levels of nitrogen in forest streams and in rain-water. The method is suitable as a routine laboratory procedure. Analytical range of the method is 0.02 to 1.5 mg/L with high recovery and excellent precision and ac-curacy. The range can be increased to...

An in vitro human skin test for assessing sensitization potential.

PubMed

Ahmed, S S; Wang, X N; Fielding, M; Kerry, A; Dickinson, I; Munuswamy, R; Kimber, I; Dickinson, A M

2016-05-01

Sensitization to chemicals resulting in an allergy is an important health issue. The current gold-standard method for identification and characterization of skin-sensitizing chemicals was the mouse local lymph node assay (LLNA). However, for a number of reasons there has been an increasing imperative to develop alternative approaches to hazard identification that do not require the use of animals. Here we describe a human in-vitro skin explant test for identification of sensitization hazards and the assessment of relative skin sensitizing potency. This method measures histological damage in human skin as a readout of the immune response induced by the test material. Using this approach we have measured responses to 44 chemicals including skin sensitizers, pre/pro-haptens, respiratory sensitizers, non-sensitizing chemicals (including skin-irritants) and previously misclassified compounds. Based on comparisons with the LLNA, the skin explant test gave 95% specificity, 95% sensitivity, 95% concordance with a correlation coefficient of 0.9. The same specificity and sensitivity were achieved for comparison of results with published human sensitization data with a correlation coefficient of 0.91. The test also successfully identified nickel sulphate as a human skin sensitizer, which was misclassified as negative in the LLNA. In addition, sensitizers and non-sensitizers identified as positive or negative by the skin explant test have induced high/low T cell proliferation and IFNγ production, respectively. Collectively, the data suggests the human in-vitro skin explant test could provide the basis for a novel approach for characterization of the sensitizing activity as a first step in the risk assessment process. Copyright © 2015 John Wiley & Sons, Ltd.

Finding the Fertile Phase: Low-Cost Luteinizing Hormone Sticks Versus Electronic Fertility Monitor.

PubMed

Barron, Mary Lee; Vanderkolk, Kaitlin; Raviele, Kathleen

To investigate if generic Wondfo ovulation sticks (WLH) are sufficiently sensitive to the luteinizing hormone (LH) surge in urine when used with the Marquette Fertility Algorithm. The electronic hormonal fertility monitor (EHFM) is highly accurate in detecting the LH surge but cost of the monitor and the accompanying test sticks has increased over the last several years. The EHFM is sensitive to detect the LH surge at 20 milli-international units per milliliter (mIU/mL); the WLH sticks are slightly less sensitive at 25 mIU/mL. A convenience sample of women using the Marquette Method of Natural Family Planning with the EHFM to avoid pregnancy were recruited (N = 54). Each participant used the EHFM every morning after cycle day 6 and tested morning and evening urine with the WLH stick until the day following detection of the LH surge on the EHFM. Forty-two women provided 219 cycles. Frequency of LH surge detection was 182/219 (83.1%) for EHFM and 203/219 (92.7%) for WLH sticks. Agreement between the EHFM and the WLH on the day of the LH surge was 97.7%. High fertility readings providing a warning of peak fertility at least 5 days before peak was 67% for the WLH; the EHFM was 47.7%. Paired sample correlations for high fertility was .174 (p = .014) and paired sample differences t was -4.729 (p = .000). The WLH stick is sufficiently sensitive to use in place of the EFHM for determining peak fertility and with the Marquette Fertility algorithm. Even with minimal use, WLH sticks cost about half the price of the monitor strips and provide more flexibility of use. Cost differences increase with the number of sticks used per cycle. Further research with a larger sample is needed to verify results.

Exercise training reverses the negative effects of chronic L-arginine supplementation on insulin sensitivity.

PubMed

Salgueiro, Rafael Barrera; Gerlinger-Romero, Frederico; Guimarães-Ferreira, Lucas; de Castro Barbosa, Thais; Nunes, Maria Tereza

2017-12-15

L-Arginine has emerged as an important supplement for athletes and non-athletes in order to improve performance. Arginine has been extensively used as substrate for nitric oxide synthesis, leading to increased vasodilatation and hormonal secretion. However, the chronic consumption of arginine has been shown to impair insulin sensitivity. In the present study, we aimed to evaluate whether chronic arginine supplementation associated with exercise training would have a beneficial impact on insulin sensitivity. We, therefore, treated Wistar rats for 4weeks with arginine, associated or not with exercise training (treadmill). We assessed the somatotropic activation, by evaluating growth hormone (GH) gene expression and protein content in the pituitary, as well is GH concentration in the serum. Additionally, we evaluate whole-body insulin sensitivity, by performing an insulin tolerance test. Skeletal muscle morpho-physiological parameters were also assessed. Insulin sensitivity was impaired in the arginine-treated rats. However, exercise training reversed the negative effects of arginine. Arginine and exercise training increased somatotropic axis function, muscle mass and body weight gain. The combination arginine and exercise training further decreased total fat mass. Our results confirm that chronic arginine supplementation leads to insulin resistance, which can be reversed in the association with exercise training. We provide further evidence that exercise training is an important tool to improve whole-body metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased conspicuousness can explain the match between visual sensitivities and blue plumage colours in fairy-wrens

PubMed Central

Delhey, Kaspar; Hall, Michelle; Kingma, Sjouke A.; Peters, Anne

2013-01-01

Colour signals are expected to match visual sensitivities of intended receivers. In birds, evolutionary shifts from violet-sensitive (V-type) to ultraviolet-sensitive (U-type) vision have been linked to increased prevalence of colours rich in shortwave reflectance (ultraviolet/blue), presumably due to better perception of such colours by U-type vision. Here we provide the first test of this widespread idea using fairy-wrens and allies (Family Maluridae) as a model, a family where shifts in visual sensitivities from V- to U-type eyes are associated with male nuptial plumage rich in ultraviolet/blue colours. Using psychophysical visual models, we compared the performance of both types of visual systems at two tasks: (i) detecting contrast between male plumage colours and natural backgrounds, and (ii) perceiving intraspecific chromatic variation in male plumage. While U-type outperforms V-type vision at both tasks, the crucial test here is whether U-type vision performs better at detecting and discriminating ultraviolet/blue colours when compared with other colours. This was true for detecting contrast between plumage colours and natural backgrounds (i), but not for discriminating intraspecific variability (ii). Our data indicate that selection to maximize conspicuousness to conspecifics may have led to the correlation between ultraviolet/blue colours and U-type vision in this clade of birds. PMID:23118438

Investigating Sensitivity to Saharan Dust in Tropical Cyclone Formation Using Nasa's Adjoint Model

NASA Technical Reports Server (NTRS)

Holdaway, Daniel

2015-01-01

As tropical cyclones develop from easterly waves coming of the coast of Africa they interact with dust from the Sahara desert. There is a long standing debate over whether this dust inhibits or advances the developing storm and how much influence it has. Dust can surround the storm and absorb incoming solar radiation, cooling the air below. As a result an energy source for the system is potentially diminished, inhibiting growth of the storm. Alternatively dust may interact with clouds through micro-physical processes, for example by causing more moisture to condense, potentially increasing the strength. As a result of climate change, concentrations and amount of dust in the atmosphere will likely change. It it is important to properly understand its effect on tropical storm formation. The adjoint of an atmospheric general circulation model provides a very powerful tool for investigating sensitivity to initial conditions. The National Aeronautics and Space Administration (NASA) has recently developed an adjoint version of the Goddard Earth Observing System version 5 (GEOS-5) dynamical core, convection scheme, cloud model and radiation schemes. This is extended so that the interaction between dust and radiation is also accounted for in the adjoint model. This provides a framework for examining the sensitivity to dust in the initial conditions. Specifically the set up allows for an investigation into the extent to which dust affects cyclone strength through absorption of radiation. In this work we investigate the validity of using an adjoint model for examining sensitivity to dust in hurricane formation. We present sensitivity results for a number of systems that developed during the Atlantic hurricane season of 2006. During this period there was a significant outbreak of Saharan dust and it is has been argued that this outbreak was responsible for the relatively calm season. This period was also covered by an extensive observation campaign. It is shown that the adjoint can provide insight into the sensitivity and reveals a relatively low sensitivity to dust compared to, for example, the thermodynamic variables. However a secondary sensitivity though moisture is seen. If dust dries the air it can significantly reduce the cyclone intensity through the moisture.

Investigating sensitivity to Saharan dust in tropical cyclone formation using NASA's adjoint model

NASA Astrophysics Data System (ADS)

Holdaway, Daniel

2015-04-01

As tropical cyclones develop from easterly waves coming off the coast of Africa they interact with dust from the Sahara desert. There is a long standing debate over whether this dust inhibits or advances the developing storm and how much influence it has. Dust can surround the storm and absorb incoming solar radiation, cooling the air below. As a result an energy source for the system is potentially diminished, inhibiting growth of the storm. Alternatively dust may interact with clouds through micro-physical processes, for example by causing more moisture to condense, potentially increasing the strength. As a result of climate change, concentrations and amount of dust in the atmosphere will likely change. It it is important to properly understand its effect on tropical storm formation. The adjoint of an atmospheric general circulation model provides a very powerful tool for investigating sensitivity to initial conditions. The National Aeronautics and Space Administration (NASA) has recently developed an adjoint version of the Goddard Earth Observing System version 5 (GEOS-5) dynamical core, convection scheme, cloud model and radiation schemes. This is extended so that the interaction between dust and radiation is also accounted for in the adjoint model. This provides a framework for examining the sensitivity to dust in the initial conditions. Specifically the set up allows for an investigation into the extent to which dust affects cyclone strength through absorption of radiation. In this work we investigate the validity of using an adjoint model for examining sensitivity to dust in hurricane formation. We present sensitivity results for a number of systems that developed during the Atlantic hurricane season of 2006. During this period there was a significant outbreak of Saharan dust and it is has been argued that this outbreak was responsible for the relatively calm season. This period was also covered by an extensive observation campaign. It is shown that the adjoint can provide insight into the sensitivity and reveals a relatively low sensitivity to dust compared to, for example, the thermodynamic variables. However a secondary sensitivity though moisture is seen. If dust dries the air it can significantly reduce the cyclone intensity through the moisture.

Pavlovian conditioning of psychomotor stimulant-induced behaviours: has convenience led us astray?

PubMed

Martin-Iverson, M.T.; Fawcett, S.L.

1996-01-01

In order to classically condition the behavioural effects of psychomotor stimulants within a test context, rats were treated for 10 days with (+)-amphetamine (1.5mg/kg), (+)-4-propyl-9-hydroxynaphthoxazine (PHNO, 30µg/kg) or vehicle prior to a 1h placement into a test box. Conditioned behavioural effects were then measured in the previously drug-paired context after a vehicle injection (drug-free test day). Each rat was videotaped for the 1h test box exposure on days 1, 4, 7 and 10 of the drug conditioning trials, and on the drug-free test day. Eleven of 28 behaviours that were scored for frequency, duration and mean bout duration (bout length) were significantly influenced by at least one of the two drugs. Amphetamine predominantly increased bout lengths while PHNO predominantly increased bout frequency. Only two measures that were influenced by the drugs exhibited clear increases over controls in a manner consistent with a classical conditioning interpretation. Behavioural sensitization clearly occurred to some of the effects of amphetamine and PHNO, but these were not the same effects as those increased on the non-drug day testing for classical conditioning. Most behavioural effects of amphetamine and PHNO are not classically conditioned, and behavioural sensitization to these drugs, while perhaps context-specific, is not due to classical conditioning. Automated measures of behaviours have provided misleading evidence concerning the similarity among behavioural effects of stimulants, sensitization and effects of exposure to an environment previously paired with stimulants. Analysis of transitions between behaviours does not support the view that stimulants increase switching or response competition, or that behavioural reorganization is responsible for sensitization. Rather, it is suggested that stimulants selectively facilitate current stimulus-guided behaviours.

Elemental Analysis in Biological Matrices Using ICP-MS.

PubMed

Hansen, Matthew N; Clogston, Jeffrey D

2018-01-01

The increasing exploration of metallic nanoparticles for use as cancer therapeutic agents necessitates a sensitive technique to track the clearance and distribution of the material once introduced into a living system. Inductively coupled plasma mass spectrometry (ICP-MS) provides a sensitive and selective tool for tracking the distribution of metal components from these nanotherapeutics. This chapter presents a standardized method for processing biological matrices, ensuring complete homogenization of tissues, and outlines the preparation of appropriate standards and controls. The method described herein utilized gold nanoparticle-treated samples; however, the method can easily be applied to the analysis of other metals.

Smart zwitterionic membranes with on/off behavior for protein transport.

PubMed

Su, Yanlei; Zheng, Lili; Li, Chao; Jiang, Zhongyi

2008-09-25

Poly(acrylonitrile) (PAN)-based zwitterionic membranes, composed of PAN and poly( N, N-dimethyl- N-methacryloxyethyl- N-(3-sulfopropyl) copolymer, are electrolyte-sensitive smart membranes. The hydrophilicity was increased and protein adsorption was remarkably decreased for the membranes in response to environmental stimuli. FTIR spectroscopic analysis directly provided molecular-level observation of the enhanced dissociation and hydration of zwitterionic sulfobetaine dipoles at higher electrolyte concentrations. The smart PAN-based zwitterionic membranes can close or open channels for protein transport under different NaCl concentrations. The electrolyte-sensitive switch of on/off behavior for protein transport is reversible.

Does providing written dietary advice improve the ingestion of non-allergic nuts in children with existing nut allergies? - A randomized controlled trial.

PubMed

Norman, M; South, C; Quinn, P; Chan, D; Palmer, S; Netting, M; Gold, M

2016-05-01

Allergy to one or more nuts is common in children and often complete nut avoidance is advised. More recently, introduction of non-allergic nuts into the diet is advised by some allergists. This study aims to determine whether the provision of additional written dietary advice increases the ingestion of non-allergic nuts by children with nut allergy. Secondary aims include determining which factors facilitate or prevent successful inclusion of non-allergic nuts in the diet, and how inclusion influences quality of life, sensitization and the rate of nut reactions. This is a randomized, double-blinded, controlled trial of children with nut allergy who were asked to ingest one or more non-allergic nuts. Participants were 75 children aged 2-16 years (Intervention=36, Control=39), recruited in Adelaide, Australia. Randomized participants were supplied with the intervention (recipe booklet and monthly reminder text messages) or provided standard verbal dietary advice. After 6 months participants were assessed by a blinded investigator with regard to nut ingestion, quality of life, sensitization and nut reactions. The intervention did not increase the ingestion of non-allergic nuts. A negative hospital challenge was a predictor of successful introduction. Parental report of child concern about a reaction was the greatest barrier. Ingestion of non-allergic nuts did not improve quality of life or change nut sensitization. Few nut reactions occurred during the study. Ingestion of non-allergic nuts by children with nut allergy was not improved by additional dietary intervention. Selective introduction of non-allergic nuts is difficult to achieve when the child is anxious about introduction and challenges cannot be done in a medically supervised setting. This dietary intervention did not improve non-allergic nut ingestion by nut allergic children. Hospital challenge increased introduction rates, whilst parentally reported child concern about a reaction reduced success. Non-allergic nut ingestion did not change quality of life or sensitization. © 2016 John Wiley & Sons Ltd.

Methamphetamine-sensitized rats show augmented dopamine release to methylphenidate stimulation: a positron emission tomography using [18F]fallypride.

PubMed

Ota, Miho; Ogawa, Shintaro; Kato, Koichi; Wakabayashi, Chisato; Kunugi, Hiroshi

2015-04-30

Previous studies demonstrated that patients with schizophrenia show greater sensitivity to psychostimulants than healthy subjects. Sensitization to psychostimulants and resultant alteration of dopaminergic neurotransmission in rodents have been suggested as a useful model of schizophrenia. This study was aimed to examine the use of methylphenidate as a psychostimulant to induce dopamine release and that of [18F]fallypride as a radioligand to estimate the release in a rat model of schizophrenia. Six rats were scanned by positron emission tomography (PET) twice before and after methylphenidate challenge to evaluate dopamine release. After the scans, these rats were sensitized by using repeated methamphetamine (MAP) administration. Then, they were re-scanned twice again before and after methylphenidate challenge to evaluate whether MAP-sensitized rats show greater sensitivity to methylphenidate. We revealed a main effect of MAP-pretreatment and that of metylphenidate challenge. We found that % change of distribution volume ratio after repeated administration of MAP was greater than that before sensitization. These results suggest that methylphenidate-induced striatal dopamine release increased after sensitization to MAP. PET scan using [18F]fallypride at methylphenidate-challenge may provide a biological marker for schizophrenia and be useful to diagnose schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Machine learning for classifying tuberculosis drug-resistance from DNA sequencing data

PubMed Central

Yang, Yang; Niehaus, Katherine E; Walker, Timothy M; Iqbal, Zamin; Walker, A Sarah; Wilson, Daniel J; Peto, Tim E A; Crook, Derrick W; Smith, E Grace; Zhu, Tingting; Clifton, David A

2018-01-01

Abstract Motivation Correct and rapid determination of Mycobacterium tuberculosis (MTB) resistance against available tuberculosis (TB) drugs is essential for the control and management of TB. Conventional molecular diagnostic test assumes that the presence of any well-studied single nucleotide polymorphisms is sufficient to cause resistance, which yields low sensitivity for resistance classification. Summary Given the availability of DNA sequencing data from MTB, we developed machine learning models for a cohort of 1839 UK bacterial isolates to classify MTB resistance against eight anti-TB drugs (isoniazid, rifampicin, ethambutol, pyrazinamide, ciprofloxacin, moxifloxacin, ofloxacin, streptomycin) and to classify multi-drug resistance. Results Compared to previous rules-based approach, the sensitivities from the best-performing models increased by 2-4% for isoniazid, rifampicin and ethambutol to 97% (P < 0.01), respectively; for ciprofloxacin and multi-drug resistant TB, they increased to 96%. For moxifloxacin and ofloxacin, sensitivities increased by 12 and 15% from 83 and 81% based on existing known resistance alleles to 95% and 96% (P < 0.01), respectively. Particularly, our models improved sensitivities compared to the previous rules-based approach by 15 and 24% to 84 and 87% for pyrazinamide and streptomycin (P < 0.01), respectively. The best-performing models increase the area-under-the-ROC curve by 10% for pyrazinamide and streptomycin (P < 0.01), and 4–8% for other drugs (P < 0.01). Availability and implementation The details of source code are provided at http://www.robots.ox.ac.uk/~davidc/code.php. Contact david.clifton@eng.ox.ac.uk Supplementary information Supplementary data are available at Bioinformatics online. PMID:29240876

Learning to Teach Culturally and Linguistically Diverse Students through Cross-Cultural Experiences

ERIC Educational Resources Information Center

Savva, Maria

2017-01-01

Teacher participation in cross-cultural experiences is often associated with the broadening of perspectives and increased intercultural sensitivity. While these qualities provide an overarching and important framework for intercultural development, they remain highly abstract. What exactly do we mean when we refer to these qualities? And in what…

Spatial Analysis for Monitoring Forest Health

Treesearch

Francis A. Roesch

1994-01-01

A plan for the spatial analysis for the sample design for the detection monitoring phase in the joint USDA Forest Service/EPA Forest Health Monitoring Program (FHM) in the United States is discussed. The spatial analysis procedure is intended to more quickly identify changes in forest health by providing increased sensitivity to localized changes. The procedure is...

Simulations for the Discipline Specific and Professional Education of Foreign Policy Graduates

ERIC Educational Resources Information Center

Kelton, Maryanne; Kingsmill, Verity

2016-01-01

Increasingly universities aim to provide students with opportunities to graduate with skills ready to perform in the workplace. However, workplace-based opportunities for students enrolled in foreign policy subjects are more limited due to the diplomatic and sensitive political nature of the professional work. Thus there exists a need for higher…

Interpreting multiscale domains of tree cover disturbance patterns in North America

Treesearch

Kurt Riitters; Jennifer K. Costanza; Brian Buma

2017-01-01

Spatial patterns at multiple observation scales provide a framework to improve understanding of pattern-related phenomena. However, the metrics that are most sensitive to local patterns are least likely to exhibit consistent scaling relations with increasing extent (observation scale). A conceptual framework based on multiscale domains (i.e., geographic locations...

Evaluating soil erodibility dynamics to improve estimates of wind erosion in drylands

USDA-ARS?s Scientific Manuscript database

Wind erosion is a key driver of land degradation in the world’s drylands. Soil loss and nutrient decline due to wind erosion increase the sensitivity of drylands to climate stressors. Better understanding the factors controlling wind erosion in drylands will provide a basis for identifying and testi...

Secure, safe, and sensitive solutions.

PubMed

Hughan, Tina

2012-04-01

Tabloid sensationalism aside, the increase in attacks on health service workers has led to many hospitals and healthcare facilities re-assessing their security systems. Here, Tina Hughan, head of marketing for specialist in door opening systems, Assa Abloy, gives her view on how security providers can help healthcare estates and facilities teams to cope with this disturbing trend.

Child-Centered, Family-Sensitive Schools: An Educator's Guide to Family Dynamics.

ERIC Educational Resources Information Center

Garanzini, Michael J.

An increasing number of children have family problems that interfere with their ability to learn at school. This book provides information about developing a clearer and more sophisticated child-centered school and classroom by making teachers and administrators more knowledgeable about the varieties of students' family structures, both healthy…

Radiosensitization of cancer cells by hydroxychalcones.

PubMed

Pruitt, Rory; Sasi, Nidhish; Freeman, Michael L; Sekhar, Konjeti R

2010-10-15

Radiation sensitization is significantly increased by proteotoxic stress, such as a heat shock. We undertook an investigation, seeking to identify natural products that induced proteotoxic stress and then determined if a compound exhibited radiosensitizing properties. The hydroxychalcones, 2',5'-dihydroxychalcone (D-601) and 2,2'-dihydroxychalcone (D-501), were found to activate heat shock factor 1 (Hsf1) and exhibited radiation sensitization properties in colon and pancreatic cancer cells. The radiosensitization ability of D-601 was blocked by pretreatment with α-napthoflavone (ANF), a specific inhibitor of cytochrome P450 1A2 (CYP1A2), suggesting that the metabolite of D-601 is essential for radiosensitization. The study demonstrated the ability of hydroxychalcones to radiosensitize cancer cells and provides new leads for developing novel radiation sensitizers. Copyright © 2010 Elsevier Ltd. All rights reserved.

Radiosensitization of Cancer Cells by Hydroxychalcones

PubMed Central

Pruitt, Rory; Sasi, Nidhish; Freeman, Michael L.; Sekhar, Konjeti R.

2010-01-01

Radiation sensitization is significantly increased by proteotoxic stress, such as a heat shock. We undertook an investigation, seeking to identify natural products that induced proteotoxic stress and then determined if a compound exhibited radiosensitizing properties. The hydroxychalcones, 2′,5′-dihydroxychalcone (D-601) and 2,2′-dihydroxychalcone (D-501), were found to activate heat shock factor 1 (Hsf1) and exhibited radiation sensitization properties in colon and pancreatic cancer cells. The radiosensitization ability of D-601 was blocked by pretreatment with α-napthoflavone (ANF), a specific inhibitor of cytochrome P450 1A2 (CYP1A2), suggesting that the metabolite of D-601 is essential for radiosensitization. The study demonstrated the ability of hydroxychalcones to radiosensitize cancer cells and provides new leads for developing novel radiation sensitizers. PMID:20826087

Gluten sensitivity: fact or fashion statement?

PubMed

Khalid, Ayesha N; McMains, Kevin C

2016-06-01

In recent years, the concern over food sensitivities in general and gluten intolerance in particular has sharply increased. Patients and medical providers are awash in various claims about the potential implications of including or excluding gluten from the diet. Three main conditions are described with respect to gluten: wheat allergy, celiac disease, and nonceliac gluten sensitivity (NCGS). Wheat allergy is a type 1 hypersensitivity reaction to nongluten proteins within wheat. Celiac disease is an autoimmune reaction to the gluten protein resulting in damage to the small intestine with genetic associations. NCGS is a diagnosis of exclusion and, to date, no biomarkers have been identified for this condition. When evaluating and treating patients with potential reactions to gluten, it is important to distinguish among wheat allergy, celiac disease, and NCGS. Each condition has distinct dietary and treatment implications.

Characterization of the insulin sensitivity of ghrelin receptor KO mice using glycemic clamps

PubMed Central

2011-01-01

Background We and others have demonstrated previously that ghrelin receptor (GhrR) knock out (KO) mice fed a high fat diet (HFD) have increased insulin sensitivity and metabolic flexibility relative to WT littermates. A striking feature of the HFD-fed GhrR KO mouse is the dramatic decrease in hepatic steatosis. To characterize further the underlying mechanisms of glucose homeostasis in GhrR KO mice, we conducted both hyperglycemic (HG) and hyperinsulinemic-euglycemic (HI-E) clamps. Additionally, we investigated tissue glucose uptake and specifically examined liver insulin sensitivity. Results Consistent with glucose tolerance-test data, in HG clamp experiments, GhrR KO mice showed a reduction in glucose-stimulated insulin release relative to WT littermates. Nevertheless, a robust 1st phase insulin secretion was still achieved, indicating that a healthy β-cell response is maintained. Additionally, GhrR KO mice demonstrated both a significantly increased glucose infusion rate and significantly reduced insulin requirement for maintenance of the HG clamp, consistent with their relative insulin sensitivity. In HI-E clamps, both LFD-fed and HFD-fed GhrR KO mice showed higher peripheral insulin sensitivity relative to WT littermates as indicated by a significant increase in insulin-stimulated glucose disposal (Rd), and decreased hepatic glucose production (HGP). HFD-fed GhrR KO mice showed a marked increase in peripheral tissue glucose uptake in a variety of tissues, including skeletal muscle, brown adipose tissue and white adipose tissue. GhrR KO mice fed a HFD also showed a modest, but significant decrease in conversion of pyruvate to glucose, as would be anticipated if these mice displayed increased liver insulin sensitivity. Additionally, the levels of UCP2 and UCP1 were reduced in the liver and BAT, respectively, in GhrR KO mice relative to WT mice. Conclusions These results indicate that improved glucose homeostasis of GhrR KO mice is characterized by robust improvements of glucose disposal in both normal and metabolically challenged states, relative to WT controls. GhrR KO mice have an intact 1st phase insulin response but require significantly less insulin for glucose disposal. Our experiments reveal that the insulin sensitivity of GhrR KO mice is due to both BW independent and dependent factors. We also provide several lines of evidence that a key feature of the GhrR KO mouse is maintenance of hepatic insulin sensitivity during metabolic challenge. PMID:21211044

Sensitivity to scale of willingness-to-pay within the context of menorrhagia.

PubMed

Sanghera, Sabina; Frew, Emma; Gupta, Janesh Kumar; Kai, Joe; Roberts, Tracy Elizabeth

2017-04-01

Willingness-to-pay (WTP) provides a broad assessment of well-being, capturing benefits beyond health. However, the validity of the approach has been questioned and the evidence relating to the sensitivity of WTP to changes in health status is mixed. Using menorrhagia (heavy menstrual bleeding) as a case study, this exploratory study assesses the sensitivity to scale of WTP to change in health status as measured by a condition-specific measure, MMAS, which includes both health and non-health benefits. The relationship between EQ-5D and change in health status is also assessed. Baseline EQ-5D and MMAS values were collected from women taking part in a randomized controlled trial for pharmaceutical treatment of menorrhagia. Following treatment, these measures were administered along with a WTP exercise. The relationship between the measures was assessed using Spearman's correlation analysis, and the sensitivity to scale of WTP was measured by identifying differences in WTP alongside differences in MMAS and EQ5D values. Our exploratory findings indicated that WTP, and not EQ-5D, was significantly positively correlated with change in MMAS, providing some evidence for convergent validity. These findings suggest that WTP is capturing the non-health benefits within the MMAS measure. Mean WTP also increased with percentage improvements in MMAS, suggesting sensitivity to scale. When compared to quality of life measured using the condition-specific MMAS measure, the convergent validity and sensitivity to scale of WTP is indicated. The findings suggest that WTP is more sensitive to change in MMAS, than with EQ-5D. © 2016 The Authors Health Expectations Published by John Wiley & Sons Ltd.

Skeletal Muscle Triglycerides, Diacylglycerols, and Ceramides in Insulin Resistance

PubMed Central

Amati, Francesca; Dubé, John J.; Alvarez-Carnero, Elvis; Edreira, Martin M.; Chomentowski, Peter; Coen, Paul M.; Switzer, Galen E.; Bickel, Perry E.; Stefanovic-Racic, Maja; Toledo, Frederico G.S.; Goodpaster, Bret H.

2011-01-01

OBJECTIVE Chronic exercise and obesity both increase intramyocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercise-trained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype. RESEARCH DESIGN AND METHODS A total of 14 normal-weight, endurance-trained athletes (NWA group) and 7 normal-weight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies. RESULTS DAG content in the NWA group was approximately twofold higher than in the OBS group and ~50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, IMTGs, DAGs, and insulin sensitivity. CONCLUSIONS Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance. PMID:21873552

Evaluation of high throughput gene expression platforms using a genomic biomarker signature for prediction of skin sensitization.

PubMed

Forreryd, Andy; Johansson, Henrik; Albrekt, Ann-Sofie; Lindstedt, Malin

2014-05-16

Allergic contact dermatitis (ACD) develops upon exposure to certain chemical compounds termed skin sensitizers. To reduce the occurrence of skin sensitizers, chemicals are regularly screened for their capacity to induce sensitization. The recently developed Genomic Allergen Rapid Detection (GARD) assay is an in vitro alternative to animal testing for identification of skin sensitizers, classifying chemicals by evaluating transcriptional levels of a genomic biomarker signature. During assay development and biomarker identification, genome-wide expression analysis was applied using microarrays covering approximately 30,000 transcripts. However, the microarray platform suffers from drawbacks in terms of low sample throughput, high cost per sample and time consuming protocols and is a limiting factor for adaption of GARD into a routine assay for screening of potential sensitizers. With the purpose to simplify assay procedures, improve technical parameters and increase sample throughput, we assessed the performance of three high throughput gene expression platforms--nCounter®, BioMark HD™ and OpenArray®--and correlated their performance metrics against our previously generated microarray data. We measured the levels of 30 transcripts from the GARD biomarker signature across 48 samples. Detection sensitivity, reproducibility, correlations and overall structure of gene expression measurements were compared across platforms. Gene expression data from all of the evaluated platforms could be used to classify most of the sensitizers from non-sensitizers in the GARD assay. Results also showed high data quality and acceptable reproducibility for all platforms but only medium to poor correlations of expression measurements across platforms. In addition, evaluated platforms were superior to the microarray platform in terms of cost efficiency, simplicity of protocols and sample throughput. We evaluated the performance of three non-array based platforms using a limited set of transcripts from the GARD biomarker signature. We demonstrated that it was possible to achieve acceptable discriminatory power in terms of separation between sensitizers and non-sensitizers in the GARD assay while reducing assay costs, simplify assay procedures and increase sample throughput by using an alternative platform, providing a first step towards the goal to prepare GARD for formal validation and adaption of the assay for industrial screening of potential sensitizers.

Active Interfacial Shear Microrheology of Aging Protein Films

PubMed Central

Dhar, Prajnaparamita; Cao, Yanyan; Fischer, Thomas M.; Zasadzinski, J. A.

2012-01-01

The magnetically driven rotation of 300 nm diameter rods shows the surface viscosity of albumin at an air-water interface increases from 10−9 to 10−5 Ns/m over two hours while the surface pressure saturates in minutes. The increase in surface viscosity is not accompanied by a corresponding increase in elasticity, suggesting that the protein film anneals with time, resulting in a more densely packed film leading to increased resistance to shear. The nanometer dimensions of the rods provide the same sensitivity as passive microrheology with an improved ability to measure more viscous films. PMID:20366371

Differential sensitivity to regional-scale drought in six central US grasslands.

PubMed

Knapp, Alan K; Carroll, Charles J W; Denton, Elsie M; La Pierre, Kimberly J; Collins, Scott L; Smith, Melinda D

2015-04-01

Terrestrial ecosystems often vary dramatically in their responses to drought, but the reasons for this are unclear. With climate change forecasts for more frequent and extensive drought in the future, a more complete understanding of the mechanisms that determine differential ecosystem sensitivity to drought is needed. In 2012, the Central US experienced the fourth largest drought in a century, with a regional-scale 40% reduction in growing season precipitation affecting ecosystems ranging from desert grassland to mesic tallgrass prairie. This provided an opportunity to assess ecosystem sensitivity to a drought of common magnitude in six native grasslands. We tested the prediction that drought sensitivity is inversely related to mean annual precipitation (MAP) by quantifying reductions in aboveground net primary production (ANPP). Long-term ANPP data available for each site (mean length = 16 years) were used as a baseline for calculating reductions in ANPP, and drought sensitivity was estimated as the reduction in ANPP per millimeter reduction in precipitation. Arid grasslands were the most sensitive to drought, but drought responses and sensitivity varied by more than twofold among the six grasslands, despite all sites experiencing 40% reductions in growing season precipitation. Although drought sensitivity generally decreased with increasing MAP as predicted, there was evidence that the identity and traits of the dominant species, as well as plant functional diversity, influenced sensitivity. A more comprehensive understanding of the mechanisms leading to differences in drought sensitivity will require multi-site manipulative experiments designed to assess both biotic and abiotic determinants of ecosystem sensitivity.

Light Promotion of Hypocotyl Gravitropism of a Starch-Deficient Tobacco Mutant Correlates with Plastid Enlargement and Sedimentation1

PubMed Central

Vitha, Stanislav; Yang, Ming; Kiss, John Z.; Sack, Fred D.

1998-01-01

Dark-grown hypocotyls of a starch-deficient mutant (NS458) of tobacco (Nicotiana sylvestris) lack amyloplasts and plastid sedimentation, and have severely reduced gravitropism. However, gravitropism improved dramatically when NS458 seedlings were grown in the light. To determine the extent of this improvement and whether mutant hypocotyls contain sedimented amyloplasts, gravitropic sensitivity (induction time and intermittent stimulation) and plastid size and position in the endodermis were measured in seedlings grown for 8 d in the light. Light-grown NS458 hypocotyls were gravitropic but were less sensitive than the wild type (WT). Starch occupied 10% of the volume of NS458 plastids grown in both the light and the dark, whereas WT plastids were essentially filled with starch in both treatments. Light increased plastid size twice as much in the mutant as in the WT. Plastids in light-grown NS458 were sedimented, presumably because of their larger size and greater total starch content. The induction by light of plastid sedimentation in NS458 provides new evidence for the role of plastid mass and sedimentation in stem gravitropic sensing. Because the mutant is not as sensitive as the WT, NS458 plastids may not have sufficient mass to provide full gravitropic sensitivity. PMID:9490754

Functional paper-based SERS substrate for rapid and sensitive detection of Sudan dyes in herbal medicine

NASA Astrophysics Data System (ADS)

Wu, Mianmian; Li, Pan; Zhu, Qingxia; Wu, Meiran; Li, Hao; Lu, Feng

2018-05-01

There has been an increasing demand for rapid and sensitive techniques for the identification of Sudan compounds that emerged as the most often illegally added fat-soluble dyes in herbal medicine. In this report, we have designed and fabricated a functionalized filter paper consisting of gold nanorods (GNRs) and mono-6-thio-cyclodextrin (HS-β-CD) as a surface-enhanced Raman spectroscopy (SERS) substrate, in which the GNR provides sufficient SERS enhancement, and the HS-β-CD with strong chemical affinity toward GNR provides the inclusion compound to capture hydrophobic molecules. Moreover, the CD-GNR were uniformly assembled on filter paper cellulose through the electrostatic adsorption and hydrogen bond, so that the CD-GNR paper-based SERS substrate (CD-GNR-paper) demonstrated higher sensitivity for the determination of Sudan III (0.1 μM) and Sudan IV (0.5 μM) than GNRs paper-based SERS substrate (GNR-paper), with high stability after the storage in the open air for 90 days. Importantly, CD-GNR-paper can effectively collect the Sudan dyes from illegally adulterated onto samples of Resina Draconis with a simple operation, further open up new exciting opportunity for SERS detection of more compounds illegally added with high sensitivity and fast signal responses.

Light promotion of hypocotyl gravitropism of a starch-deficient tobacco mutant correlates with plastid enlargement and sedimentation

NASA Technical Reports Server (NTRS)

Vitha, S.; Yang, M.; Kiss, J. Z.; Sack, F. D.

1998-01-01

Dark-grown hypocotyls of a starch-deficient mutant (NS458) of tobacco (Nicotiana sylvestris) lack amyloplasts and plastid sedimentation, and have severely reduced gravitropism. However, gravitropism improved dramatically when NS458 seedlings were grown in the light. To determine the extent of this improvement and whether mutant hypocotyls contain sedimented amyloplasts, gravitropic sensitivity (induction time and intermittent stimulation) and plastid size and position in the endodermis were measured in seedlings grown for 8 d in the light. Light-grown NS458 hypocotyls were gravitropic but were less sensitive than the wild type (WT). Starch occupied 10% of the volume of NS458 plastids grown in both the light and the dark, whereas WT plastids were essentially filled with starch in both treatments. Light increased plastid size twice as much in the mutant as in the WT. Plastids in light-grown NS458 were sedimented, presumably because of their larger size and greater total starch content. The induction by light of plastid sedimentation in NS458 provides new evidence for the role of plastid mass and sedimentation in stem gravitropic sensing. Because the mutant is not as sensitive as the WT, NS458 plastids may not have sufficient mass to provide full gravitropic sensitivity.

Effects of NCMS on access to care and financial protection in China.

PubMed

Hou, Zhiyuan; Van de Poel, Ellen; Van Doorslaer, Eddy; Yu, Baorong; Meng, Qingyue

2014-08-01

The introduction of the New Cooperative Medical Scheme (NCMS) in rural China has been the most rapid and dramatic extension of health insurance coverage in the developing world in this millennium. The literature to date has mainly used the uneven rollout of NCMS across counties as a way of identifying its effects on access to care and financial protection. This study exploits the cross-county variation in NCMS generosity in 2006 and 2008 in the Ningxia and Shandong provinces to estimate the effect of coverage generosity on utilization and financial protection. Our results confirm earlier findings of NCMS being effective in increasing access to care but not in increasing financial protection. In addition, we find NCMS enrollees to be sensitive to the price incentives set in the NCMS design when choosing their provider and providers to respond by increasing prices and/or providing more expensive care. Copyright © 2013 John Wiley & Sons, Ltd.

Differential Sensitivity to Drought in Six Central U.S. Grasslands

NASA Astrophysics Data System (ADS)

Knapp, A.; Carroll, C. J. W.; Denton, E. M.; La Pierre, K. J.; Wilcox, K. R.; Collins, S. L.; Smith, M.

2014-12-01

Terrestrial ecosystems often vary dramatically in their responses to drought, but the reasons why are unclear. With climate change forecasts for more frequent and extensive drought in the future, a more complete understanding of the mechanisms that determine differential ecosystem sensitivity to drought is needed. In 2012, the Central U.S. experienced the 4th largest drought in a century, with a regional-scale 40% reduction in growing season precipitation affecting ecosystems ranging from desert grassland to mesic tallgrass prairie. This provided an opportunity to assess ecosystem sensitivity to a drought of common magnitude in six native grasslands. We tested the prediction that drought sensitivity is inversely related to mean annual precipitation (MAP) by quantifying reductions in aboveground net primary production (ANPP). Long-term ANPP data available for each site (mean length = 16 yrs) were used as a baseline for calculating reductions in ANPP, and drought sensitivity was estimated as the reduction in ANPP per mm reduction in precipitation. Arid grasslands were the most sensitive to drought, but drought responses and sensitivity varied by more than 2-fold among the six grasslands, despite all sites experiencing 40% reductions in growing season precipitation. Although drought sensitivity generally decreased with increasing MAP as predicted, there was evidence that the identity and traits of the dominant species, as well as plant functional diversity, influenced sensitivity.

Evidence that tRNA modifying enzymes are important in vivo targets for 5-fluorouracil in yeast

PubMed Central

Gustavsson, Marie; Ronne, Hans

2008-01-01

We have screened a collection of haploid yeast knockout strains for increased sensitivity to 5-fluorouracil (5-FU). A total of 138 5-FU sensitive strains were found. Mutants affecting rRNA and tRNA maturation were particularly sensitive to 5-FU, with the tRNA methylation mutant trm10 being the most sensitive mutant. This is intriguing since trm10, like many other tRNA modification mutants, lacks a phenotype under normal conditions. However, double mutants for nonessential tRNA modification enzymes are frequently temperature sensitive, due to destabilization of hypomodified tRNAs. We therefore tested if the sensitivity of our mutants to 5-FU is affected by the temperature. We found that the cytotoxic effect of 5-FU is strongly enhanced at 38°C for tRNA modification mutants. Furthermore, tRNA modification mutants show similar synthetic interactions for temperature sensitivity and sensitivity to 5-FU. A model is proposed for how 5-FU kills these mutants by reducing the number of tRNA modifications, thus destabilizing tRNA. Finally, we found that also wild-type cells are temperature sensitive at higher concentrations of 5-FU. This suggests that tRNA destabilization contributes to 5-FU cytotoxicity in wild-type cells and provides a possible explanation why hyperthermia can enhance the effect of 5-FU in cancer therapy. PMID:18314501

Re-Evaluation of the Role of Starch in Gravitropic Sensing

NASA Technical Reports Server (NTRS)

Sack, Fred D.

1998-01-01

Plant organs grow toward or away from gravity as a way to orient those organs for optimizing growth. Starch has long been thought to be important in sensing the direction of the g-vector in gravitropism, but that hypothesis has also evoked controversy. We have previously shown that starch-deficient mutants of Arabidopsis (TC7) and Nicotiana (NS458) are impaired in their gravitropism. While this suggests that starch is not necessary for reduced gravitropism, it also indicates that the mass of the starch contributes to sensing when present and thus is necessary for full gravitropic sensitivity. The research supported by this grant focused on three related projects, (1) the effect of light on hypocotyl gravitropism in NS458, (2) the effects of root phototropism on measurements of gravitropic sensitivity, and (3) the effects of starch overproduction on sedimentation and gravitropism. Collectively, our results provide additional strong support for the importance of starch in gravitropic sensing. First, by accounting for negative phototropism in roots of two starchless mutants of Arabidopsis we have established that these mutants are much less sensitive to gravity than previously thought. This work also demonstrates the importance of designing experimental protocols that remove the influence of root phototropism on measuring root gravitropism. Second, light apparently promotes gravitropism in starch-deficient Nicotiana hypocotyls by increasing the trace amounts of starch in the plastids, by inducing limited plastid sedimentation and thus by presumably increasing the signal provided by plastid mass. And finally, we show that excess starch in Arabidopsis seedlings has little effect on gravitropic sensitivity implying that the sensing system is already saturated. However, in light-grown stems where this mutation results in starch accumulation and where the wild-type practically lacks starch in the sensing cells, the mutant is much more sensitive than the wild-type again showing that the loss of starch depresses gravity sensing.

Biomarkers of exposure, sensitivity and disease

NASA Technical Reports Server (NTRS)

Brooks, A. L.

1999-01-01

PURPOSE: This review is to evaluate the use of biomarkers as an indication of past exposure to radiation or other environmental insults, individual sensitivity and risk for the development of late occurring disease. OVERVIEW: Biomarkers can be subdivided depending on their applications. Markers of exposure and dose can be used to reconstruct and predict past accidental or occupational exposures when limited or no physical measurements were available. Markers of risk or susceptibility can help identify sensitivity individuals that are at increased risk for development of spontaneous disease and may help predict the increased risk in sensitive individuals associated with environmental or therapeutic radiation exposures. Markers of disease represent the initial cellular or molecular changes that occur during disease development. Each of these types of biomarkers serves a unique purpose. OUTLINE: This paper concentrates on biomarkers of dose and exposure and provides a brief review of biomarkers of sensitivity and disease. The review of biomarkers of dose and exposure will demonstrate the usefulness of biomarkers in evaluation of physical factors associated with radiation exposure, such as LET, doserate and dose distribution. It will also evaluate the use of biomarkers to establish relationships that exist between exposure parameters such as energy deposition, environmental concentration of radioactive materials, alpha traversals and dose. In addition, the importance of biological factors on the magnitude of the biomarker response will be reviewed. Some of the factors evaluated will be the influence of species, tissue, cell types and genetic background. The review will demonstrate that markers of sensitivity and disease often have little usefulness in dose-reconstruction and, by the same token, many markers of dose or exposure may not be applicable for prediction of sensitivity or risk.

Effect of negative emotions evoked by light, noise and taste on trigeminal thermal sensitivity.

PubMed

Yang, Guangju; Baad-Hansen, Lene; Wang, Kelun; Xie, Qiu-Fei; Svensson, Peter

2014-11-07

Patients with migraine often have impaired somatosensory function and experience headache attacks triggered by exogenous stimulus, such as light, sound or taste. This study aimed to assess the influence of three controlled conditioning stimuli (visual, auditory and gustatory stimuli and combined stimuli) on affective state and thermal sensitivity in healthy human participants. All participants attended four experimental sessions with visual, auditory and gustatory conditioning stimuli and combination of all stimuli, in a randomized sequence. In each session, the somatosensory sensitivity was tested in the perioral region with use of thermal stimuli with and without the conditioning stimuli. Positive and Negative Affect States (PANAS) were assessed before and after the tests. Subject based ratings of the conditioning and test stimuli in addition to skin temperature and heart rate as indicators of arousal responses were collected in real time during the tests. The three conditioning stimuli all induced significant increases in negative PANAS scores (paired t-test, P ≤0.016). Compared with baseline, the increases were in a near dose-dependent manner during visual and auditory conditioning stimulation. No significant effects of any single conditioning stimuli were observed on trigeminal thermal sensitivity (P ≥0.051) or arousal parameters (P ≥0.057). The effects of combined conditioning stimuli on subjective ratings (P ≤0.038) and negative affect (P = 0.011) were stronger than those of single stimuli. All three conditioning stimuli provided a simple way to evoke a negative affective state without physical arousal or influence on trigeminal thermal sensitivity. Multisensory conditioning had stronger effects but also failed to modulate thermal sensitivity, suggesting that so-called exogenous trigger stimuli e.g. bright light, noise, unpleasant taste in patients with migraine may require a predisposed or sensitized nervous system.

Challenges in Routine Implementation and Quality Control of Rapid Diagnostic Tests for Malaria–Rufiji District, Tanzania

PubMed Central

McMorrow, Meredith L.; Masanja, M. Irene; Abdulla, Salim M. K.; Kahigwa, Elizeus; Kachur, S. Patrick

2018-01-01

Rapid diagnostic tests (RDTs) represent an alternative to microscopy for malaria diagnosis and have shown high sensitivity and specificity in a variety of study settings. Current World Health Organization (WHO) guidelines for quality control of RDTs provide detailed instructions on pre-field testing, but offer little guidance for quality assurance once RDTs are deployed in health facilities. From September 2006 to April 2007, we introduced a histidine-rich protein II (HRP2)-based RDT (Paracheck) for suspected malaria cases five years of age and older in nine health facilities in Rufiji District, Tanzania, to assess sensitivity and specificity of RDTs in routine use at rural health facilities. Thick blood smears were collected for all patients tested with RDTs and stained and read by laboratory personnel in each facility. Thick smears were subsequently reviewed by a reference microscopist to determine RDT sensitivity and specificity. In all nine health facilities, there were significant problems with the quality of staining and microscopy. Sensitivity and specificity of RDTs were difficult to assess given the poor quality of routine blood smear staining. Mean operational sensitivity of RDTs based on reference microscopy was 64.8%, but varied greatly by health facility, range 18.8–85.9%. Sensitivity of RDTs increased with increasing parasite density. Specificity remained high at 87.8% despite relatively poor slide quality. Institution of quality control of RDTs based on poor quality blood smear staining may impede reliable measurement of sensitivity and specificity and undermine confidence in the new diagnostic. There is an urgent need for the development of alternative quality control procedures for rapid diagnostic tests that can be performed at the facility level. PMID:18784230

VARS-TOOL: A Comprehensive, Efficient, and Robust Sensitivity Analysis Toolbox

NASA Astrophysics Data System (ADS)

Razavi, S.; Sheikholeslami, R.; Haghnegahdar, A.; Esfahbod, B.

2016-12-01

VARS-TOOL is an advanced sensitivity and uncertainty analysis toolbox, applicable to the full range of computer simulation models, including Earth and Environmental Systems Models (EESMs). The toolbox was developed originally around VARS (Variogram Analysis of Response Surfaces), which is a general framework for Global Sensitivity Analysis (GSA) that utilizes the variogram/covariogram concept to characterize the full spectrum of sensitivity-related information, thereby providing a comprehensive set of "global" sensitivity metrics with minimal computational cost. VARS-TOOL is unique in that, with a single sample set (set of simulation model runs), it generates simultaneously three philosophically different families of global sensitivity metrics, including (1) variogram-based metrics called IVARS (Integrated Variogram Across a Range of Scales - VARS approach), (2) variance-based total-order effects (Sobol approach), and (3) derivative-based elementary effects (Morris approach). VARS-TOOL is also enabled with two novel features; the first one being a sequential sampling algorithm, called Progressive Latin Hypercube Sampling (PLHS), which allows progressively increasing the sample size for GSA while maintaining the required sample distributional properties. The second feature is a "grouping strategy" that adaptively groups the model parameters based on their sensitivity or functioning to maximize the reliability of GSA results. These features in conjunction with bootstrapping enable the user to monitor the stability, robustness, and convergence of GSA with the increase in sample size for any given case study. VARS-TOOL has been shown to achieve robust and stable results within 1-2 orders of magnitude smaller sample sizes (fewer model runs) than alternative tools. VARS-TOOL, available in MATLAB and Python, is under continuous development and new capabilities and features are forthcoming.

Reduced mtDNA copy number increases the sensitivity of tumor cells to chemotherapeutic drugs.

PubMed

Mei, H; Sun, S; Bai, Y; Chen, Y; Chai, R; Li, H

2015-04-02

Many cancer drugs are toxic to cells by activating apoptotic pathways. Previous studies have shown that mitochondria have key roles in apoptosis in mammalian cells, but the role of mitochondrial DNA (mtDNA) copy number variation in the pathogenesis of tumor cell apoptosis remains largely unknown. We used the HEp-2, HNE2, and A549 tumor cell lines to explore the relationship between mtDNA copy number variation and cell apoptosis. We first induced apoptosis in three tumor cell lines and one normal adult human skin fibroblast cell line (HSF) with cisplatin (DDP) or doxorubicin (DOX) treatment and found that the mtDNA copy number significantly increased in apoptotic tumor cells, but not in HSF cells. We then downregulated the mtDNA copy number by transfection with shRNA-TFAM plasmids or treatment with ethidium bromide and found that the sensitivity of tumor cells to DDP or DOX was significantly increased. Furthermore, we observed that levels of reactive oxygen species (ROS) increased significantly in tumor cells with lower mtDNA copy numbers, and this might be related to a low level of antioxidant gene expression. Finally, we rescued the increase of ROS in tumor cells with lipoic acid or N-acetyl-L-cysteine and found that the apoptosis rate decreased. Our studies suggest that the increase of mtDNA copy number is a self-protective mechanism of tumor cells to prevent apoptosis and that reduced mtDNA copy number increases ROS levels in tumor cells, increases the tumor cells' sensitivity to chemotherapeutic drugs, and increases the rate of apoptosis. This research provides evidence that mtDNA copy number variation might be a promising new therapeutic target for the clinical treatment of tumors.

Testing the woman abuse screening tool to identify intimate partner violence in Indonesia.

PubMed

Iskandar, Livia; Braun, Kathryn L; Katz, Alan R

2015-04-01

Intimate Partner Violence (IPV) is a global public health problem. IPV prevalence in Indonesia has been estimated to be less than 1%, based on reported cases. It is likely that IPV prevalence is underreported in Indonesia, as it is in many other countries. Screening for IPV has been found to increase IPV identification, but no screening tools are in use in Indonesia. The aim of this study was to test the translated Woman Abuse Screening Tool (WAST) for detecting IPV in Indonesia. The WAST was tested against a diagnostic interview by a trained psychologist on 240 women attending two Primary Health Centers in Jakarta. IPV prevalence and the reliability, sensitivity, and specificity of the WAST were estimated. Prevalence of IPV by diagnostic interview was 36.3%, much higher than published estimates. The most common forms of IPV identified were psychological (85%) and physical abuse (24%). Internal reliability of the WAST was high (α = .801). A WAST score of 13 (out of 24) is the recommended cutoff for identifying IPV, but only 17% of the Indonesian sample scored 13 or higher. Test sensitivity of the WAST with a cutoff score of 13 was only 41.9%, with a specificity of 96.8%. With a cutoff score of 10, the sensitivity improved to 84.9%, while the specificity decreased to 61.0%. Use of the WAST with a cutoff score of 10 provides good sensitivity and reasonable specificity and would provide a much-needed screening tool for use in Indonesia. Although a lower cutoff would yield a greater proportion of false positives, most of the true cases would be identified, increasing the possibility that women experiencing abuse would receive needed assistance. © The Author(s) 2014.

EBUS-Guided Cautery-Assisted Transbronchial Forceps Biopsies: Safety and Sensitivity Relative to Transbronchial Needle Aspiration

PubMed Central

Bramley, Kyle; Pisani, Margaret A.; Murphy, Terrence E.; Araujo, Katy; Homer, Robert; Puchalski, Jonathan

2016-01-01

Background EBUS-guided transbronchial needle aspiration (TBNA) is important in the evaluation of thoracic lymphadenopathy. Reliably providing excellent diagnostic yield for malignancy, its diagnosis of sarcoidosis is inconsistent. Furthermore, when larger “core” biopsy samples of malignant tissue are required, TBNA may not suffice. The primary objective of this study was to determine if the sequential use of TBNA and a novel technique called cautery-assisted transbronchial forceps biopsies (ca-TBFB) was safe. Secondary outcomes included sensitivity and successful acquisition of tissue. Methods Fifty unselected patients undergoing convex probe EBUS were prospectively enrolled. Under EBUS guidance, all lymph nodes ≥ 1 cm were sequentially biopsied using TBNA and ca-TBFB. Safety and sensitivity were assessed at the nodal level for 111 nodes. Results of each technique were also reported on a per-patient basis. Results There were no significant adverse events. In nodes determined to be malignant, TBNA provided higher sensitivity (100%) than ca-TBFB (78%). However, among nodes with granulomatous inflammation, ca-TBFB exhibited higher sensitivity (90%) than TBNA (33%). For analysis based on patients rather than nodes, 6 of the 31 patients with malignancy would have been missed or understaged if the diagnosis was based on samples obtained by ca-TBFB. On the other hand, 3 of 8 patients with sarcoidosis would have been missed if analysis was based only on TBNA samples. In some cases only ca-TBFB acquired sufficient tissue for the core samples needed in clinical trials of malignancy. Conclusions The sequential use of TBNA and ca-TBFB appears to be safe. The larger samples obtained from ca-TBFB increased its sensitivity to detect granulomatous disease and provided specimens for clinical trials of malignancy when needle biopsies were insufficient. For thoracic surgeons and advanced bronchoscopists, we advocate ca-TBFB as an alternative to TBNA in select clinical scenarios. PMID:26912301

Endobronchial Ultrasound-Guided Cautery-Assisted Transbronchial Forceps Biopsies: Safety and Sensitivity Relative to Transbronchial Needle Aspiration.

PubMed

Bramley, Kyle; Pisani, Margaret A; Murphy, Terrence E; Araujo, Katy L; Homer, Robert J; Puchalski, Jonathan T

2016-05-01

Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is important in the evaluation of thoracic lymphadenopathy. Reliably providing excellent diagnostic yield for malignancy, its diagnosis of sarcoidosis is inconsistent. Furthermore, TBNA may not suffice when larger "core biopsy" samples of malignant tissue are required. The primary objective of this study was to determine if the sequential use of TBNA and a novel technique called cautery-assisted transbronchial forceps biopsy (ca-TBFB) was safe. Secondary outcomes included sensitivity and successful acquisition of tissue. The study prospectively enrolled 50 unselected patients undergoing convex-probe EBUS. All lymph nodes exceeding 1 cm were sequentially biopsied under EBUS guidance using TBNA and ca-TBFB. Safety and sensitivity were assessed at the nodal level for 111 nodes. Results of each technique were also reported for each patient. There were no significant adverse events. In nodes determined to be malignant, TBNA provided higher sensitivity (100%) than ca-TBFB (78%). However, among nodes with granulomatous inflammation, ca-TBFB exhibited higher sensitivity (90%) than TBNA (33%). On the one hand, for analysis based on patients rather than nodes, 6 of the 31 patients with malignancy would have been missed or understaged if the diagnosis were based on samples obtained by ca-TBFB. On the other hand, 3 of 8 patients with sarcoidosis would have been missed if analysis were based only on TBNA samples. In some patients, only ca-TBFB acquired sufficient tissue for the core samples needed in clinical trials of malignancy. The sequential use of TBNA and ca-TBFB appears to be safe. The larger samples obtained from ca-TBFB increased its sensitivity to detect granulomatous disease and provided adequate specimens for clinical trials of malignancy when specimens from needle biopsies were insufficient. For thoracic surgeons and advanced bronchoscopists, we advocate ca-TBFB as an alternative to TBNA in select clinical scenarios. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Preparation of dual-stimuli-responsive liposomes using methacrylate-based copolymers with pH and temperature sensitivities for precisely controlled release.

PubMed

Sugimoto, Takumi; Yamazaki, Naoko; Hayashi, Takaaki; Yuba, Eiji; Harada, Atsushi; Kotaka, Aki; Shinde, Chiharu; Kumei, Takayuki; Sumida, Yasushi; Fukushima, Mitsuhiro; Munekata, Yuki; Maruyama, Keiichi; Kono, Kenji

2017-07-01

Dual-signal-sensitive copolymers were synthesized by copolymerization of methoxy diethylene glycol methacrylate, methacrylic acid, and lauroxy tetraethylene glycol methacrylate, which respectively provide temperature sensitivity, pH sensitivity, and anchoring to liposome surfaces. These novel copolymers, with water solubility that differs depending on temperature and pH, are soluble in water under neutral pH and low-temperature conditions, but they become water-insoluble and form aggregates under acidic pH and high-temperature conditions. Liposomes modified with these copolymers exhibited enhanced content release at weakly acidic pH with increasing temperature, although no temperature-dependent content release was observed in neutral conditions. Interaction between the copolymers and the lipid monolayer at the air-water interface revealed that the copolymer chains penetrate more deeply into the monolayer with increasing temperature at acidic pH than at neutral pH, where the penetration of copolymer chains was moderate and temperature-independent at neutral pH. Interaction of the copolymer-modified liposomes with HeLa cells demonstrated that the copolymer-modified liposomes were adsorbed quickly and efficiently onto the cell surface and that they were internalized more gradually than the unmodified liposomes through endocytosis. Furthermore, the copolymer-modified liposomes enhanced the content release in endosomes with increasing temperature, but no such temperature-dependent enhancement of content release was observed for unmodified liposomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Money for microbes-Pathogen avoidance and out-group helping behaviour.

PubMed

Laakasuo, Michael; Köbis, Nils; Palomäki, Jussi; Jokela, Markus

2017-02-23

Humans have evolved various adaptations against pathogens, including the physiological immune system. However, not all of these adaptations are physiological: the cognitive mechanisms whereby we avoid potential sources of pathogens-for example, disgust elicited by uncleanliness-can be considered as parts of a behavioural immune system (BIS). The mechanisms of BIS extend also to inter-group relations: Pathogen cues have been shown to increase xenophobia/ethnocentrism, as people prefer to keep their societal in-group norms unaltered and "clean." Nonetheless, little is known how pathogen cues influence people's willingness to provide humanitarian aid to out-group members. We examined how pathogen cues affected decisions of providing humanitarian aid in either instrumental (sending money) or non-instrumental form (sending personnel to help, or accepting refugees), and whether these effects were moderated by individual differences in BIS sensitivity. Data were collected in two online studies (Ns: 188 and 210). When the hypothetical humanitarian crisis involved a clear risk of infection, participants with high BIS sensitivity preferred to send money rather than personnel or to accept refugees. The results suggest that pathogen cues influence BIS-sensitive individuals' willingness to provide humanitarian aid when there is a risk of contamination to in-group members. © 2017 International Union of Psychological Science.

Does the stress tolerance of mixed grassland communities change in a future climate? A test with heavy metal stress (zinc pollution).

PubMed

Van den Berge, Joke; Naudts, Kim; Janssens, Ivan A; Ceulemans, Reinhart; Nijs, Ivan

2011-12-01

Will species that are sensitive/tolerant to Zn pollution still have the same sensitivity/tolerance in a future climate? To answer this question we analysed the response of constructed grassland communities to five levels of zinc (Zn) supply, ranging from 0 to 354 mg Zn kg(-1) dry soil, under a current climate and a future climate (elevated CO2 and warming). Zn concentrations increased in roots and shoots with Zn addition but this increase did not differ between climates. Light-saturated net CO2 assimilation rate (A(sat)) of the species, on the other hand, responded differently to Zn addition depending on climate. Still, current and future climate communities have comparable biomass responses to Zn, i.e., no change in root biomass and a 13% decrease of above-ground biomass. Provided that the different response of A(sat) in a future climate will not compromise productivity and survival on the long term, sensitivity is not altered by climate change. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Tamper-Resistant and Portable Healthcare Folder

PubMed Central

Anciaux, Nicolas; Berthelot, Morgane; Braconnier, Laurent; Bouganim, Luc; De la Blache, Martine; Gardarin, Georges; Kesmarszky, Philippe; Lartigue, Sophie; Navarre, Jean-François; Pucheral, Philippe; Vandewalle, Jean-Jacques; Zeitouni, Karine

2008-01-01

Electronic health record (EHR) projects have been launched in most developed countries to increase the quality of healthcare while decreasing its cost. The benefits provided by centralizing the healthcare information in database systems are unquestionable in terms of information quality, availability, and protection against failure. Yet, patients are reluctant to give to a distant server the control over highly sensitive data (e.g., data revealing a severe or shameful disease). This paper capitalizes on a new hardware portable device, associating the security of a smart card to the storage capacity of a USB key, to give back to the patient the control over his medical data. This paper shows how this device can complement a traditional EHR server to (1) protect and share highly sensitive data among trusted parties and (2) provide a seamless access to the data even in disconnected mode. The proposed architecture is experimented in the context of a medicosocial network providing medical care and social services at home for elderly people. PMID:18615200

Hyperspectral imaging with near-infrared-enabled mobile phones for tissue oximetry

NASA Astrophysics Data System (ADS)

Lin, Jonathan L.; Ghassemi, Pejhman; Chen, Yu; Pfefer, Joshua

2018-02-01

Hyperspectral reflectance imaging (HRI) is an emerging clinical tool for characterizing spatial and temporal variations in blood perfusion and oxygenation for applications such as burn assessment, wound healing, retinal exams and intraoperative tissue viability assessment. Since clinical HRI-based oximeters often use near-infrared (NIR) light, NIR-enabled mobile phones may provide a useful platform for future point-of-care devices. Furthermore, quantitative NIR imaging on mobile phones may dramatically increase the availability and accessibility of medical diagnostics for low-resource settings. We have evaluated the potential for phone-based NIR oximetry imaging and elucidated factors affecting performance using devices from two different manufacturers, as well as a scientific CCD. A broadband light source and liquid crystal tunable filter were used for imaging at 10 nm bands from 650 to 1000 nm. Spectral sensitivity measurements indicated that mobile phones with standard NIR blocking filters had minimal response beyond 700 nm, whereas one modified phone showed sensitivity to 800 nm and another to 1000 nm. Red pixel channels showed the greatest sensitivity up to 800 nm, whereas all channels provided essentially equivalent sensitivity at longer wavelengths. Referencing of blood oxygenation levels was performed with a CO-oximeter. HRI measurements were performed using cuvettes filled with hemoglobin solutions of different oxygen saturation levels. Good agreement between absorbance spectra measured with mobile phone and a CCD cameras were seen for wavelengths below 900 nm. Saturation estimates showed root-mean-squared-errors of 5.2% and 4.5% for the CCD and phone, respectively. Overall, this work provides strong evidence of the potential for mobile phones to provide quantitative spectral imaging in the NIR for applications such as oximetry, and generates practical insights into factors that impact performance as well as test methods for performance assessment.

Flying high: a theoretical analysis of the factors limiting exercise performance in birds at altitude.

PubMed

Scott, Graham R; Milsom, William K

2006-11-01

The ability of some bird species to fly at extreme altitude has fascinated comparative respiratory physiologists for decades, yet there is still no consensus about what adaptations enable high altitude flight. Using a theoretical model of O(2) transport, we performed a sensitivity analysis of the factors that might limit exercise performance in birds. We found that the influence of individual physiological traits on oxygen consumption (Vo2) during exercise differed between sea level, moderate altitude, and extreme altitude. At extreme altitude, haemoglobin (Hb) O(2) affinity, total ventilation, and tissue diffusion capacity for O(2) (D(To2)) had the greatest influences on Vo2; increasing these variables should therefore have the greatest adaptive benefit for high altitude flight. There was a beneficial interaction between D(To2) and the P(50) of Hb, such that increasing D(To2) had a greater influence on Vo2 when P(50) was low. Increases in the temperature effect on P(50) could also be beneficial for high flying birds, provided that cold inspired air at extreme altitude causes a substantial difference in temperature between blood in the lungs and in the tissues. Changes in lung diffusion capacity for O(2), cardiac output, blood Hb concentration, the Bohr coefficient, or the Hill coefficient likely have less adaptive significance at high altitude. Our sensitivity analysis provides theoretical suggestions of the adaptations most likely to promote high altitude flight in birds and provides direction for future in vivo studies.

Role of deposition and annealing of the top gate dielectric in a-IGZO TFT-based dual-gate ion-sensitive field-effect transistors

NASA Astrophysics Data System (ADS)

Kumar, Narendra; Sutradhar, Moitri; Kumar, Jitendra; Panda, Siddhartha

2017-03-01

The deposition of the top gate dielectric in thin film transistor (TFT)-based dual-gate ion-sensitive field-effect transistors (DG ISFETs) is critical, and expected not to affect the bottom gate TFT characteristics, while providing a higher pH sensitive surface and efficient capacitive coupling between the gates. Amorphous Ta2O5, in addition to having good sensing properties, possesses a high dielectric constant of ˜25 making it well suited as the top gate dielectric in a DG ISFET by providing higher capacitive coupling (ratio of C top/C bottom) leading to higher amplification. To avoid damage of the a-IGZO channel reported to be caused by plasma exposure, deposition of Ta2O5 by e-beam evaporation followed by annealing was investigated in this work to obtain sensitivity over the Nernst limit. The deteriorated bottom gate TFT characteristics, indicated by an increase in the channel conductance, confirmed that plasma exposure is not the sole contributor to the changes. Oxygen vacancies at the Ta2O5/a-IGZO interface, which emerged during processing, increased the channel conductivity, became filled by optimum annealing in oxygen at 400 °C for 1 h, which was confirmed by an x-ray photoelectron spectroscopy depth profiling analysis. The obtained pH sensitivity of the TFT-based DG ISFET was 402 mV pH-1, which is about 6.8 times the Nernst limit (59 mV pH-1). The concept of capacitive coupling was also demonstrated by simulating an a-IGZO-based DG TFT structure. Here, the exposure of the top gate dielectric to the electrolyte without applying any top gate bias led to changes in the measured threshold voltage of the bottom gate TFT, and this obviated the requirement of a reference electrode needed in conventional ISFETs and other reported DG ISFETs. These devices, with high sensitivities and requiring low volumes (˜2 μl) of analyte solution, could be potential candidates for utilization as chemical sensors and biosensors.

PDE 5 inhibitor improves insulin sensitivity by enhancing mitochondrial function in adipocytes.

PubMed

Yu, Hea Min; Chung, Hyo Kyun; Kim, Koon Soon; Lee, Jae Min; Hong, Jun Hwa; Park, Kang Seo

2017-11-04

Adipocytes are involved in many metabolic disorders. It was recently reported that phosphodiesterase type 5 (PDE5) is expressed in human adipose tissue. In addition, PDE5 inhibitors have been shown to improve insulin sensitivity in humans. However, the mechanism underlying the role of PDE5 inhibitors as an insulin sensitizer remains largely unknown. The present study was undertaken to investigate the role of the PDE5 inhibitor udenafil in insulin signaling in adipocytes and whether this is mediated through the regulation of mitochondrial function. To study the mechanism underlying the insulin sensitizing action of PDE5 inhibitors, we evaluated quantitative changes in protein or mRNA levels of mitochondrial oxidative phosphorylation (OxPhos) complex, oxygen consumption rate (OCR), and fatty acid oxidation with varying udenafil concentrations in 3T3-L1 cells. Our cell study suggested that udenafil enhanced the insulin signaling pathway in 3T3-L1 cells. Following udenafil treatment, basal mitochondrial OCR, maximal OxPhos capacity, and OxPhos gene expression significantly increased. Finally, we examined whether udenafil can affect the fatty acid oxidation process. Treatment of 3T3-L1 cells with udenafil (10 and 20 μM) significantly increased fatty acid oxidation rate in a dose-dependent manner. In addition, the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) significantly increased. We demonstrated that the PDE5 inhibitor udenafil enhances insulin sensitivity by improving mitochondrial function in 3T3-L1 cells. This might be the mechanism underlying the PDE5 inhibitor-enhanced insulin signaling in adipocytes. This also suggests that udenafil may provide benefit in the treatment of type 2 diabetes and other related cardiovascular diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Sexual behavior induction of c-Fos in the nucleus accumbens and amphetamine-stimulated locomotor activity are sensitized by previous sexual experience in female Syrian hamsters.

PubMed

Bradley, K C; Meisel, R L

2001-03-15

Dopamine transmission in the nucleus accumbens can be activated by drugs, stress, or motivated behaviors, and repeated exposure to these stimuli can sensitize this dopamine response. The objectives of this study were to determine whether female sexual behavior activates nucleus accumbens neurons and whether past sexual experience cross-sensitizes neuronal responses in the nucleus accumbens to amphetamine. Using immunocytochemical labeling, c-Fos expression in different subregions (shell vs core at the rostral, middle, and caudal levels) of the nucleus accumbens was examined in female hamsters that had varying amounts of sexual experience. Female hamsters, given either 6 weeks of sexual experience or remaining sexually naive, were tested for sexual behavior by exposure to adult male hamsters. Previous sexual experience increased c-Fos labeling in the rostral and caudal levels but not in the middle levels of the nucleus accumbens. Testing for sexual behavior increased labeling in the core, but not the shell, of the nucleus accumbens. To validate that female sexual behavior can sensitize neurons in the mesolimbic dopamine pathway, the locomotor responses of sexually experienced and sexually naive females to an amphetamine injection were then compared. Amphetamine increased general locomotor activity in all females. However, sexually experienced animals responded sooner to amphetamine than did sexually naive animals. These data indicate that female sexual behavior can activate neurons in the nucleus accumbens and that sexual experience can cross-sensitize neuronal responses to amphetamine. In addition, these results provide additional evidence for functional differences between the shell and core of the nucleus accumbens and across its anteroposterior axis.

Overexpression of heat shock protein 27 (HSP27) increases gemcitabine sensitivity in pancreatic cancer cells through S-phase arrest and apoptosis

PubMed Central

Guo, Yang; Ziesch, Andreas; Hocke, Sandra; Kampmann, Eric; Ochs, Stephanie; De Toni, Enrico N; Göke, Burkhard; Gallmeier, Eike

2015-01-01

We previously established a role for HSP27 as a predictive marker for therapeutic response towards gemcitabine in pancreatic cancer. Here, we investigate the underlying mechanisms of HSP27-mediated gemcitabine sensitivity. Utilizing a pancreatic cancer cell model with stable HSP27 overexpression, cell cycle arrest and apoptosis induction were analysed by flow cytometry, nuclear staining, immunoblotting and mitochondrial staining. Drug sensitivity studies were performed by proliferation assays. Hyperthermia was simulated using mild heat shock at 41.8°C. Upon gemcitabine treatment, HSP27-overexpressing cells displayed an early S-phase arrest subsequently followed by a strongly increased sub-G1 fraction. Apoptosis was characterized by PARP-, CASPASE 3-, CASPASE 8-, CASPASE 9- and BIM- activation along with a mitochondrial membrane potential loss. It was reversible through chemical caspase inhibition. Importantly, gemcitabine sensitivity and PARP cleavage were also elicited by heat shock-induced HSP27 overexpression, although to a smaller extent, in a panel of pancreatic cancer cell lines. Finally, HSP27-overexpressing pancreatic cancer cells displayed an increased sensitivity also towards death receptor-targeting agents, suggesting another pro-apoptotic role of HSP27 along the extrinsic apoptosis pathway. Taken together, in contrast to the well-established anti-apoptotic properties of HSP27 in cancer, our study reveals novel pro-apoptotic functions of HSP27—mediated through both the intrinsic and the extrinsic apoptotic pathways—at least in pancreatic cancer cells. HSP27 could represent a predictive marker of therapeutic response towards specific drug classes in pancreatic cancer and provides a novel molecular rationale for current clinical trials applying the combination of gemcitabine with regional hyperthermia in pancreatic cancer patients. PMID:25331547

Intra-population variability of ocean acidification impacts on the physiology of Baltic blue mussels (Mytilus edulis): integrating tissue and organism response.

PubMed

Stapp, L S; Thomsen, J; Schade, H; Bock, C; Melzner, F; Pörtner, H O; Lannig, G

2017-05-01

Increased maintenance costs at cellular, and consequently organism level, are thought to be involved in shaping the sensitivity of marine calcifiers to ocean acidification (OA). Yet, knowledge of the capacity of marine calcifiers to undergo metabolic adaptation is sparse. In Kiel Fjord, blue mussels thrive despite periodically high seawater PCO 2 , making this population interesting for studying metabolic adaptation under OA. Consequently, we conducted a multi-generation experiment and compared physiological responses of F1 mussels from 'tolerant' and 'sensitive' families exposed to OA for 1 year. Family classifications were based on larval survival; tolerant families settled at all PCO 2 levels (700, 1120, 2400 µatm) while sensitive families did not settle at the highest PCO 2 (≥99.8% mortality). We found similar filtration rates between family types at the control and intermediate PCO 2 level. However, at 2400 µatm, filtration and metabolic scope of gill tissue decreased in tolerant families, indicating functional limitations at the tissue level. Routine metabolic rates (RMR) and summed tissue respiration (gill and outer mantle tissue) of tolerant families were increased at intermediate PCO 2 , indicating elevated cellular homeostatic costs in various tissues. By contrast, OA did not affect tissue and routine metabolism of sensitive families. However, tolerant mussels were characterised by lower RMR at control PCO 2 than sensitive families, which had variable RMR. This might provide the energetic scope to cover increased energetic demands under OA, highlighting the importance of analysing intra-population variability. The mechanisms shaping such difference in RMR and scope, and thus species' adaptation potential, remain to be identified.

The disinhibitory zone of the striate neuron receptive field and its sensitivity to cross-like figures.

PubMed

Lazareva, N A; Shevelev, I A; Novikova, R V; Tikhomirov, A S; Sharaev, G A; Tsutskiridze, D Yu

2002-01-01

Acute experiments on immobilized anesthetized cats were used to confirm the suggestion that the sensitivity of many neurons on the primary visual cortex to cross-shaped, angular, and Y-shaped figures may be determined by the presence within their receptive fields of disinhibitory zones, which block end-stopping inhibition. A total of 55 neurons (84 functions, i.e.. on and off responses) were used for studies of sensitivity to crosses, and responses to single bars of different lengths were compared before and after stimulation of an additional lateral zone of the field (the presumptive disinhibitory zone), which was located in terms of responses to crosses. Seventeen of the 55 cells in which increases in the length of a single bar decreased responses, i.e., which demonstrated end-stopping inhibition, showed significant increases in responses (by an average factor of 2.06 +/- 0.16) during simultaneous stimulation of the lateral zone of the receptive field, which we interpreted as a disinhibitory effect on end-stopping inhibition. These data provide the first direct evidence for the role of end-stopping inhibition and its blockade by the disinhibitory zone of the receptive field in determining the sensitivity of some neurons in the primary visual cortex of the cat to cross-shaped figures.

Novel nanoarchitectures for electrochemical biosensing

NASA Astrophysics Data System (ADS)

Archibald, Michelle M.

Sensitive, real-time detection of biomarkers is of critical importance for rapid and accurate diagnosis of disease for point-of-care (POC) technologies. Current methods, while sensitive, do not adequately allow for POC applications due to several limitations, including complex instrumentation, high reagent consumption, and cost. We have investigated two novel nanoarchitectures, the nanocoax and the nanodendrite, as electrochemical biosensors towards the POC detection of infectious disease biomarkers to overcome these limitations. The nanocoax architecture is composed of vertically-oriented, nanoscale coaxial electrodes, with coax cores and shields serving as integrated working and counter electrodes, respectively. The dendritic structure consists of metallic nanocrystals extending from the working electrode, increasing sensor surface area. Nanocoaxial- and nanodendritic-based electrochemical sensors were fabricated and developed for the detection of bacterial toxins using an electrochemical enzyme-linked immunosorbent assay (ELISA) and differential pulse voltammetry (DPV). Proof-of-concept was demonstrated for the detection of cholera toxin (CT). Both nanoarchitectures exhibited levels of sensitivity that are comparable to the standard optical ELISA used widely in clinical applications. In addition to matching the detection profile of the standard ELISA, these electrochemical nanosensors provide a simple electrochemical readout and a miniaturized platform with multiplexing capabilities toward POC implementation. Further development as suggested in this thesis may lead to increases in sensitivity, enhancing the attractiveness of the architectures for future POC devices.

Drought tolerance, xylem sap abscisic acid and stomatal conductance during soil drying: a comparison of young plants of four temperate deciduous angiosperms.

PubMed

Loewenstein, Nancy J.; Pallardy, Stephen G.

1998-07-01

Patterns of water relations, xylem sap abscisic acid (ABA) concentration ([ABA]) and stomatal aperture were compared in drought-sensitive black walnut (Juglans nigra L.) and black willow (Salix nigra Marsh.), less drought-sensitive sugar maple (Acer saccharum Marsh.) and drought-tolerant white oak (Quercus alba L.). Strong correlations among reduction in predawn water potential, increase in xylem sap [ABA] and stomatal closure were observed in all species. Stomatal response was more highly correlated with xylem [ABA] than with ABA flux. Xylem sap pH and ion concentrations appeared not to play a major role in the stomatal response of these species. Stomata were more sensitive to relative changes in [ABA] in drought-sensitive black walnut and black willow than in sugar maple and white oak. In the early stages of drought, increased [ABA] in the xylem sap of black walnut and black willow was probably of root origin and provided a signal to the shoot of the water status of the roots. In sugar maple and white oak, leaf water potential declined with the onset of stomatal closure, so that stomatal closure also may have occurred in response to the change in leaf water potential.

Measurement of vibration-induced volumetric strain in the human lung.

PubMed

Hirsch, Sebastian; Posnansky, Oleg; Papazoglou, Sebastian; Elgeti, Thomas; Braun, Jürgen; Sack, Ingolf

2013-03-01

Noninvasive image-based measurement of intrinsic tissue pressure is of great interest in the diagnosis and characterization of diseases. Therefore, we propose to exploit the capability of phase-contrast MRI to measure three-dimensional vector fields of tissue motion for deriving volumetric strain induced by external vibration. Volumetric strain as given by the divergence of mechanical displacement fields is related to tissue compressibility and is thus sensitive to the state of tissue pressure. This principle is demonstrated by the measurement of three-dimensional vector fields of 50-Hz oscillations in a compressible agarose phantom and in the lungs of nine healthy volunteers. In the phantom, the magnitude of the oscillating divergence increased by about 400% with 4.8 bar excess air pressure, corresponding to an effective-medium compression modulus of 230 MPa. In lungs, the averaged divergence magnitude increased in all volunteers (N = 9) between 7 and 78% from expiration to inspiration. Measuring volumetric strain by MRI provides a compression-sensitive parameter of tissue mechanics, which varies with the respiratory state in the lungs. In future clinical applications for diagnosis and characterization of lung emphysema, fibrosis, or cancer, divergence-sensitive MRI may serve as a noninvasive marker sensitive to disease-related alterations of regional elastic recoil pressure in the lungs. Copyright © 2012 Wiley Periodicals, Inc.

Between- and within-lake responses of macrophyte richness metrics to shoreline developmen

USGS Publications Warehouse

Beck, Marcus W.; Vondracek, Bruce C.; Hatch, Lorin K.

2013-01-01

Aquatic habitat in littoral environments can be affected by residential development of shoreline areas. We evaluated the relationship between macrophyte richness metrics and shoreline development to quantify indicator response at 2 spatial scales for Minnesota lakes. First, the response of total, submersed, and sensitive species to shoreline development was evaluated within lakes to quantify macrophyte response as a function of distance to the nearest dock. Within-lake analyses using generalized linear mixed models focused on 3 lakes of comparable size with a minimal influence of watershed land use. Survey points farther from docks had higher total species richness and presence of species sensitive to disturbance. Second, between-lake effects of shoreline development on total, submersed, emergent-floating, and sensitive species were evaluated for 1444 lakes. Generalized linear models were developed for all lakes and stratified subsets to control for lake depth and watershed land use. Between-lake analyses indicated a clear response of macrophyte richness metrics to increasing shoreline development, such that fewer emergent-floating and sensitive species were correlated with increasing density of docks. These trends were particularly evident for deeper lakes with lower watershed development. Our results provide further evidence that shoreline development is associated with degraded aquatic habitat, particularly by illustrating the response of macrophyte richness metrics across multiple lake types and different spatial scales.

Determinants of total and specific IgE in infants with atopic dermatitis. ETAC Study Group. Early Treatment of the Atopic Child.

PubMed

1997-11-01

ETAC (Early Treatment of the Atopic Child), a multi-centre predominantly European study to investigate the potential for cetirizine to prevent the development of asthma in infants with atopic dermatitis has completed enrollment: 817 children have been randomised to 18 months' treatment with either active or placebo and a subsequent 18 months of post-treatment follow-up. Results of the therapeutic effects will not be available for some time, but the study has provided an opportunity to investigate influences on sensitization to allergens in a large cohort of 1-2 years olds with already established atopic dermatitis, resident in different countries and in different environments. The study shows that in infants with atopic dermatitis, raised serum total IgE has significantly different determinants from that a specific allergen sensitization. In infancy, increased total IgE is more affected by factors increasing risk of intercurrent infection and non-specific airway inflammation, such as environmental tobacco smoke exposure (p < 0.001) and the use of gas cookers (p = 0.02). Specific allergen sensitization as represented by detectable IgE antibodies is influenced primarily by allergen exposure. In Sweden, low level exposure to allergens is associated with reduced specific allergen sensitization rates even though the infants already have atopic dermatitis.

Rapid Sensitization of Physiological, Neuronal, and Locomotor Effects of Nicotine: Critical Role of Peripheral Drug Actions

PubMed Central

Lenoir, Magalie; Tang, Jeremy S.; Woods, Amina S.

2013-01-01

Repeated exposure to nicotine and other psychostimulant drugs produces persistent increases in their psychomotor and physiological effects (sensitization), a phenomenon related to the drugs' reinforcing properties and abuse potential. Here we examined the role of peripheral actions of nicotine in nicotine-induced sensitization of centrally mediated physiological parameters (brain, muscle, and skin temperatures), cortical and VTA EEG, neck EMG activity, and locomotion in freely moving rats. Repeated injections of intravenous nicotine (30 μg/kg) induced sensitization of the drug's effects on all these measures. In contrast, repeated injections of the peripherally acting analog of nicotine, nicotine pyrrolidine methiodide (nicotinePM, 30 μg/kg, i.v.) resulted in habituation (tolerance) of the same physiological, neuronal, and behavioral measures. However, after repeated nicotine exposure, acute nicotinePM injections induced nicotine-like physiological responses: powerful cortical and VTA EEG desynchronization, EMG activation, a large brain temperature increase, but weaker hyperlocomotion. Additionally, both the acute locomotor response to nicotine and nicotine-induced locomotor sensitization were attenuated by blockade of peripheral nicotinic receptors by hexamethonium (3 mg/kg, i.v.). These data suggest that the peripheral actions of nicotine, which precede its direct central actions, serve as a conditioned interoceptive cue capable of eliciting nicotine-like physiological and neural responses after repeated nicotine exposure. Thus, by providing a neural signal to the CNS that is repeatedly paired with the direct central effects of nicotine, the drug's peripheral actions play a critical role in the development of nicotine-induced physiological, neural, and behavioral sensitization. PMID:23761889

Rapid sensitization of physiological, neuronal, and locomotor effects of nicotine: critical role of peripheral drug actions.

PubMed

Lenoir, Magalie; Tang, Jeremy S; Woods, Amina S; Kiyatkin, Eugene A

2013-06-12

Repeated exposure to nicotine and other psychostimulant drugs produces persistent increases in their psychomotor and physiological effects (sensitization), a phenomenon related to the drugs' reinforcing properties and abuse potential. Here we examined the role of peripheral actions of nicotine in nicotine-induced sensitization of centrally mediated physiological parameters (brain, muscle, and skin temperatures), cortical and VTA EEG, neck EMG activity, and locomotion in freely moving rats. Repeated injections of intravenous nicotine (30 μg/kg) induced sensitization of the drug's effects on all these measures. In contrast, repeated injections of the peripherally acting analog of nicotine, nicotine pyrrolidine methiodide (nicotine(PM), 30 μg/kg, i.v.) resulted in habituation (tolerance) of the same physiological, neuronal, and behavioral measures. However, after repeated nicotine exposure, acute nicotine(PM) injections induced nicotine-like physiological responses: powerful cortical and VTA EEG desynchronization, EMG activation, a large brain temperature increase, but weaker hyperlocomotion. Additionally, both the acute locomotor response to nicotine and nicotine-induced locomotor sensitization were attenuated by blockade of peripheral nicotinic receptors by hexamethonium (3 mg/kg, i.v.). These data suggest that the peripheral actions of nicotine, which precede its direct central actions, serve as a conditioned interoceptive cue capable of eliciting nicotine-like physiological and neural responses after repeated nicotine exposure. Thus, by providing a neural signal to the CNS that is repeatedly paired with the direct central effects of nicotine, the drug's peripheral actions play a critical role in the development of nicotine-induced physiological, neural, and behavioral sensitization.

Evaluation of in silico tools to predict the skin sensitization potential of chemicals.

PubMed

Verheyen, G R; Braeken, E; Van Deun, K; Van Miert, S

2017-01-01

Public domain and commercial in silico tools were compared for their performance in predicting the skin sensitization potential of chemicals. The packages were either statistical based (Vega, CASE Ultra) or rule based (OECD Toolbox, Toxtree, Derek Nexus). In practice, several of these in silico tools are used in gap filling and read-across, but here their use was limited to make predictions based on presence/absence of structural features associated to sensitization. The top 400 ranking substances of the ATSDR 2011 Priority List of Hazardous Substances were selected as a starting point. Experimental information was identified for 160 chemically diverse substances (82 positive and 78 negative). The prediction for skin sensitization potential was compared with the experimental data. Rule-based tools perform slightly better, with accuracies ranging from 0.6 (OECD Toolbox) to 0.78 (Derek Nexus), compared with statistical tools that had accuracies ranging from 0.48 (Vega) to 0.73 (CASE Ultra - LLNA weak model). Combining models increased the performance, with positive and negative predictive values up to 80% and 84%, respectively. However, the number of substances that were predicted positive or negative for skin sensitization in both models was low. Adding more substances to the dataset will increase the confidence in the conclusions reached. The insights obtained in this evaluation are incorporated in a web database www.asopus.weebly.com that provides a potential end user context for the scope and performance of different in silico tools with respect to a common dataset of curated skin sensitization data.

Single-Tier Testing with the C6 Peptide ELISA Kit Compared with Two-Tier Testing for Lyme Disease

PubMed Central

Wormser, Gary P.; Schriefer, Martin; Aguero-Rosenfeld, Maria E.; Levin, Andrew; Steere, Allen C.; Nadelman, Robert B.; Nowakowski, John; Marques, Adriana; Johnson, Barbara J. B.; Dumler, J. Stephen

2014-01-01

Background The two-tier serologic testing protocol for Lyme disease has a number of shortcomings including low sensitivity in early disease; increased cost, time and labor; and subjectivity in the interpretation of immunoblots. Methods The diagnostic accuracy of a single-tier commercial C6 ELISA kit was compared with two-tier testing. Results The C6 ELISA was significantly more sensitive than two-tier testing with sensitivities of 66.5% (95% C.I.:61.7-71.1) and 35.2% (95%C.I.:30.6-40.1), respectively (p<0.001) in 403 sera from patients with erythema migrans. The C6 ELISA had sensitivity statistically comparable to two-tier testing in sera from Lyme disease patients with early neurological manifestations (88.6% vs. 77.3%, p=0.13) or arthritis (98.3% vs. 95.6%, p= 0.38). Te specificities of C6 ELISA and two-tier testing in over 2200 blood donors, patients with other conditions, and Lyme disease vaccine recipients were found to be 98.9% and 99.5%, respectively (p<0.05, 95% C.I. surrounding the 0.6 percentage point difference of 0.04 to 1.15). Conclusions Using a reference standard of two-tier testing, the C6 ELISA as a single step serodiagnostic test provided increased sensitivity in early Lyme disease with comparable sensitivity in later manifestations of Lyme disease. The C6 ELISA had slightly decreased specificity. Future studies should evaluate the performance of the C6 ELISA compared with two-tier testing in routine clinical practice. PMID:23062467

Self-assessment of genital anatomy, sexual sensitivity and function in women: implications for genitoplasty.

PubMed

Schober, Justine M; Meyer-Bahlburg, Heino F L; Ransley, Philip G

2004-09-01

To assess the perceptions of healthy women of their genital anatomy and sexual sensitivity, and to provide suggestions for genitoplasty based on this information, as the success of genitoplasty has historically relied upon the surgeon's perception of the patient's anatomy and function, rather than the patient's perception of outcome in terms of appearance and erotic sensitivity. Fifty healthy, sexually active, adult women (aged 20-56 years) with no history of genital surgery completed the female version of the Self-Assessment of Genital Anatomy and Sexual Function. This self- report questionnaire comprises written text and images enabling women to rate the appearance, size and position of clitoris and vagina, as well as the intensity of orgasm and effort required for achieving orgasm in specified areas around the clitoris and within the vagina. Anatomical locations were compared for these ratings by repeated-measures analysis of variance. Anatomically, 46% of women described their clitoris as 'moderate-sized and raised', 42% as 'small and raised', and 78% reported that their vaginal opening was adequate for sexual penetration. The women reported the strongest orgasm and least effort to obtain an orgasm with stimulation of the area on and above the clitoris. For vaginal sensitivity, scores for orgasm intensity increased, and for orgasm effort decreased, with increasing vaginal depth, and they indicated less sexual sensitivity for the vagina than for the external genitalia. The skin above the clitoris, and the clitoris itself, appeared to be the most sexually sensitive. During genitoplasty, attention to preserving skin-flap integrity in this area seems appropriate.

The case for treatment fidelity in active music interventions: why and how.

PubMed

Wiens, Natalie; Gordon, Reyna L

2018-05-04

As the volume of studies testing the benefits of active music-making interventions increases exponentially, it is important to document what exactly is happening during music treatment sessions in order to provide evidence for the mechanisms through which music training affects other domains. Thus, to complement systematic and rigorous attention to outcomes of the treatment, we outline four vital components of treatment fidelity and discuss their implementation in nonmusic- and music-based interventions. We then describe the design of Music Impacting Language Expertise (MILEStone), a new intervention that aims to improve grammar skills in children with specific language impairment by increasing sensitivity to rhythmic structure, which may enhance general temporal processing and sensitivity to syntactic structure. We describe the approach to addressing treatment fidelity in MILEStone adapted from intervention research from other fields, including a behavioral coding system to track instructional episodes and child participation, a treatment manual, activity checklists, provider training and monitoring, a home practice log, and teacher ratings of participant engagement. This approach takes an important first step in modeling a formalized procedure for assessing treatment fidelity in active music-making intervention research, as a means of increasing methodological rigor in support of evidence-based practice in clinical and educational settings. © 2018 New York Academy of Sciences.

Dietary Sodium and Health: More Than Just Blood Pressure

PubMed Central

Farquhar, William B.; Edwards, David G.; Jurkovitz, Claudine T.; Weintraub, William S.

2016-01-01

Sodium is essential for cellular homeostasis and physiological function. Excess dietary sodium has been linked to elevations in blood pressure (BP). Salt-sensitivity of BP varies widely, but certain subgroups tend to be more salt-sensitive. The mechanisms underlying sodium-induced increases in BP are not completely understood, but may involve alterations in renal function, fluid volume, fluid regulatory hormones, the vasculature, cardiac function, and the autonomic nervous system. Recent pre-clinical and clinical data support that even in the absence of an increase in BP, excess dietary sodium can adversely affect target organs, including the blood vessels, heart, kidneys, and brain. In this review, we address these issues and the epidemiological literature relating dietary sodium to BP and cardiovascular health outcomes, addressing recent controversies. We also provide information and strategies for reducing dietary sodium. PMID:25766952

Goddard X-ray astronomy contributions to the IAU/COSPAR (1982)

NASA Technical Reports Server (NTRS)

Holt, S. S.; Petre, R.; Shafer, R. A.; Urry, C. M.; Mushotzky, R. F.

1982-01-01

The relation of X-ray flux to both the continuum flux in the optical and radio bands, and to the line emission properties of these objects were studied. The Einstein Observatory, because of increased sensitivity and improved angular resolution, increased substantially the number of known X-ray emitting active galactic nuclei. The Einstein imaging instruments detected morphology in AGN X-ray emission, in particular from jetlike structures in Cen-A, M87, and 3C273. The improved energy resolution and sensitivity of the spectrometers onboard the Observatory provide information on the geometry and ionization structure of the region responsible for the broad optical emission lines in a few AGN's. This information, combined with theoretical modeling and IUE and optical observations, allows the construction of a moderately detailed picture of the broad line region in these objects.

Anxiety Sensitivity and Nicotine Replacement Therapy Side Effects: Examining the Role of Emotion Dysregulation Among Treatment-Seeking Smokers.

PubMed

Zvolensky, Michael J; Paulus, Daniel J; Garey, Lorra; Raines, Amanda M; Businelle, Michael; Shankman, Stewart A; Manning, Kara; Goodwin, Renee D; Schmidt, Norman B

2017-11-01

Nicotine replacement therapy (NRT) significantly increases the likelihood of quit success at least over the short term, yet some smokers prematurely discontinue use. NRT side effects are often cited as the primary reason for medication discontinuation. The current study examined a theoretical pathway by which two smoking-related emotional vulnerabilities (anxiety sensitivity and emotion dysregulation) were related to the number of NRT (nicotine patch) side effects reported 1 week following a scheduled quit attempt. It was hypothesized that anxiety sensitivity would have an indirect effect on NRT side effects through emotion dysregulation. A total of 179 treatment-seeking, adult daily smokers with elevated anxiety sensitivity (47.5% male; M age = 39.73 years, SD = 13.87) were enrolled in a smoking cessation trial. Covariate-adjusted analyses provided support for the hypothesized pathway, such that emotion dysregulation explained the association between anxiety sensitivity and NRT side effects (b = 0.02, SE = 0.01, 95% CI [0.002, 0.03]; completely standardized estimate = .15). The findings underscore the importance of developing cessation treatments that incorporate techniques to enhance emotion regulation, particularly among smokers higher in anxiety sensitivity, to decrease the risk of NRT side effects.

Aortic Baroreceptors Display Higher Mechanosensitivity than Carotid Baroreceptors.

PubMed

Lau, Eva On-Chai; Lo, Chun-Yin; Yao, Yifei; Mak, Arthur Fuk-Tat; Jiang, Liwen; Huang, Yu; Yao, Xiaoqiang

2016-01-01

Arterial baroreceptors are mechanical sensors that detect blood pressure changes. It has long been suggested that the two arterial baroreceptors, aortic and carotid baroreceptors, have different pressure sensitivities. However, there is no consensus as to which of the arterial baroreceptors are more sensitive to changes in blood pressure. In the present study, we employed independent methods to compare the pressure sensitivity of the two arterial baroreceptors. Firstly, pressure-activated action potential firing was measured by whole-cell current clamp with a high-speed pressure clamp system in primary cultured baroreceptor neurons. The results show that aortic depressor neurons possessed a higher percentage of mechano-sensitive neurons. Furthermore, aortic baroreceptor neurons show a lower pressure threshold than that of carotid baroreceptor neurons. Secondly, uniaxial stretching of baroreceptor neurons, that mimics the forces exerted on blood vessels, elicited a larger increase in intracellular Ca(2+) rise in aortic baroreceptor neurons than in carotid baroreceptor neurons. Thirdly, the pressure-induced action potential firing in the aortic depressor nerve recorded in vivo was also higher. The present study therefore provides for a basic physiological understanding on the pressure sensitivity of the two baroreceptor neurons and suggests that aortic baroreceptors have a higher pressure sensitivity than carotid baroreceptors.

The BetaCage, an ultra-sensitive screener for surface contamination

NASA Astrophysics Data System (ADS)

Bunker, R.; Ahmed, Z.; Bowles, M. A.; Golwala, S. R.; Grant, D. R.; Kos, M.; Nelson, R. H.; Schnee, R. W.; Rider, A.; Wang, B.; Zahn, A.

2013-08-01

Material screening for identifying low-energy electron emitters and alpha-decaying isotopes is now a prerequisite for rare-event searches (e.g., dark-matter direct detection and neutrinoless double-beta decay) for which surface radiocon-tamination has become an increasingly important background. The BetaCage, a gaseous neon time-projection chamber, is a proposed ultra-sensitive (and nondestructive) screener for alpha-and beta-emitting surface contaminants to which existing screening facilities are insufficiently sensitive. Sensitivity goals are 0.1 betas keV-1 m-2 day-1 and 0.1 alphas m-2 day-1, with the former limited by Compton scattering of photons in the screening samples and (thanks to tracking) the latter expected to be signal-limited; radioassays and simulations indicate backgrounds from detector materials and radon daughters should be subdominant. We report on details of the background simulations and detector design that provide the discrimination, shielding, and radiopurity necessary to reach our sensitivity goals for a chamber with a 95 × 95 cm2 sample area positioned below a 40 cm drift region and monitored by crisscrossed anode and cathode planes consisting of 151 wires each.

A novel approach for modelling vegetation distributions and analysing vegetation sensitivity through trait-climate relationships in China

PubMed Central

Yang, Yanzheng; Zhu, Qiuan; Peng, Changhui; Wang, Han; Xue, Wei; Lin, Guanghui; Wen, Zhongming; Chang, Jie; Wang, Meng; Liu, Guobin; Li, Shiqing

2016-01-01

Increasing evidence indicates that current dynamic global vegetation models (DGVMs) have suffered from insufficient realism and are difficult to improve, particularly because they are built on plant functional type (PFT) schemes. Therefore, new approaches, such as plant trait-based methods, are urgently needed to replace PFT schemes when predicting the distribution of vegetation and investigating vegetation sensitivity. As an important direction towards constructing next-generation DGVMs based on plant functional traits, we propose a novel approach for modelling vegetation distributions and analysing vegetation sensitivity through trait-climate relationships in China. The results demonstrated that a Gaussian mixture model (GMM) trained with a LMA-Nmass-LAI data combination yielded an accuracy of 72.82% in simulating vegetation distribution, providing more detailed parameter information regarding community structures and ecosystem functions. The new approach also performed well in analyses of vegetation sensitivity to different climatic scenarios. Although the trait-climate relationship is not the only candidate useful for predicting vegetation distributions and analysing climatic sensitivity, it sheds new light on the development of next-generation trait-based DGVMs. PMID:27052108

Trusted Computing Technologies, Intel Trusted Execution Technology.

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

Guise, Max Joseph; Wendt, Jeremy Daniel

2011-01-01

We describe the current state-of-the-art in Trusted Computing Technologies - focusing mainly on Intel's Trusted Execution Technology (TXT). This document is based on existing documentation and tests of two existing TXT-based systems: Intel's Trusted Boot and Invisible Things Lab's Qubes OS. We describe what features are lacking in current implementations, describe what a mature system could provide, and present a list of developments to watch. Critical systems perform operation-critical computations on high importance data. In such systems, the inputs, computation steps, and outputs may be highly sensitive. Sensitive components must be protected from both unauthorized release, and unauthorized alteration: Unauthorizedmore » users should not access the sensitive input and sensitive output data, nor be able to alter them; the computation contains intermediate data with the same requirements, and executes algorithms that the unauthorized should not be able to know or alter. Due to various system requirements, such critical systems are frequently built from commercial hardware, employ commercial software, and require network access. These hardware, software, and network system components increase the risk that sensitive input data, computation, and output data may be compromised.« less

Tuning the Sensitivity of an Optical Cavity with Slow and Fast Light

NASA Technical Reports Server (NTRS)

Smith, David D.; Myneni, Krishna; Chang, H.; Toftul, A.; Schambeau, C.; Odutola, J. A.; Diels, J. C.

2012-01-01

We have measured mode pushing by the dispersion of a rubidium vapor in a Fabry-Perot cavity and have shown that the scale factor and sensitivity of a passive cavity can be strongly enhanced by the presence of such an anomalous dispersion medium. The enhancement is the result of the atom-cavity coupling, which provides a positive feedback to the cavity response. The cavity sensitivity can also be controlled and tuned through a pole by a second, optical pumping, beam applied transverse to the cavity. Alternatively, the sensitivity can be controlled by the introduction of a second counter-propagating input beam that interferes with the first beam, coherently increasing the cavity absorptance. We show that the pole in the sensitivity occurs when the sum of the effective group index and an additional cavity delay factor that accounts for mode reshaping goes to zero, and is an example of an exceptional point, commonly associated with coupled non-Hermitian Hamiltonian systems. Additionally we show that a normal dispersion feature can decrease the cavity scale factor and can be generated through velocity selective optical pumping

In Sickness and in Health: The Co-Regulation of Inflammation and Social Behavior

PubMed Central

Eisenberger, Naomi I; Moieni, Mona; Inagaki, Tristen K; Muscatell, Keely A; Irwin, Michael R

2017-01-01

Although it has commonly been assumed that the immune system and the processes that govern social behavior are separate, non-communicating entities, research over the past several decades suggests otherwise. Considerable evidence now shows that inflammatory processes and social behavior are actually powerful regulators of one another. This review first summarizes evidence that inflammatory processes regulate social behavior, leading to characteristic changes that may help an individual navigate the social environment during times of sickness. Specifically, this review shows that inflammation: (1) increases threat-related neural sensitivity to negative social experiences (eg, rejection, negative social feedback), presumably to enhance sensitivity to threats to well-being or safety in order to avoid them and (2) enhances reward-related neural sensitivity to positive social experiences (eg, viewing close others and receiving positive social feedback), presumably to increase approach-related motivation towards others who might provide support and care during sickness. Next, this review summarizes evidence showing that social behavior also regulates aspects of inflammatory activity, preparing the body for situations in which wounding and infection may be more likely (social isolation). Here, we review research showing: (1) that exposure to social stressors increases proinflammatory activity, (2) that individuals who are more socially isolated (ie, lonely) show increased proinflammatory activity, and (3) that individuals who are more socially isolated show increased proinflammatory activity in response to an inflammatory challenge or social stressor. The implications of the co-regulation of inflammation and social behavior are discussed. PMID:27480575

Intranasal oxytocin enhances neural processing of monetary reward and loss in post-traumatic stress disorder and traumatized controls.

PubMed

Nawijn, Laura; van Zuiden, Mirjam; Koch, Saskia B J; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

2016-04-01

Anhedonia is a significant clinical problem in post-traumatic stress disorder (PTSD). PTSD patients show reduced motivational approach behavior, which may underlie anhedonic symptoms. Oxytocin administration is known to increase reward sensitivity and approach behavior. We therefore investigated whether oxytocin administration affected neural responses during motivational processing in PTSD patients and trauma-exposed controls. 35 police officers with PTSD (21 males) and 37 trauma-exposed police officers without PTSD (19 males) were included in a within-subjects, randomized, placebo-controlled fMRI study. Neural responses during anticipation of monetary reward and loss were investigated with a monetary incentive delay task (MID) after placebo and oxytocin (40 IU) administration. Oxytocin increased neural responses during reward and loss anticipation in PTSD patients and controls in the striatum, dorsal anterior cingulate cortex and insula, key regions in the reward pathway. Although PTSD patients did not differ from controls in motivational processing under placebo, anhedonia severity in PTSD patients was negatively related to reward responsiveness in the ventral striatum. Furthermore, oxytocin effects on reward processing in the ventral striatum were positively associated with anhedonia. Oxytocin administration increased reward pathway sensitivity during reward and loss anticipation in PTSD patients and trauma-exposed controls. Thus, oxytocin administration may increase motivation for goal-directed approach behavior in PTSD patients and controls, providing evidence for a neurobiological pathway through which oxytocin could potentially increase motivation and reward sensitivity in PTSD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Developmental immunotoxicity of chemicals in rodents and its possible regulatory impact.

PubMed

Hessel, Ellen V S; Tonk, Elisa C M; Bos, Peter M J; van Loveren, Henk; Piersma, Aldert H

2015-01-01

Around 25% of the children in developed countries are affected with immune-based diseases. Juvenile onset diseases such as allergic, inflammatory and autoimmune diseases have shown increasing prevalences in the last decades. The role of chemical exposures in these phenomena is unclear. It is thought that the developmental immune system is more susceptible to toxicants than the mature situation. Developmental immunotoxicity (DIT) testing is nowadays not or minimally included in regulatory toxicology requirements. We reviewed whether developmental immune parameters in rodents would provide relatively sensitive endpoints of toxicity, whose inclusion in regulatory toxicity testing might improve hazard identification and risk assessment of chemicals. For each of the nine reviewed toxicants, the developing immune system was found to be at least as sensitive or more sensitive than the general (developmental) toxicity parameters. Functional immune (antigen-challenged) parameters appear more affected than structural (non-challenged) immune parameters. Especially, antibody responses to immune challenges with keyhole limpet hemocyanine or sheep red blood cells and delayed-type hypersensitivity responses appear to provide sensitive parameters of developmental immune toxicity. Comparison with current tolerable daily intakes (TDI) and their underlying overall no observed adverse effect levels showed that for some of the compounds reviewed, the TDI may need reconsideration based on developmental immune parameters. From these data, it can be concluded that the developing immune system is very sensitive to the disruption of toxicants independent of study design. Consideration of including functional DIT parameters in current hazard identification guidelines and wider application of relevant study protocols is warranted.

"I've got somebody there, someone cares": what support is most valued following a stroke?

PubMed

Northcott, Sarah; Hilari, Katerina

2017-06-19

There is often a need for increased support following a stroke. This study explored what types of support are provided by different network members and what support functions are most valued. Adults with first stroke were recruited from a stroke unit and participated in in-depth interviews 8-15 months poststroke. Framework Analysis was used to build thematic and explanatory accounts of the data. Twenty-nine participants took part. Main themes to emerge were as follows: the spouse was the most important provider of support; children were a relatively stable source of support, although many participants expressed reservations about worrying a child; relatives and friends typically provided social companionship and emotional support rather than on-going practical support. The only universally valued support function was the sense that someone was concerned and cared. Other valued functions were as follows: social companionship including everyday social "chit chat"; practical support provided sensitively; and, for many, sharing worries and sensitive encouragement. The manner and context in which support was provided was important: support was easiest to receive when it communicated concern, and was part of a reciprocal, caring relationship. As well as measuring supportive acts, researchers and clinicians should consider the manner and context of support. Implications for rehabilitation The manner in which support was provided mattered: support was easier to receive when it communicated concern. The spouse was the most important source of all support functions; children, relatives and friends were important providers of emotional and social companionship support. Researchers and clinicians should not only focus on what support is received, but also the context (e.g., contribution, reciprocity, quality of relationship) and manner (e.g., responsiveness, sensitivity) of the support.

Mechanism of Bacillus subtilis Spore Inactivation by and Resistance to Supercritical CO2 plus Peracetic Acid

PubMed Central

Setlow, Barbara; Korza, George; Blatt, Kelly M.S.; Fey, Julien P.; Setlow, Peter

2015-01-01

Aims Determine how supercritical CO2 (scCO2) plus peracetic acid (PAA) inactivates Bacillus subtilis spores, factors important in spore resistance to scCO2-PAA, and if spores inactivated by scCO2-PAA are truly dead. Methods and Results Spores of wild-type B. subtilis and isogenic mutants lacking spore protective proteins were treated with scCO2-PAA in liquid or dry at 35°C. Wild-type wet spores (aqueous suspension) were more susceptible than dry spores. Treated spores were examined for viability (and were truly dead), dipicolinic acid (DPA), mutations, permeability to nucleic acid stains, germination under different conditions, energy metabolism and outgrowth. ScCO2-PAA-inactivated spores retained DPA, and survivors had no notable DNA damage. However, DPA was released from inactivated spores at a normally innocuous temperature (85°C), and colony formation from treated spores was salt sensitive. The inactivated spores germinated but did not outgrow, and these germinated spores had altered plasma membrane permeability and defective energy metabolism. Wet or dry coat-defective spores had increased scCO2-PAA sensitivity, and dry spores but not wet spores lacking DNA protective proteins were more scCO2-PAA sensitive. Conclusions These findings suggest that scCO2-PAA inactivates spores by damaging spores’ inner membrane. The spore coat provided scCO2-PAA resistance for both wet and dry spores. DNA protective proteins provided scCO2-PAA resistance only for dry spores. Significance and Impact of Study These results provide information on mechanisms of spore inactivation of and resistance to scCO2-PAA, an agent with increasing use in sterilization applications. PMID:26535794

Mechanism of Bacillus subtilis spore inactivation by and resistance to supercritical CO2 plus peracetic acid.

PubMed

Setlow, B; Korza, G; Blatt, K M S; Fey, J P; Setlow, P

2016-01-01

Determine how supercritical CO2 (scCO2 ) plus peracetic acid (PAA) inactivates Bacillus subtilis spores, factors important in spore resistance to scCO2 -PAA, and if spores inactivated by scCO2 -PAA are truly dead. Spores of wild-type B. subtilis and isogenic mutants lacking spore protective proteins were treated with scCO2 -PAA in liquid or dry at 35°C. Wild-type wet spores (aqueous suspension) were more susceptible than dry spores. Treated spores were examined for viability (and were truly dead), dipicolinic acid (DPA), mutations, permeability to nucleic acid stains, germination under different conditions, energy metabolism and outgrowth. ScCO2 -PAA-inactivated spores retained DPA, and survivors had no notable DNA damage. However, DPA was released from inactivated spores at a normally innocuous temperature (85°C), and colony formation from treated spores was salt sensitive. The inactivated spores germinated but did not outgrow, and these germinated spores had altered plasma membrane permeability and defective energy metabolism. Wet or dry coat-defective spores had increased scCO2 -PAA sensitivity, and dry spores but not wet spores lacking DNA protective proteins were more scCO2 -PAA sensitive. These findings suggest that scCO2 -PAA inactivates spores by damaging spores' inner membrane. The spore coat provided scCO2 -PAA resistance for both wet and dry spores. DNA protective proteins provided scCO2 -PAA resistance only for dry spores. These results provide information on mechanisms of spore inactivation of and resistance to scCO2 -PAA, an agent with increasing use in sterilization applications. © 2015 The Society for Applied Microbiology.

A Comprehensive Approach to Risk Reduction for Asian and Pacific Islander American Women With HIV/AIDS.

PubMed

Sabato, Todd M

2014-07-01

As HIV incidence rises globally, Asian and Pacific Islander communities are increasingly affected. While often overlooked, Asian and Pacific Islander American women have shown the greatest percentage increase in HIV diagnosis rates. The development of a multilevel and multistrategy approach to HIV/AIDS education, prevention, and treatment among Asian and Pacific Islander females requires health care providers to identify personal and cultural barriers to prevention and treatment and implement culturally sensitive and specific measures. The purpose of this article is to illuminate barriers to HIV-related prevention, treatment, and care among Asian and Pacific Islander American females and provide practical application-based suggestions for providers, which may enhance Asian and Pacific Islander female inclusion in comprehensive HIV prevention. © The Author(s) 2014.

Consequences of implementing a cardiac troponin assay with improved sensitivity at Swedish coronary care units: an analysis from the SWEDEHEART registry.

PubMed

Eggers, Kai M; Lindahl, Bertil; Melki, Dina; Jernberg, Tomas

2016-08-07

Cardiac troponin (cTn) assays with improved sensitivity are increasingly utilized for the assessment of patients admitted because of suspected acute coronary syndrome (ACS). However, data on the clinical consequences of the implementation of such assays are limited. In a retrospective register-based study (37 710 coronary care unit admissions; SWEDEHEART registry), we compared the case mix, the use of diagnostic procedures, treatments, and 1-year all-cause mortality 1 year before the implementation of a cTn assay with improved sensitivity (study period 1) and 1 year thereafter (study period 2). During study period 2, more at-risk patients were admitted and more patients had cTn levels above the myocardial infarction cut-off (ACS patients +13.1%; non-ACS patients +160.1%). cTn levels above this cut-off exhibited stronger associations with mortality risk in study period 2 (adjusted HR 4.45 [95% confidence interval, CI, 3.36-5.89]) compared with period 1 (adjusted HR 2.43 [95% CI 2.11-2.80]), similar as for the cTn ratio relative to the respective 99th percentile. While there was no multivariable-adjusted increase in the use of diagnostic procedures, significant trends towards more differentiated treatment depending on the cause of cTn elevation, i.e. ACS or non-ACS, were noted. The implementation of a cTn assay with improved sensitivity was associated with an increase in the number of patients who due to their cTn-status were identified as suitable for beneficial therapies. There was no inappropriate increase in hospital resource utilization. As such, cTn assays with improved sensitivity provide an opportunity to improve the clinical management of patients with suspected ACS. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Design and analysis for detection monitoring of forest health

Treesearch

F. A. Roesch

1995-01-01

An analysis procedure is proposed for the sample design of the Forest Health Monitoring Program (FHM) in the United States. The procedure is intended to provide increased sensitivity to localized but potentially important changes in forest health by explicitly accounting for the spatial relationships between plots in the FHM design. After a series of median sweeps...

Detection of mRNA by reverse transcription PCR as an indicator of viability in Phytophthora ramorum

Treesearch

Antonio Chimento; Santa Olga Cacciola; Matteo Garbelotto

2008-01-01

Real-Time PCR technologies offer increasing opportunities to detect and study phytopathogenic fungi. They combine the sensitivity of conventional PCR with the generation of a specific fluorescent signal providing both real-time analysis of the reaction kinetics and quantification of specific DNA targets. Before the development of Real-Time PCR and...

Historical and contemporary distributions of carnivores in forests of the Sierra Nevada, California, USA

Treesearch

William J Zielinski; Richard L Truex; Fredrick V. Schlexer; Lori A. Campbell; Carlos Caroll

2005-01-01

Malammalian carnivores are considered particularly sensitive indicators of environmental change. Information on the distribution of carnivores from the early 1900s provides a unique opportunity to evaluate changes in their distributions over a 75-year period during which the influence of human uses of forest resources in California greatly increased. We present...

Methods and Strategies: Using Acorns to Generate an Entire Alphabet. Nature Walks Empower Young Bilingual Learners

ERIC Educational Resources Information Center

Arreguin-Anderson, Maria Guadalupe; Alanis, Iliana; Gonzalez, Irasema Salinas

2016-01-01

The increasing presence of linguistically diverse young children in U.S. public schools has prompted science educators to recognize the need for approaches that are inclusive and sensitive to students' academic needs. The challenge is to design lessons that provide language support while actively engaging children in authentic scientific inquiry.…

Towards a Culturally Sensitive and Deeper Understanding of "Rote Learning" and Memorisation of Adult Learners

ERIC Educational Resources Information Center

Tan, Po-Li

2011-01-01

This article aims to provide evidence that "rote learning" or "memorisation" is a complex construct and is deeply embedded in the East Asian culture. An in-depth understanding of this learning approach is increasingly crucial considering the complex demography of contemporary higher education nowadays. Not only is there a rise…

The Preschool Feelings Checklist: A Brief and Sensitive Screening Measure for Depression in Young Children.

ERIC Educational Resources Information Center

Luby, Joan L.; Heffelfinger, Amy; Koenig-McNaught, Amy L.; Brown, Kathy; Spitznagel, Edward

2004-01-01

Objective: Childhood depression is widely underrecognized in primary health care settings. This phenomenon appears to increase with younger age. Evidence has been provided for a valid depressive syndrome among preschool children. Based on the need for the earliest possible identification of depression, the development of a brief screening measure…

Communities of Practice in an Arabic Culture: Wenger's Model and the United Arab Emirates Implications for Online Learning

ERIC Educational Resources Information Center

Lamontagne, Mark

2005-01-01

With the advent of globalization and the proliferation of online learning, the creation of culturally sensitive online learning environments takes on increasing importance. Online education provides new opportunities for learners from different cultural backgrounds to come together, learn, expand their knowledge, share ideas, and develop passion…

Appreciating Differences: Teaching and Learning in a Culturally Diverse Classroom. Hot Topics: Usable Research. Revised Edition.

ERIC Educational Resources Information Center

Ploumis-Devick, Evelyn; Follman, Joseph

The purpose of this publication is to provide educators with useful information on and examples of how teachers and students can better communicate and learn in today's culturally diverse classrooms. Educators are offered background information and resources for increasing sensitivity and responsiveness to the needs of students of different…

The performance characteristics of lateral flow devices with 2 strains of highly pathogenic avian influenza virus

USDA-ARS?s Scientific Manuscript database

Lateral flow devices (LFD) are commercially available and provide a fast, highly specific, on-site test for avian influenza. Because of the low analytic sensitivity of LFD tests at low virus concentrations, targeted sampling of sick and dead birds has been proposed in order to increase detection pr...

The effect of varenicline on the development and expression of nicotine-induced behavioral sensitization and cross-sensitization in rats.

PubMed

Goutier, Wouter; Kloeze, Margreet B; McCreary, Andrew C

2015-03-01

The present study focused on the evaluation of behavioral sensitization and cross-sensitization induced by nicotine and varenicline in rats. Furthermore, it examined the influence of varenicline, a partial alpha4beta2 nicotinic receptor agonist, on nicotine-induced sensitization. To assess the development of behavioral sensitization, rats were chronically treated with vehicle, varenicline (0.03-3.0 mg/kg), nicotine (0.4 mg/kg) or combinations for 5 days and locomotor activity was measured. The expression of sensitization was assessed following a withdrawal period (17-26 days). The present results confirmed previous data showing the development and expression of nicotine-induced sensitization of locomotor activity in the rat. Varenicline did not induce sensitization on its own. When varenicline and nicotine were repeatedly administered sequentially, varenicline blocked the development and expression of nicotine-induced sensitization. Acute varenicline blocked the expression of nicotine-induced sensitization in a dose-dependent manner. Acute varenicline did not significantly increase locomotor activity, nor did it attenuate nicotine-induced sensitization. However, varenicline did cross-sensitize to the effects of nicotine, and vice versa. The present study showed that varenicline produced a dose-dependent bidirectional cross-sensitization with nicotine. Taken together, these findings provide pre-clinical evidence that varenicline is able to attenuate the effects of nicotine, yet simultaneously 'substitutes' for the effects of nicotine in the rat. Longitudinal studies would be needed to see if similar effects are seen in the clinical setting, and whether such effects contribute to the actions of varenicline as a smoking cessation aid. © 2013 Society for the Study of Addiction.

Ozone and haze pollution weakens net primary productivity in China

NASA Astrophysics Data System (ADS)

Yue, Xu; Unger, Nadine; Harper, Kandice; Xia, Xiangao; Liao, Hong; Zhu, Tong; Xiao, Jingfeng; Feng, Zhaozhong; Li, Jing

2017-05-01

Atmospheric pollutants have both beneficial and detrimental effects on carbon uptake by land ecosystems. Surface ozone (O3) damages leaf photosynthesis by oxidizing plant cells, while aerosols promote carbon uptake by increasing diffuse radiation and exert additional influences through concomitant perturbations to meteorology and hydrology. China is currently the world's largest emitter of both carbon dioxide and short-lived air pollutants. The land ecosystems of China are estimated to provide a carbon sink, but it remains unclear whether air pollution acts to inhibit or promote carbon uptake. Here, we employ Earth system modeling and multiple measurement datasets to assess the separate and combined effects of anthropogenic O3 and aerosol pollution on net primary productivity (NPP) in China. In the present day, O3 reduces annual NPP by 0.6 Pg C (14 %) with a range from 0.4 Pg C (low O3 sensitivity) to 0.8 Pg C (high O3 sensitivity). In contrast, aerosol direct effects increase NPP by 0.2 Pg C (5 %) through the combination of diffuse radiation fertilization, reduced canopy temperatures, and reduced evaporation leading to higher soil moisture. Consequently, the net effects of O3 and aerosols decrease NPP by 0.4 Pg C (9 %) with a range from 0.2 Pg C (low O3 sensitivity) to 0.6 Pg C (high O3 sensitivity). However, precipitation inhibition from combined aerosol direct and indirect effects reduces annual NPP by 0.2 Pg C (4 %), leading to a net air pollution suppression of 0.8 Pg C (16 %) with a range from 0.6 Pg C (low O3 sensitivity) to 1.0 Pg C (high O3 sensitivity). Our results reveal strong dampening effects of air pollution on the land carbon uptake in China today. Following the current legislation emission scenario, this suppression will be further increased by the year 2030, mainly due to a continuing increase in surface O3. However, the maximum technically feasible reduction scenario could drastically relieve the current level of NPP damage by 70 % in 2030, offering protection of this critical ecosystem service and the mitigation of long-term global warming.

Effects of Chronic Consumption of Sugar-Enriched Diets on Brain Metabolism and Insulin Sensitivity in Adult Yucatan Minipigs.

PubMed

Ochoa, Melissa; Malbert, Charles-Henri; Meurice, Paul; Val-Laillet, David

2016-01-01

Excessive sugar intake might increase the risk to develop eating disorders via an altered reward circuitry, but it remains unknown whether different sugar sources induce different neural effects and whether these effects are dependent from body weight. Therefore, we compared the effects of three high-fat and isocaloric diets varying only in their carbohydrate sources on brain activity of reward-related regions, and assessed whether brain activity is dependent on insulin sensitivity. Twenty-four minipigs underwent 18FDG PET brain imaging following 7-month intake of high-fat diets of which 20% in dry matter weight (36.3% of metabolisable energy) was provided by starch, glucose or fructose (n = 8 per diet). Animals were then subjected to a euglycemic hyperinsulinemic clamp to determine peripheral insulin sensitivity. After a 7-month diet treatment, all groups had substantial increases in body weight (from 36.02±0.85 to 63.33±0.81 kg; P<0.0001), regardless of the diet. All groups presented similar insulin sensitivity index (ISI = 1.39±0.10 mL·min-1·μUI·kg). Compared to starch, chronic exposure to fructose and glucose induced bilateral brain activations, i.e. increased basal cerebral glucose metabolism, in several reward-related brain regions including the anterior and dorsolateral prefrontal cortex, the orbitofrontal cortex, the anterior cingulate cortex, the caudate and putamen. The lack of differences in insulin sensitivity index and body weight suggests that the observed differences in basal brain glucose metabolism are not related to differences in peripheral insulin sensitivity and weight gain. The differences in basal brain metabolism in reward-related brain areas suggest the onset of cerebral functional alterations induced by chronic consumption of dietary sugars. Further studies should explore the underlying mechanisms, such as the availability of intestinal and brain sugar transporter, or the appearance of addictive-like behavioral correlates of these brain functional characteristics.

Effects of early human handling on the pain sensitivity of young lambs.

PubMed

Guesgen, Mirjam J; Beausoleil, Ngaio J; Stewart, Mairi

2013-01-01

Pain sensitivity of lambs changes over the first weeks of life. However, the effects of early treatments such as human handling on pain sensitivity are unknown for this species. This study investigated the effects of regular early gentle human handling on the pain sensitivity of lambs, indicated by their behavioural responses to tail docking. Prospective part-blinded experimental study. Twenty-nine singleton Coopworth lambs (females n=14, males n=15). Starting at one day of age, lambs were either handled twice daily for 2 weeks (Handled), were kept in the presence of lambs who were being handled but were not handled themselves (Presence), or were exposed to a human only during routine feeding and care (Control). At 3 weeks of age, all lambs were tail docked using rubber rings. Changes in behaviour due to docking were calculated and change data were analyzed using two-way anova with treatment and test pen as main factors. All lambs showed significant increases in the frequency and duration of behaviours indicative of pain, including 'abnormal' behaviours, and decreases in the frequency and duration of 'normal' behaviours after docking. Handled lambs showed a smaller increase in the time spent lying abnormally after docking than did Control lambs (mean transformed change in proportion of 30 minutes spent±SE: Control 0.55±0.04; Handled 0.38±0.03; Presence 0.48±0.03; C versus H t=3.45, p=0.007). These results provide some evidence that handling early in life may reduce subsequent pain sensitivity in lambs. While the behavioural effects of handling on pain behaviour were subtle, the results suggest, at the very least, that early handling does not increase pain sensitivity in lambs and suggests there is still flexibility postnatally in the pain processing system of a precocial species. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Laser-evoked potentials mediated by mechano-insensitive nociceptors in human skin.

PubMed

Dusch, M; van der Ham, J; Weinkauf, B; Benrath, J; Rukwied, R; Ringkamp, M; Schmelz, M; Treede, R-D; Baumgärtner, U

2016-05-01

Laser-evoked potentials (LEP) were assessed after peripheral nerve block of the lateral femoral cutaneous nerve (LFCN) in healthy volunteers from partially anesthetized skin areas to differentially stimulate mechano-insensitive nociceptors. An ultrasound-guided nerve block of the LFCN was performed in 12 healthy male subjects with Ropivacain 1%. After 30 min, the nerve block induced significantly larger anesthetic areas to mechanical stimuli than to electrical stimuli revealing an area of differential sensitivity. LEPs, reaction times and pain ratings were recorded in response to the laser stimuli of (1) completely anesthetic skin, (2) mechano-insensitive, but electrically excitable skin ('differential sensitivity'), (3) normal skin. LEP latencies in the area of differential sensitivity were increased compared to unaffected skin (228 ± 8.5 ms, vs. 181 ± 3.6 ms, p < 0.01) and LEP amplitudes were reduced (14.8 ± 1.2 μV vs. 24.6 ± 1.7 μV, p < 0.01). Correspondingly, psychophysically assessed response latencies in the differentially anesthetic skin were increased (649 ms vs. 427 ms, p < 0.01) and pain ratings reduced (1.5/10 vs. 5/10 NRS, p < 0.01). The increase in LEP latency suggests that mechano-insensitive heat-sensitive Aδ nociceptors (MIA, type II) have a slower conduction velocity or higher utilization time than mechano-sensitive type II Aδ nociceptors. Moreover, widely branched, slowly conducting and mechano-insensitive branches of Aδ nociceptors can explain our finding. LEPs in the differentially anesthetized skin provide specific information about a mechanically insensitive but heat-sensitive subpopulation of Aδ nociceptors. These findings support the concept that A-fibre nociceptors exhibit a similar degree of modality specificity as C-fibre nociceptors. © 2015 European Pain Federation - EFIC®

Sensitivity Analysis Tailored to Constrain 21st Century Terrestrial Carbon-Uptake

NASA Astrophysics Data System (ADS)

Muller, S. J.; Gerber, S.

2013-12-01

The long-term fate of terrestrial carbon (C) in response to climate change remains a dominant source of uncertainty in Earth-system model projections. Increasing atmospheric CO2 could be mitigated by long-term net uptake of C, through processes such as increased plant productivity due to "CO2-fertilization". Conversely, atmospheric conditions could be exacerbated by long-term net release of C, through processes such as increased decomposition due to higher temperatures. This balance is an important area of study, and a major source of uncertainty in long-term (>year 2050) projections of planetary response to climate change. We present results from an innovative application of sensitivity analysis to LM3V, a dynamic global vegetation model (DGVM), intended to identify observed/observable variables that are useful for constraining long-term projections of C-uptake. We analyzed the sensitivity of cumulative C-uptake by 2100, as modeled by LM3V in response to IPCC AR4 scenario climate data (1860-2100), to perturbations in over 50 model parameters. We concurrently analyzed the sensitivity of over 100 observable model variables, during the extant record period (1970-2010), to the same parameter changes. By correlating the sensitivities of observable variables with the sensitivity of long-term C-uptake we identified model calibration variables that would also constrain long-term C-uptake projections. LM3V employs a coupled carbon-nitrogen cycle to account for N-limitation, and we find that N-related variables have an important role to play in constraining long-term C-uptake. This work has implications for prioritizing field campaigns to collect global data that can help reduce uncertainties in the long-term land-atmosphere C-balance. Though results of this study are specific to LM3V, the processes that characterize this model are not completely divorced from other DGVMs (or reality), and our approach provides valuable insights into how data can be leveraged to be better constrain projections for the land carbon sink.

The challenge of education and learning in the developing world.

PubMed

Kremer, Michael; Brannen, Conner; Glennerster, Rachel

2013-04-19

Across many different contexts, randomized evaluations find that school participation is sensitive to costs: Reducing out-of-pocket costs, merit scholarships, and conditional cash transfers all increase schooling. Addressing child health and providing information on how earnings rise with education can increase schooling even more cost-effectively. However, among those in school, test scores are remarkably low and unresponsive to more-of-the-same inputs, such as hiring additional teachers, buying more textbooks, or providing flexible grants. In contrast, pedagogical reforms that match teaching to students' learning levels are highly cost effective at increasing learning, as are reforms that improve accountability and incentives, such as local hiring of teachers on short-term contracts. Technology could potentially improve pedagogy and accountability. Improving pre- and postprimary education are major future challenges.

Pramipexole-induced disruption of behavioral processes fundamental to intertemporal choice.

PubMed

Johnson, Patrick S; Stein, Jeffrey S; Smits, Rochelle R; Madden, Gregory J

2013-05-01

Evaluating the effects of presession drug administration on intertemporal choice in nonhumans is a useful approach for identifying compounds that promote impulsive behavior in clinical populations, such as those prescribed the dopamine agonist pramipexole (PPX). Based on the results of previous studies, it is unclear whether PPX increases rats' impulsive choice or attenuates aspects of stimulus control. The present study was designed to experimentally isolate behavioral processes fundamental to intertemporal choice and challenge them pharmacologically with PPX administration. In Experiment 1, the hypothesis that PPX increases impulsive choice as a result of enhanced sensitivity to reinforcer delays was tested and disconfirmed. That is, acute PPX diminished delay sensitivity in a manner consistent with disruption of stimulus control whereas repeated PPX had no effect on delay sensitivity. Experiments 2 and 3 elaborated upon this finding by examining the effects of repeated PPX on rats' discrimination of response-reinforcer contingencies and reinforcer amounts, respectively. Accuracy of both discriminations was reduced by PPX. Collectively these results provide no support for past studies that have suggested PPX increases impulsive choice. Instead, PPX impairs stimulus control over choice behavior. The behavioral approach adopted herein could be profitably integrated with genetic and other biobehavioral models to advance our understanding of impulsive behavior associated with drug administration. © Society for the Experimental Analysis of Behavior.

Yap5 Protein-regulated Transcription of the TYW1 Gene Protects Yeast from High Iron Toxicity*

PubMed Central

Li, Liangtao; Jia, Xuan; Ward, Diane M.; Kaplan, Jerry

2011-01-01

The budding yeast Saccharomyces cerevisiae responds to high cytosolic iron by inducing Yap5-mediated transcription. We identified genes regulated by Yap5 in response to iron and show that one of the genes induced is TYW1, which encodes an iron-sulfur cluster enzyme that participates in the synthesis of wybutosine-modified tRNA. Strains deleted for TYW1 do not show a phenotype in standard yeast medium. In contrast, overexpression of TYW1 results in decreased cell growth and induction of the iron regulon, leading to increased expression of the high affinity iron transporters. We identified a minimal domain of S. cerevisiae Tyw1 that is sufficient to induce the iron regulon. CCC1, a vacuolar iron importer, is a Yap5-regulated gene, and deletion of either CCC1 or YAP5 resulted in high iron sensitivity. Deletion of TYW1 in a Δccc1 strain led to increased iron sensitivity. The increased iron sensitivity of Δccc1Δtyw1 could be suppressed by overexpression of iron-sulfur cluster enzymes. We conclude that the Yap5-mediated induction of TYW1 provides protection from high iron toxicity by the consumption of free cytosolic iron through the formation of protein-bound iron-sulfur clusters. PMID:21917924

Multiple Levels of Suffering: Discrimination in Health-Care Settings is Associated With Enhanced Laboratory Pain Sensitivity in Sickle Cell Disease.

PubMed

Mathur, Vani A; Kiley, Kasey B; Haywood, Carlton; Bediako, Shawn M; Lanzkron, Sophie; Carroll, C Patrick; Buenaver, Luis F; Pejsa, Megan; Edwards, Robert R; Haythornthwaite, Jennifer A; Campbell, Claudia M

2016-12-01

People living with sickle cell disease (SCD) experience severe episodic and chronic pain and frequently report poor interpersonal treatment within health-care settings. In this particularly relevant context, we examined the relationship between perceived discrimination and both clinical and laboratory pain. Seventy-one individuals with SCD provided self-reports of experiences with discrimination in health-care settings and clinical pain severity, and completed a psychophysical pain testing battery in the laboratory. Discrimination in health-care settings was correlated with greater clinical pain severity and enhanced sensitivity to multiple laboratory-induced pain measures, as well as stress, depression, and sleep. After controlling for relevant covariates, discrimination remained a significant predictor of mechanical temporal summation (a marker of central pain facilitation), but not clinical pain severity or suprathreshold heat pain response. Furthermore, a significant interaction between experience with discrimination and clinical pain severity was associated with mechanical temporal summation; increased experience with discrimination was associated with an increased correlation between clinical pain severity and temporal summation of pain. Perceived discrimination within health-care settings was associated with pain facilitation. These findings suggest that discrimination may be related to increased central sensitization among SCD patients, and more broadly that health-care social environments may interact with pain pathophysiology.

New Generation Live Vaccines against Human Respiratory Syncytial Virus Designed by Reverse Genetics

PubMed Central

Collins, Peter L.; Murphy, Brian R.

2005-01-01

Development of a live pediatric vaccine against human respiratory syncytial virus (RSV) is complicated by the need to immunize young infants and the difficulty in balancing attenuation and immunogenicity. The ability to introduce desired mutations into infectious virus by reverse genetics provides a method for identifying and designing highly defined attenuating mutations. These can be introduced in combinations as desired to achieve gradations of attenuation. Attenuation is based on several strategies: multiple independent temperature-sensitive point mutations in the polymerase, a temperature-sensitive point mutation in a transcription signal, a set of non–temperature-sensitive mutations involving several genes, deletion of a viral RNA synthesis regulatory protein, and deletion of viral IFN α/β antagonists. The genetic stability of the live vaccine can be increased by judicious choice of mutations. The virus also can be engineered to increase the level of expression of the protective antigens. Protective antigens from antigenically distinct RSV strains can be added or swapped to increase the breadth of coverage. Alternatively, the major RSV protective antigens can be expressed from transcription units added to an attenuated parainfluenza vaccine virus, making a bivalent vaccine. This would obviate the difficulties inherent in the fragility and inefficient in vitro growth of RSV, simplifying vaccine design and use. PMID:16113487

The acute toxic effects of 1-alkyl-3-methylimidazolium nitrate ionic liquids on Chlorella vulgaris and Daphnia magna.

PubMed

Zhang, Cheng; Zhang, Shuai; Zhu, Lusheng; Wang, Jinhua; Wang, Jun; Zhou, Tongtong

2017-10-01

Given their increasingly widespread application, the toxic effects of ionic liquids (ILs) have become the subject of significant attention in recent years. Therefore, the present study assessed the acute toxic effects of 1-alkyl-3-methylimidazolium nitrate ([C n mim]NO 3 (n = 2, 4, 6, 8, 10, 12)) on Chlorella vulgaris and Daphnia magna. The sensitivity of the tested organism Daphnia magna and the investigated IL concentrations in water using high-performance liquid chromatography (HPLC) were also evaluated to demonstrate the reliability of the present study. The results illustrated that Daphnia magna is indeed sensitive to the reference toxicant and the investigated ILs were stable in the aquatic environment. The 50% effect concentration (EC 50 ) was used to represent the acute toxic effects on Chlorella vulgaris and Daphnia magna. With the increasing alkyl-chain lengths, the toxicity of the investigated ILs increased in both the test organisms. Accordingly, the alkyl-chain lengths can cause significantly toxic effects on aquatic organisms, and Daphnia magna are much more sensitive than Chlorella vulgaris to the imidazolium-based ILs used in the present study. Furthermore, the present study provides more information on the acute toxic effects of 1-alkyl-3-methylimidazolium nitrate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metroplex Optimization Model Expansion and Analysis: The Airline Fleet, Route, and Schedule Optimization Model (AFRS-OM)

NASA Technical Reports Server (NTRS)

Sherry, Lance; Ferguson, John; Hoffman, Karla; Donohue, George; Beradino, Frank

2012-01-01

This report describes the Airline Fleet, Route, and Schedule Optimization Model (AFRS-OM) that is designed to provide insights into airline decision-making with regards to markets served, schedule of flights on these markets, the type of aircraft assigned to each scheduled flight, load factors, airfares, and airline profits. The main inputs to the model are hedged fuel prices, airport capacity limits, and candidate markets. Embedded in the model are aircraft performance and associated cost factors, and willingness-to-pay (i.e. demand vs. airfare curves). Case studies demonstrate the application of the model for analysis of the effects of increased capacity and changes in operating costs (e.g. fuel prices). Although there are differences between airports (due to differences in the magnitude of travel demand and sensitivity to airfare), the system is more sensitive to changes in fuel prices than capacity. Further, the benefits of modernization in the form of increased capacity could be undermined by increases in hedged fuel prices

Strain-sensitive upconversion for imaging biological forces (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lay, Alice; Wisser, Michael; Lin, Yu; Narayan, Tarun; Krieg, Michael; Atre, Ashwin; Goodman, Miriam; Dionne, Jennifer A.

2016-09-01

Nearly all diseases can be traced back to abnormal mechanotransduction, but few sensors can reliably measure biologically-relevant forces in vivo. Here, we investigate sub-25nm lanthanide-doped upconverting nanoparticles as novel optical force probes, which provide several biocompatible features: sharp emission peaks with near infrared illumination, a high signal-to-noise ratio, and photostability. To increase force sensitivity, we include d-metal doping in the nanoparticles; the d-metal siphons energy from the lanthanide ions with an efficiency that varies with pressure. We synthesize cubic-phase NaYF4: Er3+,Yb3+ nanoparticles doped with 0-5% Mn2+ and compress them in a hydrostatic environment using a diamond anvil cell. When illuminated at 980nm, the nanoparticles show sharp emission peaks centered at wavelengths of 522nm, 545nm, and 660nm. In 20nN increments, up to 700nN, the ratio of the red-to-green peaks in 0% Mn-doped nanoparticles increases by nearly 30%, resulting in a perceived color change from orange to red. In contrast, the 1% Mn-doped samples exhibit little color change but a large 40% decrease in upconversion intensity. In both cases, the red-to-green ratio varies linearly with strain and the optical properties are recoverable upon release. We further use atomic force microscopy to characterize optical responses at lower, pico-Newton to nano-Newton forces. To demonstrate in vivo imaging capabilities, we incubate C. elegans with nanoparticles dispersed in buffer solution (5mg/mL concentration) and image forces involved in digestion using confocal microscopy. Our nanoparticles provide a platform for the first, non-genetically-encoded in vivo force sensors, and we describe routes to increase their sensitivity to the single-pN range.

Beyond the resolution limit: subpixel resolution in animals and now in silicon

NASA Astrophysics Data System (ADS)

Wilcox, M. J.

2007-09-01

Automatic acquisition of aerial threats at thousands of kilometers distance requires high sensitivity to small differences in contrast and high optical quality for subpixel resolution, since targets occupy much less surface area than a single pixel. Targets travel at high speed and break up in the re-entry phase. Target/decoy discrimination at the earliest possible time is imperative. Real time performance requires a multifaceted approach with hyperspectral imaging and analog processing allowing feature extraction in real time. Hyperacuity Systems has developed a prototype chip capable of nonlinear increase in resolution or subpixel resolution far beyond either pixel size or spacing. Performance increase is due to a biomimetic implementation of animal retinas. Photosensitivity is not homogeneous across the sensor surface, allowing pixel parsing. It is remarkably simple to provide this profile to detectors and we showed at least three ways to do so. Individual photoreceptors have a Gaussian sensitivity profile and this nonlinear profile can be exploited to extract high-resolution. Adaptive, analog circuitry provides contrast enhancement, dynamic range setting with offset and gain control. Pixels are processed in parallel within modular elements called cartridges like photo-receptor inputs in fly eyes. These modular elements are connected by a novel function for a cell matrix known as L4. The system is exquisitely sensitive to small target motion and operates with a robust signal under degraded viewing conditions, allowing detection of targets smaller than a single pixel or at greater distance. Therefore, not only is instantaneous feature extraction possible but also subpixel resolution. Analog circuitry increases processing speed with more accurate motion specification for target tracking and identification.

INF-γ sensitizes head and neck squamous cell carcinoma cells to chemotherapy-induced apoptosis and necroptosis through up-regulation of Egr-1.

PubMed

Xu, Bei; Shu, Yongqian; Liu, Peng

2014-11-01

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Acquired resistance to standard chemotherapy accounts for most of treatment failure. Here we demonstrate that Interferon-γ (INF-γ) may up-regulate Egr-1 gene expression in HNSCC cell line SCC-25. Forced expression of Egr-1 sensitizes SCC-25 cells to chemotherapy-induced apoptosis and necroptosis, a novel form of programmed cell death. Egr-1 up-regulation also significantly increases the production of Thrombospondin-1 (TSP-1), a matricellular glycoprotein which has been described to induce cell death in HNSCC. Moreover, INF-γ-induced sensitization of cells to chemotherapy-mediated cell death and TSP-1 production could be markedly abolished by Egr-1 silencing. The present investigation provides the first evidence that INF-γ may sensitize HNSCC cells to chemotherapy-induced apoptosis and necroptosis through up-regulation of Egr-1. These data support the combination use of INF-γ and cytotoxic drugs for HNSCC Therapy.

Agaricus blazei Murill enhances doxorubicin-induced apoptosis in human hepatocellular carcinoma cells by NFκB-mediated increase of intracellular doxorubicin accumulation.

PubMed

Lee, Jong Seok; Hong, Eock Kee

2011-02-01

It has been demonstrated that the Agaricus blazei Murill (ABM) mushroom, which primarily consists of polysaccharides, possesses anti-tumor activities. However, the mechanisms by which ABM inhibits human hepatocellular carcinoma growth remain unknown. Our study demonstrates that ABM acts as an enhancer to sensitize doxorubicin (Dox)-mediated apoptotic signaling, and this sensitization can be achieved by enhancing intracellular Dox accumulation via the inhibition of NFκB activity. These findings suggest that ABM, when combined with low doses of Dox, has the potential to provide more efficient therapeutic effects against drug-resistant human hepatocellular carcinoma.

Recommendations for Assessment of the Reliability, Sensitivity, and Validity of Data Provided by Wearable Sensors Designed for Monitoring Physical Activity

PubMed Central

2018-01-01

Although it is becoming increasingly popular to monitor parameters related to training, recovery, and health with wearable sensor technology (wearables), scientific evaluation of the reliability, sensitivity, and validity of such data is limited and, where available, has involved a wide variety of approaches. To improve the trustworthiness of data collected by wearables and facilitate comparisons, we have outlined recommendations for standardized evaluation. We discuss the wearable devices themselves, as well as experimental and statistical considerations. Adherence to these recommendations should be beneficial not only for the individual, but also for regulatory organizations and insurance companies. PMID:29712629

A System Dynamics Approach to Modeling the Sensitivity of Inappropriate Emergency Department Utilization

NASA Astrophysics Data System (ADS)

Behr, Joshua G.; Diaz, Rafael

Non-urgent Emergency Department utilization has been attributed with increasing congestion in the flow and treatment of patients and, by extension, conditions the quality of care and profitability of the Emergency Department. Interventions designed to divert populations to more appropriate care may be cautiously received by operations managers due to uncertainty about the impact an adopted intervention may have on the two values of congestion and profitability. System Dynamics (SD) modeling and simulation may be used to measure the sensitivity of these two, often-competing, values of congestion and profitability and, thus, provide an additional layer of information designed to inform strategic decision making.

Estimation of arterial baroreflex sensitivity in relation to carotid artery stiffness.

PubMed

Lipponen, Jukka A; Tarvainen, Mika P; Laitinen, Tomi; Karjalainen, Pasi A; Vanninen, Joonas; Koponen, Timo; Lyyra-Laitinen, Tiina

2012-01-01

Arterial baroreflex has a significant role in regulating blood pressure. It is known that increased stiffness of the carotid sinus affects mecanotransduction of baroreceptors and therefore limits baroreceptors capability to detect changes in blood pressure. By using high resolution ultrasound video signal and continuous measurement of electrocardiogram (ECG) and blood pressure, it is possible to define elastic properties of artery simultaneously with baroreflex sensitivity parameters. In this paper dataset which consist 38 subjects, 11 diabetics and 27 healthy controls was analyzed. Use of diabetic and healthy test subjects gives wide scale of arteries with different elasticity properties, which provide opportunity to validate baroreflex and artery stiffness estimation methods.

Sensitivity, Specificity, PPV, and NPV for Predictive Biomarkers.

PubMed

Simon, Richard

2015-08-01

Molecularly targeted cancer drugs are often developed with companion diagnostics that attempt to identify which patients will have better outcome on the new drug than the control regimen. Such predictive biomarkers are playing an increasingly important role in precision oncology. For diagnostic tests, sensitivity, specificity, positive predictive value, and negative predictive are usually used as performance measures. This paper discusses these indices for predictive biomarkers, provides methods for their calculation with survival or response endpoints, and describes assumptions involved in their use. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Culturally competent substance abuse treatment with transgender persons.

PubMed

Nuttbrock, Larry A

2012-01-01

Transgender individuals are misunderstood and inadequately treated in many conventional substance abuse treatment programs. This article reviews current concepts regarding the definition and diversity of transgenderism and summarizes the existing literature on the prevalence and correlates of substance use in transgendered populations. Examples of culturally competent and gender-sensitive treatment in specialized settings are cited, with a call to extend these initiatives throughout the gamut of service venues that engage transgender individuals. Cultural competence combined with gender sensitivity should improve the effectiveness of substance abuse treatment for transgender individuals and will contribute to the goal of providing effective services in an increasingly diverse society.

Visible-light sensitization of TiO2 photocatalysts via wet chemical N-doping for the degradation of dissolved organic compounds in wastewater treatment: a review

NASA Astrophysics Data System (ADS)

Zhang, Wei; Jia, Baoping; Wang, Qiuze; Dionysiou, Dionysois

2015-05-01

Increased pollution of ground and surface water and emerging new micropollutants from a wide variety of industrial, municipal, and agricultural sources has increased demand on the development of innovative new technologies and materials whereby challenges associated with the provision of safe potable water can be addressed. Heterogeneous photocatalysis using visible-light sensitized TiO2 photocatalysts has attracted a lot of attention as it can effectively remove dissolved organic compound in water without generating harmful by-products. On this note, recent progress on visible-light sensitive TiO2 synthesis via wet chemical N-doping method is reviewed. In a typical visible-light sensitive TiO2 preparation via wet chemical methods, the chemical (e.g., N-doping content and states) and morphological properties (e.g., particle size, surface area, and crystal phase) of TiO2 in as-prepared resultants are sensitively dependent on many experimental variables during the synthesis. This has also made it very difficult to provide a universal guidance at this stage with a certainty for each variable of N-doping preparation. Instead of one-factor-at-a-time style investigation, a statistically valid parameter optimization investigation for general optima of photocatalytic activity will be certainly useful. Optimization of the preparation technique is envisaged to be beneficial to many environmental applications, i.e., dissolved organic compounds removal in wastewater treatment.

Why are freeform telescopes less alignment sensitive than a traditional unobscured TMA?

NASA Astrophysics Data System (ADS)

Thompson, Kevin P.; Schiesser, Eric; Rolland, Jannick P.

2015-10-01

As freeform optical systems emerge as interesting and innovative solutions for imaging in 3D packages there is an assumption they are going to be more sensitive particularly at assembly. While it is true that the clocking of the component becomes a relatively weak new tolerance, for the most effective new class of freeform systems the alignment sensitivity is actually lower in most cases than for a comparable traditional unobscured three mirror anastigmatic (TMA) telescope. Traditional unobscured TMA telescopes, whose designs emerged in the mid-70s and which begin to appear as hardware in the literature in the early 90s, are based on using increasingly offset apertures with otherwise coaxial rotationally symmetric mirrors. The mirrors (typically 3 to correct spherical, coma, and astigmatism) have evolved to contain more high order terms as the designs are pushed to more compact and wider field packages - the NIRCAM camera for the JWST is an excellent example of this [1]. As the higher order terms are added, the mirrors become increasingly sensitive to decenters and tilts. An emerging class of freeform telescopes that provide wider field of view and/or faster f/numbers than the traditional TMA are based on a strategy where the surface shape remains a low order Zernike-type surface even in compact, unobscured packages. This optical design strategy results in an optical form that is not only higher performance but simultaneously less sensitive to alignment.

Circadian phase, dynamics of subjective sleepiness and sensitivity to blue light in young adults complaining of a delayed sleep schedule.

PubMed

Moderie, Christophe; Van der Maren, Solenne; Dumont, Marie

2017-06-01

To assess factors that might contribute to a delayed sleep schedule in young adults with sub-clinical features of delayed sleep phase disorder. Two groups of 14 young adults (eight women) were compared: one group complaining of a delayed sleep schedule and a control group with an earlier bedtime and no complaint. For one week, each subject maintained a target bedtime reflecting their habitual sleep schedule. Subjects were then admitted to the laboratory for the assessment of circadian phase (dim light melatonin onset), subjective sleepiness, and non-visual light sensitivity. All measures were timed relative to each participant's target bedtime. Non-visual light sensitivity was evaluated using subjective sleepiness and salivary melatonin during 1.5-h exposure to blue light, starting one hour after target bedtime. Compared to control subjects, delayed subjects had a later circadian phase and a slower increase of subjective sleepiness in the late evening. There was no group difference in non-visual sensitivity to blue light, but we found a positive correlation between melatonin suppression and circadian phase within the delayed group. Our results suggest that a late circadian phase, a slow build-up of sleep need, and an increased circadian sensitivity to blue light contribute to the complaint of a delayed sleep schedule. These findings provide targets for strategies aiming to decreasing the severity of a sleep delay and the negative consequences on daytime functioning and health. Copyright © 2017 Elsevier B.V. All rights reserved.

Coronary angiography using synchrotron radiation (invited)

NASA Astrophysics Data System (ADS)

Thompson, A. C.; Rubenstein, E.; Zeman, H. D.; Hofstadter, R.; Otis, J. N.; Giacomini, J. C.; Gordon, H. J.; Brown, G. S.; Thomlinson, W.; Kernoff, R. S.

1989-07-01

Imaging of coronary arteries using a venous instead of an arterial injection of contrast agent could provide a much safer method to diagnose heart disease. The tunability, intensity, and collimation of synchrotron radiation x-ray beams makes possible imaging systems with greatly improved imaging sensitivity. A pair of fan x-ray beams, a movable patient chair, and a multielement x-ray detector are used to acquire a pair of x-ray images above and below the iodine K edge. The logarithmic subtraction of these two images produces an image with excellent sensitivity to contrast agent and minimal sensitivity to bone and tissue. High-quality images from a dog and preliminary images from five humans have been obtained. Improvements are being made to the system to increase the effective radiation flux and to measure the position of both x-ray beams.

Increasing sensitivity and angle-of-view of mid-wave infrared detectors by integration with dielectric microspheres

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

Allen, Kenneth W., E-mail: kenneth.allen@gtri.gatech.edu; Astratov, Vasily N., E-mail: astratov@uncc.edu; Air Force Research Laboratory, Sensors Directorate, Wright Patterson AFB, Ohio 45433

2016-06-13

We observed up to 100 times enhancement of sensitivity of mid-wave infrared photodetectors in the 2–5 μm range by using photonic jets produced by sapphire, polystyrene, and soda-lime glass microspheres with diameters in the 90–300 μm range. By finite-difference time-domain (FDTD) method for modeling, we gain insight into the role of the microspheres refractive index, size, and alignment with respect to the detector mesa. A combination of enhanced sensitivity with angle-of-view (AOV) up to 20° is demonstrated for individual photodetectors. It is proposed that integration with microspheres can be scaled up for large focal plane arrays, which should provide maximal light collectionmore » efficiencies with wide AOVs, a combination of properties highly attractive for imaging applications.« less

Highly Sensitive Bulk Silicon Chemical Sensors with Sub-5 nm Thin Charge Inversion Layers.

PubMed

Fahad, Hossain M; Gupta, Niharika; Han, Rui; Desai, Sujay B; Javey, Ali

2018-03-27

There is an increasing demand for mass-producible, low-power gas sensors in a wide variety of industrial and consumer applications. Here, we report chemical-sensitive field-effect-transistors (CS-FETs) based on bulk silicon wafers, wherein an electrostatically confined sub-5 nm thin charge inversion layer is modulated by chemical exposure to achieve a high-sensitivity gas-sensing platform. Using hydrogen sensing as a "litmus" test, we demonstrate large sensor responses (>1000%) to 0.5% H 2 gas, with fast response (<60 s) and recovery times (<120 s) at room temperature and low power (<50 μW). On the basis of these performance metrics as well as standardized benchmarking, we show that bulk silicon CS-FETs offer similar or better sensing performance compared to emerging nanostructures semiconductors while providing a highly scalable and manufacturable platform.

Evidence for sensitized fatigue pathways in patients with chronic fatigue syndrome.

PubMed

Staud, Roland; Mokthech, Meriem; Price, Donald D; Robinson, Michael E

2015-04-01

Patients with chronic fatigue syndrome (CFS) frequently demonstrate intolerance to physical exertion that is often reported as increased and long-lasting fatigue. Because no specific metabolic alterations have been identified in CFS patients, we hypothesized that sensitized fatigue pathways become activated during exercise corresponding with increased fatigue. After exhausting handgrip exercise, muscle metabolites were trapped in the forearm tissues of 39 CFS patients and 29 normal control (NC) by sudden occlusion for up to 5 minutes. A nonocclusive condition of similar duration was used as control. Repeated fatigue and pain ratings were obtained before and after exercise. Mechanical and heat hyperalgesia were assessed by quantitative sensory testing. All subjects fulfilled the 1994 Fukuda Criteria for CFS. Normal control and CFS subjects exercised for 6.6 (2.4) and 7.0 (2.7) minutes (P > 0.05). Forearm occlusion lasted for 4.7 (1.3) and 4.9 (1.8) minutes in NC and CFS subjects, respectively (P > 0.05). Although fatigue ratings of CFS subjects increased from 4.8 (2.0) to 5.6 (2.1) visual analogue scale (VAS) units during forearm occlusion, they decreased from 5.0 (1.8) to 4.8 (2.0) VAS units during the control condition without occlusion (P = 0.04). A similar time course of fatigue ratings was observed in NC (P > 0.05), although their ratings were significantly lower than those of CFS subjects (P < 0.001). Quantitative sensory testing demonstrated heat and mechanical hyperalgesia in CFS subjects. Our findings provide indirect evidence for significant contributions of peripheral tissues to the increased exercise-related fatigue in CFS patients consistent with sensitization of fatigue pathways. Future interventions that reduce sensitization of fatigue pathways in CFS patients may be of therapeutic benefit.

Nicotine-induced locomotor sensitization: pharmacological analyses with candidate smoking cessation aids.

PubMed

Goutier, Wouter; Kloeze, Margreet; McCreary, Andrew C

2016-03-01

There are a number of approved therapeutics for the management of alcohol dependence, which might also convey the potential as smoking cessation aids. The present study investigated the effect of a few of these therapeutics and potential candidates (non-peptide vasopressin V1b antagonists) on the expression of nicotine-induced behavioral sensitization in Wistar rats. The following compounds were included in this evaluation: rimonabant, bupropion, topiramate, acamprosate, naltrexone, mecamylamine, nelivaptan (SSR-149415, V1b antagonist) and two novel V1b antagonists. Following the development of nicotine-induced locomotor sensitization and a withdrawal period, the expression of sensitization was assessed in the presence of one of the examined agents given 30 minutes prior to the nicotine challenge injection. Acamprosate, naltrexone, rimonabant, mecamylamine, nelivaptan and V1b antagonist 'compound 2' significantly antagonized the expression of nicotine-induced sensitization. Whereas topiramate showed a trend for effects, the V1b antagonist 'compound 1' did not show any significant effects. Bupropion failed to block sensitization but increased activity alone and was therefore tested in development and cross-sensitization studies. Taken together, these findings provide pre-clinical evidence that these molecules attenuated the expression of nicotine-induced sensitization and should be further investigated as putative treatments for nicotine addiction. Moreover, V1b antagonists should be further investigated as a potential novel smoking cessation aid. © 2014 Society for the Study of Addiction.

A Large Array of Small Antennas to Support Future NASA Missions

NASA Astrophysics Data System (ADS)

Jones, D. L.; Weinreb, S.; Preston, R. A.

2001-01-01

A team of engineers and scientists at JPL is currently working on the design of an array of small radio antennas with a total collecting area up to twenty times that of the largest existing (70 m) DSN antennas. An array of this size would provide obvious advantages for high data rate telemetry reception and for spacecraft navigation. Among these advantages are an order-of-magnitude increase in sensitivity for telemetry downlink, flexible sub-arraying to track multiple spacecraft simultaneously, increased reliability through the use of large numbers of identical array elements, very accurate real-time angular spacecraft tracking, and a dramatic reduction in cost per unit area. NASA missions in many disciplines, including planetary science, would benefit from this increased DSN capability. The science return from planned missions could be increased, and opportunities for less expensive or completely new kinds of missions would be created. The DSN array would also bean immensely valuable instrument for radio astronomy. Indeed, it would be by far the most sensitive radio telescope in the world. Additional information is contained in the original extended abstract.

Rapid determination of surfactant critical micelle concentration in aqueous solutions using fiber-optic refractive index sensing.

PubMed

Tan, Chun Hua; Huang, Zhen Jian; Huang, Xu Guang

2010-06-01

We describe a simple and rapid method for determining the critical micelle concentration (CMC) of surfactants from fiber-optic measurements of refractive index. The refractive index of an aqueous surfactant solution was monitored as the surfactant concentration was increased using an automated dispensing system. On reaching the surfactant's CMC value, an abrupt change was observed in the rate of increase of the refractive index with increasing concentration. The measurement system provides rapid semiautomatic data collection and analysis, increasing the precision, sensitivity, and range of applicability of the technique while substantially decreasing the amount of manual intervention required. Measurements of CMC for sodium dodecyl sulfate (8.10mM), cetyltrimethylammonium chloride (1.58mM), and Triton X-100 (0.21mM) were in excellent agreement with values previously reported in the literature. The method is applicable to cationic, anionic, and nonionic surfactants, and it offers a facile, in situ, and sensitive means of detecting micelle formation over a broad range of CMC values larger than 10(-1)mM. Copyright 2010 Elsevier Inc. All rights reserved.

Targeting protein-trafficking pathways alters melanoma treatment sensitivity

PubMed Central

Huang, Zhi-ming; Chinen, Milka; Chang, Philip J.; Xie, Tong; Zhong, Lily; Demetriou, Stephanie; Patel, Mira P.; Scherzer, Rebecca; Sviderskaya, Elena V.; Bennett, Dorothy C.; Millhauser, Glenn L.; Oh, Dennis H.; Cleaver, James E.; Wei, Maria L.

2012-01-01

Protein-trafficking pathways are targeted here in human melanoma cells using methods independent of oncogene mutational status, and the ability to up-regulate and down-regulate tumor treatment sensitivity is demonstrated. Sensitivity of melanoma cells to cis-diaminedichloroplatinum II (cDDP, cis-platin), carboplatin, dacarbazine, or temozolomide together with velaparib, an inhibitor of poly (ADP ribose) polymerase 1, is increased by up to 10-fold by targeting genes that regulate both protein trafficking and the formation of melanosomes, intracellular organelles unique to melanocytes and melanoma cells. Melanoma cells depleted of either of the protein-trafficking regulators vacuolar protein sorting 33A protein (VPS33A) or cappuccino protein (CNO) have increased nuclear localization of cDDP, increased nuclear DNA damage by platination, and increased apoptosis, resulting in increased treatment sensitivity. Depleted cells also exhibit a decreased proportion of intracellular, mature melanosomes compared with undepleted cells. Modulation of protein trafficking via cell-surface signaling by binding the melanocortin 1 receptor with the antagonist agouti-signaling protein decreased the proportion of mature melanosomes formed and increased cDDP sensitivity, whereas receptor binding with the agonist melanocyte-stimulating hormone resulted in an increased proportion of mature melanosomes formed and in decreased sensitivity (i.e., increased resistance) to cDDP. Mutation of the protein-trafficking gene Hps6, known to impair the formation of mature melanosomes, also increased cDDP sensitivity. Together, these results indicate that targeting protein-trafficking molecules markedly increases melanoma treatment sensitivity and influences the degree of melanosomes available for sequestration of therapeutic agents. PMID:22203954

Fat-water MRI is sensitive to local adipose tissue inflammatory changes in a diet-induced obesity mouse model at 15T

NASA Astrophysics Data System (ADS)

Ong, Henry H.; Webb, Corey D.; Gruen, Marnie L.; Hasty, Alyssa H.; Gore, John C.; Welch, E. B.

2015-03-01

In obesity, fat-water MRI (FWMRI) methods provide valuable information about adipose tissue (AT) distribution. AT is known to undergo complex metabolic and endocrine changes in association with chronic inflammation including iron overloading. Here, we investigate the potential for FWMRI parameters (fat signal fraction (FSF), local magnetic field offset, and T2*) to be sensitive to AT inflammatory changes in an established diet-induced obesity mouse model. Male C57BL/6J mice were placed on a low fat (LFD) or a high fat diet (HFD). 3D multi- gradient-echo MRI at 15.2T was performed at baseline, 4, 8, 12, and 16 weeks after diet onset. A 3D fat-water separation algorithm and additional processing was used to generate FSF, local field offset, and T2* maps. We examined these parameters in perirenal AT ROIs from HFD and LFD mice. Results: The data suggest that FSF, local field offset, and T2* can differentiate time course behavior between inflamed and control AT (increasing FSF, decreasing local field offset, increasing followed by decreasing T2*). The biophysical mechanisms of these observed changes are not well understood and require further study. To the best of our knowledge, we report the first evidence that FWMRI can provide biomarkers sensitive to AT inflammation, and that FWMRI has the potential for longitudinal non-invasive assessment of AT inflammation in obesity.

RAPID DIAGNOSIS OF PNEUMOCOCCAL PNEUMONIA AMONG HIV-INFECTED ADULTS WITH URINE ANTIGEN DETECTION

PubMed Central

Boulware, David R; Daley, Charles L.; Merrifield, Cynthia; Hopewell, Philip C.; Janoff, Edward N.

2007-01-01

Objectives Streptococcus pneumoniae is the leading cause of bacterial pneumonia and associated bacteremia during HIV infection. Rapid diagnostic assays may limit inappropriate therapy. Methods Clinical signs and symptoms and sera and urine were collected prospectively from 70 adults with pneumococcal pneumonia, including 47 with HIV co-infection. Pneumococcal C-polysaccharide antigen was detected in urine using the Binax® immunochromatographic test (ICT). A systematic review of 24 published studies was conducted. Results Clinical symptoms, signs, and laboratory parameters except leukocytosis, were similar in HIV-infected and HIV-seronegative pneumonia. The performance of the urine antigen ICT was independent of HIV-status (sensitivity 81%, specificity 98%, positive (PPV) and negative predictive values (NPV) 98%, and 82%, respectively). The sensitivity of sputum Gram’s stain was 58% [34/59] with sputum unable to be provided by 16%. The CRP response was identical in HIV-infected (mean ± SD) 133 ± 88 vs. seronegative 135 ± 104 mg/L (p=0.9). In the systematic review, the ICT performance revealed 74% sensitivity (95% CI: 72% to 77%) and 94% specificity (95% CI: 93% to 95%). Urine antigen testing increases etiologic diagnosis by 23% (Range: 10% –59%) when testing adults with community acquired pneumonia of unknown etiology. Conclusions Urinary antigen detection provides a credible rapid diagnostic test for pneumococcal pneumonia regardless of HIV-status. CRP response to acute infection is similar in HIV co-infection and increases diagnostic certainty. PMID:17692384

Longitudinal Changes in Behavioral Approach System Sensitivity and Brain Structures Involved in Reward Processing during Adolescence

ERIC Educational Resources Information Center

Urosevic, Snezana; Collins, Paul; Muetzel, Ryan; Lim, Kelvin; Luciana, Monica

2012-01-01

Adolescence is a period of radical normative changes and increased risk for substance use, mood disorders, and physical injury. Researchers have proposed that increases in reward sensitivity (i.e., sensitivity of the behavioral approach system [BAS]) and/or increases in reactivity to all emotional stimuli (i.e., reward and threat sensitivities)…

Factors influencing atmospheric composition over subarctic North America during summer

NASA Technical Reports Server (NTRS)

Wofsy, Steven C.; Fan, S. -M.; Blake, D. R.; Bradshaw, J. D.; Sandholm, S. T.; Singh, H. B.; Sachse, G. W.; Harriss, R. C.

1994-01-01

Elevated concentrations of hydrocarbons, CO, and nitrogen oxides were observed in extensive haze layers over northeastern Canada in the summer of 1990, during ABLE 3B. Halocarbon concentrations remained near background in most layers, indicating a source from biomass wildfires. Elevated concentrations of C2Cl4 provided a sensitive indicator for pollution from urban/industrial sources. Detailed analysis of regional budgets for CO and hydrocarbons indicates that biomass fires accounted for approximately equal to 70% of the input to the subarctic for most hydrocarbons and for acetone and more than 50% for CO. Regional sources for many species (including CO) exceeded chemical sinks during summer, and the boreal region provided a net source to midlatitudes. Interannual variations and long-term trends in atmospheric composition are sensitive to climatic change; a shift to warmer, drier conditions could increase the areas burned and thus the sources of many trace gases.

Tip/tilt optimizations for polynomial apodized vortex coronagraphs on obscured telescope pupils

NASA Astrophysics Data System (ADS)

Fogarty, Kevin; Pueyo, Laurent; Mazoyer, Johan; N'Diaye, Mamadou

2017-09-01

Obstructions due to large secondary mirrors, primary mirror segmentation, and secondary mirror support struts all introduce diffraction artifacts that limit the performance offered by coronagraphs. However, just as vortex coronagraphs provides theoretically ideal cancellation of on-axis starlight for clear apertures, the Polynomial Apodized Vortex Coronagraph (PAVC) completely blocks on-axis light for apertures with central obscurations, and delivers off-axis throughput that improves as the topological charge of the vortex increases. We examine the sensitivity of PAVC designs to tip/tilt aberrations and stellar angular size, and discuss methods for mitigating these effects. By imposing additional constraints on the pupil plane apodization, we decrease the sensitivity of the PAVC to the small positional shifts of the on-axis source induced by either tip/tilt or stellar angular size; providing a route to overcoming an important hurdle facing the performance of vortex coronagraphs on telescopes with complicated pupils.

Temperature-independent fiber-Bragg-grating-based atmospheric pressure sensor

NASA Astrophysics Data System (ADS)

Zhang, Zhiguo; Shen, Chunyan; Li, Luming

2018-03-01

Atmospheric pressure is an important way to achieve a high degree of measurement for modern aircrafts, moreover, it is also an indispensable parameter in the meteorological telemetry system. With the development of society, people are increasingly concerned about the weather. Accurate and convenient atmospheric pressure parameters can provide strong support for meteorological analysis. However, electronic atmospheric pressure sensors currently in application suffer from several shortcomings. After an analysis and discussion, we propose an innovative structural design, in which a vacuum membrane box and a temperature-independent strain sensor based on an equal strength cantilever beam structure and fiber Bragg grating (FBG) sensors are used. We provide experimental verification of that the atmospheric pressure sensor device has the characteristics of a simple structure, lack of an external power supply, automatic temperature compensation, and high sensitivity. The sensor system has good sensitivity, which can be up to 100 nm/MPa, and repeatability. In addition, the device exhibits desired hysteresis.

Screening for modulators of cisplatin sensitivity: unbiased screens reveal common themes.

PubMed

Nijwening, Jeroen H; Kuiken, Hendrik J; Beijersbergen, Roderick L

2011-02-01

Cisplatin is a widely used chemotherapeutic agent to treat a variety of solid tumors. The cytotoxic mode of action of cisplatin is mediated by inducing conformational changes in DNA including intra- and inter-strand crosslink adducts. Recognition of these adducts results in the activation of the DNA damage response resulting in cell cycle arrest, repair, and potentially, apoptosis. Despite the clinical efficacy of cisplatin, many tumors are either intrinsically resistant or acquire resistance during treatment. The identification of cisplatin drug response modulators can help us understand these resistance mechanisms, provide biomarkers for treatment strategies, or provide drug targets for combination therapy. Here we discuss functional genetic screens, including one performed by us, set up to identify genes whose inhibition results in increased sensitivity to cisplatin. In summary, the validated genes identified in these screens mainly operate in DNA damage response including nucleotide excision repair, translesion synthesis, and homologous recombination.

Outside-the-(Cavity-prep)-Box Thinking

PubMed Central

Thompson, V.P.; Watson, T.F.; Marshall, G.W.; Blackman, B.R.K.; Stansbury, J.W.; Schadler, L.S.; Pearson, R.A.; Libanori, R.

2013-01-01

Direct placement restorative materials must interface with tooth structures that are often compromised by caries or trauma. The material must seal the interface while providing sufficient strength and wear resistance to assure function of the tooth for, ideally, the lifetime of the patient. Needed are direct restorative materials that are less technique-sensitive than current resin-based composite systems while having improved properties. The ideal material could be successfully used in areas of the world with limited infrastructure. Advances in our understanding of the interface between the restoration adhesive system and the stages of carious dentin can be used to promote remineralization. Application of fracture mechanics to adhesion at the tooth-restoration interface can provide insights for improvement. Research in polymer systems suggests alternatives to current composite resin matrix systems to overcome technique sensitivity, while advances in nano- and mesoparticle reinforcement and alignment in composite systems can increase material strength, toughness, and wear resistance, foreshadowing dental application. PMID:24129814

Using normal ranges for interpreting results of monitoring and tiering to guide future work: A case study of increasing polycyclic aromatic compounds in lake sediments from the Cold Lake oil sands (Alberta, Canada) described in Korosi et al. (2016).

PubMed

Munkittrick, Kelly R; Arciszewski, Tim J

2017-12-01

Since the publishing of the Kelly et al. papers (2009, 2010) describing elevated contaminants in snow near the Alberta oil sands, there has been a significant expansion of monitoring efforts, enhanced by $50M a year contributed by industry to a regional Joint Oil Sands Monitoring (JOSM) program. In parallel to the intensification of research and monitoring efforts, including expansion of measured indicators, techniques for chemical analysis have also become more sensitive. Both factors contribute to the increased sensitivity and power, and improve our capacity to detect any change. The increase in capability requires a counterbalance to account for trivial change. This can be done using an interpretative approach that requires contextualization of differences to meaningfully inform environmental monitoring programs and provide focus for action. Experience obtained through 25 years of involvement with Canada's Environmental Effects Monitoring (EEM) program has shown that a tiered program informed by triggers can provide the context to make decisions about monitoring priorities. Here we provide a potential interpretation framework using a case study around the Korosi et al. (2016) study which found recent increases in alkylated polycyclic aromatic compounds (aPACs) in the Cold Lake in situ oil sands area. Public contaminant profiles from the JOSM studies in the oil sands region are used to evaluate the changes using an interpretation framework based on estimated normal ranges using existing data for site-specific, local and regional (distant) levels that was modelled after the tiered Canadian EEM design. Copyright © 2017 Elsevier Ltd. All rights reserved.

Update on the effects of physical activity on insulin sensitivity in humans

PubMed Central

Bird, Stephen R; Hawley, John A

2016-01-01

Purpose and methods This review presents established knowledge on the effects of physical activity (PA) on whole-body insulin sensitivity (SI) and summarises the findings of recent (2013–2016) studies. Discussion and conclusions Recent studies provide further evidence to support the notion that regular PA reduces the risk of insulin resistance, metabolic syndrome and type 2 diabetes, and SI improves when individuals comply with exercise and/or PA guidelines. Many studies indicate a dose response, with higher energy expenditures and higher exercise intensities, including high intensity interval training (HIIT), producing greater benefits on whole-body SI, although these findings are not unanimous. Aerobic exercise interventions can improve SI without an associated increase in cardiorespiratory fitness as measured by maximal or peak oxygen consumption. Both aerobic and resistance exercise can induce improvements in glycaemic regulation, with some suggestions that exercise regimens including both may be more efficacious than either exercise mode alone. Some studies report exercise-induced benefits to SI that are independent of habitual diet and weight loss, while others indicate an association with fat reduction, hence the debate over the relative importance of PA and weight loss continues. During exercise, muscle contraction stimulated improvements in SI are associated with increases in AMPK activity, which deactivates TCB1D1, promoting GLUT4 translocation to the cell membrane and thereby increasing glucose uptake. Postexercise, increases in Akt deactivate TCB1D4 and thereby increase GLUT4 translocation to the cell membrane. The reduction in intramuscular saturated fatty acids and concomitant reductions in ceramides, but not diacylglycerols, provide a potential link between intramuscular lipid content and SI. Increased skeletal muscle capillarisation provides another independent adaptation through which SI is improved, as does enhanced β cell activity. Recent studies are combining exercise interventions with dietary and feeding manipulations to investigate the potential for augmenting the exercise-induced improvements in SI and glycaemic control. PMID:28879026

Update on the effects of physical activity on insulin sensitivity in humans.

PubMed

Bird, Stephen R; Hawley, John A

2016-01-01

This review presents established knowledge on the effects of physical activity (PA) on whole-body insulin sensitivity (SI) and summarises the findings of recent (2013-2016) studies. Recent studies provide further evidence to support the notion that regular PA reduces the risk of insulin resistance, metabolic syndrome and type 2 diabetes, and SI improves when individuals comply with exercise and/or PA guidelines. Many studies indicate a dose response, with higher energy expenditures and higher exercise intensities, including high intensity interval training (HIIT), producing greater benefits on whole-body SI, although these findings are not unanimous. Aerobic exercise interventions can improve SI without an associated increase in cardiorespiratory fitness as measured by maximal or peak oxygen consumption. Both aerobic and resistance exercise can induce improvements in glycaemic regulation, with some suggestions that exercise regimens including both may be more efficacious than either exercise mode alone. Some studies report exercise-induced benefits to SI that are independent of habitual diet and weight loss, while others indicate an association with fat reduction, hence the debate over the relative importance of PA and weight loss continues. During exercise, muscle contraction stimulated improvements in SI are associated with increases in AMPK activity, which deactivates TCB1D1, promoting GLUT4 translocation to the cell membrane and thereby increasing glucose uptake. Postexercise, increases in Akt deactivate TCB1D4 and thereby increase GLUT4 translocation to the cell membrane. The reduction in intramuscular saturated fatty acids and concomitant reductions in ceramides, but not diacylglycerols, provide a potential link between intramuscular lipid content and SI. Increased skeletal muscle capillarisation provides another independent adaptation through which SI is improved, as does enhanced β cell activity. Recent studies are combining exercise interventions with dietary and feeding manipulations to investigate the potential for augmenting the exercise-induced improvements in SI and glycaemic control.

What are Hospice Providers in the Carolinas Doing to Reach African Americans in Their Service Area?

PubMed Central

Payne, Richard; Kuchibhatla, Maragatha N.

2016-01-01

Abstract Background: Experts and national organizations recommend that hospices work to increase service to African Americans, a group historically underrepresented in hospice. Objective: The study objective was to describe strategies among hospices in North and South Carolina to increase service to African Americans and identify hospice characteristics associated with these efforts. Methods: The study was a cross-sectional survey using investigator-developed scales to measure frequency of community education/outreach, directed marketing, efforts to recruit African American staff, cultural sensitivity training, and goals to increase service to African Americans. We used nonparametric Wilcoxon tests to compare mean scale scores by sample characteristics. Results: Of 118 eligible hospices, 79 (67%) completed the survey. Over 80% were at least somewhat concerned about the low proportion of African Americans they served, and 78.5% had set goals to increase service to African Americans. Most were engaged in community education/outreach, with 92.4% reporting outreach to churches, 76.0% to social services organizations, 40.5% to businesses, 35.4% to civic groups, and over half to health care providers; 48.0% reported directed marketing via newspaper and 40.5% via radio. The vast majority reported efforts to recruit African American staff, most often registered nurses (63.75%). Nearly 90% offered cultural sensitivity training to staff. The frequency of strategies to increase service to African Americans did not vary by hospice characteristics, such as profit status, size, or vertical integration, but was greater among hospices that had set goals to increase service to African Americans. Conclusions: Many hospices are engaged in efforts to increase service to African Americans. Future research should determine which strategies are most effective. PMID:26840854

What are Hospice Providers in the Carolinas Doing to Reach African Americans in Their Service Area?

PubMed

Johnson, Kimberly S; Payne, Richard; Kuchibhatla, Maragatha N

2016-02-01

Experts and national organizations recommend that hospices work to increase service to African Americans, a group historically underrepresented in hospice. The study objective was to describe strategies among hospices in North and South Carolina to increase service to African Americans and identify hospice characteristics associated with these efforts. The study was a cross-sectional survey using investigator-developed scales to measure frequency of community education/outreach, directed marketing, efforts to recruit African American staff, cultural sensitivity training, and goals to increase service to African Americans. We used nonparametric Wilcoxon tests to compare mean scale scores by sample characteristics. Of 118 eligible hospices, 79 (67%) completed the survey. Over 80% were at least somewhat concerned about the low proportion of African Americans they served, and 78.5% had set goals to increase service to African Americans. Most were engaged in community education/outreach, with 92.4% reporting outreach to churches, 76.0% to social services organizations, 40.5% to businesses, 35.4% to civic groups, and over half to health care providers; 48.0% reported directed marketing via newspaper and 40.5% via radio. The vast majority reported efforts to recruit African American staff, most often registered nurses (63.75%). Nearly 90% offered cultural sensitivity training to staff. The frequency of strategies to increase service to African Americans did not vary by hospice characteristics, such as profit status, size, or vertical integration, but was greater among hospices that had set goals to increase service to African Americans. Many hospices are engaged in efforts to increase service to African Americans. Future research should determine which strategies are most effective.

Community structure analysis of rejection sensitive personality profiles: A common neural response to social evaluative threat?

PubMed

Kortink, Elise D; Weeda, Wouter D; Crowley, Michael J; Gunther Moor, Bregtje; van der Molen, Melle J W

2018-06-01

Monitoring social threat is essential for maintaining healthy social relationships, and recent studies suggest a neural alarm system that governs our response to social rejection. Frontal-midline theta (4-8 Hz) oscillatory power might act as a neural correlate of this system by being sensitive to unexpected social rejection. Here, we examined whether frontal-midline theta is modulated by individual differences in personality constructs sensitive to social disconnection. In addition, we examined the sensitivity of feedback-related brain potentials (i.e., the feedback-related negativity and P3) to social feedback. Sixty-five undergraduate female participants (mean age = 19.69 years) participated in the Social Judgment Paradigm, a fictitious peer-evaluation task in which participants provided expectancies about being liked/disliked by peer strangers. Thereafter, they received feedback signaling social acceptance/rejection. A community structure analysis was employed to delineate personality profiles in our data. Results provided evidence of two subgroups: one group scored high on attachment-related anxiety and fear of negative evaluation, whereas the other group scored high on attachment-related avoidance and low on fear of negative evaluation. In both groups, unexpected rejection feedback yielded a significant increase in theta power. The feedback-related negativity was sensitive to unexpected feedback, regardless of valence, and was largest for unexpected rejection feedback. The feedback-related P3 was significantly enhanced in response to expected social acceptance feedback. Together, these findings confirm the sensitivity of frontal midline theta oscillations to the processing of social threat, and suggest that this alleged neural alarm system behaves similarly in individuals that differ in personality constructs relevant to social evaluation.

Reward sensitivity deficits modulated by dopamine are associated with apathy in Parkinson’s disease

PubMed Central

Manohar, Sanjay; Ben Yehuda, Michael; Chong, Trevor T.-J.; Tofaris, George; Lennox, Graham; Bogdanovic, Marko; Hu, Michele; Husain, Masud

2016-01-01

Abstract Apathy is a debilitating and under-recognized condition that has a significant impact in many neurodegenerative disorders. In Parkinson’s disease, it is now known to contribute to worse outcomes and a reduced quality of life for patients and carers, adding to health costs and extending disease burden. However, despite its clinical importance, there remains limited understanding of mechanisms underlying apathy. Here we investigated if insensitivity to reward might be a contributory factor and examined how this relates to severity of clinical symptoms. To do this we created novel ocular measures that indexed motivation level using pupillary and saccadic response to monetary incentives, allowing reward sensitivity to be evaluated objectively. This approach was tested in 40 patients with Parkinson’s disease, 31 elderly age-matched control participants and 20 young healthy volunteers. Thirty patients were examined ON and OFF their dopaminergic medication in two counterbalanced sessions, so that the effect of dopamine on reward sensitivity could be assessed. Pupillary dilation to increasing levels of monetary reward on offer provided quantifiable metrics of motivation in healthy subjects as well as patients. Moreover, pupillary reward sensitivity declined with age. In Parkinson’s disease, reduced pupillary modulation by incentives was predictive of apathy severity, and independent of motor impairment and autonomic dysfunction as assessed using overnight heart rate variability measures. Reward sensitivity was further modulated by dopaminergic state, with blunted sensitivity when patients were OFF dopaminergic drugs, both in pupillary response and saccadic peak velocity response to reward. These findings suggest that reward insensitivity may be a contributory mechanism to apathy and provide potential new clinical measures for improved diagnosis and monitoring of apathy. 10.1093/brain/aww188_video_abstractaww188_video_abstract PMID:27452600

Value for money? Array genomic hybridization for diagnostic testing for genetic causes of intellectual disability.

PubMed

Regier, Dean A; Friedman, Jan M; Marra, Carlo A

2010-05-14

Array genomic hybridization (AGH) provides a higher detection rate than does conventional cytogenetic testing when searching for chromosomal imbalance causing intellectual disability (ID). AGH is more costly than conventional cytogenetic testing, and it remains unclear whether AGH provides good value for money. Decision analytic modeling was used to evaluate the trade-off between costs, clinical effectiveness, and benefit of an AGH testing strategy compared to a conventional testing strategy. The trade-off between cost and effectiveness was expressed via the incremental cost-effectiveness ratio. Probabilistic sensitivity analysis was performed via Monte Carlo simulation. The baseline AGH testing strategy led to an average cost increase of $217 (95% CI $172-$261) per patient and an additional 8.2 diagnoses in every 100 tested (0.082; 95% CI 0.044-0.119). The mean incremental cost per additional diagnosis was $2646 (95% CI $1619-$5296). Probabilistic sensitivity analysis demonstrated that there was a 95% probability that AGH would be cost effective if decision makers were willing to pay $4550 for an additional diagnosis. Our model suggests that using AGH instead of conventional karyotyping for most ID patients provides good value for money. Deterministic sensitivity analysis found that employing AGH after first-line cytogenetic testing had proven uninformative did not provide good value for money when compared to using AGH as first-line testing. Copyright (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Sensitivity analysis of conservative and reactive stream transient storage models applied to field data from multiple-reach experiments

USGS Publications Warehouse

Gooseff, M.N.; Bencala, K.E.; Scott, D.T.; Runkel, R.L.; McKnight, Diane M.

2005-01-01

The transient storage model (TSM) has been widely used in studies of stream solute transport and fate, with an increasing emphasis on reactive solute transport. In this study we perform sensitivity analyses of a conservative TSM and two different reactive solute transport models (RSTM), one that includes first-order decay in the stream and the storage zone, and a second that considers sorption of a reactive solute on streambed sediments. Two previously analyzed data sets are examined with a focus on the reliability of these RSTMs in characterizing stream and storage zone solute reactions. Sensitivities of simulations to parameters within and among reaches, parameter coefficients of variation, and correlation coefficients are computed and analyzed. Our results indicate that (1) simulated values have the greatest sensitivity to parameters within the same reach, (2) simulated values are also sensitive to parameters in reaches immediately upstream and downstream (inter-reach sensitivity), (3) simulated values have decreasing sensitivity to parameters in reaches farther downstream, and (4) in-stream reactive solute data provide adequate data to resolve effective storage zone reaction parameters, given the model formulations. Simulations of reactive solutes are shown to be equally sensitive to transport parameters and effective reaction parameters of the model, evidence of the control of physical transport on reactive solute dynamics. Similar to conservative transport analysis, reactive solute simulations appear to be most sensitive to data collected during the rising and falling limb of the concentration breakthrough curve. ?? 2005 Elsevier Ltd. All rights reserved.

A traits-based approach for prioritizing species for monitoring and surrogacy selection

DOE PAGES

Pracheil, Brenda M.; McManamay, Ryan A.; Bevelhimer, Mark S.; ...

2016-11-28

The bar for justifying the use of vertebrate animals for study is being increasingly raised, thus requiring increased rigor for species selection and study design. Although we have power analyses to provide quantitative backing for the numbers of organisms used, quantitative backing for selection of study species is not frequently employed. This can be especially important when measuring the impacts of ecosystem alteration, when study species must be chosen that are both sensitive to the alteration and of sufficient abundance for study. Just as important is providing justification for designation of surrogate species for study, especially when the species ofmore » interest is rare or of conservation concern and selection of an appropriate surrogate can have legal implications. In this study, we use a combination of GIS, a fish traits database and multivariate statistical analyses to quantitatively prioritize species for study and to determine potential study surrogate species. We provide two case studies to illustrate our quantitative, traits-based approach for designating study species and surrogate species. In the first case study, we select broadly representative fish species to understand the effects of turbine passage on adult fishes based on traits that suggest sensitivity to turbine passage. In our second case study, we present a framework for selecting a surrogate species for an endangered species. Lastly, we suggest that our traits-based framework can provide quantitative backing and added justification to selection of study species while expanding the inference space of study results.« less

A traits-based approach for prioritizing species for monitoring and surrogacy selection

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

Pracheil, Brenda M.; McManamay, Ryan A.; Bevelhimer, Mark S.

The bar for justifying the use of vertebrate animals for study is being increasingly raised, thus requiring increased rigor for species selection and study design. Although we have power analyses to provide quantitative backing for the numbers of organisms used, quantitative backing for selection of study species is not frequently employed. This can be especially important when measuring the impacts of ecosystem alteration, when study species must be chosen that are both sensitive to the alteration and of sufficient abundance for study. Just as important is providing justification for designation of surrogate species for study, especially when the species ofmore » interest is rare or of conservation concern and selection of an appropriate surrogate can have legal implications. In this study, we use a combination of GIS, a fish traits database and multivariate statistical analyses to quantitatively prioritize species for study and to determine potential study surrogate species. We provide two case studies to illustrate our quantitative, traits-based approach for designating study species and surrogate species. In the first case study, we select broadly representative fish species to understand the effects of turbine passage on adult fishes based on traits that suggest sensitivity to turbine passage. In our second case study, we present a framework for selecting a surrogate species for an endangered species. Lastly, we suggest that our traits-based framework can provide quantitative backing and added justification to selection of study species while expanding the inference space of study results.« less

Changes in Alpha Frequency and Power of the Electroencephalogram during Volatile-Based General Anesthesia.

PubMed

Hight, Darren; Voss, Logan J; Garcia, Paul S; Sleigh, Jamie

2017-01-01

Oscillations in the electroencephalogram (EEG) at the alpha frequency (8-12 Hz) are thought to be ubiquitous during surgical anesthesia, but the details of how this oscillation responds to ongoing changes in volatile anesthetic concentration have not been well characterized. It is not known how often alpha oscillations are absent in the clinical context, how sensitively alpha frequency and power respond to changes in anesthetic concentration, and what effect increased age has on alpha frequency. Bipolar EEG was recorded frontally from 305 patients undergoing surgery with sevoflurane or desflurane providing general anesthesia. A new method of detecting the presence of alpha oscillations based on the stability of the rate of change of the peak frequency in the alpha range was developed. Linear concentration-response curves were fitted to assess the sensitivity of alpha power and frequency measures to changing levels of anesthesia. Alpha oscillations were seen to be inexplicably absent in around 4% of patients. Maximal alpha power increased with increasing volatile anesthetic concentrations in half of the patients, and decreased in the remaining patients. Alpha frequency decreased with increasing anesthetic concentrations in near to 90% of patients. Increasing age was associated with decreased sensitivity to volatile anesthesia concentrations, and with decreased alpha frequency, which sometimes transitioned into the theta range (5-7 Hz). While peak alpha frequency shows a consistent slowing to increasing volatile concentrations, the peak power of the oscillation does not, suggesting that frequency might be more informative of depth of anesthesia than traditional power based measures during volatile-based anesthesia. The alpha oscillation becomes slower with increasing age, even when the decreased anesthetic needs of older patients were taken into account.

Does red noise increase or decrease extinction risk? Single extreme events versus series of unfavorable conditions.

PubMed

Schwager, Monika; Johst, Karin; Jeltsch, Florian

2006-06-01

Recent theoretical studies have shown contrasting effects of temporal correlation of environmental fluctuations (red noise) on the risk of population extinction. It is still debated whether and under which conditions red noise increases or decreases extinction risk compared with uncorrelated (white) noise. Here, we explain the opposing effects by introducing two features of red noise time series. On the one hand, positive autocorrelation increases the probability of series of poor environmental conditions, implying increasing extinction risk. On the other hand, for a given time period, the probability of at least one extremely bad year ("catastrophe") is reduced compared with white noise, implying decreasing extinction risk. Which of these two features determines extinction risk depends on the strength of environmental fluctuations and the sensitivity of population dynamics to these fluctuations. If extreme (catastrophic) events can occur (strong noise) or sensitivity is high (overcompensatory density dependence), then temporal correlation decreases extinction risk; otherwise, it increases it. Thus, our results provide a simple explanation for the contrasting previous findings and are a crucial step toward a general understanding of the effect of noise color on extinction risk.

Mobile technology habits: patterns of association among device usage, intertemporal preference, impulse control, and reward sensitivity.

PubMed

Wilmer, Henry H; Chein, Jason M

2016-10-01

Mobile electronic devices are playing an increasingly pervasive role in our daily activities. Yet, there has been very little empirical research investigating how mobile technology habits might relate to individual differences in cognition and affect. The research presented in this paper provides evidence that heavier investment in mobile devices is correlated with a relatively weaker tendency to delay gratification (as measured by a delay discounting task) and a greater inclination toward impulsive behavior (i.e., weaker impulse control, assessed behaviorally and through self-report) but is not related to individual differences in sensitivity to reward. Analyses further demonstrated that individual variation in impulse control mediates the relationship between mobile technology usage and delay of gratification. Although based on correlational results, these findings lend some backing to concerns that increased use of portable electronic devices could have negative impacts on impulse control and the ability to appropriately valuate delayed rewards.

Reactive oxygen species enhance insulin sensitivity

PubMed Central

Loh, Kim; Deng, Haiyang; Fukushima, Atsushi; Cai, Xiaochu; Boivin, Benoit; Galic, Sandra; Bruce, Clinton; Shields, Benjamin J.; Skiba, Beata; Ooms, Lisa M.; Stepto, Nigel; Wu, Ben; Mitchell, Christina A.; Tonks, Nicholas K.; Watt, Matthew J.; Febbraio, Mark A.; Crack, Peter J.; Andrikopoulos, Sofianos; Tiganis, Tony

2010-01-01

SUMMARY Chronic reactive oxygen species (ROS) production by mitochondria may contribute to the development of insulin resistance, a primary feature of type 2 diabetes. In recent years it has become apparent that ROS generation in response to physiological stimuli such as insulin may also facilitate signaling by reversibly oxidizing and inhibiting protein tyrosine phosphatases (PTPs). Here we report that mice lacking one of the key enzymes involved in the elimination of physiological ROS, glutathione peroxidase 1 (Gpx1), were protected from high fat diet-induced insulin resistance. The increased insulin sensitivity in Gpx1−/− mice was attributed to insulin-induced phosphatidylinositol-3-kinase/Akt signaling and glucose uptake in muscle and could be reversed by the anti-oxidant N-acetylcysteine. Increased insulin signaling correlated with enhanced oxidation of the PTP family member PTEN, which terminates signals generated by phosphatidylinositol-3-kinase. These studies provide causal evidence for the enhancement of insulin signaling by ROS in vivo. PMID:19808019

Exosomes promote cetuximab resistance via the PTEN/Akt pathway in colon cancer cells.

PubMed

Zhang, S; Zhang, Y; Qu, J; Che, X; Fan, Y; Hou, K; Guo, T; Deng, G; Song, N; Li, C; Wan, X; Qu, X; Liu, Y

2017-11-13

Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt. Furthermore, reduced PTEN and increased phosphorylated Akt levels were found in Caco-2 cells after exposure to RKO cell-derived exosomes. Moreover, an Akt inhibitor prevented RKO cell-derived exosome-induced drug resistance in Caco-2 cells. These findings provide novel evidence that exosomes derived from cetuximab-resistant cells could induce cetuximab resistance in cetuximab-sensitive cells, by downregulating PTEN and increasing phosphorylated Akt levels.

Neuroprotective role of ATP-sensitive potassium channels in cerebral ischemia

PubMed Central

Sun, Hong-shuo; Feng, Zhong-ping

2013-01-01

ATP-sensitive potassium (KATP) channels are weak, inward rectifiers that couple metabolic status to cell membrane electrical activity, thus modulating many cellular functions. An increase in the ADP/ATP ratio opens KATP channels, leading to membrane hyperpolarization. KATP channels are ubiquitously expressed in neurons located in different regions of the brain, including the hippocampus and cortex. Brief hypoxia triggers membrane hyperpolarization in these central neurons. In vivo animal studies confirmed that knocking out the Kir6.2 subunit of the KATP channels increases ischemic infarction, and overexpression of the Kir6.2 subunit reduces neuronal injury from ischemic insults. These findings provide the basis for a practical strategy whereby activation of endogenous KATP channels reduces cellular damage resulting from cerebral ischemic stroke. KATP channel modulators may prove to be clinically useful as part of a combination therapy for stroke management in the future. PMID:23123646

Dietary sodium and health: more than just blood pressure.

PubMed

Farquhar, William B; Edwards, David G; Jurkovitz, Claudine T; Weintraub, William S

2015-03-17

Sodium is essential for cellular homeostasis and physiological function. Excess dietary sodium has been linked to elevations in blood pressure (BP). Salt sensitivity of BP varies widely, but certain subgroups tend to be more salt sensitive. The mechanisms underlying sodium-induced increases in BP are not completely understood but may involve alterations in renal function, fluid volume, fluid-regulatory hormones, the vasculature, cardiac function, and the autonomic nervous system. Recent pre-clinical and clinical data support that even in the absence of an increase in BP, excess dietary sodium can adversely affect target organs, including the blood vessels, heart, kidneys, and brain. In this review, the investigators review these issues and the epidemiological research relating dietary sodium to BP and cardiovascular health outcomes, addressing recent controversies. They also provide information and strategies for reducing dietary sodium. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Sensitivity of Dielectric Properties to Wear Process on Carbon Nanofiber/High-Density Polyethylene Composites.

PubMed

Liu, Tian; Wood, Weston; Zhong, Wei-Hong

2011-12-01

We examined the correlation of wear effects with dielectric properties of carbon nanofibers (CNFs; untreated and organosilane-treated)-reinforced high-density polyethylene (HDPE) composites. Wear testing for the nanocomposites over up to 120 h was carried out, and then, dielectric permittivity and dielectric loss factor of the polymer composites with the increased wear time were studied. Scanning electron microscope and optical microscope observations were made to analyze the microstructure features of the nanocomposites. The results reveal that there exist approximate linear relationships of permittivity with wear coefficient for the nanocomposites. Composites containing silanized CNFs with the sufficiently thick coating exhibited high wear resistance. The change in permittivity was more sensitive to the increased wear coefficient for the nanocomposites with lower wear resistance. This work provides potential for further research on the application of dielectric signals to detect the effects of wear process on lifetime of polymeric materials.

Age-related differential sensitivity to MK-801-induced locomotion and stereotypy in C57BL/6 mice

PubMed Central

Qi, Chunting; Zou, Hong; Zhang, Ruizhong; Zhao, Guoping; Jin, Meilei; Yu, Lei

2009-01-01

Psychomotor effects elicited by systemic administration of the noncompetitive NMDA (N-methyl-D-aspartate) receptor antagonist MK-801 (dizocilpine maleate) represent perturbation of glutamatergic pathways, providing an animal model for psychotic symptoms of schizophrenia. Hyperlocomotion and stereotypy are the two main psychomotor behaviors induced by MK-801. This study compared MK-801-induced hyperlocomotion and stereotypy in young (1-month old) and aged mice (12-month old), in order to determine how the aging process may influence these behaviors. The tested MK-801 doses ranged from 0.015 to 1 mg/kg. The data indicated that MK-801 impacted the aged mice more pronouncedly than the young mice, as both hyperlocomotion and stereotypy were increased significantly more in the aged mice relative to the young mice. These results suggest an age-related increase in MK-801 sensitivity in mice. PMID:18053981

Ammonium and nitrate tolerance in lichens.

PubMed

Hauck, Markus

2010-05-01

Since lichens lack roots and take up water, solutes and gases over the entire thallus surface, these organisms respond more sensitively to changes in atmospheric purity than vascular plants. After centuries where effects of sulphur dioxide and acidity were in the focus of research on atmospheric chemistry and lichens, recently the globally increased levels of ammonia and nitrate increasingly affect lichen vegetation and gave rise to intense research on the tolerance of lichens to nitrogen pollution. The present paper discusses the main findings on the uptake of ammonia and nitrate in the lichen symbiosis and to the tolerance of lichens to eutrophication. Ammonia and nitrate are both efficiently taken up under ambient conditions. The tolerance to high nitrogen levels depends, among others, on the capability of the photobiont to provide sufficient amounts of carbon skeletons for ammonia assimilation. Lowly productive lichens are apparently predisposed to be sensitive to excess nitrogen. Copyright 2010 Elsevier Ltd. All rights reserved.

Current Progress of Nanomaterials in Molecularly Imprinted Electrochemical Sensing.

PubMed

Zhong, Chunju; Yang, Bin; Jiang, Xinxin; Li, Jianping

2018-01-02

Nanomaterials have received much attention during the past decade because of their excellent optical, electronic, and catalytic properties. Nanomaterials possess high chemical reactivity, also high surface energy. Thus, provide a stable immobilization platform for biomolecules, while preserving their reactivity. Due to the conductive and catalytic properties, nanomaterials can also enhance the sensitivity of molecularly imprinted electrochemical sensors by amplifying the electrode surface, increasing the electron transfer, and catalyzing the electrochemical reactions. Molecularly imprinted polymers that contain specific molecular recognition sites can be designed for a particular target analyte. Incorporating nanomaterials into molecularly imprinted polymers is important because nanomaterials can improve the response signal, increase the sensitivity, and decrease the detection limit of the sensors. This study describes the classification of nanomaterials in molecularly imprinted polymers, their analytical properties, and their applications in the electrochemical sensors. The progress of the research on nanomaterials in molecularly imprinted polymers and the application of nanomaterials in molecularly imprinted polymers is also reviewed.

Increased sensitivity of spin noise spectroscopy using homodyne detection in n -doped GaAs

NASA Astrophysics Data System (ADS)

Petrov, M. Yu.; Kamenskii, A. N.; Zapasskii, V. S.; Bayer, M.; Greilich, A.

2018-03-01

We implement the homodyne detection scheme for an increase in the polarimetric sensitivity in spin noise spectroscopy. Controlling the laser intensity of the local oscillator, which is guided around the sample and does not perturb the measured spin system, we are able to improve the signal-to-noise ratio. The opportunity for additional amplification of the measured signal strength allows us to reduce the probe laser intensity incident on the sample and therefore to approach the nonperturbative regime. The efficiency of this scheme with signal enhancement by more than a factor of 3 at low probe powers is demonstrated on bulk n -doped GaAs, where the reduced electron-spin relaxation rate is shown experimentally. Additionally, the control of the optical phase provides us with the possibility to switch between measuring Faraday rotation and ellipticity without changes in the optical setup.

A Systemwide Evaluation of a Child Abuse Policy and Staff Development Initiative.

ERIC Educational Resources Information Center

Pugh, Wesley C.; Brawner, Linda

The School District of Philadelphia initiated a child abuse awareness workshop for all schools and school district personnel in April 1988. The objective of the sessions was to provide an increased awareness and sensitivity on the part of all school district employees to the issue of child abuse and its impact on the physical, emotional, and…

Vietnamese Proverbs Compared with Other Sources in Investigating National Characteristics for Pedagogical Purposes.

ERIC Educational Resources Information Center

Mulroy, Kevin J.

The hypothesis was advanced that if the proverbs of a country could provide clues to its inhabitants' character which could be validated by reference to literature and commentaries of various types, an excellent guide would be available for educators. The information could be of value to teachers in that it would increase sensitivity to students,…

Evaluating the Effectiveness of Mental Health First Aid Training among Student Affairs Staff at a Canadian University

ERIC Educational Resources Information Center

Massey, Jennifer; Brooks, Meghan; Burrow, Jeff

2014-01-01

This study evaluates the effectiveness of providing the Mental Health First Aid training program to student affairs staff. The objective of the training was to increase knowledge of mental health, enhance sensitivity, and raise confidence to intervene and assist individuals experiencing a mental health issue. We found the training successfully met…

Characterization of an intraluminal differential frequency-domain photoacoustics system

NASA Astrophysics Data System (ADS)

Lashkari, Bahman; Son, Jungik; Liang, Simon; Castelino, Robin; Foster, F. Stuart; Courtney, Brian; Mandelis, Andreas

2016-03-01

Cardiovascular related diseases are ranked as the second highest cause of death in Canada. Among the most important cardiovascular diseases is atherosclerosis. Current methods of diagnosis of atherosclerosis consist of angiography, intravascular ultrasound (IVUS) and optical coherence tomography (OCT). None of these methods possesses adequate sensitivity, as the ideal technique should be capable of both depth profiling, as well as functional imaging. An alternative technique is photoacoustics (PA) which can perform deep imaging and spectroscopy. The presented study explores the application of wavelength-modulated differential photoacoustic radar (WM-DPAR) for characterizing arterial vessels. The wavelength-modulated differential photoacoustic technique was shown to be able to substantially increase the dynamic range and sensitivity of hemoglobin oxygenation level detection. In this work the differential PA technique was used with a very high frequency modulation range. To perform spectroscopic PA imaging, at least two wavelengths are required. The selected wavelengths for this work are 1210 nm and 980 nm. 1210 nm corresponds to the maximum optical absorption coefficient of cholesterol and cholesteryl esters which are the main constituents of plaques. Since water, elastin and collagen also have high absorption coefficients at 1210 nm, this wavelength alone cannot provide very high sensitivity and specificity. The additional wavelength, 980 nm corresponds to high absorption coefficient of those constituents of healthy artery tissue. The simultaneous application of the abovementioned wavelengths can provide higher sensitivity and improved specificity in detecting lipids in the arterial vessels.

Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications

PubMed Central

Luka, George; Ahmadi, Ali; Najjaran, Homayoun; Alocilja, Evangelyn; DeRosa, Maria; Wolthers, Kirsten; Malki, Ahmed; Aziz, Hassan; Althani, Asmaa; Hoorfar, Mina

2015-01-01

A biosensor can be defined as a compact analytical device or unit incorporating a biological or biologically derived sensitive recognition element immobilized on a physicochemical transducer to measure one or more analytes. Microfluidic systems, on the other hand, provide throughput processing, enhance transport for controlling the flow conditions, increase the mixing rate of different reagents, reduce sample and reagents volume (down to nanoliter), increase sensitivity of detection, and utilize the same platform for both sample preparation and detection. In view of these advantages, the integration of microfluidic and biosensor technologies provides the ability to merge chemical and biological components into a single platform and offers new opportunities for future biosensing applications including portability, disposability, real-time detection, unprecedented accuracies, and simultaneous analysis of different analytes in a single device. This review aims at representing advances and achievements in the field of microfluidic-based biosensing. The review also presents examples extracted from the literature to demonstrate the advantages of merging microfluidic and biosensing technologies and illustrate the versatility that such integration promises in the future biosensing for emerging areas of biological engineering, biomedical studies, point-of-care diagnostics, environmental monitoring, and precision agriculture. PMID:26633409

Freedom from equine infectious anaemia virus infection in Spanish Purebred horses

PubMed Central

Cruz, Fatima; Fores, Paloma; Ireland, Joanne; Moreno, Miguel A.; Newton, Richard

2015-01-01

Introduction No cases of equine infectious anaemia (EIA) have been reported in Spain since 1983. Factors that could increase the risk of reintroducing equine infectious anaemia virus (EIAV) into Spain include the recent occurrence of the disease in Europe and the absence of compulsory serological testing before importation into Spain. Aims and objectives Given the importance of the Spanish Purebred (SP) horse breeding industry in Spain, the aim of this cross-sectional study was to provide evidence of freedom from EIAV in SP stud farms in Central Spain. Materials and methods Serum samples from 555 SP horses, collected between September 2011 and November 2013, were tested using a commercially available EIAV ELISA with a published sensitivity of 100 per cent. Results All 555 samples were negative for antibody to EIAV, providing evidence of a true EIAV seroprevalence between 0 per cent and 0.53 per cent (95% CIs of the sensitivity and specificity of the ELISA technique used Q10 were 100 per cent and 99.3 per cent, respectively) among the SP breeding population in Central Spain. Conclusions These findings should serve to increase confidence when exporting SP horses to other countries. PMID:26392894

A sensitive assay using a native protein substrate for screening HIV-1 maturation inhibitors targeting the protease cleavage site between the matrix and capsid.

PubMed

Lee, Sook-Kyung; Cheng, Nancy; Hull-Ryde, Emily; Potempa, Marc; Schiffer, Celia A; Janzen, William; Swanstrom, Ronald

2013-07-23

The matrix/capsid processing site in the HIV-1 Gag precursor is likely the most sensitive target to inhibit HIV-1 replication. We have previously shown that modest incomplete processing at the site leads to a complete loss of virion infectivity. In the study presented here, a sensitive assay based on fluorescence polarization that can monitor cleavage at the MA/CA site in the context of the folded protein substrate is described. The substrate, an MA/CA fusion protein, was labeled with the fluorescein-based FlAsH (fluorescein arsenical hairpin) reagent that binds to a tetracysteine motif (CCGPCC) that was introduced within the N-terminal domain of CA. By limiting the size of CA and increasing the size of MA (with an N-terminal GST fusion), we were able to measure significant differences in polarization values as a function of HIV-1 protease cleavage. The sensitivity of the assay was tested in the presence of increasing amounts of an HIV-1 protease inhibitor, which resulted in a gradual decrease in the fluorescence polarization values demonstrating that the assay is sensitive in discerning changes in protease processing. The high-throughput screening assay validation in 384-well plates showed that the assay is reproducible and robust with an average Z' value of 0.79 and average coefficient of variation values of <3%. The robustness and reproducibility of the assay were further validated using the LOPAC(1280) compound library, demonstrating that the assay provides a sensitive high-throughput screening platform that can be used with large compound libraries for identifying novel maturation inhibitors targeting the MA/CA site of the HIV-1 Gag polyprotein.

Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats

PubMed Central

Eagle, Andrew L.; Singh, Robby; Kohler, Robert J.; Friedman, Amy L.; Liebowitz, Chelsea P.; Galloway, Matthew P.; Enman, Nicole M.; Jutkiewicz, Emily M.; Perrine, Shane A.

2017-01-01

Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague–Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0,10 or 20mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, asexpected. However, compared to control ratson Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. PMID:25712697

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.

Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.

PubMed

Eagle, Andrew L; Singh, Robby; Kohler, Robert J; Friedman, Amy L; Liebowitz, Chelsea P; Galloway, Matthew P; Enman, Nicole M; Jutkiewicz, Emily M; Perrine, Shane A

2015-05-01

Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague-Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0, 10 or 20 mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, as expected. However, compared to control rats on Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. Copyright © 2015. Published by Elsevier B.V.

[Vasovagal syncope and increased baroreceptor activity: evidence for increased sensibility of the baroreflex and its rapid reversal with acute administration of metoprolol].

PubMed

Pucciarelli, G; De Vecchis, R; Ebraio, F; Corigliano, G G

1997-07-01

In 17 patients suffering from recurrent episodes of vasovagal syncope as well as in 21 healthy subjects without clinical episodes of presyncope or syncope, we evaluated the reflex decrease in heart rate evoked by the phenilephrine test. In the syncopal patients, the measurements were taken 4-12 hours after the clinical appearance of syncope. We divided the syncopal patients as follows: 9 patients, undergoing pharmacological treatment, and 8 untreated patients (drug free arm). In the pharmacological arm of the study, an alternate, randomized administration of metoprolol (150 mg twice daily for 2 days) and verapamil (80 mg every 6 hours for 2 days) was provided. Therefore, in the pharmacological arm as well as in drug free patients, we tested again the baroreflex sensitivity, by means of iv phenilephrine bolus, 3 and 7 days after the clinical appearance of the syncopal event. The baroreflex sensitivity values were significantly higher in the syncopal group compared to the control group (21 +/- 5 vs 13 +/- 4.5 ms/mm Hg; p < 0.01). Of the two tested drugs, only the metoprolol produced a fast (day 3) decrease in baroreflex sensitivity. On the basis of measurements taken after 7 days, we noted a pattern of widespread reduction in baroreflex sensitivity values, found in both treated and untreated patients. In conclusion, patients with vasovagal syncope exhibited a more pronounced maximal parasympathetic activation compared to the control group. The high baroreflex sensitivity values were soon (day 3) reduced by metoprolol, but not by verapamil therapy; a spontaneous normalization in baroreflex sensitivity values was found 7 days after the clinical episode, regardless of therapy.

Improved Insulin Sensitivity After Exercise Training is Linked to Reduced Plasma C14:0 Ceramide in Obesity and Type 2 Diabetes

PubMed Central

Kasumov, Takhar; Solomon, Thomas P.J.; Hwang, Calvin; Huang, Hazel; Haus, Jacob M.; Zhang, Renliang; Kirwan, John P.

2015-01-01

Objective To assess the effect of exercise training on insulin sensitivity and plasma ceramides in obesity and type 2 diabetes (T2D). Methods Twenty-four adults with obesity and normal glucose tolerance (NGT, n=14), or diabetes (n=10) were studied before and after a 12-week supervised exercise-training program (5 d/wk, 1 hr/d, 80–85% of maximum heart rate). Changes in body composition were assessed using hydrostatic weighing and computed tomography. Peripheral tissue insulin sensitivity was assessed by a 40 mU/m2/min hyperinsulinemic euglycemic clamp. Plasma ceramides (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0 and C24:1) were quantified using electrospray ionization tandem mass spectrometry after separation with HPLC. Results Plasma ceramides were similar for the obese NGT and subjects with diabetes, despite differences in glucose tolerance. Exercise significantly reduced body weight and adiposity, and increased peripheral insulin sensitivity in both groups (P<0.05). In addition, plasma C14:0, C16:0, C18:1, and C24:0 ceramide levels were reduced in all subjects following the intervention (P<0.05). Decreases in total (r=-0.51, P=0.02) and C14:0 (r=-0.56, P=0.009) ceramide were negatively correlated with the increase in insulin sensitivity. Conclusion Ceramides are linked to exercise training-induced improvements in insulin sensitivity, and plasma C14:0 ceramide may provide a specific target for investigating lipid-related insulin resistance in obesity and T2D. PMID:25966363

Improved insulin sensitivity after exercise training is linked to reduced plasma C14:0 ceramide in obesity and type 2 diabetes.

PubMed

Kasumov, Takhar; Solomon, Thomas P J; Hwang, Calvin; Huang, Hazel; Haus, Jacob M; Zhang, Renliang; Kirwan, John P

2015-07-01

To assess the effect of exercise training on insulin sensitivity and plasma ceramides in obesity and type 2 diabetes (T2D). Twenty-four adults with obesity and normal glucose tolerance (NGT, n = 14) or diabetes (n = 10) were studied before and after a 12-week supervised exercise-training program (5 days/week, 1 h/day, 80-85% of maximum heart rate). Changes in body composition were assessed using hydrostatic weighing and computed tomography. Peripheral tissue insulin sensitivity was assessed by a 40 mU/m(2) /min hyperinsulinemic euglycemic clamp. Plasma ceramides (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1) were quantified using electrospray ionization tandem mass spectrometry after separation with HPLC. Plasma ceramides were similar for the subjects with obesity and NGT and the subjects with diabetes, despite differences in glucose tolerance. Exercise significantly reduced body weight and adiposity and increased peripheral insulin sensitivity in both groups (P < 0.05). In addition, plasma C14:0, C16:0, C18:1, and C24:0 ceramide levels were reduced in all subjects following the intervention (P < 0.05). Decreases in total (r = -0.51, P = 0.02) and C14:0 (r = -0.56, P = 0.009) ceramide were negatively correlated with the increase in insulin sensitivity. Ceramides are linked to exercise training-induced improvements in insulin sensitivity, and plasma C14:0 ceramide may provide a specific target for investigating lipid-related insulin resistance in obesity and T2D. © 2015 The Obesity Society.

Single-tier testing with the C6 peptide ELISA kit compared with two-tier testing for Lyme disease.

PubMed

Wormser, Gary P; Schriefer, Martin; Aguero-Rosenfeld, Maria E; Levin, Andrew; Steere, Allen C; Nadelman, Robert B; Nowakowski, John; Marques, Adriana; Johnson, Barbara J B; Dumler, J Stephen

2013-01-01

For the diagnosis of Lyme disease, the 2-tier serologic testing protocol for Lyme disease has a number of shortcomings including low sensitivity in early disease; increased cost, time, and labor; and subjectivity in the interpretation of immunoblots. In this study, the diagnostic accuracy of a single-tier commercial C6 ELISA kit was compared with 2-tier testing. The results showed that the C6 ELISA was significantly more sensitive than 2-tier testing with sensitivities of 66.5% (95% confidence interval [CI] 61.7-71.1) and 35.2% (95% CI 30.6-40.1), respectively (P < 0.001) in 403 sera from patients with erythema migrans. The C6 ELISA had sensitivity statistically comparable to 2-tier testing in sera from Lyme disease patients with early neurologic manifestations (88.6% versus 77.3%, P = 0.13) or arthritis (98.3% versus 95.6%, P = 0.38). The specificities of C6 ELISA and 2-tier testing in over 2200 blood donors, patients with other conditions, and Lyme disease vaccine recipients were found to be 98.9% and 99.5%, respectively (P < 0.05, 95% CI surrounding the 0.6 percentage point difference of 0.04 to 1.15). In conclusion, using a reference standard of 2-tier testing, the C6 ELISA as a single-step serodiagnostic test provided increased sensitivity in early Lyme disease with comparable sensitivity in later manifestations of Lyme disease. The C6 ELISA had slightly decreased specificity. Future studies should evaluate the performance of the C6 ELISA compared with 2-tier testing in routine clinical practice. Copyright © 2013 Elsevier Inc. All rights reserved.

Ferrocene-cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel.

PubMed

Podolski-Renić, Ana; Bősze, Szilvia; Dinić, Jelena; Kocsis, László; Hudecz, Ferenc; Csámpai, Antal; Pešić, Milica

2017-08-16

Recently, we demonstrated that ferrocene-containing compounds with a cinchona moiety displayed marked anticancer activity. Here we report on the effects of the most promising isomers encompassing quinine- (compounds 4 and 5) and quinidine-epimers (compounds 6 and 7) - synthesized using improved methods providing controlled diastereoselectivity - in three different human multidrug resistant (MDR) cancer cell lines and their sensitive counterparts (non-small cell lung carcinoma NCI-H460/R/NCI-H460, colorectal carcinoma DLD1-TxR/DLD1 and glioblastoma U87-TxR/U87). We observed that the presence of the MDR phenotype did not diminish the activity of the compounds suggesting that ferrocene quinine- and quinidine-epimers are not substrates for P-glycoprotein, which has been indicated as a major mechanism of MDR in the cell lines used. Considering that metal-based anticancer agents mainly act by increasing ROS production, we investigated the potential of ferrocene-quinidine epimers to generate ROS. We found that 6 and 7 more readily increased ROS production and induced mitochondrial damage in MDR cancer cells. According to cell death analysis, 6 and 7 were more active against MDR cancer cells showing collateral sensitivity. In addition, our data suggest that these compounds could act as inhibitors of autophagy. Importantly, simultaneous treatments of 6 and 7 with paclitaxel (PTX) increased the sensitivity of MDR cancer cells to PTX. In conclusion, the ferrocene-quinidine epimers, besides being selective towards MDR cancer cells, could also possess potential to overcome PTX resistance.

Striatal hyper-sensitivity during stress in remitted individuals with recurrent depression

PubMed Central

Admon, Roee; Holsen, Laura M.; Aizley, Harlyn; Remington, Anne; Whitfield-Gabrieli, Susan; Goldstein, Jill M.; Pizzagalli, Diego A.

2014-01-01

Background Increased sensitivity to stress and dysfunctional reward processing are two primary characteristics of Major Depressive Disorder (MDD) that may persist following remission. Preclinical work has established the pivotal role of the striatum in mediating both stress and reward responses. Human neuroimaging studies have corroborated these preclinical findings and highlighted striatal dysfunction in MDD in response to reward, but have yet to investigate striatal function during stress, in particular in individuals with recurrent depression. Methods Thirty three remitted individuals with a history of recurrent MDD (rMDD) and 35 matched healthy controls underwent a validated mild psychological stress task involving viewing of negative stimuli during fMRI. Cortisol and anxiety levels were assessed throughout scanning. Stress-related activation was investigated in three striatal regions: caudate, nucleus accumbens (Nacc), and putamen. Psychophysiological interaction (PPI) analyses probed connectivity of those regions with central structures of the neural stress circuitry, the amygdala and hippocampus. Results The task increased cortisol and anxiety levels, although to a greater extent in rMDD than healthy controls. In response to the negative stimuli, rMDD individuals, but not controls, also exhibited significantly potentiated caudate, Nacc, and putamen activations, as well as increased caudate-amygdala and caudate-hippocampus connectivity. Conclusions Findings highlight striatal hyper-sensitivity in response to a mild psychological stress in rMDD, as manifested by hyper-activation and hyper-connectivity with the amygdala and hippocampus. Striatal hyper-sensitivity during stress might thus constitute a trait mark of depression, providing a potential neural substrate for the interaction between stress and reward dysfunction in MDD. PMID:25483401

Salinomycin sensitizes antimitotic drugs-treated cancer cells by increasing apoptosis via the prevention of G2 arrest

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

Kim, Ju-Hwa; Yoo, Hye-In; Kang, Han Sung

Highlights: Black-Right-Pointing-Pointer Sal sensitizes antimitotic drugs-treated cancer cells. Black-Right-Pointing-Pointer Sal sensitizes them by prevention of G2 arrest and reduced cyclin D1 levels. Black-Right-Pointing-Pointer Sal also sensitizes them by increasing DNA damage and reducing p21 level. Black-Right-Pointing-Pointer A low concentration of Sal effectively sensitized the cancer cells to antimitotic drugs. -- Abstract: Here, we investigated whether Sal could sensitize cancer cells to antimitotic drugs. We demonstrated that Sal sensitized paclitaxcel (PAC)-, docetaxcel (DOC)-, vinblastin (VIN)-, or colchicine (COL)-treated cancer cell lines, suggesting that Sal has the ability to sensitize the cells to any form of microtubule-targeting drugs. Sensitization to the antimitoticmore » drugs could be achieved with very low concentrations of Sal, suggesting that there is a possibility to minimize Sal toxicity associated with human cancer patient treatments. Sensitization by Sal increased apoptosis, which was observed by C-PARP production. Sal sensitized the cancer cells to antimitotic drugs by preventing G2 arrest, suggesting that Sal contributes to the induction of mitotic catastrophe. Sal generally reduced cyclin D1 levels in PAC-, DOC-, and VIN-treated cells. In addition, Sal treatment increased pH2AX levels and reduced p21 levels in antimitotic drugs-treated cells. These observations suggest that the mechanisms underlying Sal sensitization to DNA-damaging compounds, radiation, and microtubule-targeting drugs are similar. Our data demonstrated that Sal sensitizes cancer cells to antimitotic drugs by increasing apoptosis through the prevention of G2 arrest via conserved Sal-sensitization mechanisms. These results may contribute to the development of Sal-based chemotherapy for cancer patients treated with antimitotic drugs.« less

A novel nutrient sensing mechanism underlies substrate-induced regulation of monocarboxylate transporter-1

PubMed Central

Priyamvada, Shubha; Kumar, Anoop; Natarajan, Arivarasu A.; Gill, Ravinder K.; Alrefai, Waddah A.; Dudeja, Pradeep K.

2012-01-01

Monocarboxylate transporter isoform-1 (MCT1) plays an important role in the absorption of short-chain fatty acids (SCFAs) in the colon. Butyrate, a major SCFA, serves as the primary energy source for the colonic mucosa, maintains epithelial integrity, and ameliorates intestinal inflammation. Previous studies have shown substrate (butyrate)-induced upregulation of MCT1 expression and function via transcriptional mechanisms. The present studies provide evidence that short-term MCT1 regulation by substrates could be mediated via a novel nutrient sensing mechanism. Short-term regulation of MCT1 by butyrate was examined in vitro in human intestinal C2BBe1 and rat intestinal IEC-6 cells and ex vivo in rat intestinal mucosa. Effects of pectin feeding on MCT1, in vivo, were determined in rat model. Butyrate treatment (30–120 min) of C2BBe1 cells increased MCT1 function {p-(chloromercuri) benzene sulfonate (PCMBS)-sensitive [14C]butyrate uptake} in a pertussis toxin-sensitive manner. The effects were associated with decreased intracellular cAMP levels, increased Vmax of butyrate uptake, and GPR109A-dependent increase in apical membrane MCT1 level. Nicotinic acid, an agonist for the SCFA receptor GPR109A, also increased MCT1 function and decreased intracellular cAMP. Pectin feeding increased apical membrane MCT1 levels and nicotinate-induced transepithelial butyrate flux in rat colon. Our data provide strong evidence for substrate-induced enhancement of MCT1 surface expression and function via a novel nutrient sensing mechanism involving GPR109A as a SCFA sensor. PMID:22982338

Differential Sensitivity to Drought in Central U.S. Grasslands Arrayed Along an Aridity Gradient

NASA Astrophysics Data System (ADS)

Knapp, Alan; Collins, Scott; Luo, Yiqi; Smith, Melinda

2015-04-01

Responses to drought often vary dramatically among terrestrial ecosystems, but the reasons why are unclear. With climate change forecasts for more frequent, severe and extensive drought in the future, a more complete understanding of the mechanisms that determine differential ecosystem sensitivity to drought is needed. In 2012, the Central U.S. experienced the 4th largest drought in a century, with a regional-scale 40% reduction in growing season precipitation affecting ecosystems ranging from desert grassland to mesic tallgrass prairie. This provided an opportunity to assess ecosystem sensitivity to a natural drought of common magnitude in six native grasslands. We tested the prediction that drought sensitivity would be inversely related to mean annual precipitation (MAP) by quantifying reductions in aboveground net primary production (ANPP). Long-term ANPP data available for each site (mean length = 16 yrs) were used as a baseline for calculating reductions in ANPP, and drought sensitivity was estimated as the reduction in ANPP per mm reduction in precipitation. Arid grasslands were the most sensitive to drought, but drought responses and sensitivity varied by more than 2-fold among the six grasslands, despite all sites experiencing similar relative reductions in growing season precipitation. Although drought sensitivity generally decreased with increasing MAP as predicted, there was evidence that the identity and traits of the dominant species, as well as plant functional diversity, influenced sensitivity. Results from this natural drought will be compared with responses to an experimentally imposed drought to determine if patterns of sensitivity are consistent between experimental and observational approaches.

Flexible Graphene Transistor Architecture for Optical Sensor Technology

NASA Astrophysics Data System (ADS)

Ordonez, Richard Christopher

The unique electrical and optoelectronic properties of graphene allow tunable conductivity and broadband electromagnetic absorption that spans the ultraviolet and infrared regimes. However, in the current state-of-art graphene sensor architectures, junction resistance and doping concentration are predominant factors that affect signal strength and sensitivity. Unfortunately, graphene produces high contact resistances with standard electrode materials ( few kilo-ohms), therefore, signal is weak and large carrier concentrations are required to probe sensitivity. Moreover, the atomic thickness of graphene enables the potential for flexible electronics, but there has not been a successful graphene sensor architecture that demonstrates stable operation on flexible substrates and with minimal fabrication cost. In this study, the author explores a novel 3-terminal transistor architecture that integrates twodimensional graphene, liquid metal, and electrolytic gate dielectrics (LM-GFETs: Liquid Metal and Graphene Field-Effect Transistors ). The goal is to deliver a sensitive, flexible, and lightweight transistor architecture that will improve sensor technology and maneuverability. The reported high thermal conductivity of graphene provides potential for room-temperature thermal management without the need of thermal-electric and gas cooling systems that are standard in sensor platforms. Liquid metals provide a unique opportunity for conformal electrodes that maximize surface area contact, therefore, enable flexibility, lower contact resistance, and reduce damage to the graphene materials involved. Lastly, electrolytic gate dielectrics provide conformability and high capacitances needed for high on/off rations and electrostatic gating. Results demonstrated that with minimal fabrication steps the proposed flexible graphene transistor architecture demonstrated ambipolar current-voltage transfer characteristics that are comparable to the current state-of-the-art. An additional investigation demonstrated PN junction operation and the successful integration of the proposed architecture into an optoelectronic application with the use of semiconductor quantum dots in contact with the graphene material that acted as optical absorbers to increase detector gain. Applications that can benefit from such technology advancement include Nano-satellites (Nanosat), Underwater autonomous vehicles (UAV), and airborne platforms in which flexibility and sensitivity are critical parameters that must be optimized to increase mission duration and range.

Syndromic Surveillance Using Veterinary Laboratory Data: Algorithm Combination and Customization of Alerts

PubMed Central

Dórea, Fernanda C.; McEwen, Beverly J.; McNab, W. Bruce; Sanchez, Javier; Revie, Crawford W.

2013-01-01

Background Syndromic surveillance research has focused on two main themes: the search for data sources that can provide early disease detection; and the development of efficient algorithms that can detect potential outbreak signals. Methods This work combines three algorithms that have demonstrated solid performance in detecting simulated outbreak signals of varying shapes in time series of laboratory submissions counts. These are: the Shewhart control charts designed to detect sudden spikes in counts; the EWMA control charts developed to detect slow increasing outbreaks; and the Holt-Winters exponential smoothing, which can explicitly account for temporal effects in the data stream monitored. A scoring system to detect and report alarms using these algorithms in a complementary way is proposed. Results The use of multiple algorithms in parallel resulted in increased system sensitivity. Specificity was decreased in simulated data, but the number of false alarms per year when the approach was applied to real data was considered manageable (between 1 and 3 per year for each of ten syndromic groups monitored). The automated implementation of this approach, including a method for on-line filtering of potential outbreak signals is described. Conclusion The developed system provides high sensitivity for detection of potential outbreak signals while also providing robustness and flexibility in establishing what signals constitute an alarm. This flexibility allows an analyst to customize the system for different syndromes. PMID:24349216

Syndromic surveillance using veterinary laboratory data: algorithm combination and customization of alerts.

PubMed

Dórea, Fernanda C; McEwen, Beverly J; McNab, W Bruce; Sanchez, Javier; Revie, Crawford W

2013-01-01

Syndromic surveillance research has focused on two main themes: the search for data sources that can provide early disease detection; and the development of efficient algorithms that can detect potential outbreak signals. This work combines three algorithms that have demonstrated solid performance in detecting simulated outbreak signals of varying shapes in time series of laboratory submissions counts. These are: the Shewhart control charts designed to detect sudden spikes in counts; the EWMA control charts developed to detect slow increasing outbreaks; and the Holt-Winters exponential smoothing, which can explicitly account for temporal effects in the data stream monitored. A scoring system to detect and report alarms using these algorithms in a complementary way is proposed. The use of multiple algorithms in parallel resulted in increased system sensitivity. Specificity was decreased in simulated data, but the number of false alarms per year when the approach was applied to real data was considered manageable (between 1 and 3 per year for each of ten syndromic groups monitored). The automated implementation of this approach, including a method for on-line filtering of potential outbreak signals is described. The developed system provides high sensitivity for detection of potential outbreak signals while also providing robustness and flexibility in establishing what signals constitute an alarm. This flexibility allows an analyst to customize the system for different syndromes.

Increased sensitivity of 3D-Well enzyme-linked immunosorbent assay (ELISA) for infectious disease detection using 3D-printing fabrication technology.

PubMed

Singh, Harpal; Shimojima, Masayuki; Fukushi, Shuetsu; Le Van, An; Sugamata, Masami; Yang, Ming

2015-01-01

Enzyme-linked Immunosorbent Assay or ELISA -based diagnostics are considered the gold standard in the demonstration of various immunological reaction including in the measurement of antibody response to infectious diseases and to support pathogen identification with application potential in infectious disease outbreaks and individual patients' treatment and clinical care. The rapid prototyping of ELISA-based diagnostics using available 3D printing technologies provides an opportunity for a further exploration of this platform into immunodetection systems. In this study, a '3D-Well' was designed and fabricated using available 3D printing platforms to have an increased surface area of more than 4 times for protein-surface adsorption compared to those of 96-well plates. The ease and rapidity in designing-product development-feedback cycle offered through 3D printing platforms provided an opportunity for its rapid assessment, in which a chemical etching process was used to make the surface hydrophilic followed by validation through the diagnostic performance of ELISA for infectious disease without modifying current laboratory practices for ELISA. The higher sensitivity of the 3D-Well (3-folds higher) compared to the 96-well ELISA provides a potential for the expansion of this technology towards miniaturization platforms to reduce time, volume of reagents and samples needed for laboratory or field diagnosis of infectious diseases including applications in other disciplines.

Development of an enrofloxacin immunosensor based on label-free electrochemical impedance spectroscopy.

PubMed

Wu, Ching-Chou; Lin, Chia-Hung; Wang, Way-Shyan

2009-06-30

Enrofloxacin is the most widespread antibiotic in the fluoroquinolone family. As such, the development of a rapid and sensitive method for the determination of trace amounts of enrofloxacin is an important issue in the health field. The interaction of the enrofloxacin antigen to a specific antibody (Ab) immobilized on an 11-mercapto-undecanoic acid-coated gold electrode was quantified by electrochemical impedance spectroscopy. Two equivalent circuits were separately used to interpret the obtained impedance spectra. These circuits included one resistor in series with one parallel circuit comprised of a resistor and a capacitor (1R//C), and one resistor in series with two parallel RC circuits (2R//C). The results indicate that the antigen-antibody reaction analyzed using the 1R//C circuit provided a more sensitive resistance increment against the enrofloxacin concentration than that of the 2R//C circuit. However, the 2R//C circuit provided a better fitting for impedance spectra, and therefore supplies more detailed results of the enrofloxacin-antibody interaction, causing the increase of electron transfer resistance selectively to the modified layer, and not the electrical double layer. The antibody-modified electrode allowed for analysis of the dynamic linear range of 1-1000 ng/ml enrofloxacin with a detection limit of 1 ng/ml. The reagentless and label-free impedimetric immunosensors provide a simple and sensitive detection method for the specific determination of enrofloxacin.

Highly sensitive troponin and coronary computed tomography angiography in the evaluation of suspected acute coronary syndrome in the emergency department.

PubMed

Ferencik, Maros; Hoffmann, Udo; Bamberg, Fabian; Januzzi, James L

2016-08-07

The evaluation of patients presenting to the emergency department with suspected acute coronary syndrome (ACS) remains a clinical challenge. The traditional assessment includes clinical risk assessment based on cardiovascular risk factors with serial electrocardiograms and cardiac troponin measurements, often followed by advanced cardiac testing as inpatient or outpatient (i.e. stress testing, imaging). Despite this costly and lengthy work-up, there is a non-negligible rate of missed ACS with an increased risk of death. There is a clinical need for diagnostic strategies that will lead to rapid and reliable triage of patients with suspected ACS. We provide an overview of the evidence for the role of highly sensitive troponin (hsTn) in the rapid and efficient evaluation of suspected ACS. Results of recent research studies have led to the introduction of hsTn with rapid rule-in and rule-out protocols into the guidelines. Highly sensitive troponin increases the sensitivity for the detection of myocardial infarction and decreases time to diagnosis; however, it may decrease the specificity, especially when used as a dichotomous variable, rather than continuous variable as recommended by guidelines; this may increase clinician uncertainty. We summarize the evidence for the use of coronary computed tomography angiography (CTA) as the rapid diagnostic tool in this population when used with conventional troponin assays. Coronary CTA significantly decreases time to diagnosis and discharge in patients with suspected ACS, while being safe. However, it may lead to increase in invasive procedures and includes radiation exposure. Finally, we outline the opportunities for the combined use of hsTn and coronary CTA that may result in increased efficiency, decreased need for imaging, lower cost, and decreased radiation dose. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

LGBTQ Youth Part 1.

PubMed

Perron, Tracy; Kartoz, Connie; Himelfarb, Chaya

2017-03-01

In order to provide holistic care, school nurses must be culturally competent by being sensitive to health disparities experienced by students in at-risk populations. Despite the growing acceptance toward gender and sexual minorities, LGBTQ youth remain an at-risk population in our communities and our schools. School nurses as well as school counselors, social workers, and psychologists can increase their cultural competence in caring for this group of students by increasing their understanding of appropriate terminology and risks associated with this vulnerable group. This article is Part 1 of a two-article series designed to increase school nurses' abilities to advocate and care for LGBTQ youth in school settings. This first article provides information regarding proper terminology and current percentages of youth who identify as LGBTQ and concludes with implications for school nurses, including resources for nurses, school staff, and families.

A facile and low-cost route for sensitive stretchable sensors by controlling kinetic and thermodynamic conductive network regulating strategies.

PubMed

Duan, Lingyan; D'hooge, Dagmar R; Spoerk, Martin; Cornillie, Pieter; Cardon, Ludwig

2018-05-29

Highly sensitive conductive polymer composites (CPCs) are designed, employing a facile and low-cost extrusion manufacturing process for both low and high strain sensing in the field of e.g. structural health/damage monitoring and human body movement tracking. Focus is on the morphology control for extrusion processed carbon black (CB)-filled CPCs, utilizing binary and ternary composites based on thermoplastic polyurethane (TPU) and olefin block copolymer (OBC). The relevance of the correct CB amount, kinetic control through a variation of the compounding sequence, and thermodynamic control induced by annealing is highlighted, considering a wide range of experimental (e.g. static and dynamic resistance/SEM/rheological measurements) and theoretical analyses. High CB mass fractions (20 m%) are needed for OBC (or TPU)-CB binary composites but only lead to an intermediate sensitivity as their conductive network is fully-packed and therefore difficult to be truly destructed. Annealing is needed to enable a monotonic increase of the relative resistance with respect to strain. With ternary composites a much higher sensitivity with a clearer monotonic increase results provided that a low CB mass fraction (10-16 m%) is used and annealing is applied. In particular, with CB first dispersed in OBC and annealing a less compact, hence, brittle conductive network (10-12 m% CB) is obtained, allowing high performance sensing.

Introduction of a hydrolysis probe PCR assay for high-throughput screening of methicillin-resistant Staphylococcus aureus with the ability to include or exclude detection of Staphylococcus argenteus.

PubMed

Bogestam, Katja; Vondracek, Martin; Karlsson, Mattias; Fang, Hong; Giske, Christian G

2018-01-01

Many countries using sensitive screening methods for detection of carriage of methicillin-resistant Staphylococcus aureus (MRSA) have a sustained low incidence of MRSA infections. For diagnostic laboratories with high sample volumes, MRSA screening requires stability, low maintenance and high performance at a low cost. Herein we designed oligonucleotides for a new nuc targeted hydrolysis probe PCR to replace the standard in-house nuc SybrGreen PCR assay. This new, more time-efficient, PCR assay resulted in a 40% increase in daily sample capacity, with maintained high specificity and sensitivity. The assay was also able to detect Staphylococcus aureus clonal cluster 75 (CC75) lineage strains, recently re-classified as Staphylococcus argenteus, with a sensitivity considerably increased compared to our previous assay. While awaiting consensus if the CC75 lineage of S. aureus should be considered as S. argenteus, and whether methicillin-resistant S. argenteus should be included in the MRSA definition, many diagnostic laboratories need to update their MRSA assay sensitivity/specificity towards this lineage/species. The MRSA screening assay presented in this manuscript is comprised of nuc oligonucleotides separately targeting S. aureus and CC75 lineage strains/S. argenteus, thus providing high user flexibility for the detection of CC75 lineage strains/S. argenteus.

Metabolomics analysis reveals the metabolic and functional roles of flavonoids in light-sensitive tea leaves.

PubMed

Zhang, Qunfeng; Liu, Meiya; Ruan, Jianyun

2017-03-20

As the predominant secondary metabolic pathway in tea plants, flavonoid biosynthesis increases with increasing temperature and illumination. However, the concentration of most flavonoids decreases greatly in light-sensitive tea leaves when they are exposed to light, which further improves tea quality. To reveal the metabolism and potential functions of flavonoids in tea leaves, a natural light-sensitive tea mutant (Huangjinya) cultivated under different light conditions was subjected to metabolomics analysis. The results showed that chlorotic tea leaves accumulated large amounts of flavonoids with ortho-dihydroxylated B-rings (e.g., catechin gallate, quercetin and its glycosides etc.), whereas total flavonoids (e.g., myricetrin glycoside, epigallocatechin gallate etc.) were considerably reduced, suggesting that the flavonoid components generated from different metabolic branches played different roles in tea leaves. Furthermore, the intracellular localization of flavonoids and the expression pattern of genes involved in secondary metabolic pathways indicate a potential photoprotective function of dihydroxylated flavonoids in light-sensitive tea leaves. Our results suggest that reactive oxygen species (ROS) scavenging and the antioxidation effects of flavonoids help chlorotic tea plants survive under high light stress, providing new evidence to clarify the functional roles of flavonoids, which accumulate to high levels in tea plants. Moreover, flavonoids with ortho-dihydroxylated B-rings played a greater role in photo-protection to improve the acclimatization of tea plants.

Constraints on High Northern Photosynthesis Increase Using Earth System Models and a Set of Independent Observations

NASA Astrophysics Data System (ADS)

Winkler, A. J.; Brovkin, V.; Myneni, R.; Alexandrov, G.

2017-12-01

Plant growth in the northern high latitudes benefits from increasing temperature (radiative effect) and CO2 fertilization as a consequence of rising atmospheric CO2 concentration. This enhanced gross primary production (GPP) is evident in large scale increase in summer time greening over the 36-year record of satellite observations. In this time period also various global ecosystem models simulate a greening trend in terms of increasing leaf area index (LAI). We also found a persistent greening trend analyzing historical simulations of Earth system models (ESM) participating in Phase 5 of the Coupled Model Intercomparison Project (CMIP5). However, these models span a large range in strength of the LAI trend, expressed as sensitivity to both key environmental factors, temperature and CO2 concentration. There is also a wide spread in magnitude of the associated increase of terrestrial GPP among the ESMs, which contributes to pronounced uncertainties in projections of future climate change. Here we demonstrate that there is a linear relationship across the CMIP5 model ensemble between projected GPP changes and historical LAI sensitivity, which allows using the observed LAI sensitivity as an "emerging constraint" on GPP estimation at future CO2 concentration. This constrained estimate of future GPP is substantially higher than the traditional multi-model mean suggesting that the majority of current ESMs may be significantly underestimating carbon fixation by vegetation in NHL. We provide three independent lines of evidence in analyzing observed and simulated CO2 amplitude as well as atmospheric CO2 inversion products to arrive at the same conclusion.

MRSA Incidence and Antibiotic Trends in Urban Hand Infections: A 10-Year Longitudinal Study.

PubMed

Kistler, Justin M; Thoder, Joseph J; Ilyas, Asif M

2018-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) is the most reported pathogen in hand infections at urban medical centers throughout the country. Antibiotic sensitivity trends are not well known. The purposes of this study were to examine and determine the drug resistance trends for MRSA infections of the hand and to provide recommendations for empiric antibiotic treatment based on sensitivity profiles. A 10-year longitudinal, retrospective chart review was performed on all culture-positive hand infections encountered at a single urban medical center from 2005 to 2014. The proportions of all organisms were calculated for each year and collectively. MRSA infections were additionally subanalyzed for antibiotic sensitivity. A total of 815 culture-positive hand infections were identified. Overall, MRSA grew on culture in 46% of cases. A trend toward decreasing annual MRSA incidence was noted over the 10-year study period. There was a steady increase in polymicrobial infections during the same time. Resistance to clindamycin increased steadily during the 10-year study, starting at 4% in 2008 but growing to 31% by 2014. Similarly, levofloxacin resistance consistently increased throughout the study, reaching its peak at 56% in 2014. The annual incidence of MRSA in hand infections has declined overall but remains the most common pathogen. There has been an alternative increase in the number of polymicrobial infections. MRSA resistance to clindamycin and levofloxacin consistently increased during the study period. Empiric antibiotic therapy for hand infections should not only avoid penicillin and other beta-lactams but should also consider avoiding clindamycin and levofloxacin for empiric treatment.

Culturally competent methods to promote organ donation rates among African-Americans using venues of the Bureau of Motor Vehicles.

PubMed

Zaramo, C E B; Morton, T; Yoo, J W; Bowen, G R; Modlin, C S

2008-05-01

The diversity of the nation is one of society's greatest assets, but this feature is overshadowed by the disproportionate burden of disease that exists among America's minorities. Evidence of the disparate health status has been documented in low life expectancy, cancer, diabetes, cardiovascular, and kidney disease as well as a plethora of disorders that necessitate organ transplantation. Many minorities have been reluctant to register to become organ donors. This circumstance can be alleviated by educating the public regarding the necessity of organ transplantation. We have developed a "unique" collaborative outreach program designed to promote acceptance of organ donation in African-Americans (AAs). Our outreach curriculum at Bureau of Motor Vehicles (BMV) has resulted in increased registrations and awareness regarding the need and positive perceptions toward donation. We developed a culturally sensitive outreach program: cultural sensitivity indicates how culture has the ability to influence communication between patients and health providers. An "Outreach Promotional Contest" was strategically targeted toward 28 Ohio BMVs to promote and assist in an outreach educational program regarding organ donation/registry. The consequence/results has been an increase of 3.4% in the BMV locations. The one BMV, with the highest increase was attended predominantly by AAs which moreover, won first place in the contest (6.425%; P < .05). To increase the number of people willing to register, we believe that both community education regarding the need and importance, as well as culturally sensitive promotion of organ donation, is the best way to increase organ donor registries particularly among minority populations.

Cocoa butter and safflower oil elicit different effects on hepatic gene expression and lipid metabolism in rats.

PubMed

Gustavsson, Carolina; Parini, Paolo; Ostojic, Jovanca; Cheung, Louisa; Hu, Jin; Zadjali, Fahad; Tahir, Faheem; Brismar, Kerstin; Norstedt, Gunnar; Tollet-Egnell, Petra

2009-11-01

The aim of this study was to compare the effects of cocoa butter and safflower oil on hepatic transcript profiles, lipid metabolism and insulin sensitivity in healthy rats. Cocoa butter-based high-fat feeding for 3 days did not affect plasma total triglyceride (TG) levels or TG-rich VLDL particles or hepatic insulin sensitivity, but changes in hepatic gene expression were induced that might lead to increased lipid synthesis, lipotoxicity, inflammation and insulin resistance if maintained. Safflower oil increased hepatic beta-oxidation, was beneficial in terms of circulating TG-rich VLDL particles, but led to reduced hepatic insulin sensitivity. The effects of safflower oil on hepatic gene expression were partly overlapping with those exerted by cocoa butter, but fewer transcripts from anabolic pathways were altered. Increased hepatic cholesterol levels and increased expression of hepatic CYP7A1 and ABCG5 mRNA, important gene products in bile acid production and cholesterol excretion, were specific effects elicited by safflower oil only. Common effects on gene expression included increased levels of p8, DIG-1 IGFBP-1 and FGF21, and reduced levels of SCD-1 and SCD-2. This indicates that a lipid-induced program for hepatic lipid disposal and cell survival was induced by 3 days of high-fat feeding, independent on the lipid source. Based on the results, we speculate that hepatic TG infiltration leads to reduced expression of SCD-1, which might mediate either neutral, beneficial or unfavorable effects on hepatic metabolism upon high-fat feeding, depending on which fatty acids were provided by the diet.

Vantage Sensitivity: Environmental Sensitivity to Positive Experiences as a Function of Genetic Differences.

PubMed

Pluess, Michael

2017-02-01

A large number of gene-environment interaction studies provide evidence that some people are more likely to be negatively affected by adverse experiences as a function of specific genetic variants. However, such "risk" variants are surprisingly frequent in the population. Evolutionary analysis suggests that genetic variants associated with increased risk for maladaptive development under adverse environmental conditions are maintained in the population because they are also associated with advantages in response to different contextual conditions. These advantages may include (a) coexisting genetic resilience pertaining to other adverse influences, (b) a general genetic susceptibility to both low and high environmental quality, and (c) a coexisting propensity to benefit disproportionately from positive and supportive exposures, as reflected in the recent framework of vantage sensitivity. After introducing the basic properties of vantage sensitivity and highlighting conceptual similarities and differences with diathesis-stress and differential susceptibility patterns of gene-environment interaction, selected and recent empirical evidence for the notion of vantage sensitivity as a function of genetic differences is reviewed. The unique contribution that the new perspective of vantage sensitivity may make to our understanding of social inequality will be discussed after suggesting neurocognitive and molecular mechanisms hypothesized to underlie the propensity to benefit disproportionately from benevolent experiences. © 2015 Wiley Periodicals, Inc.

Study of node and mass sensitivity of resonant mode based cantilevers with concentrated mass loading

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

Zhang, Kewei, E-mail: drzkw@126.com; Chai, Yuesheng; Fu, Jiahui

2015-12-15

Resonant-mode based cantilevers are an important type of acoustic wave based mass-sensing devices. In this work, the governing vibration equation of a bi-layer resonant-mode based cantilever attached with concentrated mass is established by using a modal analysis method. The effects of resonance modes and mass loading conditions on nodes and mass sensitivity of the cantilever were theoretically studied. The results suggested that the node did not shift when concentrated mass was loaded on a specific position. Mass sensitivity of the cantilever was linearly proportional to the square of the point displacement at the mass loading position for all the resonancemore » modes. For the first resonance mode, when mass loading position x{sub c} satisfied 0 < x{sub c} < ∼ 0.3l (l is the cantilever beam length and 0 represents the rigid end), mass sensitivity decreased as the mass increasing while the opposite trend was obtained when mass loading satisfied ∼0.3l ≤ x{sub c} ≤ l. Mass sensitivity did not change when concentrated mass was loaded at the rigid end. This work can provide scientific guidance to optimize the mass sensitivity of a resonant-mode based cantilever.« less

Normal range of serum highly-sensitive troponin-T in patients with chronic kidney disease stage 3-5.

PubMed

Chotivanawan, Thunnop; Krittayaphong, Rungroj

2012-02-01

Serum troponin-T concentrations are commonly increased in chronic kidney disease (CKD) without acute coronary syndrome. Highly-sensitive troponin-T the new tool that helpful for diagnosis of acute coronary syndrome, provides few data about normal value in patients with chronic kidney disease. The authors studied 89 patients with CKD stage 3-5: 40 had CKD stage 3, 26 had CKD stage 4 and 23 had CKD stage 5. Serum samples were collected for the analysis of highly-sensitive troponin-T levels. The values of highly-sensitive troponin-T of the total group and each CKD stage were presented. The level of highly-sensitive troponin-T in patients with CKD stage 3-5 was 0.044 +/- 0.076 ng/ml. For CKD stages 3, 4 and 5 levels were 0.015 +/- 0.016, 0.043 +/- 0.056, 0.098 +/- 0.121 ng/ml, respectively. 95th percentile of the total group was 0.139 ng/ml. 95th percentile for stage 3, 4 and 5 were 0.052, 0.136, 0.297 ng/ml, respectively. 95th percentile for highly-sensitive troponin-T of patients with CKD stage 3-5 was 0.139 ng/ml. This number may be considered as the cut-off value for diagnosis of acute myocardial infarction.

On the Piezoelectric Detection of Guided Ultrasonic Waves

PubMed Central

2017-01-01

In order to quantify the wave motion of guided ultrasonic waves, the characteristics of piezoelectric detectors, or ultrasonic transducers and acoustic emission sensors, have been evaluated systematically. Such guided waves are widely used in structural health monitoring and nondestructive evaluation, but methods of calibrating piezoelectric detectors have been inadequate. This study relied on laser interferometry for the base displacement measurement of bar waves, from which eight different guided wave test set-ups are developed with known wave motion using piezoelectric transmitters. Both plates and bars of 12.7 and 6.4 mm thickness were used as wave propagation media. The upper frequency limit was 2 MHz. Output of guided wave detectors were obtained on the test set-ups and their receiving sensitivities were characterized and averaged. While each sensitivity spectrum was noisy for a detector, the averaged spectrum showed a good convergence to a unique receiving sensitivity. Twelve detectors were evaluated and their sensitivity spectra determined in absolute units. Generally, these showed rapidly dropping sensitivity with increasing frequency due to waveform cancellation on their sensing areas. This effect contributed to vastly different sensitivities to guided wave and to normally incident wave for each one of the 12 detectors tested. Various other effects are discussed and recommendations on methods of implementing the approach developed are provided. PMID:29156579

Plio-Pleistocene climate sensitivity evaluated using high-resolution CO2 records

NASA Astrophysics Data System (ADS)

Martínez-Botí, M. A.; Foster, G. L.; Chalk, T. B.; Rohling, E. J.; Sexton, P. F.; Lunt, D. J.; Pancost, R. D.; Badger, M. P. S.; Schmidt, D. N.

2015-02-01

Theory and climate modelling suggest that the sensitivity of Earth's climate to changes in radiative forcing could depend on the background climate. However, palaeoclimate data have thus far been insufficient to provide a conclusive test of this prediction. Here we present atmospheric carbon dioxide (CO2) reconstructions based on multi-site boron-isotope records from the late Pliocene epoch (3.3 to 2.3 million years ago). We find that Earth's climate sensitivity to CO2-based radiative forcing (Earth system sensitivity) was half as strong during the warm Pliocene as during the cold late Pleistocene epoch (0.8 to 0.01 million years ago). We attribute this difference to the radiative impacts of continental ice-volume changes (the ice-albedo feedback) during the late Pleistocene, because equilibrium climate sensitivity is identical for the two intervals when we account for such impacts using sea-level reconstructions. We conclude that, on a global scale, no unexpected climate feedbacks operated during the warm Pliocene, and that predictions of equilibrium climate sensitivity (excluding long-term ice-albedo feedbacks) for our Pliocene-like future (with CO2 levels up to maximum Pliocene levels of 450 parts per million) are well described by the currently accepted range of an increase of 1.5 K to 4.5 K per doubling of CO2.

Sensitive and quantitative detection of botulinum neurotoxin in neurons derived from mouse embryonic stem cells.

PubMed

Pellett, Sabine; Du, Zhong-wei; Pier, Christina L; Tepp, William H; Zhang, Su-chun; Johnson, Eric A

2011-01-07

Botulinum neurotoxins (BoNTs), the most poisonous protein toxins known, represent a serious bioterrorism threat but are also used as a unique and important bio-pharmaceutical to treat an increasing myriad of neurological disorders. The only currently accepted detection method by the United States Food and Drug Administration for biological activity of BoNTs and for potency determination of pharmaceutical preparations is the mouse bioassay (MBA). Recent advances have indicated that cell-based assays using primary neuronal cells can provide an equally sensitive and robust detection platform as the MBA to reliably and quantitatively detect biologically active BoNTs. This study reports for the first time a BoNT detection assay using mouse embryonic stem cells to produce a neuronal cell culture. The data presented indicate that this assay can reliably detect BoNT/A with a similar sensitivity as the MBA. Published by Elsevier Inc.

HDAC Inhibitors Disrupt Programmed Resistance to Apoptosis During Drosophila Development.

PubMed

Kang, Yunsik; Marischuk, Khailee; Castelvecchi, Gina D; Bashirullah, Arash

2017-06-07

We have previously shown that the ability to respond to apoptotic triggers is regulated during Drosophila development, effectively dividing the fly life cycle into stages that are either sensitive or resistant to apoptosis. Here, we show that the developmentally programmed resistance to apoptosis involves transcriptional repression of critical proapoptotic genes by histone deacetylases (HDACs). Administration of HDAC inhibitors (HDACi), like trichostatin A or suberoylanilide hydroxamic acid, increases expression of proapoptotic genes and is sufficient to sensitize otherwise resistant stages. Conversely, reducing levels of proapoptotic genes confers resistance to otherwise sensitive stages. Given that resistance to apoptosis is a hallmark of cancer cells, and that HDACi have been recently added to the repertoire of FDA-approved agents for cancer therapy, our results provide new insights for how HDACi help kill malignant cells and also raise concerns for their potential unintended effects on healthy cells. Copyright © 2017 Kang et al.

HPV Genotyping of Modified General Primer-Amplicons Is More Analytically Sensitive and Specific by Sequencing than by Hybridization

PubMed Central

Meisal, Roger; Rounge, Trine Ballestad; Christiansen, Irene Kraus; Eieland, Alexander Kirkeby; Worren, Merete Molton; Molden, Tor Faksvaag; Kommedal, Øyvind; Hovig, Eivind; Leegaard, Truls Michael

2017-01-01

Sensitive and specific genotyping of human papillomaviruses (HPVs) is important for population-based surveillance of carcinogenic HPV types and for monitoring vaccine effectiveness. Here we compare HPV genotyping by Next Generation Sequencing (NGS) to an established DNA hybridization method. In DNA isolated from urine, the overall analytical sensitivity of NGS was found to be 22% higher than that of hybridization. NGS was also found to be the most specific method and expanded the detection repertoire beyond the 37 types of the DNA hybridization assay. Furthermore, NGS provided an increased resolution by identifying genetic variants of individual HPV types. The same Modified General Primers (MGP)-amplicon was used in both methods. The NGS method is described in detail to facilitate implementation in the clinical microbiology laboratory and includes suggestions for new standards for detection and calling of types and variants with improved resolution. PMID:28045981

HPV Genotyping of Modified General Primer-Amplicons Is More Analytically Sensitive and Specific by Sequencing than by Hybridization.

PubMed

Meisal, Roger; Rounge, Trine Ballestad; Christiansen, Irene Kraus; Eieland, Alexander Kirkeby; Worren, Merete Molton; Molden, Tor Faksvaag; Kommedal, Øyvind; Hovig, Eivind; Leegaard, Truls Michael; Ambur, Ole Herman

2017-01-01

Sensitive and specific genotyping of human papillomaviruses (HPVs) is important for population-based surveillance of carcinogenic HPV types and for monitoring vaccine effectiveness. Here we compare HPV genotyping by Next Generation Sequencing (NGS) to an established DNA hybridization method. In DNA isolated from urine, the overall analytical sensitivity of NGS was found to be 22% higher than that of hybridization. NGS was also found to be the most specific method and expanded the detection repertoire beyond the 37 types of the DNA hybridization assay. Furthermore, NGS provided an increased resolution by identifying genetic variants of individual HPV types. The same Modified General Primers (MGP)-amplicon was used in both methods. The NGS method is described in detail to facilitate implementation in the clinical microbiology laboratory and includes suggestions for new standards for detection and calling of types and variants with improved resolution.

Highly-sensitive and large-dynamic diffuse optical tomography system for breast tumor detection

NASA Astrophysics Data System (ADS)

Du, Wenwen; Zhang, Limin; Yin, Guoyan; Zhang, Yanqi; Zhao, Huijuan; Gao, Feng

2018-02-01

Diffuse optical tomography (DOT) as a new functional imaging has important clinical applications in many aspects such as benign and malignant breast tumor detection, tumor staging and so on. For quantitative detection of breast tumor, a three-wavelength continuous-wave DOT prototype system combined the ultra-high sensitivity of the photon-counting detection and the measurement parallelism of the lock-in technique was developed to provide high temporal resolution, high sensitivity, large dynamic detection range and signal-to-noise ratio. Additionally, a CT-analogous scanning mode was proposed to cost-effectively increase the detection data. To evaluate the feasibility of the system, a series of assessments were conducted. The results demonstrate that the system can obtain high linearity, stability and negligible inter-wavelength crosstalk. The preliminary phantom experiments show the absorption coefficient is able to be successfully reconstructed, indicating that the system is one of the ideal platforms for optical breast tumor detection.

Assessing culturally sensitive factors in the learning environment of science classrooms

NASA Astrophysics Data System (ADS)

Fisher, Darrell L.; Waldrip, Bruce G.

1997-03-01

As schools are becoming increasingly diverse in their scope and clientele, any examination of the interaction of culturally sensitive factors of students' learning environments with learning science assumes critical importance. The purpose of this exploratory study was to develop an instrument to assess learning environment factors that are culturally sensitive, to provide initial validation information on the instrument and to examine associations between students' perceptions of their learning environments and their attitudes towards science and achievement of enquiry skills. A measure of these factors of science student's learning environment, namely the Cultural Learning Environment Questionnaire (CLEQ), was developed from past learning environment instruments and influenced by Hofstede's four dimensions of culture (Power Distance, Uncertainty Avoidance, Individualism, and Masculinity/Femininity). The reliability and discriminant validity for each scale were obtained and associations between learning environment, attitude to science and enquiry skills achievement were found.

A Review of Some Superconducting Technologies for AtLAST: Parametric Amplifiers, Kinetic Inductance Detectors, and On-Chip Spectrometers

NASA Astrophysics Data System (ADS)

Noroozian, Omid

2018-01-01

The current state of the art for some superconducting technologies will be reviewed in the context of a future single-dish submillimeter telescope called AtLAST. The technologies reviews include: 1) Kinetic Inductance Detectors (KIDs), which have now been demonstrated in large-format kilo-pixel arrays with photon background-limited sensitivity suitable for large field of view cameras for wide-field imaging. 2) Parametric amplifiers - specifically the Traveling-Wave Kinetic Inductance (TKIP) amplifier - which has enormous potential to increase sensitivity, bandwidth, and mapping speed of heterodyne receivers, and 3) On-chip spectrometers, which combined with sensitive direct detectors such as KIDs or TESs could be used as Multi-Object Spectrometers on the AtLAST focal plane, and could provide low-medium resolution spectroscopy of 100 objects at a time in each field of view.

Multi-modal approach using Raman spectroscopy and optical coherence tomography for the discrimination of colonic adenocarcinoma from normal colon

PubMed Central

Ashok, Praveen C.; Praveen, Bavishna B.; Bellini, Nicola; Riches, Andrew; Dholakia, Kishan; Herrington, C. Simon

2013-01-01

We report a multimodal optical approach using both Raman spectroscopy and optical coherence tomography (OCT) in tandem to discriminate between colonic adenocarcinoma and normal colon. Although both of these non-invasive techniques are capable of discriminating between normal and tumour tissues, they are unable individually to provide both the high specificity and high sensitivity required for disease diagnosis. We combine the chemical information derived from Raman spectroscopy with the texture parameters extracted from OCT images. The sensitivity obtained using Raman spectroscopy and OCT individually was 89% and 78% respectively and the specificity was 77% and 74% respectively. Combining the information derived using the two techniques increased both sensitivity and specificity to 94% demonstrating that combining complementary optical information enhances diagnostic accuracy. These data demonstrate that multimodal optical analysis has the potential to achieve accurate non-invasive cancer diagnosis. PMID:24156073

Development and Psychometric Assessment of the Healthcare Provider Cultural Competence Instrument

PubMed Central

Schwarz, Joshua L.; Witte, Raymond; Sellers, Sherrill L.; Luzadis, Rebecca A.; Weiner, Judith L.; Domingo-Snyder, Eloiza; Page, James E.

2015-01-01

This study presents the measurement properties of 5 scales used in the Healthcare Provider Cultural Competence Instrument (HPCCI). The HPCCI measures a health care provider’s cultural competence along 5 primary dimensions: (1) awareness/sensitivity, (2) behaviors, (3) patient-centered communication, (4) practice orientation, and (5) self-assessment. Exploratory factor analysis demonstrated that the 5 scales were distinct, and within each scale items loaded as expected. Reliability statistics indicated a high level of internal consistency within each scale. The results indicate that the HPCCI effectively measures the cultural competence of health care providers and can provide useful professional feedback for practitioners and organizations seeking to increase a practitioner’s cultural competence. PMID:25911617

Genotype Modulates Age-Related Alterations in Sensitivity to the Aversive Effects of Ethanol: An 8 Inbred Strain Analysis of Conditioned Taste Aversion

PubMed Central

Moore, Eileen M.; Forrest, Robert D.; Boehm, Stephen L.

2012-01-01

Adolescent individuals display altered behavioral sensitivity to ethanol, which may contribute to the increased ethanol consumption seen in this age-group. However, genetics also exert considerable influence on both ethanol intake and sensitivity. Thus far there is little research assessing the combined influence of developmental and genetic alcohol sensitivities. Sensitivity to the aversive effects of ethanol using a conditioned taste aversion (CTA) procedure was measured during both adolescence (P30) and adulthood (P75) in 8 inbred mouse strains (C57BL/6J, DBA/2J, 129S1/SvImJ, A/J, BALB/cByJ, BTBR T+tf/J, C3H/HeJ, and FVB/NJ). Adolescent and adult mice were water deprived, and subsequently provided with access to 0.9% (v/v) NaCl solution for 1h. Immediately following access mice were administered ethanol (0, 1.5, 2.25, 3g/kg, ip). This procedure was repeated in 72h intervals for a total of 5 CTA trials. Sensitivity to the aversive effects of ethanol was highly dependent upon both strain and age. Within an inbred strain, adolescent animals were consistently less sensitive to the aversive effects of ethanol than their adult counterparts. However, the dose of ethanol required to produce an aversion response differed as a function of both age and strain. PMID:23171343

Hierarchical Nanogold Labels to Improve the Sensitivity of Lateral Flow Immunoassay

NASA Astrophysics Data System (ADS)

Serebrennikova, Kseniya; Samsonova, Jeanne; Osipov, Alexander

2018-06-01

Lateral flow immunoassay (LFIA) is a widely used express method and offers advantages such as a short analysis time, simplicity of testing and result evaluation. However, an LFIA based on gold nanospheres lacks the desired sensitivity, thereby limiting its wide applications. In this study, spherical nanogold labels along with new types of nanogold labels such as gold nanopopcorns and nanostars were prepared, characterized, and applied for LFIA of model protein antigen procalcitonin. It was found that the label with a structure close to spherical provided more uniform distribution of specific antibodies on its surface, indicative of its suitability for this type of analysis. LFIA using gold nanopopcorns as a label allowed procalcitonin detection over a linear range of 0.5-10 ng mL-1 with the limit of detection of 0.1 ng mL-1, which was fivefold higher than the sensitivity of the assay with gold nanospheres. Another approach to improve the sensitivity of the assay included the silver enhancement method, which was used to compare the amplification of LFIA for procalcitonin detection. The sensitivity of procalcitonin determination by this method was 10 times better the sensitivity of the conventional LFIA with gold nanosphere as a label. The proposed approach of LFIA based on gold nanopopcorns improved the detection sensitivity without additional steps and prevented the increased consumption of specific reagents (antibodies).

Childhood Maltreatment, Depression, and Suicidal Ideation: Critical Importance of Parental and Peer Emotional Abuse during Developmental Sensitive Periods in Males and Females

PubMed Central

Khan, Alaptagin; McCormack, Hannah C.; Bolger, Elizabeth A.; McGreenery, Cynthia E.; Vitaliano, Gordana; Polcari, Ann; Teicher, Martin H.

2015-01-01

Background: The adverse childhood experience (ACE) study found that risk for depression increased as a function of number of types of childhood maltreatment, and interpret this as a result of cumulative stress. An alternative hypothesis is that risk depends on type and timing of maltreatment. This will also present as a linear increase, since exposure to more types of abuse increases likelihood of experiencing a critical type of abuse at a critical age. Methods: 560 (223M/337F) young adults (18–25 years) were recruited from the community without regard to diagnosis and balanced to have equal exposure to 0–4 plus types of maltreatment. The Maltreatment and Abuse Chronology of Exposure Scale assessed severity of exposure to 10 types of maltreatment across each year of childhood. Major depressive disorder (MDD) and current symptoms were evaluated by SCID, interview, and self-report. Predictive analytics assessed importance of exposure at each age and evaluated whether exposure at one or two ages was a more important predictor than number, severity, or duration of maltreatment across childhood. Results: The most important predictors of lifetime history of MDD were non-verbal emotional abuse in males and peer emotional abuse (EA) in females at 14 years of age, and these were more important predictors across models than number of types of maltreatment (males: t9 = 16.39, p < 10-7; females t9 = 5.78, p < 10-4). Suicidal ideation was predicted, in part, by NVEA and peer EA at age 14, but most importantly by parental verbal abuse at age 5 in males and sexual abuse at age 18 in females. Conclusion: This study provides evidence for sensitive exposure periods when maltreatment maximally impacts risk for depression, and provides an alternative interpretation of the ACE study results. These findings fit with emerging neuroimaging evidence for regional sensitivity periods. The presence of sensitive exposure periods has important implications for prevention, preemption, and treatment of MDD. PMID:25870565

Investigating cellular network heterogeneity and modularity in cancer: a network entropy and unbalanced motif approach.

PubMed

Cheng, Feixiong; Liu, Chuang; Shen, Bairong; Zhao, Zhongming

2016-08-26

Cancer is increasingly recognized as a cellular system phenomenon that is attributed to the accumulation of genetic or epigenetic alterations leading to the perturbation of the molecular network architecture. Elucidation of network properties that can characterize tumor initiation and progression, or pinpoint the molecular targets related to the drug sensitivity or resistance, is therefore of critical importance for providing systems-level insights into tumorigenesis and clinical outcome in the molecularly targeted cancer therapy. In this study, we developed a network-based framework to quantitatively examine cellular network heterogeneity and modularity in cancer. Specifically, we constructed gene co-expressed protein interaction networks derived from large-scale RNA-Seq data across 8 cancer types generated in The Cancer Genome Atlas (TCGA) project. We performed gene network entropy and balanced versus unbalanced motif analysis to investigate cellular network heterogeneity and modularity in tumor versus normal tissues, different stages of progression, and drug resistant versus sensitive cancer cell lines. We found that tumorigenesis could be characterized by a significant increase of gene network entropy in all of the 8 cancer types. The ratio of the balanced motifs in normal tissues is higher than that of tumors, while the ratio of unbalanced motifs in tumors is higher than that of normal tissues in all of the 8 cancer types. Furthermore, we showed that network entropy could be used to characterize tumor progression and anticancer drug responses. For example, we found that kinase inhibitor resistant cancer cell lines had higher entropy compared to that of sensitive cell lines using the integrative analysis of microarray gene expression and drug pharmacological data collected from the Genomics of Drug Sensitivity in Cancer database. In addition, we provided potential network-level evidence that smoking might increase cancer cellular network heterogeneity and further contribute to tyrosine kinase inhibitor (e.g., gefitinib) resistance. In summary, we demonstrated that network properties such as network entropy and unbalanced motifs associated with tumor initiation, progression, and anticancer drug responses, suggesting new potential network-based prognostic and predictive measure in cancer.

Scrambled eggs: A highly sensitive molecular diagnostic workflow for Fasciola species specific detection from faecal samples.

PubMed

Calvani, Nichola Eliza Davies; Windsor, Peter Andrew; Bush, Russell David; Šlapeta, Jan

2017-09-01

Fasciolosis, due to Fasciola hepatica and Fasciola gigantica, is a re-emerging zoonotic parasitic disease of worldwide importance. Human and animal infections are commonly diagnosed by the traditional sedimentation and faecal egg-counting technique. However, this technique is time-consuming and prone to sensitivity errors when a large number of samples must be processed or if the operator lacks sufficient experience. Additionally, diagnosis can only be made once the 12-week pre-patent period has passed. Recently, a commercially available coprological antigen ELISA has enabled detection of F. hepatica prior to the completion of the pre-patent period, providing earlier diagnosis and increased throughput, although species differentiation is not possible in areas of parasite sympatry. Real-time PCR offers the combined benefits of highly sensitive species differentiation for medium to large sample sizes. However, no molecular diagnostic workflow currently exists for the identification of Fasciola spp. in faecal samples. A new molecular diagnostic workflow for the highly-sensitive detection and quantification of Fasciola spp. in faecal samples was developed. The technique involves sedimenting and pelleting the samples prior to DNA isolation in order to concentrate the eggs, followed by disruption by bead-beating in a benchtop homogeniser to ensure access to DNA. Although both the new molecular workflow and the traditional sedimentation technique were sensitive and specific, the new molecular workflow enabled faster sample throughput in medium to large epidemiological studies, and provided the additional benefit of speciation. Further, good correlation (R2 = 0.74-0.76) was observed between the real-time PCR values and the faecal egg count (FEC) using the new molecular workflow for all herds and sampling periods. Finally, no effect of storage in 70% ethanol was detected on sedimentation and DNA isolation outcomes; enabling transport of samples from endemic to non-endemic countries without the requirement of a complete cold chain. The commercially-available ELISA displayed poorer sensitivity, even after adjustment of the positive threshold (65-88%), compared to the sensitivity (91-100%) of the new molecular diagnostic workflow. Species-specific assays for sensitive detection of Fasciola spp. enable ante-mortem diagnosis in both human and animal settings. This includes Southeast Asia where there are potentially many undocumented human cases and where post-mortem examination of production animals can be difficult. The new molecular workflow provides a sensitive and quantitative diagnostic approach for the rapid testing of medium to large sample sizes, potentially superseding the traditional sedimentation and FEC technique and enabling surveillance programs in locations where animal and human health funding is limited.