Fractal dimension approach in postural control of subjects with Prader-Willi Syndrome

PubMed Central

2011-01-01

Background Static posturography is user-friendly technique suitable for the study of the centre of pressure (CoP) trajectory. However, the utility of static posturography in clinical practice is somehow limited and there is a need for reliable approaches to extract physiologically meaningful information from stabilograms. The aim of this study was to quantify the postural strategy of Prader-Willi patients with the fractal dimension technique in addition to the CoP trajectory analysis in time and frequency domain. Methods 11 adult patients affected by Prader-Willi Syndrome (PWS) and 20 age-matched individuals (Control group: CG) were included in this study. Postural acquisitions were conducted by means of a force platform and the participants were required to stand barefoot on the platform with eyes open and heels at standardized distance and position for 30 seconds. Platform data were analysed in time and frequency domain. Fractal Dimension (FD) was also computed. Results The analysis of CoP vs. time showed that in PWS participants all the parameters were statistically different from CG, with greater displacements along both the antero-posterior and medio-lateral direction and longer CoP tracks. As for frequency analysis, our data showed no significant differences between PWS and CG. FD evidenced that PWS individuals were characterized by greater value in comparison with CG. Conclusions Our data showed that while the analysis in the frequency domain did not seem to explain the postural deficit in PWS, the FD method appears to provide a more informative description of it and to complement and integrate the time domain analysis. PMID:21854639

Antenna structures and cloud-to-ground lightning location: 1995-2015

NASA Astrophysics Data System (ADS)

Kingfield, Darrel M.; Calhoun, Kristin M.; de Beurs, Kirsten M.

2017-05-01

Spatial analyses of cloud-to-ground (CG) lightning occurrence due to a rapid expansion in the number of antenna towers across the United States are explored by gridding 20 years of National Lightning Detection Network data at 500 m spatial resolution. The 99.8% of grid cells with ≥100 CGs were within 1 km of an antenna tower registered with the Federal Communications Commission. Tower height is positively correlated with CG occurrence; towers taller than 400 m above ground level experience a median increase of 150% in CG lightning density compared to a region 2 km to 5 km away. In the northern Great Plains, the cumulative CG lightning density near the tower was around 138% (117%) higher than a region 2 to 5 km away in the September-February (March-August) months. Higher CG frequencies typically also occur in the first full year following new tower construction, creating new lightning hot spots.

Antistaphylococcal Activity of CG400549, a New Experimental FabI Inhibitor, Compared with That of Other Agents▿

PubMed Central

Bogdanovich, Tatiana; Clark, Catherine; Kosowska-Shick, Klaudia; Dewasse, Bonifacio; McGhee, Pamela; Appelbaum, Peter C.

2007-01-01

Among 203 strains of Staphylococcus aureus, the MICs of CG400549 were 0.06 to 1.0 μg/ml, with MIC50 and MIC90 values of 0.25 μg/ml each. All strains were susceptible to linezolid and quinupristin-dalfopristin (MICs, 0.25 to 2.0 μg/ml). The daptomycin MICs were 0.25 to 2.0 μg/ml for methicillin-susceptible and 0.25 to 4.0 μg/ml against methicillin-resistant strains (including vancomycin-intermediate strains). Single-passage selection testing showed low resistance frequencies with CG400549, but multistep analysis showed that CG400549 yielded resistant mutants after 14 to 17 days in all strains tested. PMID:17875997

Genetic variants in 3'-UTRs of MTHFR in the pregnancies complicated with preeclampsia and bioinformatics analysis.

PubMed

Mohammadpour-Gharehbagh, Abbas; Salimi, Saeedeh; Keshavarzi, Farshid; Saeidian, Foozieh; Mousavi, Mahdieh; Teimoori, Batool; Esmaeilipour, Maryam; Mokhtari, Mojgan

2018-01-01

Preeclampsia (PE) as a pregnancy-specific disorder is the major cause of mortality and morbidity of mothers and fetuses. This study attempts to investigate the possible association between the 2572C>A (rs4846049) and 4869C>G (rs1537514) polymorphisms in the 3'- untranslated region of MTHFR gene and the risk of PE. A total of 198 patients diagnosed with PE and 171 unrelated, age matched healthy pregnant women, were recruited for this case-control study. The MTHFR 2572C>A and 4869C>G genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The CG genotype of MTHFR 4869C>G was associated with decreased risk of PE, and this genotype was found to be a protective factor for PE susceptibility. There was no significant difference in the genotypes of MTHFR 2572C>A polymorphism between PE patients and control group. The frequency of combined AC/CG genotypes of MTHFR 2572C>A and 4869C>G polymorphisms were less frequent in PE patients and were associated with a lower risk of PE. The C-G and A-G haplotypes of MTHFR 2572C>A and 4869C>G polymorphisms were significantly lower in PE patients. In conclusion, the CG genotype of MTHFR 4869C>G polymorphism was associated with a lower risk of PE. No association was found between MTHFR 2572C>A polymorphism and PE. © 2017 Wiley Periodicals, Inc.

Relationships between thunderstorms and cloud-to-ground lightning in the United States

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

Changnon, S.A.

Climatic assessments of cloud-to-ground (CG) flashes, and of the relationship between CG flashes and thunder events, as reported at 62 first-order stations in the contiguous US, are performed on the basis of data from networks of lightning sensors operated during 1986-1989. The adequacy of thunder-event data for describing thunderstorm occurrences at a point is determined. The average and extreme frequencies of CG lightning is delineated. Thunder events are found to provide poor estimates of CG lightning incidences and durations. CG flash data reveal that 20 percent (far west) and 50 percent (southeast US) of all thunder events are missed atmore » weather stations; 30-60 percent of all thunder events have durations too short; and 10 per cent (North and West), 40 percent (mountains), and 25 percent (southeast) of all CG flashes within 20 km of weather stations are not reported as thunderstorms. The use of historical thunder data, as a surrogate for lightning activity, is improper, and thunder values need to be adjusted with the relationships presented. 33 refs.« less

A new algorithm for construction of coarse-grained sites of large biomolecules.

PubMed

Li, Min; Zhang, John Z H; Xia, Fei

2016-04-05

The development of coarse-grained (CG) models for large biomolecules remains a challenge in multiscale simulations, including a rigorous definition of CG representations for them. In this work, we proposed a new stepwise optimization imposed with the boundary-constraint (SOBC) algorithm to construct the CG sites of large biomolecules, based on the s cheme of essential dynamics CG. By means of SOBC, we can rigorously derive the CG representations of biomolecules with less computational cost. The SOBC is particularly efficient for the CG definition of large systems with thousands of residues. The resulted CG sites can be parameterized as a CG model using the normal mode analysis based fluctuation matching method. Through normal mode analysis, the obtained modes of CG model can accurately reflect the functionally related slow motions of biomolecules. The SOBC algorithm can be used for the construction of CG sites of large biomolecules such as F-actin and for the study of mechanical properties of biomaterials. © 2015 Wiley Periodicals, Inc.

Cardiovascular autonomic control in paraplegic and quadriplegic.

PubMed

de Carvalho Abreu, Elizângela Márcia; Dias, Lucas Pinto Salles; Lima, Fernanda Pupio Silva; de Paula Júnior, Alderico Rodrigues; Lima, Mário Oliveira

2016-04-01

Spinal cord injury (SCI) is commonly associated with devastating paralysis. This condition also results in cardiovascular autonomic dysfunction associated with increased mortality from cardiovascular disease. The purpose of this study was to explore the differences in cardiovascular autonomic modulation in individuals with and without SCI. The study included 60 individuals: 30 individuals without SCI, who formed the control group-CG and 30 individuals with SCI, who formed the SCI group-SCIG. The latter group was divided into two, one group of subjects with SCI above the spinal segment T6-SCIG (above T6) and a group of individuals with SCI below T6-SCIG (below T6). The subjects were evaluated by linear and nonlinear analysis of heart rate variability (HRV). The SCIG showed significantly lower square root of the mean squares differences of successive NN intervals (rMSSD), number of pairs of adjacent NN intervals differing by more than 50 ms (pNN50), standard deviation of short-term HRV (SD1), and high frequency power (HF). Their low frequency power (LF) in absolute units (ms(2)) was significantly lower and their normalized units (n.u.) were significantly higher. Their LF/HF ratio was significantly higher, and sample entropy (SampEn), which indicates the complexity and irregularity of the NN intervals time series, was significantly lower compared to the CG. The differences between the SCIG and CG were derived mainly from the SCIG (above T6). The correlation test revealed very low values between each of the parameters evaluated for CG and SCIG. The SCIG (above T6) showed greater cardiovascular autonomic impairment compared to SCIG (below T6) and CG. The SCIG (below T6) also presented some degree of autonomic dysfunction. All parameters, linear or nonlinear, are suitable to demonstrate the differences between the SCIG and CG.

Coarse-graining of proteins based on elastic network models

NASA Astrophysics Data System (ADS)

Sinitskiy, Anton V.; Voth, Gregory A.

2013-08-01

To simulate molecular processes on biologically relevant length- and timescales, coarse-grained (CG) models of biomolecular systems with tens to even hundreds of residues per CG site are required. One possible way to build such models is explored in this article: an elastic network model (ENM) is employed to define the CG variables. Free energy surfaces are approximated by Taylor series, with the coefficients found by force-matching. CG potentials are shown to undergo renormalization due to roughness of the energy landscape and smoothing of it under coarse-graining. In the case study of hen egg-white lysozyme, the entropy factor is shown to be of critical importance for maintaining the native structure, and a relationship between the proposed ENM-mode-based CG models and traditional CG-bead-based models is discussed. The proposed approach uncovers the renormalizable character of CG models and offers new opportunities for automated and computationally efficient studies of complex free energy surfaces.

Using Cloud-to-Ground Lightning Climatologies to Initialize Gridded Lightning Threat Forecasts for East Central Florida

NASA Technical Reports Server (NTRS)

Lambert, Winnie; Sharp, David; Spratt, Scott; Volkmer, Matthew

2005-01-01

Each morning, the forecasters at the National Weather Service in Melbourn, FL (NWS MLB) produce an experimental cloud-to-ground (CG) lightning threat index map for their county warning area (CWA) that is posted to their web site (http://www.srh.weather.gov/mlb/ghwo/lightning.shtml) . Given the hazardous nature of lightning in central Florida, especially during the warm season months of May-September, these maps help users factor the threat of lightning, relative to their location, into their daily plans. The maps are color-coded in five levels from Very Low to Extreme, with threat level definitions based on the probability of lightning occurrence and the expected amount of CG activity. On a day in which thunderstorms are expected, there are typically two or more threat levels depicted spatially across the CWA. The locations of relative lightning threat maxima and minima often depend on the position and orientation of the low-level ridge axis, forecast propagation and interaction of sea/lake/outflow boundaries, expected evolution of moisture and stability fields, and other factors that can influence the spatial distribution of thunderstorms over the CWA. The lightning threat index maps are issued for the 24-hour period beginning at 1200 UTC (0700 AM EST) each day with a grid resolution of 5 km x 5 km. Product preparation is performed on the AWIPS Graphical Forecast Editor (GFE), which is the standard NWS platform for graphical editing. Currently, the forecasters create each map manually, starting with a blank map. To improve efficiency of the forecast process, NWS MLB requested that the Applied Meteorology Unit (AMU) create gridded warm season lightning climatologies that could be used as first-guess inputs to initialize lightning threat index maps. The gridded values requested included CG strike densities and frequency of occurrence stratified by synoptic-scale flow regime. The intent is to increase consistency between forecasters while enabling them to focus on the mesoscale detail of the forecast, ultimately benefiting the end-users of the product. Several studies took place at the Florida State University (FSU) and NWS Tallahassee (TAE) for which they created daily flow regimes using Florida 1200 UTC synoptic soundings and CG strike densities from National Lightning Detection Network (NLDN) data. The densities were created on a 2.5 km x 2.5 km grid for every hour of every day during the warm seasons in the years 1989-2004. The grids encompass an area that includes the entire state of Florida and adjacent Atlantic and Gulf of Mexico waters. Personnel at the two organizations provided this data and supporting software for the work performed by the AMU. The densities were first stratified by flow regime, then by time in 1-, 3-, 6-, 12-, and 24-hour increments while maintaining the 2.5 km x 2.5 km grid resolution. A CG frequency of occurrence was calculated for each stratification and grid box by counting the number of days with lightning and dividing by the total number of days in the data set. New CG strike densities were calculated for each stratification and grid box by summing the strike number values over all warm seasons, then normalized by dividing the summed values by the number of lightning days. This makes the densities conditional on whether lightning occurred. The frequency climatology values will be used by forecasters as proxy inputs for lightning prObability, while the density climatology values will be used for CG amount. In addition to the benefits outlined above, these climatologies will provide improved temporal and spatial resolution, expansion of the lightning threat area to include adjacent coastal waters, and potential to extend the forecast to include the day-2 period. This presentation will describe the lightning threat index map, discuss the work done to create the maps initialized with climatological guidance, and show examples of the climatological CG lightning densities and frequencies of occurren based on flow regime.

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

Maiolo, M., E-mail: massimo.maiolo@zhaw.ch; ZHAW, Institut für Angewandte Simulation, Grüental, CH-8820 Wädenswil; Vancheri, A., E-mail: alberto.vancheri@supsi.ch

In this paper, we apply Multiresolution Analysis (MRA) to develop sparse but accurate representations for the Multiscale Coarse-Graining (MSCG) approximation to the many-body potential of mean force. We rigorously framed the MSCG method into MRA so that all the instruments of this theory become available together with a multitude of new basis functions, namely the wavelets. The coarse-grained (CG) force field is hierarchically decomposed at different resolution levels enabling to choose the most appropriate wavelet family for each physical interaction without requiring an a priori knowledge of the details localization. The representation of the CG potential in this new efficientmore » orthonormal basis leads to a compression of the signal information in few large expansion coefficients. The multiresolution property of the wavelet transform allows to isolate and remove the noise from the CG force-field reconstruction by thresholding the basis function coefficients from each frequency band independently. We discuss the implementation of our wavelet-based MSCG approach and demonstrate its accuracy using two different condensed-phase systems, i.e. liquid water and methanol. Simulations of liquid argon have also been performed using a one-to-one mapping between atomistic and CG sites. The latter model allows to verify the accuracy of the method and to test different choices of wavelet families. Furthermore, the results of the computer simulations show that the efficiency and sparsity of the representation of the CG force field can be traced back to the mathematical properties of the chosen family of wavelets. This result is in agreement with what is known from the theory of multiresolution analysis of signals.« less

[What compensatory motor strategies do patients with multiple sclerosis develop for balance control?].

PubMed

Rougier, P; Thoumie, P; Cantalloube, S; Lamotte, D

2007-11-01

One of the main features of multiple sclerosis (MS) is the deterioration of motor pathway axons, and in some cases, sensory system axons. Consequently, experimental sensori-motor testing with the undisturbed upright stance paradigm might be useful. It can be hypothesized that the postural strategies could be differently affected depending on the degree of dysfunction of both sensory and motor tracts. Twelve and fifteen patients, classified from sensory clinical tests as ataxo-spastic (SEP-AS) or only spastic (SEP-S), respectively were included in this study and compared to 12 healthy adults matched for age. The postural strategies were assessed from the centre of pressure trajectories (CP), measured from the force platform on which the subjects were instructed to stand upright eyes open for a trial lasting 51.2 s. biomechanical modelling was applied to these trajectories to compute the movements of the centre of gravity (CG) and consequently, the vertical difference between the CP and then the CP-CG, two elementary movements known to characterize postural performance movements for CGv and horizontal acceleration communicated to the CG for the CP-CG movements, and consequently overall neuro-muscular activity. To estimate the relative contribution of each of these elementary movements, an analysis based on frequency parameters (RMS and MF) was conducted. Both SEP-AS and SEP-S groups demonstrate larger CG and CP-CG movements than the age paired individuals. However, some statistically significant differences has to be emphasised between the two MS subgroups but only for the CP-CG component: the RMS of these movements are largely increased for the SEP-AS group, as compared to the SEP-S one. Biomechanically, this feature expresses the necessity for these very patients to produce exaggerated horizontal forces, and thus an increased energy expenditure, to handle the CG movements. The lack of effect observed for the CG movements underlines the capacity for the SEP-AS group to set appropriate control mechanisms for counteracting these less favourable initial conditions. By demonstrating specific trends in the postural organisation aimed at controlling undisturbed upright stance maintenance, this study can be of interest for the practitioner by legitimating this experimental paradigm as a simple and non invasive way to diagnose appropriately the sensori-motor deficiency.

Reproductive performance of lactating dairy cows after inducing ovulation using hCG in a five-day progesterone-based fixed-time AI protocol.

PubMed

Garcia-Ispierto, I; De Rensis, F; Casas, X; Caballero, F; Mur-Novales, R; López-Gatius, F

2018-02-01

This study compares the effects of inducing ovulation using human chorionic gonadotropin (hCG) or gonadotropin releasing hormone (GnRH) at the end of a 5-day progesterone(P4)-based protocol for fixed-time artificial insemination (FTAI) in lactating dairy cows on ovarian dynamics and fertility. A P4 intravaginal device (PRID) was fitted for five days and GnRH administered upon PRID insertion and a double dose (24 h apart) of prostaglandin F 2α upon PRID removal. Cows received either GnRH (GnRH group; n = 98), 1000 IU hCG (hCG-1 group; n = 97), or 3000 IU hCG (hCG-2 group; n = 104) 36 h after PRID removal and were inseminated 50-56 h after PRID removal. Based on Tukey-Kramer tests, cows in hCG-1 and hCG-2 showed a larger follicle diameter at AI than cows in GnRH (P < 0.05). HCG-2 treatment increased corpus luteum (CL) size on Day 7 post-AI compared with the GnRH and hCG-1 treatments (P < 0.05). Based on odds ratios, the likelihood of ovulation failure decreased with increasing follicle diameter at AI (P = 0.002). Cows in hCG-1 or hCG-2 that did not become pregnant were more likely to return to estrus than cows in GnRH (P < 0.01). A larger CL size post-AI was related to an increased conception rate at FTAI (P = 0.003). Cows given hCG-2 treatment showed a 1.9-fold cumulative pregnancy rate after two rounds of AI compared to cows receiving GnRH. Our results indicate that hCG treatment hCG treatment used to induce ovulation at the end of a short protocol for FTAI improves follicular/luteal dynamics compared to GnRH treatment. Of the two hCG treatments tested, better results were obtained with the 3000 IU dose. Copyright © 2017 Elsevier Inc. All rights reserved.

PubMed Central

Bédard, S; Desrochers, A; Fecteau, G; Higgins, R

2001-01-01

This study was designed to evaluate 4 preoperative skin preparations, that is, more specifically, to compare the efficacy of chlorhexidine gluconate (CG) and povidone-iodine (PI), as well as 2 hair removal techniques (clipper alone or clipper followed by razor) for preoperative skin preparation in cattle. The 4 protocols resulted in a significant decrease in the number of bacterial colony-forming units (cfu). Group 4 (clipping + shaving + CG) had a significantly lower number of preoperative cfu per gel plate compared with groups 1 (clipping + PI) and 3 (clipping + shaving + PI). Skin reaction frequency was significantly higher in groups 3 and 4 (47.8% for both protocols) than in groups 1 and 2 (clipping + PI or CG) (8.7% for both). Wound infection frequency was 4.3% (4/92) and no significant difference was observed between the 4 treatment groups. The 4 protocols tested were equivalent as to efficacy and satisfactorily decreased skin microflora. Clipping alone was shown to be preferable to clipping plus shaving as a method of hair removal in cattle, with fewer skin reactions and no more wound infections. PMID:11265188

Marine Mammals and Low-Frequency Sound: Progress Since 1994

DTIC Science & Technology

2000-03-03

Acoustical Society of America 100:2611. Abstract. Stafford , K.M., CG. Fox, and D.S. Clark. 1998 . Long - range acoustic detection and localization ...adds further incentive for documenting the occurrence and types of vocalizations of blue whales in the Pacific Ocean ( Stafford et al., 1998 ). The...K.M. Stafford , CG. Fox, H.W. Braham, M.A. McDonald, and J. Thomason. 1999. Acoustic and visual detection of large

Animal-to-animal variability in the phasing of the crustacean cardiac motor pattern: an experimental and computational analysis

PubMed Central

Williams, Alex H.; Kwiatkowski, Molly A.; Mortimer, Adam L.; Marder, Eve; Zeeman, Mary Lou

2013-01-01

The cardiac ganglion (CG) of Homarus americanus is a central pattern generator that consists of two oscillatory groups of neurons: “small cells” (SCs) and “large cells” (LCs). We have shown that SCs and LCs begin their bursts nearly simultaneously but end their bursts at variable phases. This variability contrasts with many other central pattern generator systems in which phase is well maintained. To determine both the consequences of this variability and how CG phasing is controlled, we modeled the CG as a pair of Morris-Lecar oscillators coupled by electrical and excitatory synapses and constructed a database of 15,000 simulated networks using random parameter sets. These simulations, like our experimental results, displayed variable phase relationships, with the bursts beginning together but ending at variable phases. The model suggests that the variable phasing of the pattern has important implications for the functional role of the excitatory synapses. In networks in which the two oscillators had similar duty cycles, the excitatory coupling functioned to increase cycle frequency. In networks with disparate duty cycles, it functioned to decrease network frequency. Overall, we suggest that the phasing of the CG may vary without compromising appropriate motor output and that this variability may critically determine how the network behaves in response to manipulations. PMID:23446690

GLUTATHIONE PEROXIDASE-1 PRO200LEU POLYMORPHISM (RS1050450) IS ASSOCIATED WITH MORBID OBESITY INDEPENDENTLY OF THE PRESENCE OF PREDIABETES OR DIABETES IN WOMEN FROM CENTRAL MEXICO.

PubMed

Hernández Guerrero, César; Hernández Chávez, Paulina; Martínez Castro, Noemí; Parra Carriedo, Alicia; García Del Rio, Sandra; Pérez Lizaur, Ana

2015-10-01

obesity affects more than a third of Mexican population. Oxidative stress participates actively in the etiology of this phenomenon. Glutathione peroxidase-1 (GPX-1) plays a protective role against oxidative stress. The SNP Pro200Leu (rs10504050) has been reported to affect the activity of the enzyme. to determine the frequency of rs10504050 polymorphism in women with obesity and normal weight control, asses the concentration of peripheral TBARS and evaluate the consumption of pro and antioxidants. 104 women with obesity and 70 healthy controls (CG) were included in the study. Anthropometric, biochemical, clinical and dietary features were evaluated. GPx-1 rs10504050 was determined by PCR/RFLP method. TBARS was assayed spectrophotometrically in plasma. The subjects were stratified and compared by obesity grades and by subgroups of prediabetes and diabetes condition. Statistical analysis included ANOVA of Kruskal Wallis, Xi squared and Pearson correlation. for rs10504050 polymorphism there were differences (Xi2 = 6; p = 0.01) between frequency (0.61) of obese carriers (Pro/Leu plus Leu/Leu) and CG carriers (0.42), and between (Xi2 = 8; p = 0.004) morbid (IMC > 40) obesity (0.74) and CG carriers. The obese group (OB) showed a prevalence of 66% of prediabetes plus diabetes. There were no differences in frequencies of rs10504050 in OB with pre or diabetes versus CG, or versus obese participants without diabetes. TBARS concentration was greater in all the degrees of OB versus CG. GPx-1 Pro200Leu polymorphism was associated with obesity especially with morbid obesity, but not with obese participants with prediabetes or diabetes. Oxidative stress is present in all grades of obesity significantly. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Systematic and simulation-free coarse graining of homopolymer melts: a relative-entropy-based study.

PubMed

Yang, Delian; Wang, Qiang

2015-09-28

We applied the systematic and simulation-free strategy proposed in our previous work (D. Yang and Q. Wang, J. Chem. Phys., 2015, 142, 054905) to the relative-entropy-based (RE-based) coarse graining of homopolymer melts. RE-based coarse graining provides a quantitative measure of the coarse-graining performance and can be used to select the appropriate analytic functional forms of the pair potentials between coarse-grained (CG) segments, which are more convenient to use than the tabulated (numerical) CG potentials obtained from structure-based coarse graining. In our general coarse-graining strategy for homopolymer melts using the RE framework proposed here, the bonding and non-bonded CG potentials are coupled and need to be solved simultaneously. Taking the hard-core Gaussian thread model (K. S. Schweizer and J. G. Curro, Chem. Phys., 1990, 149, 105) as the original system, we performed RE-based coarse graining using the polymer reference interaction site model theory under the assumption that the intrachain segment pair correlation functions of CG systems are the same as those in the original system, which de-couples the bonding and non-bonded CG potentials and simplifies our calculations (that is, we only calculated the latter). We compared the performance of various analytic functional forms of non-bonded CG pair potential and closures for CG systems in RE-based coarse graining, as well as the structural and thermodynamic properties of original and CG systems at various coarse-graining levels. Our results obtained from RE-based coarse graining are also compared with those from structure-based coarse graining.

Physical therapy for airway clearance improves cardiac autonomic modulation in children with acute bronchiolitis

PubMed Central

Jacinto, Cynthia P.; Gastaldi, Ada C.; Aguiar, Daniela Y.; Maida, Karina D.; Souza, Hugo C. D.

2013-01-01

Background The effects of physical therapy on heart rate variability (HRV), especially in children, are still inconclusive. Objective We investigated the effects of conventional physical therapy (CPT) for airway clearance and nasotracheal suction on the HRV of pediatric patients with acute bronchiolitis. Method 24 children were divided into two groups: control group (CG, n=12) without respiratory diseases and acute bronchiolitis group (BG, n=12). The heart rate was recorded in the BG at four different moments: basal recording (30 minutes), 5 minutes after the CPT (10 minutes), 5 minutes after nasotracheal suction (10 minutes), and 40 minutes after nasotracheal suction (30 minutes). The CG was subjected to the same protocol, except for nasotracheal suction. To assess the HRV, we used spectrum analysis, which decomposes the heart rate oscillations into frequency bands: low frequency (LF=0.04-0.15Hz), which corresponds mainly to sympathetic modulation; and high frequency (HF=0.15-1.2Hz), corresponding to vagal modulation. Results Under baseline conditions, the BG showed higher values in LF oscillations, lower values in HF oscillations, and increased LF/HF ratio when compared to the CG. After CPT, the values for HRV in the BG were similar to those observed in the CG during basal recording. Five minutes after nasotracheal suction, the BG showed a decrease in LF and HF oscillations; however, after 40 minutes, the values were similar to those observed after application of CPT. Conclusions The CPT and nasotracheal suction, both used for airway clearance, promote improvement in autonomic modulation of HRV in children with acute bronchiolitis. PMID:24271093

Comparing distinct ground-based lightning location networks covering the Netherlands

NASA Astrophysics Data System (ADS)

de Vos, Lotte; Leijnse, Hidde; Schmeits, Maurice; Beekhuis, Hans; Poelman, Dieter; Evers, Läslo; Smets, Pieter

2015-04-01

Lightning can be detected using a ground-based sensor network. The Royal Netherlands Meteorological Institute (KNMI) monitors lightning activity in the Netherlands with the so-called FLITS-system; a network combining SAFIR-type sensors. This makes use of Very High Frequency (VHF) as well as Low Frequency (LF) sensors. KNMI has recently decided to replace FLITS by data from a sub-continental network operated by Météorage which makes use of LF sensors only (KNMI Lightning Detection Network, or KLDN). KLDN is compared to the FLITS system, as well as Met Office's long-range Arrival Time Difference (ATDnet), which measures Very Low Frequency (VLF). Special focus lies on the ability to detect Cloud to Ground (CG) and Cloud to Cloud (CC) lightning in the Netherlands. Relative detection efficiency of individual flashes and lightning activity in a more general sense are calculated over a period of almost 5 years. Additionally, the detection efficiency of each system is compared to a ground-truth that is constructed from flashes that are detected by both of the other datasets. Finally, infrasound data is used as a fourth lightning data source for several case studies. Relative performance is found to vary strongly with location and time. As expected, it is found that FLITS detects significantly more CC lightning (because of the strong aptitude of VHF antennas to detect CC), though KLDN and ATDnet detect more CG lightning. We analyze statistics computed over the entire 5-year period, where we look at CG as well as total lightning (CC and CG combined). Statistics that are considered are the Probability of Detection (POD) and the so-called Lightning Activity Detection (LAD). POD is defined as the percentage of reference flashes the system detects compared to the total detections in the reference. LAD is defined as the fraction of system recordings of one or more flashes in predefined area boxes over a certain time period given the fact that the reference detects at least one flash, compared to the total recordings in the reference dataset. The reference for these statistics is taken to be either another dataset, or a dataset consisting of flashes detected by two datasets. Extreme thunderstorm case evaluation shows that the weather alert criterion for severe thunderstorm is reached by FLITS when this is not the case in KLDN and ATD, suggesting the need for KNMI to modify that weather alert criterion when using KLDN.

NO{sub x} from lightning 1. Global distribution based on lightning physics

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

Price, C.; Penner, J.; Prather, M.

1997-03-01

This paper begins a study on the role of lightning in maintaining the global distribution of nitrogen oxides (NO{sub x}) in the troposphere. It presents the first global and seasonal distributions of lightning-produced NO{sub x} (LNO{sub x}) based on the observed distribution of electrical storms and the physical properties of lightning strokes. We derive a global rate for cloud-to-ground (CG) flashes of 20{endash}30 flashes/s with a mean energy per flash of 6.7{times}10{sup 9}J. Intracloud (IC) flashes are more frequent, 50{endash}70 flashes/s but have 10{percent} of the energy of CG strokes and, consequently, produce significantly less NO{sub x}. It appears tomore » us that the majority of previous studies have mistakenly assumed that all lightning flashes produce the same amount of NO{sub x}, thus overestimating the NO{sub x} production by a factor of 3. On the other hand, we feel these same studies have underestimated the energy released in CG flashes, resulting in two negating assumptions. For CG energies we adopt a production rate of 10{times}10{sup 16} molecules NO/J based on the current literature. Using a method to simulate global lightning frequencies from satellite-observed cloud data, we have calculated the LNO{sub x} on various spatial (regional, zonal, meridional, and global) and temporal scales (daily, monthly, seasonal, and interannual). Regionally, the production of LNO{sub x} is concentrated over tropical continental regions, predominantly in the summer hemisphere. The annual mean production rate is calculated to be 12.2 Tg N/yr, and we believe it extremely unlikely that this number is less than 5 or more than 20 Tg N/yr. Although most of LNO{sub x} is produced in the lowest 5 km by CG lightning, convective mixing in the thunderstorms is likely to deposit large amounts of NO{sub x} in the upper troposphere where it is important in ozone production. (Abstract Truncated)« less

5-Methylation of Cytosine in CG:CG Base-Pair Steps: A Physicochemical Mechanism for the Epigenetic Control of DNA Nanomechanics

NASA Astrophysics Data System (ADS)

Yusufaly, Tahir; Olson, Wilma; Li, Yun

2014-03-01

Van der Waals density functional theory is integrated with analysis of a non-redundant set of protein-DNA crystal structures from the Nucleic Acid Database to study the stacking energetics of CG:CG base-pair steps, specifically the role of cytosine 5-methylation. Principal component analysis of the steps reveals the dominant collective motions to correspond to a tensile ``opening'' mode and two shear ``sliding'' and ``tearing'' modes in the orthogonal plane. The stacking interactions of the methyl groups are observed to globally inhibit CG:CG step overtwisting while simultaneously softening the modes locally via potential energy modulations that create metastable states. The results have implications for the epigenetic control of DNA mechanics.

Cloud-to-Ground Lightning Estimates Derived from SSMI Microwave Remote Sensing and NLDN

NASA Technical Reports Server (NTRS)

Winesett, Thomas; Magi, Brian; Cecil, Daniel

2015-01-01

Lightning observations are collected using ground-based and satellite-based sensors. The National Lightning Detection Network (NLDN) in the United States uses multiple ground sensors to triangulate the electromagnetic signals created when lightning strikes the Earth's surface. Satellite-based lightning observations have been made from 1998 to present using the Lightning Imaging Sensor (LIS) on the NASA Tropical Rainfall Measuring Mission (TRMM) satellite, and from 1995 to 2000 using the Optical Transient Detector (OTD) on the Microlab-1 satellite. Both LIS and OTD are staring imagers that detect lightning as momentary changes in an optical scene. Passive microwave remote sensing (85 and 37 GHz brightness temperatures) from the TRMM Microwave Imager (TMI) has also been used to quantify characteristics of thunderstorms related to lightning. Each lightning detection system has fundamental limitations. TRMM satellite coverage is limited to the tropics and subtropics between 38 deg N and 38 deg S, so lightning at the higher latitudes of the northern and southern hemispheres is not observed. The detection efficiency of NLDN sensors exceeds 95%, but the sensors are only located in the USA. Even if data from other ground-based lightning sensors (World Wide Lightning Location Network, the European Cooperation for Lightning Detection, and Canadian Lightning Detection Network) were combined with TRMM and NLDN, there would be enormous spatial gaps in present-day coverage of lightning. In addition, a globally-complete time history of observed lightning activity is currently not available either, with network coverage and detection efficiencies varying through the years. Previous research using the TRMM LIS and Microwave Imager (TMI) showed that there is a statistically significant correlation between lightning flash rates and passive microwave brightness temperatures. The physical basis for this correlation emerges because lightning in a thunderstorm occurs where ice is first present in the cloud and electric charge separation occurs. These ice particles efficiently scatter the microwave radiation at the 85 and 37 GHz frequencies, thus leading to large brightness temperature depressions. Lightning flash rate is related to the total amount of ice passing through the convective updraft regions of thunderstorms. Confirmation of this relationship using TRMM LIS and TMI data, however, remains constrained to TRMM observational limits of the tropics and subtropics. Satellites from the Defense Meteorology Satellite Program (DMSP) have global coverage and are equipped with passive microwave imagers that, like TMI, observe brightness temperatures at 85 and 37 GHz. Unlike the TRMM satellite, however, DMSP satellites do not have a lightning sensor, and the DMSP microwave data has never been used to derive global lightning. In this presentation, a relationship between DMSP Special Sensor Microwave Imager (SSMI) data and ground-based cloud-to-ground (CG) lightning data from NLDN is investigated to derive a spatially complete time history of CG lightning for the USA study area. This relationship is analogous to the established using TRMM LIS and TMI data. NLDN has the most spatially and temporally complete CG lightning data for the USA, and therefore provides the best opportunity to find geospatially coincident observations with SSMI sensors. The strongest thunderstorms generally have minimum 85 GHz Polarized Corrected brightness Temperatures (PCT) less than 150 K. Archived radar data was used to resolve the spatial extent of the individual storms. NLDN data for that storm spatial extent defined by radar data was used to calculate the CG flash rate for the storm. Similar to results using TRMM sensors, a linear model best explained the relationship between storm-specific CG flash rates and minimum 85 GHz PCT. However, the results in this study apply only to CG lightning. To extend the results to weaker storms, the probability of CG lightning (instead of the flash rate) was calculated for storms having 85 GHz PCT greater than 150 K. NLDN data was used to determine if a CG strike occurred for a storm. This probability of CG lightning was plotted as a function of minimum 85 GHz PCT and minimum 37 GHz PCT. These probabilities were used in conjunction with the linear model to estimate the CG flash rate for weaker storms with minimum 85 GHz PCTs greater than 150 K. Results from the investigation of CG lightning and passive microwave radiation signals agree with the previous research investigating total lightning and brightness temperature. Future work will take the established relationships and apply them to the decades of available DMSP data for the USA to derive a map of CG lightning flash rates. Validation of this method and uncertainty analysis will be done by comparing the derived maps of CG lightning flash rates against existing NLDN maps of CG lightning flash rates.

Quantum theory of multiscale coarse-graining.

PubMed

Han, Yining; Jin, Jaehyeok; Wagner, Jacob W; Voth, Gregory A

2018-03-14

Coarse-grained (CG) models serve as a powerful tool to simulate molecular systems at much longer temporal and spatial scales. Previously, CG models and methods have been built upon classical statistical mechanics. The present paper develops a theory and numerical methodology for coarse-graining in quantum statistical mechanics, by generalizing the multiscale coarse-graining (MS-CG) method to quantum Boltzmann statistics. A rigorous derivation of the sufficient thermodynamic consistency condition is first presented via imaginary time Feynman path integrals. It identifies the optimal choice of CG action functional and effective quantum CG (qCG) force field to generate a quantum MS-CG (qMS-CG) description of the equilibrium system that is consistent with the quantum fine-grained model projected onto the CG variables. A variational principle then provides a class of algorithms for optimally approximating the qMS-CG force fields. Specifically, a variational method based on force matching, which was also adopted in the classical MS-CG theory, is generalized to quantum Boltzmann statistics. The qMS-CG numerical algorithms and practical issues in implementing this variational minimization procedure are also discussed. Then, two numerical examples are presented to demonstrate the method. Finally, as an alternative strategy, a quasi-classical approximation for the thermal density matrix expressed in the CG variables is derived. This approach provides an interesting physical picture for coarse-graining in quantum Boltzmann statistical mechanics in which the consistency with the quantum particle delocalization is obviously manifest, and it opens up an avenue for using path integral centroid-based effective classical force fields in a coarse-graining methodology.

Influence of a 50 hz extra low frequency electromagnetic field on spermatozoa motility and fertilization rates in rabbits.

PubMed

Roychoudhury, Shubhadeep; Jedlicka, Jaroslav; Parkanyi, Vladimir; Rafay, Jan; Ondruska, Lubomir; Massanyi, Peter; Bulla, Jozef

2009-08-01

Effects of a 50 Hz extra-low frequency electromagnetic field (ELF EMF) on in vitro rabbit spermatozoa motility were analyzed, as well as the effect on fertilization rates after insemination. Pooled semen samples and a control were exposed to 50 Hz ELF EMF. The difference of the samples of the test groups G1 and G2 with the control group CG (75.56%) for spermatozoa motility were found to be significant (P < 0.01). Differences were significant (P < 0.01) for curvilinear velocity (VCL) between the test group G3 (122.38 microm/s) and the control group CG (112.02 microm/s). Hormonally stimulated adult (9-12 months) females (n = 140) were inseminated with semen samples from G1, G2, G3 and CG (0.88 x 109 spermatozoa/0.5 mL average insemination portion) immediately after ELF EMF exposure and fertilization (kindling) rates were calculated. For the G2 it was 54.28% data indicate 50 Hz ELF EMF induced alterations of spermatozoa motility and kindling rate in rabbits, therefore influencing fertility.

The 5-HT₁A receptor C(1019)G polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation.

PubMed

Janssen, Paddy K C; van Schaik, R; Zwinderman, Aeilko H; Olivier, Berend; Waldinger, Marcel D

2014-06-01

Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 min, and has been postulated as a neurobiological dysfunction related to diminished serotonergic neurotransmission with 5-HT₁A receptor hyperfunction and 5-HT₂C hypofunction. To investigate the relationship between 5-HT₁A receptor gene (HTR₁A)-C(1019)G promoter polymorphism and IELT in men with LPE. This polymorphism is known to increase 5-HT1A receptor expression. A prospective study was conducted in 54 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for HTR₁A gene polymorphism. Allele frequencies and genotypes of C and G variants of HTR₁A polymorphism were determined. Association between CC, CG, and GG genotypes and the IELT in men with LPE were investigated. IELT measured by stopwatch, HTR₁A polymorphism. In this cohort of men with LPE, the geometric mean IELT was 23.8 s. Of the 54 men, the CC, CG and GG genotype frequency for the C(1019)G polymorphism of the 5-HT₁A gene was 33%, 43% and 24%, respectively. The geometric mean IELT for the CC, CG and GG genotypes were 14.5, 27.7 and 36.0 s, respectively (p=0.019). Compared to GG and CG genotypes, men with CC genotype had a 250% and 190% shorter ejaculation time, respectively. HTR₁A gene polymorphism is associated with the IELT in men with LPE. Men with CC genotype have shorter IELTs than men with GG and CG genotypes. Copyright © 2014 Elsevier Inc. All rights reserved.

Interleukin-6 genotypes and serum levels in Chinese Hui population

PubMed Central

Gao, Shu-Ping; Liang, Shu; Pan, Min; Sun, Rong-Liang; Chen, Chu; Luan, Hong; Jiang, Min-Hui

2014-01-01

Interleukin-6 (IL-6) is a key pro-inflammatory cytokine involved in different physiologic and pathophysiologic processes, and circulating levels of IL-6 differ greatly between individuals. The Chinese Hui is one of the largest ethnic minorities, little is known about the distribution of IL-6 genetic variations and their effects on serum levels in Hui population. The aim of the present study is to determine the prevalence of -174G/C (rs1800795), -597G/A (rs1800797), and -634C/G (rs1800796) polymorphisms in the IL-6 gene promoter region and their association with IL-6 serum levels in the Ningxia Hui population. A total of 96 Hui subjects, (57 men and 39 women; mean age 49.65 ± 19.73 years) unrelated nationality residents in Ningxia Hui Autonomous Region were enrolled. Genotyping of the three polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) combined with gel electrophoresis and then confirmed by direct sequencing. The -174G/C (97.92% GG, 2.08% GC, and 0% CC) and -597G/A (98.96% GG, 1.04% GA, and 0% AA) polymorphisms were rare. The frequencies of -634C/G genotypes CC, CG, and GG were found to be 54.17%, 40.62%, and 5.21%, respectively in total studied subjects, the derived allele frequencies for the C and G alleles were 74.48% and 25.52%. Increased IL-6 levels were correlated with the IL-6 -634G allele carriers (CG+GG genotypes). The results suggest that IL-6 -174G/C and -597G/A are rare but -634C/G is common in the Ningxia Hui population, and the -634G allele is associated with circulating levels of IL-6. PMID:25356148

Regular Football Practice Improves Autonomic Cardiac Function in Male Children.

PubMed

Fernandes, Luis; Oliveira, Jose; Soares-Miranda, Luisa; Rebelo, Antonio; Brito, Joao

2015-09-01

The role of the autonomic nervous system (ANS) in the cardiovascular regulation is of primal importance. Since it has been associated with adverse conditions such as cardiac arrhythmias, sudden death, sleep disorders, hypertension and obesity. The present study aimed to investigate the impact of recreational football practice on the autonomic cardiac function of male children, as measured by heart rate variability. Forty-seven male children aged 9 - 12 years were selected according to their engagement with football oriented practice outside school context. The children were divided into a football group (FG; n = 22) and a control group (CG; n = 25). The FG had regular football practices, with 2 weekly training sessions and occasional weekend matches. The CG was not engaged with any physical activity other than complementary school-based physical education classes. Data from physical activity, physical fitness, and heart rate variability measured in time and frequency domains were obtained. The anthropometric and body composition characteristics were similar in both groups (P > 0.05). The groups were also similar in time spent daily on moderate-to-vigorous physical activities (FG vs. CG: 114 ± 64 vs. 87 ± 55 minutes; P > 0.05). However, the FG performed better (P < 0.05) in Yo-Yo intermittent endurance test (1394 ± 558 vs. 778 ± 408 m) and 15-m sprint test (3.06 ± 0.17 vs. 3.20 ± 0.23 s). Also, the FG presented enhanced autonomic function. Significant differences were detected (P < 0.05) between groups for low frequency normalized units (38.0 ± 15.2 vs. 47.3 ± 14.2 n.u (normalized units)), high frequency normalized units (62.1 ± 15.2 vs. 52.8 ± 14.2 n.u.), and LF:HF ratio (0.7 ± 0.4 vs. 1.1 ± 0.6 ms(2)). Children engaged with regular football practice presented enhanced physical fitness and autonomic function, by increasing vagal tone at rest.

Regular Football Practice Improves Autonomic Cardiac Function in Male Children

PubMed Central

Fernandes, Luis; Oliveira, Jose; Soares-Miranda, Luisa; Rebelo, Antonio; Brito, Joao

2015-01-01

Background: The role of the autonomic nervous system (ANS) in the cardiovascular regulation is of primal importance. Since it has been associated with adverse conditions such as cardiac arrhythmias, sudden death, sleep disorders, hypertension and obesity. Objectives: The present study aimed to investigate the impact of recreational football practice on the autonomic cardiac function of male children, as measured by heart rate variability. Patients and Methods: Forty-seven male children aged 9 - 12 years were selected according to their engagement with football oriented practice outside school context. The children were divided into a football group (FG; n = 22) and a control group (CG; n = 25). The FG had regular football practices, with 2 weekly training sessions and occasional weekend matches. The CG was not engaged with any physical activity other than complementary school-based physical education classes. Data from physical activity, physical fitness, and heart rate variability measured in time and frequency domains were obtained. Results: The anthropometric and body composition characteristics were similar in both groups (P > 0.05). The groups were also similar in time spent daily on moderate-to-vigorous physical activities (FG vs. CG: 114 ± 64 vs. 87 ± 55 minutes; P > 0.05). However, the FG performed better (P < 0.05) in Yo-Yo intermittent endurance test (1394 ± 558 vs. 778 ± 408 m) and 15-m sprint test (3.06 ± 0.17 vs. 3.20 ± 0.23 s). Also, the FG presented enhanced autonomic function. Significant differences were detected (P < 0.05) between groups for low frequency normalized units (38.0 ± 15.2 vs. 47.3 ± 14.2 n.u (normalized units)), high frequency normalized units (62.1 ± 15.2 vs. 52.8 ± 14.2 n.u.), and LF:HF ratio (0.7 ± 0.4 vs. 1.1 ± 0.6 ms2). Conclusions: Children engaged with regular football practice presented enhanced physical fitness and autonomic function, by increasing vagal tone at rest. PMID:26448848

cgDNAweb: a web interface to the cgDNA sequence-dependent coarse-grain model of double-stranded DNA.

PubMed

De Bruin, Lennart; Maddocks, John H

2018-06-14

The sequence-dependent statistical mechanical properties of fragments of double-stranded DNA is believed to be pertinent to its biological function at length scales from a few base pairs (or bp) to a few hundreds of bp, e.g. indirect read-out protein binding sites, nucleosome positioning sequences, phased A-tracts, etc. In turn, the equilibrium statistical mechanics behaviour of DNA depends upon its ground state configuration, or minimum free energy shape, as well as on its fluctuations as governed by its stiffness (in an appropriate sense). We here present cgDNAweb, which provides browser-based interactive visualization of the sequence-dependent ground states of double-stranded DNA molecules, as predicted by the underlying cgDNA coarse-grain rigid-base model of fragments with arbitrary sequence. The cgDNAweb interface is specifically designed to facilitate comparison between ground state shapes of different sequences. The server is freely available at cgDNAweb.epfl.ch with no login requirement.

The Relationship between Tornado Reports and Cloud-to-Ground Lightning Polarity in the Southeastern United States during the Cool Season from 1989 to 2002

NASA Astrophysics Data System (ADS)

Carey, L. D.; Butts, D. A.

2006-12-01

Several past case and climatological studies have analyzed the relationship between tornadogenesis and cloud-to-ground (CG) lightning polarity. In particular, there has been an emphasis on investigating when and under what environmental and storm conditions tornadoes are associated with anomalous positive CG lightning in order to understand cloud electrification mechanisms and to explore tornado nowcasting opportunities using National Lightning Detection Network (NLDN) CG lightning data. Most of the case and all of the climatological studies have been conducted during the warm season (April to September). In the southeastern United States, a significant number of tornadoes occur in the cool season (October to March). To address this gap in our climatological knowledge, we extend past research by determining the NLDN ground flash properties, including polarity, flash density, peak current, and multiplicity, in the vicinity of tornado reports during the cool season from 1989 2002 in the southeastern United States (i.e., from 102 to 72 degrees west longitude and from 24 to 42 degrees north latitude). Following past studies, we examined NLDN CG lightning properties within 50 km and one hour prior to all tornado reports (i.e., F0 - F5 on the Fujita damage scale). Interestingly, no NLDN detected ground flash activity occurred in the vicinity of 967 (29 %) of the 3325 tornado reports in our sample. Only 10 % (236) of the remaining 2358 tornado reports were associated with predominately (> 50 %) positive CG (PPCG) lightning activity. About 25 % (598) of the tornado reports accompanied by ground flash activity were associated with > 25 % positive CG polarity. In our analysis domain, the geographic frequency maximum of tornadoes accompanied by PPCG lightning activity occurred in a north-south oriented region centered on central Kansas that extended northward into Nebraska and southward into Oklahoma. In this preferred region, 30 % to 60 % of all cool season tornado reports were associated with PPCG lightning activity. Secondary frequency maxima of tornadoes accompanied by PPCG lightning occurred from Louisiana to North Carolina in an arc that followed about 100 to 200 km inland from the coast. From North Carolina to Georgia, the secondary maxima were also downwind of the southern Appalachian Mountains. Another secondary frequency maximum in tornado PPCG activity was centered over northern Florida. However, the percentage of tornadoes associated with PPCG lightning activity over these secondary frequency maxima was typically less than 10 %. Interestingly, this percentage was slightly elevated (10 % to 20 %) over North Carolina on the lee side of the Appalachian Mountains. Additional results will be presented and implications of this study will be discussed.

Reference ranges and determinants of total hCG levels during pregnancy: the Generation R Study.

PubMed

Korevaar, Tim I M; Steegers, Eric A P; de Rijke, Yolanda B; Schalekamp-Timmermans, Sarah; Visser, W Edward; Hofman, Albert; Jaddoe, Vincent W V; Tiemeier, Henning; Visser, Theo J; Medici, Marco; Peeters, Robin P

2015-09-01

Human chorionic gonadotropin (hCG) is a pregnancy hormone secreted by the placental synctiotrophoblast cell layer that has been linked to fetal growth and various placental, uterine and fetal functions. In order to investigate the effects of hCG on clinical endpoints, knowledge on reference range (RR) methodology and determinants of gestational hCG levels is crucial. Moreover, a better understanding of gestational hCG physiology can improve current screening programs and future clinical management. Serum total hCG levels were determined in 8195 women participating in the Generation R Study. Gestational age specific RRs using 'ultrasound derived gestational age' (US RRs) were calculated and compared with 'last menstrual period derived gestational age' (LMP RRs) and a model-based RR. We also investigated which pregnancy characteristics were associated with hCG levels. Compared to the US RRs, the LMP RRs were lower, most notably for the median and lower limit levels. No considerable differences were found between RRs calculated in the general population or in uncomplicated pregnancies only. Maternal smoking, BMI, parity, ethnicity, fetal gender, placental weight and hyperemesis gravidarum symptoms were associated with total hCG. We provide gestational RRs for total hCG and show that total hCG values and RR cut-offs during pregnancy vary depending on pregnancy dating methodology. This is likely due to the influence of hCG on embryonic growth, suggesting that ultrasound based pregnancy dating might be less reliable in women with high/low hCG levels. Furthermore, we identify different pregnancy characteristics that influence total hCG levels considerably and should therefore be accounted for in clinical studies.

cgDNA: a software package for the prediction of sequence-dependent coarse-grain free energies of B-form DNA.

PubMed

Petkevičiūtė, D; Pasi, M; Gonzalez, O; Maddocks, J H

2014-11-10

cgDNA is a package for the prediction of sequence-dependent configuration-space free energies for B-form DNA at the coarse-grain level of rigid bases. For a fragment of any given length and sequence, cgDNA calculates the configuration of the associated free energy minimizer, i.e. the relative positions and orientations of each base, along with a stiffness matrix, which together govern differences in free energies. The model predicts non-local (i.e. beyond base-pair step) sequence dependence of the free energy minimizer. Configurations can be input or output in either the Curves+ definition of the usual helical DNA structural variables, or as a PDB file of coordinates of base atoms. We illustrate the cgDNA package by comparing predictions of free energy minimizers from (a) the cgDNA model, (b) time-averaged atomistic molecular dynamics (or MD) simulations, and (c) NMR or X-ray experimental observation, for (i) the Dickerson-Drew dodecamer and (ii) three oligomers containing A-tracts. The cgDNA predictions are rather close to those of the MD simulations, but many orders of magnitude faster to compute. Both the cgDNA and MD predictions are in reasonable agreement with the available experimental data. Our conclusion is that cgDNA can serve as a highly efficient tool for studying structural variations in B-form DNA over a wide range of sequences. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

An 11-Year Climatology of Storms in Which Most Cloud-to-Ground Flashes Lower Positive Charge

NASA Astrophysics Data System (ADS)

MacGorman, D. R.; Eddy, A.; Williams, E. R.; Calhoun, K. M.

2017-12-01

Previous studies have shown that storms which produce frequent cloud-to-ground (CG) lightning dominated by flashes lowering positive charge to ground (+CG flashes) tend to have a so called "inverted" vertical distribution of charge. Such storms have implications for our understanding of electrification processes. We have analyzed eleven years of National Lightning Detection Network data to count +CG and -CG flashes having peak currents ≥15 kA in grid cells with dimensions of 15 km x 15 km x 15 min, with overlapping grid boxes every 5 km along both x and y over the contiguous United States and grids every 5 min in time. These dimensions were chosen because 15 km corresponds roughly to the horizontal size of typical storm cells and 15 min is roughly half the typical duration of a cell. To focus on storms dominated by +CG flashes, we identified all grid cells satisfying one of four sets of thresholds: cells in which +CG flashes for 15 min constitute ≥80%, 90%, or 100% of ≥10 CG flashes or 100% of ≥20 CG flashes. These percentages are larger than those used in most previous studies of +CG flashes. Our primary goal is to investigate the environmental and storm characteristics conducive to +CG flashes and "inverted-polarity" charge distributions, but here we concentrate on the interannual and seasonal distributions of storms satisfying the above thresholds and examine also their relationship to severe weather. As in previous climatological studies of geographic variations in the +CG fraction of total CG flashes, most storms satisfying our thresholds were in a swath stretching from far eastern Colorado and western Kansas roughly northward through Nebraska, the Dakotas, and Minnesota. This region overlaps much of the region in which radar inferred that hail larger than 2.9 cm in diameter most often occurs, but is shifted westward and northward from maxima of observer reports of large-hail occurrence. Although the relationship with radar-inferred large-hail frequency suggests a common dependence on some storm characteristics, storms satisfying our thresholds for +CG flashes also occurred, although less frequently, in regions in which few storms were inferred to have produced large hail, such as east of mountain ranges in northwestern states, so relationships with severe weather will need to be examined on a storm-by-storm basis.

Quantitative ELISAs for serum soluble LHCGR and hCG-LHCGR complex: potential diagnostics in first trimester pregnancy screening for stillbirth, Down’s syndrome, preterm delivery and preeclampsia

PubMed Central

2012-01-01

Background Soluble LH/hCG receptor (sLHCGR) released from placental explants and transfected cells can be detected in sera from pregnant women. To determine whether sLHCGR has diagnostic potential, quantitative ELISAs were developed and tested to examine the correlation between pregnancy outcome and levels of serum sLHCGR and hCG-sLHCGR complex. Methods Anti-LHCGR poly- and monoclonal antibodies recognizing defined LHCGR epitopes, commerical anti-hCGbeta antibody, together with recombinant LHCGR and yoked hCGbeta-LHCGR standard calibrators were used to develop two ELISAs. These assays were employed to quantify serum sLHCGR and hCG-sLHCGR at first trimester human pregnancy. Results Two ELISAs were developed and validated. Unlike any known biomarker, sLHCGR and hCG-sLHCGR are unique because Down’s syndrome (DS), preeclampsia and preterm delivery are linked to both low (less than or equal to 5 pmol/mL), and high (equal to or greater than 170 pmol/mL) concentrations. At these cut-off values, serum hCG-sLHCGR together with PAPP-A detected additional DS pregnancies (21%) which were negative by free hCGbeta plus PAPP-A screening procedure. Therefore, sLHCGR/hCG-sLHCGR has an additive effect on the current primary biochemical screening of aneuploid pregnancies. More than 88% of pregnancies destined to end in fetal demise (stillbirth) exhibited very low serum hCG-sLHCGR(less than or equal to 5 pmol/mL) compared to controls (median 16.15 pmol/mL, n = 390). The frequency of high hCG-sLHCGR concentrations (equal to or greater than 170 pmol/mL) in pathological pregnancies was at least 3-6-fold higher than that of the control, suggesting possible modulation of the thyrotropic effect of hCG by sLHCGR. Conclusions Serum sLHCGR/hCG-sLHCGR together with PAPP-A, have significant potential as first trimester screening markers for predicting pathological outcomes in pregnancy. PMID:23245345

Hyperglycosylated hCG: a Unique Human Implantation and Invasion Factor.

PubMed

Evans, Jemma

2016-03-01

Human chorionic gonadotropin (hCG), as one of the first embryonic products, has been extensively investigated for its role in implantation and placental development. Discovery of an over-glycosylated form of this hormone, hyperglycosylated hCG (hCG-H), has provided an additional level of complexity in our understanding of the implantation and placentation process; the structure, activity and functional implications of alterations in hCG isoforms throughout pregnancy are still being characterized. HCG-H comprises up to 90% of total hCG measurable in serum and urine during the first 2-3 weeks of pregnancy when invasive trophoblast activity is high, dropping to negligible proportions, less than 5%, of total hCG at the end of the first trimester. Functionally, hCG-H promotes trophoblast invasion during early pregnancy and has potential roles in immune cell modulation and endothelial function within the uterus at the time of pregnancy initiation. Altered levels of hCG-H are characteristics of pregnancy complications of altered trophoblast function and inadequate placentation, such as pre-eclampsia, and also over-abundance of invasive cytotrophoblasts, such as Down's syndrome. Improving our basic knowledge of the functional role-specific hCG isoforms plays in the complex cascade of events involved in implantation and placental development, and determining dynamic changes in the structure and activity of hCG isoforms throughout gestation will facilitate evidence-based decisions in assisted reproduction/in vitro fertilization based on the potential of embryos to implant, provide biomarkers for diagnosis of pregnancy complications associated with altered placental development and enhance understanding of how hCG isoforms may influence receptivity of the endometrium. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Delta-Sarcoglycan Gene Polymorphism as a Risk Factor for Hypertrophic Cardiomyopathy

PubMed Central

Garrido-Garduño, Martín H.; Pérez-Martínez, Ramón A.; Ruiz, Victor M.; Herrera-Tepatlán, Esteban; Rodríguez-Cruz, Maricela; Jiménez-Vaca, Ana L.; Minauro-Sanmiguel, Fernando; Salamanca-Gómez, Fabio A.

2012-01-01

Background: The C allele of c.−94C>G polymorphism of the delta-sarcoglycan gene was associated as a risk factor for coronary spasm in Japanese patients with hypertrophic cardiomyopathy (HCM). Aim: We evaluated whether the c.−94C>G polymorphism can be a risk factor for HCM in Mexican patients. Methods: The polymorphism was genotyped and the risk was estimated in 35 HCM patients and 145 healthy unrelated individuals. Data of this polymorphism reported in Mexican Amerindian populations were included. Results: The C allele frequency in HCM patients was higher with an odds ratio (OR) of 2.37, and the risk for the CC genotype increased to 5.0. The analysis with Mexican Amerindian populations showed that the C allele frequency was significantly higher in HCM patients with an OR of 2.96 and for CC genotype the risk increased to 7.60. Conclusions: The C allele of the c.−94C>G polymorphism is a risk factor for HCM, which is increased by the Amerindian component and can play an important role in the etiology and progression of disease in Mexican patients. PMID:22524166

Analytical sensitivity of four commonly used hCG point of care devices.

PubMed

Kamer, Sandy M; Foley, Kevin F; Schmidt, Robert L; Greene, Dina N

2015-04-01

Point of care (POC) hCG assays are often used to rule-out pregnancy and therefore diagnostic sensitivity, especially at low concentrations of hCG, is important. There are very few studies in the literature that seek to verify the claimed analytical sensitivity of hCG POC devices. The analytical sensitivity of four commonly used hCG POC devices (Alere hCG Combo Cassette, ICON 20 hCG, OSOM hCG Combo Test, and Sure-Vue Serum/Urine hCG-STAT) was challenged using urine samples (n=50) selected based on quantitative hCG concentrations. The majority of these specimens (n=40) had an hCG concentration between 20 and 200 U/L. Each specimen/device combination was reviewed by three individuals. Statistical calculations were performed using Stata 12. The analytical sensitivity of the OSOM was significantly lower inferior than that of the other POC devices. There was no significant difference in the sensitivity of the Alere, ICON 20 and Sure-Vue devices. There was no significant difference in the individual interpretation of the hCG POC results. All hCG POC devices evaluated in this study were susceptible to false negative results at low concentrations of urine hCG. Laboratorians and clinicians should be aware that there are limitations when using urine hCG POC devices to rule out early pregnancy. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Development of Mycoplasma synoviae (MS) core genome multilocus sequence typing (cgMLST) scheme.

PubMed

Ghanem, Mostafa; El-Gazzar, Mohamed

2018-05-01

Mycoplasma synoviae (MS) is a poultry pathogen with reported increased prevalence and virulence in recent years. MS strain identification is essential for prevention, control efforts and epidemiological outbreak investigations. Multiple multilocus based sequence typing schemes have been developed for MS, yet the resolution of these schemes could be limited for outbreak investigation. The cost of whole genome sequencing became close to that of sequencing the seven MLST targets; however, there is no standardized method for typing MS strains based on whole genome sequences. In this paper, we propose a core genome multilocus sequence typing (cgMLST) scheme as a standardized and reproducible method for typing MS based whole genome sequences. A diverse set of 25 MS whole genome sequences were used to identify 302 core genome genes as cgMLST targets (35.5% of MS genome) and 44 whole genome sequences of MS isolates from six countries in four continents were used for typing applying this scheme. cgMLST based phylogenetic trees displayed a high degree of agreement with core genome SNP based analysis and available epidemiological information. cgMLST allowed evaluation of two conventional MLST schemes of MS. The high discriminatory power of cgMLST allowed differentiation between samples of the same conventional MLST type. cgMLST represents a standardized, accurate, highly discriminatory, and reproducible method for differentiation between MS isolates. Like conventional MLST, it provides stable and expandable nomenclature, allowing for comparing and sharing the typing results between different laboratories worldwide. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

A Carbonic Anhydrase Serves as an Important Acid-Base Regulator in Pacific Oyster Crassostrea gigas Exposed to Elevated CO2: Implication for Physiological Responses of Mollusk to Ocean Acidification.

PubMed

Wang, Xiudan; Wang, Mengqiang; Jia, Zhihao; Qiu, Limei; Wang, Lingling; Zhang, Anguo; Song, Linsheng

2017-02-01

Carbonic anhydrases (CAs) have been demonstrated to play an important role in acid-base regulation in vertebrates. However, the classification and modulatory function of CAs in marine invertebrates, especially their responses to ocean acidification remain largely unknown. Here, a cytosolic α-CA (designated as CgCAII-1) was characterized from Pacific oyster Crassostrea gigas and its molecular activities against CO 2 exposure were investigated. CgCAII-1 possessed a conserved CA catalytic domain, with high similarity to invertebrate cytoplasmic or mitochondrial α-CAs. Recombinant CgCAII-1 could convert CO 2 to HCO 3 - with calculated activity as 0.54 × 10 3  U/mg, which could be inhibited by acetazolamide (AZ). The mRNA transcripts of CgCAII-1 in muscle, mantle, hepatopancreas, gill, and hemocytes increased significantly after exposure to elevated CO 2 . CgCAII-1 could interact with the hemocyte membrane proteins and the distribution of CgCAII-1 protein became more concentrated and dense in gill and mantle under CO 2 exposure. The intracellular pH (pHi) of hemocytes under CO 2 exposure increased significantly (p < 0.05) and CA inhibition reduced the pHi value. Besides, there was no increase in CA activity in gill and mantle after CO 2 exposure. The impact of CO 2 exposure on CA activity coupled with the mRNA expression level and protein translocation of CgCAII-1 provided evidences that CgCAII-1 could respond to ocean acidification and participate in acid-base regulation. Such cytoplasmic CA-based physiological regulation mechanism might explain other physiological responses of marine organisms to OA.

Novel adducts from the reaction of 1-chloro-3-buten-2-one with 2'-deoxyguanosine. Structural characterization and potential as tools to investigate 1,3-butadiene carcinogenicity.

PubMed

Zheng, Jin; Li, Yan; Yu, Ying-Xin; An, Jing; Zhang, Xin-Yu; Elfarra, Adnan A

2015-01-25

1-Chloro-3-buten-2-one (CBO) is a potential reactive metabolite of 1,3-butadiene (BD), a carcinogenic air pollutant. To develop tools that may help investigate the role of CBO in BD carcinogenicity and to develop biomarkers that can be used to assess BD exposure, the reaction of CBO with 2'-deoxyguanosine (dG) under in vitro physiological conditions (pH 7.4, 37°C) was investigated and the products (designated as CG-1, CG-2, CG-3, CG-4, CG-5, and CG-6 based on their retention times on HPLC) were characterized by MS and NMR spectroscopy. The structures of CG-1, CG-2, CG-3, and CG-4 were 1,N2-(3-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2'-deoxyguanosine, N7-(4-chloro-3-oxobutyl)-2'-deoxyguanosine, N7,8-(3-hydroxy-3-chloromethylpropan-1,3-diyl)guanine and N2-(4-chloro-3-oxobutyl)-2'-deoxyguanosine, respectively. CG-5 and CG-6, a pair of diastereomers, were characterized as 1,N2-(3-hydroxy-3-chloromethylpropan-1,3-diyl)-2'-deoxyguanosine. CG-1 was stable under in vitro physiological conditions, whereas CG-2, CG-3, CG-4, and CG-5/6 were unstable and exhibited the half-lives at <1.0, 4.8±0.1, 6.7±0.3, and 2.7±0.1 h, respectively. CG-2 decomposed primarily via a retro-Michael reaction to produce dG and CBO, with only a small fraction of CG-2 degrading to CG-3. Decomposition of CG-4 proceeded via a cyclization reaction and/or replacement of the chlorine atom by a hydroxyl group to form 1,N2-(1-hydroxy-1-hydroxymethylpropan-1,3-diyl)-2'-deoxyguanosine (CG-4D1) and N(2)-(4-hydroxy-3-oxobutyl)-2'-deoxyguanosine (CG-4D2), whereas decomposition of CG-5/6 yielded CG-1. Collectively, the newly characterized CBO adducts could be used to investigate the role of CBO in the mechanism of BD carcinogenicity and could also be used to develop biomarkers for BD exposure. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Combined human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) treatment in gonadotropin-deficient males with pituitary dwarfism.

PubMed

Tanaka, T; Hibi, I; Tanae, A

1992-04-01

The effects of hCG-hMG treatment in 13 boys with pituitary dwarfism associated with gonadotropin deficiency, were assessed. No patients except one showed signs of puberty at a bone age of 13 years or above. The one patient with some signs of puberty did not become fully mature. The hCG-hMG was started at a mean age of 20.4 years. The hCG at a dose of 5,000 IU was injected intramuscularly twice a week and the hMG at a dose of 75 IU was given once a week at first. During treatment, the frequency of hMG injections was increased to twice a week in six patients who still had not produced normal sperm counts. After a mean duration of 19.23 months, spermatozoa appeared in eight patients, of whom four showed more than 20 x 10(6) sperm/ml. Among six patients who did not have normal sperm counts and had increased hMG injections, one produced a pregnancy and four achieved sperm counts of more than 35 x 10(6)/ml. One patient had refractory azoospermia. In 13 boys with growth hormone and gonadotropin deficiency, hCG-hMG treatment produced normal spermatogenesis in nine patients, one of whom fathered a girl. Thus, hCG-hMG treatment, especially twice-a-week injections of both hCG and hMG, appears to be effective for gonadotropin deficiency in males.

Effects of chromium and aluminum on mechanical and oxidation properties of iron-nickel-base superalloys based on CG-27

NASA Technical Reports Server (NTRS)

Schuon, S. R.

1985-01-01

The effects of chromium and aluminum on the mechanical and oxidation properties of a series of gamma-prime-strengthened alloys based on CG-27 were studied. Gamma-prime dispersion and solid-solution strengthening were the principal modes of alloy strengthening. The oxidation attack parameter K sub a decreased with increasing Cr and Al contents for each alloy group based on Al content. As a group, alloys with 3 wt % Al had the lowest attack parameters. Therefore, 3 wt % is the optimum level of Al for parabolic oxidation behavior. Spalling, due to diffusion-induced grain growth, was controlled by the overall Cr and Al levels. The alloy with 4 wt % Cr and 3 wt % Al had stress-rupture properties superior to those of the base alloy, CG-27, and maintained parabolic oxidation behavior while the Cr content was reduced by two-thirds of its value in cast CG-27.

Nested Conjugate Gradient Algorithm with Nested Preconditioning for Non-linear Image Restoration.

PubMed

Skariah, Deepak G; Arigovindan, Muthuvel

2017-06-19

We develop a novel optimization algorithm, which we call Nested Non-Linear Conjugate Gradient algorithm (NNCG), for image restoration based on quadratic data fitting and smooth non-quadratic regularization. The algorithm is constructed as a nesting of two conjugate gradient (CG) iterations. The outer iteration is constructed as a preconditioned non-linear CG algorithm; the preconditioning is performed by the inner CG iteration that is linear. The inner CG iteration, which performs preconditioning for outer CG iteration, itself is accelerated by an another FFT based non-iterative preconditioner. We prove that the method converges to a stationary point for both convex and non-convex regularization functionals. We demonstrate experimentally that proposed method outperforms the well-known majorization-minimization method used for convex regularization, and a non-convex inertial-proximal method for non-convex regularization functional.

Autonomic cardiovascular control recovery in quadriplegics after handcycle training.

PubMed

Abreu, Elizângela Márcia de Carvalho; Alves, Rani de Souza; Borges, Ana Carolina Lacerda; Lima, Fernanda Pupio Silva; Júnior, Alderico Rodrigues de Paula; Lima, Mário Oliveira

2016-07-01

The aim of this study was to investigate the cardiovascular autonomic acute response, during recovery after handcycle training, in quadriplegics with spinal cord injury (SCI). [Subjects and Methods] Seven quadriplegics (SCIG -level C6-C7, male, age 28.00 ± 6.97 years) and eight healthy subjects (CG -male, age 25.00 ± 7.38 years) were studied. Their heart rate variability (HRV) was assessed before and after one handcycle training. [Results] After the training, the SCIG showed significantly reduced: intervals between R waves of the electrocardiogram (RR), standard deviation of the NN intervals (SDNN), square root of the mean squares differences of sucessive NN intervals (rMSSD), low frequency power (LF), high frequency power (HF), and Poincaré plot (standard deviation of short-term HRV -SD1 and standard deviation of long-term HRV -SD2). The SDNN, LF, and SD2 remained decreased during the recovery time. The CG showed significantly reduced: RR, rMSSD, number of pairs of adjacent NN intervals differing by more than 50 ms (pNN50), LF, HF, SD1, and sample entropy (SampEn). Among these parameters, only RR remained decreased during recovery time. Comparisons of the means of HRV parameters evaluated between the CG and SCIG showed that the SCIG had significantly lower pNN50, LF, HF, and SampEn before training, while immediately after training, the SCIG had significantly lower SDNN, LF, HF, and SD2. The rMSSD30s of the SCIG significantly reduced in the windows 180 and 330 seconds and between the windows 300 seconds in the CG. [Conclusion] There was a reduction of sympathetic and parasympathetic activity in the recovery period after the training in both groups; however, the CG showed a higher HRV. The parasympathetic activity also gradually increased after training, and in the SCIG, this activity remained reduced even at three minutes after the end of training, which suggests a deficiency in parasympathetic reactivation in quadriplegics after SCI.

Persistent low levels of serum hCG due to heterophilic mouse antibodies: an unrecognized pitfall in the diagnosis of trophoblastic disease.

PubMed

González Aguilera, B; Syrios, P; Gadisseur, R; Luyckx, F; Cavalier, E; Beckers, A; Valdes-Socin, H

2016-06-01

Phantom hCG refers to persistent mild elevations of hCG, leading physicians to unnecessary treatments whereas neither a true hCG nor a trophoblastic disease is present. We report the case of a 23-year-old woman with persistent low levels of serum hCG detected one month after miscarriage. As choriocarcinoma was suspected, a chemotherapy trial of methotrexate was prescribed, without any hCG reduction. Subsequently, laparoscopy ruled out a trophoblastic residue and the patient was referred to the Endocrine Unit for further investigations. While low levels of hCG were still detected in serum, no hCG was detected in the urine. In addition, when serum was processed in a HBT tube for revealing heterophilic antibodies, hCG was no longer detected. Such finding indicated the presence of phantom hCG due to heterophilic mouse antibodies interaction. This case raises the need of clinico-biological discussion to avoid inappropriate therapeutic decisions. Based on this case experience and after review of the literature, we suggest that current gynecological protocols for the diagnosis and treatment of trophoblastic disease should consider the inclusion of urinary hCG and/or a test for serum heterophilic antibodies when appropriate.

Serum hCG Levels following the Ovulatory Injection: Associations with Patient Weight and Implantation Time

PubMed Central

Noorhasan, Dorette J.; McGovern, Peter G.; Cho, Michael; Seungdamrong, Aimee; Ahmad, Khaliq; McCulloh, David H.

2015-01-01

Objective. To test if serum hCG levels the morning after the ovulatory hCG injection correlate with (1) retrieval efficiency, (2) oocyte maturity, (3) embryo quality, (4) pregnancy, and/or (5) time to implantation in patients undergoing in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). Design. Retrospective cohort analysis. Setting. University-based IVF clinic. Patient(s). All IVF/ICSI cycles from April 2005 to February 2008 whose hCG administration was confirmed (n = 472 patients). Intervention(s). Serum hCG was measured the morning following the ovulatory injection, on the 16th day following retrieval, and repeated on day 18 for those with positive results. Main Outcome Measure(s). Number of follicles on the day of hCG injection, number of oocytes retrieved, maturity of oocytes, embryo quality, pregnancy outcome, and time to implantation. Result(s). hCG levels did not correlate with retrieval efficiency, oocyte maturity, embryo quality, or pregnancy. Postinjection hCG levels were inversely associated with patient weight and time to implantation. Conclusion(s). No correlation was found between hCG level and any parameter of embryo quality. Patient weight affected hCG levels following hCG injection and during the early period of pregnancy following implantation. No association between postinjection hCG level and time of implantation (adjusted for patient weight) was apparent. PMID:26587025

“I Was Just Trying To Stick It Out Until I Realized That I Couldn't”: A Phenomenological Investigation of Support Seeking Among Older Adults With Complicated Grief*

PubMed Central

Ghesquiere, Angela

2014-01-01

Complicated Grief (CG) is a prolonged, impairing mental health condition affecting about 7% of the bereaved. CG may be especially prevalent in older adults. Though evidence-based treatments for CG have been developed, little is known about support-seeking in older adults with CG. This study used the descriptive phenomenological approach to explore the CG support-seeking process. In-depth interviews were conducted with 8 CG-positive older adults who had completed participation in a randomized clinical trial of CG treatment. Five primary themes arose: observing that grief was causing a great deal of distress and impairment; grief not meeting expectations of what grief “should be”; an important influence of social relationships on support-seeking; lack of effectiveness of grief support groups and/or care from mental health professionals prior to study enrollment; and strong reactions to the label of CG. Themes may hep inform efforts to engage older adults with CG in effective care. PMID:24547662

A new modified conjugate gradient coefficient for solving system of linear equations

NASA Astrophysics Data System (ADS)

Hajar, N.; ‘Aini, N.; Shapiee, N.; Abidin, Z. Z.; Khadijah, W.; Rivaie, M.; Mamat, M.

2017-09-01

Conjugate gradient (CG) method is an evolution of computational method in solving unconstrained optimization problems. This approach is easy to implement due to its simplicity and has been proven to be effective in solving real-life application. Although this field has received copious amount of attentions in recent years, some of the new approaches of CG algorithm cannot surpass the efficiency of the previous versions. Therefore, in this paper, a new CG coefficient which retains the sufficient descent and global convergence properties of the original CG methods is proposed. This new CG is tested on a set of test functions under exact line search. Its performance is then compared to that of some of the well-known previous CG methods based on number of iterations and CPU time. The results show that the new CG algorithm has the best efficiency amongst all the methods tested. This paper also includes an application of the new CG algorithm for solving large system of linear equations

A paralogue of the phosphomutase-like gene family in Candida glabrata, CgPmu2, gained broad-range phosphatase activity due to a small number of clustered substitutions.

PubMed

Orlando, Kelly A; Iosue, Christine L; Leone, Sarah G; Davies, Danielle L; Wykoff, Dennis D

2015-10-15

Inorganic phosphate is required for a range of cellular processes, such as DNA/RNA synthesis and intracellular signalling. The phosphate starvation-inducible phosphatase activity of Candida glabrata is encoded by the gene CgPMU2 (C. glabrata phosphomutase-like protein). CgPMU2 is part of a three-gene family (∼75% identical) created through gene duplication in the C. glabrata clade; only CgPmu2 is a PHO-regulated broad range acid phosphatase. We identified amino acids that confer broad range phosphatase activity on CgPmu2 by creating fusions of sections of CgPMU2 with CgPMU1, a paralogue with little broad range phosphatase activity. We used site-directed mutagenesis on various fusions to sequentially convert CgPmu1 to CgPmu2. Based on molecular modelling of the Pmu proteins on to a histidine phosphatase crystal structure, clusters of amino acids were found in two distinct regions that were able to confer phosphatase activity. Substitutions in these two regions together conferred broad phosphatase activity on CgPmu1. Interestingly, one change is a histidine adjacent to the active site histidine of CgPmu2 and it exhibits a novel ability to partially replace the conserved active site histidine in CgPmu2. Additionally, a second amino acid change was able to confer nt phosphatase activity to CgPmu1, suggesting single amino acid changes neofunctionalize CgPmu2. © 2015 Authors; published by Portland Press Limited.

Immunochemical mapping of gonadotropins.

PubMed

Berger, P; Bidart, J M; Delves, P S; Dirnhofer, S; Hoermann, R; Isaacs, N; Jackson, A; Klonisch, T; Lapthorn, A; Lund, T; Mann, K; Roitt, I; Schwarz, S; Wick, G

1996-12-20

As a glycoprotein hormone, human chorionic gonadotropic (hCG) is not a single molecular entity but this term rather comprises an array of molecular variants such as hCG, hCG beta, hCGn, hCG beta n, hCG beta cf, -CTPhCG, hCG beta CTP, deglyhCG, asialohCG, hCGav and the closely related molecules hLH, hLH beta and hLH beta ef. The advent of monoclonal antibodies (MCA), the availability of ultrasensitive detection systems and the recent determination of the crystal structure of hCG, made it possible to design special purpose diagnostic and clinical research immunoassays for hCG-like molecules. For more than a decade we and others have tried to refine epitope maps for hCG and related molecules by means of a large panel of MCA, naturally occurring metabolic variants of hCG (hCGn, hCG beta, hCG alpha, hCG beta cf, hCG beta CTP), homologous hormones and subunits of various species (e.g. hLH, hLH beta, hFSH, hTSH, oLH, rLH beta), chemically modified molecules (deglyhCG, asialohCG, tryptic and chymotryptic hCG beta and hCG alpha fragments) and synthetic peptides (octapeptides and longer). It appeared that all epitopes on molecular hCG-variants recognized by our MCA are determined by the protein backbone. Except for the two major epitopes on hCG beta CTP and parts of two antigenic domains on hCG alpha, epitopes on hCG-derived molecules are determined by the tertiary and quarternary structure. Operationally useful descriptive epitope maps were designed including information on assay suitability of antigenic determinants. On this basis we established ultrasensitive time-resolved fluoroimmuno-assays for hCG, hCG and hCGn, hCG beta and hCG beta n and hCG beta cf, hCG alpha and additional assays recognizing different spectra of hCG-variants. Such assay have been applied by us and others to the detection of pregnancy, early pregnancy loss, choriocarcinoma, testicular cancer, other cancers and prenatal diagnosis. However, as the molecular structure of many epitopes utilized in immunoassays of different laboratories was not resolved, comparability of results was not satisfactory. Consequently, attempts were made to compare schematic epitope maps from different research institutions. The situation has been much improved by solving the three-dimensional (3D) structure of hCG. It has been shown that hCG is a member of the structural superfamily of cystine knot growth factors like NGF, PDGF-B and TGF-beta. Each of its subunits is stabilized in its topology by three disulfide bonds forming a cystine knot. Moreover, it turned out that the disulfide bridges in their majority have previously been wrongly assigned. Computer molecular modeling of crystallographic coordinates of hCG and subsequent selective combined--PCR-based and immunological--mutational analyses of hCG beta expressed via the transmembrane region of a MHC molecule made it possible to more precisely localize epitopes on hCG-derived molecules. Although the entire surface of hCG has to be regarded as potentially immunogenic there seems to be hot spots where epitopes are clustered in antigenic domains. These are located on the first and third loops protuding from the cystine knots of both subunits and are possibly centered around the knot itself. Ultimate answers on epitope localizations will be given by the crystal structure determination of hCG complexed with different Fabs.

Hierarchical Coarse-Graining Via a Generalized Yvon-Born Green Framework: Many-Body Correlations, Mappings, and Structural Accuracy

NASA Astrophysics Data System (ADS)

Rudzinski, Joseph F.

Atomically-detailed molecular dynamics simulations have emerged as one of the most powerful theoretic tools for studying complex, condensed-phase systems. Despite their ability to provide incredible molecular insight, these simulations are insufficient for investigating complex biological processes, e.g., protein folding or molecular aggregation, on relevant length and time scales. The increasing scope and sophistication of atomically-detailed models has motivated the development of "hierarchical" approaches, which parameterize a low resolution, coarse-grained (CG) model based on simulations of an atomically-detailed model. The utility of hierarchical CG models depends on their ability to accurately incorporate the correct physics of the underlying model. One approach for ensuring this "consistency" between the models is to parameterize the CG model to reproduce the structural ensemble generated by the high resolution model. The many-body potential of mean force is the proper CG energy function for reproducing all structural distributions of the atomically-detailed model, at the CG level of resolution. However, this CG potential is a configuration-dependent free energy function that is generally too complicated to represent or simulate. The multiscale coarse-graining (MS-CG) method employs a generalized Yvon-Born-Green (g-YBG) relation to directly determine a variationally optimal approximation to the many-body potential of mean force. The MS-CG/g-YBG method provides a convenient and transparent framework for investigating the equilibrium structure of the system, at the CG level of resolution. In this work, we investigate the fundamental limitations and approximations of the MS-CG/g-YBG method. Throughout the work, we propose several theoretic constructs to directly relate the MS-CG/g-YBG method to other popular structure-based CG approaches. We investigate the physical interpretation of the MS-CG/g-YBG correlation matrix, the quantity responsible for disentangling the various contributions to the average force on a CG site. We then employ an iterative extension of the MS-CG/g-YBG method that improves the accuracy of a particular set of low order correlation functions relative to the original MS-CG/g-YBG model. We demonstrate that this method provides a powerful framework for identifying the precise source of error in an MS-CG/g-YBG model. We then propose a method for identifying an optimal CG representation, prior to the development of the CG model. We employ these techniques together to demonstrate that in the cases where the MS-CG/g-YBG method fails to determine an accurate model, a fundamental problem likely exists with the chosen CG representation or interaction set. Additionally, we explicitly demonstrate that while the iterative model successfully improves the accuracy of the low order structure, it does so by distorting the higher order structural correlations relative to the underlying model. Finally, we apply these methods to investigate the utility of the MS-CG/g- YBG method for developing models for systems with complex intramolecular structure. Overall, our results demonstrate the power of the g-YBG framework for developing accurate CG models and for investigating the driving forces of equilibrium structures for complex condensed-phase systems. This work also explicitly motivates future development of bottom-up CG methods and highlights some outstanding problems in the field. iii.

Urine reference intervals for human chorionic gonadotropin (hCG) isoforms by immunoextraction-tandem mass spectrometry to detect hCG use.

PubMed

Butch, Anthony W; Ahrens, Brian D; Avliyakulov, Nuraly K

2017-11-03

Human chorionic gonadotropin (hCG) stimulates testosterone production by the testicles and can normalize suppressed testosterone concentrations in males following prolonged anabolic steroid use. Because of the potential for abuse by males, hCG is on the World Anti-Doping Agency (WADA) list of prohibited substances. The majority of WADA-accredited laboratories measure urinary hCG using an automated immunoassay. Only immunoassays that recognize the intact alpha and beta heterodimer of hCG (intact hCG) should be used to measure urinary hCG for doping control purposes since intact hCG is the only biologically active molecule. WADA further requires that confirmation testing is performed using an intact hCG immunoassay that is different from the one used in the initial testing procedure or by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study we measured the concentration of intact hCG, free β-subunit (hCGβ) and β-subunit core fragment (hCGβcf) in 570, 275, and 256 male urine samples, respectively, by an immunoextraction LC-MS/MS method. Mean concentrations of intact hCG, hCGβ and hCGβcf were 0.04 IU/L, 0.47 pmol/L and 0.16 pmol/L, respectively. The upper reference limits (97.5 th percentile) for intact hCG, hCGβ and hCGβcf were 0.21 IU/L, 0.40 pmol/L, and 1.86 pmol/L, respectively. Based on these data, we recommend a threshold of 1.0 IU/L for intact hCG (false positive rate of <1 in 10 000) for detecting male athletes that dope with hCG. Copyright © 2017 John Wiley & Sons, Ltd.

Hyperglycosylated human chorionic gonadotropin does not increase progesterone production by luteinized granulosa cells.

PubMed

Crochet, John R; Shah, Anish A; Schomberg, David W; Price, Thomas M

2012-09-01

Trophoblast-derived human chorionic gonadotropin (hCG) promotes corpus luteum progesterone (P4) production, and wide ranges of serum P4 levels are noted in various pregnancy outcomes, despite similar hCG concentrations. There are five unique biologically active hCG variants in human pregnancy urine, and previous studies of P4 production in response to hCG have used only preparations containing all isoforms. Understanding exactly which hCG variant is primarily responsible for stimulating corpus luteum steroidogenesis may have great clinical and diagnostic implications, including in the setting of ectopic pregnancy. Our objective was to delineate the role of the standard and hyperglycosylated (H)-hCG isoforms in stimulating P4 production by luteinized granulosa cells. Cell culture, ELISA, and fluorometric-based protein assays were done at Duke University Medical Center. Patients were anonymous oocyte donors. Cultured luteinized granulosa cells were treated with 0.25, 0.5, and 1.0 ng/ml total hCG, which contains all isoforms, purified standard hCG (37.1 kDa), and purified H-hCG (42.8 kDa). P4 produced per total cellular protein (nanograms per microgram) was measured via ELISA and fluorometric protein determination kits. Both total hCG (P = 0.0003) and purified standard hCG (P < 0.0001) stimulated a dose-dependent increase in P4 production. Purified H-hCG did not change the P4 produced per total cellular protein response (P value not significant). Standard hCG stimulated P4 production by cultured granulosa cells and likely supports corpus luteum function via interactions with the LH/hCG receptor. In contrast, H-hCG did not increase P4 production, which indicates a nonsteroidogenic role for this protein during early gestation.

Defining and Evaluating a Core Genome Multilocus Sequence Typing Scheme for Genome-Wide Typing of Clostridium difficile.

PubMed

Bletz, Stefan; Janezic, Sandra; Harmsen, Dag; Rupnik, Maja; Mellmann, Alexander

2018-06-01

Clostridium difficile , recently renamed Clostridioides difficile , is the most common cause of antibiotic-associated nosocomial gastrointestinal infections worldwide. To differentiate endogenous infections and transmission events, highly discriminatory subtyping is necessary. Today, methods based on whole-genome sequencing data are increasingly used to subtype bacterial pathogens; however, frequently a standardized methodology and typing nomenclature are missing. Here we report a core genome multilocus sequence typing (cgMLST) approach developed for C. difficile Initially, we determined the breadth of the C. difficile population based on all available MLST sequence types with Bayesian inference (BAPS). The resulting BAPS partitions were used in combination with C. difficile clade information to select representative isolates that were subsequently used to define cgMLST target genes. Finally, we evaluated the novel cgMLST scheme with genomes from 3,025 isolates. BAPS grouping ( n = 6 groups) together with the clade information led to a total of 11 representative isolates that were included for cgMLST definition and resulted in 2,270 cgMLST genes that were present in all isolates. Overall, 2,184 to 2,268 cgMLST targets were detected in the genome sequences of 70 outbreak-associated and reference strains, and on average 99.3% cgMLST targets (1,116 to 2,270 targets) were present in 2,954 genomes downloaded from the NCBI database, underlining the representativeness of the cgMLST scheme. Moreover, reanalyzing different cluster scenarios with cgMLST were concordant to published single nucleotide variant analyses. In conclusion, the novel cgMLST is representative for the whole C. difficile population, is highly discriminatory in outbreak situations, and provides a unique nomenclature facilitating interlaboratory exchange. Copyright © 2018 American Society for Microbiology.

Storm-based Cloud-to-Ground Lightning Probabilities and Warnings

NASA Astrophysics Data System (ADS)

Calhoun, K. M.; Meyer, T.; Kingfield, D.

2017-12-01

A new cloud-to-ground (CG) lightning probability algorithm has been developed using machine-learning methods. With storm-based inputs of Earth Networks' in-cloud lightning, Vaisala's CG lightning, multi-radar/multi-sensor (MRMS) radar derived products including the Maximum Expected Size of Hail (MESH) and Vertically Integrated Liquid (VIL), and near storm environmental data including lapse rate and CAPE, a random forest algorithm was trained to produce probabilities of CG lightning up to one-hour in advance. As part of the Prototype Probabilistic Hazard Information experiment in the Hazardous Weather Testbed in 2016 and 2017, National Weather Service forecasters were asked to use this CG lightning probability guidance to create rapidly updating probability grids and warnings for the threat of CG lightning for 0-60 minutes. The output from forecasters was shared with end-users, including emergency managers and broadcast meteorologists, as part of an integrated warning team.

A general approach to one-pot fabrication of crumpled graphene-based nanohybrids for energy applications.

PubMed

Mao, Shun; Wen, Zhenhai; Kim, Haejune; Lu, Ganhua; Hurley, Patrick; Chen, Junhong

2012-08-28

Crumpled graphene oxide (GO)/graphene is a new type of carbon nanostructure that has drawn growing attention due to its three-dimensional open structure and excellent stability in an aqueous solution. Here we report a general and one-step approach to produce crumpled graphene (CG)-nanocrystal hybrids, which are produced by direct aerosolization of a GO suspension mixed with precursor ions. Nanocrystals spontaneously grow from precursor ions and assemble on both external and internal surfaces of CG balls during the solvent evaporation and GO crumpling process. More importantly, CG-nanocrystal hybrids can be directly deposited onto various current-collecting substrates, enabling their tremendous potential for energy applications. As a proof of concept, we demonstrate the use of hybrid electrodes of CG-Mn(3)O(4) and CG-SnO(2) in an electrochemical supercapacitor and a lithium-ion battery, respectively. The performance of the resulting capacitor/battery is attractive and outperforms conventional flat graphene-based hybrid devices. This study provides a new and facile route to fabricating high-performance hybrid CG-nanocrystal electrodes for various energy systems.

Radio frequency observations of lightning discharges by the forte satellite.

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

Shao, X.; Jacobson, A. R.; Light, T.

2002-01-01

FORTE-observed VHF signatures for different lightning discharges are presented. For in-cloud discharges, a pulse pair is typically recorded and is named a 'transionospheric pulse pair' (TIPP). Many intense TIPPs are coherent and polarized, whereas initial and dart leaders do not show a recognizable degree of polarization. TIPPs are optically weaker than cloud-to-ground (CG) strokes, and stronger VHF TIPPs are optically darker. About 10% of CG strokes, mostly over seawater, produce extremely narrow, powerful VHF pulses at the very beginning of the return strokes. These narrow pulses are found to form an upward beam pattern.

In vivo levels of S-adenosylmethionine modulate C:G to T:A mutations associated with repeat-induced point mutation in Neurospora crassa.

PubMed

Rosa, Alberto Luis; Folco, Hernán Diego; Mautino, Mario Ricardo

2004-04-14

In Neurospora crassa, the mutagenic process termed repeat-induced point mutation (RIP) inactivates duplicated DNA sequences during the sexual cycle by the introduction of C:G to T:A transition mutations. In this work, we have used a collection of N. crassa strains exhibiting a wide range of cellular levels of S-adenosylmethionine (AdoMet), the universal donor of methyl groups, to explore whether frequencies of RIP are dependent on the cellular levels of this metabolite. Mutant strains met-7 and eth-1 carry mutations in genes of the AdoMet pathway and have low levels of AdoMet. Wild type strains with high levels of AdoMet were constructed by introducing a chimeric transgene of the AdoMet synthetase (AdoMet-S) gene fused to the constitutive promoter trpC from Aspergillus nidulans. Crosses of these strains against tester duplications of the pan-2 and am genes showed that frequencies of RIP, as well as the total number of C:G to T:A transition mutations found in randomly selected am(RIP) alleles, are inversely correlated to the cellular level of AdoMet. These results indicate that AdoMet modulates the biochemical pathway leading to RIP.

Core Genome Multilocus Sequence Typing Scheme for High-Resolution Typing of Enterococcus faecium

PubMed Central

de Been, Mark; Pinholt, Mette; Top, Janetta; Bletz, Stefan; van Schaik, Willem; Brouwer, Ellen; Rogers, Malbert; Kraat, Yvette; Bonten, Marc; Corander, Jukka; Westh, Henrik; Harmsen, Dag

2015-01-01

Enterococcus faecium, a common inhabitant of the human gut, has emerged in the last 2 decades as an important multidrug-resistant nosocomial pathogen. Since the start of the 21st century, multilocus sequence typing (MLST) has been used to study the molecular epidemiology of E. faecium. However, due to the use of a small number of genes, the resolution of MLST is limited. Whole-genome sequencing (WGS) now allows for high-resolution tracing of outbreaks, but current WGS-based approaches lack standardization, rendering them less suitable for interlaboratory prospective surveillance. To overcome this limitation, we developed a core genome MLST (cgMLST) scheme for E. faecium. cgMLST transfers genome-wide single nucleotide polymorphism (SNP) diversity into a standardized and portable allele numbering system that is far less computationally intensive than SNP-based analysis of WGS data. The E. faecium cgMLST scheme was built using 40 genome sequences that represented the diversity of the species. The scheme consists of 1,423 cgMLST target genes. To test the performance of the scheme, we performed WGS analysis of 103 outbreak isolates from five different hospitals in the Netherlands, Denmark, and Germany. The cgMLST scheme performed well in distinguishing between epidemiologically related and unrelated isolates, even between those that had the same sequence type (ST), which denotes the higher discriminatory power of this cgMLST scheme over that of conventional MLST. We also show that in terms of resolution, the performance of the E. faecium cgMLST scheme is equivalent to that of an SNP-based approach. In conclusion, the cgMLST scheme developed in this study facilitates rapid, standardized, and high-resolution tracing of E. faecium outbreaks. PMID:26400782

Validating and determining the weight of items used for evaluating clinical governance implementation based on analytic hierarchy process model.

PubMed

Hooshmand, Elaheh; Tourani, Sogand; Ravaghi, Hamid; Vafaee Najar, Ali; Meraji, Marziye; Ebrahimipour, Hossein

2015-04-08

The purpose of implementing a system such as Clinical Governance (CG) is to integrate, establish and globalize distinct policies in order to improve quality through increasing professional knowledge and the accountability of healthcare professional toward providing clinical excellence. Since CG is related to change, and change requires money and time, CG implementation has to be focused on priority areas that are in more dire need of change. The purpose of the present study was to validate and determine the significance of items used for evaluating CG implementation. The present study was descriptive-quantitative in method and design. Items used for evaluating CG implementation were first validated by the Delphi method and then compared with one another and ranked based on the Analytical Hierarchy Process (AHP) model. The items that were validated for evaluating CG implementation in Iran include performance evaluation, training and development, personnel motivation, clinical audit, clinical effectiveness, risk management, resource allocation, policies and strategies, external audit, information system management, research and development, CG structure, implementation prerequisites, the management of patients' non-medical needs, complaints and patients' participation in the treatment process. The most important items based on their degree of significance were training and development, performance evaluation, and risk management. The least important items included the management of patients' non-medical needs, patients' participation in the treatment process and research and development. The fundamental requirements of CG implementation included having an effective policy at national level, avoiding perfectionism, using the expertise and potentials of the entire country and the coordination of this model with other models of quality improvement such as accreditation and patient safety. © 2015 by Kerman University of Medical Sciences.

Core Genome Multilocus Sequence Typing Scheme for High- Resolution Typing of Enterococcus faecium.

PubMed

de Been, Mark; Pinholt, Mette; Top, Janetta; Bletz, Stefan; Mellmann, Alexander; van Schaik, Willem; Brouwer, Ellen; Rogers, Malbert; Kraat, Yvette; Bonten, Marc; Corander, Jukka; Westh, Henrik; Harmsen, Dag; Willems, Rob J L

2015-12-01

Enterococcus faecium, a common inhabitant of the human gut, has emerged in the last 2 decades as an important multidrug-resistant nosocomial pathogen. Since the start of the 21st century, multilocus sequence typing (MLST) has been used to study the molecular epidemiology of E. faecium. However, due to the use of a small number of genes, the resolution of MLST is limited. Whole-genome sequencing (WGS) now allows for high-resolution tracing of outbreaks, but current WGS-based approaches lack standardization, rendering them less suitable for interlaboratory prospective surveillance. To overcome this limitation, we developed a core genome MLST (cgMLST) scheme for E. faecium. cgMLST transfers genome-wide single nucleotide polymorphism(SNP) diversity into a standardized and portable allele numbering system that is far less computationally intensive than SNP-based analysis of WGS data. The E. faecium cgMLST scheme was built using 40 genome sequences that represented the diversity of the species. The scheme consists of 1,423 cgMLST target genes. To test the performance of the scheme, we performed WGS analysis of 103 outbreak isolates from five different hospitals in the Netherlands, Denmark, and Germany. The cgMLST scheme performed well in distinguishing between epidemiologically related and unrelated isolates, even between those that had the same sequence type (ST), which denotes the higher discriminatory power of this cgMLST scheme over that of conventional MLST. We also show that in terms of resolution, the performance of the E. faecium cgMLST scheme is equivalent to that of an SNP-based approach. In conclusion, the cgMLST scheme developed in this study facilitates rapid, standardized, and high-resolution tracing of E. faecium outbreaks.

78 FR 42102 - Termination of Radiotelephone Medium Frequency 2182 kHz Watchkeeping, 2187.5 kHz Digital...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-15

... questions on this Notice, contact Larry S. Solomon, Spectrum Management and Telecommunications Policy Counsel (Commandant CG-652) telephone: 202-475-3556; email: larry.s.solomon@uscg.mil . SUPPLEMENTARY...

Structure-based coarse-graining for inhomogeneous liquid polymer systems.

PubMed

Fukuda, Motoo; Zhang, Hedong; Ishiguro, Takahiro; Fukuzawa, Kenji; Itoh, Shintaro

2013-08-07

The iterative Boltzmann inversion (IBI) method is used to derive interaction potentials for coarse-grained (CG) systems by matching structural properties of a reference atomistic system. However, because it depends on such thermodynamic conditions as density and pressure of the reference system, the derived CG nonbonded potential is probably not applicable to inhomogeneous systems containing different density regimes. In this paper, we propose a structure-based coarse-graining scheme to devise CG nonbonded potentials that are applicable to different density bulk systems and inhomogeneous systems with interfaces. Similar to the IBI, the radial distribution function (RDF) of a reference atomistic bulk system is used for iteratively refining the CG nonbonded potential. In contrast to the IBI, however, our scheme employs an appropriately estimated initial guess and a small amount of refinement to suppress transfer of the many-body interaction effects included in the reference RDF into the CG nonbonded potential. To demonstrate the application of our approach to inhomogeneous systems, we perform coarse-graining for a liquid perfluoropolyether (PFPE) film coated on a carbon surface. The constructed CG PFPE model favorably reproduces structural and density distribution functions, not only for bulk systems, but also at the liquid-vacuum and liquid-solid interfaces, demonstrating that our CG scheme offers an easy and practical way to accurately determine nonbonded potentials for inhomogeneous systems.

DNA polymerase θ contributes to the generation of C/G mutations during somatic hypermutation of Ig genes

PubMed Central

Masuda, Keiji; Ouchida, Rika; Takeuchi, Arata; Saito, Takashi; Koseki, Haruhiko; Kawamura, Kiyoko; Tagawa, Masatoshi; Tokuhisa, Takeshi; Azuma, Takachika; O-Wang, Jiyang

2005-01-01

Somatic hypermutation of Ig variable region genes is initiated by activation-induced cytidine deaminase; however, the activity of multiple DNA polymerases is required to ultimately introduce mutations. DNA polymerase η (Polη) has been implicated in mutations at A/T, but polymerases involved in C/G mutations have not been identified. We have generated mutant mice expressing DNA polymerase (Polθ) specifically devoid of polymerase activity. Compared with WT mice, Polq-inactive (Polq, the gene encoding Polθ) mice exhibited a reduced level of serum IgM and IgG1. The mutant mice mounted relatively normal primary and secondary immune responses to a T-dependent antigen, but the production of high-affinity specific antibodies was partially impaired. Analysis of the JH4 intronic sequences revealed a slight reduction in the overall mutation frequency in Polq-inactive mice. Remarkably, although mutations at A/T were unaffected, mutations at C/G were significantly decreased, indicating an important, albeit not exclusive, role for Polθ activity. The reduction of C/G mutations was particularly focused on the intrinsic somatic hypermutation hotspots and both transitions and transversions were similarly reduced. These findings, together with the recent observation that Polθ efficiently catalyzes the bypass of abasic sites, lead us to propose that Polθ introduces mutations at C/G by replicating over abasic sites generated via uracil-DNA glycosylase. PMID:16172387

An update on the clinical diagnostic value of β-hCG and αFP for intracranial germ cell tumors.

PubMed

Hu, Mingming; Guan, Hongzhi; Lau, Ching C; Terashima, Keita; Jin, Zimeng; Cui, Liying; Wang, Yuzhou; Li, Guilin; Yao, Yong; Guo, Yi; Li, Yan Michael; Zhong, Dingrong; Xiao, Juan; Wan, Xirun; Lian, Xin; Feng, Feng; Ren, Haitao; Zhao, Yanhuan; Cheng, Xinqi; Gu, Feng

2016-03-12

Pathological examination combined with tumor markers has become a standard for the diagnosis of intracranial germ cell tumors (ICGCTs), but the current concept of 'secreting germ cell tumors' and three empirically highly specific diagnostic criteria (β-hCG ≥ 50 IU/L or αFP ≥ 10 ng/mL; β-hCG ≥ 100 IU/L or αFP ≥ 50 ng/mL; β-hCG > 50 IU/L or αFP > 25 ng/mL) are not based upon pathology examination or CSF cytology. Further investigation is needed to re-evaluate their value. A multidisciplinary diagnostic team was created. Valid β-hCG/αFP data were collected from cases of ICGCTs confirmed by pathology and CSF cytology (n = 58) between 1991 and 2012, and from suspected ICGCTs cases (n = 17) between 2011 and 2012 as controls [Langerhans cell histiocytosis (LCH), n = 12; and other intracranial tumor (ICT), n = 5]. The cut-off points for β-hCG and αFP were calculated using receiver operating characteristic (ROC) curves. This study clarifies the relative rationality of one criteria (β-hCG > 50 IU/L and αFP > 25 ng/mL); confirms new β-hCG diagnostic cut-off points: CSF β-hCG ≥ 8.2 IU/L and serum β-hCG ≥ 2.5 IU/L (sensitivity of 47 and 34%, respectively, specificity of 100%, both; P < 0.05); and empirically adjusts the criteria for αFP to ≥ 3.8 ng/mL in CSF and to ≥ 25 ng/mL in serum. The total diagnostic sensitivity for ICGCTs finally increased from 34.6 to 65.4% (P < 0.05, diagnostic value of CSF β-hCG exceeds 90%). Subtype diagnosis improved with αFP in 16.7% of non-geminomatous germ cell tumor cases. New evidence-based criteria of β-hCG and αFP can help improving early and formal diagnosis of ICGCTs, and is of great clinical significance.

Organic-inorganic hybrid nanocomposites based on chitosan derivatives and layered double hydroxides with intercalated phacolysin as ocular delivery system

NASA Astrophysics Data System (ADS)

Qin, Zhiguo; Zhang, Jie; Chi, Huibo; Cao, Feng

2015-12-01

This study was mainly aimed to evaluate the potential use of a novel ocular drug delivery system, organic-inorganic hybrid nanocomposites based on chitosan derivatives and layered double hydroxides (LDH). Organic polymers of chitosan-glutathione (CG) and pre-activated chitosan-glutathione (CG-2MNA) were successfully synthesized and characterized. LDH with intercalated phacolysin (PCL), including larger hexagonal LDH-PCL (Lh-LDH-PCL), larger spherical LDH-PCL (Ls-LDH-PCL), smaller hexagonal LDH-PCL (Sh-LDH-PCL), CG hybrid LDH-PCL (LDH-PCL-CG), and CG-2MNA hybrid LDH-PCL (LDH-PCL-CG-2MNA), were prepared. The nanocomposites with particle size of 107.2-274.9 nm were characterized by powder X-ray diffraction, Fourier transform infrared, transmission electron micrographs, etc. In vivo precorneal retention studies showed that the detectable time of all nanocomposites was prolonged from 2 to 6 h in comparison to PCL saline. Accordingly, the AUC0-6h values of Lh-LDH-PCL, Ls-LDH-PCL, Sh-LDH-PCL, LDH-PCL-CG, and LDH-PCL-CG-2MNA nanocomposites were increased by 2.27-, 2.08-, 3.08-, 4.67-, and 3.36-fold, respectively. The Draize test and hematoxylin and eosin staining demonstrated that modified LDH had no eye irritation after single and repeated administration. These results indicated that chitosan derivatives-LDH hybrid nanocomposite dispersion could be a promising ocular drug delivery system to improve precorneal retention time of drugs.

The relationship of TP53 R72P polymorphism to disease outcome and TP53 mutation in myelodysplastic syndromes

PubMed Central

McGraw, K L; Zhang, L M; Rollison, D E; Basiorka, A A; Fulp, W; Rawal, B; Jerez, A; Billingsley, D L; Lin, H-Y; Kurtin, S E; Yoder, S; Zhang, Y; Guinta, K; Mallo, M; Solé, F; Calasanz, M J; Cervera, J; Such, E; González, T; Nevill, T J; Haferlach, T; Smith, A E; Kulasekararaj, A; Mufti, G; Karsan, A; Maciejewski, J P; Sokol, L; Epling-Burnette, P K; Wei, S; List, A F

2015-01-01

Nonsynonymous TP53 exon 4 single-nucleotide polymorphism (SNP), R72P, is linked to cancer and mutagen susceptibility. R72P associations with specific cancer risk, particularly hematological malignancies, have been conflicting. Myelodysplastic syndrome (MDS) with chromosome 5q deletion is characterized by erythroid hypoplasia arising from lineage-specific p53 accumulation resulting from ribosomal insufficiency. We hypothesized that apoptotically diminished R72P C-allele may influence predisposition to del(5q) MDS. Bone marrow and blood DNA was sequenced from 705 MDS cases (333 del(5q), 372 non-del(5q)) and 157 controls. Genotype distribution did not significantly differ between del(5q) cases (12.6% CC, 38.1% CG, 49.2% GG), non-del(5q) cases (9.7% CC, 44.6% CG, 45.7% GG) and controls (7.6% CC, 37.6% CG, 54.8% GG) (P=0.13). Allele frequency did not differ between non-del(5q) and del(5q) cases (P=0.91) but trended towards increased C-allele frequency comparing non-del(5q) (P=0.08) and del(5q) (P=0.10) cases with controls. Median lenalidomide response duration increased proportionate to C-allele dosage in del(5q) patients (2.2 (CC), 1.3 (CG) and 0.89 years (GG)). Furthermore, C-allele homozygosity in del(5q) was associated with prolonged overall and progression-free survival and non-terminal interstitial deletions that excluded 5q34, whereas G-allele homozygozity was associated with inferior outcome and terminal deletions involving 5q34 (P=0.05). These findings comprise the largest MDS R72P SNP analysis. PMID:25768405

Human chorionic gonadotropin (hCG) concentrations during the late first trimester are associated with fetal growth in a fetal sex-specific manner.

PubMed

Barjaktarovic, Mirjana; Korevaar, Tim I M; Jaddoe, Vincent W V; de Rijke, Yolanda B; Visser, Theo J; Peeters, Robin P; Steegers, Eric A P

2017-02-01

Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates placental development. hCG concentrations vary widely throughout gestation and differ based on fetal sex. Abnormal hCG concentrations are associated with adverse pregnancy outcomes including fetal growth restriction. We studied the association of hCG concentrations with fetal growth and birth weight. In addition, we investigated effect modification by gestational age of hCG measurement and fetal sex. Total serum hCG (median 14.4 weeks, 95 % range 10.1-26.2), estimated fetal weight (measured by ultrasound during 18-25th weeks and >25th weeks) and birth weight were measured in 7987 mother-child pairs from the Generation R cohort and used to establish fetal growth. Small for gestational age (SGA) was defined as a standardized birth weight lower than the 10th percentile of the study population. There was a non-linear association of hCG with birth weight (P = 0.009). However, only low hCG concentrations measured during the late first trimester (11th and 12th week) were associated with birth weight and SGA. Low hCG concentrations measured in the late first trimester were also associated with decreased fetal growth (P = 0.0002). This was the case for both male and female fetuses. In contrast, high hCG concentrations during the late first trimester were associated with increased fetal growth amongst female, but not male fetuses. Low hCG in the late first trimester is associated with lower birth weight due to a decrease in fetal growth. Fetal sex differences exist in the association of hCG concentrations with fetal growth.

Transcobalamin II (TCN2 67A>G and TCN2 776C>G) and transcobalamin II receptor (TCblR 1104C>T) polymorphisms in Korean patients with idiopathic recurrent spontaneous abortion.

PubMed

Kim, Hyun Seok; Lee, Bo Eun; Jeon, Young Joo; Rah, HyungChul; Lee, Woo Sik; Shin, Ji Eun; Choi, Dong Hee; Kim, Nam Keun

2014-09-01

The transcobalamin II (TCN2) 776C>G polymorphism has been reported to be a genetic risk factor for idiopathic recurrent spontaneous abortion (RSA). However, the sample size in previous studies was small, and other TCN2 polymorphisms have not been studied. Moreover, the TCN2 67A>G and 776C>G polymorphisms, and the transcobalamin II receptor (TCblR/CD320) 1104C>T polymorphism, have demonstrated associations with immune responses. Three hundred and seventy-eight RSA patients who had at least two consecutive spontaneous abortions were enrolled. Two hundred and seven control subjects were collected from a convenience sample. Polymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the TCN2 67A>G and 776C>G polymorphisms, and the TCblR 1104C>T polymorphism. RSA patients showed significantly different frequencies of the TCN2 67AG+GG genotypes compared with control subjects. The TCN2 67G allele is a possible risk factor for idiopathic RSA. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The effect of vision on postural strategies in Prader-Willi patients.

PubMed

Cimolin, Veronica; Galli, Manuela; Vismara, Luca; Grugni, Graziano; Priano, Lorenzo; Capodaglio, Paolo

2011-01-01

The aim of this study was to quantify the role of visual contribution in patients with Prader-Willi syndrome (PWS) on balance maintenance using a force platform. We enrolled 14 individuals with PWS free from conditions associated with impaired balance, 44 obese (OG) and 20 healthy controls (CG). Postural sway was measured for 60s while standing on a force platform (Kistler, CH; acquisition frequency: 500 Hz) integrated with a video system. Patients maintained an upright standing position with Open Eyes (OE) and then with Closed Eyes (CE). The ratio between the value of the parameter under OE and CE conditions was measured. Under OE condition PWS and OG were characterized by higher postural instability than CG, with the PWS group showing poorer balance capacity than OG. The Romberg ratio showed that while OG and CG had lower balance without vision, PWS maintained the same performance changing from OE to CE. The integration of different sensory inputs appears similar in OG and CG with higher postural stability under OE than CE. Balance in PWS is not influenced by the elimination of visual input. Copyright © 2011 Elsevier Ltd. All rights reserved.

Educating resident physicians using virtual case-based simulation improves diabetes management: a randomized controlled trial.

PubMed

Sperl-Hillen, JoAnn; O'Connor, Patrick J; Ekstrom, Heidi L; Rush, William A; Asche, Stephen E; Fernandes, Omar D; Appana, Deepika; Amundson, Gerald H; Johnson, Paul E; Curran, Debra M

2014-12-01

To test a virtual case-based Simulated Diabetes Education intervention (SimDE) developed to teach primary care residents how to manage diabetes. Nineteen primary care residency programs, with 341 volunteer residents in all postgraduate years (PGY), were randomly assigned to a SimDE intervention group or control group (CG). The Web-based interactive educational intervention used computerized virtual patients who responded to provider actions through programmed simulation models. Eighteen distinct learning cases (L-cases) were assigned to SimDE residents over six months from 2010 to 2011. Impact was assessed using performance on four virtual assessment cases (A-cases), an objective knowledge test, and pre-post changes in self-assessed diabetes knowledge and confidence. Group comparisons were analyzed using generalized linear mixed models, controlling for clustering of residents within residency programs and differences in baseline knowledge. The percentages of residents appropriately achieving A-case composite clinical goals for glucose, blood pressure, and lipids were as follows: A-case 1: SimDE = 21.2%, CG = 1.8%, P = .002; A-case 2: SimDE = 15.7%, CG = 4.7%, P = .02; A-case 3: SimDE = 48.0%, CG = 10.4%, P < .001; and A-case 4: SimDE = 42.1%, CG = 18.7%, P = .004. The mean knowledge score and pre-post changes in self-assessed knowledge and confidence were significantly better for SimDE group than CG participants. A virtual case-based simulated diabetes education intervention improved diabetes management skills, knowledge, and confidence for primary care residents.

Three-dimensional forward modeling of DC resistivity using the aggregation-based algebraic multigrid method

NASA Astrophysics Data System (ADS)

Chen, Hui; Deng, Ju-Zhi; Yin, Min; Yin, Chang-Chun; Tang, Wen-Wu

2017-03-01

To speed up three-dimensional (3D) DC resistivity modeling, we present a new multigrid method, the aggregation-based algebraic multigrid method (AGMG). We first discretize the differential equation of the secondary potential field with mixed boundary conditions by using a seven-point finite-difference method to obtain a large sparse system of linear equations. Then, we introduce the theory behind the pairwise aggregation algorithms for AGMG and use the conjugate-gradient method with the V-cycle AGMG preconditioner (AGMG-CG) to solve the linear equations. We use typical geoelectrical models to test the proposed AGMG-CG method and compare the results with analytical solutions and the 3DDCXH algorithm for 3D DC modeling (3DDCXH). In addition, we apply the AGMG-CG method to different grid sizes and geoelectrical models and compare it to different iterative methods, such as ILU-BICGSTAB, ILU-GCR, and SSOR-CG. The AGMG-CG method yields nearly linearly decreasing errors, whereas the number of iterations increases slowly with increasing grid size. The AGMG-CG method is precise and converges fast, and thus can improve the computational efficiency in forward modeling of three-dimensional DC resistivity.

The multiscale coarse-graining method. XI. Accurate interactions based on the centers of charge of coarse-grained sites

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

Cao, Zhen; Voth, Gregory A., E-mail: gavoth@uchicago.edu

It is essential to be able to systematically construct coarse-grained (CG) models that can efficiently and accurately reproduce key properties of higher-resolution models such as all-atom. To fulfill this goal, a mapping operator is needed to transform the higher-resolution configuration to a CG configuration. Certain mapping operators, however, may lose information related to the underlying electrostatic properties. In this paper, a new mapping operator based on the centers of charge of CG sites is proposed to address this issue. Four example systems are chosen to demonstrate this concept. Within the multiscale coarse-graining framework, CG models that use this mapping operatormore » are found to better reproduce the structural correlations of atomistic models. The present work also demonstrates the flexibility of the mapping operator and the robustness of the force matching method. For instance, important functional groups can be isolated and emphasized in the CG model.« less

Development of DPD coarse-grained models: From bulk to interfacial properties

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

Solano Canchaya, José G.; Dequidt, Alain, E-mail: alain.dequidt@univ-bpclermont.fr; Goujon, Florent

2016-08-07

A new Bayesian method was recently introduced for developing coarse-grain (CG) force fields for molecular dynamics. The CG models designed for dissipative particle dynamics (DPD) are optimized based on trajectory matching. Here we extend this method to improve transferability across thermodynamic conditions. We demonstrate the capability of the method by developing a CG model of n-pentane from constant-NPT atomistic simulations of bulk liquid phases and we apply the CG-DPD model to the calculation of the surface tension of the liquid-vapor interface over a large range of temperatures. The coexisting densities, vapor pressures, and surface tensions calculated with different CG andmore » atomistic models are compared to experiments. Depending on the database used for the development of the potentials, it is possible to build a CG model which performs very well in the reproduction of the surface tension on the orthobaric curve.« less

Effects of Ca2+ channel blockers on transmitter release and presynaptic currents at the frog neuromuscular junction.

PubMed Central

Katz, E; Ferro, P A; Cherksey, B D; Sugimori, M; Llinás, R; Uchitel, O D

1995-01-01

1. The effects of the calcium channel blockers, funnel-web spider toxin (FTX), omega-agatoxin IVA (omega-Aga IVA) and omega-conotoxin GVIA (omega-CgTX), were tested on transmitter release and presynaptic currents in frog motor nerve endings. 2. Evoked transmitter release was blocked by FTX (IC50 = 0.02 microliter ml-1) and omega-CgTX (1 microM) but was not affected by omega-Aga IVA (0.5 microM). When FTX (0.1 microliter ml-1) was assayed on spontaneous release either in normal Ringer solution or in low Ca(2+)-high Mg2+ solution, it was found not to affect miniature endplate potential (MEPP) amplitude but to increase MEPP frequency by approximately 2-fold in both conditions. 3. Presynaptic calcium currents (ICa), measured by the perineurial technique in the presence of 10 mM tetraethylammonium chloride (TEA) and 200 microM BaCl2 to block K+ currents, were blocked by omega-CgTX (5 microM), partially blocked by FTX (1 microliter ml-1) and not affected by omega-Aga IVA (0.5 microM). 4. The presynaptic calcium-activated potassium current (IK(Ca)) measured by the perineurial technique in the presence of 0.5 microM 3,4-aminopyridine (DAP) to block voltage-dependent K+ currents, was strongly affected by charybdotoxin (ChTX) (300 nM) and completely abolished by BaCl2 (200 microM). This current was also blocked by omega-CgTX (5 microM) and by CdCl2 (200 microM) but was not affected by FTX (1 microliter ml-1). The blockade by omega-CgTX could not be reversed by elevating [Ca]o to 10 mM. 5. The results suggest that in frog synaptic terminals two omega-CgTX-sensitive populations might coexist. The transmitter release process seems to be mediated by calcium influx through a omega-CgTX- and FTX-sensitive population. PMID:7473230

Effects of Ca2+ channel blockers on transmitter release and presynaptic currents at the frog neuromuscular junction.

PubMed

Katz, E; Ferro, P A; Cherksey, B D; Sugimori, M; Llinás, R; Uchitel, O D

1995-08-01

1. The effects of the calcium channel blockers, funnel-web spider toxin (FTX), omega-agatoxin IVA (omega-Aga IVA) and omega-conotoxin GVIA (omega-CgTX), were tested on transmitter release and presynaptic currents in frog motor nerve endings. 2. Evoked transmitter release was blocked by FTX (IC50 = 0.02 microliter ml-1) and omega-CgTX (1 microM) but was not affected by omega-Aga IVA (0.5 microM). When FTX (0.1 microliter ml-1) was assayed on spontaneous release either in normal Ringer solution or in low Ca(2+)-high Mg2+ solution, it was found not to affect miniature endplate potential (MEPP) amplitude but to increase MEPP frequency by approximately 2-fold in both conditions. 3. Presynaptic calcium currents (ICa), measured by the perineurial technique in the presence of 10 mM tetraethylammonium chloride (TEA) and 200 microM BaCl2 to block K+ currents, were blocked by omega-CgTX (5 microM), partially blocked by FTX (1 microliter ml-1) and not affected by omega-Aga IVA (0.5 microM). 4. The presynaptic calcium-activated potassium current (IK(Ca)) measured by the perineurial technique in the presence of 0.5 microM 3,4-aminopyridine (DAP) to block voltage-dependent K+ currents, was strongly affected by charybdotoxin (ChTX) (300 nM) and completely abolished by BaCl2 (200 microM). This current was also blocked by omega-CgTX (5 microM) and by CdCl2 (200 microM) but was not affected by FTX (1 microliter ml-1). The blockade by omega-CgTX could not be reversed by elevating [Ca]o to 10 mM. 5. The results suggest that in frog synaptic terminals two omega-CgTX-sensitive populations might coexist. The transmitter release process seems to be mediated by calcium influx through a omega-CgTX- and FTX-sensitive population.

Modeling Structural Dynamics of Biomolecular Complexes by Coarse-Grained Molecular Simulations.

PubMed

Takada, Shoji; Kanada, Ryo; Tan, Cheng; Terakawa, Tsuyoshi; Li, Wenfei; Kenzaki, Hiroo

2015-12-15

Due to hierarchic nature of biomolecular systems, their computational modeling calls for multiscale approaches, in which coarse-grained (CG) simulations are used to address long-time dynamics of large systems. Here, we review recent developments and applications of CG modeling methods, focusing on our methods primarily for proteins, DNA, and their complexes. These methods have been implemented in the CG biomolecular simulator, CafeMol. Our CG model has resolution such that ∼10 non-hydrogen atoms are grouped into one CG particle on average. For proteins, each amino acid is represented by one CG particle. For DNA, one nucleotide is simplified by three CG particles, representing sugar, phosphate, and base. The protein modeling is based on the idea that proteins have a globally funnel-like energy landscape, which is encoded in the structure-based potential energy function. We first describe two representative minimal models of proteins, called the elastic network model and the classic Go̅ model. We then present a more elaborate protein model, which extends the minimal model to incorporate sequence and context dependent local flexibility and nonlocal contacts. For DNA, we describe a model developed by de Pablo's group that was tuned to well reproduce sequence-dependent structural and thermodynamic experimental data for single- and double-stranded DNAs. Protein-DNA interactions are modeled either by the structure-based term for specific cases or by electrostatic and excluded volume terms for nonspecific cases. We also discuss the time scale mapping in CG molecular dynamics simulations. While the apparent single time step of our CGMD is about 10 times larger than that in the fully atomistic molecular dynamics for small-scale dynamics, large-scale motions can be further accelerated by two-orders of magnitude with the use of CG model and a low friction constant in Langevin dynamics. Next, we present four examples of applications. First, the classic Go̅ model was used to emulate one ATP cycle of a molecular motor, kinesin. Second, nonspecific protein-DNA binding was studied by a combination of elaborate protein and DNA models. Third, a transcription factor, p53, that contains highly fluctuating regions was simulated on two perpendicularly arranged DNA segments, addressing intersegmental transfer of p53. Fourth, we simulated structural dynamics of dinucleosomes connected by a linker DNA finding distinct types of internucleosome docking and salt-concentration-dependent compaction. Finally, we discuss many of limitations in the current approaches and future directions. Especially, more accurate electrostatic treatment and a phospholipid model that matches our CG resolutions are of immediate importance.

Protease-Activated Receptor 2 Activation Inhibits N-Type Ca2+ Currents in Rat Peripheral Sympathetic Neurons

PubMed Central

Kim, Young-Hwan; Ahn, Duck-Sun; Kim, Myeong Ok; Joeng, Ji-Hyun; Chung, Seungsoo

2014-01-01

The protease-activated receptor (PAR)-2 is highly expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although several mechanisms have been suggested to explain PAR-2-induced hypotension, the precise mechanism remains to be elucidated. To investigate this possibility, we investigated the effects of PAR-2 activation on N-type Ca2+ currents (ICa-N) in isolated neurons of the celiac ganglion (CG), which is involved in the sympathetic regulation of mesenteric artery vascular tone. PAR-2 agonists irreversibly diminished voltage-gated Ca2+ currents (ICa), measured using the patch-clamp method, in rat CG neurons, whereas thrombin had little effect on ICa. This PAR-2-induced inhibition was almost completely prevented by ω-CgTx, a potent N-type Ca2+ channel blocker, suggesting the involvement of N-type Ca2+ channels in PAR-2-induced inhibition. In addition, PAR-2 agonists inhibited ICa–N in a voltage-independent manner in rat CG neurons. Moreover, PAR-2 agonists reduced action potential (AP) firing frequency as measured using the current-clamp method in rat CG neurons. This inhibition of AP firing induced by PAR-2 agonists was almost completely prevented by ω-CgTx, indicating that PAR-2 activation may regulate the membrane excitability of peripheral sympathetic neurons through modulation of N-type Ca2+ channels. In conclusion, the present findings demonstrate that the activation of PAR-2 suppresses peripheral sympathetic outflow by modulating N-type Ca2+ channel activity, which appears to be involved in PAR-2-induced hypotension, in peripheral sympathetic nerve terminals. PMID:25410909

Pelvic floor muscle training included in a pregnancy exercise program is effective in primary prevention of urinary incontinence: a randomized controlled trial.

PubMed

Pelaez, Mireia; Gonzalez-Cerron, Silvia; Montejo, Rocío; Barakat, Rubén

2014-01-01

To investigate the effect of pelvic floor muscle training (PFMT) taught in a general exercise class during pregnancy on the prevention of urinary incontinence (UI) in nulliparous continent pregnant women. This was a unicenter two armed randomized controlled trial. One hundred sixty-nine women were randomized by a central computer system to an exercise group (EG) (exercise class including PFMT) (n = 73) or a control group (CG) (n = 96). 10.1% loss to follow-up: 10 from EG and 7 from CG. The intervention consisted of 70-75 sessions (22 weeks, three times per week, 55-60 min/session including 10 min of PFMT). The CG received usual care (which included follow up by midwifes including information about PFMT). Questions on prevalence and degree of UI were posed before (week 10-14) and after intervention (week 36-39) using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). At the end of the intervention, there was a statistically significant difference in favor of the EG. Reported frequency of UI [Never: CG: 54/60.7%, EG: 60/95.2% (P < 0.001)]. Amount of leakage [None: CG: 45/60.7%, EG: 60/95.2% (P < 0.001)]. There was also a statistically significant difference in ICIQ-UI SF Score between groups after the intervention period [CG: 2.7 (SD 4.1), EG: 0.2 (SD 1.2) (P < 0.001)]. The estimated effect size was 0.8. PFMT taught in a general exercise class three times per week for at least 22 weeks, without former assessment of ability to perform a correct contraction was effective in primary prevention of UI in primiparous pregnant women. © 2013 Wiley Periodicals, Inc.

Star formation, structure, and formation mechanism of cometary globules: near-infrared observations of CG 1 and CG 2

NASA Astrophysics Data System (ADS)

Mäkelä, M. M.; Haikala, L. K.

2013-02-01

Context. Cometary globule (CG) 1 and CG 2 are "classic" cometary globules in the Gum Nebula. They have compact heads and long dusty tails that point away from the centre of the Gum Nebula. Aims: We study the structure of CG 1 and CG 2 and the star formation in them to find clues to the CG formation mechanism. The two possible CG formation mechanisms, radiation-driven implosion (RDI) and a supernova blast wave, produce a characteristic mass distribution where the major part of the mass is situated in either the head (RDI) or the tail (supernova blast). Methods: CG 1 and CG 2 were imaged in the near infrared (NIR) JsHKs bands. NIR photometry was used to locate NIR excess objects and to create visual extinction maps of the CGs. The AV maps allow us to analyse the large-scale structure of CG 1 and CG 2. Archival images from the WISE and Spitzer satellites and HIRES-processed IRAS images were used to study the globule's small-scale structure. Fits were made to the spectral energy distribution plots of the NIR-excess stars to estimate their age and mass. Results: In addition to the previously known CG 1 IRS 1 we discovered three new NIR-excess objects in IR imaging, two in CG 1 and one in CG 2. CG 2 IRS 1 is the first detection of star formation in CG 2. The objects are young low-mass stars. CG 1 IRS 1 is probably a class I protostar in the head of CG 1. CG 1 IRS 1 drives a bipolar outflow, which is very weak in CO, but the cavity walls are seen in reflected light in our NIR and in the Spitzer 3.6 and 4.5 μm images. Strong emission from excited polycyclic aromatic hydrocarbon particles and very small grains were detected in the CG 1 tail. The total mass of CG 1 in the observed area is 41.9 M⊙ of which 16.8 M⊙ lies in the head. For CG 2 these values are 31.0 M⊙ total and 19.1 M⊙ in the head. The observed mass distribution does not offer a firm conclusion for the formation mechanism of the two CGs: CG 1 is in too evolved a state, and in CG 2 part of the globule tail was outside the observed area. Conclusions: Even though the masses of the two CGs are similar, star formation has been more efficient in CG 1. By now, altogether six young low-mass stars have been detected in CG 1 and only one in CG 2. A possible new outflow was discovered to be emanating from CG 1 IRS 1. Based partly on observations done at the European Southern Observatory, La Silla, Chile (ESO programme 078.C-0490).Appendices A and B are available in electronic form at http://www.aanda.orgTables 1-3 are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr 130.79.128.5 or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/550/A83

Multifunctional organic–inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery

PubMed Central

Chi, Huibo; Gu, Yan; Xu, Tingting; Cao, Feng

2017-01-01

To study the cellular uptake mechanism of multifunctional organic–inorganic hybrid nanoparticles and nanosheets, new chitosan–glutathione–valine–valine-layered double hydroxide (CG-VV-LDH) nanosheets with active targeting to peptide transporter-1 (PepT-1) were prepared, characterized and further compared with CG-VV-LDH nanoparticles. Both organic–inorganic hybrid nanoparticles and nanosheets showed a sustained release in vitro and prolonged precorneal retention time in vivo, but CG-VV-LDH nanoparticles showed superior permeability in the isolated cornea of rabbits than CG-VV-LDH nanosheets. Furthermore, results of cellular uptake on human corneal epithelial primary cells (HCEpiC) and retinal pigment epithelial (ARPE-19) cells indicated that both clathrin-mediated endocytosis and active transport of PepT-1 are involved in the internalization of CG-VV-LDH nanoparticles and CG-VV-LDH nanosheets. In summary, the CG-VV-LDH nanoparticle may be a promising carrier as a topical ocular drug delivery system for the treatment of ocular diseases of mid-posterior segments, while the CG-VV-LDH nanosheet may be suitable for the treatment of ocular surface diseases. PMID:28280329

Distant neighbor base sequence context effects in human nucleotide excision repair of a benzo[a]pyrene-derived DNA lesion

PubMed Central

Cai, Yuqin; Kropachev, Konstantin; Xu, Rong; Tang, Yijin; Kolbanovskii, Marina; Kolbanovskii, Alexander; Amin, Shantu; Patel, Dinshaw J.; Broyde, Suse; Geacintov, Nicholas E.

2010-01-01

Summary The effects of non-nearest base sequences, beyond the nucleotides flanking a DNA lesion on either side, on nucleotide excision repair (NER) in extracts from human cells were investigated. We constructed two duplexes containing the same minor groove-aligned 10S (+)-trans-anti-B[a]P-N2-dG (G*) DNA adduct, derived from the environmental carcinogen benzo[a]pyrene (B[a]P): 5′-C-C-A-T-C-G*-C-T-A-C-C-3′ (CG*C-I), and 5′-C-A-C3-A4-C5-G*-C-A-C-A-C-3′ (CG*C-II). We utilized gel electrophoresis to compare the extent of DNA bending, and molecular dynamics (MD) simulations to analyze the structural characteristics of these two DNA duplexes. The NER efficiencies are 1.6 ± 0.2 times greater in the case of the CG*C-II than the CG*C-I sequence context in 135-mer duplexes. Gel electrophoresis and self-ligation circularization experiments revealed that the CG*C-II duplex is more bent than the CG*C-I duplex, while MD simulations showed that the unique -C3-A4-C5- segment in the CG*C-II duplex plays a key role. The presence of a minor groove-positioned guanine amino group, namely, the Watson-Crick partner to C3, acts as a wedge; facilitated by a highly deformable local -C3-A4- base step, this amino group allows the B[a]P ring system to produce a more enlarged minor groove in CG*C-II than in CG*C-I, as well as a local untwisting and enlarged and flexible Roll only in the CG*C-II sequence. These structural properties fit well with our prior findings that in the case of the family of minor groove 10S (+)-trans-anti-B[a]P-N2-dG lesions, flexible bends and enlarged minor groove widths (Cai et al. (2009) J. Mol. Biol., 385: 30–44) constitute NER recognition signals, and extend our understanding of sequence context effects on NER to the neighbors that are distant to the lesion. PMID:20399214

Multi-rotor internal rotations and conformational equilibria in oxiraneethanol and assignment of its vibrational spectra

NASA Astrophysics Data System (ADS)

Badawi, Hassan M.; Ali, Shaikh A.

2009-09-01

The complex internal rotations and conformational equilibria in oxiraneethanol were investigated at the DFT-B3LYP/6-311G** level of theory. Four minima were predicted in the CCOH potential energy scans of the molecule to have relative energies of about 2 kcal/mol or less and all were calculated to have real frequencies upon full optimization of structural parameters and the calculation of the Gibb's free-energies at the DFT level of calculation. At the DFT-B3LYP, the MP2 and the MP4(SDQ) levels of theory, the G1gg1 conformation, predicted to be the lowest energy conformation for oxiraneethanol, was in excellent agreement with the rotational microwave study. The equilibrium mixture was calculated to be about 47% G1gg1, 32% Cg1g, 15% Gg1t and 6% G1g1g at the B3LYP/6-311G** level of theory at 298.15 K. Solvent study corroborated the presence of the high energy Cg1g form in the liquid phase of oxiraneethanol. The vibrational frequencies of oxiraneethanol in its two stable forms were computed at the B3LYP level and vibrational assignments were made for the two lowest energy G1gg1 and Cg1g forms on the basis of calculated and experimental data of the molecule.

Classification of pregnancies of unknown location according to four different hCG-based protocols.

PubMed

Fistouris, J; Bergh, C; Strandell, A

2016-10-01

How do four protocols based on serial human chorionic gonadotropin (hCG) measurements perform when classifying pregnancies of unknown location (PULs) as low or high risk of being an ectopic pregnancy (EP)? The use of cut-offs in hCG level changes published by NICE, and a logistic regression model, M4, correctly classify more PULs as high risk, compared with two other protocols. A logistic regression model, M4, based on the mean of two consecutive hCG values and the hCG ratio (hCG 48 h/hCG 0 h) that classify PULs into low- and high-risk groups for triage purposes, identifies more EPs than a protocol using the cut-offs between a 13% decline and a 66% rise in hCG levels over 48 h. A retrospective comparative study of four different hCG-based protocols classifying PULs as low or high risk of being an EP was performed at a gynaecological emergency unit over 3 years. We identified 915 women with a PUL. Initial transvaginal ultrasonography (TVS) findings categorised 187 of the PULs as probable intrauterine pregnancies (IUPs) and 16 as probable EPs. The rate of change in hCG levels over 48 h was calculated for each patient and subjected to three different hCG threshold intervals and a logistic regression model for outcome prediction. Each PUL was subsequently dichotomised to either low-risk (i.e. failed PUL/IUP) or high-risk (i.e. EP) classification, which allowed us to compare the diagnostic performance. In 'Protocol A', a PUL was classified as low risk if >13% hCG level decline or >66% hCG level rise was achieved; otherwise, the PUL was classified as high risk of being an EP. 'Protocol B' classified a PUL as low or high risk using cut-offs of 35-50% declining hCG levels and of 53% rising hCG levels. Similarly, 'Protocol C' used hCG level cut-offs published by NICE, 50% for declining hCG levels and 63% for rising hCG levels. Finally, if a logistic regression model 'Protocol M4' calculated a ≥5% risk of the PUL being an EP, it was classified as high risk, and otherwise the PUL was classified as low risk. When the time interval between two hCG measurements failed to meet an exact 48 h, extrapolation and interpolation of hCG values was made, using log linear transformation. Protocols A, B, C and M4 classified 73, 66, 55 and 56% of PULs as low risk. The sensitivity for protocols A, B, C and M4 was 68% (95% confidence interval (CI) 61-75%), 81% (74-86%), 87% (82-92%) and 88% (83-93%), respectively. The specificity was 82% (80-85%), 77% (74-80%), 66% (62-69%) and 67% (63-70%) for protocols A, B, C and M4, respectively. All comparisons of sensitivity and specificity between the protocols were statistically significant except for protocol C versus protocol M4. In protocol C, 87% (66-97%) of misclassified EPs had rising hCG levels, compared with 19% (6-41%) for protocol M4 (P < 0.01). In a secondary analysis excluding probable IUPs and probable EPs, the results for 712 PULs were analysed. The sensitivity subsequently remained stable for all protocols. Protocol M4 reached a 78% (74-81%) specificity, which was significantly higher than 70% (66-74%) for protocol C (P = 0.01) and protocol M4 classified 63% of PULs as low risk compared with 58% for protocol C. The retrospective design of the study is a limitation. The results are derived from a population where laparoscopy played an important role in PUL management and diagnosis of EPs, although it did reflect real clinical practice. Although we tried to adhere to definitions of PUL and final outcomes as in previous studies and a recent consensus statement, potential differences in this regard must be acknowledged. Where the time interval between two serial hCG measurements deviated from 48 h we estimated 48 h hCG values. A logistic regression model, M4, classifies more PULs correctly as low risk in a selected PUL population without probable IUPs and EPs and identifies as many EPs, in comparison with the cut-offs available in the NICE guideline. This advantage for model M4 may result in a reduction of unnecessary follow-up visits, when fewer low-risk PULs are misclassified as high risk. These findings, however, ought to be clarified in a randomised controlled trial. The study was supported by LUA/ALF grant No. 70940. There are no competing interests. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Extravehicular Activity Testing in Analog Environments: Evaluating the Effects of Center of Gravity and Environment on Human Performance

NASA Technical Reports Server (NTRS)

Chappell, Steve P.; Gernhardt, Michael L.

2009-01-01

Center of gravity (CG) is likely to be an important variable in astronaut performance during partial gravity extravehicular activity (EVA). The Apollo Lunar EVA experience revealed challenges with suit stability and control. The EVA Physiology, Systems and Performance Project (EPSP) in conjunction with the Constellation EVA Systems Project Office have developed plans to systematically understand the role of suit weight, CG and suit pressure on astronaut performance in partial gravity environments. This presentation based upon CG studies seeks to understand the impact of varied CG on human performance in lunar gravity.

Structural and thermodynamic insight into E. coli UvrABC mediated incision of cluster di-acetylaminofluorene adducts on the NarI sequence

PubMed Central

Jain, Vipin; Hilton, Benjamin; Lin, Bin; Jain, Anshu; MacKerell, Alexander D.; Zou, Yue; Cho, Bongsup P.

2014-01-01

Cluster DNA damage refers to two or more lesions in a single turn of the DNA helix. Such clustering may occur with bulky DNA lesions, which may be responsible for their sequence dependent repair and mutational outcomes. Here we prepared three 16-mer cluster duplexes in which two fluoroacetylaminofluorene adducts (dG-FAAF) are separated by none, one and two nucleotides in the E. coli NarI mutational hot spot (5'-CTCTCG1G2CG3CCATCAC-3'): i.e. 5'-- CG1*G2*CG3CC--3', 5'--CG1G2*CG3*CC--3', and 5'--CG1*G2CG3*CC--3' [G*=dG-FAAF], respectively. We conducted spectroscopic, thermodynamic, and molecular dynamics studies of these di-FAAF duplexes and the results were compared with those of the corresponding mono- FAAF adducts in the same NarI sequence (Nucleic Acids Res. 2012, 3939–3951). Our nucleotide excision repair results showed greater reparability of the di-adducts in comparison to the corresponding mono-adducts. Moreover, we observed dramatic flanking base sequence effects on their repair efficiency in the order of NarI-G2G3 > -G1G3 > -G1G2. The NMR/CD/UV-melting and MD-simulation results revealed that in contrast to the mono-adducts, di-adducts produced synergistic effect on duplex destabilization. In addition, dG-FAAF at G2G3 and G1G3 destack the neighboring bases with greater destabilization occurring with the former. Overall, the results indicate the importance of base stacking and related thermal/thermodynamic destabilization in the repair of bulky cluster arylamine DNA adducts. PMID:23841451

Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience.

PubMed

Andersen, C Yding; Fischer, R; Giorgione, V; Kelsey, Thomas W

2016-10-01

For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e. 1.500 IU) is too strong, and that daily micro-dose hCG administration is likely to provide an optimised LPS with the current available drugs. Initial clinical results with the micro-dose hCG approach are presented.

New Coarse-Grained Model and Its Implementation in Simulations of Graphene Assemblies.

PubMed

Shang, Jun-Jun; Yang, Qing-Sheng; Liu, Xia

2017-08-08

Graphene is a one-atom thick layer of carbon atoms arranged in a hexagonal pattern, which makes it the strongest material in the world. The Tersoff potential is a suitable potential for simulating the mechanical behavior of the complex covalently bonded system of graphene. In this paper, we describe a new coarse-grained (CG) potential, TersoffCG, which is based on the function form of the Tersoff potential. The TersoffCG applies to a CG model of graphene that uses the same hexagonal pattern as the atomistic model. The parameters of the TersoffCG potential are determined using structural feature and potential-energy fitting between the CG model and the atomic model. The modeling process of graphene is highly simplified using the present CG model as it avoids the necessity to define bonds/angles/dihedrals connectivity. What is more, the present CG model provides a new perspective of coarse-graining scheme for crystal structures of nanomaterials. The structural changes and mechanical properties of multilayer graphene were calculated using the new potential. Furthermore, a CG model of a graphene aerogel was built in a specific form of assembly. The chemical bonding in the joints of graphene-aerogel forms automatically during the energy relaxation process. The compressive and recover test of the graphene aerogel was reproduced to study its high elasticity. Our computational examples show that the TersoffCG potential can be used for simulations of graphene and its assemblies, which have many applications in areas of environmental protection, aerospace engineering, and others.

Construction of a multiplex mutation hot spot PCR panel: the first step towards colorectal cancer genotyping on the GS Junior platform.

PubMed

Péterfia, Bálint; Kalmár, Alexandra; Patai, Árpád V; Csabai, István; Bodor, András; Micsik, Tamás; Wichmann, Barnabás; Egedi, Krisztina; Hollósi, Péter; Kovalszky, Ilona; Tulassay, Zsolt; Molnár, Béla

2017-01-01

Background: To support cancer therapy, development of low cost library preparation techniques for targeted next generation sequencing (NGS) is needed. In this study we designed and tested a PCR-based library preparation panel with limited target area for sequencing the top 12 somatic mutation hot spots in colorectal cancer on the GS Junior instrument. Materials and Methods: A multiplex PCR panel was designed to amplify regions of mutation hot spots in 12 selected genes ( APC, BRAF, CTNNB1, EGFR, FBXW7, KRAS, NRAS, MSH6, PIK3CA, SMAD2, SMAD4, TP53 ). Amplicons were sequenced on a GS Junior instrument using ligated and barcoded adaptors. Eight samples were sequenced in a single run. Colonic DNA samples (8 normal mucosa; 33 adenomas; 17 adenocarcinomas) as well as HT-29 and Caco-2 cell lines with known mutation profiles were analyzed. Variants found by the panel on APC, BRAF, KRAS and NRAS genes were validated by conventional sequencing. Results: In total, 34 kinds of mutations were detected including two novel mutations ( FBXW7 c.1740:C>G and SMAD4 c.413C>G) that have not been recorded in mutation databases, and one potential germline mutation ( APC ). The most frequently mutated genes were APC, TP53 and KRAS with 30%, 15% and 21% frequencies in adenomas and 29%, 53% and 29% frequencies in carcinomas, respectively. In cell lines, all the expected mutations were detected except for one located in a homopolymer region. According to re-sequencing results sensitivity and specificity was 100% and 92% respectively. Conclusions: Our NGS-based screening panel denotes a promising step towards low cost colorectal cancer genotyping on the GS Junior instrument. Despite the relatively low coverage, we discovered two novel mutations and obtained mutation frequencies comparable to literature data. Additionally, as an advantage, this panel requires less template DNA than sequence capture colon cancer panels currently available for the GS Junior instrument.

Is the -174 C/G polymorphism of the IL6 gene associated with elite power performance? A replication study with two different Caucasian cohorts.

PubMed

Eynon, Nir; Ruiz, Jonatan R; Meckel, Yoav; Santiago, Catalina; Fiuza-Luces, Carmen; Gómez-Gallego, Félix; Oliveira, José; Lucia, Alejandro

2011-02-01

A functional -174 C/G polymorphism in the interleukin-6 gene (IL6) is a candidate to explain individual variations in exercise-related phenotypes. To replicate recent findings showing an association between the G allele and GG genotype of elite power sports performance in European (Spanish) Caucasian males, we compared allelic and genotypic frequencies of the IL6 -174 C/G polymorphism among elite endurance athletes (n = 74) and power athletes (n = 81) and non-athletic control subjects (n = 205) of both sexes from Israel. All subjects were Israeli Caucasians (with an equivalent ratio of non-Ashkenazi and Ashkenazi descent in each group; 2:1). We found no differences in the genotype or allele frequencies among groups (all P > 0.3). We further compared the genotype and allele frequencies between national- (n = 109) and international-level Israeli athletes (n = 46) in the endurance and power group, and found no significant genotype or allele differences after adjusting for multiple comparisons. We repeated all the analyses after pooling the Israeli and Spanish control subjects, endurance and power elite athletes, and found no genotypic and allelic differences among groups. The results did not change when the analyses were repeated including only the best Israeli athletes (i.e. the international-level group) together with the group of elite Spanish athletes (P > 0.2). In conclusion, the results of the present study did not show an association between the G allele of the IL6 -174 G/C polymorphism and power sports performance in the Israeli (Caucasian) population. Our findings support the need to replicate association results between genetic polymorphisms and athletic status in populations of different ethnic backgrounds with the largest possible population samples.

Mutational effects of γ-rays and carbon ion beams on Arabidopsis seedlings

PubMed Central

Yoshihara, Ryouhei; Nozawa, Shigeki; Hase, Yoshihiro; Narumi, Issay; Hidema, Jun; Sakamoto, Ayako N.

2013-01-01

To assess the mutational effects of radiation on vigorously proliferating plant tissue, the mutation spectrum was analyzed with Arabidopsis seedlings using the plasmid-rescue method. Transgenic plants containing the Escherichia coli rpsL gene were irradiated with γ-rays and carbon ion beams (320-MeV 12C6+), and mutations in the rpsL gene were analyzed. Mutant frequency increased significantly following irradiation by γ-rays, but not by 320-MeV 12C6+. Mutation spectra showed that both radiations increased the frequency of frameshifts and other mutations, including deletions and insertions, but only γ-rays increased the frequency of total base substitutions. These results suggest that the type of DNA lesions which cause base substitutions were less often induced by 320-MeV 12C6+ than by γ-rays in Arabidopsis seedlings. Furthermore, γ-rays never increased the frequencies of G:C to T:A or A:T to C:G transversions, which are caused by oxidized guanine; 320-MeV 12C6+, however, produced a slight increase in both transversions. Instead, γ-rays produced a significant increase in the frequency of G:C to A:T transitions. These results suggest that 8-oxoguanine has little effect on mutagenesis in Arabidopsis cells. PMID:23728320

Coarse-grained molecular dynamics simulations for giant protein-DNA complexes

NASA Astrophysics Data System (ADS)

Takada, Shoji

Biomolecules are highly hierarchic and intrinsically flexible. Thus, computational modeling calls for multi-scale methodologies. We have been developing a coarse-grained biomolecular model where on-average 10-20 atoms are grouped into one coarse-grained (CG) particle. Interactions among CG particles are tuned based on atomistic interactions and the fluctuation matching algorithm. CG molecular dynamics methods enable us to simulate much longer time scale motions of much larger molecular systems than fully atomistic models. After broad sampling of structures with CG models, we can easily reconstruct atomistic models, from which one can continue conventional molecular dynamics simulations if desired. Here, we describe our CG modeling methodology for protein-DNA complexes, together with various biological applications, such as the DNA duplication initiation complex, model chromatins, and transcription factor dynamics on chromatin-like environment.

Variation, Evolution, and Correlation Analysis of C+G Content and Genome or Chromosome Size in Different Kingdoms and Phyla

PubMed Central

Li, Xiu-Qing; Du, Donglei

2014-01-01

C+G content (GC content or G+C content) is known to be correlated with genome/chromosome size in bacteria but the relationship for other kingdoms remains unclear. This study analyzed genome size, chromosome size, and base composition in most of the available sequenced genomes in various kingdoms. Genome size tends to increase during evolution in plants and animals, and the same is likely true for bacteria. The genomic C+G contents were found to vary greatly in microorganisms but were quite similar within each animal or plant subkingdom. In animals and plants, the C+G contents are ranked as follows: monocot plants>mammals>non-mammalian animals>dicot plants. The variation in C+G content between chromosomes within species is greater in animals than in plants. The correlation between average chromosome C+G content and chromosome length was found to be positive in Proteobacteria, Actinobacteria (but not in other analyzed bacterial phyla), Ascomycota fungi, and likely also in some plants; negative in some animals, insignificant in two protist phyla, and likely very weak in Archaea. Clearly, correlations between C+G content and chromosome size can be positive, negative, or not significant depending on the kingdoms/groups or species. Different phyla or species exhibit different patterns of correlation between chromosome-size and C+G content. Most chromosomes within a species have a similar pattern of variation in C+G content but outliers are common. The data presented in this study suggest that the C+G content is under genetic control by both trans- and cis- factors and that the correlation between C+G content and chromosome length can be positive, negative, or not significant in different phyla. PMID:24551092

Serum human chorionic gonadotropin (hCG) trend within the first few days after medical abortion: a prospective study.

PubMed

Pocius, Katherine D; Bartz, Deborah; Maurer, Rie; Stenquist, Asha; Fortin, Jennifer; Goldberg, Alisa B

2017-03-01

To prospectively describe the decline in serum human chorionic gonadotropin (hCG) in the first 5 days after complete medical abortion and evaluate the influence of initial hCG and gestational duration. We conducted a prospective, physiologic study of women ≤63 days gestation who underwent medical abortion with 200 mg mifepristone and 800 mcg buccal misoprostol. We stratified enrollment into two gestational cohorts, <49 days and 49-63 days, to ensure gestational variability. We collected serum quantitative hCG values on Day 1 (day of mifepristone), Day 3, Day 5 and a routine follow up hCG on Days 7-14. We calculated the percent hCG decline from Day 1 to each repeat measure and evaluated trends based on initial serum hCG level and gestation. We enrolled 66 women; 59 were protocol-adherent and included in our analysis. Mean gestation on Day 1 was 49 days and mean baseline hCG was 72,332 IU. Fifty-seven subjects (97%) had a complete medical abortion without further intervention. The mean serum hCG decline among subjects with complete medical abortion was 70.0±10.6% [range 36.9-98.6%] on Day 3 and 91.4±4.4% [range 68.4-97.7%] on Day 5. The mean serum hCG decline from Day 1 to routine follow-up on Days 7-9 was 97.1±1.7% [range 92.4-99.2%], from Day 1 to Day 10-11 was 98.5±1.4% [range 94.7-99.6%] and from Day 1 to Day 12-14 was 98.7±2.8% [range 86.7-99.9%]. There was no difference in percent hCG decline stratified by initial hCG or gestation. There is a rapid and predictable decline in serum hCG as early as Day 5 after complete medical abortion through 63 days gestation. Rate of hCG decline is not affected by initial hCG or gestational duration. For women who require confirmation of complete abortion sooner than 1 week after mifepristone, due to patient preference, logistical constraints or in the setting of pregnancy of unconfirmed location, a single repeat hCG on Day 5 may be clinically useful. Copyright © 2016 Elsevier Inc. All rights reserved.

Design of Launch Vehicle Flight Control Augmentors and Resulting Flight Stability and Control (Center Director's Discretionary Fund Project 93-05, Part III)

NASA Technical Reports Server (NTRS)

Barret, C.

1997-01-01

This publication presents the control requirements, the details of the designed Flight Control Augmentor's (FCA's), the static stability and dynamic stability wind tunnel test programs, the static stability and control analyses, the dynamic stability characteristics of the experimental Launch Vehicle (LV) with the designed FCA's, and a consideration of the elastic vehicle. Dramatic improvements in flight stability have been realized with all the FCA designs; these ranged from 41 percent to 72 percent achieved by the blunt TE design. The control analysis showed that control increased 110 percent with only 3 degrees of FCA deflection. The dynamic stability results showed improvements with all FCA designs tested at all Mach numbers tested. The blunt TE FCA's had the best overall dynamic stability results. Since the lowest elastic vehicle frequency must be well separated from that of the control system, the significant frequencies and modes of vibration have been identified, and the response spectra compared for the experimental LV in both the conventional and the aft cg configuration. Although the dynamic response was 150 percent greater in the aft cg configuration, the lowest bending mode frequency decreased by only 2.8 percent.

[ASSOCIATION BETWEEN DIETARY GLYCEMIC INDEX AND GLYCEMIC LOAD AND INTIMA MEDIA THICKNESS IN A POPULATION AT HIGH CARDIOVASCULAR RISK: A SUBGROUP ANALYSIS IN THE PREDIMED TRIAL].

PubMed

Goñi Ruiz, Nuria; Martínez González, Miguel Ángel; Salas Salvadó, Jordi; Buil Cosiales, Pilar; Diez Espino, Javier; Martinez Vila, Eduardo; Irimia Sierra, Pablo; Ros Rahola, Emilio; Toledo Atucha, Estefania

2015-11-01

increased carotid íntima-media thickness (IMT) is a marker of atherosclerosis and a predictor of future cardiovascular events. Although a beneficial effect of Mediterranean diets, in particular, enhanced with virgin olive oil and nuts, on longitudinal changes in IMT has been reported, the association between carbohydrates and the development of atherosclerosis is still unclear. to assess the association between glycemic index (IG) and glycemic load (CG) of the diet and intima media thickness (GIMC) in a population at high cardiovascular risk with no clinical symptoms. one hundred eighty seven participants of the PREDIMED-NAVARRA center (PREDIMED means in Spanish "PREvención con DIeta MEDiterránea") were randomly selected to undergo baseline and 1-year measurement of GIMC. Dietary information was collected at baseline and yearly using a validated 137-item food frequency questionnaire. Participants were categorized into four groups of energy-adjusted IG and CG intake. Multivariate analysis models (ANCOVA) were used to study the association between dietary IG and CG and GIMC and its changes. in our study we found no significant association between IG or CG and GIMC at baseline or after one year. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Accurate optimization of amino acid form factors for computing small-angle X-ray scattering intensity of atomistic protein structures

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

Tong, Dudu; Yang, Sichun; Lu, Lanyuan

2016-06-20

Structure modellingviasmall-angle X-ray scattering (SAXS) data generally requires intensive computations of scattering intensity from any given biomolecular structure, where the accurate evaluation of SAXS profiles using coarse-grained (CG) methods is vital to improve computational efficiency. To date, most CG SAXS computing methods have been based on a single-bead-per-residue approximation but have neglected structural correlations between amino acids. To improve the accuracy of scattering calculations, accurate CG form factors of amino acids are now derived using a rigorous optimization strategy, termed electron-density matching (EDM), to best fit electron-density distributions of protein structures. This EDM method is compared with and tested againstmore » other CG SAXS computing methods, and the resulting CG SAXS profiles from EDM agree better with all-atom theoretical SAXS data. By including the protein hydration shell represented by explicit CG water molecules and the correction of protein excluded volume, the developed CG form factors also reproduce the selected experimental SAXS profiles with very small deviations. Taken together, these EDM-derived CG form factors present an accurate and efficient computational approach for SAXS computing, especially when higher molecular details (represented by theqrange of the SAXS data) become necessary for effective structure modelling.« less

Contemporary group estimates adjusted for climatic effects provide a finer definition of the unknown environmental challenges experienced by growing pigs.

PubMed

Guy, S Z Y; Li, L; Thomson, P C; Hermesch, S

2017-12-01

Environmental descriptors derived from mean performances of contemporary groups (CGs) are assumed to capture any known and unknown environmental challenges. The objective of this paper was to obtain a finer definition of the unknown challenges, by adjusting CG estimates for the known climatic effects of monthly maximum air temperature (MaxT), minimum air temperature (MinT) and monthly rainfall (Rain). As the unknown component could include infection challenges, these refined descriptors may help to better model varying responses of sire progeny to environmental infection challenges for the definition of disease resilience. Data were recorded from 1999 to 2013 at a piggery in south-east Queensland, Australia (n = 31,230). Firstly, CG estimates of average daily gain (ADG) and backfat (BF) were adjusted for MaxT, MinT and Rain, which were fitted as splines. In the models used to derive CG estimates for ADG, MaxT and MinT were significant variables. The models that contained these significant climatic variables had CG estimates with a lower variance compared to models without significant climatic variables. Variance component estimates were similar across all models, suggesting that these significant climatic variables accounted for some known environmental variation captured in CG estimates. No climatic variables were significant in the models used to derive the CG estimates for BF. These CG estimates were used to categorize environments. There was no observable sire by environment interaction (Sire×E) for ADG when using the environmental descriptors based on CG estimates on BF. For the environmental descriptors based on CG estimates of ADG, there was significant Sire×E only when MinT was included in the model (p = .01). Therefore, this new definition of the environment, preadjusted by MinT, increased the ability to detect Sire×E. While the unknown challenges captured in refined CG estimates need verification for infection challenges, this may provide a practical approach for the genetic improvement of disease resilience. © 2017 Blackwell Verlag GmbH.

Development of a High-Resolution Multi-Locus Microsatellite Typing Method for Colletotrichum gloeosporioides.

PubMed

Mehta, Nikita; Hagen, Ferry; Aamir, Sadaf; Singh, Sanjay K; Baghela, Abhishek

2017-12-01

Colletotrichum gloeosporioides is an economically important fungal pathogen causing substantial yield losses indifferent host plants. To understand the genetic diversity and molecular epidemiology of this fungus, we have developed a novel, high-resolution multi-locus microsatellite typing (MLMT) method. Bioinformatic analysis of C. gloeosporioides unannotated genome sequence yielded eight potential microsatellite loci, of which five, CG1 (GT) n , CG2 (GT1) n , CG3 (TC) n , CG4 (CT) n , and CG5 (CT1) n were selected for further study based on their universal amplification potential, reproducibility, and repeat number polymorphism. The selected microsatellites were used to analyze 31 strains of C. gloeosporioides isolated from 20 different host plants from India. All microsatellite loci were found to be polymorphic, and the approximate fragment sizes of microsatellite loci CG1, CG2, CG3, CG4, and CG5 were in ranges of 213-241, 197-227, 231-265, 209-275, and 132-188, respectively. Among the 31 isolates, 55 different genotypes were identified. The Simpson's index of diversity (D) values for the individual locus ranged from 0.79 to 0.92, with the D value of all combined five microsatellite loci being 0.99. Microsatellite data analysis revealed that isolates from Ocimum sanctum , Capsicum annuum (chili pepper), and Mangifera indica (mango) formed distinct clusters, therefore exhibited some level of correlation between certain genotypes and host. The developed MLMT method would be a powerful tool for studying the genetic diversity and any possible genotype-host correlation in C. gloeosporioides .

A novel histone deacetylase inhibitor, CG200745, potentiates anticancer effect of docetaxel in prostate cancer via decreasing Mcl-1 and Bcl-XL.

PubMed

Hwang, Jung Jin; Kim, Yong Sook; Kim, Taelim; Kim, Mi Joung; Jeong, In Gab; Lee, Je-Hwan; Choi, Jene; Jang, Sejin; Ro, Seonggu; Kim, Choung-Soo

2012-08-01

We synthesized a novel hydroxamate-based pan-histone deacetylase inhibitor (HDACI), CG200745 {(E)-2-(Naphthalen-1-yloxymethyl)-oct-2-enedioic acid 1-[(3-dimethylamino-propyl)-amide] 8-hydroxyamide]}. Like other inhibitors, for example vorinostat and belinostat, CG200745 has the hydroxamic acid moiety to bind zinc at the bottom of catalytic pocket. Firstly, we analyzed its inhibitory activity against histone deacetylase (HDAC) in hormone-dependent LNCaP cells and hormone-independent DU145 and PC3 cells. CG200745 inhibited deacetylation of histone H3 and tubulin as much as vorinostat and belinostat did. CG200745 also inhibited growth of prostate cancer cells, increased sub-G1 population, and activated caspase-9, -3 and -8 in LNCaP, DU145 and PC3 cells. These results indicate that CG200745 induces apoptosis. Next, we examined the effect of CG200745 on cell death induced by docetaxel in DU145 cells in vitro and in vivo. Compared to mono-treatment with each drug, pre-treatment of DU145 cells with docetaxel followed by CG200745 showed synergistic cytotoxicity, and increased the apoptotic sub-G1 population, caspase activation, and tubulin acetylation. Moreover, the combination treatment decreased Mcl-1 and Bcl-(XL). Docetaxel and CG200745 combination reduced tumor size in the DU145 xenograft model. These preclinical results show that combination treatment with docetaxel and new HDACI, CG200745, potentiated anti-tumor effect in hormone-refractory prostate cancer (HRPC) cells via activation of apoptosis.

The impact of dietary organic and transgenic soy on the reproductive system of female adult rat.

PubMed

Brasil, Flávia Bittencourt; Soares, Lavínia Leal; Faria, Tatiane Silva; Boaventura, Gilson Telles; Sampaio, Francisco José Barcellos; Ramos, Cristiane Fonte

2009-04-01

The goal of this article was to compare the effects of a prolonged use of organic and transgenic soy on the lipid profile and ovary and uterus morphology. Wistar rats were fed three different diets from weaning until sacrifice at 15 months of age. The three diets were: casein-based diet control group (CG), organic soy-based diet group (OSG), or transgenic soy-based diet group (GMSG). There were no differences in food consumption or in the diet isoflavone components among the groups. Compared with the CG diet, both the OSG and GMSG diets were associated with significant reductions in body weight, serum triglycerides, and cholesterol (P < 0.05) (CG = 406 +/- 23.1; 104.3 +/- 13.2; 119.9 +/- 7.3 GMSG = 368 +/- 17.6; 60.3 +/- 4.6; 83.3 +/- 5.7 OSG = 389 +/- 23.5; 72.3 +/- 12.5; 95.5 +/- 8.0, respectively). The volume density of endometrial glandular epithelium was greater in the GMSG group (29.5 +/- 7.17, P < 0.001) when compared with the CG (18.5 +/- 7.4) and OSG (20.3 +/- 10.6) groups. The length density of endometrial glandular epithelium was shorter in both GMSG (567.6 +/- 41.1) and OSG (514.8 +/- 144.5) diets compared with the CG (P < 0.05) diet. GMSG also resulted in reduced follicle number and increased corpus luteum number compared to the OSG or CG diets (P < 0.05). In summary, both GMSG and OSG diets resulted in decreased body weight and lower serum triglyceride and cholesterol levels, and alterations in uterine and ovarian morphology were also observed. The prolonged use of soy-based diets and their relation to reproductive health warrants further investigation.

[PCR-based evaluation of sequence specificity of DNA fragmentation by ultrasound].

PubMed

Garafutdinov, R R; Galimova, A A; Sakhabutdinova, A R; Chemeris, A V

2016-01-01

Ultrasonic fragmentation, which is a simple and convenient method for the mechanical degradation of DNA, is widely used in modern genome studies as one of the sample preparation steps. It has been recently found that the DNA breaks occur more often in the regions containing 5'-CG-3' dinucleotides. We studied the influence of the 5'-CG-3' dinucleotides on the efficiency of the 28S rRNA gene amplification during PCR with sonicated DNA of Mantis religiosa. It was shown that the amplification rate depends on the template length and the number of 5'-CG-3' dinucleotides. Amplification of the DNA regions with a higher 5'-CG-3' density is less efficient because of their higher sensitivity to ultrasound. The amount of the amplified DNA templates is inversely proportional to the 5'-CG-3'number.

Prevalence and psychological correlates of complicated grief among bereaved adults 2.5-3.5 years after September 11th attacks.

PubMed

Neria, Yuval; Gross, Raz; Litz, Brett; Maguen, Shira; Insel, Beverly; Seirmarco, Gretchen; Rosenfeld, Helena; Suh, Eun Jung; Kishon, Ronit; Cook, Joan; Marshall, Randall D

2007-06-01

A Web-based survey of adults who experienced loss during the September 11, 2001, terrorist attacks was conducted to examine the prevalence and correlates of complicated grief (CG) 2.5-3.5 years after the attacks. Forty-three percent of a study group of 704 bereaved adults across the United States screened positive for CG. In multivariate analyses, CG was associated with female gender, loss of a child, death of deceased at the World Trade Center, and live exposure to coverage of the attacks on television. Posttraumatic stress disorder, major depression, anxiety, suicidal ideation, and increase in post-9/11 smoking were common among participants with CG. A majority of the participants with CG reported receiving grief counseling and psychiatric medication after 9/11. Clinical and policy implications are discussed.

Autoclavable physically-crosslinked chitosan cryogel as a wound dressing.

PubMed

Takei, Takayuki; Danjo, So; Sakoguchi, Shogo; Tanaka, Sadao; Yoshinaga, Takuma; Nishimata, Hiroto; Yoshida, Masahiro

2018-04-01

Moist wounds were known to heal more rapidly than dry wounds. Hydrogel wound dressings were suitable for the moist wound healing because of their hyperhydrous structure. Chitosan was a strong candidate as a base material for hydrogel wound dressings because the polymer had excellent biological properties that promoted wound healing. We previously developed physically-crosslinked chitosan cryogels, which were prepared solely by freeze-thawing of a chitosan-gluconic acid conjugate (CG) aqueous solution, for wound treatment. The CG cryogels were disinfected by immersing in 70% ethanol before applying to wounds in our previous study. In the present study, we examined the influence of autoclave sterilization (121°C, 20 min) on the characteristics of CG cryogel because complete sterilization was one of the fundamental requirements for medical devices. We found that optimum value of gluconic acid content of CG, defined as the number of the incorporated gluconic acid units per 100 glucosamine units of chitosan, was 11 for autoclaving. An increased crosslinking level of CG cryogel on autoclaving enhanced resistance of the gels to enzymatic degradation. Furthermore, the autoclaved CG cryogels retained favorable biological properties of the pre-autoclaved CG cryogels in that they showed the same hemostatic activity and efficacy in repairing full-thickness skin wounds as the pre-autoclaved CG cryogels. These results showed the great potential of autoclavable CG cryogels as a practical wound dressing. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Cheilitis glandularis: immunohistochemical expression of protein water channels (aquaporins) in minor labial salivary glands.

PubMed

Nico, M M S; Melo, J N; Lourenço, S V

2014-03-01

Cheilitis glandularis (CG) is a rare condition in which thick saliva is secreted from dilated ostia of swollen minor salivary glands from the lips. Aquaporins (AQPs) are membrane proteins that exhibit channel activity specific for water and small solutes. AQPs are essential for corporal homeostasis, and are widely expressed through human tissues. Most AQPs studies are based on renal and nervous pathophysiology; few involve salivary glands. Some previous investigators hypothesized that minor salivary gland structure and function is normal on CG. To study possible salivary synthesis alterations in CG, we compared the expression of AQPs present in minor salivary glands in specimens with CG and controls by using immunohistochemistry.   Seven cases of CG and three normal controls were studied. Intensity and patterns of expression of AQP 1, 2 and 8 differed in CG compared with controls. AQP 4 and 5 (the most important AQP in salivary function) showed identical patterns in CG and controls. Our findings suggest that the expression and arguably, function of some of the AQPs may be altered in CG; consequently, water flow mechanism abnormalities with possible alteration in salivary composition seem to occur. External factors (mainly UV rays) seem to play an important role in CG; nonetheless, our findings suggest that there might be some degree of alteration on water transportation. © 2013 The Authors. Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology.

Identification of metabolic profiling of cell culture of licorice compared with its native one.

PubMed

Man, Shuli; Guo, Songbo; Gao, Wenyuan; Wang, Juan; Zhang, Liming; Li, Xinglin

2013-04-01

Glycyrrhiza uralensis has long been used as a flavoring and sweetening agent in food products. In the last ten years, suspensions of Glycyrhiza cells have been successfully established. However, there is no report of full metabolic profiling research on these cells. To identify their composition we used HPLC-DAD coupled with ESI(+/-)-MS (n) to compare the constituents of cultured Glycyrhiza (CG) cells with those the native cells (NG). We identified 60 compounds including flavonoids, phenols, and triterpenoids. Among these compounds, 42 occurred both in NG and CG, nine were present in NG only and nine were present in CG alone. The number of the triterpenoid aglycones without glycones in CG was smaller than that in NG. The number of flavanone, isoflavone, isoflavan, and benzenoid compounds was also smaller in CG than that in NG, whereas the number of pterocarpans was much higher. Although differences existed between CG and NG, the extract of CG was similar to that of NG. With the development of cell suspension culture-based biotransformation, cell culture of Glycyrrhiza has the potential to be more profitable than field cultivation in some areas.

Cockcroft-Gault revisited: New de-liver-ance on recommendations for use in cirrhosis.

PubMed

Scappaticci, Gianni B; Regal, Randolph E

2017-01-28

The Cockcroft-Gault (CG) equation has become perhaps the most popular practical approach for estimating renal function among health care professionals. Despite its widespread use, clinicians often overlook not only the limitations of the original serum creatinine (SCr) based equation, but also may not appreciate the validity of the many variations used to compensate for these limitations. For cirrhotic patients in particular, the underlying pathophysiology of the disease contributes to a falsely low SCr, thereby overestimating renal function with use of the CG equation in this population. We reviewed the original CG trial from 1976 along with data surrounding clinician specific alterations to the CG equation that followed through time. These alterations included different formulas for body weight in obese patients and the "rounding up" approach in patients with low SCr. Additionally, we described the pathophysiology and hemodynamic changes that occur in cirrhosis; and reviewed several studies that attempted to estimate renal function in this population. The evidence we reviewed regarding the most accurate manipulation of the original CG equation to estimate creatinine clearance (CrCl) was inconclusive. Unfortunately, the homogeneity of the patient population in the original CG trial limited its external validity. Elimination of body weight in the CG equation actually produced the estimate closest to the measure CrCl. Furthermore, "rounding up" of SCr values often underestimated CrCl. This approach could lead to suboptimal dosing of drug therapies in patients with low SCr. In cirrhotic patients, utilization of SCr based methods overestimated true renal function by about 50% in the literature we reviewed.

A majorized Newton-CG augmented Lagrangian-based finite element method for 3D restoration of geological models

NASA Astrophysics Data System (ADS)

Tang, Peipei; Wang, Chengjing; Dai, Xiaoxia

2016-04-01

In this paper, we propose a majorized Newton-CG augmented Lagrangian-based finite element method for 3D elastic frictionless contact problems. In this scheme, we discretize the restoration problem via the finite element method and reformulate it to a constrained optimization problem. Then we apply the majorized Newton-CG augmented Lagrangian method to solve the optimization problem, which is very suitable for the ill-conditioned case. Numerical results demonstrate that the proposed method is a very efficient algorithm for various large-scale 3D restorations of geological models, especially for the restoration of geological models with complicated faults.

Effects of a Controlled Family-Based Health Education/Counseling Intervention

ERIC Educational Resources Information Center

Salminen, Marika; Vahlberg, Tero; Ojanlatva, Ansa; Kivela, Sirkka-Liisa

2005-01-01

Objective: To describe the effects of a controlled family-based health education/counseling intervention on health behaviors of children with a familial history of cardiovascular diseases (FH-CVDs). Methods: The intervention group (IG, n=432) received 5 counseling sessions. The control groups 1 (CG1, n=200) and 2 (CG2, n=423) received no…

Comparative analysis of core genome MLST and SNP typing within a European Salmonella serovar Enteritidis outbreak.

PubMed

Pearce, Madison E; Alikhan, Nabil-Fareed; Dallman, Timothy J; Zhou, Zhemin; Grant, Kathie; Maiden, Martin C J

2018-06-02

Multi-country outbreaks of foodborne bacterial disease present challenges in their detection, tracking, and notification. As food is increasingly distributed across borders, such outbreaks are becoming more common. This increases the need for high-resolution, accessible, and replicable isolate typing schemes. Here we evaluate a core genome multilocus typing (cgMLST) scheme for the high-resolution reproducible typing of Salmonella enterica (S. enterica) isolates, by its application to a large European outbreak of S. enterica serovar Enteritidis. This outbreak had been extensively characterised using single nucleotide polymorphism (SNP)-based approaches. The cgMLST analysis was congruent with the original SNP-based analysis, the epidemiological data, and whole genome MLST (wgMLST) analysis. Combination of the cgMLST and epidemiological data confirmed that the genetic diversity among the isolates predated the outbreak, and was likely present at the infection source. There was consequently no link between country of isolation and genetic diversity, but the cgMLST clusters were congruent with date of isolation. Furthermore, comparison with publicly available Enteritidis isolate data demonstrated that the cgMLST scheme presented is highly scalable, enabling outbreaks to be contextualised within the Salmonella genus. The cgMLST scheme is therefore shown to be a standardised and scalable typing method, which allows Salmonella outbreaks to be analysed and compared across laboratories and jurisdictions. Copyright © 2018. Published by Elsevier B.V.

Impact of an Acceptance Facilitating Intervention on Patients' Acceptance of Internet-based Pain Interventions: A Randomized Controlled Trial.

PubMed

Baumeister, Harald; Seifferth, Holger; Lin, Jiaxi; Nowoczin, Lisa; Lüking, Marianne; Ebert, David

2015-06-01

Results from clinical trials indicate that Internet-based psychological pain interventions are effective in treating chronic pain. However, little is known about patients' acceptance of these programs and how to positively influence patients' intention to engage in them. Therefore, the present study aimed (1) to assess patients' acceptance of Internet-based interventions, and (2) to examine whether patients' acceptance can be increased by an acceptance facilitating intervention. A total of 104 patients with chronic pain from 2 pain units were randomly allocated to an intervention group (IG) and a no-intervention control group (CG). The IG was shown a short informational video about Internet-based psychological pain interventions before receiving a questionnaire on patients' acceptance of Internet-based psychological pain interventions and predictors of acceptance (performance expectancy, effort expectancy, social influence, facilitating conditions, Internet usage, and Internet anxiety). The CG filled out the questionnaire immediately. Patients' acceptance was measured with a 4-item scale (sum score ranging from 4 to 20). Baseline acceptance of Internet-based interventions was reported as low (sum-score:4-9) by 53.8%, moderate (10 to 15) by 42.3%, and high (16 to 20) by 3.9% of the patients with chronic pain in the CG. The IG showed a significantly higher acceptance (M = 12.17, SD = 4.22) than the CG (M = 8.94, SD = 3.71) with a standardized mean difference of d = 0.81 (95% CI, 0.41, 1.21). All predictor variables were significantly improved in the IG compared with the CG, except for Internet usage. Patients with chronic pain display a relatively low acceptance of Internet-based psychological pain interventions, which can be substantially increased by a short informational video.

Soy β-conglycinin improves glucose uptake in skeletal muscle and ameliorates hepatic insulin resistance in Goto-Kakizaki rats.

PubMed

Tachibana, Nobuhiko; Yamashita, Yoko; Nagata, Mayuko; Wanezaki, Satoshi; Ashida, Hitoshi; Horio, Fumihiko; Kohno, Mitsutaka

2014-02-01

Although the underlying mechanism is unclear, β-conglycinin (βCG), the major component of soy proteins, regulates blood glucose levels. Here, we hypothesized that consumption of βCG would normalize blood glucose levels by ameliorating insulin resistance and stimulating glucose uptake in skeletal muscles. To test our hypothesis, we investigated the antidiabetic action of βCG in spontaneously diabetic Goto-Kakizaki (GK) rats. Our results revealed that plasma adiponectin levels and adiponectin receptor 1 messenger RNA expression in skeletal muscle were higher in βCG-fed rats than in casein-fed rats. Phosphorylation of adenosine monophosphate-activated protein kinase (AMP kinase) but not phosphatidylinositol-3 kinase was activated in βCG-fed GK rats. Subsequently, βCG increased translocation of glucose transporter 4 to the plasma membrane. Unlike the results in skeletal muscle, the increase in adiponectin receptor 1 did not lead to AMP kinase activation in the liver of βCG-fed rats. The down-regulation of sterol regulatory element-binding factor 1, which is induced by low insulin levels, promoted the increase in hepatic insulin receptor substrate 2 expression. Based on these findings, we concluded that consumption of soy βCG improves glucose uptake in skeletal muscle via AMP kinase activation and ameliorates hepatic insulin resistance and that these actions may help normalize blood glucose levels in GK rats. Copyright © 2014 Elsevier Inc. All rights reserved.

Probabilistic Sensitivity Analysis for Launch Vehicles with Varying Payloads and Adapters for Structural Dynamics and Loads

NASA Technical Reports Server (NTRS)

McGhee, David S.; Peck, Jeff A.; McDonald, Emmett J.

2012-01-01

This paper examines Probabilistic Sensitivity Analysis (PSA) methods and tools in an effort to understand their utility in vehicle loads and dynamic analysis. Specifically, this study addresses how these methods may be used to establish limits on payload mass and cg location and requirements on adaptor stiffnesses while maintaining vehicle loads and frequencies within established bounds. To this end, PSA methods and tools are applied to a realistic, but manageable, integrated launch vehicle analysis where payload and payload adaptor parameters are modeled as random variables. This analysis is used to study both Regional Response PSA (RRPSA) and Global Response PSA (GRPSA) methods, with a primary focus on sampling based techniques. For contrast, some MPP based approaches are also examined.

A Hybrid Coarse-graining Approach for Lipid Bilayers at Large Length and Time Scales

PubMed Central

Ayton, Gary S.; Voth, Gregory A.

2009-01-01

A hybrid analytic-systematic (HAS) coarse-grained (CG) lipid model is developed and employed in a large-scale simulation of a liposome. The methodology is termed hybrid analyticsystematic as one component of the interaction between CG sites is variationally determined from the multiscale coarse-graining (MS-CG) methodology, while the remaining component utilizes an analytic potential. The systematic component models the in-plane center of mass interaction of the lipids as determined from an atomistic-level MD simulation of a bilayer. The analytic component is based on the well known Gay-Berne ellipsoid of revolution liquid crystal model, and is designed to model the highly anisotropic interactions at a highly coarse-grained level. The HAS CG approach is the first step in an “aggressive” CG methodology designed to model multi-component biological membranes at very large length and timescales. PMID:19281167

Gay-Berne and electrostatic multipole based coarse-grain potential in implicit solvent

NASA Astrophysics Data System (ADS)

Wu, Johnny; Zhen, Xia; Shen, Hujun; Li, Guohui; Ren, Pengyu

2011-10-01

A general, transferable coarse-grain (CG) framework based on the Gay-Berne potential and electrostatic point multipole expansion is presented for polypeptide simulations. The solvent effect is described by the Generalized Kirkwood theory. The CG model is calibrated using the results of all-atom simulations of model compounds in solution. Instead of matching the overall effective forces produced by atomic models, the fundamental intermolecular forces such as electrostatic, repulsion-dispersion, and solvation are represented explicitly at a CG level. We demonstrate that the CG alanine dipeptide model is able to reproduce quantitatively the conformational energy of all-atom force fields in both gas and solution phases, including the electrostatic and solvation components. Replica exchange molecular dynamics and microsecond dynamic simulations of polyalanine of 5 and 12 residues reveal that the CG polyalanines fold into "alpha helix" and "beta sheet" structures. The 5-residue polyalanine displays a substantial increase in the "beta strand" fraction relative to the 12-residue polyalanine. The detailed conformational distribution is compared with those reported from recent all-atom simulations and experiments. The results suggest that the new coarse-graining approach presented in this study has the potential to offer both accuracy and efficiency for biomolecular modeling.

Severe storm electricity

NASA Technical Reports Server (NTRS)

Rust, W. D.; Macgorman, D. R.

1985-01-01

During FY-85, Researchers conducted a field program and analyzed data. The field program incorporated coordinated measurements made with a NASA U2. Results include the following: (1) ground truth measurements of lightning for comparison with those obtained by the U2; (2) analysis of dual-Doppler radar and dual-VHF lightning mapping data from a supercell storm; (3) analysis of synoptic conditions during three simultaneous storm systems on 13 May 1983 when unusually large numbers of positive cloud-to-ground (+CG) flashes occurred; (4) analysis of extremely low frequency (ELF) wave forms; and (5) an assessment of a cloud -ground strike location system using a combination of mobile laboratory and fixed-base TV video data.

Managing pregnancy of unknown location based on initial serum progesterone and serial serum hCG levels: development and validation of a two-step triage protocol.

PubMed

Van Calster, B; Bobdiwala, S; Guha, S; Van Hoorde, K; Al-Memar, M; Harvey, R; Farren, J; Kirk, E; Condous, G; Sur, S; Stalder, C; Timmerman, D; Bourne, T

2016-11-01

A uniform rationalized management protocol for pregnancies of unknown location (PUL) is lacking. We developed a two-step triage protocol to select PUL at high risk of ectopic pregnancy (EP), based on serum progesterone level at presentation (step 1) and the serum human chorionic gonadotropin (hCG) ratio, defined as the ratio of hCG at 48 h to hCG at presentation (step 2). This was a cohort study of 2753 PUL (301 EP), involving a secondary analysis of prospectively and consecutively collected PUL data from two London-based university teaching hospitals. Using a chronological split we used 1449 PUL for development and 1304 for validation. We aimed to assign PUL as low risk with high confidence (high negative predictive value (NPV)) while classifying most EP as high risk (high sensitivity). The first triage step assigned PUL as low risk using a threshold of serum progesterone at presentation. The remaining PUL were triaged using a novel logistic regression risk model based on hCG ratio and initial serum progesterone (second step), defining low risk as an estimated EP risk of < 5%. On validation, initial serum progesterone ≤ 2 nmol/L (step 1) classified 16.1% PUL as low risk. Second-step classification with the risk model selected an additional 46.0% of all PUL as low risk. Overall, the two-step protocol classified 62.1% of PUL as low risk, with an NPV of 98.6% and a sensitivity of 92.0%. When the risk model was used in isolation (i.e. without the first step), 60.5% of PUL were classified as low risk with 99.1% NPV and 94.9% sensitivity. PUL can be classified efficiently into being either high or low risk for complications using a two-step protocol involving initial progesterone and hCG levels and the hCG ratio. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Transcutaneous electrical nerve stimulation for the relief of post-partum uterine contraction pain during breast-feeding: a randomized clinical trial.

PubMed

de Sousa, Ligia; Gomes-Sponholz, Flávia A; Nakano, Ana Márcia S

2014-05-01

To evaluate transcutaneous electrical nerve stimulation (TENS) used to relieve uterine contraction pain during breast-feeding in multiparous women. A controlled and randomized clinical trial was performed with 32 post-partum multiparous women who were breast-feeding. The participants were randomized into an experimental (EG, n = 16) and a control group (CG, n = 16). Pain was assessed using the Numerical Rating Scale and the descriptors of the Present Pain Intensity (PPI - McGill) during two sequential feeds. In the first assessment, the post-partum women in the EG and CG were monitored while breast-feeding and questioned regarding the degree of uterine contraction pain. In the second assessment, which was performed at the next feed, the EG used TENS while the CG was monitored, with pain being reassessed following. In the EG, the TENS electrodes were placed between T10-L1 and S2-S4, with a frequency of 100 Hz, a pulse duration of 75 μs and amplitude adjusted to produce a strong and tolerable sensation for 40 min. A descriptive analysis of the data and comparative intra- and intergroup analyses were performed by means of a non-parametrical test, with a significance level P ≤ 0.05. The level of basal pain was 5.56 in the EG and 5.50 in the CG. In the intragroup analysis, the EG (P < 0.0001) and CG (P = 0.04) presented significant pain reduction. In the intergroup analysis, the EG had significant pain reduction (P < 0.01) in comparison to the CG. In the PPI analysis, a non-significant decrease in pain intensity was observed in the EG. TENS was found to be effective in reducing post-partum uterine contraction pain during breast-feeding. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Twin Town in South Brazil: A Nazi's Experiment or a Genetic Founder Effect?

PubMed Central

Tagliani-Ribeiro, Alice; Oliveira, Mariana; Sassi, Adriana K.; Rodrigues, Maira R.; Zagonel-Oliveira, Marcelo; Steinman, Gary; Matte, Ursula; Fagundes, Nelson J. R.; Schuler-Faccini, Lavinia

2011-01-01

Cândido Godói (CG) is a small municipality in South Brazil with approximately 6,000 inhabitants. It is known as the “Twins' Town” due to its high rate of twin births. Recently it was claimed that such high frequency of twinning would be connected to experiments performed by the German Nazi doctor Joseph Mengele. It is known, however, that this town was founded by a small number of families and therefore a genetic founder effect may represent an alternatively explanation for the high twinning prevalence in CG. In this study, we tested specific predictions of the “Nazi's experiment” and of the “founder effect” hypotheses. We surveyed a total of 6,262 baptism records from 1959–2008 in CG catholic churches, and identified 91 twin pairs and one triplet. Contrary to the “Nazi's experiment hypothesis”, there is no spurt in twinning between the years (1964–1968) when Mengele allegedly was in CG (P = 0.482). Moreover, there is no temporal trend for a declining rate of twinning since the 1960s (P = 0.351), and no difference in twinning among CG districts considering two different periods: 1927–1958 and 1959–2008 (P = 0.638). On the other hand, the “founder effect hypothesis” is supported by an isonymy analysis that shows that women who gave birth to twins have a higher inbreeding coefficient when compared to women who never had twins (0.0148, 0.0081, respectively, P = 0.019). In summary, our results show no evidence for the “Nazi's experiment hypothesis” and strongly suggest that the “founder effect hypothesis” is a much more likely alternative for explaining the high prevalence of twinning in CG. If this hypothesis is correct, then this community represents a valuable population where genetic factors linked to twinning may be identified. PMID:21687665

Twin Town in South Brazil: a Nazi's experiment or a genetic founder effect?

PubMed

Tagliani-Ribeiro, Alice; Oliveira, Mariana; Sassi, Adriana K; Rodrigues, Maira R; Zagonel-Oliveira, Marcelo; Steinman, Gary; Matte, Ursula; Fagundes, Nelson J R; Schuler-Faccini, Lavinia

2011-01-01

Cândido Godói (CG) is a small municipality in South Brazil with approximately 6,000 inhabitants. It is known as the "Twins' Town" due to its high rate of twin births. Recently it was claimed that such high frequency of twinning would be connected to experiments performed by the German Nazi doctor Joseph Mengele. It is known, however, that this town was founded by a small number of families and therefore a genetic founder effect may represent an alternatively explanation for the high twinning prevalence in CG. In this study, we tested specific predictions of the "Nazi's experiment" and of the "founder effect" hypotheses. We surveyed a total of 6,262 baptism records from 1959-2008 in CG catholic churches, and identified 91 twin pairs and one triplet. Contrary to the "Nazi's experiment hypothesis", there is no spurt in twinning between the years (1964-1968) when Mengele allegedly was in CG (P = 0.482). Moreover, there is no temporal trend for a declining rate of twinning since the 1960s (P = 0.351), and no difference in twinning among CG districts considering two different periods: 1927-1958 and 1959-2008 (P = 0.638). On the other hand, the "founder effect hypothesis" is supported by an isonymy analysis that shows that women who gave birth to twins have a higher inbreeding coefficient when compared to women who never had twins (0.0148, 0.0081, respectively, P = 0.019). In summary, our results show no evidence for the "Nazi's experiment hypothesis" and strongly suggest that the "founder effect hypothesis" is a much more likely alternative for explaining the high prevalence of twinning in CG. If this hypothesis is correct, then this community represents a valuable population where genetic factors linked to twinning may be identified.

Recognition of N-Glycoforms in Human Chorionic Gonadotropin by Monoclonal Antibodies and Their Interaction Motifs*

PubMed Central

Li, Daoyuan; Zhang, Ping; Li, Fei; Chi, Lequan; Zhu, Deyu; Zhang, Qunye; Chi, Lianli

2015-01-01

The glycosylation of human chorionic gonadotropin (hCG) plays an important role in reproductive tumors. Detecting hCG N-glycosylation alteration may significantly improve the diagnostic accuracy and sensitivity of related cancers. However, developing an immunoassay directly against the N-linked oligosaccharides is unlikely because of the heterogeneity and low immunogenicity of carbohydrates. Here, we report a hydrogen/deuterium exchange and MS approach to investigate the effect of N-glycosylation on the binding of antibodies against different hCG glycoforms. Hyperglycosylated hCG was purified from the urine of invasive mole patients, and the structure of its N-linked oligosaccharides was confirmed to be more branched by MS. The binding kinetics of the anti-hCG antibodies MCA329 and MCA1024 against hCG and hyperglycosylated hCG were compared using biolayer interferometry. The binding affinity of MCA1024 changed significantly in response to the alteration of hCG N-linked oligosaccharides. Hydrogen/deuterium exchange-MS reveals that the peptide β65–83 of the hCG β subunit is the epitope for MCA1024. Site-specific N-glycosylation analysis suggests that N-linked oligosaccharides at Asn-13 and Asn-30 on the β subunit affect the binding affinity of MCA1024. These results prove that some antibodies are sensitive to the structural change of N-linked oligosaccharides, whereas others are not affected by N-glycosylation. It is promising to improve glycoprotein biomarker-based cancer diagnostics by developing combined immunoassays that can determine the level of protein and measure the degree of N-glycosylation simultaneously. PMID:26240146

The Risk of Preeclampsia According to High Thyroid Function in Pregnancy Differs by hCG Concentration.

PubMed

Korevaar, Tim I M; Steegers, Eric A P; Chaker, Layal; Medici, Marco; Jaddoe, Vincent W V; Visser, Theo J; de Rijke, Yolanda B; Peeters, Robin P

2016-12-01

During pregnancy, there is an increased demand for thyroid hormone. The pregnancy hormone human chorionic gonadotropin (hCG) is an important physiological stimulator of thyroid function. Already high-normal maternal free T 4 concentrations are associated with a higher risk of preeclampsia. The objective of the investigation was to study our hypothesis that hCG concentrations can distinguish a physiological form of high thyroid function from a more pathological form of high thyroid function and that the risk of preeclampsia would differ accordingly. TSH, free T 4 , hCG, or thyroperoxidase antibody concentrations were determined in pregnant women participating in a population-based prospective cohort study. The study was conducted in the general community. A nonselected sample of 5146 pregnant women participated in the study. There were no interventions. Preeclampsia was measured. Women with high hCG-associated high thyroid function did not have a higher risk of preeclampsia than women with normal thyroid function. In contrast, women with low hCG and high thyroid function had a 3.4- to 11.1-fold higher risk of preeclampsia. These risk estimates were amplified in women with a high body mass index. Women with a low hCG and suppressed TSH (<0.10 mU/L) had a 3.2- to 8.9-fold higher risk of preeclampsia. hCG was not associated with preeclampsia, and results remained similar after exclusion of thyroperoxidase antibody-positive women. This study suggests that, in contrast to women with a high hCG associated high thyroid function, women with low hCG and high thyroid function during pregnancy are at a higher risk of developing preeclampsia. The additional measurement of hCG may therefore help to distinguish a more pathological form of high thyroid function and women at a high risk of preeclampsia.

Impact and duration effect of telemonitoring on ΗbA1c, BMI and cost in insulin-treated Diabetes Mellitus patients with inadequate glycemic control: A randomized controlled study.

PubMed

Fountoulakis, Stelios; Papanastasiou, Labrini; Gryparis, Alexandros; Markou, Athina; Piaditis, George

2015-01-01

To monitor and control the blood glucose levels in inefficiently insulin-treated patients with type 1 and 2 diabetes mellitus (DM) using a telemonitoring system and determine whether the improvement of HbA1c has a lasting effect following its discontinuation. Seventy inefficiently controlled insulin-treated DM patients using telemonitoring (telemonitoring group-TG) [HbA1c 9.9±2.3% (85±24.9mmol/mol)] and 35 age-, body mass index (BMI)- and Hba1c-matched insulin-treated patients receiving outpatient care (control group-CG) [HbA1c 9.7±2.1% (82±23.4mmol/mol)] were enrolled. Data of TG were transmitted from the glucose-meters to our computers via modem. Communication was achieved via e-mails and mobile phone text-messages through integrated software. HbA1c and BMI were evaluated at enrollment, 3 and 6 months, and 6 months after telemonitoring discontinuation. Frequency of hypo- and hyperglycemias and cost were also analyzed. Significant reduction in HbA1c was observed in TG both at 3 [7.1±1.0% (54±10.5mmol/mol) p<0.001] and 6 months [6.9±0.9% (52±9.5mmol/mol) p<0.001], compared to the CG group at the same timepoints. Significant reduction was also observed in the TG subgroups with ΗbA1c≥10% and 10>HbA1c≥7.5% at 3 and 6 months, compared to CG. No statistically significant differences in BMI were observed between TG and CG. Six months after telemonitoring discontinuation, HbA1c in TG was slightly increased [7.3±1.0% (56±10.4mol/mol)]. Attenuation was also observed in both TG subgroups. Compared to CG, the number of monthly hypo- and hyperglycemias was reduced in TG. The intervention had a financial benefit for patients living more than 100 km from the health care provider. Telemonitoring can result in reduction of HbA1c and frequency of hypo- and hyperglycemias. This beneficial effect is slightly attenuated 6 months after terminating telemonitoring.

Impact of counselling on exclusive breast-feeding practices in a poor urban setting in Kenya: a randomized controlled trial.

PubMed

Ochola, Sophie A; Labadarios, Demetre; Nduati, Ruth W

2013-10-01

To determine the impact of facility-based semi-intensive and home-based intensive counselling in improving exclusive breast-feeding (EBF) in a low-resource urban setting in Kenya. A cluster randomized controlled trial in which nine villages were assigned on a 1:1:1 ratio, by computer, to two intervention groups and a control group. The home-based intensive counselling group (HBICG) received seven counselling sessions at home by trained peers, one prenatally and six postnatally. The facility-based semi-intensive counselling group (FBSICG) received only one counselling session prenatally. The control group (CG) received no counselling from the research team. Information on infant feeding practices was collected monthly for 6 months after delivery. The data-gathering team was blinded to the intervention allocation. The outcome was EBF prevalence at 6 months. Kibera slum, Nairobi. A total of 360 HIV-negative women, 34-36 weeks pregnant, were selected from an antenatal clinic in Kibera; 120 per study group. Of the 360 women enrolled, 265 completed the study and were included in the analysis (CG n 89; FBSICG n 87; HBICG n 89). Analysis was by intention to treat. The prevalence of EBF at 6 months was 23.6% in HBICG, 9.2% in FBSICG and 5.6% in CG. HBICG mothers had four times increased likelihood to practise EBF compared with those in the CG (adjusted relative risk = 4.01; 95% CI 2.30, 7.01; P=0.001). There was no significant difference between EBF rates in FBSICG and CG. EBF can be promoted in low socio-economic conditions using home-based intensive counselling. One session of facility-based counselling is not sufficient to sustain EBF.

Acoustic absorbance measurements in neonates exposed to smoking during pregnancy.

PubMed

Pucci, Beatriz Paloma Corrêa; Roque, Nayara Michelle Costa de Freitas; Gamero, Marcella Scigliano; Durante, Alessandra Spada

2017-04-01

To analyze acoustic absorbance using wideband tympanometry in neonates exposed to passive smoking during pregnancy. A study comprising 54 neonates in the control group (CG - unexposed) and 19 in the study group (SG - exposed) was carried out. Subjects were submitted to the wideband tympanometry test and subsequent analysis of absorbance of 17 frequencies. Low frequencies had a lower level of absorbance compared to high frequencies for both ambient and peak pressures, with no difference between the groups. No effect of passive smoking on acoustic absorbance measurements in neonates was observed. Copyright © 2017 Elsevier B.V. All rights reserved.

Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial.

PubMed

Alberola, V; Camps, C; Provencio, M; Isla, D; Rosell, R; Vadell, C; Bover, I; Ruiz-Casado, A; Azagra, P; Jiménez, U; González-Larriba, J L; Diz, P; Cardenal, F; Artal, A; Carrato, A; Morales, S; Sanchez, J J; de las Peñas, R; Felip, E; López-Vivanco, G

2003-09-01

To compare the survival benefit obtained with cisplatin plus gemcitabine, a cisplatin-based triplet, and nonplatinum sequential doublets in advanced non-small-cell lung cancer (NSCLC). Stage IIIB to IV NSCLC patients were randomly assigned to receive cisplatin 100 mg/m2 day 1 plus gemcitabine 1,250 mg/m2 days 1 and 8, every 3 weeks for six cycles (CG); cisplatin 100 mg/m2 day 1 plus gemcitabine 1,000 mg/m2 and vinorelbine 25 mg/m2 days 1 and 8, every 3 weeks for six cycles (CGV); or gemcitabine 1,000 mg/m2 plus vinorelbine 30 mg/m2 days 1 and 8, every 3 weeks for three cycles, followed by vinorelbine 30 mg/m2 days 1 and 8 plus ifosfamide 3 g/m2 day 1, every 3 weeks for three cycles (GV-VI). Five hundred fifty-seven patients were assigned to treatment (182 CG, 188 CGV, 187 GV-VI). Response rates were significantly inferior for the nonplatinum sequential doublet (CG, 42%; CGV, 41%; GV-VI, 27%; CG v GV-VI, P =.003). No differences in median survival or time to progression were observed. Toxicity was higher for the triplet: grade 3 to 4 neutropenia (GC, 32%; CGV, 57%; GV-VI, 27%; P <.05); neutropenic fever (CG, 4%; CGV, 19%; GV-VI, 5%; P <.0001); grade 3 to 4 thrombocytopenia (CG, 19%; CGV, 23%; GV-VI, 3%; P =.0001); and grade 3 to 4 emesis (GC, 22%; GCV, 32%; GV-VI, 6%; P <.0001). On the basis of these results, CG remains a standard regimen for first-line treatment of advanced NSCLC.

Comparison of creatinine clearance estimates in subgroups based on Body Mass Index and albumin.

PubMed

Grapsa, Eirini; Pipili, Chrysoula; Angelopoulos, Epameinondas; Pantelias, Kostantinos; Kapetanaki, Antigoni; Deda, Edmond; Kiousi, Eva; Tzanatos, Helen

2016-02-01

The establishment of accurate equations for glomerular filtration rate (GFR) estimations is still far from the realization. Factors such as age, diabetes, stage of CKD, pregnancy, muscle mass and ethic nation are associated with less reliance upon commonly utilized estimation equations. We aimed to compare the routine use of 24-hour creatinine clearance (CrCl) and GFR estimates calculated by Crockoft-Gault (CG) and modification of diet in renal disease (MDRD) formulas in patients with different levels of renal dysfunction in subgroups, based on Body Mass Index (BMI) and serum albumin (Alb) levels. Two hundred and seventy-nine non diabetic patients (172 men and 107 women), aged 54±23 years, with BMI 27.3±4.4 were enrolled in the study. All patients presented creatinine 1.8±1.2 (mg/dL) and Alb 3.5±1.3g/dL. The comparison of CrCl versus CG had bias 3.1 while the comparison of CrCl versus MDRD had a bias of 6.6. Univariate analysis showed that age, sex and BMI were not significant biases related to the CG, MDRD and CrCl. Indeed, the bias related to the CG was significantly lower than that related to MDRD in patients with either low or high serum albumin. Interestingly, the bias associated with CG was 1.3 in non-diabetic patients with Alb ≤3.5 mg /dL suggesting that CG equation could be used interchangeable to CrCl in these patients. CG gave a better prediction of measured CrCl than MDRD in Mediterranean, non-diabetic, non-hospitalized patients although misclassification of patients with regard to renal impairment stage was not present.

Lightning activity observed in upper and lower portions of storms and its relationship to storm structure from VHF mapping and Doppler radar

NASA Technical Reports Server (NTRS)

Taylor, W. L.; Rust, W. D.; Macgorman, D. R.; Brandes, E. A.

1983-01-01

Space time mapping of very high frequencies (VHF) sources reveals lightning processes for cloud to ground (CG) and for large intracloud (IC) flashes are confined to an altitude below about 10 km and closely associated with the central high reflectivity region of a storm. Another class of IC flashes was identified that produces a splattering of small sources within the main electrically active volume of a storm and also within a large divergent wind canopy at the top of a storm. There is no apparent temporal association between the small high altitude IC flashes occurring almost continuously and the large IC and CG flashes sporadically occurring in the lower portions of storms.

The influence of resistance exercise training on the levels of anxiety in ischemic stroke.

PubMed

Aidar, Felipe José; de Oliveira, Ricardo Jacó; Silva, António José; de Matos, Dihogo Gama; Mazini Filho, Mauro Lúcio; Hickner, Robert C; Machado Reis, Victor

2012-01-01

The aim of this pilot study was to analyze the effect of a strength training program on indicators of trait and state anxiety in patients with ischemic stroke. The subjects were divided into two groups: experimental group (EG) consisting of 11 subjects aged 51.7 ± 8.0 years and a control group (CG) with 13 subjects aged 52.5 ± 7.7 years. EG underwent 12 weeks of strength training, with a frequency of three times a week. For data collection, a State-Trait Anxiety Inventory (STAI) was used. Significant differences were found between pre- and posttest in EG for trait anxiety (43.2 ± 12.5 pretest 39.9 ± 7.3 posttest) and state anxiety (46.9 ± 7.6 pretest 44.9 ± 7.7 posttest) with no differences in CG for trait anxiety (42.9 ± 12.2 pretest 42.6 ± 12.1 posttest) and state anxiety (47.4 ± 8.1 pretest 47.5 ± 8.0 posttest). In the evaluation between the groups, significant differences were found for all indicators of trait anxiety (39.9 ± 7.3 EG; 42.6 ± 12.1 CG) and state anxiety (44.9 ± 7.7 EG; 47.5 ± 8.0 CG). This pilot study indicates that strength training may provide an improvement in trait and state anxiety more than one year after stroke.

Negative Mood Increases Selective Attention to Negatively Valenced Body Parts in Female Adolescents with Anorexia Nervosa.

PubMed

Svaldi, Jennifer; Bender, Caroline; Caffier, Detlef; Ivanova, Viliana; Mies, Nina; Fleischhaker, Christian; Tuschen-Caffier, Brunna

2016-01-01

Previous research has yielded evidence of increased attentional processing of negatively valenced body parts in women with anorexia nervosa (AN), especially for those with high depressive symptomatology. The present study extended previous research by implementing an experimental mood manipulation. In a within-subjects design, female adolescents with AN (n = 12) and an age matched female control group (CG; n = 12) were given a negative and a positive mood induction at a one-week interval. After each mood induction, participants underwent a 3-min mirror exposure, while their eye movements were recorded. After the positive mood induction, both AN and CG participants displayed longer and more frequent gazes towards their self-defined most ugly relative to their self-defined most beautiful body part. However, after the negative mood induction, only females with AN were characterized by increased attention to their most ugly compared to their most beautiful body part, while CG participants' attention distribution was balanced. Furthermore, in the negative (but not in the positive) mood induction condition gaze frequency and duration towards the most ugly body part was significantly stronger in the AN group relative to the CG. The results emphasize the role of negative mood in the maintenance of pathological information processing of the self-body. This increased body-related negativity-bias during negative mood may lead to the persistence and aggravation of AN patients' body image disturbance.

The Influence of Resistance Exercise Training on the Levels of Anxiety in Ischemic Stroke

PubMed Central

Aidar, Felipe José; de Oliveira, Ricardo Jacó; Silva, António José; de Matos, Dihogo Gama; Mazini Filho, Mauro Lúcio; Hickner, Robert C.; Machado Reis, Victor

2012-01-01

The aim of this pilot study was to analyze the effect of a strength training program on indicators of trait and state anxiety in patients with ischemic stroke. The subjects were divided into two groups: experimental group (EG) consisting of 11 subjects aged 51.7 ± 8.0 years and a control group (CG) with 13 subjects aged 52.5 ± 7.7 years. EG underwent 12 weeks of strength training, with a frequency of three times a week. For data collection, a State-Trait Anxiety Inventory (STAI) was used. Significant differences were found between pre- and posttest in EG for trait anxiety (43.2 ± 12.5 pretest 39.9 ± 7.3 posttest) and state anxiety (46.9 ± 7.6 pretest 44.9 ± 7.7 posttest) with no differences in CG for trait anxiety (42.9 ± 12.2 pretest 42.6 ± 12.1 posttest) and state anxiety (47.4 ± 8.1 pretest 47.5 ± 8.0 posttest). In the evaluation between the groups, significant differences were found for all indicators of trait anxiety (39.9 ± 7.3 EG; 42.6 ± 12.1 CG) and state anxiety (44.9 ± 7.7 EG; 47.5 ± 8.0 CG). This pilot study indicates that strength training may provide an improvement in trait and state anxiety more than one year after stroke. PMID:23213625

Massage and Storytelling Reduce Aggression and Improve Academic Performance in Children Attending Elementary School.

PubMed

Gonçalves, Lia Lopes; Voos, Mariana Callil; de Almeida, Maria Helena Morgani; Caromano, Fátima Aparecida

2017-01-01

Aggressive behaviors must be addressed in elementary schools. Massage and storytelling can be strategies to deal with aggression because both involve experience exchange and social interaction. Both can decrease stress and anxiety and increase self-esteem. To evaluate the effect of two interventions (massage and storytelling) on aggressive behaviors and academic performance of elementary school children. Three groups ( n = 35 children in each group) of the second grade participated (aged 6.5-8.1 years). One group received ten extra classes of massage (MG), another group received extra classes of storytelling (SG), and the control group received extra classes of random subjects (CG). Extra classes lasted for 50 minutes, once a week. Aggressive behaviors were recorded on diaries, by the teachers and the coordinator. The frequency of aggressive behaviors and the academic performance of MG, SG, and CG were observed for six months and the groups were compared. ANOVAs evidenced that MG and SG, but not CG, showed a reduction in aggressive behaviors registered by the teachers and coordinator, after the intervention. Academic performance of MG and SC improved after the intervention ( p < 0.05).

Is socially integrated community day care for people with dementia associated with higher user satisfaction and a higher job satisfaction of staff compared to nursing home-based day care?

PubMed

Marijke van Haeften-van Dijk, A; Hattink, Bart J J; Meiland, Franka J M; Bakker, Ton J E M; Dröes, Rose-Marie

2017-06-01

To investigate whether community-based (CO) day care with carer support according to the proven effective Meeting Centres Support Programme model is associated with higher satisfaction of people with dementia (PwD) and their informal caregivers (CG) and with a higher job satisfaction among care staff compared to traditional nursing home-based (NH) day care. Data were collected in 11 NH day care centres and 11 CO day care centres. User satisfaction of PwD and CG was evaluated in the 11 NH day care centres (n PwD = 41, n CG = 39) and 11 CO day care centres (n PwD = 28, n CG = 36) with a survey after six months of participation. Job satisfaction was measured only in the six NH day care centres that recently transformed to CO day care, with two standard questionnaires before (n STAFF = 35), and six months after the transition (n STAFF = 35). PwD were more positive about the communication and listening skills of staff and the atmosphere and activities at the CO day care centre. Also, CG valued the communication with, and expertise of, staff in CO day care higher, and were more satisfied with the received emotional, social and practical support. After the transition, satisfaction of staff with the work pace increased, but satisfaction with learning opportunities decreased. PwD and CG were more satisfied about the communication with the staff and the received support in CO day care than in NH day care. Overall job satisfaction was not higher, except satisfaction about work pace.

Utilization of dipeptide/protein based diets in larval and juvenile Koi carp--post-prandial free amino acid levels.

PubMed

Kwasek, K; Zhang, Y; Dabrowski, K

2010-02-01

We have shown previously that diets in which the nitrogen portion is based on synthetic dipeptides (PP) resulted in weight gain by rainbow trout alevins when free amino acid (FAA) based diets did not. However, the protein-based diet used as a control in the previous study resulted in a significantly better performance of fish than peptide- or FAA based diet fed fish. Therefore, the objectives of our study were (i) to test how stomachless fish respond to peptide-based diets, (ii) to evaluate PP and protein-PP mixture diets and (iii) to examine if post-prandial response to FAA concentrations in the fish body can be used as an indicator of the availability of dietary amino acid sources. The first experiment was conducted with a 4-day old Koi carp (Cyprinus carpio) larvae and included groups fed a casein-gelatin (CG) based diet, a commercial diet and live Artemia nauplii. In the second experiment, fish fed live Artemia for 3 weeks (69 +/- 12 mg) were placed in glass aquaria in triplicate per dietary treatment. Four diets provided equivalent amounts of nitrogen in the form of a CG, a PP, a 50% PP and 50% CG (PP50) mix and as FAA. Fish were fed at 1 and 3 h intervals, and the survival and growth were monitored during the second and third weeks of experiments 1 and 2 respectively. Following the completion of feeding, juvenile carp were sampled prior to feeding and 3 h after a meal. Whole body FAA analyses were carried out. We observed marginal suitability of the CG diet for larval Koi carp, as earlier indicated in common carp. Juvenile Koi carp fed the CG diet achieved 236 +/- 19 mg, whereas PP50, PP and FAA diet fed fish grew to 140 +/- 37, 70 +/- 8 and 73 +/- 5 mg respectively. Free amino acids in the fish body, and in particular indispensable amino acids (IDAA), were excellent indicators of dietary availability. The present experiment shows that a dietary 1:1 ratio of protein to synthetic PPs results in better growth, survival and whole body IDAA concentrations in relation to FAA- and PP-based diets confirming earlier reports on the use of synthetic PP-based diets, although this diet does not match the performance of complete protein, CG-based diet.

[Influence of human chorionic gonadotropin (hCG) in combination with a 500 calorie diet on clinical and laboratory parameters in premenopausal women with and without hormonal contraception].

PubMed

Rabe, T; Richter, S; Kiesel, L; Zaloumis, M; Runnebaum, B

1987-07-01

82 premenopausal, healthy, nonpregnant volunteers were treated with a 500 kcal reduction diet for 28 days. They were randomized into 2 groups--OC and non-OC users. In addition, 1 of the subgroups in each main group was treated with hCG injections (250 IU/day im for 21 days. The non-OC users (both with and without hCG injections) consisted of 24 subjects each. In the groups of OC users, 13 patients were treated with hCG, 16 were not treated; 5 volunteers discontinued their diet. All groups experienced strong sensations of hunger during the 1st week of the diet (9-16%) which decreased slowly thereafter. No differences between the individual groups could be found. Diet adjustment improved more greatly in those groups who had not received hCG (15-20%) than in the groups with hCG (2-12%). No change was found during the dieting among the subgroups. Serum electrolytes, urea, uric acid, creatinine, and liver enzymes did not change during the dieting. Slight changes were observed in serum cholesterol and triglycerides. Side effects were seen in 2 volunteers from the hCG group, 1 of whom suffered from severe headache and the other who suffered from ovarian cysts which were punctured by laparoscopy. The success of the diet was based on motivation and good information, rather than on the hCG administration. (author's modified)

The Drosophila genes CG14593 and CG30106 code for G-protein-coupled receptors specifically activated by the neuropeptides CCHamide-1 and CCHamide-2.

PubMed

Hansen, Karina K; Hauser, Frank; Williamson, Michael; Weber, Stine B; Grimmelikhuijzen, Cornelis J P

2011-01-07

Recently, a novel neuropeptide, CCHamide, was discovered in the silkworm Bombyx mori (L. Roller et al., Insect Biochem. Mol. Biol. 38 (2008) 1147-1157). We have now found that all insects with a sequenced genome have two genes, each coding for a different CCHamide, CCHamide-1 and -2. We have also cloned and deorphanized two Drosophila G-protein-coupled receptors (GPCRs) coded for by genes CG14593 and CG30106 that are selectively activated by Drosophila CCH-amide-1 (EC(50), 2×10(-9) M) and CCH-amide-2 (EC(50), 5×10(-9) M), respectively. Gene CG30106 (symbol synonym CG14484) has in a previous publication (E.C. Johnson et al., J. Biol. Chem. 278 (2003) 52172-52178) been wrongly assigned to code for an allatostatin-B receptor. This conclusion is based on our findings that the allatostatins-B do not activate the CG30106 receptor and on the recent findings from other research groups that the allatostatins-B activate an unrelated GPCR coded for by gene CG16752. Comparative genomics suggests that a duplication of the CCHamide neuropeptide signalling system occurred after the split of crustaceans and insects, about 410 million years ago, because only one CCHamide neuropeptide gene is found in the water flea Daphnia pulex (Crustacea) and the tick Ixodes scapularis (Chelicerata). Copyright © 2010 Elsevier Inc. All rights reserved.

iMARS--mutation analysis reporting software: an analysis of spontaneous cII mutation spectra.

PubMed

Morgan, Claire; Lewis, Paul D

2006-01-31

The sensitivity of any mutational assay is determined by the level at which spontaneous mutations occur in the corresponding untreated controls. Establishing the type and frequency at which mutations occur naturally within a test system is essential if one is to draw scientifically sound conclusions regarding chemically induced mutations. Currently, mutation-spectra analysis is laborious and time-consuming. Thus, we have developed iMARS, a comprehensive mutation-spectrum analysis package that utilises routinely used methodologies and visualisation tools. To demonstrate the use and capabilities of iMARS, we have analysed the distribution, types and sequence context of spontaneous base substitutions derived from the cII gene mutation assay in transgenic animals. Analysis of spontaneous mutation spectra revealed variation both within and between the transgenic rodent test systems Big Blue Mouse, MutaMouse and Big Blue Rat. The most common spontaneous base substitutions were G:C-->A:T transitions and G:C-->T:A transversions. All Big Blue Mouse spectra were significantly different from each other by distribution and nearly all by mutation type, whereas the converse was true for the other test systems. Twenty-eight mutation hotspots were observed across all spectra generally occurring in CG, GA/TC, GG and GC dinucleotides. A mutation hotspot at nucleotide 212 occurred at a higher frequency in MutaMouse and Big Blue Rat. In addition, CG dinucleotides were the most mutable in all spectra except two Big Blue Mouse spectra. Thus, spontaneous base-substitution spectra showed more variation in distribution, type and sequence context in Big Blue Mouse relative to spectra derived from MutaMouse and Big Blue Rat. The results of our analysis provide a baseline reference for mutation studies utilising the cII gene in transgenic rodent models. The potential differences in spontaneous base-substitution spectra should be considered when making comparisons between these test systems. The ease at which iMARS has allowed us to carry out an exhaustive investigation to assess mutation distribution, mutation type, strand bias, target sequences and motifs, as well as predict mutation hotspots provides us with a valuable tool in helping to distinguish true chemically induced hotspots from background mutations and gives a true reflection of mutation frequency.

Can we improve gait skills in chronic hemiplegics? A randomised control trial with gait trainer.

PubMed

Dias, D; Laíns, J; Pereira, A; Nunes, R; Caldas, J; Amaral, C; Pires, S; Costa, A; Alves, P; Moreira, M; Garrido, N; Loureiro, L

2007-12-01

Partial body weight support (PBWS) is an accepted treatment for hemiplegic patients. The aim of this study is to compare the efficiency of gait trainer with conventional treatment on the gait management after stroke. Forty chronic post-stroke hemiplegics were part of a prospective research. Inclusion criteria were: first ever stroke in a chronic stage with stabilised motor deficits; age >18 and <80 years; cognitive and communication skills to understand the treatment; absence of cardiac, psychological and orthopedic contraindications. Patients were randomised into two groups: the control group (CG) that used the Bobath method in 40 minutes sessions, 5 times a week, for 5 weeks, and the experimental group (EG) that used the gait trainer, for the same period of time and frequency. Assessment tools: Motricity Index (MI); Toulouse Motor Scale (TMS); modified Ashworth Spasticity Scale (mASS); Berg Balance Scale (BBS); Rivermead Mobility Index (RMI); Fugl-Meyer Stroke Scale (F-MSS); Functional Ambulation Category (FAC); Barthel Index (BI); 10 meters, time up and go (TUG), 6 minutes, and step tests. EG and CG did the assessments before treatment (T(0)), right after treatment (T(1)), and on follow-up, 3 months later (T(2)). CG and EG were homogenous in all the variables at T(0). CG and EG showed improvement in almost all the assessment scales after treatment, although only some with relevant differences. EG showed statistically relevant improvement on T(1) and on T(2) in several of the assessment tools, whereas CG only showed statistically significant improvement after T(1) and only in some of the assessment tools. Both groups of chronic hemiplegic patients improved after either PBWS with gait trainer or Bobath treatment. Only subjects undergoing PBWS with gait trainer maintained functional gain after 3 months.

Novel SNPs in the exon region of bovine DKK4 gene and their association with body measurement traits in Qinchuan cattle.

PubMed

Gao, J B; Li, Y K; Yang, N; Ma, X H; Adoligbe, C; Jiang, B J; Fu, C Z; Cheng, G; Zan, L S

2013-02-28

The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of bovine Dickkopf homolog 4 (DKK4) are associated with body measurement traits in Qinchuan cattle. By using PCR-SSCP technology and DNA sequencing, we discovered 5 DKK4 SNPs in Qingchuan cattle, including -65G>A and -77G>T in the 5'-untranslated region, 1532C>G and 1533T>C in exon 2, and 2088C>T in exon 3. The sequencing map showed that 1532C>G and 1533T>C were in close linkage disequilibrium and were treated as 1532C>G-1533T>C in this study. Allele frequencies were calculated and analyzed by the chi-square test, which showed that -65G>A and 1532C>G-1533T>C were in Hardy-Weinberg equilibrium (P > 0.05), whereas -77G>T and 2088C>T were not in all 633 tested Qinchuan cattle individuals (P < 0.01). Gene heterozygosity (HE), effective allele number (NE), and polymorphism information content (PIC) were 0.407, 1.686, and 0.324 at -65G>A; 0.472, 1.894, and 0.361 at -77G>T; 0.476, 1.908, and 0.363 at 1532C>G-1533T>C; and 0.218, 1.279, and 0.195 at 2088C>T. We also evaluated the potential association of these SNPs with body measurement traits in all 633 individuals; the results suggest that several SNPs in Qinchuan cattle DKK4 were significantly associated with body length, hip height, rump length, hip width, heart girth, and pin bone width (P < 0.05 and P < 0.01). These results suggest that bovine DKK4 could be used as candidate gene for Qinchuan cattle breeding.

Can organic and transgenic soy be used as a substitute for animal protein by rats?

PubMed

Soares, L L; Lucas, A M M; Boaventura, G T

2005-04-01

We evaluated the protein quality of organic and transgenic soy fed to rats throughout life. Thirty female Wistar rats were divided into three groups (N = 10): organic soy group (OSG) receiving organic soy-based diet, genetically modified soy group (GMSG) receiving transgenic soy-based diet, and a control group (CG) receiving casein-based diet. All animals received water and isocaloric diet (10% protein), ad libitum for 291 days. After this, the weight of GMSG animals (290.9 +/- 9.1 g) was significantly lower (P <= 0.04) than CG (323.2 +/- 7.9 g). The weight of OSG (302.2 +/- 8.7 g) was between that of the GMSG and the CG. Protein intake was similar for OSG (308.4 +/- 6.8 g) and GMSG (301.5 +/- 2.5 g), and significantly lower (P <= 0.0005) than the CG (358.4 +/- 8.1 g). Growth rate was similar for all groups: OSG (0.80 +/- 0.02 g), GMSG (0.81 +/- 0.03 g) and CG (0.75 +/- 0.02 g). In addition to providing a good protein intake and inducing less weight gain, both types of soy were utilized in a manner similar to that of casein, suggesting that the protein quality of soy is similar to that of the standard protein casein. The groups fed soy-based diet gained less weight, which may be considered to be beneficial for health. We conclude that organic and transgenic soy can be fed throughout life to rats in place of animal protein, because contain high quality protein and do not cause a marked increase in body weight.

32 CFR 623.2 - Loan policies.

Code of Federal Regulations, 2013 CFR

2013-07-01

... America (world or national jamborees) 3 10 U.S.C. 2544; AR 725-1, ch. 7 MACOM CG on behalf of CG DARCOM...) Military requirements and priorities. (B) Continuity of military operations, troop survival, and the rehabilitation of essential military bases. (C) Stocks and programed Army requirements. This includes...

32 CFR 623.2 - Loan policies.

Code of Federal Regulations, 2014 CFR

2014-07-01

... America (world or national jamborees) 3 10 U.S.C. 2544; AR 725-1, ch. 7 MACOM CG on behalf of CG DARCOM...) Military requirements and priorities. (B) Continuity of military operations, troop survival, and the rehabilitation of essential military bases. (C) Stocks and programed Army requirements. This includes...

32 CFR 623.2 - Loan policies.

Code of Federal Regulations, 2012 CFR

2012-07-01

... America (world or national jamborees) 3 10 U.S.C. 2544; AR 725-1, ch. 7 MACOM CG on behalf of CG DARCOM...) Military requirements and priorities. (B) Continuity of military operations, troop survival, and the rehabilitation of essential military bases. (C) Stocks and programed Army requirements. This includes...

Hybrid DFP-CG method for solving unconstrained optimization problems

NASA Astrophysics Data System (ADS)

Osman, Wan Farah Hanan Wan; Asrul Hery Ibrahim, Mohd; Mamat, Mustafa

2017-09-01

The conjugate gradient (CG) method and quasi-Newton method are both well known method for solving unconstrained optimization method. In this paper, we proposed a new method by combining the search direction between conjugate gradient method and quasi-Newton method based on BFGS-CG method developed by Ibrahim et al. The Davidon-Fletcher-Powell (DFP) update formula is used as an approximation of Hessian for this new hybrid algorithm. Numerical result showed that the new algorithm perform well than the ordinary DFP method and proven to posses both sufficient descent and global convergence properties.

Approximation of Point-Set Images by Plane Curves.

DTIC Science & Technology

1980-12-01

required. A function g satisfying these requirements will be called an influence function . [In practice we choose cg based on the 2g variance a2 of the...noise; for example P(IXl-< ) = .75 where X is a N(0, 2 ) r.v. The influence function could take 2 2 the form g(r) = s(cg - r ) for Oirscg, and some s>OI...value cg as defined in the influence function . We can then expect R( ) to be maximal (locally) at the E’s that fit the largest proportion of the data

Gay-Berne and electrostatic multipole based coarse-grain potential in implicit solvent

PubMed Central

Wu, Johnny; Zhen, Xia; Shen, Hujun; Li, Guohui; Ren, Pengyu

2011-01-01

A general, transferable coarse-grain (CG) framework based on the Gay-Berne potential and electrostatic point multipole expansion is presented for polypeptide simulations. The solvent effect is described by the Generalized Kirkwood theory. The CG model is calibrated using the results of all-atom simulations of model compounds in solution. Instead of matching the overall effective forces produced by atomic models, the fundamental intermolecular forces such as electrostatic, repulsion-dispersion, and solvation are represented explicitly at a CG level. We demonstrate that the CG alanine dipeptide model is able to reproduce quantitatively the conformational energy of all-atom force fields in both gas and solution phases, including the electrostatic and solvation components. Replica exchange molecular dynamics and microsecond dynamic simulations of polyalanine of 5 and 12 residues reveal that the CG polyalanines fold into “alpha helix” and “beta sheet” structures. The 5-residue polyalanine displays a substantial increase in the “beta strand” fraction relative to the 12-residue polyalanine. The detailed conformational distribution is compared with those reported from recent all-atom simulations and experiments. The results suggest that the new coarse-graining approach presented in this study has the potential to offer both accuracy and efficiency for biomolecular modeling. PMID:22029338

Efficient Inversion of Mult-frequency and Multi-Source Electromagnetic Data

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

Gary D. Egbert

2007-03-22

The project covered by this report focused on development of efficient but robust non-linear inversion algorithms for electromagnetic induction data, in particular for data collected with multiple receivers, and multiple transmitters, a situation extremely common in eophysical EM subsurface imaging methods. A key observation is that for such multi-transmitter problems each step in commonly used linearized iterative limited memory search schemes such as conjugate gradients (CG) requires solution of forward and adjoint EM problems for each of the N frequencies or sources, essentially generating data sensitivities for an N dimensional data-subspace. These multiple sensitivities allow a good approximation to themore » full Jacobian of the data mapping to be built up in many fewer search steps than would be required by application of textbook optimization methods, which take no account of the multiplicity of forward problems that must be solved for each search step. We have applied this idea to a develop a hybrid inversion scheme that combines features of the iterative limited memory type methods with a Newton-type approach using a partial calculation of the Jacobian. Initial tests on 2D problems show that the new approach produces results essentially identical to a Newton type Occam minimum structure inversion, while running more rapidly than an iterative (fixed regularization parameter) CG style inversion. Memory requirements, while greater than for something like CG, are modest enough that even in 3D the scheme should allow 3D inverse problems to be solved on a common desktop PC, at least for modest (~ 100 sites, 15-20 frequencies) data sets. A secondary focus of the research has been development of a modular system for EM inversion, using an object oriented approach. This system has proven useful for more rapid prototyping of inversion algorithms, in particular allowing initial development and testing to be conducted with two-dimensional example problems, before approaching more computationally cumbersome three-dimensional problems.« less

Hearing evaluation of intratympanic methylprednisolone perfusion for refractory sudden sensorineural hearing loss.

PubMed

She, Wandong; Dai, Yanhong; Du, Xiaoping; Yu, Chenjie; Chen, Feng; Wang, Junguo; Qin, Xiaoming

2010-02-01

To investigate the effectiveness and safety of intratympanic methylprednisolone perfusion (IMP) through a microcatheter in patients with sudden sensorineural hearing loss (SSNHL) who failed a conventional treatment. Prospective clinical study. This study was conducted in Nanjing Drum Tower Hospital, Nanjing University Medical School. Patients who had failed a minimum 10-day conventional treatment were included. Twenty-six patients in the study group (SG) received methylprednisolone perfusion through a microcatheter placed into the tympanum once a day for 10 days and the conventional treatment. Twenty-three patients who received a second conventional treatment (no steroid) served as the comparison group (CG). All patients were followed up for three months after the end of treatment. The effective rates for SG and CG were 50 percent (61.9% when only patients with an interval from onset to IMP < or = 60 days were included) and 21.7 percent, respectively (chi(2) = 4.194, P = 0.041). The pure-tone average improvement was 20.2 +/- 15.6 dB in SG, and 9.2 +/- 13.7 dB in CG (z = 2.51, P = 0.011). In SG, hearing improvement at low frequencies was better than that at high frequencies. The interval from onset to IMP affected the efficacy of IMP. IMP through a microcatheter is a promising treatment for refractory SSNHL. The data suggest that the treatment may be more effective when administered at the earlier stages of SSNHL when the conventional treatment has failed. Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

Production of specific antisera for radioimmunoassay of human luteinizing hormone (LH) in the presence of human chorionic gonadotropin (hCG). [/sup 125/I

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

Thorell, J.I.; Jeppsson, S.; Holmstrom, B.

1976-09-01

A specific radioimmunoassay for LH, which measures plasma LH in the presence of human chorionic gonadotropin (hCG) is described. Rabbits were immunized with highly purified native LH. One of the antisera with a difference in its reactivity against LH and hCG was further purified by affinity chromatography on a column with hCG coupled to Sepharose 4B. The adsorbed antiserum and /sup 125/I-LH was used in a double antibody assay. The LH standard (MRC/68/40) efficiently inhibited the binding of /sup 125/I-LH, and the standard curve showed a sensitivity of 0.5 ng/ml in the sample. hCG up to 10,000 ng/ml did notmore » inhibit the binding of /sup 125/I-LH. The plasma level of LH in pregnant women in the first trimester was low (1.3 +- 0.1 ng/ml). When LH was measured in fertile or menopausal women with or without stimulation with LH/FSH releasing hormone (LH-RH)/sup x/ the results agreed to those found with our conventional LH-assay based on antiserum against hCG.« less

Ecology of ephemeroptera, plecoptera and trichoptera (insecta) in rivers of the gunung jerai forest reserve: diversity and distribution of functional feeding groups.

PubMed

Hamid, Suhaila Ab; Md Rawi, Che Salmah

2014-08-01

A field study was performed to describe the functional feeding groups (FFGs) of Ephemeroptera, Plecoptera and Trichoptera (EPT) in the Tupah, Batu Hampar and Teroi Rivers in the Gunung Jerai Forest Reserve (GJFR), Kedah, Malaysia. Twenty-nine genera belonging to 19 families were identified. The EPTs were classified into five FFGs: collector-gatherers (CG), collector-filterers (CF), shredders (SH), scrapers (SC) and predators (P). In this study, CG and CF were the dominant groups inhabiting all three rivers. Ephemeroptera dominated these rivers due to their high abundance, and they were also the CG (90.6%). SC were the lowest in abundance among all groups. Based on the FFGs, the Teroi River was suitable for CG, whereas the Tupah and Batu Hampar Rivers were suitable for CG and CF. The distribution of FFGs differed among the rivers (CG, χ(2) = 23.6, p = 0.00; SH, χ(2) = 10.02, p = 0.007; P, χ(2) = 25.54, p = 0.00; CF, χ(2) = 21.95, p = 0.00; SC, χ(2) = 9.31, p = 0.01). These findings indicated that the FFGs found in rivers of the GJFR represent high river quality.

Interactions of the apolipoprotein C-III 3238C>G polymorphism and alcohol consumption on serum triglyceride levels

PubMed Central

2010-01-01

Background Both apolipoprotein (Apo) C-III gene polymorphism and alcohol consumption have been associated with increased serum triglyceride (TG) levels, but their interactions on serum TG levels are not well known. The present study was undertaken to detect the interactions of the ApoC-III 3238C>G (rs5128) polymorphism and alcohol consumption on serum TG levels. Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoC-III 3238C>G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Interactions of the ApoC-III 3238C>G genotype and alcohol consumption was assessed by using a cross-product term between genotypes and the aforementioned factor. Results Serum total cholesterol (TC), TG, high-density lipoprotein cholesterol (HDL-C), ApoA-I and ApoB levels were higher in drinkers than in nondrinkers (P < 0.05-0.001). There was no significant difference in the genotypic and allelic frequencies between the two groups. Serum TG levels in nondrinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, low-density lipoprotein cholesterol (LDL-C) and ApoB levels in drinkers were higher in GG genotype than in CC or CG genotype (P < 0.01 for all). Serum HDL-C levels in drinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, HDL-C and ApoA-I levels in CC genotype, TC, HDL-C, ApoA-I levels and the ratio of ApoA-I to ApoB in CG genotype, and TC, TG, LDL-C, ApoA-I and ApoB levels in GG genotype were higher in drinkers than in nondrinkers (P < 0.05-0.01). But the ratio of ApoA-I to ApoB in GG genotype was lower in drinkers than in nondrinkers (P < 0.01). Multivariate logistic regression analysis showed that the levels of TC, TG and ApoB were correlated with genotype in nondrinkers (P < 0.05 for all). The levels of TC, LDL-C and ApoB were associated with genotype in drinkers (P < 0.01 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index in both groups. Conclusions This study suggests that the ApoC-III 3238CG heterozygotes benefited more from alcohol consumption than CC and GG homozygotes in increasing serum levels of HDL-C, ApoA-I, and the ratio of ApoA-I to ApoB, and lowering serum levels of TC and TG. PMID:20716347

Interactions of the apolipoprotein C-III 3238C>G polymorphism and alcohol consumption on serum triglyceride levels.

PubMed

Ruixing, Yin; Yiyang, Li; Meng, Li; Kela, Li; Xingjiang, Long; Lin, Zhang; Wanying, Liu; Jinzhen, Wu; Dezhai, Yang; Weixiong, Lin

2010-08-17

Both apolipoprotein (Apo) C-III gene polymorphism and alcohol consumption have been associated with increased serum triglyceride (TG) levels, but their interactions on serum TG levels are not well known. The present study was undertaken to detect the interactions of the ApoC-III 3238C>G (rs5128) polymorphism and alcohol consumption on serum TG levels. A total of 516 unrelated nondrinkers and 514 drinkers aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoC-III 3238C>G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Interactions of the ApoC-III 3238C>G genotype and alcohol consumption was assessed by using a cross-product term between genotypes and the aforementioned factor. Serum total cholesterol (TC), TG, high-density lipoprotein cholesterol (HDL-C), ApoA-I and ApoB levels were higher in drinkers than in nondrinkers (P < 0.05-0.001). There was no significant difference in the genotypic and allelic frequencies between the two groups. Serum TG levels in nondrinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, low-density lipoprotein cholesterol (LDL-C) and ApoB levels in drinkers were higher in GG genotype than in CC or CG genotype (P < 0.01 for all). Serum HDL-C levels in drinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, HDL-C and ApoA-I levels in CC genotype, TC, HDL-C, ApoA-I levels and the ratio of ApoA-I to ApoB in CG genotype, and TC, TG, LDL-C, ApoA-I and ApoB levels in GG genotype were higher in drinkers than in nondrinkers (P < 0.05-0.01). But the ratio of ApoA-I to ApoB in GG genotype was lower in drinkers than in nondrinkers (P < 0.01). Multivariate logistic regression analysis showed that the levels of TC, TG and ApoB were correlated with genotype in nondrinkers (P < 0.05 for all). The levels of TC, LDL-C and ApoB were associated with genotype in drinkers (P < 0.01 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index in both groups. This study suggests that the ApoC-III 3238CG heterozygotes benefited more from alcohol consumption than CC and GG homozygotes in increasing serum levels of HDL-C, ApoA-I, and the ratio of ApoA-I to ApoB, and lowering serum levels of TC and TG.

Reduced representation bisulphite sequencing of the cattle genome reveals DNA methylation patterns

USDA-ARS?s Scientific Manuscript database

Using reduced representation bisulphite sequencing (RRBS), we obtained the first single-base-resolution maps of bovine DNA methylation in ten somatic tissues. In total, we observed 1,868,049 cytosines in the CG-enriched regions. Similar to the methylation patterns in other species, the CG context wa...

Assessment of serum β-hCG and lipid profile in early second trimester as predictors of hypertensive disorders of pregnancy.

PubMed

Revankar, Vijaya M; Narmada, Lavu

2017-09-01

To assess and compare the ability of serum β-human chorionic gonadotropin (β-hCG) and serum lipid profile in early second trimester as predictors of hypertensive disorders of pregnancy. The present hospital-based prospective study was conducted between November 24, 2012, and April 30, 2014, at a tertiary hospital in Mangalore, India. Women of any parity with a pregnancy of 14-20 weeks were included. Venous blood (3 mL) was collected, and serum β-hCG and lipid profile were estimated by enzyme-linked immunosorbent assay and an enzymatic colorimetric test with lipid clearing factor, respectively. A cutoff value of β-hCG for predicting hypertensive disorders was obtained by receiver operating curve analysis. Serum β-hCG was significantly higher among women who subsequently developed hypertension (71 142 IU/L [n=27]) than among those who did not (20 541 IU/L [n=137]; P<0.001). The sensitivity and specificity of serum β-hCG to predict hypertension were 92.6% and 94.9% respectively. The positive and negative predictive values were 78.1% and 98.5%, respectively. Serum β-hCG might be used as a predictor of hypertensive disorders that complicate pregnancy. Dyslipidemia was not found to be a useful marker. © 2017 International Federation of Gynecology and Obstetrics.

Bereavement and Complicated Grief

PubMed Central

Ghesquiere, Angela; Glickman, Kim

2013-01-01

Bereavement is a common experience in adults age 60 and older. Loss of a loved one usually leads to acute grief characterized by yearning and longing, decreased interest in ongoing activities, and frequent thoughts of the deceased. For most, acute grief naturally evolves into a state of integrated grief, where the bereaved is able to reengage with everyday activities and find interest or pleasure. About 7% of bereaved older adults, however, will develop the mental health condition of Complicated Grief (CG). In CG, the movement from acute to integrated grief is derailed, and grief symptoms remain severe and impairing. This article reviews recent publications on the diagnosis of CG, risk factors for the condition, and evidenced-based treatments for CG. Greater attention to complicated grief detection and treatment in older adults is needed. PMID:24068457

Accelerated development and flight evaluation of active controls concepts for subsonic transport aircraft. Volume 2: AFT C.G. simulation and analysis

NASA Technical Reports Server (NTRS)

Urie, D. M.

1979-01-01

Relaxed static stability and stability augmentation with active controls were investigated for subsonic transport aircraft. Analytical and simulator evaluations were done using a contemporary wide body transport as a baseline. Criteria for augmentation system performance and unaugmented flying qualities were evaluated. Augmentation control laws were defined based on selected frequency response and time history criteria. Flying qualities evaluations were conducted by pilots using a moving base simulator with a transport cab. Static margin and air turbulence intensity were varied in test with and without augmentation. Suitability of a simple pitch control law was verified at neutral static margin in cruise and landing flight tasks. Neutral stability was found to be marginally acceptable in heavy turbulence in both cruise and landing conditions.

Patterns of IgE responses to multiple allergen components and clinical symptoms at age 11 years

PubMed Central

Simpson, Angela; Lazic, Nevena; Belgrave, Danielle C.M.; Johnson, Phil; Bishop, Christopher; Mills, Clare; Custovic, Adnan

2015-01-01

Background The relationship between sensitization to allergens and disease is complex. Objective We sought to identify patterns of response to a broad range of allergen components and investigate associations with asthma, eczema, and hay fever. Methods Serum specific IgE levels to 112 allergen components were measured by using a multiplex array (Immuno Solid-phase Allergen Chip) in a population-based birth cohort. Latent variable modeling was used to identify underlying patterns of component-specific IgE responses; these patterns were then related to asthma, eczema, and hay fever. Results Two hundred twenty-one of 461 children had IgE to 1 or more components. Seventy-one of the 112 components were recognized by 3 or more children. By using latent variable modeling, 61 allergen components clustered into 3 component groups (CG1, CG2, and CG3); protein families within each CG were exclusive to that group. CG1 comprised 27 components from 8 plant protein families. CG2 comprised 7 components of mite allergens from 3 protein families. CG3 included 27 components of plant, animal, and fungal origin from 12 protein families. Each CG included components from different biological sources with structural homology and also nonhomologous proteins arising from the same biological source. Sensitization to CG3 was most strongly associated with asthma (odds ratio [OR], 8.20; 95% CI, 3.49-19.24; P < .001) and lower FEV1 (P < .001). Sensitization to CG1 was associated with hay fever (OR, 12.79; 95% CI, 6.84-23.90; P < .001). Sensitization to CG2 was associated with both asthma (OR, 3.60; 95% CI, 2.05-6.29) and hay fever (OR, 2.52; 95% CI, 1.38-4.61). Conclusions Latent variable modeling with a large number of allergen components identified 3 patterns of IgE responses, each including different protein families. In 11-year-old children the pattern of response to components of multiple allergens appeared to be associated with current asthma and hay fever but not eczema. PMID:25935108

Proportion hyperglycosylated hCG: a new test for discriminating gestational trophoblastic diseases.

PubMed

Cole, Laurence A

2014-11-01

Hyperglycosylated human chorionic gonadotropin (hCG) is a variant of hCG with large oligosaccharide side chains. Although hCG is produced by syncytiotrophoblast cells, hyperglycosylated hCG marks cytotrophoblast cell. Hyperglycosylated hCG signals placental implantation. Total hCG in serum and urine is measured by the Siemens Immulite hCG pregnancy test; the result is in milli-international unit per milliliter. Hyperglycosylated hCG is determined by the B152 microtiter plate assay; the result is in nanogram per milliliter. Hyperglycosylated hCG results can be converted to milli-international unit per milliliter equivalents by multiplying by 11. The test measures proportion hyperglycosylated hCG, hyperglycosylated hCG / total hCG. Proportion hyperglycosylated hCG marks cases intent on developing persistent hydatidiform mole (68% detection at 17% false detection). Proportion hyperglycosylated hCG also marks persistent hydatidiform mole (100% detection at 5.1% false detection). Proportion hyperglycosylated hCG distinguishes choriocarcinoma and gestational trophoblastic neoplasm cases, absolutely discriminating aggressive cases and minimally aggressive cases. Proportion hyperglycosylated hCG identifies quiescent gestational trophoblastic disease cases. It recognizes quiescent cases that become persistent disease (100% detection at 0% false positive). Proportion hyperglycosylated hCG is an invaluable test for discriminating gestational trophoblastic diseases.

Effects of Conjugate Gradient Methods and Step-Length Formulas on the Multiscale Full Waveform Inversion in Time Domain: Numerical Experiments

NASA Astrophysics Data System (ADS)

Liu, Youshan; Teng, Jiwen; Xu, Tao; Badal, José; Liu, Qinya; Zhou, Bing

2017-05-01

We carry out full waveform inversion (FWI) in time domain based on an alternative frequency-band selection strategy that allows us to implement the method with success. This strategy aims at decomposing the seismic data within partially overlapped frequency intervals by carrying out a concatenated treatment of the wavelet to largely avoid redundant frequency information to adapt to wavelength or wavenumber coverage. A pertinent numerical test proves the effectiveness of this strategy. Based on this strategy, we comparatively analyze the effects of update parameters for the nonlinear conjugate gradient (CG) method and step-length formulas on the multiscale FWI through several numerical tests. The investigations of up to eight versions of the nonlinear CG method with and without Gaussian white noise make clear that the HS (Hestenes and Stiefel in J Res Natl Bur Stand Sect 5:409-436, 1952), CD (Fletcher in Practical methods of optimization vol. 1: unconstrained optimization, Wiley, New York, 1987), and PRP (Polak and Ribière in Revue Francaise Informat Recherche Opertionelle, 3e Année 16:35-43, 1969; Polyak in USSR Comput Math Math Phys 9:94-112, 1969) versions are more efficient among the eight versions, while the DY (Dai and Yuan in SIAM J Optim 10:177-182, 1999) version always yields inaccurate result, because it overestimates the deeper parts of the model. The application of FWI algorithms using distinct step-length formulas, such as the direct method ( Direct), the parabolic search method ( Search), and the two-point quadratic interpolation method ( Interp), proves that the Interp is more efficient for noise-free data, while the Direct is more efficient for Gaussian white noise data. In contrast, the Search is less efficient because of its slow convergence. In general, the three step-length formulas are robust or partly insensitive to Gaussian white noise and the complexity of the model. When the initial velocity model deviates far from the real model or the data are contaminated by noise, the objective function values of the Direct and Interp are oscillating at the beginning of the inversion, whereas that of the Search decreases consistently.

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.

The effect of practical cooling strategies on physiological response and cognitive function during simulated firefighting tasks

PubMed Central

Hemmatjo, Rasoul; Motamedzade, Majid; Aliabadi, Mohsen; Kalatpour, Omid; Farhadian, Maryam

2017-01-01

Background: Firefighters often perform multiple tasks during firefighting operations under unknown and unpredictable conditions in hot and hostile environments. Methods: In this interventional study each firefighters engaged in 4 conditions: namely (1) no cooling device; control (NC), (2) cooling gel (CG), (3) cool vest (CV), and (4) CG+CV. Cooling effects of the employed interventions were evaluated based on heart rate (HR), temporal temperature (TT), reaction time (RT), and the correct response (CR). Results: HR and TT values for use of CG+CV (147.47 bpm [SD 4.8]; 37.88°C [SD 0.20]) and CV bpm (147.53 [SD 4.67]; 37.90°C [SD 0.22]) were significantly lower than the CG (153.67 bpm [SD 4.82]; 38.10°C [SD 0.22]) and NC (154.4 bpm [SD 4.91]; 38.11°C [SD 0.23]) at the end of the activity. RT and CR for use of CG + CV (389.87 ms [SD 6.12]; 143.53 [SD 1.24]) and CV (389.53 ms [SD 6.24]; 143.47 [SD 1.18]) were significantly higher than the CG (385.73 [SD 7.25] ms; 143.07 [SD 0.88]) and NC (385.67 ms [SD 7.19]; 143.00 [SD 0.84]) at the end of the activity. Conclusion: It is concluded that CV was more effective than the CG in attenuating physiological responses and cognitive functions during firefighting operations. Furthermore, combining CV with CG provides no additional benefit. PMID:28326286

Diamagnetic region(s): structure of the unmagnetized plasma around Comet 67P/CG

NASA Astrophysics Data System (ADS)

Henri, P.; Vallières, X.; Hajra, R.; Goetz, C.; Richter, I.; Glassmeier, K.-H.; Galand, M.; Rubin, M.; Eriksson, A. I.; Nemeth, Z.; Vigren, E.; Beth, A.; Burch, J. L.; Carr, C.; Nilsson, H.; Tsurutani, B.; Wattieaux, G.

2017-07-01

The ESA's comet chaser Rosetta has monitored the evolution of the ionized atmosphere of comet 67P/Churyumov-Gerasimenko (67P/CG) and its interaction with the solar wind, during more than 2 yr. Around perihelion, while the cometary outgassing rate was highest, Rosetta crossed hundreds of unmagnetized regions, but did not seem to have crossed a large-scale diamagnetic cavity as anticipated. Using in situ Rosetta observations, we characterize the structure of the unmagnetized plasma found around comet 67P/CG. Plasma density measurements from RPC-MIP are analysed in the unmagnetized regions identified with RPC-MAG. The plasma observations are discussed in the context of the cometary escaping neutral atmosphere, observed by ROSINA/COPS. The plasma density in the different diamagnetic regions crossed by Rosetta ranges from ˜100 to ˜1500 cm-3. They exhibit a remarkably systematic behaviour that essentially depends on the comet activity and the cometary ionosphere expansion. An effective total ionization frequency is obtained from in situ observations during the high outgassing activity phase of comet 67P/CG. Although several diamagnetic regions have been crossed over a large range of distances to the comet nucleus (from 50 to 400 km) and to the Sun (1.25-2.4 au), in situ observations give strong evidence for a single diamagnetic region, located close to the electron exobase. Moreover, the observations are consistent with an unstable contact surface that can locally extend up to about 10 times the electron exobase.

Long-lasting upper D-region ionospheric modifications caused by intense +/- CG lightning discharges

NASA Astrophysics Data System (ADS)

Haldoupis, Christos

2013-04-01

In a recent Geophysical Research Letter we have presented observations from a single maritime storm showing that intense positive cloud-to-ground (+CG) lightning discharges during nighttime, which trigger both an elve and a sprite, are associated with long-lasting conductivity modifications in the upper D-region ionosphere. The ionospheric disturbances can be observed as perturbations in the amplitude and phase of VLF (very low frequency) signals propagating through or near the disturbed region. They are manifested as LOng Recovery early VLF Events (LOREs) which can last up to 20 - 30 minutes. The same ionospheric modifications may also produce abrupt step-like changes in VLF transmissions which offset signal levels for longer times (>30-60 min). Here we discuss these observations supplementing them with new evidence and some statistics. Among other things, the unpublished results show that very intense (currents > 250-300 kA) CG lightning discharges of either positive or negative polarity are always accompanied mainly by step-like LOREs. The evidence suggests that the electromagnetic pulse (EMP) of a very high peak current CG lightning stroke, which is likely able to produce an elve, produces by electron impact long lasting and spatially extended elevations in electron density at VLF ionospheric reflection heights in the upper D region ionosphere. The results identify a mechanism for the LORE VLF signatures and confirm predictions and postulations that elves may be accompanied by significant and long-lasting electron density perturbations in the upper D- lower E- region ionosphere.

Negative Mood Increases Selective Attention to Negatively Valenced Body Parts in Female Adolescents with Anorexia Nervosa

PubMed Central

Svaldi, Jennifer; Bender, Caroline; Caffier, Detlef; Ivanova, Viliana; Mies, Nina; Fleischhaker, Christian; Tuschen-Caffier, Brunna

2016-01-01

Objective Previous research has yielded evidence of increased attentional processing of negatively valenced body parts in women with anorexia nervosa (AN), especially for those with high depressive symptomatology. The present study extended previous research by implementing an experimental mood manipulation. Method In a within-subjects design, female adolescents with AN (n = 12) and an age matched female control group (CG; n = 12) were given a negative and a positive mood induction at a one-week interval. After each mood induction, participants underwent a 3-min mirror exposure, while their eye movements were recorded. Results After the positive mood induction, both AN and CG participants displayed longer and more frequent gazes towards their self-defined most ugly relative to their self-defined most beautiful body part. However, after the negative mood induction, only females with AN were characterized by increased attention to their most ugly compared to their most beautiful body part, while CG participants’ attention distribution was balanced. Furthermore, in the negative (but not in the positive) mood induction condition gaze frequency and duration towards the most ugly body part was significantly stronger in the AN group relative to the CG. Discussion The results emphasize the role of negative mood in the maintenance of pathological information processing of the self-body. This increased body-related negativity-bias during negative mood may lead to the persistence and aggravation of AN patients’ body image disturbance. PMID:27123587

Identification of a Novel PMS2 Alteration c.505C>G (R169G) In Trans with a PMS2 Pathogenic Mutation in a Patient with Constitutional Mismatch Repair Deficiency

PubMed Central

Mork, Maureen E.; Borras, Ester; Taggart, Melissa W.; Cuddy, Amanda; Bannon, Sarah A.; You, Y. Nancy; Lynch, Patrick M.; Ramirez, Pedro T.; Rodriguez-Bigas, Miguel A.; Vilar, Eduardo

2016-01-01

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare autosomal recessive predisposition to colorectal polyposis and other malignancies, often childhood-onset, that is caused by biallelic inheritance of mutations in the same mismatch repair gene. Here, we describe a patient with a clinical diagnosis of CMMRD based on colorectal polyposis and young-onset endometrial cancer who was identified to have two alterations in trans in PMS2: one known pathogenic mutation (c.1831insA; p.Ile611Asnfs*2) and one novel variant of uncertain significance (c.505C>G; p.Arg169Glu), a missense alteration. We describe the clinical and molecular features in the patient harboring this novel alteration c.505C>G, who meets clinical criteria for CMMRD and exhibits molecular evidence supporting a diagnosis of CMMRD. Although experimental validation is needed to confirm its pathogenicity, PMS2 c.505C>G likely has functional consequences that contributes to our patient's phenotype based on the patient's clinical presentation, tumor studies, and bioinformatics analysis. PMID:27017610

Identification of a novel PMS2 alteration c.505C>G (R169G) in trans with a PMS2 pathogenic mutation in a patient with constitutional mismatch repair deficiency.

PubMed

Mork, Maureen E; Borras, Ester; Taggart, Melissa W; Cuddy, Amanda; Bannon, Sarah A; You, Y Nancy; Lynch, Patrick M; Ramirez, Pedro T; Rodriguez-Bigas, Miguel A; Vilar, Eduardo

2016-10-01

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare autosomal recessive predisposition to colorectal polyposis and other malignancies, often childhood-onset, that is caused by biallelic inheritance of mutations in the same mismatch repair gene. Here, we describe a patient with a clinical diagnosis of CMMRD based on colorectal polyposis and young-onset endometrial cancer who was identified to have two alterations in trans in PMS2: one known pathogenic mutation (c.1831insA; p.Ile611Asnfs*2) and one novel variant of uncertain significance (c.505C>G; p.Arg169Glu), a missense alteration. We describe the clinical and molecular features in the patient harboring this novel alteration c.505C>G, who meets clinical criteria for CMMRD and exhibits molecular evidence supporting a diagnosis of CMMRD. Although experimental validation is needed to confirm its pathogenicity, PMS2 c.505C>G likely has functional consequences that contributes to our patient's phenotype based on the patient's clinical presentation, tumor studies, and bioinformatics analysis.

Characterisation and functional comparison of single-CRD and multidomain containing galectins CgGal-2 and CgGal-3 from oyster Crassostrea gigas.

PubMed

Huang, Mengmeng; Zhou, Tao; Wu, Yuehong; Fei, Hui; Wang, Gaoyang; Li, Zhi; Lei, Yutong; Liu, Qian; Sun, Cong; Lv, Zhengbing; Xu, Xue-Wei

2018-04-18

Galectins are β-galactoside binding lectins that play crucial roles in innate immunity in vertebrates and invertebrates through their conserved carbohydrate-recognition domains (CRDs). In the present study, single- and four-CRD-containing galectins were identified in oyster Crassostrea gigas (designated CgGal-2 and CgGal-3). The open reading frames (ORFs) of CgGal-2 and CgGal-3 encode polypeptides of 200 and 555 amino acids, respectively. All CRDs of CgGal-3 include two consensus motifs essential for ligand-binding, and a novel motif is present in CgGal-2. Pathogen-associated molecular pattern (PAMP) profiles were determined for recombinant rCgGal-2 and rCgGal-3, and rCgGal-2 displayed low binding affinity for PAMPs, while rCgGal-3 bound various PAMPs including glucan, lipopolysaccharide (LPS), and peptidoglycan (PGN) with relatively high affinity. Furthermore, rCgGal-2 and rCgGal-3 exhibited different microbe binding profiles; rCgGal-2 bound to Gram-negative bacteria (Escherichia coli and Vibrio vulnificus) and fungi (Saccharomyces cerevisiae and Pichia pastoris), while rCgGal-3 bound to these microbes but also to Gram-positive bacteria (Micrococcus luteus). In addition, rCgGal-3 possessed microbial agglutinating activity and coagulation activity against fungi and erythrocytes, respectively, but rCgGal-2 lacked any agglutinating activity. Carbohydrate binding specificity analysis showed that rCgGal-3 specifically bound D-galactose. Furthermore, rCgGal-2 and rCgGal-3 functioned as opsonin participating in the clearance against invaders in C. gigas. Thus, CgGal-2 with one CRD and CgGal-3 with four CRDs are new members of the galectin family involved in immune responses against bacterial infection. Differences in the organisation and amino acid sequences of CRDs may affect their specificity and affinity for nonself substances. Copyright © 2018 Elsevier Ltd. All rights reserved.

A modified form of conjugate gradient method for unconstrained optimization problems

NASA Astrophysics Data System (ADS)

Ghani, Nur Hamizah Abdul; Rivaie, Mohd.; Mamat, Mustafa

2016-06-01

Conjugate gradient (CG) methods have been recognized as an interesting technique to solve optimization problems, due to the numerical efficiency, simplicity and low memory requirements. In this paper, we propose a new CG method based on the study of Rivaie et al. [7] (Comparative study of conjugate gradient coefficient for unconstrained Optimization, Aus. J. Bas. Appl. Sci. 5(2011) 947-951). Then, we show that our method satisfies sufficient descent condition and converges globally with exact line search. Numerical results show that our proposed method is efficient for given standard test problems, compare to other existing CG methods.

Stable Epigenetic Variants Selected from an Induced Hypomethylated Fragaria vesca Population.

PubMed

Xu, Jihua; Tanino, Karen K; Robinson, Stephen J

2016-01-01

Epigenetic inheritance was transmitted through selection over five generations of extreme early, but not late flowering time phenotypic lines in Fragaria vesca . Epigenetic variation was initially artificially induced using the DNA demethylation reagent 5-azacytidine (5-azaC). It is the first report to explore epigenetic variant selection and phenotypic trait inheritance in strawberry. Transmission frequency of these traits was determined across generations. The early flowering (EF4) and late stolon (LS) phenotypic traits were successfully transmitted across five and three generations through meiosis, respectively. Stable mitotic transmission of the early flowering phenotype was also demonstrated using clonal daughters derived from the 4th Generation (S4) mother plant. In order to further explore the DNA methylation patterns underlying the early flowering trait, the standard MSAP method using isoschizomers Hpa II/Msp I, and newly modified MSAP method using isoschizomers Tfi I/Pfe I which detected DNA methylation at CG, CHG, CHH sites were used in two early flowering lines, EF lines 1 (P2) and EF lines 2 (P3), and control lines (P1). A significant reduction in the number of fully-methylated bands was detected in P2 and P3 when compared to P1 using the novel MSAP method. In the standard MSAP, the symmetric CG and CHG methylation was maintained over generations in the early flowering lines based on the clustering in P2 and P3, the novel MSAP approach revealed the asymmetric CHH methylation pattern was not maintained over generations. This study provides evidence of stable selection of phenotypic traits, particularly early flowering through both meiosis and mitosis, which is meaningful to both breeding programs and commercial horticulture. The maintenance in CG and CHG methylation over generations suggests the early flowering phenotype might be related to DNA methylation alterations at the CG or CHG sites. Finally, this work provides a new approach for studying the role of epigenetics on complex quantitative trait improvement in strawberry, as well as providing a tool to expand phenotypic diversity and expedite potential new horticulture cultivar releases through either seed or vegetative propagation.

Trinucleotide's quadruplet symmetries and natural symmetry law of DNA creation ensuing Chargaff's second parity rule.

PubMed

Rosandić, Marija; Vlahović, Ines; Glunčić, Matko; Paar, Vladimir

2016-07-01

For almost 50 years the conclusive explanation of Chargaff's second parity rule (CSPR), the equality of frequencies of nucleotides A=T and C=G or the equality of direct and reverse complement trinucleotides in the same DNA strand, has not been determined yet. Here, we relate CSPR to the interstrand mirror symmetry in 20 symbolic quadruplets of trinucleotides (direct, reverse complement, complement, and reverse) mapped to double-stranded genome. The symmetries of Q-box corresponding to quadruplets can be obtained as a consequence of Watson-Crick base pairing and CSPR together. Alternatively, assuming Natural symmetry law for DNA creation that each trinucleotide in one strand of DNA must simultaneously appear also in the opposite strand automatically leads to Q-box direct-reverse mirror symmetry which in conjunction with Watson-Crick base pairing generates CSPR. We demonstrate quadruplet's symmetries in chromosomes of wide range of organisms, from Escherichia coli to Neanderthal and human genomes, introducing novel quadruplet-frequency histograms and 3D-diagrams with combined interstrand frequencies. These "landscapes" are mutually similar in all mammals, including extinct Neanderthals, and somewhat different in most of older species. In human chromosomes 1-12, and X, Y the "landscapes" are almost identical and slightly different in the remaining smaller and telocentric chromosomes. Quadruplet frequencies could provide a new robust tool for characterization and classification of genomes and their evolutionary trajectories.

Massage and Storytelling Reduce Aggression and Improve Academic Performance in Children Attending Elementary School

PubMed Central

Gonçalves, Lia Lopes; de Almeida, Maria Helena Morgani

2017-01-01

Background Aggressive behaviors must be addressed in elementary schools. Massage and storytelling can be strategies to deal with aggression because both involve experience exchange and social interaction. Both can decrease stress and anxiety and increase self-esteem. Objective To evaluate the effect of two interventions (massage and storytelling) on aggressive behaviors and academic performance of elementary school children. Method Three groups (n = 35 children in each group) of the second grade participated (aged 6.5–8.1 years). One group received ten extra classes of massage (MG), another group received extra classes of storytelling (SG), and the control group received extra classes of random subjects (CG). Extra classes lasted for 50 minutes, once a week. Aggressive behaviors were recorded on diaries, by the teachers and the coordinator. The frequency of aggressive behaviors and the academic performance of MG, SG, and CG were observed for six months and the groups were compared. Findings ANOVAs evidenced that MG and SG, but not CG, showed a reduction in aggressive behaviors registered by the teachers and coordinator, after the intervention. Academic performance of MG and SC improved after the intervention (p < 0.05). PMID:29097967

Digital computer program DF1758 fully coupled natural frequencies and mode shapes of a helicopter rotor blade

NASA Technical Reports Server (NTRS)

Bennett, R. L.

1975-01-01

The analytical techniques and computer program developed in the fully-coupled rotor vibration study are described. The rotor blade natural frequency and mode shape analysis was implemented in a digital computer program designated DF1758. The program computes collective, cyclic, and scissor modes for a single blade within a specified range of frequency for specified values of rotor RPM and collective angle. The analysis includes effects of blade twist, cg offset from reference axis, and shear center offset from reference axis. Coupled inplane, out-of-plane, and torsional vibrations are considered. Normalized displacements, shear forces and moments may be printed out and Calcomp plots of natural frequencies as a function of rotor RPM may be produced.

Telephone-Based Adiposity Prevention for Families with Overweight Children (T.A.F.F.-Study): One Year Outcome of a Randomized, Controlled Trial

PubMed Central

Markert, Jana; Herget, Sabine; Petroff, David; Gausche, Ruth; Grimm, Andrea; Kiess, Wieland; Blüher, Susann

2014-01-01

The one-year outcome of the randomized controlled T.A.F.F. (Telephone based Adiposity prevention For Families) study is presented. Screening of overweight (BMI-SDS > 90th centile) children 3.5–17.4 years was performed via the German CrescNet database, and candidates were randomized to an intervention group (IG) and control group (CG). The intervention consisted of computer-aided telephone counselling for one year, supported by mailed newsletters. The primary endpoint was change in BMI-SDS; secondary endpoints were eating behavior, physical activity, media consumption, quality of life. Data from 289 families (145 IG (51% females); 144 CG (50% females)) were analyzed (Full Analysis Set: FAS; Per Protocol Set: PPS). Successful intervention was defined as decrease in BMI-SDS ≥ 0.2. In the FAS, 21% of the IG was successful as compared to 16% from the CG (95% CI for this difference: (−4, 14), p = 0.3, mean change in BMI-SDS: −0.02 for IG vs. 0.02 for CG; p = 0.4). According to the PPS, however, the success rate was 35% in the IG compared to 19% in the CG (mean change in BMI-SDS: −0.09 for IG vs. 0.02 for CG; p = 0.03). Scores for eating patterns (p = 0.01), media consumption (p = 0.007), physical activity (p = 9 × 10−9), quality of life (p = 5 × 10−8) decreased with age, independent of group or change in BMI-SDS. We conclude that a telephone-based obesity prevention program suffers from well-known high attrition rates so that its effectiveness could only be shown in those who adhered to completion. The connection between lifestyle and weight status is not simple and requires further research to better understand. PMID:25286167

Impact of ENPP1 K121Q on change of insulin resistance after web-based intervention in Korean men with diabetes and impaired fasting glucose.

PubMed

Kang, Ji Yeon; Sung, Sook Hee; Lee, Yeon Ju; Choi, Tae In; Choi, Seung Jin

2014-10-01

Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) gene has been studied in relation to type 2 diabetes mellitus (T2DM) and insulin resistance (IR). We hypothesized that the difference in genotype may be one of the factors that affect the outcome of intervention. We genotyped 448 men with fasting glucose≥5.6 mM/L, including 371 in subjects with K allele (KK) (69 control group [CG]; and 302 intervention group [IG]) and 77 in subjects with Q allele (KQ+QQ) (13 CG and 64 IG). The web-based intervention based on a lifestyle modification was delivered by e-mail once a month for 10 months. In the KK, IG demonstrated significantly decreased levels of fasting serum insulin (FSI) as compared to CG and homeostasis model of assessment of insulin resistance (HOMA-IR). In the KQ+QQ IG group, hemoglobin A1c (HbA1c), FSI and HOMA-IR were significantly decreased, and showed further reduction in the HOMA-IR than KQ+QQ CG. After analysis of covariance, K121Q did significantly influence the change of HbA1c in CG after appropriate adjustment. In a multivariate model, BMI change predicted HOMA-IR change (adjusted β=0.801; P=0.022) in KK IG subjects with T2DM. ENPP1 K121Q did not influence the change in IR. However, individuals with T2DM carrying the K121 variant are very responsive to the effect of BMI reduction on HOMA-IR.

Effect of Binary Source Companions on the Microlensing Optical Depth Determination toward the Galactic Bulge Field

NASA Astrophysics Data System (ADS)

Han, Cheongho

2005-11-01

Currently, gravitational microlensing survey experiments toward the Galactic bulge field use two different methods of minimizing the blending effect for the accurate determination of the optical depth τ. One is measuring τ based on clump giant (CG) source stars, and the other is using ``difference image analysis'' (DIA) photometry to measure the unblended source flux variation. Despite the expectation that the two estimates should be the same assuming that blending is properly considered, the estimates based on CG stars systematically fall below the DIA results based on all events with source stars down to the detection limit. Prompted by the gap, we investigate the previously unconsidered effect of companion-associated events on τ determination. Although the image of a companion is blended with that of its primary star and thus not resolved, the event associated with the companion can be detected if the companion flux is highly magnified. Therefore, companions work effectively as source stars to microlensing, and thus the neglect of them in the source star count could result in a wrong τ estimation. By carrying out simulations based on the assumption that companions follow the same luminosity function as primary stars, we estimate that the contribution of the companion-associated events to the total event rate is ~5fbi% for current surveys and can reach up to ~6fbi% for future surveys monitoring fainter stars, where fbi is the binary frequency. Therefore, we conclude that the companion-associated events comprise a nonnegligible fraction of all events. However, their contribution to the optical depth is not large enough to explain the systematic difference between the optical depth estimates based on the two different methods.

A Generic Force Field for Protein Coarse-Grained Molecular Dynamics Simulation

PubMed Central

Gu, Junfeng; Bai, Fang; Li, Honglin; Wang, Xicheng

2012-01-01

Coarse-grained (CG) force fields have become promising tools for studies of protein behavior, but the balance of speed and accuracy is still a challenge in the research of protein coarse graining methodology. In this work, 20 CG beads have been designed based on the structures of amino acid residues, with which an amino acid can be represented by one or two beads, and a CG solvent model with five water molecules was adopted to ensure the consistence with the protein CG beads. The internal interactions in protein were classified according to the types of the interacting CG beads, and adequate potential functions were chosen and systematically parameterized to fit the energy distributions. The proposed CG force field has been tested on eight proteins, and each protein was simulated for 1000 ns. Even without any extra structure knowledge of the simulated proteins, the Cα root mean square deviations (RMSDs) with respect to their experimental structures are close to those of relatively short time all atom molecular dynamics simulations. However, our coarse grained force field will require further refinement to improve agreement with and persistence of native-like structures. In addition, the root mean square fluctuations (RMSFs) relative to the average structures derived from the simulations show that the conformational fluctuations of the proteins can be sampled. PMID:23203075

The granulocytes are the main immunocompetent hemocytes in Crassostrea gigas.

PubMed

Wang, Weilin; Li, Meijia; Wang, Lingling; Chen, Hao; Liu, Zhaoqun; Jia, Zhihao; Qiu, Limei; Song, Linsheng

2017-02-01

Hemocytes comprise diverse cell types with morphological and functional heterogeneity and play indispensable roles in immunological homeostasis of invertebrates. The morphological classification of different hemocytes in mollusk has been studied since the 1970's, yet the involvement of the different sub-populations in immune functions is far from clear. In the present study, three types of hemocytes were morphologically identified and separated as agranulocytes, semi-granulocytes and granulocytes by flow cytometry and Percoll ® density gradient centrifugation. The granulocytes were characterized functionally as the main phagocytic and encapsulating population, while semi-granulocytes and agranulocytes exhibited low or no such capacities, respectively. Meanwhile, the lysosome activity and the productions of ROS and NO were all mainly concentrated in granulocytes under both normal and immune-activated situations. Further, the mRNA transcripts of some immune related genes, including CgTLR, CgClathrin, CgATPeV, CgLysozyme, CgDefensin and CgIL-17, were mainly expressed in granulocytes, lower in semi-granulocytes and agranulocytes. These results collectively suggested that the granulocytes were the main immunocompetent hemocytes in oyster C. gigas, and a differentiation relationship among these three sub-population hemocytes was inferred based on the gradual changes in morphological, functional and molecular features. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ecology of Ephemeroptera, Plecoptera and Trichoptera (Insecta) in Rivers of the Gunung Jerai Forest Reserve: Diversity and Distribution of Functional Feeding Groups

PubMed Central

Hamid, Suhaila Ab; Md Rawi, Che Salmah

2014-01-01

A field study was performed to describe the functional feeding groups (FFGs) of Ephemeroptera, Plecoptera and Trichoptera (EPT) in the Tupah, Batu Hampar and Teroi Rivers in the Gunung Jerai Forest Reserve (GJFR), Kedah, Malaysia. Twenty-nine genera belonging to 19 families were identified. The EPTs were classified into five FFGs: collector-gatherers (CG), collector-filterers (CF), shredders (SH), scrapers (SC) and predators (P). In this study, CG and CF were the dominant groups inhabiting all three rivers. Ephemeroptera dominated these rivers due to their high abundance, and they were also the CG (90.6%). SC were the lowest in abundance among all groups. Based on the FFGs, the Teroi River was suitable for CG, whereas the Tupah and Batu Hampar Rivers were suitable for CG and CF. The distribution of FFGs differed among the rivers (CG, χ2 = 23.6, p = 0.00; SH, χ2 = 10.02, p = 0.007; P, χ2 = 25.54, p = 0.00; CF, χ2 = 21.95, p = 0.00; SC, χ2 = 9.31, p = 0.01). These findings indicated that the FFGs found in rivers of the GJFR represent high river quality. PMID:25210588

Somatostatin analogs and disease control in castration-resistant prostate cancer: different biological behavior? Case series and review of the literature.

PubMed

D'Angelillo, Rolando Maria; Greco, Carlo; Fiore, Michele; Ippolito, Edy; Eolo Trodella, Luca; Iurato, Aurelia; Molfese, Elisabetta; Ramella, Sara; Trodella, Lucio

2014-01-01

Castration-resistant prostate cancer is a recent biological behavior where disease can elude androgen deprivation therapy (ADT). Several pathways have been described, including neuroendocrine dedifferentiation. Patients with neuroendocrine dedifferentiation show an increase in chromogranin A (CgA) along with a PSA increase. Our aim was to evaluate the response of patients with castration-resistant prostate cancer and high CgA serum levels after treatment with inhibitors of neuroendocrine cells (somatostatin analogs) in combination with ADT. From January 2009 to April 2011, 10 patients with castration-resistant prostate cancer and rising PSA levels along with a CgA increase were evaluated. The therapy was based on somatostatin analogs and LHRH anologs. Total PSA and CgA were measured every 2 months. In 9 of the 10 patients, a reduction of the values of pre-treatment CgA was detected, while a reduction of PSA was found in 8 patients. No grade 2 or higher toxicity was recorded. Only 3 patients had grade 1 gastrointestinal toxicity. Time to progression was 13 months. Therapy with somatostatin analogs could increase the therapeutic window of ADT with a low toxicity profile in a subpopulation of patients with castration-resistant prostate cancer who experience a rise in CgA due to neuroendocrine regulation.

Missing value imputation in DNA microarrays based on conjugate gradient method.

PubMed

Dorri, Fatemeh; Azmi, Paeiz; Dorri, Faezeh

2012-02-01

Analysis of gene expression profiles needs a complete matrix of gene array values; consequently, imputation methods have been suggested. In this paper, an algorithm that is based on conjugate gradient (CG) method is proposed to estimate missing values. k-nearest neighbors of the missed entry are first selected based on absolute values of their Pearson correlation coefficient. Then a subset of genes among the k-nearest neighbors is labeled as the best similar ones. CG algorithm with this subset as its input is then used to estimate the missing values. Our proposed CG based algorithm (CGimpute) is evaluated on different data sets. The results are compared with sequential local least squares (SLLSimpute), Bayesian principle component analysis (BPCAimpute), local least squares imputation (LLSimpute), iterated local least squares imputation (ILLSimpute) and adaptive k-nearest neighbors imputation (KNNKimpute) methods. The average of normalized root mean squares error (NRMSE) and relative NRMSE in different data sets with various missing rates shows CGimpute outperforms other methods. Copyright © 2011 Elsevier Ltd. All rights reserved.

Four base recognition by triplex-forming oligonucleotides at physiological pH

PubMed Central

Rusling, David A.; Powers, Vicki E. C.; Ranasinghe, Rohan T.; Wang, Yang; Osborne, Sadie D.; Brown, Tom; Fox, Keith R.

2005-01-01

We have achieved recognition of all 4 bp by triple helix formation at physiological pH, using triplex-forming oligonucleotides that contain four different synthetic nucleotides. BAU [2′-aminoethoxy-5-(3-aminoprop-1-ynyl)uridine] recognizes AT base pairs with high affinity, MeP (3-methyl-2 aminopyridine) binds to GC at higher pHs than cytosine, while APP (6-(3-aminopropyl)-7-methyl-3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one) and S [N-(4-(3-acetamidophenyl)thiazol-2-yl-acetamide)] bind to CG and TA base pairs, respectively. Fluorescence melting and DNase I footprinting demonstrate successful triplex formation at a 19mer oligopurine sequence that contains two CG and two TA interruptions. The complexes are pH dependent, but are still stable at pH 7.0. BAU, MeP and APP retain considerable selectivity, and single base pair changes opposite these residues cause a large reduction in affinity. In contrast, S is less selective and tolerates CG pairs as well as TA. PMID:15911633

Detection of buried targets using a new enhanced very early time electromagnetic (VETEM) prototype system

USGS Publications Warehouse

Cui, T.J.; Chew, W.C.; Aydiner, A.A.; Wright, D.L.; Smith, D.V.

2001-01-01

In this paper, numerical simulations of a new enhanced very early time electromagnetic (VETEM) prototype system are presented, where a horizontal transmitting loop and two horizontal receiving loops are used to detect buried targets, in which three loops share the same axis and the transmitter is located at the center of receivers. In the new VETEM system, the difference of signals from two receivers is taken to eliminate strong direct-signals from the transmitter and background clutter and furthermore to obtain a better SNR for buried targets. Because strong coupling exists between the transmitter and receivers, accurate analysis of the three-loop antenna system is required, for which a loop-tree basis function method has been utilized to overcome the low-frequency breakdown problem. In the analysis of scattering problem from buried targets, a conjugate gradient (CG) method with fast Fourier transform (FFT) is applied to solve the electric field integral equation. However, the convergence of such CG-FFT algorithm is extremely slow at very low frequencies. In order to increase the convergence rate, a frequency-hopping approach has been used. Finally, the primary, coupling, reflected, and scattered magnetic fields are evaluated at receiving loops to calculate the output electric current. Numerous simulation results are given to interpret the new VETEM system. Comparing with other single-transmitter-receiver systems, the new VETEM has better SNR and ability to reduce the clutter.

Human Chorionic Gonadotropin Stimulation Test in Prepubertal Children with Micropenis Can Accurately Predict Leydig Cell Function in Pubertal or Postpubertal Adolescents.

PubMed

Ishii, Tomohiro; Matsuo, Nobutake; Sato, Seiji; Ogata, Tsutomu; Tamai, Shinya; Anzo, Makoto; Kamimaki, Tsutomu; Sasaki, Goro; Inokuchi, Mikako; Hori, Naoaki; Amano, Naoko; Narumi, Satoshi; Shibata, Hironori; Hasegawa, Tomonobu

2015-01-01

To evaluate the accuracy of the human chorionic gonadotropin (hCG) stimulation test in children with micropenis in predicting later Leydig cell function. We conducted a retrospective investigation of testosterone response to a 3-day hCG test (3,000 IU/m2/day) in prepuberty to indicate the need for hormone replacement therapy (HRT) in adolescence. Fifty Japanese boys (range, 0.8-15.4 years of age; median, 8.9) with micropenis were enrolled. Thirty-four spontaneously developed puberty and preserved the ability of testosterone production (group 1), while 16 did not develop any pubertal signs without HRT (group 2). Serum testosterone levels after the hCG test (post-hCG T) in group 2 (range, <0.05-1.1 ng/ml; median, 0.24) were significantly lower than in group 1 (range, 0.5-8.7 ng/ml; median, 2.4; p < 0.0001). Based on true positives who required continuous HRT, the area under the receiver-operating characteristics curve for post-hCG T was 0.983 [95% confidence interval (CI), 0.90-1.00]. The post-hCG T cut-off level corresponding to the Youden index was 1.1 ng/ml (95% CI, 1.0-1.1), with a sensitivity of 100.0% (95% CI, 79.4-100.0) and a specificity of 94.1% (95% CI, 80.3-99.3). The hCG test in prepubertal children with micropenis can be useful for predicting Leydig cell function in pubertal or postpubertal adolescents. The post-hCG T cut-off level of 1.1 ng/ml is recommended to screen for those who will likely require HRT for pubertal development. © 2015 S. Karger AG, Basel.

Human LH and hCG stimulate differently the early signalling pathways but result in equal testosterone synthesis in mouse Leydig cells in vitro.

PubMed

Riccetti, Laura; De Pascali, Francesco; Gilioli, Lisa; Potì, Francesco; Giva, Lavinia Beatrice; Marino, Marco; Tagliavini, Simonetta; Trenti, Tommaso; Fanelli, Flaminia; Mezzullo, Marco; Pagotto, Uberto; Simoni, Manuela; Casarini, Livio

2017-01-05

Human luteinizing hormone (LH) and chorionic gonadotropin (hCG) are glycoprotein hormones regulating development and reproductive functions by acting on the same receptor (LHCGR). We compared the LH and hCG activity in gonadal cells from male mouse in vitro, i.e. primary Leydig cells, which is a common tool used for gonadotropin bioassay. Murine Leydig cells are naturally expressing the murine LH receptor (mLhr), which binds human LH/hCG. Cultured Leydig cells were treated by increasing doses of recombinant LH and hCG, and cell signaling, gene expression and steroid synthesis were evaluated. We found that hCG is about 10-fold more potent than LH in cAMP recruitment, and slightly but significantly more potent on cAMP-dependent Erk1/2 phosphorylation. However, no significant differences occur between LH and hCG treatments, measured as activation of downstream signals, such as Creb phosphorylation, Stard1 gene expression and testosterone synthesis. These data demonstrate that the responses to human LH/hCG are only quantitatively and not qualitatively different in murine cells, at least in terms of cAMP and Erk1/2 activation, and equal in activating downstream steroidogenic events. This is at odds with what we previously described in human primary granulosa cells, where LHCGR mediates a different pattern of signaling cascades, depending on the natural ligand. This finding is relevant for gonadotropin quantification used in the official pharmacopoeia, which are based on murine, in vivo bioassay and rely on the evaluation of long-term, testosterone-dependent effects mediated by rodent receptor.

Three-dimensional kinematic analysis of upper and lower limb motion during gait of post-stroke patients

PubMed Central

Carmo, A.A.; Kleiner, A.F.R.; Lobo da Costa, P.H.; Barros, R.M.L.

2012-01-01

The aim of this study was to analyze the alterations of arm and leg movements of patients during stroke gait. Joint angles of upper and lower limbs and spatiotemporal variables were evaluated in two groups: hemiparetic group (HG, 14 hemiparetic men, 53 ± 10 years) and control group (CG, 7 able-bodied men, 50 ± 4 years). The statistical analysis was based on the following comparisons (P ≤ 0.05): 1) right versus left sides of CG; 2) affected (AF) versus unaffected (UF) sides of HG; 3) CG versus both the affected and unaffected sides of HG, and 4) an intracycle comparison of the kinematic continuous angular variables between HG and CG. This study showed that the affected upper limb motion in stroke gait was characterized by a decreased range of motion of the glenohumeral (HG: 6.3 ± 4.5, CG: 20.1 ± 8.2) and elbow joints (AF: 8.4 ± 4.4, UF: 15.6 ± 7.6) on the sagittal plane and elbow joint flexion throughout the cycle (AF: 68.2 ± 0.4, CG: 46.8 ± 2.7). The glenohumeral joint presented a higher abduction angle (AF: 14.2 ± 1.6, CG: 11.5 ± 4.0) and a lower external rotation throughout the cycle (AF: 4.6 ± 1.2, CG: 22.0 ± 3.0). The lower limbs showed typical alterations of the stroke gait patterns. Thus, the changes in upper and lower limb motion of stroke gait were identified. The description of upper limb motion in stroke gait is new and complements gait analysis. PMID:22473324

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame.

PubMed

Marotta, Vincenzo; Zatelli, Maria Chiara; Sciammarella, Concetta; Ambrosio, Maria Rosaria; Bondanelli, Marta; Colao, Annamaria; Faggiano, Antongiulio

2018-01-01

Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up and definition of treatment strategy. This review is focused on chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assays still lack standardization, thus hampering not only clinical management but also the comparison between different analyses. In the diagnostic setting, clinical utility of CgA is limited as hampered by (a) the variety of oncological and non-oncological conditions affecting marker levels, which impairs specificity; (b) the fact that 30-50% of NENs show normal CgA, which impairs sensitivity. Regarding the prognostic phase, there is prospective evidence which demonstrates that advanced NENs secreting CgA have poorer outcome, as compared with those showing non-elevated marker levels. Although the identification of cut-offs allowing a proper risk stratification of CgA-secreting patients has not been performed, this represents the most important clinical application of the marker. By contrast, based on prospective studies, the trend of elevated circulating CgA does not represent a valid indicator of morphological evolution and has therefore no utility for the follow-up phase. Ultimately, current knowledge about the role of the marker for the definition of treatment strategy is poor and is limited by the small number of available studies, their prevalent retrospective nature and the absence of control groups of untreated subjects. © 2018 Society for Endocrinology.

Comparisons of Lower Cambrian ( ) Chilhowee Group siliciclastics of the frontal Blue Ridge with possible equivalents in the central Blue Ridge and basement massifs in the southern Appalachians

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

Aylor, J.G. Jr.; Tull, J.F.

1993-03-01

The Lower Cambrian Chilhowee Group (CG) along the Blue Ridge (BR) foreland boundary may also be represented in more internal parts of the orogen. The relative palinspastic positions of these more internal CG( ) sequences are poorly constrained, but they are believed to represent more outboard facies than those along the frontal BR. Although correlation with CG rocks of the frontal BR is indefinite due to metamorphism and polydeformation, correlative sequences may include the cover of the Corbin and Salem Church gneisses (Pinelog Fm.), Grandfather Mountain window, Murphy belt (MB) (Hiwassee River Group), Tallulah and Toxaway domes (TTD) (quartzite-schist membermore » of the Tallulah Falls Fm.), Pine Mountain window (Hollis Quartzite), and Sauratown Mountains window (Hogan Creek and Sauratown Fms.). The CG is generally bounded on the west by the Great Smoky fault. Siliciclastics of the CG represent stacked, coarsening upward sequences, separated by transgressive facies, and capped by a highstand of the Shady Dolomite or its equivalents. CG correlations in the Kahatchee Mountain Group of the Talladega belt and the siliciclastics in the Hiwassee River Group of the MB are supported by fossil constraints. Other units are correlated with CG based upon intimate associations with marble believed to be equivalent to the overlying Lower Cambrian Shady Dolomite, or upon presumed uncomformable relationships above Grenville basement. The CG averages about 1,260 meters thickness at the frontal BR, whereas lower siliciclastics in the MB average 1,830 meters. The Pinelog Fm. is up to 600 meters thick. The Hollis Quartzite is approximately 325 meters thick, and the estimated thickness of the quartz-schist member at Tallulah Falls is up to 900 meters. More distal siliciclastics of the central BR in the MB and distal siliciclastics overlying basement were deposited farther out on the shelf as stratigraphic, litho-facies equivalents of shallower marine and continental deposits of the CG.« less

Coarse-Graining of Polymer Dynamics via Energy Renormalization

NASA Astrophysics Data System (ADS)

Xia, Wenjie; Song, Jake; Phelan, Frederick; Douglas, Jack; Keten, Sinan

The computational prediction of the properties of polymeric materials to serve the needs of materials design and prediction of their performance is a grand challenge due to the prohibitive computational times of all-atomistic (AA) simulations. Coarse-grained (CG) modeling is an essential strategy for making progress on this problem. While there has been intense activity in this area, effective methods of coarse-graining have been slow to develop. Our approach to this fundamental problem starts from the observation that integrating out degrees of freedom of the AA model leads to a strong modification of the configurational entropy and cohesive interaction. Based on this observation, we propose a temperature-dependent systematic renormalization of the cohesive interaction in the CG modeling to recover the thermodynamic modifications in the system and the dynamics of the AA model. Here, we show that this energy renormalization approach to CG can faithfully estimate the diffusive, segmental and glassy dynamics of the AA model over a large temperature range spanning from the Arrhenius melt to the non-equilibrium glassy states. Our proposed CG strategy offers a promising strategy for developing thermodynamically consistent CG models with temperature transferability.

Two-bead polarizable water models combined with a two-bead multipole force field (TMFF) for coarse-grained simulation of proteins.

PubMed

Li, Min; Zhang, John Z H

2017-03-08

The development of polarizable water models at coarse-grained (CG) levels is of much importance to CG molecular dynamics simulations of large biomolecular systems. In this work, we combined the newly developed two-bead multipole force field (TMFF) for proteins with the two-bead polarizable water models to carry out CG molecular dynamics simulations for benchmark proteins. In our simulations, two different two-bead polarizable water models are employed, the RTPW model representing five water molecules by Riniker et al. and the LTPW model representing four water molecules. The LTPW model is developed in this study based on the Martini three-bead polarizable water model. Our simulation results showed that the combination of TMFF with the LTPW model significantly stabilizes the protein's native structure in CG simulations, while the use of the RTPW model gives better agreement with all-atom simulations in predicting the residue-level fluctuation dynamics. Overall, the TMFF coupled with the two-bead polarizable water models enables one to perform an efficient and reliable CG dynamics study of the structural and functional properties of large biomolecules.

Negative βhCG and Molar Pregnancy: The Hook Effect.

PubMed

Lobo Antunes, Isabel; Curado, Joana; Quintas, Ana; Pereira, Alcides

2017-09-29

Molar pregnancy, included in gestational trophoblastic disease, is a benign pathology with ability to metastasize, usually occurring with excessively high βhCG levels. Clinical scenario is usually a woman in extremes of reproductive age presenting with amenorrhoea, pain and vaginal blood loss; signs derived from high βhCG levels may be present (hyperthyroidism, hyperemesis). Diagnosis is based on a positive pregnancy test - usually a qualitative urinary test. The limitation of this test results from its inability to become positive in presence of markedly high levels of βhCG, saturating the antigens used - known as the 'hook effect'. With the widespread use of gynaecological ultrasound cases of molar pregnancy have been diagnosed in timely fashion. We describe a case referred as a degenerating fibroid, with a negative urinary pregnancy test. Transvaginal ultrasound was highly suggestive of molar pregnancy, which was confirmed with a quantitative βhCG test, allowing for timely treatment. The importance of a high index of suspicion for this pathology is tremendous to avoid the devastating consequences of a delayed diagnosis.

Cascadia GeoSciences: Community-Based Earth Science Research Focused on Geologic Hazard Assessment and Environmental Restoration.

NASA Astrophysics Data System (ADS)

Williams, T. B.; Patton, J. R.; Leroy, T. H.

2007-12-01

Cascadia GeoSciences (CG) is a new non-profit membership governed corporation whose main objectives are to conduct and promote interdisciplinary community based earth science research. The primary focus of CG is on geologic hazard assessment and environmental restoration in the Western U.S. The primary geographic region of interest is Humboldt Bay, NW California, within the southern Cascadia subduction zone (SCSZ). This region is the on-land portion of the accretionary prism to the SCSZ, a unique and exciting setting with numerous hazards in an active, dynamic geologic environment. Humboldt Bay is also a region rich in history. Timber harvesting has been occurring in California's coastal forestlands for approximately 150 years. Timber products transported with ships and railroads from Mendocino and Humboldt Counties helped rebuild San Francisco after the 1906 earthquake. Historic land-use of this type now commonly requires the services of geologists, engineers, and biologists to restore road networks as well as provide safe fish passage. While Humboldt Bay is a focus of some of our individual research goals, we welcome regional scientists to utilize CG to support its mission while achieving their goals. An important function of CG is to provide student opportunities in field research. One of the primary charitable contributions of the organization is a student grant competition. Funds for the student grant will come from member fees and contributions, as well as a percent of all grants awarded to CG. A panel will review and select the student research proposal annually. In addition to supporting student research financially, professional members of CG will donate their time as mentors to the student researchers, promoting a student mentor program. The Humboldt Bay region is well suited to support annual student research. Thorough research like this will help unravel some of the mysteries of regional earthquake-induced land-level changes, as well as possible fault segmentation in the SCSZ. CG will also provide educational materials and resources to the public regarding environmental restoration and earthquake hazards. All research conducted through CG will be published to a publicly accessible digital archive. Education and outreach activities include the student grant program, a digital public archive (maps, reports, geospatial data, guidebooks, MS theses, etc), web-based resources, bi-monthly publications, and annual reports. We invite all types of earth scientists to help support student field research and join us in promoting collaboration, communication, and cooperation with Cascadia GeoSciences.

Results of a pilot study in the U.S. and Vietnam to assess the utility and acceptability of a multi-level pregnancy test (MLPT) for home monitoring of hCG trends after assisted reproduction.

PubMed

Shochet, Tara; Comstock, Ioanna A; Ngoc, Nguyen Thi Nhu; Westphal, Lynn M; Sheldon, Wendy R; Loc, Ly Thai; Blum, Jennifer; Winikoff, Beverly; Blumenthal, Paul D

2017-08-22

To evaluate the utility and acceptability of using multi-level pregnancy tests (MLPTs) at home to monitor hCG trends following assisted reproductive technology (ART). One hundred and four women presenting for ART at either Stanford Medicine Fertility and Reproductive Health Clinic (Stanford, CA) or Hung Vuong Hospital (Ho Chi Minh City, Vietnam) participated in this pilot study. Women were asked to perform the MLPT at home, primarily on days when they were also scheduled to receive standard clinic-based serum hCG testing. These tests were administered up to 6 times over the 6-week period following embryo transfer or intrauterine insemination (IUI). Concordance of serial hCG readings for each time point was assessed by comparing trends in urine MLPT results with trends in serum hCG. Stable or increasing hCG level was interpreted as an indication of a progressing pregnancy, while a declining hCG was interpreted as a lack of established or progressing pregnancy. At study end, all participants were asked about the acceptability and convenience of using the MLPT at home for monitoring hCG trends following ART. Data from both urine and serum testing are available for 156 of 179 clinic visits (87.2%). There was high concordance of serial trend results between the two types of tests: among the 156 sets of serum and urine hCG data points, 150 (96.2%) showed a matching trend in hCG pattern and 6 (3.8%) resulted in a discordant trend. Seventy-three percent of women reported being satisfied or very satisfied with using the MLPTs at home. Almost all (96.6%) said that the MLPT was easy or very easy to use. The MLPT offers women and health care providers a client-friendly diagnostic tool to detect very early pregnancy and monitor its progress. This study was registered on clinicaltrials.gov as NCT01846403 (May 1, 2013), and NCT01919502 (August 5, 2013).

An attachment-based model of complicated grief including the role of avoidance

PubMed Central

Monk, Timothy; Houck, Patricia; Melhem, Nadine; Frank, Ellen; Reynolds, Charles; Sillowash, Russell

2009-01-01

Introduction Complicated grief is a prolonged grief disorder with elements of a stress response syndrome. We have previously proposed a biobehavioral model showing the pathway to complicated grief. Avoidance is a component that can be difficult to assess and pivotal to treatment. Therefore we developed an avoidance questionnaire to characterize avoidance among patients with CG. Methods We further explain our complicated grief model and provide results of a study of 128 participants in a treatment study of CG who completed a 15-item Grief-related Avoidance Questionnaire (GRAQ). Results of Avoidance Assessment Mean (SD) GRAQ score was 25. 0 ± 12.5 with a range of 0–60. Cronbach's alpha was 0.87 and test re-test correlation was 0.88. Correlation analyses showed good convergent and discriminant validity. Avoidance of reminders of the loss contributed to functional impairment after controlling for other symptoms of complicated grief. Discussion In this paper we extend our previously described attachment-based biobehavioral model of CG. We envision CG as a stress response syndrome that results from failure to integrate information about death of an attachment figure into an effectively functioning secure base schema and/or to effectively re-engage the exploratory system in a world without the deceased. Avoidance is a key element of the model. PMID:17629727

Coarse-Grained Models Reveal Functional Dynamics – II. Molecular Dynamics Simulation at the Coarse-Grained Level – Theories and Biological Applications

PubMed Central

Chng, Choon-Peng; Yang, Lee-Wei

2008-01-01

Molecular dynamics (MD) simulation has remained the most indispensable tool in studying equilibrium/non-equilibrium conformational dynamics since its advent 30 years ago. With advances in spectroscopy accompanying solved biocomplexes in growing sizes, sampling their dynamics that occur at biologically interesting spatial/temporal scales becomes computationally intractable; this motivated the use of coarse-grained (CG) approaches. CG-MD models are used to study folding and conformational transitions in reduced resolution and can employ enlarged time steps due to the absence of some of the fastest motions in the system. The Boltzmann-Inversion technique, heavily used in parameterizing these models, provides a smoothed-out effective potential on which molecular conformation evolves at a faster pace thus stretching simulations into tens of microseconds. As a result, a complete catalytic cycle of HIV-1 protease or the assembly of lipid-protein mixtures could be investigated by CG-MD to gain biological insights. In this review, we survey the theories developed in recent years, which are categorized into Folding-based and Molecular-Mechanics-based. In addition, physical bases in the selection of CG beads/time-step, the choice of effective potentials, representation of solvent, and restoration of molecular representations back to their atomic details are systematically discussed. PMID:19812774

hCG Test (Pregnancy Test)

MedlinePlus

... Time and International Normalized Ratio (PT/INR) PSEN1 Quantitative Immunoglobulins Red Blood Cell (RBC) Antibody Identification Red ... Us Also Known As Pregnancy Test Qualitative hCG Quantitative hCG Beta hCG Total hCG Total beta hCG ...

Suitable strategy to improve nitrogen utilization and reduce the environmental impact of Nellore bulls supplemented on tropical pasture.

PubMed

Jose Neto, A; Zervoudakis, J T; da Silva-Marques, R P; Silva, L C R P; Hatamoto-Zervoudakis, L K; Klopfenstein, T J

2016-03-01

Expansion of the biodiesel industry has increased the crude glycerin (CG) supply. Crude glycerin has the potential of replacing corn in ruminant diets because the glycerol can be converted to glucose in the liver of ruminants, providing energy for cellular metabolism. The objective was to evaluate the effects of CG with urea, soybean meal, cottonseed meal, and corn gluten feed, respectively, on intake, digestibility, microbial protein yield, and efficiency of N utilization. Five Nellore bulls (initial BW of 448 kg [SD 14]) grazing tropical pasture were used in a 5 × 5 Latin square design. The supplements were control (no supplementation; only free-choice mineral mixture ad libitum), CG with urea (CG-Urea), CG with soybean meal, CG with cottonseed meal, and CG with corn gluten. Crude glycerin was used in all supplements to replace corn (15% of DM supplement). There were differences between CG-Urea and other supplements with regard to intake of DM (% of BW and total; < 0.01), OM ( < 0.01), CP ( < 0.01), and TDN ( < 0.01). The digestibility of CP was greater ( = 0.04) for animals supplemented with CG-Urea than for those fed other supplements. Animals supplemented with CG-Urea showed greater N intake ( < 0.01) and N ammonia ( = 0.04) than those supplemented with other treatments. Nitrogen retained (g/d) was not affected by protein source but was greater for cattle fed a protein supplement compared with cattle fed the control supplement ( < 0.01). Supplementing the animals with protein sources increased ( = 0.02) the daily production of rumen microbial nitrogen (g/d) compared with the control group. Microbial protein (g/d) was lesser for the control than for protein sources ( = 0.02). However, when expressed relative to TDN ( = 0.35) and CP ( = 0.82), there were no differences across treatments. Crude protein intake per digestible OM intake (g CP/kg digestible OM intake) was greater for animals fed protein sources compared with animals fed control supplements ( < 0.01). Based on nutrients intake and microbial protein yield, CG-Urea supplement has a greater feeding value compared with other protein sources. Crude glycerin, when used to replace corn in 15% of DM supplement, may be effective to improved N utilization and microbial protein yield in rumen of Nellore bulls grazing cv. Marandu.

Audio-Visual and Autogenic Relaxation Alter Amplitude of Alpha EEG Band, Causing Improvements in Mental Work Performance in Athletes.

PubMed

Mikicin, Mirosław; Kowalczyk, Marek

2015-09-01

The aim of the present study was to investigate the effect of regular audio-visual relaxation combined with Schultz's autogenic training on: (1) the results of behavioral tests that evaluate work performance during burdensome cognitive tasks (Kraepelin test), (2) changes in classical EEG alpha frequency band, neocortex (frontal, temporal, occipital, parietal), hemisphere (left, right) versus condition (only relaxation 7-12 Hz). Both experimental (EG) and age-and skill-matched control group (CG) consisted of eighteen athletes (ten males and eight females). After 7-month training EG demonstrated changes in the amplitude of mean electrical activity of the EEG alpha bend at rest and an improvement was significantly changing and an improvement in almost all components of Kraepelin test. The same examined variables in CG were unchanged following the period without the intervention. Summing up, combining audio-visual relaxation with autogenic training significantly improves athlete's ability to perform a prolonged mental effort. These changes are accompanied by greater amplitude of waves in alpha band in the state of relax. The results suggest usefulness of relaxation techniques during performance of mentally difficult sports tasks (sports based on speed and stamina, sports games, combat sports) and during relax of athletes.

HYPERGLYCOSYLATED HUMAN CHORIONIC GONADOTROPIN AS AN EARLY PREDICTOR OF PREGNANCY OUTCOMES AFTER IN VITRO FERTILIZATION

PubMed Central

Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H. Irene

2014-01-01

Objective To determine if hyperglycosylated hCG (hhCG), produced by invasive trophoblasts, measured as early as 9 days after egg retrieval can predict ongoing pregnancies (OP) after in vitro fertilization and fresh embryo transfer (IVF-ET). Design Cohort Setting Academic ART center Patients Consecutive patients undergoing IVF-ET Interventions Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Outcome Ongoing pregnancy (OP) beyond 9 weeks of gestation Results OP (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. D9 hhCG levels >110 pg/mL was 96% specific for OP, yielding a positive predictive value of 95%. Compared to D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67). Diagnostic test characteristics were similar between D16 hhCG and hCG levels. Conclusions In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable. HhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. At this early assessment, hhCG is superior to traditional hCG and highly predictive of ongoing pregnancies. PMID:24355054

The Drosha rs10719 T>C polymorphism is associated with preeclampsia susceptibility.

PubMed

Rezaei, Mahnaz; Eskandari, Fatemeh; Mohammadpour-Gharehbagh, Abbas; Teimoori, Batool; Yaghmaei, Minoo; Mokhtari, Mojgan; Salimi, Saeedeh

2018-01-01

Drosha is a member of the micro RNA (miRNA) processing machinery that affects miRNA processing. Single-nucleotide polymorphisms (SNPs) in the Drosha gene might affect microRNA processing and the expression of various genes. The aim of this study is to investigate the association between SNPs in the Drosha gene and preeclampsia (PE) in the southeast of Iran. Genotyping of Drosha rs10719 and rs6877842 was performed using blood samples from 219 PE women and 205 healthy control subjects by a polymerase chain reaction-restriction fragment length polymorphism method. The Drosha rs10719TC genotype was significantly associated with 1.6-fold higher risk of PE (odds ratio (OR, 1.6 [95% CI, 1.1-2.4], P = 0.026). In addition, the frequency of the Drosha rs10719CC genotype was significantly higher in PE women and was associated with threefold higher risk of PE (OR 3 [95% CI 1.4-6.3], P = 0.004). There was no association between the Drosha rs6877842 polymorphism and PE susceptibility. The CC-GG combined genotype was associated with 3.4-fold higher risk of PE (OR 3.4 [95% CI 1.4-8.1], P = 0.007). The haplotype-based association analysis showed higher frequency of C-G haplotype of Drosha rs10719 and rs6877842 polymorphisms with the increased risk of PE 1.5-fold (OR 1.5 [95% CI 1.1 - 2], P = 0.01). The Drosha rs10719TC and CC genotypes were associated with PE risk. The CC-GG combined genotype and C-G haplotype of Drosha rs10719 and rs6877842 polymorphisms may increase PE susceptibility.

Effects of whole body vibration on bone mineral density and falls: results of the randomized controlled ELVIS study with postmenopausal women.

PubMed

von Stengel, S; Kemmler, W; Engelke, K; Kalender, W A

2011-01-01

We determined whether the effect of exercise on bone mineral density (BMD) and falls can be enhanced by whole body vibration (WBV). In summary, the multi-purpose exercise training was effective to increase lumbar BMD but added WBV did not enhance this effect. However, falls were lowest in the exercise program combined with WBV. WBV is a new approach to reduce the risk of osteoporotic fractures. In the "Erlangen Longitudinal Vibration Study" (ELVIS), we investigated whether WBV enhances the effect of multifunctional exercise on BMD and falls. One hundred fifty-one postmenopausal women (68.5 ± 3.1 years) were randomly assigned to a: (1) conventional training group (TG); (2) conventional training group including vibration (TGV); and (3) wellness control group (CG). TG conducted an exercise program consisting of 20 min dancing aerobics, 5 min balance training, 20 min functional gymnastics, and 15 min dynamic leg-strength training on vibration plates (without vibration) twice a week. TGV performed an identical exercise regimen with vibration (25-35 Hz) during the leg-strengthening sequence. CG performed a low-intensity wellness program. BMD was measured at the hip and lumbar spine at baseline and follow-up using the DXA method. Falls were recorded daily via the calendar method. After 18 months, an increase in BMD at the lumbar spine was observed in both training groups (TGV: +1.5% vs. TG: +2.1%). The difference between the TG and the CG (1.7%) was significant. At the hip no changes were determined in either group. The fall frequency was significantly lower in TGV (0.7 falls/person) compared with CG (1.5), whereas the difference between TG (0.96) and CG was not significant. A multifunctional training program had a positive impact on lumbar BMD. The application of vibration did not enhance these effects. However, only the training including WBV affected the number of falls significantly.

In vivo reflectance confocal microscopy evaluation of cheilitis glandularis: a report of 5 cases.

PubMed

Lourenço, Silvia V; Kos, Eliana; Borguezan Nunes, Thais; Bologna, Sheyla B; Sangueza, Martin; Nico, Marcello M S

2015-03-01

Cheilitis glandularis (CG) is an uncommon condition of unknown origin; it is clinically characterized by variable degrees of macrocheilia associated with red dilated ostia of minor salivary glands on the vermilion area, which secrete viscous saliva. Histopathological characteristics of CG are comprised of chronic sialadenitis with engorged acinar lobules and dilated ducts; CG also features chronic sun damage (actinic cheilitis and squamous cell carcinoma). These changes may be localized, and a punch biopsy specimen might fail to reveal enough criteria to support the diagnosis of CG. Reflectance confocal microscopy (RCM) is a noninvasive imaging technique that enables an in vivo en face visualization of tissues with a resolution close to conventional histopathology. Its use allows analysis of the entire lip, without excision. We reported the evaluation of 5 cases of CG based on clinical RCM and histopathological correlation. RCM examination of the lip vermilion mainly revealed a bright aspect of the superficial epithelial layers, which corresponded to labial keratosis. Alteration of the classical epithelial honeycomb pattern was observed in RCM, which corresponded to epithelial changes in actinic cheilitis at histopathology. Round, dark empty spaces intermingling the epithelium, corresponded to the ectopic excretory salivary gland ducts that open their ostia within the lip vermilion. In the lamina propria, the most striking feature was superficial salivary gland lobules, seen as dark gray lobular structures. Our study, demonstrated the use of RCM in the evaluation of CG, showing that a correlation between the clinical, digital RCM images and histopathology improved the diagnostic skills in CG evaluation.

USA300-related methicillin-resistant Staphylococcus aureus clone is the predominant cause of community and hospital MRSA infections in Colombian children.

PubMed

Márquez-Ortiz, Ricaurte Alejandro; Álvarez-Olmos, Martha I; Escobar Pérez, Javier Antonio; Leal, Aura Lucia; Castro, Betsy Esperanza; Mariño, Ana Cristina; Barrero, Esther Rocio; Mujica, Sandra Celina; Gaines, Sebastián; Vanegas, Natasha

2014-08-01

Community-genotype methicillin-resistant Staphylococcus aureus (CG-MRSA) isolates are known to be more virulent and clinically aggressive in children. The goal of the present study was characterize the molecular epidemiology of MRSA isolates causing infections in Colombian children. An observational and prospective study was conducted between April 2009 and June 2011 at 15 hospitals in Bogotá, Colombia. A detailed epidemiological profile was made of 162 children infected with MRSA. The isolates were subjected to antimicrobial susceptibility testing, molecular characterization including 21 virulence genes, SCCmec, spa and agr typing, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Among all isolates included in the study, 85.8% were obtained from patients whose infectious process was initiated in the community; of these, 69,8% occurred in patients without healthcare-associated risk factors. The molecular characterization of the isolates showed a high proportion (95.1%) containing a community-genotype profile with a high prevalence of SCCmec type IV, PVL-positives, and also related to CC8. Most CG-MRSA isolates (143, 92.9%) were genetically related to the pandemic clone USA300, differing by the presence of SCCmec IVc and the absence of the arginine catabolic mobile element (ACME). An increase in the frequency of CG-MRSA infections has been reported worldwide. In this study we found that almost all MRSA infections in our pediatric population were caused by community-genotype isolates, supporting the success of the CG-MRSA clones. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Vocal Acoustic and Auditory-Perceptual Characteristics During Fluctuations in Estradiol Levels During the Menstrual Cycle: A Longitudinal Study.

PubMed

Arruda, Polyanna; Diniz da Rosa, Marine Raquel; Almeida, Larissa Nadjara Alves; de Araujo Pernambuco, Leandro; Almeida, Anna Alice

2018-03-07

Estradiol production varies cyclically, changes in levels are hypothesized to affect the voice. The main objective of this study was to investigate vocal acoustic and auditory-perceptual characteristics during fluctuations in the levels of the hormone estradiol during the menstrual cycle. A total of 44 volunteers aged between 18 and 45 were selected. Of these, 27 women with regular menstrual cycles comprised the test group (TG) and 17 combined oral contraceptive users comprised the control group (CG). The study was performed in two phases. In phase 1, anamnesis was performed. Subsequently, the TG underwent blood sample collection for measurement of estradiol levels and voice recording for later acoustic and auditory-perceptual analysis. The CG underwent only voice recording. Phase 2 involved the same measurements as phase 1 for each group. Variables were evaluated using descriptive and inferential analysis to compare groups and phases and to determine relationships between variables. Voice changes were found during the menstrual cycle, and such changes were determined to be related to variations in estradiol levels. Impaired voice quality was observed to be associated with decreased levels of estradiol. The CG did not demonstrate significant vocal changes during phases 1 and 2. The TG showed significant increases in vocal parameters of roughness, tension, and instability during phase 2 (the period of low estradiol levels) when compared with the CG. Low estradiol levels were also found to be negatively correlated with the parameters of tension, instability, and jitter and positively correlated with fundamental voice frequency. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Cell Mergers and Their Impact on Cloud-to-Ground Lightning Over the Houston Area

NASA Technical Reports Server (NTRS)

Gauthier, Michael L.; Petersen, Walter A.; Carey, Lawrence D.

2009-01-01

A previous hypothesis advanced from observational studies such as METROMEX suggests that the intensity, frequency, and organization of cumulus convection may be impacted by the forcing of enhanced merger activity downstream of urban zones. A resulting corollary is that cities may exert an indirect anthropogenic forcing of parameters related to convection and associated phenomena such as lightning and precipitation. This paper investigates the urban merger hypothesis by examining the role of convective cell mergers on the existence and persistence of the Houston lightning "anomaly", a local maximum in cloud-to-ground (CG) lightning activity documented to exist over and east of Houston. Using eight summer seasons of peak columnar radar reflectivity, CG lightning data and a cell-tracking algorithm, a two-dimensional cell merger climatology is created for portions of eastern Texas and Louisiana. Results from the tracking and analysis of over 3.8 million cells indicate that merger-driven enhancements in convection induce a positive response (O 46%) in ground-flash densities throughout the domain, with areas of enhanced lightning typically being co-located with areas of enhanced merger activity. However, while mergers over the Houston area (relative to elsewhere in the domain) do result in more vigorous convective cells that produce larger CG flash densities, we find that CG lightning contributions due to mergers are distributed similarly throughout the domain. Hence while we demonstrate that cell mergers do greatly impact the production of lightning, the urban cell merger hypothesis does not uniquely explain the presence of a local lightning maximum near and downstream of Houston.

The effect of administering equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) post artificial insemination on fertility of lactating dairy cows.

PubMed

Bartolome, J A; Wallace, S Perez; de la Sota, R L; Thatcher, W W

2012-09-15

The objective was to evaluate the effect of equine chorionic gonadotropin (eCG) and hCG post artificial insemination (AI) on fertility of lactating dairy cows. In Experiment 1, cows were either treated with eCG on Day 22 post AI (400 IU; n = 80) or left untreated (n = 84). On Day 29, pregnant cows were either treated with hCG (2500 IU; n = 32) or left untreated (n = 36). Pregnancy and progesterone were evaluated on Days 29 and 45. In Experiment 2, cows (n = 28) were either treated with eCG on Day 22 (n = 13) or left untreated (n = 15) and either treated with hCG on Day 29 (n = 14) or left untreated (n = 14). Blood sampling and ultrasonography were conducted between Days 22 and 45. In Experiment 3, cows were either treated with eCG on Day 22 post AI (n = 229) or left untreated (n = 241). Pregnancy was evaluated on Days 36 and 85. In Experiment 1, eCG on Day 22 increased (P < 0.02) the number of pregnant cows on Day 29 (50.0 vs. 33.3%) and on Day 45, the increase was higher (P < 0.01) in cows with timed AI (41.2 vs. 6.5%) than in cows AI at detected estrus (50.0 vs. 37.8%). Pregnancy losses were reduced by eCG and hCG, but increased in cows that did not receive eCG but were given hCG (P < 0.01). Treatment with hCG tended (P < 0.06) to increase progesterone in control cows, but not in cows treated with eCG. In Experiment 2, hCG increased (P < 0.01) the number of accessory CLs on Day 35 (28.5 vs. 0.0%) and tended (P < 0.07) to increase progesterone. In Experiment 3, eCG increased the number of pregnant cows (P < 0.05) on Days 36 and 85, but only in cows with low body condition (eCG = 45.6 and 43.5%; Control = 22.9 and 22.9%). In conclusion, eCG at 22 days post insemination increased fertility, primarily in cows with low body condition and reduced pregnancy losses when given 7 days before hCG; hCG induced accessory CLs and slightly increased progesterone, but hCG given in the absence of a prior eCG treatment reduced fertility. Copyright © 2012 Elsevier Inc. All rights reserved.

Standardised simulation-based emergency and intensive care nursing curriculum to improve nursing students' performance during simulated resuscitation: A quasi-experimental study.

PubMed

Chen, Jie; Yang, Jian; Hu, Fen; Yu, Si-Hong; Yang, Bing-Xiang; Liu, Qian; Zhu, Xiao-Ping

2018-06-01

Simulation-based curriculum has been demonstrated as crucial to nursing education in the development of students' critical thinking and complex clinical skills during a resuscitation simulation. Few studies have comprehensively examined the effectiveness of a standardised simulation-based emergency and intensive care nursing curriculum on the performance of students in a resuscitation simulation. To evaluate the impact of a standardised simulation-based emergency and intensive care nursing curriculum on nursing students' response time in a resuscitation simulation. Two-group, non-randomised quasi-experimental design. A simulation centre in a Chinese University School of Nursing. Third-year nursing students (N = 39) in the Emergency and Intensive Care course were divided into a control group (CG, n = 20) and an experimental group (EG, n = 19). The experimental group participated in a standardised high-technology, simulation-based emergency and intensive care nursing curriculum. The standardised simulation-based curriculum for third-year nursing students consists of three modules: disaster response, emergency care, and intensive care, which include clinical priorities (e.g. triage), basic resuscitation skills, airway/breathing management, circulation management and team work with eighteen lecture hours, six skill-practice hours and twelve simulation hours. The control group took part in the traditional curriculum. This course included the same three modules with thirty-four lecture hours and two skill-practice hours (trauma). Perceived benefits included decreased median (interquartile ranges, IQR) seconds to start compressions [CG 32 (25-75) vs. EG 20 (18-38); p < 0.001] and defibrillation [CG 204 (174-240) vs. EG 167 (162-174); p < 0.001] at the end of the course, compared with compressions [CG 41 (32-49) vs. EG 42 (33-46); p > 0.05] and defibrillation [CG 222 (194-254) vs. EG 221 (214-248); p > 0.05] at the beginning of the course. A simulation-based emergency and intensive care nursing curriculum was created and well received by third-year nursing students and associated with decreased response time in a resuscitation simulation. Copyright © 2018 Elsevier Ltd. All rights reserved.

The impact of losing a child on the clinical presentation of complicated grief

PubMed Central

Zetumer, Samuel; Young, Ilanit; Shear, M. Katherine; Skritskaya, Natalia; Lebowitz, Barry; Simon, Naomi; Reynolds, Charles; Mauro, Christine; Zisook, Sidney

2014-01-01

Background It is unclear whether bereaved parents with Complicated Grief (CG) struggle with their grief differently than others with CG. This study addressed this question by comparing CG severity, CG-related symptoms, thoughts and behaviors, and comorbid psychiatric diagnoses of bereaved parents with CG to the diagnoses and symptoms of others with CG. Methods Baseline data from 345 participants enrolled in the Healing Emotions After Loss (HEAL) study, a multi-site CG treatment study, were used to compare parents with CG (n = 75) to others with CG (n = 275). Data from the parent group was then used to compare parents with CG who had lost a younger child (n = 24) to parents with CG who had lost an older child (n = 34). Demographic and loss-related data were also gathered and used to control for confounders between groups. Results Parents with CG demonstrated slightly higher levels of CG (p = .025), caregiver self-blame (p = .007), and suicidality (p = .025) than non-parents with CG. Parents who had lost younger children were more likely to have had a wish to be dead since the loss than parents who had lost older children (p = .041). Limitations All data were gathered from a treatment research study, limiting the of these results. No corrections were made for multiple comparisons. The comparison of parents who lost younger children to parents who lost older children was limited by a small sample size. Conclusions Even in the context of CG, the relationship to the deceased may have a bearing on the degree and severity of grief symptoms and associated features. Bereaved parents with CG reported more intense CG, self-blame, and suicidality than other bereaved groups with CG, though this finding requires confirmation. The heightened levels of suicidal ideation experienced by parents with CG, especially after losing a younger child, suggest the value of routinely screening for suicidal thoughts and behaviors in this group. PMID:25217759

Ultrasensitive colorimetric immunoassay for hCG detection based on dual catalysis of Au@Pt core-shell nanoparticle functionalized by horseradish peroxidase

NASA Astrophysics Data System (ADS)

Wang, Weiguo; Zou, Yake; Yan, Jinwu; Liu, Jing; Chen, Huixiong; Li, Shan; Zhang, Lei

2018-03-01

In this paper, an ultrasensitive colorimetric biosensor for human chorionic gonadotrophin (hCG) detection was designed from bottom-up method based on the dual catalysis of the horseradish peroxidase (HRP) and Au@Pt nanoparticles (NPs) relative to H2O2-TEM system. HRP and monoclonal mouse anti-hCG antibody (β-submit, mAb1) were co-immobilized onto the Au@Pt NP surface to improve catalytic efficiency and specificity, which formed a dual functionalized Au@Pt-HRP probe with the mean size of 42.8 nm (D50). The colorimetric immunoassay was developed for the hCG detection, and the Au@Pt-HRP probe featured a higher sensitivity in the concentration range of 0.4-12.8 IU L- 1 with a low limit of detection (LOD) of 0.1 IU L- 1 compared with the LODs of 0.8 IU L- 1 for BA-ELISA and of 2.0 IU L- 1 for Au@Pt, which indicated that the Au@Pt-HRP probe possessed higher catalytic efficiency with 2.8-fold increase over Au@Pt and 33.8-fold increase over HRP. Also, the Au@Pt-HRP probe exhibited good precision and reproducibility, high specificity and acceptable accuracy with CV being less than 15%. The dual functionalized Au@Pt-HRP probe as a type of signal amplified method was firstly applied in the colorimetric immunoassay for the hCG detection.

Some properties of negative cloud-to-ground flashes from observations of a local thunderstorm based on accurate-stroke-count studies

NASA Astrophysics Data System (ADS)

Zhu, Baoyou; Ma, Ming; Xu, Weiwei; Ma, Dong

2015-12-01

Properties of negative cloud-to-ground (CG) lightning flashes, in terms of number of strokes per flash, inter-stroke intervals and the relative intensity of subsequent and first strokes, were presented by accurate-stroke-count studies based on all 1085 negative flashes from a local thunderstorm. The percentage of single-stroke flashes and stroke multiplicity evolved significantly during the whole life cycle of the study thunderstorm. The occurrence probability of negative CG flashes decreased exponentially with the increasing number of strokes per flash. About 30.5% of negative CG flashes contained only one stroke and number of strokes per flash averaged 3.3. In a subset of 753 negative multiple-stroke flashes, about 41.4% contained at least one subsequent stroke stronger than the corresponding first stroke. Subsequent strokes tended to decrease in strength with their orders and the ratio of subsequent to first stroke peaks presented a geometric mean value of 0.52. Interestingly, negative CG flashes of higher multiplicity tended to have stronger initial strokes. 2525 inter-stroke intervals showed a more or less log-normal distribution and gave a geometric mean value of 62 ms. For CG flashes of particular multiplicity geometric mean inter-stroke intervals tended to decrease with the increasing number of strokes per flash, while those intervals associated with higher order strokes tended to be larger than those associated with low order strokes.

Teaching the English Active and Passive Voice with the Help of Cognitive Grammar: An Empirical Study

ERIC Educational Resources Information Center

Bielak, Jakub; Pawlak, Mirosuaw; Mystkowska-Wiertelak, Anna

2013-01-01

Functionally-oriented linguistic theories, such as cognitive grammar (CG), offer nuanced descriptions of the meanings and uses of grammatical features. A simplified characterization of the semantics of the English active and passive voice grounded in CG terms and based on the reference point model is presented, as it is the basis of the…

A prediction model of drug-induced ototoxicity developed by an optimal support vector machine (SVM) method.

PubMed

Zhou, Shu; Li, Guo-Bo; Huang, Lu-Yi; Xie, Huan-Zhang; Zhao, Ying-Lan; Chen, Yu-Zong; Li, Lin-Li; Yang, Sheng-Yong

2014-08-01

Drug-induced ototoxicity, as a toxic side effect, is an important issue needed to be considered in drug discovery. Nevertheless, current experimental methods used to evaluate drug-induced ototoxicity are often time-consuming and expensive, indicating that they are not suitable for a large-scale evaluation of drug-induced ototoxicity in the early stage of drug discovery. We thus, in this investigation, established an effective computational prediction model of drug-induced ototoxicity using an optimal support vector machine (SVM) method, GA-CG-SVM. Three GA-CG-SVM models were developed based on three training sets containing agents bearing different risk levels of drug-induced ototoxicity. For comparison, models based on naïve Bayesian (NB) and recursive partitioning (RP) methods were also used on the same training sets. Among all the prediction models, the GA-CG-SVM model II showed the best performance, which offered prediction accuracies of 85.33% and 83.05% for two independent test sets, respectively. Overall, the good performance of the GA-CG-SVM model II indicates that it could be used for the prediction of drug-induced ototoxicity in the early stage of drug discovery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Quantum mechanics/coarse-grained molecular mechanics (QM/CG-MM)

NASA Astrophysics Data System (ADS)

Sinitskiy, Anton V.; Voth, Gregory A.

2018-01-01

Numerous molecular systems, including solutions, proteins, and composite materials, can be modeled using mixed-resolution representations, of which the quantum mechanics/molecular mechanics (QM/MM) approach has become the most widely used. However, the QM/MM approach often faces a number of challenges, including the high cost of repetitive QM computations, the slow sampling even for the MM part in those cases where a system under investigation has a complex dynamics, and a difficulty in providing a simple, qualitative interpretation of numerical results in terms of the influence of the molecular environment upon the active QM region. In this paper, we address these issues by combining QM/MM modeling with the methodology of "bottom-up" coarse-graining (CG) to provide the theoretical basis for a systematic quantum-mechanical/coarse-grained molecular mechanics (QM/CG-MM) mixed resolution approach. A derivation of the method is presented based on a combination of statistical mechanics and quantum mechanics, leading to an equation for the effective Hamiltonian of the QM part, a central concept in the QM/CG-MM theory. A detailed analysis of different contributions to the effective Hamiltonian from electrostatic, induction, dispersion, and exchange interactions between the QM part and the surroundings is provided, serving as a foundation for a potential hierarchy of QM/CG-MM methods varying in their accuracy and computational cost. A relationship of the QM/CG-MM methodology to other mixed resolution approaches is also discussed.

Quantum mechanics/coarse-grained molecular mechanics (QM/CG-MM).

PubMed

Sinitskiy, Anton V; Voth, Gregory A

2018-01-07

Numerous molecular systems, including solutions, proteins, and composite materials, can be modeled using mixed-resolution representations, of which the quantum mechanics/molecular mechanics (QM/MM) approach has become the most widely used. However, the QM/MM approach often faces a number of challenges, including the high cost of repetitive QM computations, the slow sampling even for the MM part in those cases where a system under investigation has a complex dynamics, and a difficulty in providing a simple, qualitative interpretation of numerical results in terms of the influence of the molecular environment upon the active QM region. In this paper, we address these issues by combining QM/MM modeling with the methodology of "bottom-up" coarse-graining (CG) to provide the theoretical basis for a systematic quantum-mechanical/coarse-grained molecular mechanics (QM/CG-MM) mixed resolution approach. A derivation of the method is presented based on a combination of statistical mechanics and quantum mechanics, leading to an equation for the effective Hamiltonian of the QM part, a central concept in the QM/CG-MM theory. A detailed analysis of different contributions to the effective Hamiltonian from electrostatic, induction, dispersion, and exchange interactions between the QM part and the surroundings is provided, serving as a foundation for a potential hierarchy of QM/CG-MM methods varying in their accuracy and computational cost. A relationship of the QM/CG-MM methodology to other mixed resolution approaches is also discussed.

Global gene expression in the bovine corpus luteum is altered after stimulatory and superovulatory treatments.

PubMed

Fátima, Luciana A; Baruselli, Pietro S; Gimenes, Lindsay U; Binelli, Mario; Rennó, Francisco P; Murphy, Bruce D; Papa, Paula C

2013-01-01

Equine chorionic gonadotrophin (eCG) has been widely used in superovulation and artificial insemination programmes and usually promotes an increase in corpus luteum (CL) volume and stimulates progesterone production. Therefore, to identify eCG-regulated genes in the bovine CL, the transcriptome was evaluated by microarray analysis and the expression of selected genes was validated by qPCR and western blot. Eighteen Nelore crossbred cows were divided into control (n=5), stimulated (n=6) and superovulated groups (n=7). Ovulation was synchronised using a progesterone device-based protocol. Stimulated animals received 400 IU of eCG at device removal and superovulated animals received 2000 IU of eCG 4 days prior. Corpora lutea were collected 7 days after gonadotrophin-releasing hormone administration. Overall, 242 transcripts were upregulated and 111 transcripts were downregulated in stimulated cows (P ≤ 0.05) and 111 were upregulated and 113 downregulated in superovulated cows compared to the control animals (1.5-fold, P ≤ 0.05). Among the differentially expressed genes, many were involved in lipid biosynthesis and progesterone production, such as PPARG, STAR, prolactin receptors and follistatin. In conclusion, eCG modulates gene expression differently depending on the treatment, i.e. stimulatory or superovulatory. Our data contribute to the understanding of the pathways involved in increased progesterone levels observed after eCG treatment.

Mixing coarse-grained and fine-grained water in molecular dynamics simulations of a single system.

PubMed

Riniker, Sereina; van Gunsteren, Wilfred F

2012-07-28

The use of a supra-molecular coarse-grained (CG) model for liquid water as solvent in molecular dynamics simulations of biomolecules represented at the fine-grained (FG) atomic level of modelling may reduce the computational effort by one or two orders of magnitude. However, even if the pure FG model and the pure CG model represent the properties of the particular substance of interest rather well, their application in a hybrid FG/CG system containing varying ratios of FG versus CG particles is highly non-trivial, because it requires an appropriate balance between FG-FG, FG-CG, and CG-CG energies, and FG and CG entropies. Here, the properties of liquid water are used to calibrate the FG-CG interactions for the simple-point-charge water model at the FG level and a recently proposed supra-molecular water model at the CG level that represents five water molecules by one CG bead containing two interaction sites. Only two parameters are needed to reproduce different thermodynamic and dielectric properties of liquid water at physiological temperature and pressure for various mole fractions of CG water in FG water. The parametrisation strategy for the FG-CG interactions is simple and can be easily transferred to interactions between atomistic biomolecules and CG water.

USA hCG reference service, 10-year report.

PubMed

Cole, Laurence A; Laidler, Laura L; Muller, Carolyn Y

2010-08-01

The USA hCG Reference Service has been dealing with cases of persistent low levels of hCG and gestational trophoblastic diseases for 10years. Here we present the complete experience. Total hCG in serum and urine was measured using the Siemen's Immulite 1000 assay. Hyperglycosylated hCG, nicked hCG, free ss-subunit and ss-core fragment were measured using microtiterplate assays with antibodies B152, B151, FBT11 and B210, respectively. The USA hCG Reference Service has identified 83 cases of false-positive hCG, 71 cases of aggressive gestational trophoblastic disease (GTD), 52 cases of minimally invasive GTD, 168 cases of quiescent GTD and 22 cases of placenta site trophoblastic tumor (PSTT). In addition, 103 cases of pituitary hCG have been identified, 60 cases of nontrophoblastic tumor, 4 cases of inherited hCG and 2 cases of Munchausen's syndrome. This is 565 cases total. Multiple new methods are described and tested for diagnosing all of these disorders. The USA hCG Reference Service experience shows new methods for detecting multiple hCG-related disorders and recommends new approaches for detecting these hCG-related disorders. 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Analysis on RF parameters of nanoscale tunneling field-effect transistor based on InAs/InGaAs/InP heterojunctions.

PubMed

Woo, Sung Yun; Yoon, Young Jun; Cho, Seongjae; Lee, Jung-Hee; Kang, In Man

2013-12-01

Tunneling field-effect transistors (TFETs) based on the quantum mechanical band-to-band tunneling (BTBT) have advantages such as low off-current and subthreshold swing (S) below 60 mV/dec at room temperature. For these reasons, TFETs are considered as promising devices for low standby power (LSTP) applications. On the other hand, silicon (Si)-based TFETs have a drawback in low on-state current (lon) drivability. In this work, we suggest a gate-all-around (GAA) TFET based on compound semiconductors to improve device performances. The proposed device materials consist of InAs (source), InGaAs (channel), and InP (drain). According to the composition (x) of Ga in In1-xGa(x)As layer of the channel region, simulated devices have been investigated in terms of both direct-current (DC) and RF parameters including tunneling rate, transconductance (g(m)), gate capacitance (Cg), intrinsic delay time (tau), cut-off frequency (fT) and maximum oscillation frequency (f(max)). In this study, the obtained maximum values of tau, fT, and f(max) for GAA InAs/In0.9Ga0.1As/InP heterojunction TFET were 21.2 fs, 7 THz, and 18 THz, respectively.

A Unique Human Chorionic Gonadotropin Antagonist Suppresses Ovarian Hyperstimulation Syndrome in Rats

PubMed Central

Vardhana, Pratibhasri A.; Julius, Martin A.; Pollak, Susan V.; Lustbader, Evan G.; Trousdale, Rhonda K.; Lustbader, Joyce W.

2009-01-01

Ovarian hyperstimulation syndrome (OHSS) is a complication of in vitro fertilization associated with physiological changes after hCG administration to induce final oocyte maturation. It presents as widespread increases in vascular permeability and, in rare cases, results in cycle cancellation, multi-organ dysfunction, and pregnancy termination. These physiological changes are due primarily to activation of the vascular endothelial growth factor (VEGF) system in response to exogenous human chorionic gonadotropin (hCG). An hCG antagonist (hCG-Ant) could attenuate these effects by competitively binding to the LH/CG receptor, thereby blocking LH activity in vivo. We expressed a form of hCG that lacks three of its four N-linked glycosylation sites and tested its efficacy as an antagonist. The hCG-Ant binds the LH receptor with an affinity similar to native hCG and inhibits cAMP response in vitro. In a rat model for ovarian stimulation, hCG-Ant dramatically reduces ovulation and steroid hormone production. In a well-established rat OHSS model, vascular permeability and vascular endothelial growth factor (VEGF) expression are dramatically reduced after hCG-Ant treatment. Finally, hCG-Ant does not appear to alter blastocyst development when given after hCG in mice. These studies demonstrate that removing specific glycosylation sites on native hCG can produce an hCG-Ant that is capable of binding without activating the LH receptor and blocking the actions of hCG. Thus hCG-Ant will be investigated as a potential therapy for OHSS. PMID:19443574

Familial HCG syndrome.

PubMed

Cole, Laurence A

2012-01-01

An explanation is needed for why some men and women show positive in hCG screening tests when they are not pregnant, do not have cancer and are otherwise asymptomatic. In this study, a total of 10 families comprising 30 persons with a history of positive hCG tests were investigated. Total hCG was measured in serum and urine samples using the Siemens Immulite hCG test. Total hCG, C-terminal peptide determinant, and hCGβ were measured in 96 well plate assays. Twenty-four of 30 family members produced only hCGβ, and hCG or hCGβ missing the β-subunit C-terminal peptide, two rarely detected hCG degradation products as the only source of hCG immunoreactivity. In every one of the 10 families, hCG related molecules were detected first in one member and then later detected in other family members. In 8 of 10 families, all members produced comparable hCG concentration (Cases 1-8). All of the 10 original family members investigated were otherwise asymptomatic, and tested negative in ordered head and pelvis MRI scans and CT chest cancer tests. None had been administered hCG for dietary, anabolic or fertility reasons. Therefore Familial hCG Syndrome, a genetic defect, was indicated in each of the 10 families. In these cases of Familial hCG Syndrome only biologically inactive variants of hCG were detected. It is inferred that in Familial hCG Syndrome, hCG gene expression does not interfere with fertility. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial.

PubMed

Strug, Michael R; Su, Renwei; Young, James E; Dodds, William G; Shavell, Valerie I; Díaz-Gimeno, Patricia; Ruíz-Alonso, Maria; Simón, Carlos; Lessey, Bruce A; Leach, Richard E; Fazleabas, Asgerally T

2016-07-01

Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation? Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival. The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1. Oocyte donors (n=15) were randomly assigned to receive an intrauterine infusion of 500 IU hCG (n=7) or embryo culture media vehicle (n=8) 3 days following oocyte retrieval during their donor stimulation cycle. Endometrial biopsies were performed 2 days later, followed by either RNA isolation or tissue fixation in formalin and paraffin embedding. Reverse transcription of total RNA from endometrial biopsies generated cDNA, which was used for analysis in the endometrial receptivity array (ERA; n = 5/group) or quantitative RT-PCR to determine relative expression of ESR1, PGR, C3 and NOTCH1. Tissue sections were stained with hematoxylin and eosin followed by blinded staging analysis for dating of endometrial glands and stroma. Immunostaining for ESR1, PGR, α-SMA, C3 and NOTCH1 was performed to determine their tissue localization. Intrauterine hCG infusion was associated with endometrial synchrony and reprograming of stromal development following ovarian stimulation. ESR1 and PGR were significantly elevated in the endometrium of hCG-treated patients, consistent with earlier staging. The ERA did not predict an overall positive impact of intrauterine hCG on endometrial receptivity. However, ACTA2, encoding α-SMA was significantly increased in response to intrauterine hCG. Similar to the hCG-treated non-human primate, sub-epithelial and peri-vascular α-SMA expression was induced in women following hCG infusion. Other known targets of hCG in the baboon were also found to be increased, including C3 and NOTCH1, which have known roles in endometrial receptivity. This study differs from our previous work in the hCG-treated non-human primate along with clinical studies in infertile patients. Specifically, we performed a single intrauterine infusion in oocyte donors instead of either continuous hCG via an osmotic mini-pump in the baboon or infusion followed by blastocyst-derived hCG in infertile women undergoing embryo transfer. Therefore, the full impact of intrauterine hCG in promoting endometrial receptivity may not have been evident. Our findings suggest a potential clinical benefit for intrauterine hCG prior to embryo transfer on Day 3 in counteracting endometrial dyssynchrony from ovarian stimulation and promoting expression of markers important for stromal survival. Finally, there were no obvious negative effects of intrauterine hCG treatment. Funding for this work was provided by NICHD R01 HD042280 (A.T.F.) and NICHD F30 HD082951 (M.R.S.). C.S. and P.D.-G are co-inventors of the patented ERA, which is owned by IGENOMIX SL and was used in this study, and C.S. is a shareholder in IGENOMIX SL. M.R.-A. is employed by IGENOMIX SL. No other authors have any conflicts of interest to report. This study was registered with ClinicalTrials.gov (NCT01786252). 5 February 2013. 10 May 2013. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hyperglycosylated human chorionic gonadotropin as an early predictor of pregnancy outcomes after in vitro fertilization.

PubMed

Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H Irene

2014-02-01

To determine whether serum hyperglycosylated human chorionic gonadotropin (hhCG) measured as early as 9 days after egg retrieval can predict ongoing pregnancies after in vitro fertilization and fresh embryo transfer (IVF-ET). Cohort Academic assisted reproduction center. Consecutive patients undergoing IVF-ET INTERVENTION(S): Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Ongoing pregnancy beyond 9 weeks of gestation. Ongoing pregnancy (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG. However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. A D9 hhCG level of >110 pg/mL was 96% specific for an ongoing pregnancy, yielding a positive predictive value of 94%. Compared with the D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67, respectively). The diagnostic test characteristics were similar between the D16 hhCG and hCG levels. In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable, and hhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. In this early assessment, hhCG was superior to traditional hCG and highly predictive of ongoing pregnancies. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The multiscale coarse-graining method. II. Numerical implementation for coarse-grained molecular models

PubMed Central

Noid, W. G.; Liu, Pu; Wang, Yanting; Chu, Jhih-Wei; Ayton, Gary S.; Izvekov, Sergei; Andersen, Hans C.; Voth, Gregory A.

2008-01-01

The multiscale coarse-graining (MS-CG) method [S. Izvekov and G. A. Voth, J. Phys. Chem. B 109, 2469 (2005);J. Chem. Phys. 123, 134105 (2005)] employs a variational principle to determine an interaction potential for a CG model from simulations of an atomically detailed model of the same system. The companion paper proved that, if no restrictions regarding the form of the CG interaction potential are introduced and if the equilibrium distribution of the atomistic model has been adequately sampled, then the MS-CG variational principle determines the exact many-body potential of mean force (PMF) governing the equilibrium distribution of CG sites generated by the atomistic model. In practice, though, CG force fields are not completely flexible, but only include particular types of interactions between CG sites, e.g., nonbonded forces between pairs of sites. If the CG force field depends linearly on the force field parameters, then the vector valued functions that relate the CG forces to these parameters determine a set of basis vectors that span a vector subspace of CG force fields. The companion paper introduced a distance metric for the vector space of CG force fields and proved that the MS-CG variational principle determines the CG force force field that is within that vector subspace and that is closest to the force field determined by the many-body PMF. The present paper applies the MS-CG variational principle for parametrizing molecular CG force fields and derives a linear least squares problem for the parameter set determining the optimal approximation to this many-body PMF. Linear systems of equations for these CG force field parameters are derived and analyzed in terms of equilibrium structural correlation functions. Numerical calculations for a one-site CG model of methanol and a molecular CG model of the EMIM+∕NO3− ionic liquid are provided to illustrate the method. PMID:18601325

Using a simulation model to assess risk of false negative point-of-care urinary human chorionic gonadotropin device results due to high-dose hook interference.

PubMed

Milhorn, Denise; Korpi-Steiner, Nichole

2015-02-01

It is unclear if the point-of-care (POC) Clinitest hCG device is subject to high-dose hook interference from physiological concentrations of intact human chorionic gonadotropin (hCG), β-core fragment of hCG (hCGβcf), and hCG free β-subunit (hCGβ) found in urine during pregnancy. We used a simulation model to address this question and related our findings to our institution's pregnant population in order to assess risk for potential false-negative hCG results. The expected distribution of days relative to ovulation during routine POC hCG testing was estimated from 182 patients. Clinitest-Clinitek Status hCG device susceptibility to high-dose hook interference from hCG variants and potential risk of false-negative results as it relates to this population were evaluated by testing increasing concentrations of hCG, hCGβcf, hCGβ as well as urine simulating physiological hCG, hCGβcf and hCGβ concentrations expected during early pregnancy (≤44 days post-ovulation). The Clinitest-Clinitek Status hCG device exhibited high-dose hook interference from hCGβcf alone, but not from hCG, hCGβ, or simulated physiological urinary concentrations of combined hCG, hCGβcf and hCGβ expected during early pregnancy. The majority of our patient population had urinary hCG testing conducted during early pregnancy. The Clinitest-Clinitek Status hCG device is unlikely to exhibit false-negative urinary hCG results due to high-dose hook interference for women in early healthy pregnancy, although additional studies are necessary to determine potential risk in other patient populations. Visual interpretation of POC urinary hCG device results is an important failure mode to consider in risk analyses for erroneous urinary hCG device results. Published by Elsevier Inc.

Differentiation of the root of Cultivated Ginseng, Mountain Cultivated Ginseng and Mountain Wild Ginseng using FT-IR and two-dimensional correlation IR spectroscopy

NASA Astrophysics Data System (ADS)

Liu, Dan; Li, Yong-Guo; Xu, Hong; Sun, Su-Qin; Wang, Zheng-Tao

2008-07-01

Ginseng is one of the most widely used herbal medicines. Based on the grown environments and the cultivate method, three kinds of ginseng, Cultivated Ginseng (CG), Mountain Cultivated Ginseng (MCG) and Mountain Wild Ginseng (MWG) are classified. A novel and scientific-oriented method was developed and established to discriminate and identify three kinds of ginseng using Fourier transform infrared spectroscopy (FT-IR), secondary derivative IR spectra and two-dimensional correlation infrared spectroscopy (2D-IR). The findings indicated that the relative contents of starch in the CG were more than that in MCG and MWG, while the relative contents of calcium oxalate and lipids in MWG were more than that in CG and MCG, and the relative contents of fatty acid in MCG were more than that in CG and MWG. The hierarchical cluster analysis was applied to data analysis of MWG, CG and MWG, which could be classified successfully. The results demonstrated the macroscopic IR fingerprint method, including FT-IR, secondary derivative IR and 2D-IR, can be applied to discriminate different ginsengs rapidly, effectively and non-destructively.

Transferable Coarse-Grained Models for Ionic Liquids.

PubMed

Wang, Yanting; Feng, Shulu; Voth, Gregory A

2009-04-14

The effective force coarse-graining (EF-CG) method was applied to the imidazolium-based nitrate ionic liquids with various alkyl side-chain lengths. The nonbonded EF-CG forces for the ionic liquid with a short side chain were extended to generate the nonbonded forces for the ionic liquids with longer side chains. The EF-CG force fields for the ionic liquids exhibit very good transferability between different systems at various temperatures and are suitable for investigating the mesoscopic structural properties of this class of ionic liquids. The good additivity and ease of manipulation of the EF-CG force fields can allow for an inverse design methodology of ionic liquids at the coarse-grained level. With the EF-CG force field, the molecular dynamics (MD) simulation at a very large scale has been performed to check the significance of finite size effects on the structural properties. From these MD simulation results, it can be concluded that the finite size effect on the phenomenon of ionic liquid spatial heterogeneity (Wang, Y.; Voth, G. A. J. Am. Chem. Soc. 2005, 127, 12192) is small and that this phenomenon is indeed a nanostructural behavior which leads to the experimentally observed mesoscopic heterogeneous structure of ionic liquids.

Incorporating a guanidine-modified cytosine base into triplex-forming PNAs for the recognition of a C-G pyrimidine–purine inversion site of an RNA duplex

PubMed Central

Toh, Desiree-Faye Kaixin; Devi, Gitali; Patil, Kiran M.; Qu, Qiuyu; Maraswami, Manikantha; Xiao, Yunyun; Loh, Teck Peng; Zhao, Yanli; Chen, Gang

2016-01-01

RNA duplex regions are often involved in tertiary interactions and protein binding and thus there is great potential in developing ligands that sequence-specifically bind to RNA duplexes. We have developed a convenient synthesis method for a modified peptide nucleic acid (PNA) monomer with a guanidine-modified 5-methyl cytosine base. We demonstrated by gel electrophoresis, fluorescence and thermal melting experiments that short PNAs incorporating the modified residue show high binding affinity and sequence specificity in the recognition of an RNA duplex containing an internal inverted Watson-Crick C-G base pair. Remarkably, the relatively short PNAs show no appreciable binding to DNA duplexes or single-stranded RNAs. The attached guanidine group stabilizes the base triple through hydrogen bonding with the G base in a C-G pair. Selective binding towards an RNA duplex over a single-stranded RNA can be rationalized by the fact that alkylation of the amine of a 5-methyl C base blocks the Watson–Crick edge. PNAs incorporating multiple guanidine-modified cytosine residues are able to enter HeLa cells without any transfection agent. PMID:27596599

Mutagenicity of furan in female Big Blue B6C3F1 mice

PubMed Central

Terrell, Ashley N.; Huynh, Mailee; Grill, Alex E.; Kovi, Ramesh C.; O’Sullivan, M. Gerard; Guttenplan, Joseph B.; Ho, Yen-Yi; Peterson, Lisa A.

2014-01-01

Furan is an abundant food and environmental contaminant that is a potent liver carcinogen in rodent models. To determine if furan is genotoxic in vivo, female B6C3F1 Big Blue transgenic mice were treated with 15 mg/kg bw furan by gavage 5 days a week for 6 weeks, or once weekly for 3 weeks. Liver cII trans-gene mutation-frequency and mutation spectra were determined. Furan did not increase the mutation frequency under either treatment condition. In the 6-week treatment regimen, there was a change in the cII transgene mutation-spectrum, with the fraction of GC to AT transitions significantly reduced. The only other significant change was an increase in GC to CG transversions; these represented a minor contribution to the overall mutation spectrum. A much larger furan-dependent shift was observed in the 3-week study. There was a significant increase in transversion mutations, predominantly GC to TA transversions as well as smaller non-significant changes in GC to CG and AT to TA transversions. To determine if these mutations were caused by cis-2-butene-1,4-dial (BDA), a reactive metabolite of furan, the mutagenic activity and the mutation spectrum of BDA was determined in vitro, in Big Blue mouse embryonic fibroblasts. This compound did not increase the cII gene mutation-frequency but caused a substantial increase in AT to CG transversions. This increase, however, lost statistical significance when adjusted for multiple comparisons. Together, these findings suggest that BDA may not be directly responsible for the in-vivo effects of furan on mutational spectra. Histopathological analysis of livers from furan-treated mice revealed that furan induced multifocal, hepatocellular necrosis admixed with reactive leukocytes and pigment-laden Kupffer cells, enhanced oval-cell hyperplasia, and increased hepatocyte mitoses, some of which were atypical. An indirect mechanism of genotoxicity is proposed in which chronic toxicity followed by inflammation and secondary cell proliferation triggers cancer development in furan-exposed rodents. PMID:25344163

Effects of the Finnish Alzheimer disease exercise trial (FINALEX): a randomized controlled trial.

PubMed

Pitkälä, Kaisu H; Pöysti, Minna M; Laakkonen, Marja-Liisa; Tilvis, Reijo S; Savikko, Niina; Kautiainen, Hannu; Strandberg, Timo E

2013-05-27

Few rigorous clinical trials have investigated the effectiveness of exercise on the physical functioning of patients with Alzheimer disease (AD). To investigate the effects of intense and long-term exercise on the physical functioning and mobility of home-dwelling patients with AD and to explore its effects on the use and costs of health and social services. A randomized controlled trial. A total of 210 home-dwelling patients with AD living with their spousal caregiver. The 3 trial arms included (1) group-based exercise (GE; 4-hour sessions with approximately 1-hour training) and (2) tailored home-based exercise (HE; 1-hour training), both twice a week for 1 year, and (3) a control group (CG) receiving the usual community care. The Functional Independence Measure (FIM), the Short Physical Performance Battery, and information on the use and costs of social and health care services. All groups deteriorated in functioning during the year after randomization, but deterioration was significantly faster in the CG than in the HE or GE group at 6 (P = .003) and 12 (P = .015) months. The FIM changes at 12 months were -7.1 (95% CI, -3.7 to -10.5), -10.3 (95% CI, -6.7 to -13.9), and -14.4 (95% CI, -10.9 to -18.0) in the HE group, GE group, and CG, respectively. The HE and GE groups had significantly fewer falls than the CG during the follow-up year. The total costs of health and social services for the HE patient-caregiver dyads (in US dollars per dyad per year) were $25,112 (95% CI, $17,642 to $32,581) (P = .13 for comparison with the CG), $22,066 in the GE group ($15,931 to $28,199; P = .03 vs CG), and $34,121 ($24,559 to $43,681) in the CG. An intensive and long-term exercise program had beneficial effects on the physical functioning of patients with AD without increasing the total costs of health and social services or causing any significant adverse effects. anzctr.org.au Identifier: ACTRN12608000037303.

hCG, the wonder of today's science

PubMed Central

2012-01-01

Background hCG is a wonder. Firstly, because hCG is such an extreme molecule. hCG is the most acidic glycoprotein containing the highest proportion of sugars. Secondly, hCG exists in 5 common forms. Finally, it has so many functions ranging from control of human pregnancy to human cancer. This review examines these molecules in detail. Content These 5 molecules, hCG, sulfated hCG, hyperglycosylated hCG, hCG free beta and hyperglycosylated free beta are produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells (group 1), and by placental cytotrophoblast cells and human malignancies (group 2). Group 1 molecules are both hormones that act on the hCG/LH receptor. These molecules are central to human menstrual cycle and human pregnancy. Group 2 molecules are autocrines, that act by antagonizing a TGF beta receptor. These molecules are critical to all advanced malignancies. Conclusions The hCG groups are molecules critical to both the molecules of pregnancy or human life, and to the advancement of cancer, or human death. PMID:22455390

Evidence for, and Associated Risks with, the Human Chorionic Gonadotropin Supplemented Diet.

PubMed

Butler, Stephen A; Cole, Laurence A

2016-11-01

Trend diets can be commonplace amongst those who are trying to lose weight but in most cases there is some shred of evidence to suggest they might be of some benefit. Seldom is there a diet which is such a fad that it is not only completely unfounded but also potential harmful. The human chorionic gonadotropin or "hCG diet" is such a diet, which after half a century still has no evidence to support its efficacy; in fact all scientific publications subsequent to the original article counter these claims. In this short communication, we review the literature and present data on exactly what some of the hCG diet preparations actually contain and highlight that, based on current data, these may do more harm than good. It is worrying that more consideration is not given to the possible danger of administration of hCG preparations to individuals without an evidence-based rational.

Impact of a congregation-based intervention on uptake of HIV testing and linkage to care among pregnant women in Nigeria: The Baby Shower cluster randomized trial

PubMed Central

Ezeanolue, Echezona E.; Obiefune, Michael C; Ezeanolue, Chinenye O; Ehiri, John E.; Osuji, Alice; Ogidi, Amaka G.; Hunt, Aaron T.; Patel, Dina; Yang, Wei; Pharr, Jennifer; Ogedegbe, Gbenga

2016-01-01

Summary Background There is a dearth of effective community-based interventions to increase HIV testing and uptake of antiretroviral therapy (ART) among pregnant women in hard–to-reach resource-limited settings. We assessed whether a faith-based intervention, the Healthy Beginning Initiative (HBI), would increase uptake of HIV testing and ART among pregnant women as compared to health facility referral. Methods This trial was conducted in southeast Nigeria, between January 20, 2013, and August 31, 2014. Eligible churches had at least 20 annual infant baptisms. Forty churches (clusters), stratified by number of infant baptisms (<80 vs. >80) were randomized 1:1 to intervention (IG) or control (CG). Three thousand and two (3002) self-identified pregnant women aged 18 and older participated. Intervention included heath education and onsite laboratory testing implemented during baby shower in IG churches, while participants in CG churches were referred to health facilities. Primary outcome (confirmed HIV testing) and secondary outcome (receipt of ART during pregnancy) were assessed at the individual level. Findings Antenatal care attendance was similar in both groups (IG=79.4% [1309/1647] vs. CG=79.7% [1080/1355], P=0.8). The intervention was associated with higher HIV testing (CG=54.6% [740/1355] vs. IG =91.9% [1514/1647]; [AOR= 11.2; 95% CI: 8.77-14.25, P-value=<0.001]. Women in the IG were significantly more likely to be linked to care prior to delivery (P<0.01) and more likely to have received ART during pregnancy (P=0.042) compared to those in the CG. Interpretation Culturally-adapted, community-based programs such as HBI can be effective in increasing HIV screening and ART among pregnant women in resource-limited settings. Funding National Institute of Health and President's Emergency Plan for AIDS Relief PMID:26475016

The systematic regulation of oyster CgIL17-1 and CgIL17-5 in response to air exposure.

PubMed

Xin, Lusheng; Zhang, Huan; Du, Xinyu; Li, Yiqun; Li, Meijia; Wang, Lingling; Wang, Hao; Qiu, Limei; Song, Linsheng

2016-10-01

As a proinflammatory cytokine, vertebrate interleukin 17 (IL17) plays a vital role in the balance of inflammation and homeostasis, and is involved in a systemic regulation of glucose homeostasis. In the present study, a remarkable increase of glucose concentration was observed in oyster serum after 2 d air exposure, which was followed by a rapid up-regulation of CgIL17-1 and CgIL17-5. After oysters was received an injection of extra glucose, the mRNA expressions of CgIL17-1 and CgIL17-5 were also significantly up-regulated. The histopathological changes of hepatopancreas were observed after the oysters were treated by the recombinant proteins of CgIL17-1 and CgIL17-5 in vivo or subjected to air exposure. A significant decrease of GSK3β (Glycogen synthase kinase-3β) protein was also observed after the injection of CgIL17-1 and CgIL17-5 recombinant proteins in vivo. When the oysters with CgIL17-1 and CgIL17-5 genes knocked down were subjected to air exposure, the decline of GSK3β concentration was slowed down and it could still be obviously detected after 7 d compared with that in the control. Meanwhile, the expression of CgDefensin and CgDFFA was inhibited, while CgIAP was up-regulated when CgIL17-1 and CgIL17-5 genes were knocked down, and the oysters exhibited higher mortality (p < 0.05) at 3 d, whereas lower at the late stage of air exposure compared with that in the controls. The results collectively suggested that once oysters were exposed to air, the synthesis of proinflammatory cytokines CgIL17-1 and CgIL17-5 was induced by the up-regulated glucose concentration in oyster serum, which would be not only a negative feedback to the high glucose concentration through mediating the regulation of GSK3β, but also an inducer on tissue damage and immunocompetence as well as the adaptability to stresses. Copyright © 2016 Elsevier Ltd. All rights reserved.

A temperature-dependent coarse-grained model for the thermoresponsive polymer poly(N-isopropylacrylamide).

PubMed

Abbott, Lauren J; Stevens, Mark J

2015-12-28

A coarse-grained (CG) model is developed for the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAM), using a hybrid top-down and bottom-up approach. Nonbonded parameters are fit to experimental thermodynamic data following the procedures of the SDK (Shinoda, DeVane, and Klein) CG force field, with minor adjustments to provide better agreement with radial distribution functions from atomistic simulations. Bonded parameters are fit to probability distributions from atomistic simulations using multi-centered Gaussian-based potentials. The temperature-dependent potentials derived for the PNIPAM CG model in this work properly capture the coil-globule transition of PNIPAM single chains and yield a chain-length dependence consistent with atomistic simulations.

A new nonlinear conjugate gradient coefficient under strong Wolfe-Powell line search

NASA Astrophysics Data System (ADS)

Mohamed, Nur Syarafina; Mamat, Mustafa; Rivaie, Mohd

2017-08-01

A nonlinear conjugate gradient method (CG) plays an important role in solving a large-scale unconstrained optimization problem. This method is widely used due to its simplicity. The method is known to possess sufficient descend condition and global convergence properties. In this paper, a new nonlinear of CG coefficient βk is presented by employing the Strong Wolfe-Powell inexact line search. The new βk performance is tested based on number of iterations and central processing unit (CPU) time by using MATLAB software with Intel Core i7-3470 CPU processor. Numerical experimental results show that the new βk converge rapidly compared to other classical CG method.

A modified conjugate gradient coefficient with inexact line search for unconstrained optimization

NASA Astrophysics Data System (ADS)

Aini, Nurul; Rivaie, Mohd; Mamat, Mustafa

2016-11-01

Conjugate gradient (CG) method is a line search algorithm mostly known for its wide application in solving unconstrained optimization problems. Its low memory requirements and global convergence properties makes it one of the most preferred method in real life application such as in engineering and business. In this paper, we present a new CG method based on AMR* and CD method for solving unconstrained optimization functions. The resulting algorithm is proven to have both the sufficient descent and global convergence properties under inexact line search. Numerical tests are conducted to assess the effectiveness of the new method in comparison to some previous CG methods. The results obtained indicate that our method is indeed superior.

Effects of eCG and FSH on ovarian response, recovery rate and number and quality of oocytes obtained by ovum pick-up in Holstein cows.

PubMed

Sendag, Sait; Cetin, Yunus; Alan, Muhammet; Hadeler, Klaus-Gerd; Niemann, Heiner

2008-06-01

The goal of the present study was to compare the ovarian response, oocyte yields per animal, and the morphological quality of oocytes collected by ultrasound guided follicular aspiration from Holstein cows treated either with FSH or eCG. Twenty four normal cyclic, German Holstein cows were randomly divided into two groups. Fourteen cows received 3000 IU eCG on day-4 prior to ovum pick-up (OPU) (day 0), 2 days later (day-2), 625 microg cloprostenol was administered. On day-1 GnRH was administered i.m. and 24h later OPU (day 0) was performed. In ten cows a total dose of 500 IU follicle stimulating hormone (Pluset) was administered intramuscularly in a constant dosage for 4 days with intervals of 12h, starting on day-5. Luteolysis was induced by application of 625 microg cloprostenol on day-2. On day-1 (24h after the last FSH treatment) GnRH was administered i.m. and 24h later OPU (day 0) was performed. Ovarian follicles were visualized on the ultrasound monitor, counted and recorded. All visible antral follicles were punctured. Recovered oocytes were graded morphologically based on the cumulus investment. Average follicle number in ovaries was higher in FSH group than eCG group (p<0.05). Oocyte yields per animal did not differ between FSH and eCG groups. The proportion of grade A oocytes was higher in the FSH group in the than eCG group (p<0.05). Likewise, rate of grade C oocytes in FSH group were lower than eCG group (p<0.05). In conclusion, these results suggest that ovarian response, follicle number in ovaries and oocyte quality are affected by the type of gonadotropin and FSH is better alternative than eCG for OPU treatment.

Validation of the Predictive Value of Modeled Human Chorionic Gonadotrophin Residual Production in Low-Risk Gestational Trophoblastic Neoplasia Patients Treated in NRG Oncology/Gynecologic Oncology Group-174 Phase III Trial.

PubMed

You, Benoit; Deng, Wei; Hénin, Emilie; Oza, Amit; Osborne, Raymond

2016-01-01

In low-risk gestational trophoblastic neoplasia, chemotherapy effect is monitored and adjusted with serum human chorionic gonadotrophin (hCG) levels. Mathematical modeling of hCG kinetics may allow prediction of methotrexate (MTX) resistance, with production parameter "hCGres." This approach was evaluated using the GOG-174 (NRG Oncology/Gynecologic Oncology Group-174) trial database, in which weekly MTX (arm 1) was compared with dactinomycin (arm 2). Database (210 patients, including 78 with resistance) was split into 2 sets. A 126-patient training set was initially used to estimate model parameters. Patient hCG kinetics from days 7 to 45 were fit to: [hCG(time)] = hCG7 * exp(-k * time) + hCGres, where hCGres is residual hCG tumor production, hCG7 is the initial hCG level, and k is the elimination rate constant. Receiver operating characteristic (ROC) analyses defined putative hCGRes predictor of resistance. An 84-patient test set was used to assess prediction validity. The hCGres was predictive of outcome in both arms, with no impact of treatment arm on unexplained variability of kinetic parameter estimates. The best hCGres cutoffs to discriminate resistant versus sensitive patients were 7.7 and 74.0 IU/L in arms 1 and 2, respectively. By combining them, 2 predictive groups were defined (ROC area under the curve, 0.82; sensitivity, 93.8%; specificity, 70.5%). The predictive value of hCGres-based groups regarding resistance was reproducible in test set (ROC area under the curve, 0.81; sensitivity, 88.9%; specificity, 73.1%). Both hCGres and treatment arm were associated with resistance by logistic regression analysis. The early predictive value of the modeled kinetic parameter hCGres regarding resistance seems promising in the GOG-174 study. This is the second positive evaluation of this approach. Prospective validation is warranted.

A product of the bicistronic Drosophila melanogaster gene CG31241, which also encodes a trimethylguanosine synthase, plays a role in telomere protection.

PubMed

Komonyi, Orban; Schauer, Tamas; Papai, Gabor; Deak, Peter; Boros, Imre M

2009-03-15

Although telomere formation occurs through a different mechanism in Drosophila compared with other organisms, telomere associations result from mutations in homologous genes, indicating the involvement of similar pathways in chromosome end protection. We report here that mutations of the Drosophila melanogaster gene CG31241 lead to high frequency chromosome end fusions. CG31241 is a bicistronic gene that encodes trimethylguanosine synthase (TGS1), which forms the m3G caps of noncoding small RNAs, and a novel protein, DTL. We show that although TGS1 has no role in telomere protection, DTL is localized at specific sites, including the ends of polytene chromosomes, and its loss results in telomere associations. Mutations of ATM- and Rad3-related (ATR) kinase suppress telomere fusions in the absence of DTL. Thus, genetic interactions place DTL in an ATR-related pathway in telomere protection. In contrast to ATR kinase, mutations of ATM (ataxia telangiectasia mutated) kinase, which acts in a partially overlapping pathway of telomere protection, do not suppress formation of telomere associations in the absence of DTL. Thus, uncovering the role of DTL will help to dissect the evolutionary conserved pathway(s) controlling ATM-ATR-related telomere protection.

[Impact of a psychosocial intervention in caregiver burden of children with cerebral palsy].

PubMed

Martínez Lazcano, Félix; Avilés Cura, Manuel; Ramírez Aranda, José Manuel; Riquelme Heras, Héctor; Garza Elizondo, Teófilo; Barrón Garza, Fabiola

2014-10-01

To demonstrate that problem-solving therapy is effective in reducing the burden on caregivers of children with cerebral palsy. Randomized clinical trial. Check primary care within a private nonprofit association. 140caregivers divided into control group (CG) and experimental group (EG). We performed in both groups a psychosocial intervention with a frequency of one session per week for three weeks to complete 120minutes. In the EG performed a shortened form of problem-solving therapy with a focus on caregiver burden and the CG performed an educational intervention focusing on respiratory diseases. The response variable corresponds to the score obtained by Zarit questionnaire. The independent variable accounted for psychosocial intervention. In the EG according to Zarit questionnaire score was obtained by averaging 45.0 points pre intervention against 45.3 points in the CP after intervention Zarit was obtained by averaging 29.8 points in the EG and 44.3 points in the CG (P<.0001). The catalog groups according to their score Zarit in charge: none, mild, moderate and severe impact differences were found in the different intervention categories (Wilcoxon test Z=6.281, P<.00001). Problem solving therapy is effective in reducing the burden on caregivers of children with cerebral palsy. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

In situ measurements of contributions to the global electrical circuit by a thunderstorm in southeastern Brazil

USGS Publications Warehouse

Thomas, J.N.; Holzworth, R.H.; McCarthy, M.P.

2009-01-01

The global electrical circuit, which maintains a potential of about 280??kV between the earth and the ionosphere, is thought to be driven mainly by thunderstorms and lightning. However, very few in situ measurements of electrical current above thunderstorms have been successfully obtained. In this paper, we present dc to very low frequency electric fields and atmospheric conductivity measured in the stratosphere (30-35??km altitude) above an active thunderstorm in southeastern Brazil. From these measurements, we estimate the mean quasi-static conduction current during the storm period to be 2.5 ?? 1.25??A. Additionally, we examine the transient conduction currents following a large positive cloud-to-ground (+ CG) lightning flash and typical - CG flashes. We find that the majority of the total current is attributed to the quasi-static thundercloud charge, rather than lightning, which supports the classical Wilson model for the global electrical circuit.

Working on the "Write" Path: Improving EFL Students' Argumentative-Writing Performance through L1-Mediated Structural Cognitive Modification

ERIC Educational Resources Information Center

Salmani Nodoushan, Mohammad Ali

2016-01-01

Based on their scores on a proficiency test, the 894 participants in this study were grouped into three experimental groups (EG) and three control groups (CG). They attempted an argumentative writing task and the Cornell Critical Thinking Test, Form Z (CCTT-Form Z) as the pre-test. While CG participants received no treatment or placebo, EG…

Actively station: Effects on global cognition of mature adults and healthy elderly program using eletronic games

PubMed Central

Ordonez, Tiago Nascimento; Borges, Felipe; Kanashiro, Camila Sato; Santos, Carolina Carneiro das Neves; Hora, Samara Santos; Lima-Silva, Thais Bento

2017-01-01

Studies show that aging is accompanied by decline in cognitive functions but also indicate that interventions, such as training on electronic games, can enhance performance and promote maintenance of cognitive abilities in healthy older adults. Objective To investigate the effects of an electronic game program, called Actively Station, on the performance of global cognition of adults aged over 50 years. Methods 124 mature and elderly adults enrolled in the "Actively Station" cognitive stimulation program of São Caetano do Sul City, in the State of São Paulo, participated in training for learning of electronic games. Participants were divided into two groups: training group (TG) n=102 and control group (CG) n=22. Protocol: a sociodemographic questionnaire, the Mini-Mental State Examination (MMSE), the Addenbrooke's Cognitive Examination Revised (ACE-R), the Memory Complaint Questionnaire (MAC-Q), the scale of frequency of forgetfulness, the Geriatric Depression Scale (GDS-15), the Geriatric Anxiety Inventory (GAI), the Global Satisfaction with Life Scale, and two scales on learning in the training. Results The cognitive performance of the TG improved significantly after the program, particularly in the domains of language and memory, and there was a decrease on the anxiety index and frequency of memory complaints, when compared to the CG. Conclusion These findings suggest that the acquisition of new knowledge and the use of new stimuli, such as electronic games, can promote improvements in cognition and mood and reduce the frequency of memory complaints. PMID:29213510

Fundamental relationship between the noise properties of grating-based differential phase contrast CT and absorption CT: theoretical framework using a cascaded system model and experimental validation.

PubMed

Li, Ke; Bevins, Nicholas; Zambelli, Joseph; Chen, Guang-Hong

2013-02-01

Using a grating interferometer, a conventional x-ray cone beam computed tomography (CT) data acquisition system can be used to simultaneously generate both conventional absorption CT (ACT) and differential phase contrast CT (DPC-CT) images from a single data acquisition. Since the two CT images were extracted from the same set of x-ray projections, it is expected that intrinsic relationships exist between the noise properties of the two contrast mechanisms. The purpose of this paper is to investigate these relationships. First, a theoretical framework was developed using a cascaded system model analysis to investigate the relationship between the noise power spectra (NPS) of DPC-CT and ACT. Based on the derived analytical expressions of the NPS, the relationship between the spatial-frequency-dependent noise equivalent quanta (NEQ) of DPC-CT and ACT was derived. From these fundamental relationships, the NPS and NEQ of the DPC-CT system can be derived from the corresponding ACT system or vice versa. To validate these theoretical relationships, a benchtop cone beam DPC-CT/ACT system was used to experimentally measure the modulation transfer function (MTF) and NPS of both DPC-CT and ACT. The measured three-dimensional (3D) MTF and NPS were then combined to generate the corresponding 3D NEQ. Two fundamental relationships have been theoretically derived and experimentally validated for the NPS and NEQ of DPC-CT and ACT: (1) the 3D NPS of DPC-CT is quantitatively related to the corresponding 3D NPS of ACT by an inplane-only spatial-frequency-dependent factor 1∕f (2), the ratio of window functions applied to DPC-CT and ACT, and a numerical factor C(g) determined by the geometry and efficiency of the grating interferometer. Note that the frequency-dependent factor is independent of the frequency component f(z) perpendicular to the axial plane. (2) The 3D NEQ of DPC-CT is related to the corresponding 3D NEQ of ACT by an f (2) scaling factor and numerical factors that depend on both the attenuation and refraction properties of the image object, as well as C(g) and the MTF of the grating interferometer. The performance of a DPC-CT system is intrinsically related to the corresponding ACT system. As long as the NPS and NEQ of an ACT system is known, the corresponding NPS and NEQ of the DPC-CT system can be readily estimated using additional characteristics of the grating interferometer.

A 43-year-old woman with unexplained elevation of hCG.

PubMed

Johnson, Lisa M; Gniadek, Thomas J; Cohn, Claudia S; Bachowski, Gary; Karger, Amy B

2018-05-01

This case report investigates an unusual hCG result in a woman who is not pregnant. A 43-year-old woman was admitted for recurrence of thrombotic thrombocytopenic purpura (TTP) and therapeutic plasma exchange (TPE) was initiated. Prior to transitioning the patient from TPE to immunosuppressive therapy, a serum qualitative hCG test was performed and was positive. Several etiologies for elevated hCG were considered and investigated, including heterophile antibody interference, endogenous hCG from pituitary or malignancy, and exogenous hCG. Retrospective measurement of hCG levels in remnant samples, including a sample obtained prior to TPE initiation, demonstrated that the hCG elevation occurred with plasma administration for TPE. Further investigation with the American Red Cross confirmed that a plasma donor was unknowingly pregnant and in the latter half of the first trimester at the time of donation, when hCG levels peak. In plasma recipients with unexplained hCG elevation, passive transfer of hCG from plasma should be considered in the differential diagnosis. Retrospective measurement of hCG in remnant samples obtained prior to plasma exchange can assist in confirming the source. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Preliminary evidence for associations between second-trimester human chorionic gonadotropin and unconjugated oestriol levels with pregnancy outcome in Down syndrome pregnancies.

PubMed

Benn, P A

1998-04-01

Fifty-six cases of Down syndrome were identified in a population of women who had undergone maternal serum triple marker screening [alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated oestriol (uE3) analyses]. These affected pregnancies represented all known cases present in the population of 34,368 women screened. Using a 1:270 mid-trimester Down syndrome risk to define the screen-positive group, 42 affected pregnancies were screen-positive (medians: AFP = 0.79 MOM, hCG = 2.13 MOM, uE3 = 0.62 MOM, age 34.6 years) and 14 pregnancies were screen-negative (medians: AFP = 0.82 MOM, hCG = 1.57 MOM, uE3 = 0.92 MOM, age 24.2 years). Four affected pregnancies were associated with in utero death and each of these cases was associated with relatively extreme values of AFP, hCG, and uE3, including the three highest levels of hCG in the entire series of Down syndrome pregnancies. Twenty-nine (15 screen-positive and 14 screen-negative) affected pregnancies resulted in liveborns. Down syndrome pregnancies had a significantly shorter gestational term than controls, and Down syndrome babies were also lighter than controls, even after adjustment for sex and gestational age. In affected pregnancies, a low uE3 level appeared to be associated with a greater chance of a small-for-gestational age baby. No correlations could be demonstrated between AFP or hCG levels and gestational age-adjusted term weight. Based on this small series, it would appear that uE3 may be particularly useful in detecting those Down syndrome cases associated with small-for-gestational age fetuses. A very high hCG value may indicate a higher probability of fetal death.

Promoting healthy weight among elementary school children via a health report card approach.

PubMed

Chomitz, Virginia R; Collins, Jessica; Kim, Juhee; Kramer, Ellen; McGowan, Robert

2003-08-01

As overweight continues to rise among children, schools seek effective and sensitive ways to engage parents in promoting healthy weight. To evaluate a school-based health report card on the family awareness of and concern about the child weight status, plans for weight control, and preventive behaviors. Quasi-experimental field trial with a personalized weight and fitness health report card intervention (PI), a general-information intervention (GI), and a control group (CG). Outcomes were assessed using a postintervention telephone survey, including process and outcome measures. The intervention included 1396 ethnically diverse students at 4 elementary schools in an urban area. Telephone surveys were completed by 399 families from an evaluation sample of 793. Intervention Families were randomly assigned to the PI, GI, or CG and mailed intervention materials. The CG was mailed GI materials after the survey. Parent awareness of child weight status, concerns, weight-control plans, and preventive behaviors. Group effects were significantly different by the child's weight status, so results were stratified. Among overweight students, intervention parents were more likely to know their child's weight status (PI, 44%; GI, 41%; CG, 23%) (P =.02). The PI parents planned medical help (PI, 25%; GI, 7%; CG, 9%) (P =.004), dieting activities (PI, 19%; GI and CG, <5 cases) (P =.02) and physical activities (PI, 42%; GI, 27%; CG, 13%) (P<.001) for their overweight children. No group effect on concern or preventive behaviors was detected. Most parents of overweight children who read materials requested annual weight and health information on their child (PI, 91%; GI, 67%). Among overweight children, the PI was associated with increased parental awareness of their child's weight status. Although parents wanted PI for their children, more research is needed to test this approach on children's self-esteem and plans for weight control.

Role of community group exposure in reducing sexually transmitted infection-related risk among female sex workers in India.

PubMed

Yadav, Diwakar; Ramanathan, Shreena; Goswami, Prabuddhagopal; Ramakrishnan, Lakshmi; Saggurti, Niranjan; Sen, Shrabanti; George, Bitra; Paranjape, Ramesh

2013-01-01

Empowering female sex workers (FSWs) to address structural barriers and forming community groups (CGs) through community mobilization are seen as essential components of HIV prevention programs in India. Taking the membership of a CG as an exposure intervention, we hypothesized whether participation in a CG lead to reduced sexually transmitted infections (STIs) and increased treatment-seeking behavior among FSWs in three selected states of India--Andhra Pradesh, Maharashtra and Tamil Nadu. The propensity score matching (PSM) approach examined the effect of CG membership, as against no membership, on STI-related risk, described as selected outcome measures--presence of any STI, self-reported STI symptoms, and treatment-seeking behavior among FSWs. A cross sectional bio-behavioral survey was administered in 2009-2010 and covered 7,806 FSWs through two-stage probability-based conventional and time location cluster sampling in 23 administrative districts of Andhra Pradesh, Maharashtra and Tamil Nadu. Only 2,939 FSWs were reported to be members of a CG and among them 4.5% had any STIs. A majority of FSWs were aged above 24 years (86.4%), had ever been married (73%), operated from a public place for solicitation (81.5%), and had ever received HIV test results (75.6%). The average effect of CG exposure was reduction in STI prevalence by 4%, while self-reported STI symptom treatment-seeking behavior increased by 13.7%. FSWs who were exposed to a CG were at a substantially lower risk of STIs than those who were unexposed. The FSWs exposed to a CG had a higher chance of seeking STI treatment from public and private health facilities. Collectivization related challenges must be overcome to provide access to tailored STI prevention and care services.

Role of Community Group Exposure in Reducing Sexually Transmitted Infection-Related Risk among Female Sex Workers in India

PubMed Central

Yadav, Diwakar; Ramanathan, Shreena; Goswami, Prabuddhagopal; Ramakrishnan, Lakshmi; Saggurti, Niranjan; Sen, Shrabanti; George, Bitra; Paranjape, Ramesh

2013-01-01

Background Empowering female sex workers (FSWs) to address structural barriers and forming community groups (CGs) through community mobilization are seen as essential components of HIV prevention programs in India. Taking the membership of a CG as an exposure intervention, we hypothesized whether participation in a CG lead to reduced sexually transmitted infections (STIs) and increased treatment-seeking behavior among FSWs in three selected states of India — Andhra Pradesh, Maharashtra and Tamil Nadu. Methods and Findings The propensity score matching (PSM) approach examined the effect of CG membership, as against no membership, on STI-related risk, described as selected outcome measures — presence of any STI, self-reported STI symptoms, and treatment-seeking behavior among FSWs. A cross sectional bio-behavioral survey was administered in 2009–2010 and covered 7,806 FSWs through two-stage probability-based conventional and time location cluster sampling in 23 administrative districts of Andhra Pradesh, Maharashtra and Tamil Nadu. Only 2,939 FSWs were reported to be members of a CG and among them 4.5% had any STIs. A majority of FSWs were aged above 24 years (86.4%), had ever been married (73%), operated from a public place for solicitation (81.5%), and had ever received HIV test results (75.6%). The average effect of CG exposure was reduction in STI prevalence by 4%, while self-reported STI symptom treatment-seeking behavior increased by 13.7%. Conclusion FSWs who were exposed to a CG were at a substantially lower risk of STIs than those who were unexposed. The FSWs exposed to a CG had a higher chance of seeking STI treatment from public and private health facilities. Collectivization related challenges must be overcome to provide access to tailored STI prevention and care services. PMID:24205210

Ten tandem repeats of {beta}-hCG 109-118 enhance immunogenicity and anti-tumor effects of {beta}-hCG C-terminal peptide carried by mycobacterial heat-shock protein HSP65

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

Zhang Yankai; Yan Rong; He Yi

2006-07-14

The {beta}-subunit of human chorionic gonadotropin ({beta}-hCG) is secreted by many kinds of tumors and it has been used as an ideal target antigen to develop vaccines against tumors. In view of the low immunogenicity of this self-peptide,we designed a method based on isocaudamer technique to repeat tandemly the 10-residue sequence X of {beta}-hCG (109-118), then 10 tandemly repeated copies of the 10-residue sequence combined with {beta}-hCG C-terminal 37 peptides were fused to mycobacterial heat-shock protein 65 to construct a fusion protein HSP65-X10-{beta}hCGCTP37 as an immunogen. In this study, we examined the effect of the tandem repeats of this 10-residuemore » sequence in eliciting an immune by comparing the immunogenicity and anti-tumor effects of the two immunogens, HSP65-X10-{beta}hCGCTP37 and HSP65-{beta}hCGCTP37 (without the 10 tandem repeats). Immunization of mice with the fusion protein HSP65-X10-{beta}hCGCTP37 elicited much higher levels of specific anti-{beta}-hCG antibodies and more effectively inhibited the growth of Lewis lung carcinoma (LLC) in vivo than with HSP65-{beta}hCGCTP37, which should suggest that HSP65-X10-{beta}hCGCTP37 may be an effective protein vaccine for the treatment of {beta}-hCG-dependent tumors and multiple tandem repeats of a certain epitope are an efficient method to overcome the low immunogenicity of self-peptide antigens.« less

The Role of Serum Beta hCG in Early Diagnosis and Management Strategy of Ectopic Pregnancy.

PubMed

Surampudi, Kameswari; Gundabattula, Sirisha Rao

2016-07-01

The presentation of Ectopic Pregnancy (EP) can be highly variable and serum Beta hCG estimation plays an important role in early diagnosis. Aim of the study was to determine the trends of hCG levels in EP and to explore the role of hCG in decisions related to management and follow-up of EPs. A retrospective study of women who had EPs from January 2006 to December 2012 at an advanced tertiary care centre in southern India was carried out. These women had undergone treatment based on the hospital protocol. The study identified 337 women with EP. Thirty one surgically confirmed cases were diagnosed below the discriminatory zone of 1500 mIU/ml. Among women who had Beta hCG estimations 48 hours apart, plateauing was observed in 22.5% while decrease >15% was noted in 26.8%. Almost half (47.9%) of the cases had an increase >15% and a few (2.8%) demonstrated an initial fall followed by a rise in titres. In 23.9% of these women, there was a rise >53% similar to intrauterine pregnancy. The average pre-treatment Beta hCG was 429.8, 3866.2 and 12961.5 mIU/ml for those who received expectant, medical and direct surgical treatment respectively. 43 women with relative contraindications received medical management and 39 were lost to follow-up after medical and expectant management. Excluding them, the success rate of these two modalities was 76.6% and 85.0% respectively. No single level of Beta hCG is diagnostic of EP and serial levels can demonstrate atypical trends in some cases. Hence, interpretation of these results should be done in conjunction with clinical and sonographic findings to arrive at a correct diagnosis.

Use of equine chorionic gonadotropin to control reproduction of the dairy cow: a review.

PubMed

De Rensis, F; López-Gatius, F

2014-04-01

Equine chorionic gonadotropin (eCG) is a member of the glycoprotein family of hormones along with LH, FSH and thyroid-stimulating hormone. In non-equid species, eCG shows high LH- and FSH-like activities and has a high affinity for both FSH and LH receptors in the ovaries. On the granulosa and thecal cells of the follicle, eCG has long-lasting LH- and FSH-like effects that stimulate oestradiol and progesterone secretion. Thus, eCG administration in dairy cattle results in fewer atretic follicles, the recruitment of more small follicles showing an elevated growth rate, the sustained growth of medium and large follicles and improved development of the dominant and pre-ovulatory follicle. In consequence, the quality of the ensuing CL is improved, and thereby progesterone secretion increased. Based on these characteristics, eCG treatment is utilized in veterinary medicine to control the reproductive activity of the cow by i) improving reproductive performance during early post-partum stages; ii) increasing ovulation and pregnancy rates in non-cyclic cows; iii) improving the conception rate in cows showing delayed ovulation; and finally, iv) eCG is currently included in protocols for fixed-time artificial insemination since after inducing the synchrony of ovulation using a progesterone-releasing device, eCG has beneficial effects on embryo development and survival. The above effects are not always observed in cyclic animals, but they are evident in animals in which LH secretion and ovarian activity are reduced or compromised, for instance, during the early post-partum period, under seasonal heat stress, in anoestrus animals or in animals with a low body condition score. © 2014 Blackwell Verlag GmbH.

miRNA-Processing Gene Methylation and Cancer Risk.

PubMed

Joyce, Brian T; Zheng, Yinan; Zhang, Zhou; Liu, Lei; Kocherginsky, Masha; Murphy, Robert; Achenbach, Chad J; Musa, Jonah; Wehbe, Firas; Just, Allan; Shen, Jincheng; Vokonas, Pantel; Schwartz, Joel; Baccarelli, Andrea A; Hou, Lifang

2018-05-01

Background: Dysregulation of miRNA and methylation levels are epigenetic hallmarks of cancer, potentially linked via miRNA-processing genes. Studies have found genetic alterations to miRNA-processing genes in cancer cells and human population studies. Our objective was to prospectively examine changes in DNA methylation of miRNA-processing genes and their associations with cancer risk. Methods: We examined cohort data from the Department of Veterans' Affairs Normative Aging Study. Participants were assessed every 3 to 5 years starting in 1999 through 2013 including questionnaires, medical record review, and blood collection. Blood from 686 consenting participants was analyzed using the Illumina 450K BeadChip array to measure methylation at CpG sites throughout the genome. We selected 19 genes based on a literature review, with 519 corresponding CpG sites. We then used Cox proportional hazards models to examine associations with cancer incidence, and generalized estimating equations to examine associations with cancer prevalence. Associations at false discovery rate < 0.05 were considered statistically significant. Results: Methylation of three CpGs ( DROSHA : cg23230564, TNRC6B : cg06751583, and TNRC6B : cg21034183) was prospectively associated with time to cancer development (positively for cg06751583, inversely for cg23230564 and cg21034183), whereas methylation of one CpG site ( DROSHA : cg16131300) was positively associated with cancer prevalence. Conclusions: DNA methylation of DROSHA , a key miRNA-processing gene, and TNRC6B may play a role in early carcinogenesis. Impact: Changes in miRNA processing may exert multiple effects on cancer development, including protecting against it via altered global miRNAs, and may be a useful early detection biomarker of cancer. Cancer Epidemiol Biomarkers Prev; 27(5); 550-7. ©2018 AACR . ©2018 American Association for Cancer Research.

Postmolar gestational trophoblastic neoplasia: beyond the traditional risk factors.

PubMed

Bakhtiyari, Mahmood; Mirzamoradi, Masoumeh; Kimyaiee, Parichehr; Aghaie, Abbas; Mansournia, Mohammd Ali; Ashrafi-Vand, Sepideh; Sarfjoo, Fatemeh Sadat

2015-09-01

To investigate the slope of linear regression of postevacuation serum hCG as an independent risk factor for postmolar gestational trophoblastic neoplasia (GTN). Multicenter retrospective cohort study. Academic referral health care centers. All subjects with confirmed hydatidiform mole and at least four measurements of β-hCG titer. None. Type and magnitude of the relationship between the slope of linear regression of β-hCG as a new risk factor and GTN using Bayesian logistic regression with penalized log-likelihood estimation. Among the high-risk and low-risk molar pregnancy cases, 11 (18.6%) and 19 cases (13.3%) had GTN, respectively. No significant relationship was found between the components of a high-risk pregnancy and GTN. The β-hCG return slope was higher in the spontaneous cure group. However, the initial level of this hormone in the first measurement was higher in the GTN group compared with in the spontaneous recovery group. The average time for diagnosing GTN in the high-risk molar pregnancy group was 2 weeks less than that of the low-risk molar pregnancy group. In addition to slope of linear regression of β-hCG (odds ratio [OR], 12.74, confidence interval [CI], 5.42-29.2), abortion history (OR, 2.53; 95% CI, 1.27-5.04) and large uterine height for gestational age (OR, 1.26; CI, 1.04-1.54) had the maximum effects on GTN outcome, respectively. The slope of linear regression of β-hCG was introduced as an independent risk factor, which could be used for clinical decision making based on records of β-hCG titer and subsequent prevention program. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Single-dose pharmacokinetic study comparing the pharmacokinetics of recombinant human chorionic gonadotropin in healthy Japanese and Caucasian women and recombinant human chorionic gonadotropin and urinary human chorionic gonadotropin in healthy Japanese women.

PubMed

Bagchus, Wilhelmina; Wolna, Peter; Uhl, Wolfgang

2018-01-01

Recombinant hCG (r-hCG) was approved in Japan in 2016. As a prerequisite for a Phase III study in Japan related to this approval, the pharmacokinetic (PK) profile of r-hCG was investigated. An open-label, partly randomized, single-center, single-dose, group-comparison, Phase I PK-bridging study was done that compared a single 250 μg dose of r-hCG with a single 5000 IU dose of urinary hCG (u-hCG) in healthy Japanese women, as well as comparing a single 250 μg dose of r-hCG in Japanese and Caucasian women. The Japanese participants were randomized 1:1 to receive either r-hCG or u-hCG, while the Caucasian participants were weight-matched to the Japanese participants who were receiving r-hCG in a 1:1 fashion. The primary PK parameters were the area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC 0-∞ ) and the maximum serum concentration (C max ). The mean serum hCG concentration-time profiles of r-hCG in the Japanese and Caucasian participants were a similar shape, but the level of overall exposure was ~20% lower in the Japanese participants. For the Japanese participants, r-hCG resulted in an 11% lower C max but a 19% higher AUC 0-∞ compared with u-hCG. No new safety signal was identified. This study cannot exclude a potential difference in the PK profile of r-hCG between Japanese and Caucasian participants. However, this study does not indicate that there are clinically relevant differences in the serum PK of r-hCG and u-hCG in the Japanese participants.

Thyrotropic action of human chorionic gonadotropin.

PubMed

Yoshimura, M; Hershman, J M

1995-10-01

Hyperthyroidism or increased thyroid function has been reported in many patients with trophoblastic tumors. In these cases, greatly increased human chorionic gonadotropin (hCG) levels and suppressed TSH levels suggest that hCG has thyrotropic activity. Recent investigations have clarified the structural homology not only in the hCG and TSH molecules but also in their receptors, and this homology suggests the basis for the reactivity of hCG with the TSH receptor. The clinical significance of the thyrotropic action of hCG is now also recognized in normal pregnancy and hyperemesis gravidarum. Highly purified hLH binds to recombinant hTSH receptor and is about 10 times as potent as purified hCG in increasing cAMP. The beta-subunits of hCG and hLH share 85% sequence identity in their first 114 amino acids but differ in the carboxy-terminal peptide because hCG beta contains a 31-amino acid extension (beta-CTP). A recombinant mutant hCG that lacks beta-CTP showed almost identical potency to LH on stimulation of recombinant hTSH receptor. If intact hCG were as potent as hLH in regard to its thyrotropic activity, most pregnant women would become thyrotoxic. One of the roles of the beta-CTP may be to prevent overt hyperthyroidism in the first trimester of pregnancy when a large amount of hCG is produced by the placenta. Nicked hCG preparations, obtained from patients with trophoblastic disease or by enzymatic digestion of intact hCG, showed approximately 1.5- to 2-fold stimulation of recombinant hTSH receptor compared with intact hCG. This suggests that the thyrotropic activity of hCG may be influenced by the metabolism of the hCG molecule itself. Deglycosylation and/or desialylation of hCG enhances its thyrotropic potency. Basic hCG isoforms with lower sialic acid content extracted from hydatidiform moles were more potent in activating adenylate cyclase, and showed high bioactivity/immunoactivity (B/I) ratio in CHO cells expressing human TSH receptors. This is consistent with the finding that the beta-CTP truncated hCG with higher thyrotropic potency is substantially deglycosylated and desialylated in the beta-subunit relative to intact hCG because all four O-linked glycosylation sites occur within the missing C-terminal extension. The desialylated hCG variant also interacts directly with recombinant hTSH receptors transfected into human thyroid cancer cells. There is thyroid-stimulating activity in sera of normal pregnant women, and this correlates with serum hCG levels. The thyroid gland of normal pregnant women may be stimulated by hCG to secrete slightly excessive quantities of T4 and induce a slight suppression of TSH, perhaps being about 1 mU/L less than nongravid levels, but not high enough to induce overt hyperthyroidism. Maternal thyroid glands may secrete more thyroid hormone during early pregnancy in response to the thyrotropic activity of hCG that overrides the normal operation of the hypothalamic-pituitary-thyroid feedback system. Biochemical hyperthyroidism associated with hyperemesis gravidarum has been attributed to hCG. In patients with hyperemesis gravidarum, thyrotropic in serum correlated with hCG immunoreactivity, and the severity of vomiting as indicated by clinical and biochemical parameters correlated with the degree of thyroid stimulation. To understand the thyrotropic action of hCG, it is necessary to know whether hCG activates the same domain of the TSH receptor as does TSH. The identification of the molecular structure of the hCG isoform with the highest thyrotropic potency will resolve the enigma of gestational thyrotoxicosis and the hyperthyroidism associated with trophoblastic disease and hCG-producing tumors.

Correlates of Caregiver Participation in a Brief, Community-Based Dementia Care Management Program.

PubMed

Mavandadi, Shahrzad; Patel, Samir; Benson, Amy; DiFilippo, Suzanne; Streim, Joel; Oslin, David

2017-11-10

The evidence base for dementia care management interventions for informal caregivers (CGs) is strong, yet enrollment and sustained engagement in academic and community-based research trials is low. This study sought to examine rates and correlates of participation in a community-based, telephone-delivered dementia care management program designed to address logistic and practical barriers to participation in CG trials and services. Participants included 290 CGs of older, community-dwelling, low-income care recipients (CRs) who met criteria for enrollment in a collaborative dementia care management program that provides assessment, psychosocial support and education, and connection to community resources via telephone. Cross-sectional analyses examined the association between CG-related (e.g., financial status, relationship to CR, caregiving burden) and CR-related (e.g., functional limitations, symptom severity) factors and CG enrollment and engagement. The majority of CGs were non-Hispanic White, female, financially stable, and adult children of the CRs. Over half of CGs lived with the CR and provided 20 or more hours of care per week. Roughly half of CGs refused care management services. Adjusted logistic regression models revealed that perceived caregiving burden and financial status were related to initial enrollment and engagement in services once enrolled, respectively. A significant proportion of CGs refuse free, convenient, evidence-based dementia care management services, underscoring the need for further examination of correlates of program acceptance. Nonetheless, community-based programs that address barriers may improve enrollment and engagement rates among CGs, including those who are especially vulnerable to negative CG and CR outcomes. Published by Oxford University Press on behalf of The Gerontological Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children

PubMed Central

2012-01-01

Background Several association studies have shown that -844 G/A and HindIII C/G PAI-1 polymorphisms are related with increase of PAI-1 levels, obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia, which are components of metabolic syndrome. The aim of this study was to analyze the allele and genotype frequencies of these polymorphisms in PAI-1 gene and its association with metabolic syndrome and its components in a sample of Mexican mestizo children. Methods This study included 100 children with an age range between 6-11 years divided in two groups: a) 48 children diagnosed with metabolic syndrome and b) 52 children metabolically healthy without any clinical and biochemical alteration. Metabolic syndrome was defined as the presence of three or more of the following criteria: fasting glucose levels ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, HDL-cholesterol < 40 mg/dL, obesity BMI ≥ 95th percentile, systolic blood pressure (SBP) and diastolic blood pressure (DBP) ≥ 95th percentile and insulin resistance HOMA-IR ≥ 2.4. The -844 G/A and HindIII C/G PAI-1 polymorphisms were analyzed by PCR-RFLP. Results For the -844 G/A polymorphism, the G/A genotype (OR = 2.79; 95% CI, 1.11-7.08; p = 0.015) and the A allele (OR = 2.2; 95% CI, 1.10-4.43; p = 0.015) were associated with metabolic syndrome. The -844 G/A and A/A genotypes were associated with increase in plasma triglycerides levels (OR = 2.6; 95% CI, 1.16 to 6.04; p = 0.02), decrease in plasma HDL-cholesterol levels (OR = 2.4; 95% CI, 1.06 to 5.42; p = 0.03) and obesity (OR = 2.6; 95% CI, 1.17-5.92; p = 0.01). The C/G and G/G genotypes of the HindIII C/G polymorphism contributed to a significant increase in plasma total cholesterol levels (179 vs. 165 mg/dL; p = 0.02) in comparison with C/C genotype. Conclusions The -844 G/A PAI-1 polymorphism is related with the risk of developing metabolic syndrome, obesity and atherogenic dyslipidemia, and the HindIII C/G PAI-1 polymorphism was associated with the increase of total cholesterol levels in Mexican children. PMID:22459021

Is early weight bearing resumption beneficial after total hip replacement?

PubMed

Merle, J; Rougier, P; Belaid, D; Cantalloube, S; Lamotte, D

2009-04-01

Current rehabilitation protocols of patients following total hip replacement recommend weight bearing on the operated extremity as early as possible. This strategy is likely to induce specific consequences on postural balance control; this study seeks to highlight these reactions to early loading. Eight men and six women, ranging in age from 57 to 85 years, volunteered enrolling this study on their arrival at our rehabilitation center. This study assessed their postural behavior using a system composed of two separate force platforms under two loading situations; in the course of these tests they were required to minimize their body sway as much as possible by keeping their eyes open. In the natural uncontrolled situation, the subjects adopted a comfortable body weight distribution. In the imposed (IMP) situation, they had to load their operated extremity more than in regular natural conditions in order to distribute their body weight more evenly. Three successive 32-s trials (sampled at 64 Hz) with intermediate recovery periods of equivalent duration were performed allowing period of rest between each trial. The balance strategies were evaluated through a frequency analysis of the resultant and plantar centers of pressure (CP(Res)) of each foot and of the estimated trajectories of the vertical projection of the center of gravity (CG), and from the difference CP(Res)-CG. No difference was found for the plantar CP trajectories in the situation where body weight is spontaneously distributed, whereas loading the implanted extremity induced increased CP(Res), CG, and CP(Res)-CG trajectory amplitudes along the mediolateral axis. No effect was observed along the anteroposterior axis. Finally, when comparing the two limbs for each testing condition, the statistical analysis demonstrated greater displacements along the ML axis for the trajectories measured under the healthy leg than under the implanted extremity. Loading the operated extremity early in the rehabilitation process leads to less stability (an increase in the CG movements) and to increased energy expenditure (an increase in the CP(Res)-CG movements). These postural behavior alterations can be explained by various factors including a loss of muscle strength, residual apprehension due to the disuse of this limb, and persistent pain, all of which are increased by limb loading. These features should be taken into consideration when elaborating the rehabilitation protocol for these patients.

Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children.

PubMed

De la Cruz-Mosso, Ulises; Muñoz-Valle, José F; Salgado-Goytia, Lorenzo; García-Carreón, Adrián; Illades-Aguiar, Berenice; Castañeda-Saucedo, Eduardo; Parra-Rojas, Isela

2012-03-29

Several association studies have shown that -844 G/A and HindIII C/G PAI-1 polymorphisms are related with increase of PAI-1 levels, obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia, which are components of metabolic syndrome. The aim of this study was to analyze the allele and genotype frequencies of these polymorphisms in PAI-1 gene and its association with metabolic syndrome and its components in a sample of Mexican mestizo children. This study included 100 children with an age range between 6-11 years divided in two groups: a) 48 children diagnosed with metabolic syndrome and b) 52 children metabolically healthy without any clinical and biochemical alteration. Metabolic syndrome was defined as the presence of three or more of the following criteria: fasting glucose levels ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, HDL-cholesterol < 40 mg/dL, obesity BMI ≥ 95th percentile, systolic blood pressure (SBP) and diastolic blood pressure (DBP) ≥ 95th percentile and insulin resistance HOMA-IR ≥ 2.4. The -844 G/A and HindIII C/G PAI-1 polymorphisms were analyzed by PCR-RFLP. For the -844 G/A polymorphism, the G/A genotype (OR = 2.79; 95% CI, 1.11-7.08; p = 0.015) and the A allele (OR = 2.2; 95% CI, 1.10-4.43; p = 0.015) were associated with metabolic syndrome. The -844 G/A and A/A genotypes were associated with increase in plasma triglycerides levels (OR = 2.6; 95% CI, 1.16 to 6.04; p = 0.02), decrease in plasma HDL-cholesterol levels (OR = 2.4; 95% CI, 1.06 to 5.42; p = 0.03) and obesity (OR = 2.6; 95% CI, 1.17-5.92; p = 0.01). The C/G and G/G genotypes of the HindIII C/G polymorphism contributed to a significant increase in plasma total cholesterol levels (179 vs. 165 mg/dL; p = 0.02) in comparison with C/C genotype. The -844 G/A PAI-1 polymorphism is related with the risk of developing metabolic syndrome, obesity and atherogenic dyslipidemia, and the HindIII C/G PAI-1 polymorphism was associated with the increase of total cholesterol levels in Mexican children.

How primordial is the structure of comet 67P/C-G (and of comets in general)?

NASA Astrophysics Data System (ADS)

Morbidelli, Alessandro; Jutzi, Martin; Benz, Willy; Toliou, Anastasia; Rickman, Hans; Bottke, William; Brasser, Ramon

2016-10-01

Several properties of the comet 67P-CG suggest that it is a primordial planetesimal. On the other hand, the size-frequency distribution (SFD) of the craters detected by the New Horizons missions at the surface of Pluto and Charon reveal that the SFD of trans-Neptunian objects smaller than 100km in diameter is very similar to that of the asteroid belt. Because the asteroid belt SFD is at collisional equilibrium, this observation suggests that the SFD of the trans-Neptunian population is at collisional equilibrium as well, implying that comet-size bodies should be the product of collisional fragmentation and not primordial objects. To test whether comet 67P-CG could be a (possibly lucky) survivor of the original population, we conducted a series of numerical impact experiments, where an object with the shape and the density of 67P-CG, and material strength varying from 10 to 1,000 Pa, is hit on the "head" by a 100m projectile at different speeds. From these experiments we derive the impact energy required to disrupt the body catastrophically, or destroy its bi-lobed shape, as a function of impact speed. Next, we consider a dynamical model where the original trans-Neptunian disk is dispersed during a phase of temporary dynamical instability of the giant planets, which successfully reproduces the scattered disk and Oort cloud populations inferred from the current fluxes of Jupiter-family and long period comets. We find that, if the dynamical dispersal of the disk occurs late, as in the Late Heavy Bombardment hypothesis, a 67P-CG-like body has a negligible probability to avoid all catastrophic collisions. During this phase, however, the collisional equilibrium SFD measured by the New Horizons mission can be established. Instead, if the dispersal of the disk occurred as soon as gas was removed, a 67P-CG-like body has about a 20% chance to avoid catastrophic collisions. Nevertheless it would still undergo 10s of reshaping collisions. We estimate that, statistically, the last reshaping collision should have happened 250My-1Gy ago, implying that the actual morphology of 67P-CG should be younger than this age.

PRKAG3 polymorphisms associated with sporadic Wolff-Parkinson-White syndrome among a Taiwanese population.

PubMed

Weng, Ken-Pen; Yuh, Yeong-Seng; Huang, Shih-Hui; Hsiao, Hsiang-Chiang; Wu, Huang-Wei; Chien, Jen-Hung; Chen, Bo-Hau; Huang, Shih-Ming; Chien, Kuang-Jen; Ger, Luo-Ping

2016-12-01

The aim of this study was to investigate whether mutation in AMP-activated protein kinase (AMPK) subunit genes (PRKAG3-230) is associated with sporadic, isolated Wolff-Parkinson-White (WPW) syndrome. This study consisted of 87 patients with symptomatic WPW syndrome and 93 healthy controls. PRKAG3-230 genotypes were determined using real-time polymerase chain reaction assay. Genotype and allele frequencies of PRKAG3-230 between patients with WPW syndrome and healthy controls were ascertained using chi-square test or Fisher exact test when appropriate. PRKAG3-230 were genotyped in 87 patients (53 men and 34 women; age=24.4±18.0 years) with WPW syndrome and 93 healthy controls (57 men and 36 women; age=16.8±4.2 years). There were no significant differences between the two groups in terms of age and sex. The patients with CG and CG+CC genotypes had a significantly increased risk of WPW syndrome compared with those with GG genotype [odds ratio (OR)=1.99, 95% confidence interval (CI)=1.01-3.89, p=0.045; OR=1.99, 95% CI=1.04-3.78, p=0.037, respectively]. The allelic types were not associated with the risk of WPW syndrome. The patients with manifest type with CG and CG+CC genotypes had a significantly increased risk of WPW syndrome compared with those with GG genotype (OR=2.86, 95% CI=1.16-7.05, p=0.022; OR=2.84, 95% CI=1.19-6.80, p=0.019, respectively). The patients with right-side accessory pathways with CG and CG+CC genotypes had a significantly increased risk of WPW syndrome compared with those with GG genotype (OR=3.07, 95% CI=1.25-7.51, p=0.014; OR=2.84, 95% CI=1.19-6.80, p=0.019, respectively). The allelic types were not associated with the risk of WPW types and locations. This study shows that PRKAG3-230 may be associated with sporadic WPW syndrome among a Taiwanese population. Further studies are warranted to elucidate the role of mutations in AMPK subunit genes other than PRKAG3-230 in sporadic WPW syndrome. Copyright © 2016. Published by Elsevier Taiwan LLC.

The use of equine chorionic gonadotropin in the treatment of anestrous dairy cows in gonadotropin-releasing hormone/progesterone protocols of 6 or 7 days.

PubMed

Bryan, M A; Bó, G; Mapletoft, R J; Emslie, F R

2013-01-01

In seasonally calving, pasture-based dairy farm systems, the interval from calving to first estrus is a critical factor affecting reproductive efficiency. This study evaluated the effects of equine chorionic gonadotropin (eCG) on the reproductive response of lactating, seasonally calving dairy cows diagnosed with anovulatory anestrus by rectal palpation. Cows on 15 commercial dairy farms were selected for initial inclusion based on nonobserved estrus by 7 d before the planned start of mating. All cows were palpated rectally and evaluated for body condition score and ovary score, and were included for treatment according to the trial protocol if diagnosed with anovulatory anestrus. All cows received a standard anestrous treatment protocol consisting of insertion of a progesterone device, injection of 100 µg of GnRH at the time of device insertion, and injection of PGF(2α) at device removal (GPG/P4). Cows were randomly assigned to 1 of 2 groups (6 d or 7 d) for duration of progesterone device insertion. Within each of these groups, cows were further randomly assigned to receive either 400 IU of eCG at device removal or to remain untreated as controls, resulting in a 2×2 arrangement of treatment groups: (1) 6-d device and no eCG (n=484); (2) 6-d device and eCG (n=462); (3) 7-d device and no eCG (n=546); and (4) 7-d device and eCG (n=499). Cows were detected for estrus from the time of progesterone device removal and were inseminated; those not detected in estrus within 60 h after progesterone device removal received 100 µg of GnRH and were inseminated at 72 h. The primary outcomes considered were proportion of cows conceiving within 7 d of the beginning of breeding (7-d conception rate; 7-d CR), proportion pregnant within 28 d (28-d in calf rate; 28-d ICR), and days to conception (DTC). We found no significant differences between the 6- and 7-d insertion periods and found no 6- or 7-d insertion period × eCG treatment interactions. Inclusion of eCG into either length of GPG/P4 protocol increased 7-d CR (36.0 vs. 30.6%) and 28-d ICR (58.6 vs. 52.3%) and decreased median days to conception. The use of eCG in GPG/P4 breeding protocols will improve reproductive efficiency in seasonally calving, anestrous dairy cattle. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Tumor-associated antigen human chorionic gonadotropin beta contains numerous antigenic determinants recognized by in vitro-induced CD8+ and CD4+ T lymphocytes.

PubMed

Dangles, Virginie; Halberstam, Ilan; Scardino, Antonio; Choppin, Jeannine; Wertheimer, Mireille; Richon, Sophie; Quelvennec, Erwann; Moirand, Romain; Guillet, Jean-Gérard; Kosmatopoulos, Kostas; Bellet, Dominique; Zeliszewski, Dominique

2002-02-01

The beta subunit of human chorionic gonadotropin (hCG beta) is markedly overexpressed by neoplastic cells of differing histological origin including those present in colon, breast, prostate and bladder tumors. We have previously shown that some patients with hCG beta-producing urothelial tumors have circulating T cells that proliferate in response to hCG beta. To make a comprehensive study of hCG beta as a potential target for cancer immunotherapy, we investigated whether hCG beta peptides could induce CD4+ or CD8+ T-cell responses in vitro. By stimulating peripheral blood mononuclear cells (PBMCs) from three donors with mixtures of overlapping 16-mer synthetic peptides analogous to portions of either the hCG beta 20-71 or the hCG beta 102-129 region, we established six CD4+ T-cell lines that proliferated specifically in response to five distinct determinants located within these two hCG beta regions. Three antigenic determinants (hCG beta 52-67, 106-121 and 114-125) were presented by HLA-DR molecules, while the two other antigenic determinants (hCG beta 48-63 and 56-67) were presented by HLA-DQ molecules. Interestingly, one T-cell line specific for peptide hCG beta 106-121 recognized hCG beta peptides comprising, at position 117, either an alanine or an aspartic acid residue, with the latter residue being present within the protein expressed by some tumor cells. In addition, three other hCG beta-derived peptides that exhibited HLA-A*0201 binding ability were able to stimulate CD8+ cytotoxic T cells from two HLA-A*0201 donors. These three immunogenic peptides corresponded to regions hCG beta 40-48, hCG beta 44-52 and hCG beta 75-84. Our results indicate that the tumor-associated antigen hCG beta possesses numerous antigenic determinants liable to stimulate CD4+ and CD8+ T lymphocytes, and might thus be an effective target antigen for the immunotherapy of hCG beta-producing tumors.

Effects of preventing O-glycosylation on the secretion of human chorionic gonadotropin in Chinese hamster ovary cells

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

Matzuk, M.M.; Krieger, M.; Corless, C.L.

1987-09-01

Human chorionic gonadotropin (hCG) is a member of a family of heterodimeric glycoprotein hormones that have a common ..cap alpha.. subunit but differ in their hormone-specific ..beta..-subunits. The ..beta.. subunit of hCG (hCG..beta..) is unique among the ..beta.. subunits in that it contains four mucin-like O-linked oligosaccharides attached to a carboxyl-terminal extension. To study the effects of O-glycosylation on the secretion and assembly of hCG, expression vectors containing either hCG..beta.. gene alone or together with the hCG..cap alpha.. gene were transfected into a mutant Chinese hamster ovary cell line, 1d1D, which exhibits a reversible defect in O-glycosylation. The results revealmore » that hCG..beta.. can be secreted normally in the absence of its O-linked oligosaccharides. hCG..beta.. devoid of O-linked carbohydrate can also combine efficiently with hCG..cap alpha.. and be secreted as an intact dimer. The authors conclude that in Chinese hamster ovary cells, the hCG..beta.. O-linked chains play no role in the assembly and secretion of hCG. The normal and O-linked oligosaccharide-deficient forms of hCG secreted by these cells should prove useful in examining the role of O-linked chains on the biological function of hCG.« less

Microvascularization of corpus luteum of bovine treated with equine chorionic gonadotropin.

PubMed

Moura, Carlos Eduardo Bezerra; Rigoglio, Nathia Nathaly; Braz, Janine Karla França S; Machado, Marcello; Baruselli, Pietro S; Papa, Paula De Carvalho

2015-09-01

This study aimed to evaluate the morphological changes in microvascular density and corpus luteum (CL) vascularization in cows treated with eCG during stimulatory and superovulatory protocols. Sixteen cows were synchronized and divided into three groups: control (n = 6), stimulated (n = 4) and superovulated (n =6), one was submitted to estrous synchronization (ES) and received no eCG (control), and those that were submitted to ES and received eCG before or after follicular deviation (superovulation and stimulation of the dominant follicle, respectively). Ovulation was synchronized using a progesterone device-based protocol. After six days of ovulation, the cows were slaughtered and the ovaries and CL were collected. The CLs were processed and photomicrographs were taken under light microscopy to assess the vascular volume density (Vv) by stereology, and scanning electron microscopy (SEM) was used to perform ultrastructural analysis of the microvasculature. The Vv in stimulated and superovulated cows significantly increased (P ≤ 0.0001) when compared to control, indicating that the eCG is able to induce angiogenic activity in bovine CL. However, no significant differences were observed between stimulated and superovulated cows. The SEM demonstrated ratings indicative of angiogenesis, marked by several button-shaped projections in the capillaries, and the presence of more dilated capillaries in CL treated with eCG. These morphological findings are evidence of an angiogenic effect of the eCG treatment in CL of cows. © 2015 Wiley Periodicals, Inc.

Coincident Observation of Lightning using Spaceborne Spectrophotometer and Ground-Level Electromagnetic Sensors

NASA Technical Reports Server (NTRS)

Adachi, Toru; Cohen, Morris; Li, Jingbo; Cummer, Steve; Blakeslee, Richard; Marshall, THomas; Stolzenberg, Maribeth; Karunarathne, Sumedhe; Hsu, Rue-Ron; Su, Han-Tzong;

The comparison of microdose flare-up and multiple dose antagonist protocols based on hCG day estradiol (E2), progesterone (P) and P/E2 ratio among poor responder patients in ICSI-ET cycles.

PubMed

Cicek, M N; Kahyaoglu, I; Kahyaoglu, S

2015-02-01

Elevated progesterone levels surpassing exact treshold values impede endometrial receptivity and decrease clinical pregnancy rates in different responder patients during assisted reproductive techniques. A progesterone (P): estradiol (E2) ratio of > 1 on the day of hCG administration has also been suggested to be a manifestation of low ovarian reserve. The clinical significance of P/E2 ratio on the day of hCG administration was investigated among poor responder patients. Based on the ESHRE Bologna consensus criteria related to poor ovarian response diagnosis, 48 poor responder patients were treated with the microdose flare-up regimen and 34 patients were treated with the multiple-dose GnRH antagonist protocol. All patients were destined to perform a ICSI-ET procedure at the end of the stimulation protocols. Progesterone levels and P/E2 ratios have been detected during controlled ovarian hyperstimulation. In the microdose flare-up group; the duration of stimulation, total gonadotropin dose used and hCG day E2 levels were significantly higher than the multiple dose antagonist group. However, the mean hCG day P/E2 rate in the microdose flare-up group was less than that in the multiple-dose antagonist group. The clinical pregnancy rates were non significantly higher in the multiple dose antagonist protocol group than in microdose flare-up group. Impaired endometrial receptivity caused by elevated P levels results with lower pregnancy rates. Regardless of the selected stimulation protocol, poor responder patients are not prone to exhibit high P and E2 secretion. Increased P/E2 ratio of > 1 on hCG day has limited value to predict cycle outcomes in poor responder patients because of ovarian follicle depletion.

Identification and Functional Characterization of the Glycogen Synthesis Related Gene Glycogenin in Pacific Oysters (Crassostrea gigas).

PubMed

Li, Busu; Meng, Jie; Li, Li; Liu, Sheng; Wang, Ting; Zhang, Guofan

2017-09-06

High glycogen levels in the Pacific oyster (Crassostrea gigas) contribute to its flavor, quality, and hardiness. Glycogenin (CgGN) is the priming glucosyltransferase that initiates glycogen biosynthesis. We characterized the full sequence and function of C. gigas CgGN. Three CgGN isoforms (CgGN-α, β, and γ) containing alternative exon regions were isolated. CgGN expression varied seasonally in the adductor muscle and gonadal area and was the highest in the adductor muscle. Autoglycosylation of CgGN can interact with glycogen synthase (CgGS) to complete glycogen synthesis. Subcellular localization analysis showed that CgGN isoforms and CgGS were located in the cytoplasm. Additionally, a site-directed mutagenesis experiment revealed that the Tyr200Phe and Tyr202Phe mutations could affect CgGN autoglycosylation. This is the first study of glycogenin function in marine bivalves. These findings will improve our understanding of glycogen synthesis and accumulation mechanisms in mollusks. The data are potentially useful for breeding high-glycogen oysters.

Serum human chorionic gonadotropin levels on the day before oocyte retrieval do not correlate with oocyte maturity.

PubMed

Levy, Gary; Hill, Micah J; Ramirez, Christina; Plowden, Torrie; Pilgrim, Justin; Howard, Robin S; Segars, James H; Csokmay, John

2013-05-01

To evaluate the correlation of preretrieval quantitative serum hCG level with oocyte maturity. Retrospective cohort study. Military assisted reproductive technology (ART) program. Fresh autologous ART cycles. Serum hCG level the day before oocyte retrieval. Linear regression was used to correlate serum hCG levels and oocyte maturity rates. Normal oocyte maturity was defined as ≥75% and the Wilcoxon rank sum test was used to compare serum hCG levels in patients with normal and low oocyte maturity. Threshold analysis was performed to determine hCG levels that could predict oocyte maturity. A total of 468 ART cycles were analyzed. Serum hCG level was not correlated with hCG dose; however, it was negatively correlated with body mass index (BMI). Serum hCG levels did not differ between patients with oocyte maturity of <75% and ≥75%. Serum hCG levels did not correlate with oocyte maturity rates. Receiver operator characteristic and less than efficiency curves failed to demonstrate thresholds at which hCG could predict oocyte maturity. Serum hCG levels were not correlated with oocyte maturity. Although a positive hCG was reassuring that mature oocytes would be retrieved for most patients, the specific value was not helpful. Copyright © 2013. Published by Elsevier Inc.

Sensitivity Analysis of a Cognitive Architecture for the Cultural Geography Model

DTIC Science & Technology

2011-12-01

developmental inquiry. American Psychologist, 34(10), 906–911. Gazzaniga, M. S . (2004) The cognitive neurosciences III. Cambridge: MIT Press. Greeno, J. G...129 ix LIST OF FIGURES Situation-Based Cognitive Architecture (From Alt et al., 2011) .....................13 Figure 1. Theory of Planned...Harold, CG Model developer at TRAC-MTRY, who spend countless hours explaining to me the implementation of the Cognitive Architecture and CG model

Effects of neutron irradiation on the strength of continuous fiber reinforced SiC/SiC composites

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

Youngblood, G.E.; Henager, C.H. Jr.; Jones, R.H.

1997-04-01

Flexural strength data as a function of irradiation temperature and dose for a SiC{sub f}/SiC composite made with Nicalon-CG fiber suggest three major degradation mechanisms. Based on an analysis of tensile strength and microstructural data for irradiated Nicalon-CG and Hi-Nicalon fibers, it is anticipated that these degradation mechanisms will be alleviated in Hi-Nicalon reinforced composites.

Applying Systems Engineering to Improve the Main Gas Turbine Exhaust System Maintenance Strategy for the CG-47 Ticonderoga Class Cruiser

DTIC Science & Technology

2015-09-01

15 4. Commander, Naval Regional Maintenance Center .................. 15 5 . Private Ship Repair Industry...TURBINE EXHAUST SYSTEM MAINTENANCE STRATEGY FOR THE CG-47 TICONDEROGA CLASS CRUISER 5 . FUNDING NUMBERS 6. AUTHOR(S) Sparks, Robert D. 7. PERFORMING...condition-based maintenance, condition-directed, failure finding, fault tree analysis 15 . NUMBER OF PAGES 133 16. PRICE CODE 17. SECURITY

Association of CagPAI integrity with severeness of Helicobacter pylori infection in patients with gastritis.

PubMed

Ahmadzadeh, A; Ghalehnoei, H; Farzi, N; Yadegar, A; Alebouyeh, M; Aghdaei, H A; Molaei, M; Zali, M R; Pour Hossein Gholi, M A

2015-12-01

The Helicobacter pylori cag pathogenicity island (cagPAI) is involved in delivery of CagA effector protein and peptidoglycan into host cells and also in IL-8 induction in the human gastric tissue. Diversity of cagPAI may affect disease status and clinical outcome of the infected patients. Our study was aimed to investigate diversity of this island and its intactness in Iranian patients to investigate possible associations between cagPAI integrity and pathological changes of the infected tissue. Out of the 75 patients, H. pylori strains were obtained from 30 patients with severe active gastritis (SAG) (n=11), moderate chronic gastritis (CG) (n=14) and intestinal metaplasia/dysplasia (IM) (n=5). Intactness of the cagPAI was determined using 12 sets of primer pairs specific for functionally important loci of cagPAI by polymerase chain reaction (PCR). The cagPAI positive strains were significantly observed in patients with SAG (52.4%) in comparison to those presenting CG (33.3%) and IM (14.3%). In addition, the presence of intact cagPAI was 87.5% in H. pylori strains isolated from patients with SAG, which was higher than those obtained from patients with CG (12.5%) or IM (0%). A significant increase in the frequency of cagα-cagY and cagW-cagT segments, as exterior proteins of the CagPAI, was illustrated in strains from SAG patients compared with those from patients with CG. Overall, these results strongly proposed an association between the severity of histopathological changes and intactness of cagPAI in the gastric tissue of patients infected with H. pylori. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Revealing the Effects of the Herbal Pair of Euphorbia kansui and Glycyrrhiza on Hepatocellular Carcinoma Ascites with Integrating Network Target Analysis and Experimental Validation

PubMed Central

Zhang, Yanqiong; Lin, Ya; Zhao, Haiyu; Guo, Qiuyan; Yan, Chen; Lin, Na

2016-01-01

Although the herbal pair of Euphorbia kansui (GS) and Glycyrrhiza (GC) is one of the so-called "eighteen antagonistic medicaments" in Chinese medicinal literature, it is prescribed in a classic Traditional Chinese Medicine (TCM) formula Gansui-Banxia-Tang for cancerous ascites, suggesting that GS and GC may exhibit synergistic or antagonistic effects in different combination designs. Here, we modeled the effects of GS/GC combination with a target interaction network and clarified the associations between the network topologies involving the drug targets and the drug combination effects. Moreover, the "edge-betweenness" values, which is defined as the frequency with which edges are placed on the shortest paths between all pairs of modules in network, were calculated, and the ADRB1-PIK3CG interaction exhibited the greatest edge-betweenness value, suggesting its crucial role in connecting the other edges in the network. Because ADRB1 and PIK3CG were putative targets of GS and GC, respectively, and both had functional interactions with AVPR2 approved as known therapeutic target for ascites, we proposed that the ADRB1-PIK3CG-AVPR2 signal axis might be involved in the effects of the GS-GC combination on ascites. This proposal was further experimentally validated in a H22 hepatocellular carcinoma (HCC) ascites model. Collectively, this systems-level investigation integrated drug target prediction and network analysis to reveal the combination principles of the herbal pair of GS and GC. Experimental validation in an in vivo system provided convincing evidence that different combination designs of GS and GC might result in synergistic or antagonistic effects on HCC ascites that might be partially related to their regulation of the ADRB1-PIK3CG-AVPR2 signal axis. PMID:27143956

Fibromyalgia with severe forms of progression in a multidisciplinary therapy setting with emphasis on hyperthermia therapy--a prospective controlled study.

PubMed

Romeyke, Tobias; Scheuer, Hans Christoph; Stummer, Harald

2015-01-01

Fibromyalgia syndrome (FMS) is a multi-factorial disease involving physiological as well as psychological factors. The aim of the study was to investigate a multidisciplinary inpatient treatment with emphasis on hyperthermia therapy by patients with widespread pain. The study involved 104 patients suffering from severely progressive FMS. A convenience sample and a prospective cohort design were used. The patients were treated in an acute hospital focusing on rheumatologic pain therapy and multidisciplinary complementary medicine. One patient group was treated with inclusion of hyperthermia therapy and the other group without. The therapy density (number of performed therapies per patient) was determined for every patient. Functional capacity measured by the Hannover functional status questionnaire (Funktionsfragebogen Hannover) and symptoms (von Zerssen complaint list) were analyzed for both groups on admission and on discharge. On admission, no significant difference could be established between control group (CG; multimodal without hyperthermia) and hyperthermia group (HG; multimodal with hyperthermia) (functional capacity, P=0.936). Functional capacity improved for the CG and the HG. On discharge, there was a significant difference between the two groups (functional capacity, P=0.039). There were no significant differences in fibromyalgia symptoms between CG (mean 41.8) and HG (mean 41.8) on their admission to hospital (P=0.988). On discharge, there was a significant difference (P=0.024) between the two groups (HG, mean 30.6; CG, mean 36.6). The inpatient therapy of patients with severely progressive fibromyalgia is characterized by a high frequency of therapy input. FMS, especially with severe progression and a high degree of chronification, demands a multidisciplinary approach. In addition to the use of complementary medical procedures, integration of hyperthermia in the treatment process is a useful option.

First Cloud-to-Ground Lightning Timing Study

NASA Technical Reports Server (NTRS)

Huddleston, Lisa L.

2013-01-01

NASA's LSP, GSDO and other programs use the probability of cloud-to-ground (CG) lightning occurrence issued by the 45th Weather Squadron (45 WS) in their daily and weekly lightning probability forecasts. These organizations use this information when planning potentially hazardous outdoor activities, such as working with fuels, or rolling a vehicle to a launch pad, or whenever personnel will work outside and would be at-risk from lightning. These organizations would benefit greatly if the 45 WS could provide more accurate timing of the first CG lightning strike of the day. The Applied Meteorology Unit (AMU) has made significant improvements in forecasting the probability of lightning for the day, but forecasting the time of the first CG lightning with confidence has remained a challenge. To address this issue, the 45 WS requested the AMU to determine if flow regimes, wind speed categories, or a combination of the two could be used to forecast the timing of the first strike of the day in the Kennedy Space Center (KSC)/Cape Canaveral Air Force Station (CCAFS) lightning warning circles. The data was stratified by various sea breeze flow regimes and speed categories in the surface to 5,000-ft layer. The surface to 5,000-ft layer was selected since that is the layer the 45 WS uses to predict the behavior of sea breeze fronts, which are the dominant influence on the occurrence of first lightning in Florida during the warm season. Due to small data sample sizes after stratification, the AMU could not determine a statistical relationship between flow regimes or speed categories and the time of the first CG strike.. As expected, although the amount and timing of lightning activity varies by time of day based on the flow regimes and speed categories, there are extended tails of low lightning activity making it difficult to specify times when the threat of the first lightning flash can be avoided. However, the AMU developed a graphical user interface with input from the 45 WS that allows forecasters to visualize the climatological frequencies of the timing of the first lightning strike. This tool should contribute directly to the 45 WS goal of improving lightning timing capability for its NASA, US Air Force and commercial customers.

Identifying a long-term/chronic, non-cancer pain population using a one-dimensional verbal pain rating scale: an epidemiological study.

PubMed

Jensen, Marianne Kjettrup; Sjøgren, Per; Ekholm, Ola; Rasmussen, Niels Kristian; Eriksen, Jørgen

2004-04-01

The usefulness of the verbal pain rating scale (VRS) included in the Short Form 36 (SF-36) in identifying characteristics of long-term pain conditions, was analyzed using data from the 1994 Danish Health and Morbidity Survey. Based on the rating of pain intensity during a 4-week recall period the respondents were categorized into three groups: a high pain group (HPG) consisting of persons reporting moderate to severe pain (VRS 4-6), a low pain group (LPG) who rated their pain as very mild or mild (VRS 2-3), and a control group (CG) with no pain (VRS 1). The investigated sample comprised 3992 persons (HPG=563 persons, LPG=1714, and CG=1715 persons). Older age, educational level (< 10 years of schooling), cohabitation status (divorce/separation), and moderate to severe physical job strain were found to be significant risk factors for reporting high pain intensity (HPG). Only minor differences were observed between the LPG and CG. The proportion of respondents with good perceived health was significantly lower in the HPG compared with LPG and CG. The dominant complaints in the HPG were related to the musculoskeletal system. During a 14-day period prior to the interview persons in the HPG had a mean of 1.19 working days lost due to illness compared with a mean of 0.2 for the LPG and CG. Analyzing the use of medical services during the year before the interview, persons belonging to the HPG had an average number of nine contacts to general practitioners and specialized doctors in the primary sector as compared to six for the LPG and four for the CG. Mean numbers of hospital admissions were 0.29 for the HPG, 0.15 for the LPG and 0.10 for the CG. Mean numbers of in-hospital days were 1.60, 0.80, and 0.43 for the HPG, LPG, and CG, respectively. Our study suggest that one-dimensional pain intensity scoring using a simple VRS-scoring is useful as a screening instrument for identifying persons suffering from pain of a more complex nature. High intensity scores on a pain intensity scale should indicate to the investigator that she/he might be facing a person whose pain complaints and behavior are not only based on a pure biological background, but in whom also severe psychological and social problems might be present.

Effectiveness and cost-effectiveness of an integrated care program for schizophrenia: an analysis of routine data.

PubMed

Kerkemeyer, Linda; Wasem, Jürgen; Neumann, Anja; Brannath, Werner; Mester, Benjamin; Timm, Jürgen; Wobrock, Thomas; Bartels, Claudia; Falkai, Peter; Biermann, Janine

2017-08-08

In Germany, a regional social health insurance fund provides an integrated care program for patients with schizophrenia (IVS). Based on routine data of the social health insurance, this evaluation examined the effectiveness and cost-effectiveness of the IVS compared to the standard care (control group, CG). The primary outcome was the reduction of psychiatric inpatient treatment (days in hospital), and secondary outcomes were schizophrenia-related inpatient treatment, readmission rates, and costs. To reduce selection bias, a propensity score matching was performed. The matched sample included 752 patients. Mean number of psychiatric and schizophrenia-related hospital days of patients receiving IVS (2.3 ± 6.5, 1.7 ± 5.0) per quarter was reduced, but did not differ statistically significantly from CG (2.7 ± 7.6, 1.9 ± 6.2; p = 0.772, p = 0.352). Statistically significant between-group differences were found in costs per quarter per person caused by outpatient treatment by office-based psychiatrists (IVS: €74.18 ± 42.30, CG: €53.20 ± 47.96; p < 0.001), by psychiatric institutional outpatient departments (IVS: €4.83 ± 29.57, CG: €27.35 ± 76.48; p < 0.001), by medication (IVS: €471.75 ± 493.09, CG: €429.45 ± 532.73; p = 0.015), and by psychiatric outpatient nursing (IVS: €3.52 ± 23.83, CG: €12.67 ± 57.86, p = 0.045). Mean total psychiatric costs per quarter per person in IVS (€1117.49 ± 1662.73) were not significantly lower than in CG (€1180.09 ± 1948.24; p = 0.150). No statistically significant differences in total schizophrenia-related costs per quarter per person were detected between IVS (€979.46 ± 1358.79) and CG (€989.45 ± 1611.47; p = 0.084). The cost-effectiveness analysis showed cost savings of €148.59 per reduced psychiatric and €305.40 per reduced schizophrenia-related hospital day. However, limitations, especially non-inclusion of costs related to management of the IVS and additional home treatment within the IVS, restrict the interpretation of the results. Therefore, the long-term impact of this IVS deserves further evaluation.

Contact allergy to a contaminant in Kathon CG in the guinea pig.

PubMed

Bruze, M; Gruvberger, B; Persson, K

1987-01-01

Kathon CG is a commercial preservative, consisting of the two active ingredients, 2-methyl-4-isothiazolin-3-one and 5-chloro-2-methyl-4-isothiazolin-3-one (5243-K-CG) and other components. 4,5-dichloro-2-methyl-4-isothiazolin-3-one (45243-K-CG) is a contaminant in Kathon CG. The chemically related active ingredients are known to be contact sensitizers in humans and guinea pigs. Aims of this study were to determine the sensitizing capacity of this contaminant and also to investigate the cross-reaction pattern by guinea pig sensitization tests. 45243-K-CG was demonstrated to be a strong sensitizer; all animals reacting to 45243-K-CG also reacted to 5243-K-CG when rechallenged.

HCG-. beta. -subunit radioimmunoassay: potential error in HCG measurement related to choice of labeled antigen. [/sup 125/I

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

Tyrey, L.; Hammond, C.B.

1976-05-15

Antiserum generated against the hormone-specific ..beta..-subunit of hCG was used with different labeled antigens to measure circulating hCG in patients having trophoblastic disease. When /sup 125/I-hCG..beta.. served as the labeled antigen, a small number of patient sera failed to show parallelism with the second IS-hCG reference and erroneous estimates of hormone concentrations were obtained. Replacement of the /sup 125/I-hCG..beta.. with labeled hCG corrected the nonparallelism exhibited by these samples. Inhibition curves obtained with purified hCG and hCG..beta.. suggested that both the nonparallelism and its correction with the change in labeled antigen would be consistent with the possibility that this assaymore » aberration may result from the presence of free hCG..beta.. in these sera. (auth)« less

hCG - related molecules and their measurement.

PubMed

Szczerba, Anna; Białas, Piotr; Pięta, Paweł Piotr; Jankowska, Anna

2016-01-01

Measurements of human chorionic gonadotropin (hCG) synthesized by trophoblast cells is a powerful tool of pregnancy monitoring. It was showed that similarly to pregnancy also trophoblastic and nontrophoblastic malignancies produce variety of hCG molecules. In urine and serum of both pregnant women and tumors patients a fifteen various forms of hCG, such as: regular hCG, hyperglycosylated hCG and predominant hyperglycosylated hCG free β, were identified. These forms might be useful in order to recognize between physiological and pathological pregnancies as well as cancers. Even the presence of these different hormone variants is well documented the commercially available biochemical tests detecting hCG failed to identified and distinguish among these forms. Especially hard is to identify glycan chains linked to heterodimer. Thus, a detailed analysis of hCG-related molecules produced during physiological and pathological condition, together with a new tests development are needed.

Anxiety Sensitivity in Bereaved Adults with and without Complicated Grief

PubMed Central

Robinaugh, Donald J.; McNally, Richard J.; LeBlanc, Nicole J.; Pentel, Kimberly Z.; Schwarz, Noah R.; Shah, Riva M.; Nadal-Vicens, Mireya F.; Moore, Cynthia W.; Marques, Luana; Bui, Eric; Simon, Naomi M.

2014-01-01

Complicated grief (CG) is a bereavement specific syndrome chiefly characterized by symptoms of persistent separation distress. Physiological reactivity to reminders of the loss and repeated acute pangs or waves of severe anxiety and psychological pain are prominent features of CG. Fear of this grief-related physiological arousal may contribute to CG by increasing the distress associated with grief reactions and increasing the likelihood of maladaptive coping strategies and grief-related avoidance. Here, we examined anxiety sensitivity (i.e., the fear of anxiety-related sensations; AS) in two studies of bereaved adults with and without CG. In both studies, bereaved adults with CG exhibited elevated AS relative to those without CG. In Study 2, AS was positively associated with CG symptom severity among those with CG. These findings are consistent with the possibility that AS contributes to the development or maintenance of CG symptoms. PMID:25075646

SDS-PAGE Electrophoretic Property of Human Chorionic Gonadotropin (hCG) and its β-subunit

PubMed Central

2005-01-01

The microheterogeneity property of hCG with regards to its sialic acid contents resulted in variable mobility of the glycoprotein in SDS-PAGE. The intact hCG molecule is composed of two dissimilar subunits, namely α- and β-subunits. The identification of hCG bands in SDS-PAGE was accomplished by the immunoblotting experiment, whereby the antibody directed toward the specific region of β-subunit of hCG was used. The data shows that the different mobility of intact hCG was attributed to the different degree of desialylation of the glycoprotein. Nevertheless, unlike the intact hCG, the mobility of its β-subunit was not affected by its variety sialic acid content. This characteristic of β-hCG is beneficial when semi-quantification of total hCG is required. Quantification of hCG using the HPLC-reversed phase C18 analytical column is not possible as the glycoprotein was eluted in multiple fractions at different retention times. The identification of denatured hCG (HPLC eluted fractions) was carried out by immunoblotting experiment whilst immunoassay technique failed to detect its presence in any fraction. PMID:16094462

Effect of carrageenan addition on the rennet-induced gelation of skim milk.

PubMed

Wang, Fang; Zhang, Wei; Ren, Fazheng

2016-09-01

Carrageenan (CG) (κ-CG, ι-CG and λ-CG) was added to skim milk and the rennet-induced aggregation was studied. Caseinomacropeptide (CMP) release, diffusing wave spectroscopy (DWS) and rheology were used to follow the structural dynamics of casein micelles during gelation. The influence of carrageenan on the nature of protein interactions in the gels was investigated using a combination of ultracentrifugation and specific dissociating agents. For the recombined samples containing κ-CG and low concentrations of ι-CG and λ-CG, the CMP release was slowed down; however, the development of DWS and rheological parameters was similar to that of the control sample, and the increase in the incorporation of proteins through calcium bridges and hydrophobic interactions may be the most likely contributors. For the recombined samples containing high concentrations of ι-CG and λ-CG, other factors may impede the gel formation process. High concentrations of ι-CG and λ-CG strongly interfered with the rennet-induced aggregation, interrupted the interaction of caseins and therefore may contribute to good quality of low-fat cheese. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Human chorionic gonadotropin (hCG) in the secretome of cultured embryos: hyperglycosylated hCG and hCG-free beta subunit are potential markers for infertility management and treatment.

PubMed

Butler, Stephen A; Luttoo, Jameel; Freire, Maísa O T; Abban, Thomas K; Borrelli, Paola T A; Iles, Ray K

2013-09-01

Human chorionic gonadotropin (hCG) is produced by trophoblast cells throughout pregnancy, and gene expression studies have indicated that hCG-beta subunit (hCGβ) expression is active at the 2 blastomere stage. Here, we investigated the qualitative hCG output of developing embryos in culture and hCG isoforms expressed in the secretome as a novel sensitive method for detecting hCG. Culture media was collected from the culture plates of 118 embryos in culture (including controls and embryos at different stages of culture) from 16 patients undergoing routine fertility treatment. The hCGβ was detectable in media from 2 pronuclear (2PN) stage embryos through to the blastocyst stage. The hCGβ was absent in 1PN and arrested embryos as well as all media controls. Prior to hatching, hyperglycosylated hCG (hCGh) was observed selectively in 3PN embryos, but after hatching, along with hCG, became the dominant hCG molecule observed. We have reported at the 2PN stage the earliest evidence of hCGβ expression in embryos. There is a suggestion this may be indicative of quality in early embryos, and hCGh seen at the pronuclear stage may suggest triploid abnormality. The dominance of hCG, and hCGh expression, seen after blastocyst hatching may be indicative of potential implantation success. Thus, hCG isoforms have potential roles as biomarkers of embryo viability for embryo/blastocyst transfer.

Pituitary origin of persistently elevated human chorionic gonadotropin in a patient with gonadal failure.

PubMed

Merhi, Zaher; Pollack, Staci E

2013-01-01

To report a case of persistently elevated low levels of hCG to increase awareness of pituitary origin of persistently elevated hCG in patients with gonadal failure. Case report and literature review. Large university-affiliated infertility practice. A 16-year-old patient with primary amenorrhea, normal secondary sex characteristics, ovarian failure, and a 46,XY karyotype. Her past medical history was significant for focal segmental glomerulosclerosis, leading to a diagnosis of Frasier syndrome. At age 31 years, she desired pregnancy by oocyte donation and was found to have persistently elevated low levels of hCG (>35 mIU/mL). Pituitary hCG. Both serum free β-hCG and hyperglycosylated hCG were undetectable. Total serum hCG diluted appropriately was not blocked by blocking agent and was detected in the urine. Subsequent treatment with exogenous E(2), in preparation of a donor oocyte cycle, suppressed her hCG levels (down to 8 mIU/mL). These results indicated a pituitary source of the serum hCG. This report reinforces the need to consider pituitary hCG as the origin of persistently elevated hCG levels in patients with gonadal failure. Although levels of hCG <14 mIU/mL have been considered normal in postmenopausal women, our case suggests that patients with gonadal failure at younger ages might have a higher pituitary output of hCG. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

New discoveries on the biology and detection of human chorionic gonadotropin

PubMed Central

Cole, Laurence A

2009-01-01

Human chorionic gonadotropin (hCG) is a glycoprotein hormone comprising 2 subunits, alpha and beta joined non covalently. While similar in structure to luteinizing hormone (LH), hCG exists in multiple hormonal and non-endocrine agents, rather than as a single molecule like LH and the other glycoprotein hormones. These are regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG. For 88 years regular hCG has been known as a promoter of corpus luteal progesterone production, even though this function only explains 3 weeks of a full gestations production of regular hCG. Research in recent years has explained the full gestational production by demonstration of critical functions in trophoblast differentiation and in fetal nutrition through myometrial spiral artery angiogenesis. While regular hCG is made by fused villous syncytiotrophoblast cells, extravillous invasive cytotrophoblast cells make the variant hyperglycosylated hCG. This variant is an autocrine factor, acting on extravillous invasive cytotrophoblast cells to initiate and control invasion as occurs at implantation of pregnancy and the establishment of hemochorial placentation, and malignancy as occurs in invasive hydatidiform mole and choriocarcinoma. Hyperglycosylated hCG inhibits apoptosis in extravillous invasive cytotrophoblast cells promoting cell invasion, growth and malignancy. Other non-trophoblastic malignancies retro-differentiate and produce a hyperglycosylated free beta-subunit of hCG (hCG free beta). This has been shown to be an autocrine factor antagonizing apoptosis furthering cancer cell growth and malignancy. New applications have been demonstrated for total hCG measurements and detection of the 3 hCG variants in pregnancy detection, monitoring pregnancy outcome, determining risk for Down syndrome fetus, predicting preeclampsia, detecting pituitary hCG, detecting and managing gestational trophoblastic diseases, diagnosing quiescent gestational trophoblastic disease, diagnosing placental site trophoblastic tumor, managing testicular germ cell malignancies, and monitoring other human malignancies. There are very few molecules with such wide and varying functions as regular hCG and its variants, and very few tests with such a wide spectrum of clinical applications as total hCG. PMID:19171054

Cloud-to-ground lightning and surface rainfall in warm-season Florida thunderstorms

USGS Publications Warehouse

Gungle, B.; Krider, E.P.

2006-01-01

Relationships between cloud-to-ground (CG) lightning and surface rainfall have been examined in nine isolated, warm-season thunderstorms on the east coast of central Florida. CG flashes and the associated rain volumes were measured as a function of time in storm-centered reference frames that followed each storm over a network of rain gauges. Values of the storm-average rain volume per CG flash ranged from 0.70 ?? 104 to 6.4 ?? 104 m3/CG flash, with a mean (and standard deviation) of 2.6 ?? 104 ?? 2.1 ?? 104 m3/CG flash. Values of the rain volume concurrent with CG flashes ranged from 0.11 ?? 104 to 4.9 ?? 104 m3/CG flash with a mean of 2.1 ?? 104 ?? 2.0 ?? 104 m3/CG flash. The lag-time between the peak CG flash rate and the peak rainfall rate (using 5 min bins), and the results of a lag correlation analysis, show that surface rainfall tends to follow the lightning (positive lag) by up to 20 min in six storms. In one storm the rainfall preceded the lightning by 5 min, and two storms had nonsignificant lags. Values of the lagged rain volume concurrent with CG flashes ranged from 0.43 ?? 104 to 4.9 ?? 104 m3/CG flash, and the mean was 1.9 ?? 104 ?? 1.7 ?? 104 m3/CG flash. For the five storms that produced 12 or more flashes and had significant lags, a plot of the optimum lag time versus the total number of CG flashes shows a linear trend (R2 = 0.56). The number of storms is limited, but the lag results do indicate that large storms tend to have longer lags. A linear fit to the lagged rain volume vs. the number of concurrent CG flashes has a slope of 1.9 ?? 104 m3/CG flash (R2 = 0.83). We conclude that warm-season Florida thunderstorms produce a roughly constant rain volume per CG flash and that CG lightning can be used to estimate the location and intensity of convective rainfall in that weather regime. Copyright 2006 by the American Geophysical Union.

Human Chorionic Gonadotropin: Unknown about Known.

PubMed

Borisova, M A; Moiseenko, D Yu; Smirnova, O V

2017-01-01

The last two decade discoveries shift the accent from consideration of human chorionic gonadotripin (hCG) as a hormone, that controls progesterone production by corpus luteum cells, to a powerful paracrine regulator which'in the tandem with its hyperglycozilated analog (hCG-H) induces successful implantation and coordinated dialog between blastocyst and uterus tissues. Ability of hCG to interact with TSH receptor and hCG-H with TGF-beta-RII extend significantly the spectrum of processes controlled by these molecules. Differences between intracellular pathways of signal transduction between hCG and LH mediated by the same receptor (LH/hCG-R) impugn unity of their effector mechanisms previously considered as obvious. Paracine properties-of hCG comprise control of fusing of trophoblasts into syncytiotrophoblasts, angiogenesis, immunity regulation and endometrium predisposition to implantation. Angiogenesis is associated with LH/hCG-R expressed on mural cells of uterine spiral arteries as well as induced secretion of soluble VEGF type by endometrial cells. hCG.regulates ratio between different forms of T-helper cells in maternal organism on the initial gestation stage determining high level of Th2 cells. hCG supports local immunotolerance acting as chemoattractant for T-suppressors (T-Treg) and apoptotic factor for T-lymphocytes. Endometrial susceptibility arises from activation of osteopantin secretion and decline of mucin secretion by epithelial cells. hCG-H acts on the same tissues as hCG as a paracrine agent regulating multiple cascades of cytokines. hCG-H plays the key role in trophoblast invasion into,uterine decidua as a result of gelatinase secretion by these cells.The degree of angiogenic effect of hCG-H is compatiblewith hCG but its signal transduction is mediated by TGF-beta signal transduction pathway that stimulates mural cell proliferation. hCG-H acts as mitogen on NK-cells and is able to activate them and direct to angiogenesis maintenance. In this article the attempt was made to elucidate the most important discoveries about the role of hCG and its hyperglycosylated analog yet accomplished and still upcoming.

Introducing reproductive life plan-based information in contraceptive counselling: an RCT.

PubMed

Stern, J; Larsson, M; Kristiansson, P; Tydén, T

2013-09-01

Can reproductive life plan (RLP)-based information in contraceptive counselling before pregnancy increase women's knowledge of reproduction, and of the importance of folic acid intake in particular? The RLP-based information increased women's knowledge of reproduction including knowledge of folic acid intake. Many women have insufficient knowledge of reproduction, including a health-promoting lifestyle prior to conception, and highly educated women in particular postpone childbearing until an age when their fertile capacity has started to decrease. The study was an randomized controlled trial with one intervention group (IG) and two control groups (CG1, CG2). A sample size calculation indicated that 82 women per group would be adequate. Recruitment took place during 3 months in 2012 and 299 women were included. The women were randomized in blocks of three. All groups received standard care (contraceptive counselling, Chlamydia testing, cervical screening). In addition, women in the IG were given oral and written RLP-based information about reproduction. A total of 299 out of 338 (88%) Swedish-speaking women visiting a Student Health Centre were included (mean age 23 years); response rate was 88%. Before the counselling, women in the IG and the CG1 completed a baseline questionnaire, including questions about lifestyle changes in connection to pregnancy planning, family planning intentions and knowledge of reproduction (e.g. the fecundity of an ovum). At follow-up 2 months after inclusion, a structured telephone interview was performed in all groups (n = 262, 88% participation rate). There was no difference between the groups regarding the mean knowledge score at baseline. The IG scored higher at follow-up than at baseline (P < 0.001); the mean increased from 6.4 to 9.0 out of a maximum 20 points. The women in the CG1 scored no differently at follow-up than at baseline. The difference in the knowledge score between the IG and the two CGs was significant (P < 0.001), whereas no difference was shown between the two CGs. There was no difference between the groups at baseline regarding how many women could mention folic acid intake among the things to do when planning to get pregnant. At follow-up, 22% in the IG, 3% in CG1 and 1% in CG2 mentioned folic acid intake (P < 0.001). At follow-up, more women in the IG also wished to have their last child earlier in life (P < 0.001) than at baseline, while there was no difference in the CG1. As the study sample consisted of university students, it is possible that the effect of the intervention was connected to a high level of education and conclusions for all women of reproductive age should be drawn with caution. The provision of RLP-based information seems to be a feasible tool for promoting reproductive health. Study funding was received from the Faculty of Medicine, Uppsala University, Sweden. There are no conflicts of interest. ClinicalTrial.gov Identifier NCT01739101.

A temperature-dependent coarse-grained model for the thermoresponsive polymer poly(N-isopropylacrylamide)

DOE PAGES

Abbott, Lauren J.; Stevens, Mark J.

2015-12-22

In this study, a coarse-grained (CG) model is developed for the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAM), using a hybrid top-down and bottom-up approach. Nonbonded parameters are fit to experimental thermodynamic data following the procedures of the SDK (Shinoda, DeVane, and Klein) CG force field, with minor adjustments to provide better agreement with radial distribution functions from atomistic simulations. Bonded parameters are fit to probability distributions from atomistic simulations using multi-centered Gaussian-based potentials. The temperature-dependent potentials derived for the PNIPAM CG model in this work properly capture the coil–globule transition of PNIPAM single chains and yield a chain-length dependence consistent with atomisticmore » simulations.« less

First-trimester maternal serum human chorionic gonadotrophin as a marker for fetal chromosomal disorders. The Dutch Working Party on Prenatal Diagnosis.

PubMed

Van Lith, J M

1992-06-01

The Dutch Working Party on Prenatal Diagnosis has initiated a study on the possibilities of first-trimester screening for fetal chromosomal disorders. We report on maternal serum human chorionic gonadotrophin (MS-hCG) measurements in 1348 pregnancies with a chromosomally normal fetus and 53 pregnancies with a chromosomally abnormal fetus. The median MS-hCG concentration in 24 pregnancies with Down's syndrome was 1.19 multiples of the normal median (MoM). The MS-hCG distributions in normal and Down's syndrome pregnancies did not differ significantly (t-test: t = 1.945, p greater than 0.05). We also found no difference between normal pregnancies and pregnancies with other chromosomal disorders (six cases of trisomy 18, MoM = 0.80; four cases of sex chromosome abnormality, MoM = 1.01; 17 cases of chromosomal mosaicism in chorionic villi, MoM = 1.11). Selecting an upper limit at the 90th centile could detect 25 per cent of pregnancies with Down's syndrome. We conclude that, in the first trimester, MS-hCG as a screening factor for Down's syndrome is of minor value. However, MS-hCG could be a useful factor in a first-trimester screening programme based on a combination of markers.

Observations of lightning in convective supercells within tropical storms and hurricanes

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

Lyons, W.A.; Keen, C.S.

1994-08-01

Cloud-to-ground (CG) lightning observations from land-based lightning detection networks now allow monitoring this component of the electrical structure of tropical storms and hurricanes within a few hundred kilometers of the United States coastline. Several case studies confirm the long-held opinion that lightning is rather common within the outer rainbands. The general absence of CG lightning within the interior of mature tropical cyclones is also apparent. On the other hand, bursts of CG lightning near the circulation center of developing storms appear to precede periods of further deepening. The CG events are associated with convective supercells, whose anvil canopies can oftenmore » obscure much of the underlying storm. Near-eyewall CG bursts preceding periods of intensification were noted in Hurricanes Diana (1984) and Florence (1988). A detailed case study of the 1987 unnamed tropical storm that struck the Texas-Louisiana coastline reveals that lightning was associated with two large supercells. These supercells appeared to be the trigger for the development of a closed circulation that formed several hours after the apparent low pressure center made landfall. Further studies of lightning may provide additional insight into the role of convective supercells in tropical storm intensification. It may also provide a useful diagnostic of impending deepening.« less

Center of gravity estimation using a reaction board instrumented with fiber Bragg gratings

NASA Astrophysics Data System (ADS)

Oliveira, Rui; Roriz, Paulo; Marques, Manuel B.; Frazão, Orlando

2018-03-01

The purpose of the present work is to construct a reaction board based on fiber Bragg gratings (FBGs) that could be used for estimation of the 2D coordinates of the projection of center of gravity (CG) of an object. The apparatus is consisted of a rigid equilateral triangular board mounted on three supports at the vertices, two of which have cantilevers instrumented with FBGs. When an object of known weight is placed on the board, the bending strain of the cantilevers is measured by a proportional wavelength shift of the FBGs. Applying the equilibrium conditions of a rigid body and proper calibration procedures, the wavelength shift is used to estimate the vertical reaction forces and moments of force at the supports and the coordinates of the object's CG projection on the board. This method can be used on a regular basis to estimate the CG of the human body or objects with complex geometry and density distribution. An example is provided for the estimation of the CG projection coordinates of two orthopaedic femur bone models, one intact, and the other with a hip stem implant encased. The clinical implications of changing the normal CG location by means of a prosthesis have been discussed.

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

Li, Zhen; Bian, Xin; Karniadakis, George Em, E-mail: george-karniadakis@brown.edu

We construct effective coarse-grained (CG) models for polymeric fluids by employing two coarse-graining strategies. The first one is a forward-coarse-graining procedure by the Mori-Zwanzig (MZ) projection while the other one applies a reverse-coarse-graining procedure, such as the iterative Boltzmann inversion (IBI) and the stochastic parametric optimization (SPO). More specifically, we perform molecular dynamics (MD) simulations of star polymer melts to provide the atomistic fields to be coarse-grained. Each molecule of a star polymer with internal degrees of freedom is coarsened into a single CG particle and the effective interactions between CG particles can be either evaluated directly from microscopic dynamicsmore » based on the MZ formalism, or obtained by the reverse methods, i.e., IBI and SPO. The forward procedure has no free parameters to tune and recovers the MD system faithfully. For the reverse procedure, we find that the parameters in CG models cannot be selected arbitrarily. If the free parameters are properly defined, the reverse CG procedure also yields an accurate effective potential. Moreover, we explain how an aggressive coarse-graining procedure introduces the many-body effect, which makes the pairwise potential invalid for the same system at densities away from the training point. From this work, general guidelines for coarse-graining of polymeric fluids can be drawn.« less

The glass transition in cured epoxy thermosets: A comparative molecular dynamics study in coarse-grained and atomistic resolution

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

Langeloth, Michael; Böhm, Michael C.; Müller-Plathe, Florian

2015-12-28

We investigate the volumetric glass transition temperature T{sub g} in epoxy thermosets by means of molecular dynamics simulations. The epoxy thermosets consist of the resin bisphenol A diglycidyl ether and the hardener diethylenetriamine. A structure based coarse-grained (CG) force field has been derived using iterative Boltzmann inversion in order to facilitate simulations of larger length scales. We observe that T{sub g} increases clearly with the degree of cross-linking for all-atomistic (AA) and CG simulations. The transition T{sub g} in CG simulations of uncured mixtures is much lower than in AA-simulations due to the soft nature of the CG potentials, butmore » increases all the more with the formation of rigid cross-links. Additional simulations of the CG mixtures in contact with a surface show the existence of an interphase region of about 3 nm thickness in which the network properties deviate significantly from the bulk. In accordance to experimental studies, we observe that T{sub g} is reduced in this interphase region and gradually increases to its bulk value with distance from the surface. The present study shows that the glass transition is a local phenomenon that depends on the network structure in the immediate environment.« less

Serum Human Chorionic Gonadotropin (β- hCG) Clearance Curves in Women with Successfully Expectantly Managed Tubal Ectopic Pregnancies: A Retrospective Cohort Study

PubMed Central

Helmy, Samir; Mavrelos, Dimitrios; Sawyer, Elinor; Ben-Nagi, Jara; Koch, Marianne; Day, Andrea; Jurkovic, Davor

2015-01-01

Objective To establish clearance curves for serum β -hCG in women with successfully expectantly managed tubal ectopic pregnancies. Design Retrospective cohort study. Non- viable tubal ectopic pregnancy was diagnosed on transvaginal ultrasound. If initial serum β hCG was less than 5000 IU/L and patients were asymptomatic, expectant management was offered. Patients underwent serial β hCG measurements until serum β hCG was less than 20 IU/l, or the urine pregnancy test was negative. Setting Early Pregnancy and Gynaecology Assessment Unit, Kings College Hospital, London (December 1998 to July 2006). Patients We included 161 women with diagnosed non-viable tubal ectopic pregnancy who underwent successful expectant management. Main outcome measure Serum β hCG level. Results Mean initial serum β- hCG was 488 IU/L (41 - 4883) and median serum β hCG clearance time was 19 days (5 - 82). The average half-life of β hCG clearance was 82.5 hours (±SD 50.2) in patients with steadily declining serum β- hCG levels compared to 106.7 hours (±SD 72.0) in patients with primarily plateauing β-hCG levels in the declining phase. However, these differences were not significant (p>0.05). Conclusion We identified a median follow-up of 19 days until serum β hCG clearance in women with tubal ectopic pregnancy and successful expectant management. Although non- significant, women with initially plateauing serum β hCG showed a longer follow-up time until clearance compared to women with steadily declining β hCG levels. This information may serve as a guideline enabling clinicians to predict the length of follow-up for women with tubal ectopic pregnancy and expectant management. PMID:26135923

A novel HLA-A*0201 restricted peptide derived from cathepsin G is an effective immunotherapeutic target in acute myeloid leukemia.

PubMed

Zhang, Mao; Sukhumalchandra, Pariya; Enyenihi, Atim A; St John, Lisa S; Hunsucker, Sally A; Mittendorf, Elizabeth A; Sergeeva, Anna; Ruisaard, Kathryn; Al-Atrache, Zein; Ropp, Patricia A; Jakher, Haroon; Rodriguez-Cruz, Tania; Lizee, Gregory; Clise-Dwyer, Karen; Lu, Sijie; Molldrem, Jeffrey J; Glish, Gary L; Armistead, Paul M; Alatrash, Gheath

2013-01-01

Immunotherapy targeting aberrantly expressed leukemia-associated antigens has shown promise in the management of acute myeloid leukemia (AML). However, because of the heterogeneity and clonal evolution that is a feature of myeloid leukemia, targeting single peptide epitopes has had limited success, highlighting the need for novel antigen discovery. In this study, we characterize the role of the myeloid azurophil granule protease cathepsin G (CG) as a novel target for AML immunotherapy. We used Immune Epitope Database and in vitro binding assays to identify immunogenic epitopes derived from CG. Flow cytometry, immunoblotting, and confocal microscopy were used to characterize the expression and processing of CG in AML patient samples, leukemia stem cells, and normal neutrophils. Cytotoxicity assays determined the susceptibility of AML to CG-specific cytotoxic T lymphocytes (CTL). Dextramer staining and cytokine flow cytometry were conducted to characterize the immune response to CG in patients. CG was highly expressed and ubiquitinated in AML blasts, and was localized outside granules in compartments that facilitate antigen presentation. We identified five HLA-A*0201 binding nonameric peptides (CG1-CG5) derived from CG, and showed immunogenicity of the highest HLA-A*0201 binding peptide, CG1. We showed killing of primary AML by CG1-CTL, but not normal bone marrow. Blocking HLA-A*0201 abrogated CG1-CTL-mediated cytotoxicity, further confirming HLA-A*0201-dependent killing. Finally, we showed functional CG1-CTLs in peripheral blood from AML patients following allogeneic stem cell transplantation. CG is aberrantly expressed and processed in AML and is a novel immunotherapeutic target that warrants further development.

Hybrid Quantum Mechanics/Molecular Mechanics/Coarse Grained Modeling: A Triple-Resolution Approach for Biomolecular Systems.

PubMed

Sokkar, Pandian; Boulanger, Eliot; Thiel, Walter; Sanchez-Garcia, Elsa

2015-04-14

We present a hybrid quantum mechanics/molecular mechanics/coarse-grained (QM/MM/CG) multiresolution approach for solvated biomolecular systems. The chemically important active-site region is treated at the QM level. The biomolecular environment is described by an atomistic MM force field, and the solvent is modeled with the CG Martini force field using standard or polarizable (pol-CG) water. Interactions within the QM, MM, and CG regions, and between the QM and MM regions, are treated in the usual manner, whereas the CG-MM and CG-QM interactions are evaluated using the virtual sites approach. The accuracy and efficiency of our implementation is tested for two enzymes, chorismate mutase (CM) and p-hydroxybenzoate hydroxylase (PHBH). In CM, the QM/MM/CG potential energy scans along the reaction coordinate yield reaction energies that are too large, both for the standard and polarizable Martini CG water models, which can be attributed to adverse effects of using large CG water beads. The inclusion of an atomistic MM water layer (10 Å for uncharged CG water and 5 Å for polarizable CG water) around the QM region improves the energy profiles compared to the reference QM/MM calculations. In analogous QM/MM/CG calculations on PHBH, the use of the pol-CG description for the outer water does not affect the stabilization of the highly charged FADHOOH-pOHB transition state compared to the fully atomistic QM/MM calculations. Detailed performance analysis in a glycine-water model system indicates that computation times for QM energy and gradient evaluations at the density functional level are typically reduced by 40-70% for QM/MM/CG relative to fully atomistic QM/MM calculations.

A novel siglec (CgSiglec-1) from the Pacific oyster (Crassostrea gigas) with broad recognition spectrum and inhibitory activity to apoptosis, phagocytosis and cytokine release.

PubMed

Liu, Conghui; Jiang, Shuai; Wang, Mengqiang; Wang, Lingling; Chen, Hao; Xu, Jiachao; Lv, Zhao; Song, Linsheng

2016-08-01

Sialic acid binding immunoglobulin-type lectin (siglec) belongs to the immunoglobulin superfamily (IgSF), which acts as regulator involved in glycan recognition and signal transduction in the immune and nervous systems. In the present study, a siglec gene (designated CgSiglec-1) was characterized from the Pacific oyster, Crassostrea gigas. The cDNA of CgSiglec-1 was of 1251 bp encoding a predicted polypeptide of 416 amino acids. CgSiglec-1 was composed of two I-set immunoglobulin (Ig) domains, one transmembrane (TM) domain and two ITIM motifs, sharing a sequence similarity with vertebrate CD22 homologs. The mRNA expression of CgSiglec-1 could be detected in all the selected tissues, with the highest level in hemocytes and labial palps. The confocal analysis revealed that CgSiglec-1 mainly distributed on the cytoplasmic membrane of the oyster hemocytes. In addition, the mRNA transcripts of CgSiglec-1 in hemocytes increased significantly (4.29-fold to that of control group, p < 0.05) after Vibrio splendidus stimulation. The recombinant CgSiglec-1 protein (rCgSiglec-1) could bind to poly sialic acid (pSIAS), lipopolysaccharides (LPS) and peptidoglycan (PGN) in a dose-dependent manner. The blockade of CgSiglec-1 by specific polyclonal antibodies could enhance the LPS-induced cell apoptosis, phagocytosis towards V. splendidus and the release of cytokines, such as CgTNF-1, CgIFNLP and CgIL-17. The results collectively indicated that CgSiglec-1 could act as a bridge molecule between invader recognition and signal transduction cascade, and modulate the immune response by inhibiting various important processes of immunity in oyster. Copyright © 2016 Elsevier Ltd. All rights reserved.

Optimization of Analytical Potentials for Coarse-Grained Biopolymer Models.

PubMed

Mereghetti, Paolo; Maccari, Giuseppe; Spampinato, Giulia Lia Beatrice; Tozzini, Valentina

2016-08-25

The increasing trend in the recent literature on coarse grained (CG) models testifies their impact in the study of complex systems. However, the CG model landscape is variegated: even considering a given resolution level, the force fields are very heterogeneous and optimized with very different parametrization procedures. Along the road for standardization of CG models for biopolymers, here we describe a strategy to aid building and optimization of statistics based analytical force fields and its implementation in the software package AsParaGS (Assisted Parameterization platform for coarse Grained modelS). Our method is based on the use and optimization of analytical potentials, optimized by targeting internal variables statistical distributions by means of the combination of different algorithms (i.e., relative entropy driven stochastic exploration of the parameter space and iterative Boltzmann inversion). This allows designing a custom model that endows the force field terms with a physically sound meaning. Furthermore, the level of transferability and accuracy can be tuned through the choice of statistical data set composition. The method-illustrated by means of applications to helical polypeptides-also involves the analysis of two and three variable distributions, and allows handling issues related to the FF term correlations. AsParaGS is interfaced with general-purpose molecular dynamics codes and currently implements the "minimalist" subclass of CG models (i.e., one bead per amino acid, Cα based). Extensions to nucleic acids and different levels of coarse graining are in the course.

Serum human chorionic gonadotropin levels on the day before oocyte retrieval do not correlate with oocyte maturity

PubMed Central

Levy, Gary; Hill, Micah J.; Ramirez, Christina; Plowden, Torrie; Pilgrim, Justin; Howard, Robin S.; Segars, James H.; Csokmay, John

2014-01-01

Objective To evaluate the correlation of preretrieval quantitative serum hCG level with oocyte maturity. Design Retrospective cohort study. Setting Military assisted reproductive technology (ART) program. Patient(s) Fresh autologous ART cycles. Intervention(s) Serum hCG level the day before oocyte retrieval. Main Outcome Measure(s) Linear regression was used to correlate serum hCG levels and oocyte maturity rates. Normal oocyte maturity was defined as ≥ 75% and the Wilcoxon rank sum test was used to compare serum hCG levels in patients with normal and low oocyte maturity. Threshold analysis was performed to determine hCG levels that could predict oocyte maturity. Result(s) A total of 468 ART cycles were analyzed. Serum hCG level was not correlated with hCG dose; however, it was negatively correlated with body mass index (BMI). Serum hCG levels did not differ between patients with oocyte maturity of <75% and ≥ 75%. Serum hCG levels did not correlate with oocyte maturity rates. Receiver operator characteristic and less than efficiency curves failed to demonstrate thresholds at which hCG could predict oocyte maturity. Conclusion(s) Serum hCG levels were not correlated with oocyte maturity. Although a positive hCG was reassuring that mature oocytes would be retrieved for most patients, the specific value was not helpful. PMID:23375205

Absence of TGF-β Receptor Activation by Highly Purified hCG Preparations.

PubMed

Koistinen, Hannu; Hautala, Laura; Koli, Katri; Stenman, Ulf-Håkan

2015-12-01

Recently, several LH/human chorionic gonadotropin (hCG) receptor-independent activities for hCG have been described, including activation of the TGF-β receptor (TGFβR) by hyperglycosylated hCG and stimulation of trophoblast invasion. Because the hCG concentrations used in these studies have been rather high, reflecting physiological hCG levels in pregnancy, even a minor contamination with growth factors, which act at very low concentrations, may be significant. Several commercial hCG preparations have been found to contain significant amounts of epidermal growth factor (EGF), which we also confirmed here. Furthermore, we found that some hCG preparations also contain significant amounts of TGF-β1. These hCG preparations were able to activate ERK1/2 in JEG-3 choriocarcinoma cells or TGFβR in mink lung epithelial cells transfected with a reporter gene for TGFβR activation. No such activation was found with highly purified hCG or its free β-subunit (hCGβ), irrespective of whether they were hyperglycosylated or not. Taken together, our results suggest that the growth factor contaminations in the hCG preparations can cause activation of TGFβR and, at least in JEG-3 cells, MAPK signaling. This highlights the importance to carefully control for potential contaminations and that highly purified hCG preparations have to be used for biological studies.

Absence of TGF-β Receptor Activation by Highly Purified hCG Preparations

PubMed Central

Hautala, Laura; Koli, Katri; Stenman, Ulf-Håkan

2015-01-01

Recently, several LH/human chorionic gonadotropin (hCG) receptor-independent activities for hCG have been described, including activation of the TGF-β receptor (TGFβR) by hyperglycosylated hCG and stimulation of trophoblast invasion. Because the hCG concentrations used in these studies have been rather high, reflecting physiological hCG levels in pregnancy, even a minor contamination with growth factors, which act at very low concentrations, may be significant. Several commercial hCG preparations have been found to contain significant amounts of epidermal growth factor (EGF), which we also confirmed here. Furthermore, we found that some hCG preparations also contain significant amounts of TGF-β1. These hCG preparations were able to activate ERK1/2 in JEG-3 choriocarcinoma cells or TGFβR in mink lung epithelial cells transfected with a reporter gene for TGFβR activation. No such activation was found with highly purified hCG or its free β-subunit (hCGβ), irrespective of whether they were hyperglycosylated or not. Taken together, our results suggest that the growth factor contaminations in the hCG preparations can cause activation of TGFβR and, at least in JEG-3 cells, MAPK signaling. This highlights the importance to carefully control for potential contaminations and that highly purified hCG preparations have to be used for biological studies. PMID:26495869

On the representability problem and the physical meaning of coarse-grained models

NASA Astrophysics Data System (ADS)

Wagner, Jacob W.; Dama, James F.; Durumeric, Aleksander E. P.; Voth, Gregory A.

2016-07-01

In coarse-grained (CG) models where certain fine-grained (FG, i.e., atomistic resolution) observables are not directly represented, one can nonetheless identify indirect the CG observables that capture the FG observable's dependence on CG coordinates. Often, in these cases it appears that a CG observable can be defined by analogy to an all-atom or FG observable, but the similarity is misleading and significantly undermines the interpretation of both bottom-up and top-down CG models. Such problems emerge especially clearly in the framework of the systematic bottom-up CG modeling, where a direct and transparent correspondence between FG and CG variables establishes precise conditions for consistency between CG observables and underlying FG models. Here we present and investigate these representability challenges and illustrate them via the bottom-up conceptual framework for several simple analytically tractable polymer models. The examples provide special focus on the observables of configurational internal energy, entropy, and pressure, which have been at the root of controversy in the CG literature, as well as discuss observables that would seem to be entirely missing in the CG representation but can nonetheless be correlated with CG behavior. Though we investigate these problems in the framework of systematic coarse-graining, the lessons apply to top-down CG modeling also, with crucial implications for simulation at constant pressure and surface tension and for the interpretations of structural and thermodynamic correlations for comparison to experiment.

Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial

PubMed Central

Strug, Michael R.; Su, Renwei; Young, James E.; Dodds, William G.; Shavell, Valerie I.; Díaz-Gimeno, Patricia; Ruíz-Alonso, Maria; Simón, Carlos; Lessey, Bruce A.; Leach, Richard E.; Fazleabas, Asgerally T.

2016-01-01

STUDY QUESTION Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation? SUMMARY ANSWER Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival. WHAT IS KNOWN ALREADY The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1. STUDY DESIGN, SIZE, DURATION Oocyte donors (n=15) were randomly assigned to receive an intrauterine infusion of 500 IU hCG (n=7) or embryo culture media vehicle (n=8) 3 days following oocyte retrieval during their donor stimulation cycle. Endometrial biopsies were performed 2 days later, followed by either RNA isolation or tissue fixation in formalin and paraffin embedding. PARTICIPANTS/MATERIALS, SETTING, METHODS Reverse transcription of total RNA from endometrial biopsies generated cDNA, which was used for analysis in the endometrial receptivity array (ERA; n = 5/group) or quantitative RT–PCR to determine relative expression of ESR1, PGR, C3 and NOTCH1. Tissue sections were stained with hematoxylin and eosin followed by blinded staging analysis for dating of endometrial glands and stroma. Immunostaining for ESR1, PGR, α-SMA, C3 and NOTCH1 was performed to determine their tissue localization. MAIN RESULTS AND THE ROLE OF CHANCE Intrauterine hCG infusion was associated with endometrial synchrony and reprograming of stromal development following ovarian stimulation. ESR1 and PGR were significantly elevated in the endometrium of hCG-treated patients, consistent with earlier staging. The ERA did not predict an overall positive impact of intrauterine hCG on endometrial receptivity. However, ACTA2, encoding α-SMA was significantly increased in response to intrauterine hCG. Similar to the hCG-treated non-human primate, sub-epithelial and peri-vascular α-SMA expression was induced in women following hCG infusion. Other known targets of hCG in the baboon were also found to be increased, including C3 and NOTCH1, which have known roles in endometrial receptivity. LIMITATIONS, REASONS FOR CAUTION This study differs from our previous work in the hCG-treated non-human primate along with clinical studies in infertile patients. Specifically, we performed a single intrauterine infusion in oocyte donors instead of either continuous hCG via an osmotic mini-pump in the baboon or infusion followed by blastocyst-derived hCG in infertile women undergoing embryo transfer. Therefore, the full impact of intrauterine hCG in promoting endometrial receptivity may not have been evident. WIDER IMPLICATIONS OF THE FINDINGS Our findings suggest a potential clinical benefit for intrauterine hCG prior to embryo transfer on Day 3 in counteracting endometrial dyssynchrony from ovarian stimulation and promoting expression of markers important for stromal survival. Finally, there were no obvious negative effects of intrauterine hCG treatment. STUDY FUNDING/COMPETING INTEREST(S) Funding for this work was provided by NICHD R01 HD042280 (A.T.F.) and NICHD F30 HD082951 (M.R.S.). C.S. and P.D.-G are co-inventors of the patented ERA, which is owned by IGENOMIX SL and was used in this study, and C.S. is a shareholder in IGENOMIX SL. M.R.-A. is employed by IGENOMIX SL. No other authors have any conflicts of interest to report. TRIAL REGISTRATION NUMBER This study was registered with ClinicalTrials.gov (NCT01786252). TRIAL REGISTRATION DATE 5 February 2013. DATE OF FIRST PATIENT'S ENROLLMENT 10 May 2013. PMID:27122490

PNPLA3 as a Genetic Determinant of Risk for and Severity of Non-alcoholic Fatty Liver Disease Spectrum.

PubMed

Salameh, Habeeb; Hanayneh, Muhannad Al; Masadeh, Maen; Naseemuddin, Mohammed; Matin, Tasnia; Erwin, Angelika; Singal, Ashwani K

2016-09-28

Background and Aims: Patatin-like phospholipase domain protein 3 ( PNPLA3 ) polymorphisms ( rs738409 C>G) are associated with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis to examine the association of PNPLA3 polymorphisms with the spectrum and severity of this disease. Methods: Studies evaluating the association between the PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) and NAFLD were included. Pooled data are reported as odds ratios (ORs) with 95% confidence intervals. Results: Of 393 potentially relevant studies, 35 on NAFLD were included in the analysis. Compared to healthy controls, the pooled ORs for rs738409 CG and GG compared to CC among patients with non-alcoholic fatty liver (NAFL) were 1.46 (1.16-1.85) and 2.76 (2.30-3.13), and were 1.75 (1.24-2.46) and 4.44 (2.92-6.76) among patients with non-alcoholic steatohepatitis respectively. The respective ORs for CG and GG compared to the CC genotype were 2.35 (0.90-6.13) and 5.05 (1.47-17.29) when comparing non-alcoholic hepatocellular carcinoma to NAFL patients. Among the NAFLD patients, the ORs for G allele frequency when comparing steatosis grade 2-3 to grade 0-1 NAFL, when comparing the NAFLD activity score of ≥ 4 to score ≤ 3, when comparing NASH to NAFLD, when comparing the presence of lobular inflammation to absence, and when comparing the presence of hepatocyte ballooning to absence were 2.33 (1.43-3.80), 1.80 (1.36-2.37), 1.66 (1.42-1.94), 1.58 (1.19-2.10), and 2.63 (1.87-3.69) respectively. Subgroup analysis based on ethnicity showed similar results. Conclusions: PNPLA3 polymorphisms have strong association with the risk for and severity of NAFLDs. PNPLA3 polymorphism plays an evolving role in diagnosis and treatment decisions in patients with NAFLD.

Social skills training for children with autism spectrum disorder using a robotic behavioral intervention system.

PubMed

Yun, Sang-Seok; Choi, JongSuk; Park, Sung-Kee; Bong, Gui-Young; Yoo, HeeJeong

2017-07-01

We designed a robot system that assisted in behavioral intervention programs of children with autism spectrum disorder (ASD). The eight-session intervention program was based on the discrete trial teaching protocol and focused on two basic social skills: eye contact and facial emotion recognition. The robotic interactions occurred in four modules: training element query, recognition of human activity, coping-mode selection, and follow-up action. Children with ASD who were between 4 and 7 years old and who had verbal IQ ≥ 60 were recruited and randomly assigned to the treatment group (TG, n = 8, 5.75 ± 0.89 years) or control group (CG, n = 7; 6.32 ± 1.23 years). The therapeutic robot facilitated the treatment intervention in the TG, and the human assistant facilitated the treatment intervention in the CG. The intervention procedures were identical in both groups. The primary outcome measures included parent-completed questionnaires, the Autism Diagnostic Observation Schedule (ADOS), and frequency of eye contact, which was measured with the partial interval recording method. After completing treatment, the eye contact percentages were significantly increased in both groups. For facial emotion recognition, the percentages of correct answers were increased in similar patterns in both groups compared to baseline (P > 0.05), with no difference between the TG and CG (P > 0.05). The subjects' ability to play, general behavioral and emotional symptoms were significantly diminished after treatment (p < 0.05). These results showed that the robot-facilitated and human-facilitated behavioral interventions had similar positive effects on eye contact and facial emotion recognition, which suggested that robots are useful mediators of social skills training for children with ASD. Autism Res 2017,. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1306-1323. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

AtPP2CG1, a protein phosphatase 2C, positively regulates salt tolerance of Arabidopsis in abscisic acid-dependent manner

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

Liu, Xin, E-mail: fangfei6073@126.com; Zhu, Yanming, E-mail: ymzhu2001@neau.edu.cn; Zhai, Hong, E-mail: Zhai.h@neigaehrb.ac.cn

2012-06-15

Highlights: Black-Right-Pointing-Pointer AtPP2CG1 positively regulates salt tolerance in ABA-dependent manner. Black-Right-Pointing-Pointer AtPP2CG1 up-regulates the expression of marker genes in different pathways. Black-Right-Pointing-Pointer AtPP2CG1 expresses in the vascular system and trichomes of Arabidopsis. -- Abstract: AtPP2CG1 (Arabidopsis thaliana protein phosphatase 2C G Group 1) was predicted as an abiotic stress candidate gene by bioinformatic analysis in our previous study. The gene encodes a putative protein phosphatase 2C that belongs to Group G of PP2C. There is no report of Group G genes involved in abiotic stress so far. Real-time RT-PCR analysis showed that AtPP2CG1 expression was induced by salt, drought, andmore » abscisic acid (ABA) treatment. The expression levels of AtPP2CG1 in the ABA synthesis-deficient mutant abi2-3 were much lower than that in WT plants under salt stress suggesting that the expression of AtPP2CG1 acts in an ABA-dependent manner. Over-expression of AtPP2CG1 led to enhanced salt tolerance, whereas its loss of function caused decreased salt tolerance. These results indicate that AtPP2CG1 positively regulates salt stress in an ABA-dependent manner. Under salt treatment, AtPP2CG1 up-regulated the expression levels of stress-responsive genes, including RD29A, RD29B, DREB2A and KIN1. GUS activity was detected in roots, leaves, stems, flower, and trichomes of AtPP2CG1 promoter-GUS transgenic plants. AtPP2CG1 protein was localized in nucleus and cytoplasm via AtPP2CG1:eGFP and YFP:AtPP2CG1 fusion approaches.« less

Highly sensitive radioimmunoassay for chorionic gonadotropin in human urine. [/sup 125/I tracer technique

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

Ayala, A.R.; Nisula, B.C.; Chen, H.C.

1978-10-01

The value of RIAs that measure hCG levels in human urine has been limited principally because of cross-reactivity with human LH. Recently, antisera generated to antigenic determinants on the intact hCG..beta.. subunit and its carboxyl-terminal peptide have been shown to exhibit substantially reduced human LH cross-reactivity. To take maximal advantage of these antisera and to minimize interference by nonspecific substances in urine, a procedure for extracting and concentrating hCG from 24-h urine samples was developed. The procedure involves preparation of a standard kaolin-acetone urine concentrate and adsorption of the hCG in the concentrate to Concanavalin A covalently linked to agarosemore » for purification and subsequent RIA. In urine samples obtained from patients with gestational trophoblastic disease, there was a direct correlation between hCG levels measured by RIA and those estimated by mouse uterine weight bioassy. In individual subjects, hCG levels were determined in serum and urine obtained the same day. When hCG was clearly detectable in the serum at levels greater than 1 ng/ml, the quantity of hCG measured in the urine concentrate exceeded 500 ng/24 h. The concentrates prepared from the urine of normal persons contained an hCG-like glycoprotein substance with antigenic determinants similar to those of the carboxyl-terminal peptide of hCG..beta... As the range of hCG immunoreactivity measured in the urine concentrates of normal subjects was 6 to 52 ng/24 h, specific and sensitive detection of urinary hCG could be accomplished in patients whose sera contained hCG undetectable by conventional RIA. Partial purification and concentration of urinary hCG by this procedure with subsequent RIA provides a sensitive and reliable method for detecting hCG in urine.« less

hCGbeta core fragment is a metabolite of hCG: evidence from infusion of recombinant hCG.

PubMed

Norman, R J; Buchholz, M M; Somogyi, A A; Amato, F

2000-03-01

The availability of recombinant human chorionic gonadotrophin (r-hCG) has allowed us to measure its metabolic and renal clearance rates and to study the origin of the beta core fragment of hCG (hCGbetacf). Serum and urine samples were collected from six subjects, after an intravenous injection of 2 mg (equivalent to 44 000 IU Urinary hCG) r-hCG, and assayed for hCG and the beta subunit (hCGbeta). Urine from four of the subjects was also subjected to gel chromatography and assayed for hCGbetacf and hCG. r-hCG, administered as an intravenous dose, was distributed, initially in a volume of 3.4+/-0.7 l (mean+/-s.d.) and then in 6.5+/-1.15 l at steady-state. The disappearance of r-hCG from serum was bi-exponential, with an initial half-life of 4.5+/-0.7 h and a terminal half-life of 29.0+/-4.6 h. The mean residence time was 28. 6+/- 3.6 h and the total systemic clearance rate of r-hCG was 226+/-18 ml/h. The renal clearance rate was 28.75+/-6.2 ml/h (mean+/-s.d). hCGbetacf was detected in all urine samples collected at 6 h intervals. Over the 138 h period of urine collection, 12.9% (range 10.1-17.3% ) of r-hCG injected was recovered as the intact molecule and 1.7% (range 0.8-2.9%) was recovered as the hCGbetacf, in 4 subjects. The molar ratio of hCGbetacf to hCG in urine increased from 3.1+/-1.7%, on day 1, to 76+/-34.3% (mean+/-s.e.m.) on day 5, after r-hCG infusion, suggesting that hCGbetacf is a metabolic product of the infused r-hCG.

Circadian gene methylation profiles are associated with obesity, metabolic disturbances and carbohydrate intake.

PubMed

Ramos-Lopez, Omar; Samblas, Mirian; Milagro, Fermin I; Riezu-Boj, Jose I; Crujeiras, A B; Martinez, J Alfredo; Project, Mena

2018-03-26

The circadian clock regulates the daily rhythms of several physiological and behavioral processes. Disruptions in clock genes have been associated with obesity and related comorbidities. This study aimed to analyze the association of DNA methylation signatures at circadian rhythm pathway genes with body mass index (BMI), metabolic profiles and dietary intakes. DNA methylation profiling was determined by microarray in white blood cells from 474 adults from the Methyl Epigenome Network Association (MENA) project. Kyoto Encyclopedia of Genes and Genomes database was used to identify the genes integrating the circadian rhythm pathway. Network enrichment analyses were performed with the PathDIP platform. Associations between circadian methylation patterns with anthropometric measurements, the metabolic profile, clinical data and dietary intakes were analyzed. DNA methylation patterns of nine CpG sites at six circadian rhythm pathway genes were strongly correlated with BMI (false discovery rates <0.0001). These CpGs encompassed cg09578018 (RORA), cg20406576 (PRKAG2), cg10059324 (PER3), cg01180628 (BHLHE40), cg23871860 (FBXL3), cg16964728 (RORA), cg14129040 (CREB1), cg07012178 (PRKAG2) and cg24061580 (PRKAG2). Interestingly, network enrichment analyses revealed that the six BMI-associated genes statistically contributed to the regulation of the circadian rhythm pathway (p = 1.9E-10). In addition, methylation signatures at cg09578018 (RORA), cg24061580 (PRKAG2), cg01180628 (BHLHE40) and cg10059324 (PER3) also correlated with insulin resistance (p < 0.0001) and mean arterial blood pressure (p < 0.0001). Furthermore, relevant correlations (p < 0.05) between methylation at cg09578018 (RORA) and cg01180628 (BHLHE40) with total energy and carbohydrate intakes were found. This investigation revealed potential associations of DNA methylation profiles at circadian genes with obesity, metabolic disturbances and carbohydrate intake, with potential impact on weight homeostasis.

Genomic analysis of NF-κB signaling pathway reveals its complexity in Crassostrea gigas.

PubMed

Yu, Mingjia; Chen, Jianming; Bao, Yongbo; Li, Jun

2018-01-01

NF-κB signaling pathway is an evolutionarily conserved pathway that plays highly important roles in several developmental, cellular and immune response processes. With the recent release of the draft Pacific oyster (Crassostra gigas) genome sequence, we have sought to identify the various components of the NF-κB signaling pathway in these mollusks and investigate their gene structure. We further constructed phylogenetic trees to establish the evolutionary relationship of the oyster proteins with their homologues in vertebrates and invertebrates using BLASTX and neighbor-joining method. We report the presence of two classic NF-κB/Rel homologues in the pacific oyster namely Cgp100 and CgRel, which possess characteristic RHD domain and a consensus nuclear localization signal, similar to mammalian homologues and an additional CgRel-like protein, unique to C. gigas. Further, in addition to two classical IκB homologues, CgIκB1 and CgIκB2, we have identified three atypical IκB family members namely CgIκB3, CgIκB4 and CgBCL3 which lack the IκB degradation motif and consist of only one exon that might have arisen by retrotransposition from CgIκB1. Finally, we report the presence of three IKKs and one NEMO genes in oyster genome, named CgIKK1, CgIKK2, CgIKK3 and CgNEMO, respectively. While CgIKK1 and CgIKK3 domain structure is similar to their mammalian homologues, CgIKK2 was found to lack the HLH and NBD domains. Overall, the high conservation of the NF-κB/Rel, IκB and IKK family components in the pacific oyster and their structural similarity to the vertebrate and invertebrate homologues underline the functional importance of this pathway in regulation of critical cellular processes across species. Copyright © 2017 Elsevier Ltd. All rights reserved.

One year double blind study of high vs low frequency subcallosal cingulate stimulation for depression.

PubMed

Eitan, Renana; Fontaine, Denys; Benoît, Michel; Giordana, Caroline; Darmon, Nelly; Israel, Zvi; Linesky, Eduard; Arkadir, David; Ben-Naim, Shiri; Iserlles, Moshe; Bergman, Hagai; Hulse, Natasha; Abdelghani, Mohamed; McGuffin, Peter; Farmer, Anne; DeLea, Peichel; Ashkan, Keyoumars; Lerer, Bernard

2018-01-01

Subcallosal Brodmann's Area 25 (Cg25) Deep Brain Stimulation (DBS) is a new promising therapy for treatment resistant major depressive disorder (TR-MDD). While different DBS stimulating parameters may have an impact on the efficacy and safety of the therapy, there is no data to support a protocol for optimal stimulation parameters for depression. Here we present a prospective multi-center double-blind randomized crossed-over 13-month study that evaluated the effects of High (130 Hz) vs Low (20 Hz) frequency Cg25 stimulation for nine patients with TR-MDD. Four out of nine patients achieved response criteria (≥40% reduction of symptom score) compared to mean baseline values at the end of the study. The mean percent change of MADRS score showed a similar improvement in the high and low frequency stimulation groups after 6 months of stimulation (-15.4 ± 21.1 and -14.7 ± 21.1 respectively). The mean effect at the end of the second period (6 months after cross-over) was higher than the first period (first 6 months of stimulation) in all patients (-23.4 ± 19.9 (n = 6 periods) and -13.0 ± 22 (n = 9 periods) respectively). At the end of the second period, the mean percent change of the MADRS scores improved more in the high than low frequency groups (-31.3 ± 19.3 (n = 4 patients) and -7.7 ± 10.9 (n = 2 patients) respectively). Given the small numbers, detailed statistical analysis is challenging. Nonetheless the results of this study suggest that long term high frequency stimulation might confer the best results. Larger scale, randomized double blind trials are needed in order to evaluate the most effective stimulation parameters. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanisms of strand break formation in DNA due to the direct effect of ionizing radiation: the dependency of free base release on the length of alternating CG oligodeoxynucleotides.

PubMed

Sharma, Kiran K; Razskazovskiy, Yuriy; Purkayastha, Shubhadeep; Bernhard, William A

2009-06-11

The question of how NA base sequence influences the yield of DNA strand breaks produced by the direct effect of ionizing radiation was investigated in a series of oligodeoxynucleotides of the form (d(CG)(n))(2) and (d(GC)(n))(2). The yields of free base release from X-irradiated DNA films containing 2.5 waters/nucleotide were measured by HPLC as a function of oligomer length. For (d(CG)(n))(2), the ratio of the Gua yield to Cyt yield, R, was relatively constant at 2.4-2.5 for n = 2-4 and it decreased to 1.2 as n increased from 5 to 10. When Gua was moved to the 5' end, for example going from d(CG)(5) to d(GC)(5), R dropped from 1.9 +/- 0.1 to 1.1 +/- 0.1. These effects are poorly described if the chemistry at the oligomer ends is assumed to be independent of the remainder of the oligomer. A mathematical model incorporating charge transfer through the base stack was derived to explain these effects. In addition, EPR was used to measure the yield of trapped-deoxyribose radicals at 4 K following X-irradiation at 4 K. The yield of free base release was substantially greater, by 50-100 nmol/J, than the yield of trapped-deoxyribose radicals. Therefore, a large fraction of free base release stems from a nonradical intermediate. For this intermediate, a deoxyribose carbocation formed by two one-electron oxidations is proposed. This reaction pathway requires that the hole (electron loss site) transfers through the base stack and, upon encountering a deoxyribose hole, oxidizes that site to form a deoxyribose carbocation. This reaction mechanism provides a consistent way of explaining both the absence of trapped radical intermediates and the unusual dependence of free base release on oligomer length.

Home Telehealth and Caregiving Appraisal in Chronic Illness.

PubMed

Wakefield, Bonnie J; Vaughan-Sarrazin, Mary

2017-04-01

Remote health monitoring applications are being adopted to improve the health of chronically ill individuals. Little work has focused on the effects of these technologies on informal caregivers (CG) of patients with chronic illnesses. To examine differences in caregiving appraisal between CG of enrolled and nonenrolled Veterans in the home telehealth (HT) program. Cross-sectional survey methodology in 244 dyads (Veteran and CG) from 6 rural Midwestern Veterans Affairs Medical Centers. Survey variables were derived from the 2004 National Alliance for Caregiving survey, along with measures of caregiving strain, burden, and satisfaction. We found no differences when comparing HT and non-HT CG. In multivariate analyses combining the two groups, CG characteristics associated with CG strain included younger age, providing help with activities of daily living and instrumental activities of daily living, use of coping skills, depressive symptoms, and less use of unpaid help (all p ≤ 0.001). Burden was associated with CG use of coping skills, caregiving confidence, and relationship quality with the Veteran (all p < 0.0001). CG satisfaction was associated with presence of social support (p < 0.0001). High CG strain was associated with Veteran hospitalization in the combined group (p = 0.03). Burden (p = 0.0002) was significantly associated with CG satisfaction. Existing HT infrastructure provides an opportunity to incorporate training and support programs for CG of chronically ill patients. Such programs could improve CG confidence and use of positive coping skills, lower strain and burden, and potentially improve the health of both the care recipient and CG.

Complicated grief among individuals with major depression: prevalence, comorbidity, and associated features.

PubMed

Sung, Sharon C; Dryman, M Taylor; Marks, Elizabeth; Shear, M Katherine; Ghesquiere, Angela; Fava, Maurizio; Simon, Naomi M

2011-11-01

Growing data suggest that complicated grief (CG) may be common in clinical care settings, but there are few prior reports about CG in outpatients presenting with primary mood disorders. The present study examined rates of bereavement and threshold CG symptoms (defined as a score ≥ 25 on the Inventory of Complicated Grief scale) in 111 outpatients with major depressive disorder (MDD) and 142 healthy controls participating in a study of stress and depression. Clinical and demographic characteristics were also compared for bereaved individuals with CG (MDD+CG) to those without (MDD-CG). Participants completed structured diagnostic interviews as well as measures of CG, depression, anxiety, exposure to traumatic events, and perceived social support. Lifetime history of a significant loss did not differ for the MDD and control groups (79.3% vs. 76.1%), but bereaved participants with MDD had higher rates of threshold CG (25.0% vs. 2.8%). Among those with MDD, CG was associated with a higher prevalence of lifetime alcohol dependence, greater exposure to traumatic events, and lower perceived social support. Depressed women, but not men, with CG also had higher rates of panic disorder, social anxiety disorder, and posttraumatic stress disorder. Our findings are limited by the lack of a clinician confirmatory assessment of CG diagnosis, absence of complete information about the nature and timing of the loss, and relatively narrow generalizability. We found high rates of CG in a group of psychiatric outpatients with chronic MDD, suggesting that patients with depression should be routinely screened for CG. Copyright © 2011 Elsevier B.V. All rights reserved.

Complicated grief among individuals with major depression: Prevalence, comorbidity, and associated features

PubMed Central

Sung, Sharon C.; Dryman, M. Taylor; Marks, Elizabeth; Shear, M. Katherine; Ghesquiere, Angela; Fava, Maurizio; Simon, Naomi M.

2011-01-01

Background Growing data suggest that complicated grief (CG) may be common in clinical care settings, but there are few prior reports about CG in outpatients presenting with primary mood disorders. Methods The present study examined rates of bereavement and threshold CG symptoms (defined as a score ≥ 25 on the Inventory of Complicated Grief scale) in 111 outpatients with major depressive disorder (MDD) and 142 healthy controls participating in a study of stress and depression. Clinical and demographic characteristics were also compared for bereaved individuals with CG (MDD + CG) to those without (MDD – CG). Participants completed structured diagnostic interviews as well as measures of CG, depression, anxiety, exposure to traumatic events, and perceived social support. Results Lifetime history of a significant loss did not differ for the MDD and control groups (79.3% vs. 76.1%), but bereaved participants with MDD had higher rates of threshold CG (25.0% vs. 2.8%). Amongst those with MDD, CG was associated with a higher prevalence of lifetime alcohol dependence, greater exposure to traumatic events, and lower perceived social support. Depressed women, but not men, with CG also had higher rates of panic disorder, social anxiety disorder, and posttraumatic stress disorder. Limitations Our findings are limited by the lack of a clinician confirmatory assessment of CG diagnosis, absence of complete information about the nature and timing of the loss, and relatively narrow generalizability. Conclusions We found high rates of CG in a group of psychiatric outpatients with chronic MDD, suggesting that patients with depression should be routinely screened for CG. PMID:21621849

Promoting Physical Activity Through a Manual Wheelchair Propulsion Intervention in Persons With Multiple Sclerosis.

PubMed

Rice, Ian M; Rice, Laura A; Motl, Robert W

2015-10-01

To examine the efficacy and feasibility of a multifactorial intervention to increase lifestyle physical activity in nonambulatory persons with multiple sclerosis (MS) based on wheelchair optimization, propulsion skill/technique training, and behavioral strategies based on social cognitive theory. Randomized controlled trial, 3-month postintervention follow-up. Home and general community, and university research laboratory. Nonambulatory individuals with MS (N=14; mean age ± SD, 53.6±8.7y) were randomly assigned to an intervention group (IG) or a control group (CG). After baseline testing, the IG participants received custom-fit, ultralightweight manual wheelchairs with propulsion/skills training, followed by 3 months of at-home use with the custom ultralightweight wheelchair and weekly phone calls to deliver support through a multifactorial intervention. The CG participants received no training and used their own wheelchairs at home during this time. All subjects were assessed at baseline and 3 months later for fatigue (Fatigue Severity Scale), upper extremity strength (digital handheld dynamometer), and propulsion technique (on a treadmill [0.5m/s] with instrumented wheels). Two 1-week bouts of physical activity were measured in both groups from home with wrist-worn accelerometry at the beginning (IG and CG in own wheelchairs) and end (IG in study wheelchair, CG in own) of the 3-month period of home use. The intervention was well tolerated, and no adverse events were reported. The IG demonstrated increased strength (P=.008) and a trend toward less fatigue (P=.068), both with large effect sizes (d>0.8), as well as reduced application of braking torque during propulsion (P=.003) with a moderate/large effect size (d=.73), compared with the CG. Findings suggest a 3-month physical activity intervention based on manual wheelchair propulsion and training is safe and feasible for some wheelchair users living with MS and may produce secondary benefits in strength, fatigue, and propulsion technique. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Longitudinal analysis of haplotypes and polymorphisms of the APOA5 and APOC3 genes associated with variation in serum triglyceride levels: the Bogalusa Heart Study.

PubMed

Hallman, D Michael; Srinivasan, Sathanur R; Chen, Wei; Boerwinkle, Eric; Berenson, Gerald S

2006-12-01

Polymorphisms in the APOC3 and APOA5 genes, from the APOA1/APOC3/APOA4/APOA5 gene cluster on chromosome 11q23, have been associated with interindividual variation in plasma triglycerides. APOA5 polymorphisms implicated include 2 in the promoter region (-1131 T/C and -3 A/G) and 1 in exon 2 (+56 C/G). APOC3 polymorphisms implicated include 1 (SstI) in the 3' untranslated region and 1 (-2854 G/T) in the APOC3-APOA4 intergenic region. We analyzed the associations of haplotypes and multilocus genotypes of these polymorphisms on longitudinal serum triglyceride profiles in 360 African American and 823 white subjects from the Bogalusa Heart Study. Subjects were examined from 2 to 8 times (mean +/- SD, 5.4 +/- 1.3) between 1973 and 1996, at ages ranging from 4 to 38 years, with 1978 observations in African Americans and 4465 in whites. Serum triglycerides were significantly higher among whites across all ages. Allele frequencies differed significantly between African Americans and whites at all but the APOA5 +56 C/G locus. Linkage disequilibrium among the loci was higher in whites and haplotype diversity lower: 6 haplotypes had estimated frequencies of more than 1% in African Americans, 5 in whites. Individually, all polymorphisms except APOC3 -2854 G/T showed significant associations with triglyceride levels in the full sample. However, genotype models including all 5 loci showed significant triglyceride associations for only 3 (APOC3 SstI, APOA5 -1131 T/C, and APOA5 +56 C/G); significant interactions among them indicated their effects were not independent. Neither APOC3 -2854 G/T nor APOA5 -3 A/G had significant effects when the other 3 loci were in the models. The EM algorithm was used to estimate haplotype frequencies and assign haplotype probabilities to individuals, which is conditional on their genotypes; individuals' haplotype probability vectors were then used as predictors in multilevel mixed models of longitudinal triglyceride profiles. Of haplotypes comprising, in order, APOC3 SstI and -2854 G/T and APOA5 -1131 T/C, -3 A/G, and +56 C/G, 3 were significantly associated with higher triglycerides, even after adjusting for multiple tests: GGTAG (P = .002), GTTAG (P < .0001), and CGCGC (P = .0002). Each GGTAG haplotype carried would be expected to raise triglyceride levels (relative to those of GTTAC homozygotes) by approximately 19 mg/dL, each GTTAG haplotype by approximately 15 mg/dL, and each CGCGC haplotype by approximately 7 mg/dL. Haplotypes comprising the 3 loci implicated by genotype analyses (SstI, -1131 T/C, and +56 C/G) were also tested: haplotypes C_C_C and G_T_G significantly raised triglycerides, even after adjustment for multiple comparisons (P < .002 for both), with each copy of C_C_C expected to raise triglycerides by approximately 7 mg/dL and each copy of G_T_G by approximately 15 mg/dL. Overall, our findings support those of others in associating specific polymorphisms and haplotypes in the APOA1/C3/A4/A5 gene cluster with higher serum triglyceride levels. However, the degree to which polymorphisms in the APOC3 and APOA5 genes may be independently associated with triglyceride levels remains to be determined.

Overview of the Cancer Genetics and Pathway Curation tasks of BioNLP Shared Task 2013

PubMed Central

2015-01-01

Background Since their introduction in 2009, the BioNLP Shared Task events have been instrumental in advancing the development of methods and resources for the automatic extraction of information from the biomedical literature. In this paper, we present the Cancer Genetics (CG) and Pathway Curation (PC) tasks, two event extraction tasks introduced in the BioNLP Shared Task 2013. The CG task focuses on cancer, emphasizing the extraction of physiological and pathological processes at various levels of biological organization, and the PC task targets reactions relevant to the development of biomolecular pathway models, defining its extraction targets on the basis of established pathway representations and ontologies. Results Six groups participated in the CG task and two groups in the PC task, together applying a wide range of extraction approaches including both established state-of-the-art systems and newly introduced extraction methods. The best-performing systems achieved F-scores of 55% on the CG task and 53% on the PC task, demonstrating a level of performance comparable to the best results achieved in similar previously proposed tasks. Conclusions The results indicate that existing event extraction technology can generalize to meet the novel challenges represented by the CG and PC task settings, suggesting that extraction methods are capable of supporting the construction of knowledge bases on the molecular mechanisms of cancer and the curation of biomolecular pathway models. The CG and PC tasks continue as open challenges for all interested parties, with data, tools and resources available from the shared task homepage. PMID:26202570

Oocyte maturation and origin of the germline as revealed by the expression of Nanos-like in the Pacific oyster Crassostrea gigas.

PubMed

Xu, Rui; Li, Qi; Yu, Hong; Kong, Lingfeng

2018-04-13

Nanos gene plays an important role in germline development in animals. However, the molecular mechanisms involved in germline development in Mollusca, the second largest animal phylum, are still poorly understood. Here we identified the Nanos orthologue from the Pacific oyster Crassostrea gigas (Cg-Nanos-like), and investigated the expression patterns of Nanos during gametogenesis and embryogenesis in C. gigas. Tissue expression analysis showed that Cg-Nanos-like was specifically expressed in female gonads. During the reproductive cycle, the expression of Cg-Nanos-like mRNA increased matching the seasonal development of the ovarian tissues in diploids, while the expression levels were significantly lower in the ovaries of sterile triploids compared to diploids. High expression of Cg-Nanos-like transcripts were detected in early embryonic stages, while the expression significantly dropped at gastrulation and was barely detectable in veliger stages. In situ hybridization showed that Cg-Nanos-like was expressed at different stages of developing oocytes, whereas positive signals were detected only in spermatogonia during the spermatogenic cycle. These findings indicated that Cg-Nanos-like was involved in the development of germ cells, and maintenance of oocyte maturation. In early embryogenesis, the transcripts were broadly expressed; following gastrulation, the expression was restricted to two cell clumps, which might be the putative primordial germ cells (PGCs) or their precursors. Based on the results, the formation of the PGCs in C. gigas was consistent with the model of transition from epigenesis to preformation. Copyright © 2017. Published by Elsevier B.V.

Gentamicin-Eluting Titanium Dioxide Nanotubes Grown on the Ultrafine-Grained Titanium.

PubMed

Nemati, Sima Hashemi; Hadjizadeh, Afra

2017-08-01

Titanium (Ti)-based materials is the most appropriate choices for the applications as orthopedic and dental implants. In this regard, ultrafine-grained (UFG) titanium with an enhanced mechanical properties and surface energy has attracted more attention. Titanium dioxide (TiO 2 ) nanotubes grown on the titanium could enhance bone bonding, cellular response and are good reservoirs for loading drugs and antibacterial agents. This article investigates gentamicin loading into and release from the TiO 2 nanotubes, grown on the UFG compared to coarse-grained (CG) titanium substrate surfaces. Equal Channel Angular Pressing (ECAP) was employed to produce the UFG structure titanium. TiO 2 nanotubes were grown by the anodizing technique on both UFG and CG titanium substrate surfaces. Scanning electron microscopy (SEM) imaging confirmed TiO 2 nanotube growth on the surface. The UV-vis spectroscopy analysis results show that the amount of gentamicin load-release in the anodized UFG titanium sample is higher than that of CG one which can be explained in terms of thicker TiO 2 nanotube arrays layer formed on UFG sample. Moreover, the anodized UFG titanium samples released the drug in a longer time than CG (1 day for the UFG titanium vs. 3 h for the CG one). Regarding wettability analysis, anodized UFG titanium sample showed more enhanced hydrophilicity than CG counterpart. Therefore, the significantly smaller grain size of pure titanium provided by the ECAP technique coupled with appropriate subsequent anodization treatment not only offers a good combination of biocompatibility and adequate mechanical properties but also it provides a delayed release condition for gentamicin.

Bipolar cloud-to-ground lightning flash observations

NASA Astrophysics Data System (ADS)

Saba, Marcelo M. F.; Schumann, Carina; Warner, Tom A.; Helsdon, John H.; Schulz, Wolfgang; Orville, Richard E.

2013-10-01

lightning is usually defined as a lightning flash where the current waveform exhibits a polarity reversal. There are very few reported cases of cloud-to-ground (CG) bipolar flashes using only one channel in the literature. Reports on this type of bipolar flashes are not common due to the fact that in order to confirm that currents of both polarities follow the same channel to the ground, one necessarily needs video records. This study presents five clear observations of single-channel bipolar CG flashes. High-speed video and electric field measurement observations are used and analyzed. Based on the video images obtained and based on previous observations of positive CG flashes with high-speed cameras, we suggest that positive leader branches which do not participate in the initial return stroke of a positive cloud-to-ground flash later generate recoil leaders whose negative ends, upon reaching the branch point, traverse the return stroke channel path to the ground resulting in a subsequent return stroke of opposite polarity.

The potential of cashew gum functionalization as building blocks for layer-by-layer films.

PubMed

Leite, Álvaro J; Costa, Rui R; Costa, Ana M S; Maciel, Jeanny S; Costa, José F G; de Paula, Regina C M; Mano, João F

2017-10-15

Cashew gum (CG), an exudate polysaccharide from Anacardium occidentale trees, was carboxymethylated (CGCm) and oxidized (CGO). These derivatives were characterized by FTIR and zeta potential measurements confirming the success of carboxymethylation and oxidation reactions. Nanostructured multilayered films were then produced through layer-by-layer (LbL) assembly in conjugation with chitosan via electrostatic interactions or Schiff bases covalent bonds. The films were analyzed by QCM-D and AFM. CG functionalization increased the film thickness, with the highest thickness being achieved for the lowest oxidation degree. The roughest surface was obtained for the CGO with the highest oxidation degree due to the predominance of covalent Schiff bases. This work shows that nanostructured films can be assembled and stabilized by covalent bonds in alternative to the conventional electrostatic ones. Moreover, the functionalization of CG can increase its feasibility in multilayers films, widening its potential in biomedical, food industry, or environmental applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pregnancy testing with hCG--future prospects.

PubMed

Berger, Peter; Sturgeon, Catharine

2014-12-01

Pregnancy tests for human chorionic gonadotrophin (hCG) are used widely in hospital and home settings. Assays measuring hCG also have uses in prenatal screening and oncology. The output from three recent international workshops provides a framework for reliable measurement of hCG. Requirements for future hCG assays include use of clear descriptive nomenclature, informed selection of antibodies of well-defined epitope specificities, and design of robust methods. Tests will be precisely characterized and calibrated in SI units using six International Reference Reagents (IRR) for hCG and variants, and the Fifth International Standard for hCG 07/364, making it possible to report clinical results in molar units. These measures will help to increase patient safety by reducing the risk of erroneous or misleading hCG results. Copyright © 2014 Elsevier Ltd. All rights reserved.

Kathon CG and cosmetic products.

PubMed

Rastogi, S C

1990-03-01

Kathon CG was determined in 156 of the most commonly used cosmetic products in Denmark. 42% of the cosmetic products were found to contain Kathon CG. Kathon CG was present in 48% of "rinse off" and 31% of "leave on" cosmetic products. The 3:1 ratio of chloromethyl isothiazolinone (CMI): methyl isothiazolinone (MI) in Kathon CG was found to be disturbed in 41% of Kathon CG preserved cosmetic products. The disturbed CMI/MI ratio was shown in 29% "rinse off" and 73% "leave on" cosmetic products. It is suggested that the chemical reaction of the ketone group of the isothizaolinones with other ingredients in cosmetic products may disturb the CMI/MI ratio of Kathon CG. The results of the study have been discussed in relation to the use of Kathon CG in cosmetic products as well as test material for allergic reaction.

How Well Do Computer-Generated Faces Tap Face Expertise?

PubMed

Crookes, Kate; Ewing, Louise; Gildenhuys, Ju-Dith; Kloth, Nadine; Hayward, William G; Oxner, Matt; Pond, Stephen; Rhodes, Gillian

2015-01-01

The use of computer-generated (CG) stimuli in face processing research is proliferating due to the ease with which faces can be generated, standardised and manipulated. However there has been surprisingly little research into whether CG faces are processed in the same way as photographs of real faces. The present study assessed how well CG faces tap face identity expertise by investigating whether two indicators of face expertise are reduced for CG faces when compared to face photographs. These indicators were accuracy for identification of own-race faces and the other-race effect (ORE)-the well-established finding that own-race faces are recognised more accurately than other-race faces. In Experiment 1 Caucasian and Asian participants completed a recognition memory task for own- and other-race real and CG faces. Overall accuracy for own-race faces was dramatically reduced for CG compared to real faces and the ORE was significantly and substantially attenuated for CG faces. Experiment 2 investigated perceptual discrimination for own- and other-race real and CG faces with Caucasian and Asian participants. Here again, accuracy for own-race faces was significantly reduced for CG compared to real faces. However the ORE was not affected by format. Together these results signal that CG faces of the type tested here do not fully tap face expertise. Technological advancement may, in the future, produce CG faces that are equivalent to real photographs. Until then caution is advised when interpreting results obtained using CG faces.

On the representability problem and the physical meaning of coarse-grained models

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

Wagner, Jacob W.; Dama, James F.; Durumeric, Aleksander E. P.

2016-07-28

In coarse-grained (CG) models where certain fine-grained (FG, i.e., atomistic resolution) observables are not directly represented, one can nonetheless identify indirect the CG observables that capture the FG observable’s dependence on CG coordinates. Often, in these cases it appears that a CG observable can be defined by analogy to an all-atom or FG observable, but the similarity is misleading and significantly undermines the interpretation of both bottom-up and top-down CG models. Such problems emerge especially clearly in the framework of the systematic bottom-up CG modeling, where a direct and transparent correspondence between FG and CG variables establishes precise conditions formore » consistency between CG observables and underlying FG models. Here we present and investigate these representability challenges and illustrate them via the bottom-up conceptual framework for several simple analytically tractable polymer models. The examples provide special focus on the observables of configurational internal energy, entropy, and pressure, which have been at the root of controversy in the CG literature, as well as discuss observables that would seem to be entirely missing in the CG representation but can nonetheless be correlated with CG behavior. Though we investigate these problems in the framework of systematic coarse-graining, the lessons apply to top-down CG modeling also, with crucial implications for simulation at constant pressure and surface tension and for the interpretations of structural and thermodynamic correlations for comparison to experiment.« less

Interactions of chromogranin A-derived vasostatins and monolayers of phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine.

PubMed

Blois, Anna; Holmsen, Holm; Martino, Guglielmo; Corti, Angelo; Metz-Boutigue, Marie-Hélène; Helle, Karen B

2006-03-15

Vasostatin-I (CgA1-76) is a naturally occurring and biologically active N-terminal peptide derived from chromogranin A (CgA), produced and secreted at high concentrations by neuroendocrine tissues and also from a range of neuroendocrine tumors. This study aims to examine the hypothesis that in the absence of classical protein receptors CgA1-76 may, like its two derived peptides CgA1-40 and CgA47-66, perturb the lipid microenvironment of other membrane receptors, as a basis for the largely inhibitory activities of these CgA peptides. The nature of the interactions between phospholipids and vasostatin-derived fragments was studied in the Langmuir film balance apparatus at 37 degrees C. The synthetic peptides CgA1-40 and CgA47-66 and a recombinant fragment (VS-I) containing vasostatin-I (Ser-Thr-Ala-CgA1-78) were compared for their effects on monolayers of phosphatidylcholine and phosphatidylethanolamine from pig brain and defined species of phosphatidylserine. Marked differences in surface pressure-area isotherms and phase-transition plateaus were apparent with the three classes of phospholipids on VS-I, CgA1-40 and CgA47-66 in physiological buffer or pure water. The results indicate that VS-I and CgA47-66 at 5-10 nM concentrations may engage in electrostatic as well as hydrophobic interactions with membrane-relevant phospholipids at physiological conditions, VS-I in particular enhancing the fluidity of saturated species of phosphatidylserine.

Occult abnormal pregnancies after first post-embryo transfer serum beta-human chorionic gonadotropin levels of 1.0-5.0 mIU/mL.

PubMed

Maslow, Bat-Sheva L; Bartolucci, Alison; Sueldo, Carolina; Engmann, Lawrence; Benadiva, Claudio; Nulsen, John C

2016-04-01

To assess the occult pregnancy rate after "negative" first post-embryo transfer (ET) serum β-hCG results. Two-part retrospective cohort study and nested case series. University-based fertility center. A total of 1,571 negative first post-ET serum β-hCG results were included in the study; 1,326 results (primary cohort, June 2009-December 2013) were initially reported as <5 mIU/mL and 245 results (secondary cohort, January 2014-March 2015) were reported as discrete values from 1.0 to 5.0 mIU/mL. None. Rates of occult pregnancy, ectopic pregnancy, and complications after negative first post-ET serum β-hCG results. A total of 88.8% (1,178/1,326) of the negative first post-ET results reported as <5 were actually <1.0 mIU/mL. Occult pregnancy was incidentally identified in 1.2% (12/1,041) of subjects with follow-up. Six had ectopic pregnancies, and seven experienced serious complications; 11 (91.7%) of the 12 occult pregnancies had a first post-ET serum β-hCG level of 1.0-5.0 mIU/mL and 1 (8.3%) <1.0 mIU/mL. All pregnancies with serious complications had initial β-hCG levels of 1.0-5.0 mIU/mL. Of the 245 results reported as discreet values, occult pregnancies were diagnosed in 5.5% (9/163) of subjects with follow-up. One had an ectopic pregnancy, which was treated with methotrexate. There were no serious complications in the secondary cohort. The majority of negative first post-ET serum β-hCG levels are <1.0 mIU/mL. Results from 1.0 to 5.0 mIU/mL may fail to exclude abnormal pregnancy and are associated with poor outcomes compared with β-hCG levels <1.0 mIU/mL. Serial serum β-hCG may be warranted in this population. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Cloning retinoid and peroxisome proliferator-activated nuclear receptors of the Pacific oyster and in silico binding to environmental chemicals

PubMed Central

Vogeler, Susanne; Galloway, Tamara S.; Isupov, Michail

2017-01-01

Disruption of nuclear receptors, a transcription factor superfamily regulating gene expression in animals, is one proposed mechanism through which pollution causes effects in aquatic invertebrates. Environmental pollutants have the ability to interfere with the receptor’s functions through direct binding and inducing incorrect signals. Limited knowledge of invertebrate endocrinology and molecular regulatory mechanisms, however, impede the understanding of endocrine disruptive effects in many aquatic invertebrate species. Here, we isolated three nuclear receptors of the Pacific oyster, Crassostrea gigas: two isoforms of the retinoid X receptor, CgRXR-1 and CgRXR-2, a retinoic acid receptor ortholog CgRAR, and a peroxisome proliferator-activated receptor ortholog CgPPAR. Computer modelling of the receptors based on 3D crystal structures of human proteins was used to predict each receptor’s ability to bind to different ligands in silico. CgRXR showed high potential to bind and be activated by 9-cis retinoic acid and the organotin tributyltin (TBT). Computer modelling of CgRAR revealed six residues in the ligand binding domain, which prevent the successful interaction with natural and synthetic retinoid ligands. This supports an existing theory of loss of retinoid binding in molluscan RARs. Modelling of CgPPAR was less reliable due to high discrepancies in sequence to its human ortholog. Yet, there are suggestions of binding to TBT, but not to rosiglitazone. The effect of potential receptor ligands on early oyster development was assessed after 24h of chemical exposure. TBT oxide (0.2μg/l), all-trans retinoic acid (ATRA) (0.06 mg/L) and perfluorooctanoic acid (20 mg/L) showed high effects on development (>74% abnormal developed D-shelled larvae), while rosiglitazone (40 mg/L) showed no effect. The results are discussed in relation to a putative direct (TBT) disruption effect on nuclear receptors. The inability of direct binding of ATRA to CgRAR suggests either a disruptive effect through a pathway excluding nuclear receptors or an indirect interaction. Our findings provide valuable information on potential mechanisms of molluscan nuclear receptors and the effects of environmental pollution on aquatic invertebrates. PMID:28426724

hCG-induced endoplasmic reticulum stress triggers apoptosis and reduces steroidogenic enzyme expression through activating transcription factor 6 in Leydig cells of the testis

PubMed Central

Park, Sun-Ji; Kim, Tae-Shin; Park, Choon-Keun; Lee, Sang-Hee; Kim, Jin-Man; Lee, Kyu-Sun; Lee, In-kyu; Park, Jeen-Woo; Lawson, Mark A; Lee, Dong-Seok

2014-01-01

Endoplasmic reticulum (ER) stress generally occurs in secretory cell types. It has been reported that Leydig cells, which produce testosterone in response to human chorionic gonadotropin (hCG), express key steroidogenic enzymes for the regulation of testosterone synthesis. In this study, we analyzed whether hCG induces ER stress via three unfolded protein response (UPR) pathways in mouse Leydig tumor (mLTC-1) cells and the testis. Treatment with hCG induced ER stress in mLTC-1 cells via the ATF6, IRE1a/XBP1, and eIF2α/GADD34/ATF4 UPR pathways, and transient expression of 50 kDa protein activating transcription factor 6 (p50ATF6) reduced the expression level of steroidogenic 3β-hydroxy-steroid dehydrogenase Δ5-Δ4-isomerase (3β-HSD) enzyme. In an in vivo model, high-level hCG treatment induced expression of p50ATF6 while that of steroidogenic enzymes, especially 3β-HSD, 17α-hydroxylase/C17–20 lyase (CYP17), and 17β-hydrozysteroid dehydrogenase (17β-HSD), was reduced. Expression levels of steroidogenic enzymes were restored by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA). Furthermore, lentivirus-mediated transient expression of p50ATF6 reduced the expression level of 3β-HSD in the testis. Protein expression levels of phospho-JNK, CHOP, and cleaved caspases-12 and -3 as markers of ER stress-mediated apoptosis markedly increased in response to high-level hCG treatment in mLTC-1 cells and the testis. Based on transmission electron microscopy and H&E staining of the testis, it was shown that abnormal ER morphology and destruction of testicular histology induced by high-level hCG treatment were reversed by the addition of TUDCA. These findings suggest that hCG-induced ER stress plays important roles in steroidogenic enzyme expression via modulation of the ATF6 pathway as well as ER stress-mediated apoptosis in Leydig cells. PMID:23256993

Enhanced Sampling of an Atomic Model with Hybrid Nonequilibrium Molecular Dynamics-Monte Carlo Simulations Guided by a Coarse-Grained Model.

PubMed

Chen, Yunjie; Roux, Benoît

2015-08-11

Molecular dynamics (MD) trajectories based on a classical equation of motion provide a straightforward, albeit somewhat inefficient approach, to explore and sample the configurational space of a complex molecular system. While a broad range of techniques can be used to accelerate and enhance the sampling efficiency of classical simulations, only algorithms that are consistent with the Boltzmann equilibrium distribution yield a proper statistical mechanical computational framework. Here, a multiscale hybrid algorithm relying simultaneously on all-atom fine-grained (FG) and coarse-grained (CG) representations of a system is designed to improve sampling efficiency by combining the strength of nonequilibrium molecular dynamics (neMD) and Metropolis Monte Carlo (MC). This CG-guided hybrid neMD-MC algorithm comprises six steps: (1) a FG configuration of an atomic system is dynamically propagated for some period of time using equilibrium MD; (2) the resulting FG configuration is mapped onto a simplified CG model; (3) the CG model is propagated for a brief time interval to yield a new CG configuration; (4) the resulting CG configuration is used as a target to guide the evolution of the FG system; (5) the FG configuration (from step 1) is driven via a nonequilibrium MD (neMD) simulation toward the CG target; (6) the resulting FG configuration at the end of the neMD trajectory is then accepted or rejected according to a Metropolis criterion before returning to step 1. A symmetric two-ends momentum reversal prescription is used for the neMD trajectories of the FG system to guarantee that the CG-guided hybrid neMD-MC algorithm obeys microscopic detailed balance and rigorously yields the equilibrium Boltzmann distribution. The enhanced sampling achieved with the method is illustrated with a model system with hindered diffusion and explicit-solvent peptide simulations. Illustrative tests indicate that the method can yield a speedup of about 80 times for the model system and up to 21 times for polyalanine and (AAQAA)3 in water.

Enhanced Sampling of an Atomic Model with Hybrid Nonequilibrium Molecular Dynamics—Monte Carlo Simulations Guided by a Coarse-Grained Model

PubMed Central

2015-01-01

Molecular dynamics (MD) trajectories based on a classical equation of motion provide a straightforward, albeit somewhat inefficient approach, to explore and sample the configurational space of a complex molecular system. While a broad range of techniques can be used to accelerate and enhance the sampling efficiency of classical simulations, only algorithms that are consistent with the Boltzmann equilibrium distribution yield a proper statistical mechanical computational framework. Here, a multiscale hybrid algorithm relying simultaneously on all-atom fine-grained (FG) and coarse-grained (CG) representations of a system is designed to improve sampling efficiency by combining the strength of nonequilibrium molecular dynamics (neMD) and Metropolis Monte Carlo (MC). This CG-guided hybrid neMD-MC algorithm comprises six steps: (1) a FG configuration of an atomic system is dynamically propagated for some period of time using equilibrium MD; (2) the resulting FG configuration is mapped onto a simplified CG model; (3) the CG model is propagated for a brief time interval to yield a new CG configuration; (4) the resulting CG configuration is used as a target to guide the evolution of the FG system; (5) the FG configuration (from step 1) is driven via a nonequilibrium MD (neMD) simulation toward the CG target; (6) the resulting FG configuration at the end of the neMD trajectory is then accepted or rejected according to a Metropolis criterion before returning to step 1. A symmetric two-ends momentum reversal prescription is used for the neMD trajectories of the FG system to guarantee that the CG-guided hybrid neMD-MC algorithm obeys microscopic detailed balance and rigorously yields the equilibrium Boltzmann distribution. The enhanced sampling achieved with the method is illustrated with a model system with hindered diffusion and explicit-solvent peptide simulations. Illustrative tests indicate that the method can yield a speedup of about 80 times for the model system and up to 21 times for polyalanine and (AAQAA)3 in water. PMID:26574442

Rheological profiling of organogels prepared at critical gelling concentrations of natural waxes in a triacylglycerol solvent.

PubMed

Patel, Ashok R; Babaahmadi, Mehrnoosh; Lesaffer, Ans; Dewettinck, Koen

2015-05-20

The aim of this study was to use a detailed rheological characterization to gain new insights into the gelation behavior of natural waxes. To make a comprehensive case, six natural waxes (differing in the relative proportion of chemical components: hydrocarbons, fatty alcohols, fatty acids, and wax esters) were selected as organogelators to gel high-oleic sunflower oil. Flow and dynamic rheological properties of organogels prepared at critical gelling concentrations (Cg) of waxes were studied and compared using drag (stress ramp and steady flow) and oscillatory shear (stress and frequency sweeps) tests. Although, none of the organogels satisfied the rheological definition of a "strong gel" (G″/G' (ω) ≤ 0.1), on comparing the samples, the strongest gel (highest critical stress and dynamic, apparent, and static yield stresses) was obtained not with wax containing the highest proportion of wax esters alone (sunflower wax, SFW) but with wax containing wax esters along with a higher proportion of fatty alcohols (carnauba wax, CRW) although at a comparatively higher Cg (4%wt for latter compared to 0.5%wt for former). As expected, gel formation by waxes containing a high proportion of lower melting fatty acids (berry, BW, and fruit wax, FW) required a comparatively higher Cg (6 and 7%wt, respectively), and in addition, these gels showed the lowest values for plateau elastic modulus (G'LVR) and a prominent crossover point at higher frequency. The gelation temperatures (TG'=G″) for all the studied gels were lower than room temperature, except for SFW and CRW. The yielding-type behavior of gels was evident, with most gels showing strong shear sensitivity and a weak thixotropic recovery. The rheological behavior was combined with the results of thermal analysis and microstructure studies (optical, polarized, and cryo-scanning electron microscopy) to explain the gelation properties of these waxes.

[Both patients and physicians benefit from internet-based communication (APIKAP study)].

PubMed

Gersch, Christian; Ebel, Martin

2014-07-24

Internet-based applications are becoming more common in our modern world. While electronic health records (EHR) are available for patients and health care providers outside of Germany, most of the available data on EHR address only monetary advantages.This study explores whether or not internet-based communication between family physicians (FP) and patients is as safe as traditional oral communication and if it may lead to further benefits. 500 patients from 14 family doctors' offices were included in this 6 months RCT. Both groups were treated in the same manner by their respective physicians, but members of the study group (SG) were able to access an individual developed web-based software where they could view their diagnosis and medication, and send an electronic message to their doctors who would respond. Their satisfication with the FP, certain health data and the FP's workload were recorded. a) Patients' satisfaction: When e.g. asked about the organization of the family practice or trust in the doctor, there were no significant differences between the control (CG) and the SG (p = 0.07; p = 0.53). However, patients of the SG felt better informed (p = 0.01), and generally more satisfied with their FP (p = 0.04). b) FP workload: Members of the CG had 8.44 contacts with their doctors during the study, while the SG only had 7.96 recorded contacts (including web-based contacts, p = 0.32). It took physicians 3:52 minutes less to read and respond to an electronic message than to see a patient during the consultation hours. c) Changes in patients' health: During the study the blood pressure (BP) in the CG rose 4.44/2.80 mmHg, while it dropped 3.13/4.36 mmHg in the SG (p = 0.19/0.01).The HbA(1C) dropped in both groups (p = 0.91). One week after the first visit to the family doctor, patients of the SG rated their pain 0.28 points lower on a VAS than the CG (p = 0.75). 91% from the CG and 96% from the SG requested the re-prescription of long-term medication on time (p = 0.16). Using an optional web-based communication platform is as safe as traditional consultations can be. Both patients and doctors may benefit from using the internet in this context.

Thyroid Function and Premature Delivery in TPO Antibody-Negative Women: The Added Value of hCG.

PubMed

Korevaar, Tim I M; Steegers, Eric A P; Chaker, Layal; Medici, Marco; Jaddoe, Vincent W V; Visser, Theo J; de Rijke, Yolanda B; Peeters, Robin P

2017-09-01

Human chorionic gonadotropin (hCG) stimulates thyroid function during pregnancy. We recently showed that thyroid autoimmunity severely attenuated the thyroidal response to hCG stimulation and that this may underlie the higher risk of premature delivery in thyroperoxidase antibody (TPOAb)-positive women. We hypothesized that a lower thyroidal response to hCG stimulation in TPOAb-negative women is also associated with a higher risk of premature delivery and preterm premature rupture of membranes (pPROM). Thyrotropin (TSH), free thyroxine (FT4), and hCG concentrations were available in 5644 TPOAb-negative women from a prospective cohort. We tested for interaction between TSH or FT4 and hCG in linear regression models for duration of pregnancy and logistic regression models for premature delivery/pPROM. Accordingly, analyses were stratified per TSH percentile (TSH ≥ 85th percentile) and hCG per 10,000 IU/L. Women with high TSH and low hCG concentrations did not have a higher risk of premature delivery or pPROM, with protective effect estimates. In contrast, women with a high TSH concentration despite a high hCG concentration had twofold to 10-fold higher risk of premature delivery (Pdifference = 0.022) and an up to fourfold higher risk of pPROM (Pdifference = 0.079). hCG concentrations were not associated with premature delivery or pPROM. In TPOAb-negative women with high-normal TSH concentrations, only women with high hCG concentrations had a higher risk of premature delivery or pPROM. These results suggest a lower thyroidal response to hCG stimulation is also associated with premature delivery in TPOAb-negative women and that an additional measurement of hCG may improve thyroid-related risk assessments during pregnancy. Copyright © 2017 Endocrine Society

Biological functions of hCG and hCG-related molecules

PubMed Central

2010-01-01

Background hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary. Results and discussion hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle. PMID:20735820

The CgHaa1-Regulon Mediates Response and Tolerance to Acetic Acid Stress in the Human Pathogen Candida glabrata

PubMed Central

Bernardo, Ruben T.; Cunha, Diana V.; Wang, Can; Pereira, Leonel; Silva, Sónia; Salazar, Sara B.; Schröder, Markus S.; Okamoto, Michiyo; Takahashi-Nakaguchi, Azusa; Chibana, Hiroji; Aoyama, Toshihiro; Sá-Correia, Isabel; Azeredo, Joana; Butler, Geraldine; Mira, Nuno Pereira

2016-01-01

To thrive in the acidic vaginal tract, Candida glabrata has to cope with high concentrations of acetic acid. The mechanisms underlying C. glabrata tolerance to acetic acid at low pH remain largely uncharacterized. In this work, the essential role of the CgHaa1 transcription factor (encoded by ORF CAGL0L09339g) in the response and tolerance of C. glabrata to acetic acid is demonstrated. Transcriptomic analysis showed that CgHaa1 regulates, directly or indirectly, the expression of about 75% of the genes activated under acetic acid stress. CgHaa1-activated targets are involved in multiple physiological functions including membrane transport, metabolism of carbohydrates and amino acids, regulation of the activity of the plasma membrane H+-ATPase, and adhesion. Under acetic acid stress, CgHaa1 increased the activity and the expression of the CgPma1 proton pump and contributed to increased colonization of vaginal epithelial cells by C. glabrata. CgHAA1, and two identified CgHaa1-activated targets, CgTPO3 and CgHSP30, are herein demonstrated to be determinants of C. glabrata tolerance to acetic acid. The protective effect of CgTpo3 and of CgHaa1 was linked to a role of these proteins in reducing the accumulation of acetic acid inside C. glabrata cells. In response to acetic acid stress, marked differences were found in the regulons controlled by CgHaa1 and by its S. cerevisiae ScHaa1 ortholog, demonstrating a clear divergent evolution of the two regulatory networks. The results gathered in this study significantly advance the understanding of the molecular mechanisms underlying the success of C. glabrata as a vaginal colonizer. PMID:27815348

Disulfide bond rearrangement during formation of the chorionic gonadotropin beta-subunit cystine knot in vivo.

PubMed

Wilken, Jason A; Bedows, Elliott

2004-05-04

The intracellular kinetic folding pathway of the human chorionic gonadotropin beta-subunit (hCG-beta) reveals the presence of a disulfide between Cys residues 38-57 that is not detected by X-ray analysis of secreted hCG-beta. This led us to propose that disulfide rearrangement is an essential feature of cystine knot formation during CG-beta folding. To test this, we used disulfide bond formation to monitor progression of intracellular folding intermediates of a previously uncharacterized protein, the CG-beta subunit of cynomolgous macaque (Macaca fascicularis). Like its human counterpart hCG-beta with which it shares 81% identity, macaque (m)CG-beta is a cystine knot-containing subunit that assembles with an alpha-subunit common to all glycoprotein hormone members of its species to form a biologically active heterodimer, mCG, which, like hCG, is required for pregnancy maintenance. An early mCG-beta folding intermediate, mpbeta1, contained two disulfide bonds, one between Cys34 and Cys88 and the other between Cys38 and Cys57. The subsequent folding intermediate, mpbeta2-early, was represented by an ensemble of folding forms that, in addition to the two disulfides mentioned above, included disulfide linkages between Cys9 and Cys57 and between Cys38 and Cys90. These latter two disulfides are those contained within the beta-subunit cystine knot and reveal that a disulfide exchange occurred during the mpbeta2-early folding step leading to formation of the mCG-beta knot. Thus, while defining the intracellular kinetic protein folding pathway of a monkey homologue of CG-beta, we detected the previously predicted disulfide exchange event crucial for CG-beta cystine knot formation and attainment of CG-beta assembly competence.

Association between anticonvulsant drugs and teeth-grinding in children and adolescents with cerebral palsy.

PubMed

Ortega, A O L; Dos Santos, M T B R; Mendes, F M; Ciamponi, A L

2014-09-01

The relation between teeth-grinding and the use of drugs acting on the central nervous system of cerebral palsy (CP) patients has not yet been described. The aim of this research was to evaluate the presence or absence of teeth-grinding (sleep and/or awake periods) in normal and in CP children and adolescents, as well as the association of teeth-grinding and use of anticonvulsant drugs. The sample consisted of 207 children and adolescents, divided into three groups: G1, individuals with CP who did not take anticonvulsant drugs; G2, individuals with CP administered medications on a regular basis; and CG, normal individuals. Logistic regression analyses were performed to evaluate the association of teeth-grinding with some variables. No significant statistical differences were observed regarding the presence or absence of teeth-grinding when G1 and G2 were compared. However, compared with the CG, a statistically significant difference was determined, with the CG showing fewer children presenting teeth-grinding (P < 0·001). Among those children/adolescents prescribed drug therapy, the barbiturate group showed a greater frequency of teeth-grinding. CP children and adolescents show a greater and significant presence of grinding of the teeth compared with normal individuals. Subjects taking barbiturate drugs showed greater presence of teeth-grinding, than those who were taking medications from the other groups of anticonvulsant drugs. © 2014 John Wiley & Sons Ltd.

[Children with hyperthyroidism due to elevated hCG levels].

PubMed

Jöbsis, Jasper J; van Trotsenburg, A S Paul; Merks, Johannes H M; Kamp, Gerdine A

2014-01-01

We describe two children with hyperthyroidism secondary to elevated hCG levels: one patient with gestational trophoblastic disease and one patient with choriocarcinoma. hCG resembles other glycoproteins that can lead to hyperthyroidism through TSH receptor activation. Also, through its LH-mimicking effect, hCG can induce high oestradiol levels, resulting in stormy pubertal development. False negative hCG tests due to the high-dose hook effect may complicate the diagnostic process. In patients with antibody-negative thyrotoxicosis, the diagnosis of hCG-induced hyperthyroidism must be considered.

Immunoextraction-Tandem Mass Spectrometry Method for Measuring Intact Human Chorionic Gonadotropin, Free β-Subunit, and β-Subunit Core Fragment in Urine

PubMed Central

Woldemariam, Getachew A.; Butch, Anthony W.

2015-01-01

BACKGROUND Human chorionic gonadotropin (hCG) stimulates testosterone production by the testicles. Because of the potential for abuse, hCG is banned (males only) in most sports and has been placed on the World Anti-Doping Agency list of prohibited substances. Intact hCG, free β-subunit (hCGβ), and β-subunit core fragment (hCGβcf) are the major variants or isoforms in urine. Immunoassays are used by antidoping laboratories to measure urinary hCG. Cross-reactivity with isoforms differs among immunoassays, resulting in widely varying results. We developed a sequential im-munoextraction method with LC-MS/MS detection for quantification of intact hCG, hCGβ, and hCGβcf in urine. METHODS hCG isoforms were immunoextracted with antibody-conjugated magnetic beads and digested with trypsin, and hCGβ and hCGβcf unique peptides were quantified by LC-MS/MS with the corresponding heavy peptides as internal standard. hCG isoform concentrations were determined in urine after administration of hCG, and the intact hCG results were compared to immunoassay results. RESULTS The method was linear to 20 IU/L. Total imprecision was 6.6%-13.7% (CV), recovery ranged from 91% to 109%, and the limit of quantification was 0.2 IU/L. Intact hCG predominated in the urine after administration of 2 hCG formulations. The window of detection ranged from 6 to 9 days. Mean immunoassay results were 12.4-15.5 IU/L higher than LC-MS/MS results. CONCLUSIONS The performance characteristics of the method are acceptable for measuring hCG isoforms, and the method can quantify intact hCG and hCGβ separately. The limit of quantification will allow LC-MS/MS hCG reference intervals to be established in nondoping male athletes for improved doping control. PMID:24899693

Species differences in the formation of vabicaserin carbamoyl glucuronide.

PubMed

Tong, Zeen; Chandrasekaran, Appavu; DeMaio, William; Jordan, Ronald; Li, Hongshan; Moore, Robin; Poola, Nagaraju; Burghart, Peter; Hultin, Theresa; Scatina, JoAnn

2010-04-01

Vabicaserin is a potent 5-hydroxtryptamine 2C full agonist with therapeutic potential for a wide array of psychiatric disorders. Metabolite profiles indicated that vabicaserin was extensively metabolized via carbamoyl glucuronidation after oral administration in humans. In the present study, the differences in the extent of vabicaserin carbamoyl glucuronide (CG) formation in humans and in animals used for safety assessment were investigated. After oral dosing, the systemic exposure ratios of CG to vabicaserin were approximately 12 and up to 29 in monkeys and humans, respectively, and the ratios of CG to vabicaserin were approximately 1.5 and 1.7 in mice and dogs, respectively. These differences in systemic levels of CG are likely related to species differences in the rate and extent of CG formation and elimination. Whereas CG was the predominant circulating metabolite in humans and a major metabolite in mice, dogs, and monkeys, it was a relatively minor metabolite in rats, in which oxidative metabolism was the major metabolic pathway. Although the CG was not detected in plasma or urine of rats, approximately 5% of the dose was excreted in bile as CG in the 24-h collection postdose, indicating the rat had the metabolic capability of producing the CG. In vitro, in a CO(2)-enriched environment, the CG was the predominant metabolite in dog and human liver microsomes, a major metabolite in monkey and mice, and only a very minor metabolite in rats. Carbamoyl glucuronidation and hydroxylation had similar contributions to vabicaserin metabolism in mouse and monkey liver microsomes. However, only trace amounts of CG were formed in rat liver microsomes, and other metabolites were more prominent than the CG. In conclusion, significant differences in the extent of formation of the CG were observed among the various species examined. The exposure ratios of CG to vabicaserin were highest in humans, followed by monkeys, then mice and dogs, and lowest in rats, and the in vitro metabolite profiles generally correlated well with the in vivo metabolites.

Clebsch-Gordan coefficients of discrete groups in subgroup bases

NASA Astrophysics Data System (ADS)

Chen, Gaoli

2018-04-01

We express each Clebsch-Gordan (CG) coefficient of a discrete group as a product of a CG coefficient of its subgroup and a factor, which we call an embedding factor. With an appropriate definition, such factors are fixed up to phase ambiguities. Particularly, they are invariant under basis transformations of irreducible representations of both the group and its subgroup. We then impose on the embedding factors constraints, which relate them to their counterparts under complex conjugate and therefore restrict the phases of embedding factors. In some cases, the phase ambiguities are reduced to sign ambiguities. We describe the procedure of obtaining embedding factors and then calculate CG coefficients of the group 𝒫𝒮ℒ2(7) in terms of embedding factors of its subgroups S4 and 𝒯7.

hCG stimulates angiogenic signals in lymphatic endothelial and circulating angiogenic cells.

PubMed

Schanz, Andrea; Lukosz, Margarete; Hess, Alexandra P; Baston-Büst, Dunja M; Krüssel, Jan S; Heiss, Christian

2015-08-01

Human chorionic gonadotropin (hCG) has long been associated with the initiation and maintenance of pregnancy, where angiogenesis plays an important role. However, the function of hCG in angiogenesis and the recruitment of vascular active cells are not fully understood. In this study, the role of hCG and its receptor in circulating angiogenic and human endothelial cells, including lymphatic, uterine microvascular, and umbilical vein endothelial cells, was examined. Immunohistochemistry and immunoblot analysis were used to detect LH/hCG receptor expression and the expression of hCG-induced angiogenic molecules. HIF-1α was determined via ELISA and downstream molecules, such as CXCL12 and CXCR4, via real-time PCR. Chemotaxis was analyzed using Boyden chambers. Our results show that the LH/hCG receptor was present in all tested cells. Furthermore, hCG was able to stimulate LH/hCG-receptor-specific migration in a dose-dependent fashion and induce key angiogenic molecules, including HIF-1α, CXCL12, and CXCR4. In conclusion, our findings underscore the importance of hCG as one of the first angiogenic molecules produced by the conceptus. hCG itself alters endothelial motility, recruitment, and expression of pro-angiogenic molecules and may therefore play an important role in vascular adaption during implantation and early placental formation. Copyright © 2015. Published by Elsevier Ireland Ltd.

All-in-one theranostic nanoagent for head and neck cancer treatment

NASA Astrophysics Data System (ADS)

Dreifuss, Tamar; Davidi, Erez Shmuel; Motiei, Menachem; Barnoy, Eran; Bragilovski, Dimitri; Lubimov, Leon; Kindler, Marc Jose Jonathan; Popovtzer, Aron; Popovtzer, Rachela

2018-02-01

Despite the significant improvement in the treatment paradigm of head and neck cancer, owing to advanced radiation techniques in combination with chemotherapy, resistance of tumors remains a critical problem, leading to poor outcomes and negative prognosis. In addition, chemotherapeutic agents result in severe systemic toxicity due to nonselective damaging of normal cells. Recently, nanoparticle-based approaches have gained broad attention for improving both radiation therapy and chemotherapy. In this study, we present a dual effect nanoplatform, consists of gold nanoparticles coated with glucose and cisplatin (CG-GNPs), which simultaneously acts as a radiosensitizer and as a carrier which specifically deliver cisplatin to head and neck tumor. Our CG-GNPs showed significant penetration into tumor cells and similar cellular toxicity as cisplatin alone. Moreover, in combination with radiation treatment, CG-GNPs led to greater tumor reduction than that of free cisplatin with radiation. Furthermore, our CG-GNPs also demonstrated highly efficient imaging capabilities, as they act as ideal tumor-targeted CT contrast agent. Therefore, this single nano-formulation is a promising theranostic agent that has the potential to increase the antitumor effect and allow imaging guided therapy.

Small GTPases are involved in sprout formation in human granulosa lutein cells.

PubMed

Franz, Maximilian B; Daube, Stefanie; Keck, Christoph; Sator, Michael; Pietrowski, Detlef

2013-04-01

The corpus luteum (CL), develops from the ruptured follicle after gonadotropin stimulation. Based on intracellular reorganization of the cytoskeleton an human chorionic gonadotropin (hCG) dependent sprouting and migration of luteinizing granulosa cells (LGCs) and endothelial cells is observed. Rho-GTPases are shown to be key regulators of cytoskeletal restructuring. In the present study we analyzed the role of Rho-GTPases in the sprouting activity of LGCs. We used the Rho-GTPase-inhibitors Toxin A and -B and the Cdc42-activator Bradykinin in a LGC-spheroid sprouting assay to determine the effect of these modulators in LGCs. Toxin A and Toxin B reduces sprout formation in LGC spheroids. However, the reduction is less than in hCG treated cells. The usage of Bradykinin demonstrates both, a reduction of sprouts in untreated spheroids and an increase of sprouting in previous hCG treated spheroids. The presented results let us suggest that small Rho-GTPases may regulate the sprouting activity of LGCs after stimulation by hCG and that this mechanism may play a role in CL formation.

Coarse grained modeling of directed assembly to form functional nanoporous films

NASA Astrophysics Data System (ADS)

Al Khatib, Amir

A coarse-grained (CG) simulation of polyethylene glycol (PEG) and Polymethylsilsesquixane nanoparticle (PMSSQ) referred to as (NP) at different sizes and concentrations were done using the Martini coarse-grained (CG) force field. The interactions between CG PEG and CG NP were parameterized from the chemical compound of each molecule and based on Martini force field. NP particles migrates to the surface of the substrate in an agreement with the experimental output at high temperature of 800K. This demonstration of nanoparticles-polymer film to direct it to self-assemble a systematically spatial pattern using the substrate surface energy as the key gating parameter. Validation of the model comparing molecular dynamics simulations with experimental data collected from previous study. NP interaction with the substrate at low interactions energy using Lennard-Johns potential were able to direct the NP to self-assemble in a hexagonal shape up to 4 layers above the substrate. This thesis established that substrate surface energy is a key gating parameter to direct the collective behavior of functional nanoparticles to form thin nanoporous films with spatially predetermined optical/dielectric constants.

Determination of serum hCG levels by radioreactor assay in the clinical laboratory

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

Boyko, W.L.

1979-09-01

The radioreceptorassay (RRA) has been used for measuring human chorionic gonadotropin (hCG) in sera from 751 individuals. The RRA is shown to be sensitive (98%) and specific (99.8%) in detecting hCG in a wide variety of conditions, including normal pregnancy and threatened or missed abortions. As a rapid qualitative or semiquantitative assay for hCG, the RRA is a valuable adjunct in the laboratory to less sensitive tests for hCG. Variation among different quantitative assays for hCG is examined, and it is concluded that the same assay system should be used for monitoring hCG levels in a single individual over amore » period of time in order to avoid inconsistent results. Application of the quantitative RRA for hCG in detecting the midcycle luteinizing hormone surge in infertillity is also presented.« less

[Influence of hCG glycosylation on its functions in female reproduction].

PubMed

Oborná, I; Fingerová, H

To review contemporary knowledge of the hCG molecule, its isoforms and the importance of glycosylation. Biologic variants and glycoforms of hCG have different biological activities and functions related to the control of menstrual cycle, conception, gestation as well as gynaecologic and non-gynaecologic malignancies. A review. Department of Obstetrics and Gynaecology, University Hospital Olomouc. To present own experience and an overview of recent literature in molecular biology, clinical biochemistry and clinical practice. Recent knowledge of the role of hCG glycosylation in physiologic and pathologic events in female organism will provide a better understanding of regulation of processes like ovulation (co-operation of pituitary hCG with LH), implantation and hemochorial placentation (invasivity of hyperglycosylated hCG). Some biologic variants and isoforms of hCG are important for the prediction of certain pathologies of pregnancy, prenatal screening of inborn errors (free beta hCG) as well as in the treatment of infertility.

Contributions of arginines-43 and -94 of human choriogonadotropin. beta. to receptor binding and activation as determined by oligonucleotide-based mutagenesis

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

Fang Chen; Puett, D.

1991-10-22

Members of the glycoprotein hormone family contain a common {alpha} subunit and a hormone-specific {beta} subunit. Human choriogonadotropin (hCG) {beta} is a 145 amino acid residue protein glycosylated at 6 positions (2 N-linked and 4 O-linked oligosaccharides). In an effort to elucidate receptor determinants on hCG{beta}, the authors have used site-directed mutagenesis to prepare and express several mutant cDNAs with replacements at arginines-43 and -94. Arg-43 is invariant in all known mammalian CG/lutropin {beta} amino acid sequences, and Arg-94 is conserved in 10 of the 12 sequences. Moreover, various studies involving synthetic peptides and enzymatic digestions of intact {beta} chainsmore » suggest that these residues may be important in hCG receptor binding. Point mutants were made in which these two arginines were replaced with the corresponding residues in human follitropin {beta}, Leu-43 and Asp-94. The wild-type and mutant {beta} chains were expressed in CHO cells containing a stably integrated gene for bovine {alpha}, and heterodimer formation occurred. These heterologous gonadotropins were active in assays using transformed Leydig cells, competitive binding with standard {sup 125}I-hCG, and cAMP and progesterone production, but the potency was considerably less than that associated with the hCG{beta} wild-type-containing gonadotropin. The double-mutant protein Arg-43 to Leu/Arg-94 to Asp also associated with bovine {alpha}, but the resultant heterodimer exhibited only low activity. Replacement but the Lys-43-containing {beta} chain appeared to exhibit a low degree of subunit association or reduced stability relative to the expressed hCG{beta} wild type. These results demonstrate that arginines-43 and -94 contribute to receptor binding through a positive charge.« less

Probing the role of nonmuscle tropomyosin isoforms in intracellular granule movement by microinjection of monoclonal antibodies

PubMed Central

1989-01-01

Chicken embryo fibroblast (CEF) cells were microinjected with several different monoclonal antibodies that recognize certain nonmuscle isoforms of tropomyosin. Immediately after injection, cells were recorded with a time-lapse video imaging system; later analysis of the tapes revealed that particles in cells injected with one of these antibodies (CG1, specific for CEF tropomyosin isoforms 1 and 3) showed a dramatic decrease in instantaneous speed while moving, distance moved per saltation, and proportion of time spent in motion. Injection of Fab fragments of CG1 resulted in similar changes in the pattern of granule movement. This inhibition of granule movement by CG1 antibody was reversible; at 2.5 h after injection, granules in injected cells had already reached three-fourths of normal speed. The speed of granule movement in cells injected either with antibody specific for tropomyosin isoforms not present in CEF cells, or with CG1 antibody preabsorbed with tropomyosin, was not significantly different from the speed of granules in uninjected cells. When cells were injected with CG1 or Fab fragments of CG1, fixed, and counter-stained with rabbit antibodies to reveal the microtubule, microfilament, and intermediate filament systems, no obvious differences from the patterns normally seen in uninjected cells were observed. Examination of the ultrastructure of injected cells by EM confirmed the presence of apparently intact and normal microtubule, actin, and intermediate filament networks. These experiments suggest that tropomyosin may play an important role in the movement of vesicles and organelles in the cell cytoplasm. Also, we have shown previously that the CG1 determinant can undergo a motility-dependent change in reactivity, that may be important for the regulatory function of nonmuscle tropomyosin (Hegmann, T. E., J. L.-C. Lin, and J. J.-C. Lin. 1988. J. Cell Biol. 106:385-393). Therefore, in addition to postulated microtubule-based motors, microfilaments may play a critical role in regulating granule movement in nonmuscle cells. PMID:2670955

The Alternative Epac/cAMP Pathway and the MAPK Pathway Mediate hCG Induction of Leptin in Placental Cells

PubMed Central

Maymó, Julieta Lorena; Pérez Pérez, Antonio; Maskin, Bernardo; Dueñas, José Luis; Calvo, Juan Carlos; Sánchez Margalet, Víctor; Varone, Cecilia Laura

2012-01-01

Pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in the placenta, where it works as an autocrine hormone. In this work, we demonstrated that human chorionic gonadotropin (hCG) added to JEG-3 cell line or to placental explants induces endogenous leptin expression. We also found that hCG increased cAMP intracellular levels in BeWo cells in a dose-dependent manner, stimulated cAMP response element (CRE) activity and the cotransfection with an expression plasmid of a dominant negative mutant of CREB caused a significant inhibition of hCG stimulation of leptin promoter activity. These results demonstrate that hCG indeed activates cAMP/PKA pathway, and that this pathway is involved in leptin expression. Nevertheless, we found leptin induction by hCG is dependent on cAMP levels. Treatment with (Bu)2cAMP in combination with low and non stimulatory hCG concentrations led to an increase in leptin expression, whereas stimulatory concentrations showed the opposite effect. We found that specific PKA inhibition by H89 caused a significant increase of hCG leptin induction, suggesting that probably high cAMP levels might inhibit hCG effect. It was found that hCG enhancement of leptin mRNA expression involved the MAPK pathway. In this work, we demonstrated that hCG leptin induction through the MAPK signaling pathway is inhibited by PKA. We observed that ERK1/2 phosphorylation increased when hCG treatment was combined with H89. In view of these results, the involvement of the alternative cAMP/Epac signaling pathway was studied. We observed that a cAMP analogue that specifically activates Epac (CPT-OMe) stimulated leptin expression by hCG. In addition, the overexpression of Epac and Rap1 proteins increased leptin promoter activity and enhanced hCG. In conclusion, we provide evidence suggesting that hCG induction of leptin gene expression in placenta is mediated not only by activation of the MAPK signaling pathway but also by the alternative cAMP/Epac signaling pathway. PMID:23056265

Antistaphylococcal activities of CG400549, a new bacterial enoyl-acyl carrier protein reductase (FabI) inhibitor.

PubMed

Park, Hee Soo; Yoon, Yu Min; Jung, Sung Ji; Kim, Cheol Min; Kim, Jeong Mi; Kwak, Jin-Hwan

2007-09-01

This study was performed to analyse in vitro and in vivo activities of CG400549, a new FabI inhibitor, against clinical isolates of staphylococci. The mode of action of CG400549 and resistance mechanism of Staphylococcus aureus against CG400549 were also investigated by genetic approaches. In vitro activity of CG400549 was evaluated by the 2-fold agar sdilution method as described by the CLSI, and compared with those of oxacillin, erythromycin, ciprofloxacin, sparfloxacin, moxifloxacin, gemifloxacin, vancomycin, linezolid and quinupristin-dalfopristin. In vivo activity of CG400549 was determined against systemic infections in mice. Time-kill curves of CG400549 were analysed at concentrations of 1 x , 2 x and 4 x MIC against S. aureus strains. CG400549 had the lowest MICs among the test compounds against 238 clinical isolates of S. aureus (MIC90, 0.25 mg/L) and 51 clinical isolates of coagulase-negative staphylococci (MIC90, 1 mg/L). The activity of CG400549 was irrespective of whether the strains were methicillin-susceptible or -resistant. Furthermore, CG400549 was effective by oral or subcutaneous administration against systemic infections in mice. In a time-kill study, CG400549 at concentrations of 1 x MIC, 2 x MIC and 4 x MIC had a bacteriostatic activity during 24 h. A FabI-overexpressing S. aureus strain gave rise to an increase in the MIC of CG400549 compared with the parental strain, while the susceptibilities of the FabI-overexpressing S. aureus strain to the other antibacterial agents such as oxacillin, erythromycin and ciprofloxacin were not affected. This result showed that the mode of action of CG400549 was via inhibition of FabI, which is involved in biosynthesis of fatty acids in bacteria. Study of the resistance mechanism of S. aureus showed that CG400549-resistant mutants of S. aureus had an alteration in FabI at Phe-204 to Leu. CG400549 had potent in vitro and in vivo activity against staphylococci, including methicillin-, ciprofloxacin- and multidrug-resistant staphylococci strains. This compound could be a good candidate for clinical development as a novel anti-MRSA drug.

CgIκB3, the third novel inhibitor of NF-kappa B (IκB) protein, is involved in the immune defense of the Pacific oyster, Crassostrea gigas.

PubMed

Xu, Fengjiao; Li, Jun; Zhang, Yuehuan; Li, Xiaomei; Zhang, Yang; Xiang, Zhiming; Yu, Ziniu

2015-10-01

Inhibitor of NF-κB (IκB), the important regulator of NF-κB/Rel signaling pathway, plays the crucial role in immune response of both vertebrates and invertebrates. Here, a novel homologue of IκB was cloned from Crassostrea gigas, and designated as CgIκB3. The complete CgIκB3 cDNA was 1282 bp in length, including a 942 bp open reading frame (ORF), a 51 bp 5' UTR and a 289 bp 3' UTR. The ORF encodes a putative protein of 313 amino acids with a predicted molecular weight of approximately 34.7 kDa. Sequence analysis reveals that CgIκB3 contains a conserved degradation motif but with only five ankyrin repeats. Neither a PEST domain nor a C-terminal casein kinase II phosphorylation site was identified through either alignment or bioinformatic prediction. Phylogenetic analysis suggested that CgIκB3 shares common ancestor with CgIκB1 rather CgIκB2, and theoretically it may originate from one duplication event prior to divergence of CgIκB1 and CgIκB2. Tissue expression analyses demonstrated that CgIκB3 mRNA is the most abundant in gills and heart. The expression following PAMP infection showed that CgIκB3 was significantly up-regulated in a similar pattern when challenged with LPS, HKLM or HKVA, respectively. Moreover, similar to CgIκB1 and CgIκB2, CgIκB3 can also inhibit Rel dependent NF-κB activation in HEK293 cells in a dose-dependent manner. In summary, these findings suggest that CgIκB3 can be as the functional inhibitor of NF-κB/Rel and involved in the host defense of C. gigas. The discovery of the third IκB emphasizes the complexity and importance of the regulation on NF-κB activation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chitosan-based hydrogel tissue scaffolds made by 3D plotting promotes osteoblast proliferation and mineralization.

PubMed

Liu, I-Hsin; Chang, Shih-Hsin; Lin, Hsin-Yi

2015-05-13

A 3D plotting system was used to make chitosan-based tissue scaffolds with interconnected pores using pure chitosan (C) and chitosan cross-linked with pectin (CP) and genipin (CG). A freeze-dried chitosan scaffold (CF/D) was made to compare with C, to observe the effects of structural differences. The fiber size, pore size, porosity, compression strength, swelling ratio, drug release efficacy, and cumulative weight loss of the scaffolds were measured. Osteoblasts were cultured on the scaffolds and their proliferation, type I collagen production, alkaline phosphatase activity, calcium deposition, and morphology were observed. C had a lower swelling ratio, degradation, porosity and drug release efficacy and a higher compressional stiffness and cell proliferation compared to CF/D (p < 0.05). Of the 3D-plotted samples, cells on CP exhibited the highest degree of mineralization after 21 d (p < 0.05). CP also had the highest swelling ratio and fastest drug release, followed by C and CG (p < 0.05). Both CP and CG were stiffer and degraded more slowly in saline solution than C (p < 0.05). In summary, 3D-plotted scaffolds were stronger, less likely to degrade and better promoted osteoblast cell proliferation in vitro compared to the freeze-dried scaffolds. C, CP and CG were structurally similar, and the different crosslinking caused significant changes in their physical and biological performances.

TMV-Cg Coat Protein stabilizes DELLA proteins and in turn negatively modulates salicylic acid-mediated defense pathway during Arabidopsis thaliana viral infection.

PubMed

Rodriguez, Maria Cecilia; Conti, Gabriela; Zavallo, Diego; Manacorda, Carlos Augusto; Asurmendi, Sebastian

2014-08-03

Plant viral infections disturb defense regulatory networks during tissue invasion. Emerging evidence demonstrates that a significant proportion of these alterations are mediated by hormone imbalances. Although the DELLA proteins have been reported to be central players in hormone cross-talk, their role in the modulation of hormone signaling during virus infections remains unknown. This work revealed that TMV-Cg coat protein (CgCP) suppresses the salicylic acid (SA) signaling pathway without altering defense hormone SA or jasmonic acid (JA) levels in Arabidopsis thaliana. Furthermore, it was observed that the expression of CgCP reduces plant growth and delays the timing of floral transition. Quantitative RT-qPCR analysis of DELLA target genes showed that CgCP alters relative expression of several target genes, indicating that the DELLA proteins mediate transcriptional changes produced by CgCP expression. Analyses by fluorescence confocal microscopy showed that CgCP stabilizes DELLA proteins accumulation in the presence of gibberellic acid (GA) and that the DELLA proteins are also stabilized during TMV-Cg virus infections. Moreover, DELLA proteins negatively modulated defense transcript profiles during TMV-Cg infection. As a result, TMV-Cg accumulation was significantly reduced in the quadruple-DELLA mutant Arabidopsis plants compared to wild type plants. Taken together, these results demonstrate that CgCP negatively regulates the salicylic acid-mediated defense pathway by stabilizing the DELLA proteins during Arabidopsis thaliana viral infection, suggesting that CgCP alters the stability of DELLAs as a mechanism of negative modulation of antiviral defense responses.

Elevated β-hCG associated with aggressive Osteoblastoma.

PubMed

Morris, Carol D; Hameed, Meera R; Agaram, Narasimhan P; Hwang, Sinchun

2017-09-01

We present a unique case of an aggressive scapular osteoblastoma that produced β-hCG as a paraneoplastic manifestation in a 20-year-old woman. Serum β-hCG was found to be elevated during presurgical workup and consequently delayed surgical resection of the increasingly painful tumor because of suspected pregnancy. The paraneoplastic production of β-hCG was later proven by positive immunohistochemical stain of β-hCG in a curettage specimen and normalization of β-hCG levels after surgical resection of the aggressive osteoblastoma. Production of beta-human chorionic gonadotropin (β-hCG) has been reported in several carcinomas and sarcomas but, to our knowledge, it has not been reported in osteoblastoma in the English-language literature.

50 MHz-10 GHz low-power resistive feedback current-reuse mixer with inductive peaking for cognitive radio receiver.

PubMed

Vitee, Nandini; Ramiah, Harikrishnan; Chong, Wei-Keat; Tan, Gim-Heng; Kanesan, Jeevan; Reza, Ahmed Wasif

2014-01-01

A low-power wideband mixer is designed and implemented in 0.13 µm standard CMOS technology based on resistive feedback current-reuse (RFCR) configuration for the application of cognitive radio receiver. The proposed RFCR architecture incorporates an inductive peaking technique to compensate for gain roll-off at high frequency while enhancing the bandwidth. A complementary current-reuse technique is used between transconductance and IF stages to boost the conversion gain without additional power consumption by reusing the DC bias current of the LO stage. This downconversion double-balanced mixer exhibits a high and flat conversion gain (CG) of 14.9 ± 1.4 dB and a noise figure (NF) better than 12.8 dB. The maximum input 1-dB compression point (P1dB) and maximum input third-order intercept point (IIP3) are -13.6 dBm and -4.5 dBm, respectively, over the desired frequency ranging from 50 MHz to 10 GHz. The proposed circuit operates down to a supply headroom of 1 V with a low-power consumption of 3.5 mW.

Probabilistic image modeling with an extended chain graph for human activity recognition and image segmentation.

PubMed

Zhang, Lei; Zeng, Zhi; Ji, Qiang

2011-09-01

Chain graph (CG) is a hybrid probabilistic graphical model (PGM) capable of modeling heterogeneous relationships among random variables. So far, however, its application in image and video analysis is very limited due to lack of principled learning and inference methods for a CG of general topology. To overcome this limitation, we introduce methods to extend the conventional chain-like CG model to CG model with more general topology and the associated methods for learning and inference in such a general CG model. Specifically, we propose techniques to systematically construct a generally structured CG, to parameterize this model, to derive its joint probability distribution, to perform joint parameter learning, and to perform probabilistic inference in this model. To demonstrate the utility of such an extended CG, we apply it to two challenging image and video analysis problems: human activity recognition and image segmentation. The experimental results show improved performance of the extended CG model over the conventional directed or undirected PGMs. This study demonstrates the promise of the extended CG for effective modeling and inference of complex real-world problems.

Convenient radioimmunoassay for urinary human choriogonadotropin without interference by urinary human lutropin

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

Wehmann, R.E.; Harman, S.M.; Birken, S.

1981-12-01

We have devised a radioimmunoassay (RIA) for human choriogonadotropin (hCG) in first morning-voided urine specimens. Concanavalin A, a lectin, is used to extract and concentrate the hCG from urine. A high-affinity antiserum is used, directed to the hCG..beta.. carboxy-terminal peptide, a unique immunological determinant not shared by the beta subunit of human lutropin. This ensures that urinary human lutropin-related molecules, which interfere with RIAs involving antisera to the intact hCG..beta.. subunit, will not cross react in this assay. A concentration of hCG as low as 0.4 ..mu..g/L can be detected in the first morning-voided urine. The effective sensitivity of thismore » assay for the unequivocal detection of hCG production is somewhat better than that achieved with the serum hCG RIA involving antisera to the hCG..beta.. subunit. The improved specificity and sensitivity of this assay, and the greater convenience of collecting samples of urine rather than blood, are clinically useful advantages of this approach to assessing hCG production in humans.« less

Influence of structural features of carrageenan on the formation of polyelectrolyte complexes with chitosan.

PubMed

Volod'ko, A V; Davydova, V N; Glazunov, V P; Likhatskaya, G N; Yermak, I M

2016-03-01

The polyelectrolyte complexes (PEC) of carrageenans (CG)-κ-, κ/β-, λ-and x-CG with chitosan were obtained. The formation of PEC was detected by Fourier-transform infrared (FTIR) spectroscopy and by centrifugation in a Percoll gradient. The influence of the structural peculiarities of CG on its interaction with chitosan was studied. The results of centrifugation showed that x-CG with a high degree of sulphation (SD) was completely bound to chitosan, unlike low SD κ-CG and κ/β-CG. Binding constant values showed there was a high affinity of CG for chitosan. CG with flexible macromolecule conformation and high SD exhibited the greatest binding affinity for chitosan. The full-atomic 3D-structures of the PEC κ-CG: chitosan in solution have been obtained by the experiments in silico for the first time. The amino groups of chitosan make the largest contribution to the energy of the complex formation by means of hydrogen and ionic bonds. The most probable complexes have stoichiometries of 1:1 and 1:1.5. Copyright © 2015 Elsevier B.V. All rights reserved.

A comparative study of coarse-graining methods for polymeric fluids: Mori-Zwanzig vs. iterative Boltzmann inversion vs. stochastic parametric optimization

NASA Astrophysics Data System (ADS)

Li, Zhen; Bian, Xin; Yang, Xiu; Karniadakis, George Em

2016-07-01

We construct effective coarse-grained (CG) models for polymeric fluids by employing two coarse-graining strategies. The first one is a forward-coarse-graining procedure by the Mori-Zwanzig (MZ) projection while the other one applies a reverse-coarse-graining procedure, such as the iterative Boltzmann inversion (IBI) and the stochastic parametric optimization (SPO). More specifically, we perform molecular dynamics (MD) simulations of star polymer melts to provide the atomistic fields to be coarse-grained. Each molecule of a star polymer with internal degrees of freedom is coarsened into a single CG particle and the effective interactions between CG particles can be either evaluated directly from microscopic dynamics based on the MZ formalism, or obtained by the reverse methods, i.e., IBI and SPO. The forward procedure has no free parameters to tune and recovers the MD system faithfully. For the reverse procedure, we find that the parameters in CG models cannot be selected arbitrarily. If the free parameters are properly defined, the reverse CG procedure also yields an accurate effective potential. Moreover, we explain how an aggressive coarse-graining procedure introduces the many-body effect, which makes the pairwise potential invalid for the same system at densities away from the training point. From this work, general guidelines for coarse-graining of polymeric fluids can be drawn.

Alteration of Cyclic-AMP Response Element Binding Protein in the Postmortem Brain of Subjects with Bipolar Disorder and Schizophrenia

PubMed Central

Ren, Xinguo; Rizavi, Hooriyah S.; Khan, Mansoor A.; Bhaumik, Runa; Dwivedi, Yogesh; Pandey, Ghanshyam N.

2013-01-01

Background Abnormalities of cyclic-AMP (cAMP) response element binding protein (CREB) function has been suggested in bipolar (BP) illness and schizophrenia (SZ), based on both indirect and direct evidence. To further elucidate the role of CREB in these disorders, we studied CREB expression and function in two brain areas implicated in these disorders, i.e., dorsolateral prefrontal cortex (DLPFC) and cingulate gyrus (CG). Methods We determined CREB protein expression using Western blot technique, CRE-DNA binding using gel shift assay, and mRNA expression using real-time RT-polymerase chain reaction (qPCR) in DLPFC and CG of the postmortem brain of BP (n = 19), SZ (n = 20), and normal control (NC, n = 20) subjects. Results We observed that CREB protein and mRNA expression and CRE-DNA binding activity were significantly decreased in the nuclear fraction of DLPFC and CG obtained from BP subjects compared with NC subjects. However, the protein and mRNA expression and CRE-DNA binding in SZ subjects was significantly decreased in CG, but not in DLPFC, compared with NC. Conclusion These studies thus indicate region-specific abnormalities of CREB expression and function in both BP and SZ. They suggest that abnormalities of CREB in CG may be associated with both BP and SZ, but its abnormality in DLPFC is specific to BP illness. PMID:24148789

Grazed Riparian Management and Stream Channel Response in Southeastern Minnesota (USA) Streams

NASA Astrophysics Data System (ADS)

Magner, Joseph A.; Vondracek, Bruce; Brooks, Kenneth N.

2008-09-01

The U.S. Department of Agriculture-Natural Resources Conservation Service has recommended domestic cattle grazing exclusion from riparian corridors for decades. This recommendation was based on a belief that domestic cattle grazing would typically destroy stream bank vegetation and in-channel habitat. Continuous grazing (CG) has caused adverse environmental damage, but along cohesive-sediment stream banks of disturbed catchments in southeastern Minnesota, short-duration grazing (SDG), a rotational grazing system, may offer a better riparian management practice than CG. Over 30 physical and biological metrics were gathered at 26 sites to evaluate differences between SDG, CG, and nongrazed sites (NG). Ordinations produced with nonmetric multidimensional scaling (NMS) indicated a gradient with a benthic macroinvertebrate index of biotic integrity (IBI) and riparian site management; low IBI scores associated with CG sites and higher IBI scores associated with NG sites. Nongrazed sites were associated with reduced soil compaction and higher bank stability, as measured by the Pfankuch stability index; whereas CG sites were associated with increased soil compaction and lower bank stability, SDG sites were intermediate. Bedrock geology influenced NMS results: sites with carbonate derived cobble were associated with more stable channels and higher IBI scores. Though current riparian grazing practices in southeastern Minnesota present pollution problems, short duration grazing could reduce sediment pollution if managed in an environmentally sustainable fashion that considers stream channel response.

A comparative study of coarse-graining methods for polymeric fluids: Mori-Zwanzig vs. iterative Boltzmann inversion vs. stochastic parametric optimization.

PubMed

Li, Zhen; Bian, Xin; Yang, Xiu; Karniadakis, George Em

2016-07-28

We construct effective coarse-grained (CG) models for polymeric fluids by employing two coarse-graining strategies. The first one is a forward-coarse-graining procedure by the Mori-Zwanzig (MZ) projection while the other one applies a reverse-coarse-graining procedure, such as the iterative Boltzmann inversion (IBI) and the stochastic parametric optimization (SPO). More specifically, we perform molecular dynamics (MD) simulations of star polymer melts to provide the atomistic fields to be coarse-grained. Each molecule of a star polymer with internal degrees of freedom is coarsened into a single CG particle and the effective interactions between CG particles can be either evaluated directly from microscopic dynamics based on the MZ formalism, or obtained by the reverse methods, i.e., IBI and SPO. The forward procedure has no free parameters to tune and recovers the MD system faithfully. For the reverse procedure, we find that the parameters in CG models cannot be selected arbitrarily. If the free parameters are properly defined, the reverse CG procedure also yields an accurate effective potential. Moreover, we explain how an aggressive coarse-graining procedure introduces the many-body effect, which makes the pairwise potential invalid for the same system at densities away from the training point. From this work, general guidelines for coarse-graining of polymeric fluids can be drawn.

Grazed riparian management and stream channel response in southeastern Minnesota (USA) streams

USGS Publications Warehouse

Magner, J.A.; Vondracek, B.; Brooks, K.N.

2008-01-01

The U.S. Department of Agriculture-Natural Resources Conservation Service has recommended domestic cattle grazing exclusion from riparian corridors for decades. This recommendation was based on a belief that domestic cattle grazing would typically destroy stream bank vegetation and in-channel habitat. Continuous grazing (CG) has caused adverse environmental damage, but along cohesive-sediment stream banks of disturbed catchments in southeastern Minnesota, short-duration grazing (SDG), a rotational grazing system, may offer a better riparian management practice than CG. Over 30 physical and biological metrics were gathered at 26 sites to evaluate differences between SDG, CG, and nongrazed sites (NG). Ordinations produced with nonmetric multidimensional scaling (NMS) indicated a gradient with a benthic macroinvertebrate index of biotic integrity (IBI) and riparian site management; low IBI scores associated with CG sites and higher IBI scores associated with NG sites. Nongrazed sites were associated with reduced soil compaction and higher bank stability, as measured by the Pfankuch stability index; whereas CG sites were associated with increased soil compaction and lower bank stability, SDG sites were intermediate. Bedrock geology influenced NMS results: sites with carbonate derived cobble were associated with more stable channels and higher IBI scores. Though current riparian grazing practices in southeastern Minnesota present pollution problems, short duration grazing could reduce sediment pollution if managed in an environmentally sustainable fashion that considers stream channel response. ?? 2008 Springer Science+Business Media, LLC.

The Impact of Risk Information Exposure on Women’s Beliefs about Direct-to-Consumer Genetic Testing for BRCA Mutations

PubMed Central

Gray, Stacy W.; Hornik, Robert C.; Schwartz, J. Sanford; Armstrong, Katrina

2011-01-01

Despite an increase in direct-to-consumer (DTC) genetic testing, little is known about how variations in website content might alter consumer behavior. We evaluated the impact of risk information provision on women’s attitudes about DTC BRCA testing. We conducted a randomized experiment; women viewed a “mock” BRCA testing website without (control group: CG) or with information on the potential risks of DTC testing (RG; framed two ways: unattributed information [UR] and information presented by experts [ER]). 767 women participated; mean age was 37 years, mean education was 15 years, and 79% of subjects were white. Women in the RG had less positive beliefs about DTC testing (mean RG=23.8, CG=25.2; p=0.001), lower intentions to get tested (RG= 2.8, CG= 3.1; p=0.03), were more likely to prefer clinic-based testing (RG=5.1, CG=4.8; p=0.03) and to report that they had seen enough risk information (RG=5.3, CG= 4.7; p<0.001). UR and ER exposure produced similar effects. Effects did not differ for women with or without a personal/family history of breast/ovarian cancer. Exposing women to the potential risks of DTC BRCA testing altered their beliefs, preferences, and intentions. Risk messages appear to be salient to women irrespective of their chance of having a BRCA mutation. PMID:21992449

hCG Triggering in ART: An Evolutionary Concept.

PubMed

Hershko Klement, Anat; Shulman, Adrian

2017-05-17

Human chorionic gonadotropin (hCG) is no longer a single, omnipotent ovulation triggering option. Gonadotropin releasing hormone (GnRH) agonist, initially presented as a substitute for hCG, has led to a new era of administering GnRH agonist followed by hCG triggering. According to this new concept, GnRH agonist enables successful ovum maturation, while hCG supports the luteal phase and pregnancy until placental shift.

Constructing Optimal Coarse-Grained Sites of Huge Biomolecules by Fluctuation Maximization.

PubMed

Li, Min; Zhang, John Zenghui; Xia, Fei

2016-04-12

Coarse-grained (CG) models are valuable tools for the study of functions of large biomolecules on large length and time scales. The definition of CG representations for huge biomolecules is always a formidable challenge. In this work, we propose a new method called fluctuation maximization coarse-graining (FM-CG) to construct the CG sites of biomolecules. The defined residual in FM-CG converges to a maximal value as the number of CG sites increases, allowing an optimal CG model to be rigorously defined on the basis of the maximum. More importantly, we developed a robust algorithm called stepwise local iterative optimization (SLIO) to accelerate the process of coarse-graining large biomolecules. By means of the efficient SLIO algorithm, the computational cost of coarse-graining large biomolecules is reduced to within the time scale of seconds, which is far lower than that of conventional simulated annealing. The coarse-graining of two huge systems, chaperonin GroEL and lengsin, indicates that our new methods can coarse-grain huge biomolecular systems with up to 10,000 residues within the time scale of minutes. The further parametrization of CG sites derived from FM-CG allows us to construct the corresponding CG models for studies of the functions of huge biomolecular systems.

beta-Citryl-L-glutamate is an endogenous iron chelator that occurs naturally in the developing brain.

PubMed

Hamada-Kanazawa, Michiko; Kouda, Makiko; Odani, Akira; Matsuyama, Kaori; Kanazawa, Kiyoka; Hasegawa, Tatsuya; Narahara, Masanori; Miyake, Masaharu

2010-01-01

The compound beta-citryl-L-glutamate (beta-CG) was initially isolated from developing brains, while it has also been found in high concentrations in testes and eyes. However, its functional roles are unclear. To evaluate its coordination with metal ions, we performed pH titration experiments. The stability constant, logbeta(pqr) for M(p)(beta-CG)(q)H(r) was calculated from pH titration data, which showed that beta-CG forms relatively strong complexes with Fe(III), Cu(II), Fe(II) and Zn(II). beta-CG was also found able to solubilize Fe more effectively from Fe(OH)(2) than from Fe(OH)(3). Therefore, we examined the effects of beta-CG on Fe-dependent reactive oxygen species (ROS)-generating systems, as well as the potential ROS-scavenging activities of beta-CG and metal ion-(beta-CG) complexes. beta-CG inhibited the Fe-dependent degradation of deoxyribose and Fe-dependent damage to DNA or plasmid DNA in a dose-dependent manner, whereas it had no effect on Cu-mediated DNA damage. In addition, thermodynamic data showed that beta-CG in a physiological pH solution is an Fe(II) chelator rather than an Fe(III) chelator. Taken together, these findings suggest that beta-CG is an endogenous low molecular weight Fe chelator.

Analytical and Clinical Validation of the Immulite 1000 hCG Assay for Quantitative Analysis in Urine

PubMed Central

Cate, Frances L.; Moffett, Courtney; Gronowski, Ann M.; Grenache, David G.; Hartmann, Katherine E.; Woodworth, Alison

2013-01-01

Background The Siemens Immulite hCG assay detects all major hCG variants in serum. Currently, this assay is only FDA approved for qualitative measurement of hCG in urine. Methods Complete validation of the hCG assay in urine was performed on the Siemens Immulite 1000 immunoassay platform. Reference intervals were established for females <55 y, females ≥55 y, and males 20–70 y. Results The limit of quantitation was 2.0 IU/l. The Immulite hCG assay was precise for measuring hCG in urine from pregnant patients with intra- and inter-assay imprecision of <11% CV. The assay was linear over a dynamic range of 2–2600 IU/l and 2–3500 IU/l for hCG and hCGβ respectively. The assay was non-linear for hCGβcf. No hook effect was observed at concentrations up to 1,200,000 pmol/l, for hCGβ or hCGβcf. The reference intervals were <2.0 IU/l for males, <2.2 IU/l for females <55 y, and <12.2 IU/l for females ≥55 y. Conclusion The Immulite 1000 hCG assay can accurately quantify hCG in urine. PMID:23470427

Lipid modulatory activities of Cichorium glandulosum Boiss et Huet are mediated by multiple components within hepatocytes

PubMed Central

Ding, Lin; Liu, Jun-Lin; Hassan, Waseem; Wang, Lu-Lu; Yan, Fang-Rong; Shang, Jing

2014-01-01

To investigate a possible methodology of exploiting herbal medicine and design polytherapy for the treatment of non-alcoholic fatty liver disease (NAFLD), we have made use of Cichorium glandulosum Boiss et Huet (CG), a traditional Chinese herbal medicine that has been proven to be effective in treating hepatic diseases. Here, we report that the extract of CG effectively reduced lipid accumulation under conditions of lipid overloading in vivo and in vitro (in a rat high-fat diet model and a hepG2 cell model of free fatty acid treatment). CG extract also protected hepatocytes from injury and inflammation to aid its lipid-lowering properties (in a rat high-fat diet model and a L02 cell model of acetaminophen treatment). Serum chemistry analysis accompanied by in vitro drug screening confirmed that CG-4, CG-10 and CG-14 are the lipo-effective components of CG. Western blotting analysis revealed that these components can regulate key lipid targets at the molecular level, including CD36, FATP5 and PPAR-α, thus the lipid oxidation and lipid absorption pathways. Finally, we adopted the experimental design and statistical method to calculate the best combination proportion (CG-4: CG-10: CG-14 = 2.065: 1.782: 2.153) to optimize its therapeutic effect. PMID:24797163

Hook effect in Abbott i-STAT β-human chorionic gonadotropin (β-hCG) point of care assay.

PubMed

Wilgen, Urs; Pretorius, Carel J; Gous, Rehna S; Martin, Cameron; Hale, Vincent J; Ungerer, Jacobus P J

2014-09-01

Point-of-care testing for β-hCG has been widely advocated to allow rapid diagnosis/exclusion of pregnancy in the emergency department. A quantitative blood β-hCG assay has the additional benefit of being able to monitor the viability of pregnancy, using serial measurements, to determine the appropriate expected increase in β-hCG levels over time (e.g. ectopic pregnancy), and aiding in determining if an intrauterine gestational sac should be visible on sonographic imaging. Evaluation of the newly released Abbott i-STAT β-hCG point-of-care assay with the Beckman Coulter β-hCG laboratory assay in use. Whole blood, plasma and serum samples with a wide range of β-hCG concentrations were analysed by both methods. The Abbott I-STAT β-hCG compares favourably, can be performed on heparinised whole blood, plasma and serum, and shows acceptable accuracy and precision. However a hook effect at elevated β-hCG was shown in gestational trophoblastic disease as well as normal pregnancies. The i-STAT β-hCG performs acceptably in its intended use in the early detection of pregnancy, but results should always be interpreted within the clinical context, as a hook effect may occur. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Effect of communication skills training program for oncologists based on patient preferences for communication when receiving bad news: a randomized controlled trial.

PubMed

Fujimori, Maiko; Shirai, Yuki; Asai, Mariko; Kubota, Kaoru; Katsumata, Noriyuki; Uchitomi, Yosuke

2014-07-10

The aim of this study was to identify the effects of a communication skills training (CST) program for oncologists, developed based on patient preferences regarding oncologists' communication. Thirty oncologists were randomly assigned to either an intervention group (IG; 2-day CST workshop) or control group (CG). Participants were assessed on their communication performance during simulated consultation and their confidence in communicating with patients at baseline and follow-up. A total of 1,192 patients (response rate, 84.6%) who had consultations with the participating oncologists at baseline and/or follow-up were assessed regarding their distress using the Hospital Anxiety and Depression Scale, satisfaction with the consultation, and trust in their oncologist after the consultation. At the follow-up survey, the performance scores of the IG had improved significantly, in terms of their emotional support (P = .011), setting up a supportive environment (P = .002), and ability to deliver information (P = .001), compared with those of the CG. Oncologists in the IG were rated higher at follow-up than those in the CG in terms of their confidence in themselves (P = .001). Patients who met with oncologists after they had undergone the CST were significantly less depressed than those who met with oncologists in the CG (P = .027). However, the CST program did not affect patient satisfaction with oncologists' style of communication. A CST program based on patient preferences is effective for both oncologists and patients with cancer. Oncologists should consider CST as an approach to enhancing their communication skills. © 2014 by American Society of Clinical Oncology.

The impact of 2013 UK NICE guidelines on the management of varicose veins at the Heart of England NHS Foundation Trust, Birmingham, UK.

PubMed

Davies, Huw Ob; Popplewell, Matthew; Bate, Gareth; Kelly, Lisa; Darvall, Katy; Bradbury, Andrew W

2016-10-01

Although varicose veins are a common cause of morbidity, the UK National Health Service and private medical insurers have previously sought to ration their treatment in a non-evidence based manner in order to limit health-care expenditure and reimbursement. In July 2013, the UK National Institute for Health and Care Excellence published new national Clinical Guidelines (CG168) to promote evidence-based commissioning and management of varicose veins. The aim of this study was to evaluate the impact of CG168 on the referral and management of varicose veins at the Heart of England NHS Foundation Trust, Birmingham, UK. Interrogation of a prospectively gathered database, provided by the Heart of England NHS Foundation Trust Performance Unit, of patients undergoing interventions for varicose veins since 1 January 2012. Patients treated before (group 1) and after (group 2) publication of CG168 were compared. There were 253 patients, 286 legs (48% male, mean (range) age 54 (20-91) years) treated in group 1, and 417 patients, 452 legs, (46% male, mean (range) age 54 (14-90) years) treated in group 2, an increase of 65%. CG168 was associated with a significant reduction in the use of surgery (131 patients (52%) group 1 vs. 127 patients (30%) group 2, p = 0.0003, χ(2)), no change in endothermal ablation (30 patients (12%) group 1 vs. 45 patients (11%) group 2), a significant increase in ultrasound-guided foam sclerotherapy (92 patients (36%) group 1 and 245 patients (59%) group 2, p = 0.0001, χ(2)) and an increase in treatment for C2/3 disease (53% group 1 and 65.2% group 2, p = 0.0022, χ(2)). Publication of National Institute for Health and Care Excellence CG168 has been associated with a significant increase (65%) in the number of patients treated, referral at an earlier (CEAP C) stage and increased use of endovenous treatment. CG 168 has been highly effective in improving access to, and quality of care, for varicose veins at Heart of England NHS Foundation Trust. © The Author(s) 2015.

Representing environment-induced helix-coil transitions in a coarse grained peptide model

NASA Astrophysics Data System (ADS)

Dalgicdir, Cahit; Globisch, Christoph; Sayar, Mehmet; Peter, Christine

2016-10-01

Coarse grained (CG) models are widely used in studying peptide self-assembly and nanostructure formation. One of the recurrent challenges in CG modeling is the problem of limited transferability, for example to different thermodynamic state points and system compositions. Understanding transferability is generally a prerequisite to knowing for which problems a model can be reliably used and predictive. For peptides, one crucial transferability question is whether a model reproduces the molecule's conformational response to a change in its molecular environment. This is of particular importance since CG peptide models often have to resort to auxiliary interactions that aid secondary structure formation. Such interactions take care of properties of the real system that are per se lost in the coarse graining process such as dihedral-angle correlations along the backbone or backbone hydrogen bonding. These auxiliary interactions may then easily overstabilize certain conformational propensities and therefore destroy the ability of the model to respond to stimuli and environment changes, i.e. they impede transferability. In the present paper we have investigated a short peptide with amphiphilic EALA repeats which undergoes conformational transitions between a disordered and a helical state upon a change in pH value or due to the presence of a soft apolar/polar interface. We designed a base CG peptide model that does not carry a specific (backbone) bias towards a secondary structure. This base model was combined with two typical approaches of ensuring secondary structure formation, namely a C α -C α -C α -C α pseudodihedral angle potential or a virtual site interaction that mimics hydrogen bonding. We have investigated the ability of the two resulting CG models to represent the environment-induced conformational changes in the helix-coil equilibrium of EALA. We show that with both approaches a CG peptide model can be obtained that is environment-transferable and that correctly represents the peptide's conformational response to different stimuli compared to atomistic reference simulations. The two types of auxiliary interactions lead to different kinetic behavior as well as to different structural properties for fully formed helices and folding intermediates, and we discuss the advantages and disadvantages of these approaches.

The use of modern dressings in managing split-thickness skin graft donor sites: a single-centre randomised controlled trial.

PubMed

Kazanavičius, M; Cepas, A; Kolaityte, V; Simoliuniene, R; Rimdeika, R

2017-06-02

To identify the most appropriate, most suitable and most efficient dressing for split-thickness skin graft (STSG) donor sites. Comparing the wound healing rate, pain severity and duration, as well as the dressing change frequency in four randomised patient groups. A single-centre non-blinded randomised controlled trial was carried out during 2010-2014. All patients treated for skin defects/lesions (due to burns, trauma or ulcers) using STSG were included in the study. All patients were randomly allocated in four different donor site treatment groups; polyurethane (PU group, Mepilex); polyurethane with silicone membrane (PUSM group; Mepilex border,); transparent, breathable film (TBF group; Mepitel film) and cotton gauze dressings (CG group) using Excel 2007. We evaluated: wound healing time, pain severity and duration, the frequency of dressing change, donor site re-epithelialisation, donor site complications (signs of inflammation or infection). Patients were assessed on postoperative days: 1, 3, 6, 9, 12, 15, 18 and 21. After random allocation of study participants the number of patients in each group were: PU group n=25; PUSM group n=24; TBF group n=24; CG group n=25. The groups were homogenous according to gender, age, main pathology, donor site area and wound size. The STSG donor site healing time varied from 9 to 21 days. The mean healing time in the CG group was 14.76 days, whereas in the PU, PUSM, and TBF group it was significantly shorter; 12.25 days, 11.63 days and 10 days, respectively. Patients in the TBF group demonstrated the most rapid healing time with 66.7% of STSG donor sites healed by postoperative day 9. The pain duration interval in modern dressing groups (PU, PUSM and TBF groups) was 0-9 days, whereas it was 6-18 day in the CS group. Pain intensity mean on postoperative day 1 was 2.21 in the PU group; 1.67 in the PUSM group; 1.46 in the TBF group and 3.04 in the CG group. The average pain duration in Group PU, PUSM, and TBF was 4.08 days; 2.5 days; 2.29 days, respectively. The average number of times each dressing was changed in each group was, 2.83 times in the PU group and PUSM group and 1.46 times in the TBF group. The CG dressing group were changed once when the donor site wound re-epithelialised. There was one patient in the PU group who experienced signs of infection, was treated accordingly and excluded from the study. The fastest healing time was demonstrated by patients in the TBF group. The pain was not as severe and for a shorter period of time in modern dressing study groups. However, the pain was lightest and felt shortest in TBF dressing group. The modern dressings PU and PUSM had to be changed more frequently than TBF.

On the damping of right hand circularly polarized waves in spin quantum plasmas

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

Iqbal, Z.; Hussain, A., E-mail: ah-gcu@yahoo.com; Department of Physics, Quaid-i-Azam University Islamabad, Islamabad 45320

2014-12-15

General dispersion relation for the right hand circularly polarized waves has been derived using non-relativistic spin quantum kinetic theory. Employing the derived dispersion relation, temporal and spatial damping of the right hand circularly polarized waves are studied for both the degenerate and non-degenerate plasma regimes for two different frequency domains: (i) k{sub ∥}v≫(ω+ω{sub ce}),(ω+ω{sub cg}) and (ii) k{sub ∥}v≪(ω+ω{sub ce}),(ω+ω{sub cg}). Comparison of the cold and hot plasma regimes shows that the right hand circularly polarized wave with spin-effects exists for larger k-values as compared to the spinless case, before it damps completely. It is also found that the spin-effectsmore » can significantly influence the phase and group velocities of the whistler waves in both the degenerate and non-degenerate regimes. The results obtained are also analyzed graphically for some laboratory parameters to demonstrate the physical significance of the present work.« less

Protease nexin-1 promotes secretory granule biogenesis by preventing granule protein degradation.

PubMed

Kim, Taeyoon; Loh, Y Peng

2006-02-01

Dense-core secretory granule (DCG) biogenesis is a prerequisite step for the sorting, processing, and secretion of neuropeptides and hormones in (neuro)endocrine cells. Previously, chromogranin A (CgA) has been shown to play a key role in the regulation of DCG biogenesis in vitro and in vivo. However, the underlying mechanism of CgA-mediated DCG biogenesis has not been explored. In this study, we have uncovered a novel mechanism for the regulation of CgA-mediated DCG biogenesis. Transfection of CgA into endocrine 6T3 cells lacking CgA and DCGs not only recovered DCG formation and regulated secretion but also prevented granule protein degradation. Genetic profiling of CgA-expressing 6T3 versus CgA- and DCG-deficient 6T3 cells, followed by real-time reverse transcription-polymerase chain reaction and Western blotting analyses, revealed that a serine protease inhibitor, protease nexin-1 (PN-1), was significantly up-regulated in CgA-expressing 6T3 cells. Overexpression of PN-1 in CgA-deficient 6T3 cells prevented degradation of DCG proteins at the Golgi apparatus, enhanced DCG biogenesis, and recovered regulated secretion. Moreover, depletion of PN-1 by antisense RNAs in CgA-expressing 6T3 cells resulted in the specific degradation of DCG proteins. We conclude that CgA increases DCG biogenesis in endocrine cells by up-regulating PN-1 expression to stabilize granule proteins against degradation.

Protease Nexin-1 Promotes Secretory Granule Biogenesis by Preventing Granule Protein Degradation

PubMed Central

Kim, Taeyoon; Loh, Y. Peng

2006-01-01

Dense-core secretory granule (DCG) biogenesis is a prerequisite step for the sorting, processing, and secretion of neuropeptides and hormones in (neuro)endocrine cells. Previously, chromogranin A (CgA) has been shown to play a key role in the regulation of DCG biogenesis in vitro and in vivo. However, the underlying mechanism of CgA-mediated DCG biogenesis has not been explored. In this study, we have uncovered a novel mechanism for the regulation of CgA-mediated DCG biogenesis. Transfection of CgA into endocrine 6T3 cells lacking CgA and DCGs not only recovered DCG formation and regulated secretion but also prevented granule protein degradation. Genetic profiling of CgA-expressing 6T3 versus CgA- and DCG-deficient 6T3 cells, followed by real-time reverse transcription-polymerase chain reaction and Western blotting analyses, revealed that a serine protease inhibitor, protease nexin-1 (PN-1), was significantly up-regulated in CgA-expressing 6T3 cells. Overexpression of PN-1 in CgA-deficient 6T3 cells prevented degradation of DCG proteins at the Golgi apparatus, enhanced DCG biogenesis, and recovered regulated secretion. Moreover, depletion of PN-1 by antisense RNAs in CgA-expressing 6T3 cells resulted in the specific degradation of DCG proteins. We conclude that CgA increases DCG biogenesis in endocrine cells by up-regulating PN-1 expression to stabilize granule proteins against degradation. PMID:16319172

Novel mechanism of conjoined gene formation in the human genome.

PubMed

Kim, Ryong Nam; Kim, Aeri; Choi, Sang-Haeng; Kim, Dae-Soo; Nam, Seong-Hyeuk; Kim, Dae-Won; Kim, Dong-Wook; Kang, Aram; Kim, Min-Young; Park, Kun-Hyang; Yoon, Byoung-Ha; Lee, Kang Seon; Park, Hong-Seog

2012-03-01

Recently, conjoined genes (CGs) have emerged as important genetic factors necessary for understanding the human genome. However, their formation mechanism and precise structures have remained mysterious. Based on a detailed structural analysis of 57 human CG transcript variants (CGTVs, discovered in this study) and all (833) known CGs in the human genome, we discovered that the poly(A) signal site from the upstream parent gene region is completely removed via the skipping or truncation of the final exon; consequently, CG transcription is terminated at the poly(A) signal site of the downstream parent gene. This result led us to propose a novel mechanism of CG formation: the complete removal of the poly(A) signal site from the upstream parent gene is a prerequisite for the CG transcriptional machinery to continue transcribing uninterrupted into the intergenic region and downstream parent gene. The removal of the poly(A) signal sequence from the upstream gene region appears to be caused by a deletion or truncation mutation in the human genome rather than post-transcriptional trans-splicing events. With respect to the characteristics of CG sequence structures, we found that intergenic regions are hot spots for novel exon creation during CGTV formation and that exons farther from the intergenic regions are more highly conserved in the CGTVs. Interestingly, many novel exons newly created within the intergenic and intragenic regions originated from transposable element sequences. Additionally, the CGTVs showed tumor tissue-biased expression. In conclusion, our study provides novel insights into the CG formation mechanism and expands the present concepts of the genetic structural landscape, gene regulation, and gene formation mechanisms in the human genome.

Web-Based Computational Chemistry Education with CHARMMing II: Coarse-Grained Protein Folding

PubMed Central

Schalk, Vinushka; Lerner, Michael G.; Woodcock, H. Lee; Brooks, Bernard R.

2014-01-01

A lesson utilizing a coarse-grained (CG) G-like model has been implemented into the CHARMM INterface and Graphics (CHARMMing) web portal (www.charmming.org) to the Chemistry at HARvard Macromolecular Mechanics (CHARMM) molecular simulation package. While widely used to model various biophysical processes, such as protein folding and aggregation, CG models can also serve as an educational tool because they can provide qualitative descriptions of complex biophysical phenomena for a relatively cheap computational cost. As a proof of concept, this lesson demonstrates the construction of a CG model of a small globular protein, its simulation via Langevin dynamics, and the analysis of the resulting data. This lesson makes connections between modern molecular simulation techniques and topics commonly presented in an advanced undergraduate lecture on physical chemistry. It culminates in a straightforward analysis of a short dynamics trajectory of a small fast folding globular protein; we briefly describe the thermodynamic properties that can be calculated from this analysis. The assumptions inherent in the model and the data analysis are laid out in a clear, concise manner, and the techniques used are consistent with those employed by specialists in the field of CG modeling. One of the major tasks in building the G-like model is determining the relative strength of the nonbonded interactions between coarse-grained sites. New functionality has been added to CHARMMing to facilitate this process. The implementation of these features into CHARMMing helps automate many of the tedious aspects of constructing a CG G model. The CG model builder and its accompanying lesson should be a valuable tool to chemistry students, teachers, and modelers in the field. PMID:25058338

Web-based computational chemistry education with CHARMMing II: Coarse-grained protein folding.

PubMed

Pickard, Frank C; Miller, Benjamin T; Schalk, Vinushka; Lerner, Michael G; Woodcock, H Lee; Brooks, Bernard R

2014-07-01

A lesson utilizing a coarse-grained (CG) Gō-like model has been implemented into the CHARMM INterface and Graphics (CHARMMing) web portal (www.charmming.org) to the Chemistry at HARvard Macromolecular Mechanics (CHARMM) molecular simulation package. While widely used to model various biophysical processes, such as protein folding and aggregation, CG models can also serve as an educational tool because they can provide qualitative descriptions of complex biophysical phenomena for a relatively cheap computational cost. As a proof of concept, this lesson demonstrates the construction of a CG model of a small globular protein, its simulation via Langevin dynamics, and the analysis of the resulting data. This lesson makes connections between modern molecular simulation techniques and topics commonly presented in an advanced undergraduate lecture on physical chemistry. It culminates in a straightforward analysis of a short dynamics trajectory of a small fast folding globular protein; we briefly describe the thermodynamic properties that can be calculated from this analysis. The assumptions inherent in the model and the data analysis are laid out in a clear, concise manner, and the techniques used are consistent with those employed by specialists in the field of CG modeling. One of the major tasks in building the Gō-like model is determining the relative strength of the nonbonded interactions between coarse-grained sites. New functionality has been added to CHARMMing to facilitate this process. The implementation of these features into CHARMMing helps automate many of the tedious aspects of constructing a CG Gō model. The CG model builder and its accompanying lesson should be a valuable tool to chemistry students, teachers, and modelers in the field.

Gait analysis in anorexia and bulimia nervosa.

PubMed

Cimolin, Veronica; Galli, Manuela; Vismara, Luca; Vimercati, Sara Laura; Precilios, Helmer; Cattani, Laila; Fabris De Souza, Shirley; Petroni, Maria Letizia; Capodaglio, Paolo

2013-09-13

Anorexia (AN) and Bulimia Nervosa (BN) are two common eating disorders, which appear to share some reduced motor capacities, such as a reduced balance. The presence and the extent of other motor disorders have not been investigated in a comprehensive way. The aim of this study was to quantify gait pattern in AN and BN individuals in order to ascertain possible differences from the normality range and provide novel data for developing some evidence-based rehabilitation strategies. Nineteen AN patients (age 30.16+9.73) and 20 BN patients (age 26.8+8.41) were assessed with quantitative 3D computerized Gait Analysis. Results were compared with a group of healthy controls (CG; 30.7+5.6). AN and BN patients were characterized by different gait strategies compared to CG. Spatio-temporal parameters indicated shorter step length, with AN showing the shortest values. AN walked slower than BN and CG. As for kinematics, AN and BN showed a nonphysiologic pattern at pelvis and hip level on the sagittal and frontal plane, with BN yielding the most abnormal values. Both AN and BN patients were characterized by high ankle plantar flexion capacity at toe-off when compared to CG. As for ankle kinetics, both AN and BN showed physiologic patterns. Stiffness at hip level was close to CG in both pathologic groups; at the ankle level, stiffness was significantly decreased in both groups, with AN displaying lower values. Both AN and BN were characterized by an altered gait pattern compared to CG. Biomechanical differences were evident mainly at pelvis and hip level. Loss of lean mass may lead to musculoskeletal adaptation, ultimately causing alterations in the gait pattern.

Fixed-time Insemination in Pasture-based Medium-sized Dairy Operations of Northern Germany and an Attempt to Replace GnRH by hCG.

PubMed

Marthold, D; Detterer, J; Koenig von Borstel, U; Gauly, M; Holtz, W

2016-02-01

A field study was conducted aimed at (i) evaluating the practicability of a fixed-time insemination regime for medium-sized dairy operations of north-western Germany, representative for many regions of Central Europe and (ii) substituting hCG for GnRH as ovulation-inducing agent at the end of a presynch or ovsynch protocol in an attempt to reduce the incidence of premature luteal regression. Cows of two herds synchronized by presynch and two herds synchronized by ovsynch protocol were randomly allotted to three subgroups; in one group ovulation was induced by the GnRH analog buserelin, in another by hCG, whereas a third group remained untreated. The synchronized groups were fixed-time inseminated; the untreated group bred to observed oestrus. Relative to untreated herd mates, pregnancy rate in cows subjected to a presynch protocol with buserelin as ovulation-inducing agent was 74%; for hCG it was 60%. In cows subjected to an ovsynch protocol, the corresponding relative pregnancy rates reached 138% in the case of buserelin and 95% in the case of hCG. Average service interval was shortened by 1 week in the presynch and delayed by 2 weeks in the ovsynch group. It may be concluded that fixed-time insemination of cows synchronized via ovsynch protocol with buserelin as ovulation-inducing agent is practicable and may help improve efficiency and reduce the work load involved with herd management in medium-sized dairy operations. The substitution of hCG for buserelin was found to be not advisable. © 2015 Blackwell Verlag GmbH.

Development of an assay for a biomarker of pregnancy and early fetal loss

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

Canfield, R.E.; O'Connor, J.F.; Birken, S.

1987-10-01

Human chorionic gonadotropin (hCG) is a glycoprotein hormone, secreted by the syncytiotrophoblast cells of the fertilized ovum, that enters the maternal circulation at the time of endometrial implantation. It is composed of two nonidentical subunits; ..cap alpha.. and ..beta.., with molecular weights of 14 kD and 23 kD, respectively. Human chorionic gonadotropin binds to the same receptor as hLH and displays the same biological response, namely, to stimulate the declining function of the corpus luteum to produce progestins and estrogen late in the menstrual cycle. The differences in the structures of hCG and hLH have been exploited to develop antibodiesmore » that can measure hCG specifically in the presence of hLH. Two-site antibody binding assays have been developed, based on a surface immunological concept of hCG epitopes, that involve four distinct regions to which antibodies against hCG can bind simultaneously. Antibody cooperative effects, in conjunction with kinetic advantages derived from the concentration factors by use of the sandwich assay technique (immunoradiometric assay, IRMA), have enabled development of extremely sensitive and specific measurement protocols for urinary hCG. The assay described herein permits the detection of pregnancy on an average 25.4 days after the first day of the preceding menses, as opposed to 29.5 days for conventional radioimmunoassay techniques. In addition, the greater sensitivity and specificity of this assay method has permitted the detection of episodes of fetal loss not detected by radioimmunoassay of urine specimens. A large scale epidemiological study is in progress using this assay technique as a way to identify pregnancies that are lost before becoming clinically apparent.« less

Biochemical characterization and synergism of cellulolytic enzyme system from Chaetomium globosum on rice straw saccharification.

PubMed

Wanmolee, Wanwitoo; Sornlake, Warasirin; Rattanaphan, Nakul; Suwannarangsee, Surisa; Laosiripojana, Navadol; Champreda, Verawat

2016-11-21

Efficient hydrolysis of lignocellulosic materials to sugars for conversion to biofuels and chemicals is a key step in biorefinery. Designing an active saccharifying enzyme system with synergy among their components is considered a promising approach. In this study, a lignocellulose-degrading enzyme system of Chaetomium globosum BCC5776 (CG-Cel) was characterized for its activity and proteomic profiles, and synergism with accessory enzymes. The highest cellulase productivity of 0.40 FPU/mL was found for CG-Cel under the optimized submerged fermentation conditions on 1% (w/v) EPFB (empty palm fruit bunch), 2% microcrystalline cellulose (Avicel®) and 1% soybean meal (SBM) at 30 °C, pH 5.8 for 6 d. CG-Cel worked optimally at 50-60 °C in an acidic pH range. Proteomics analysis by LC/MS/MS revealed a complex enzyme system composed of core cellulases and accessory hydrolytic/non-hydrolytic enzymes attacking plant biopolymers. A synergistic enzyme system comprising the CG-Cel, a β-glucosidase (Novozyme® 188) and a hemicellulase Accellerase® XY was optimized on saccharification of alkaline-pretreated rice straw by a mixture design approach. Applying a full cubic model, the optimal ratio of ternary enzyme mixture containing CG-Cel: Novozyme® 188: Accellerase® XY of 44.4:20.6:35.0 showed synergistic enhancement on reducing sugar yield with a glucose releasing efficiency of 256.4 mg/FPU, equivalent to a 2.9 times compared with that from CG-Cel alone. The work showed an approach for developing an active synergistic enzyme system based on the newly characterized C. globosum for lignocellulose saccharification and modification in bio-industries.

Coarse-grained versus atomistic simulations: realistic interaction free energies for real proteins.

PubMed

May, Ali; Pool, René; van Dijk, Erik; Bijlard, Jochem; Abeln, Sanne; Heringa, Jaap; Feenstra, K Anton

2014-02-01

To assess whether two proteins will interact under physiological conditions, information on the interaction free energy is needed. Statistical learning techniques and docking methods for predicting protein-protein interactions cannot quantitatively estimate binding free energies. Full atomistic molecular simulation methods do have this potential, but are completely unfeasible for large-scale applications in terms of computational cost required. Here we investigate whether applying coarse-grained (CG) molecular dynamics simulations is a viable alternative for complexes of known structure. We calculate the free energy barrier with respect to the bound state based on molecular dynamics simulations using both a full atomistic and a CG force field for the TCR-pMHC complex and the MP1-p14 scaffolding complex. We find that the free energy barriers from the CG simulations are of similar accuracy as those from the full atomistic ones, while achieving a speedup of >500-fold. We also observe that extensive sampling is extremely important to obtain accurate free energy barriers, which is only within reach for the CG models. Finally, we show that the CG model preserves biological relevance of the interactions: (i) we observe a strong correlation between evolutionary likelihood of mutations and the impact on the free energy barrier with respect to the bound state; and (ii) we confirm the dominant role of the interface core in these interactions. Therefore, our results suggest that CG molecular simulations can realistically be used for the accurate prediction of protein-protein interaction strength. The python analysis framework and data files are available for download at http://www.ibi.vu.nl/downloads/bioinformatics-2013-btt675.tgz.

Complexity of cardiovascular rhythms during head-up tilt test by entropy of patterns.

PubMed

Wejer, Dorota; Graff, Beata; Makowiec, Danuta; Budrejko, Szymon; Struzik, Zbigniew R

2017-05-01

The head-up tilt (HUT) test, which provokes transient dynamical alterations in the regulation of cardiovascular system, provides insights into complex organization of this system. Based on signals with heart period intervals (RR-intervals) and/or systolic blood pressure (SBP), differences in the cardiovascular regulation between vasovagal patients (VVS) and the healthy people group (CG) are investigated. Short-term relations among signal data represented symbolically by three-beat patterns allow to qualify and quantify the complexity of the cardiovascular regulation by Shannon entropy. Four types of patterns: permutation, ordinal, deterministic and dynamical, are used, and different resolutions of signal values in the the symbolization are applied in order to verify how entropy of patterns depends on a way in which values of signals are preprocessed. At rest, in the physiologically important signal resolution ranges, independently of the type of patterns used in estimates, the complexity of SBP signals in VVS is different from the complexity found in CG. Entropy of VVS is higher than CG what could be interpreted as substantial presence of noisy ingredients in SBP of VVS. After tilting this relation switches. Entropy of CG occurs significantly higher than VVS for SBP signals. In the case of RR-intervals and large resolutions, the complexity after the tilt becomes reduced when compared to the complexity of RR-intervals at rest for both groups. However, in the case of VVS patients this reduction is significantly stronger than in CG. Our observations about opposite switches in entropy between CG and VVS might support a hypothesis that baroreflex in VVS affects stronger the heart rate because of the inefficient regulation (possibly impaired local vascular tone alternations) of the blood pressure.

Complicated grief associated with hurricane Katrina.

PubMed

Shear, M Katherine; McLaughlin, Katie A; Ghesquiere, Angela; Gruber, Michael J; Sampson, Nancy A; Kessler, Ronald C

2011-08-01

Although losses are important consequences of disasters, few epidemiological studies of disasters have assessed complicated grief (CG) and none assessed CG associated with losses other than death of loved one. Data come from the baseline survey of the Hurricane Katrina Community Advisory Group, a representative sample of 3,088 residents of the areas directly affected by Hurricane Katrina. A brief screen for CG was included containing four items consistent with the proposed DSM-V criteria for a diagnosis of bereavement-related adjustment disorder. Fifty-eight and half percent of respondents reported a significant hurricane-related loss: Most-severe losses were 29.0% tangible, 9.5% interpersonal, 8.1% intangible, 4.2% work/financial, and 3.7% death of loved one. Twenty-six point one percent respondents with significant loss had possible CG and 7.0% moderate-to-severe CG. Death of loved one was associated with the highest conditional probability of moderate-to-severe CG (18.5%, compared to 1.1-10.5% conditional probabilities for other losses), but accounted for only 16.5% of moderate-to-severe CG due to its comparatively low prevalence. Most moderate-to-severe CG was due to tangible (52.9%) or interpersonal (24.0%) losses. Significant predictors of CG were mostly unique to either bereavement (racial-ethnic minority status, social support) or other losses (prehurricane history of psychopathology, social competence.). Nonbereavement losses accounted for the vast majority of hurricane-related possible CG despite risk of CG being much higher in response to bereavement than to other losses. This result argues for expansion of research on CG beyond bereavement and alerts clinicians to the need to address postdisaster grief associated with a wide range of losses. © 2011 Wiley-Liss, Inc.

Complicated grief associated with Hurricane Katrina

PubMed Central

Shear, M. Katherine; McLaughlin, Katie A.; Ghesquiere, Angela; Gruber, Michael J.; Sampson, Nancy A.; Kessler, Ronald C.

2011-01-01

Background Although losses are important consequences of disasters, few epidemiological studies of disasters have assessed complicated grief (CG) and none assessed CG associated with losses other than death of loved one. Methods Data come from the baseline survey of the Hurricane Katrina Community Advisory Group (CAG), a representative sample of 3,088 residents of the areas directly affected by Hurricane Katrina. A brief screen for CG was included containing four items consistent with the proposed DSM 5 criteria for a diagnosis of bereavement-related adjustment disorder. Results 58.5% of respondents reported a significant hurricane-related loss: Most-severe losses were 29.0% tangible, 9.5% interpersonal, 8.1% intangible, 4.2% work-financial, and 3.7% death of loved one. 26.1% of respondents with significant loss had possible CG and 7.0% moderate-severe CG. Death of loved one was associated with the highest conditional probability of moderate-severe CG (18.5%, compared to 1.1–10.5% conditional probabilities for other losses) but accounted for only 16.5% of moderate-severe CG due to its comparatively low prevalence. Most moderate-severe CG was due to tangible (52.9%) or interpersonal (24.0%) losses. Significant predictors of CG were mostly unique to either bereavement (racial-ethnic minority status, social support) or other losses (pre-hurricane history of psychopathology, social competence.). Conclusions Non-bereavement losses accounted for the vast majority of hurricane-related possible CG despite risk of CG being much higher in response to bereavement than to other losses. This result argues for expansion of research on CG beyond bereavement and alerts clinicians to the need to address post-disaster grief associated with a wide range of losses. PMID:21796740

Cholesterol-α-glucosyltransferase gene is present in most Helicobacter species including gastric non-Helicobacter pylori helicobacters obtained from Japanese patients.

PubMed

Kawakubo, Masatomo; Horiuchi, Kazuki; Matsumoto, Takehisa; Nakayama, Jun; Akamatsu, Taiji; Katsuyama, Tsutomu; Ota, Hiroyoshi; Sagara, Junji

2018-02-01

Non-Helicobacter pylori helicobacters (NHPHs) besides H. pylori infect human stomachs and cause chronic gastritis and mucosa-associated lymphoid tissue lymphoma. Cholesteryl-α-glucosides have been identified as unique glycolipids present in H. pylori and some Helicobacter species. Cholesterol-α-glucosyltransferase (αCgT), a key enzyme for the biosynthesis of cholesteryl-α-glucosides, plays crucial roles in the pathogenicity of H. pylori. Therefore, it is important to examine αCgTs of NHPHs. Six gastric NHPHs were isolated from Japanese patients and maintained in mouse stomachs. The αCgT genes were amplified by PCR and inverse PCR. We retrieved the αCgT genes of other Helicobacter species by BLAST searches in GenBank. αCgT genes were present in most Helicobacter species and in all Japanese isolates examined. However, we could find no candidate gene for αCgT in the whole genome of Helicobacter cinaedi and several enterohepatic species. Phylogenic analysis demonstrated that the αCgT genes of all Japanese isolates show high similarities to that of a zoonotic group of gastric NHPHs including Helicobacter suis, Helicobacter heilmannii, and Helicobacter ailurogastricus. Of 6 Japanese isolates, the αCgT genes of 4 isolates were identical to that of H. suis, and that of another 2 isolates were similar to that of H. heilmannii and H. ailurogastricus. All gastric NHPHs examined showed presence of αCgT genes, indicating that αCgT may be beneficial for these helicobacters to infect human and possibly animal stomachs. Our study indicated that NHPHs could be classified into 2 groups, NHPHs with αCgT genes and NHPHs without αCgT genes. © 2017 John Wiley & Sons Ltd.

Altered newborn gender distribution in patients with low mid-trimester maternal serum human chorionic gonadotropin (MShCG).

PubMed

Santolaya-Forgas, J; Meyer, W J; Burton, B K; Scommegna, A

1997-01-01

to determine if the sex ratio (male/female) is altered in infants born to patients with low mid-trimester maternal serum human chorionic gonadotropin (MShCG). Between 2/1/90 and 1/3/91, 3,116 patients underwent prenatal screening using second-trimester maternal serum alpha-fetoprotein (MSAFP), MShCG, and maternal serum unconjugated estriol (MSuE3). Among these, there were 132 patients with low second-trimester MShCG (< 0.4 MoM), normal MSAFP and MSuE3. The gender distribution of these term, normal newborns was compared to that of 237 controls, matched for race, maternal age, and referral source and delivered at term to mothers with normal mid-trimester MSAFP, MSuE3, and MShCG. The gender distribution of these two groups of newborns was also compared to that of 78 term newborns from the same obstetrical population delivered to mothers with second-trimester MShCG > 2.5 MoM and normal MSAFP and MSuE3. All patients had a complete obstetrical history. Forty-nine percent of the controls were male vs. 62% of the group with slow second-trimester MShCG (P < .01). Within the group with low MShCG, 59% of infants were male when the MShCG was between 0.19 and 0.4 MoM (A) and 80% when the MShCG was < 0.2 MoM (B) (control vs. A vs. B P < .005). The sex ratio in the high-MShCG group was similar to control. The data suggest that gender distribution is different from normal in patients with low mid-trimester MShCG.

The effect of post-mating hCG or progesterone administration on reproductive performance of Afshari × Booroola-Merino crossbred ewes.

PubMed

Rostami, Behnam; Hajizadeh, Rahman; Shahir, Mohammad-Hossein; Aliyari, Davood

2017-02-01

To investigate the efficiency of hCG/CIDR after breeding to increase the reproductive performance, 35 synchronized ewes were mated with fertile rams and were assigned to three treatment groups. Ewes in hCG group (n = 12) received 400 IU hCG on day 11 post-mating, and ewes in CIDR group (n = 11) received CIDR from day 7 until day 19 post-mating. Ewes in the control group (n = 12) did not receive any treatment. Blood samples were collected on days 7, 12, 17, and 22 post-mating. Plasma P 4 concentrations were higher on days 12 and 17 post-mating in hCG- and CIDR-treated groups (P < 0.05). However, the concentrations of P 4 on day 22 post-mating in hCG and control groups were higher than that in CIDR group (P < 0.05). Ewes in hCG group produced more quadruplets (P < 0.05) and triplets, and as a result, they had a larger litter size (P < 0.05). The lamb mortality rate by weaning in hCG group (3.6%) was less than that in control (11.8%; P < 0.05) and CIDR (9.1%; P > 0.05) groups. Post-mating administration of hCG or CIDR did not affect the lamb birth weight in single and quadruplet births (P > 0.05), but the birth weight of twin lambs was higher in the hCG and CIDR groups (P < 0.05). Weaning weights of twin lambs were higher in the hCG and CIDR groups (P < 0.05). In conclusion, hCG/CIDR administration post-mating increased the maternal P 4 concentrations and enhanced reproductive performance.

Change of maternal thyroid function in twin-twin transfusion syndrome.

PubMed

Hanaoka, Masachi; Arata, Naoko; Sago, Haruhiko

2015-01-01

Human chorionic gonadotropin (hCG) has weak thyroid-stimulating activity because of its homology with thyroid stimulating hormone (TSH). In twin-twin transfusion syndrome (TTTS), which is a severe complication of monochorionic twin pregnancies, a close association between maternal serum hCG concentration and TTTS has been reported. And, TTTS can be treated by fetoscopic laser coagulation of the communicating vessels. To clarify the relationship between maternal serum hCG and maternal thyroid function in TTTS, the present study investigated the change in thyroid hormone and hCG levels after laser therapy. The protocol included collection of serial maternal blood samples in TTTS before laser therapy, and at two and four weeks after laser therapy. For 131 cases of TTTS, the following parameters were determined at each point: hCG, TSH, free triiodothyronine (fT3), and free thyroxine (fT4). The multiple of the median (MoM) of pre-operative hCG concentration in TTTS was 5.39 MoM (interquartile range, 2.83 - 8.64). There was a moderate positive correlation between hCG and fT3 in TTTS pre-operatively (R = 0.22, P = 0.030). fT4 was also positively correlated with hCG (R = 0.33, P < 0.001). Some cases showed very high concentration in fT3. When laser therapy for TTTS was effective, the hCG concentration significantly decreased, and fT3 and fT4 decreased progressively in concert with the decrease in hCG. The relationship between hCG and thyroid function in TTTS supports the finding of TTTS as a novel etiology of hCG-mediated hyperthyroidism during pregnancy.

A single dose of a MIV-150/Zinc acetate gel provides 24 h of protection against vaginal simian human immunodeficiency virus reverse transcriptase infection, with more limited protection rectally 8-24 h after gel use.

PubMed

Kenney, Jessica; Singer, Rachel; Derby, Nina; Aravantinou, Meropi; Abraham, Ciby J; Menon, Radhika; Seidor, Samantha; Zhang, Shimin; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Fernández-Romero, José A; Zydowsky, Thomas M; Robbiani, Melissa

2012-11-01

Previously we showed that repeated vaginal application of a MIV-150/zinc acetate carrageenan (MIV-150/ZA/CG) gel and a zinc acetate carrageenan (ZA/CG) gel significantly protected macaques from vaginal simian human immunodeficiency virus reverse transcriptase (SHIV-RT) infection. Gels were applied either daily for 2 weeks or every other day for 4 weeks, and the animals were challenged 4-24 h later. Herein, we examined the effects of a single vaginal dose administered either before or after virus challenge. Encouraged by the vaginal protection seen with MIV-150/ZA/CG, we also tested it rectally. Vaginal applications of MIV-150/ZA/CG, ZA/CG, and CG gel were performed once 8-24 h before, 1 h after, or 24 h before and 1 h after vaginal challenge. Rectal applications of MIV-150/ZA/CG and CG gel were performed once 8 or 24 h before rectal challenge. While vaginal pre-challenge and pre/post-challenge application of MIV-150/ZA/CG gel offered significant protection (88%, p<0.002), post-challenge application alone did not significantly protect. ZA/CG gel reduced infection prechallenge, but not significantly, and the effect was completely lost post-challenge. Rectal application of MIV-150/ZA/CG gel afforded limited protection against rectal challenge when applied 8-24 h before challenge. Thus, MIV-150/ZA/CG gel is a highly effective vaginal microbicide that demonstrates 24 h of protection from vaginal infection and may demonstrate efficacy against rectal infection when given close to the time of HIV exposure.

A Single Dose of a MIV-150/Zinc Acetate Gel Provides 24 h of Protection Against Vaginal Simian Human Immunodeficiency Virus Reverse Transcriptase Infection, with More Limited Protection Rectally 8–24 h After Gel Use

PubMed Central

Kenney, Jessica; Singer, Rachel; Derby, Nina; Aravantinou, Meropi; Abraham, Ciby J.; Menon, Radhika; Seidor, Samantha; Zhang, Shimin; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D.; Fernández-Romero, José A.; Zydowsky, Thomas M.

2012-01-01

Abstract Previously we showed that repeated vaginal application of a MIV-150/zinc acetate carrageenan (MIV-150/ZA/CG) gel and a zinc acetate carrageenan (ZA/CG) gel significantly protected macaques from vaginal simian human immunodeficiency virus reverse transcriptase (SHIV-RT) infection. Gels were applied either daily for 2 weeks or every other day for 4 weeks, and the animals were challenged 4–24 h later. Herein, we examined the effects of a single vaginal dose administered either before or after virus challenge. Encouraged by the vaginal protection seen with MIV-150/ZA/CG, we also tested it rectally. Vaginal applications of MIV-150/ZA/CG, ZA/CG, and CG gel were performed once 8–24 h before, 1 h after, or 24 h before and 1 h after vaginal challenge. Rectal applications of MIV-150/ZA/CG and CG gel were performed once 8 or 24 h before rectal challenge. While vaginal pre-challenge and pre/post-challenge application of MIV-150/ZA/CG gel offered significant protection (88%, p<0.002), post-challenge application alone did not significantly protect. ZA/CG gel reduced infection prechallenge, but not significantly, and the effect was completely lost post-challenge. Rectal application of MIV-150/ZA/CG gel afforded limited protection against rectal challenge when applied 8–24 h before challenge. Thus, MIV-150/ZA/CG gel is a highly effective vaginal microbicide that demonstrates 24 h of protection from vaginal infection and may demonstrate efficacy against rectal infection when given close to the time of HIV exposure. PMID:22737981

D1 dopamine receptor is involved in shell formation in larvae of Pacific oyster Crassostrea gigas.

PubMed

Liu, Zhaoqun; Wang, Lingling; Yan, Yunchen; Zheng, Yan; Ge, Wenjing; Li, Meijia; Wang, Weilin; Song, Xiaorui; Song, Linsheng

2018-07-01

Dopamine (DA), a significant member of catecholamines, is reported to induce biomineralization of calcium carbonate vaterite microspheres via dopamine receptor (DR) in bivalves, implying the modulation of dopaminergic system on shell formation during larval development. In this research, a homologue of D1 type DR (CgD1DR-1) was identified from oyster Crassostrea gigas, whose full length cDNA was 1197 bp. It was widely expressed in various tissues of C. gigas, with the significantly higher levels in hepatopancreas, mantle, muscle and gill. During developmental stages, the mRNA transcripts of CgD1DR-1 in D-shape larvae were obviously higher (p < 0.05) than those in trochophore and umbo larvae, and CO 2 exposure could inhibit the synthesis of DA and mRNA expression of CgD1DR-1. After cell transfection and DA treatment, intracellular cAMP in cells with the expression of CgD1DR-1 increased significantly (p < 0.05). Furthermore, the incubation with SCH 23390 for the blockage of CgD1DR-1 significantly restrained the expressions of six shell formation-related genes including CgTyrosinase-1, CgTyrosinase-3, CgChitinaseLP, CgAMC, CgBMP and CgBMPR in trochophore and D-shape larvae. These results jointly suggested that DA together with its receptor CgD1DR-1 might be involved in shell formation during oyster larval development from trochophore to D-shape larvae, and CO 2 -induced ocean acidification (OA) might influence marine bivalves by inhibiting the DA-D1DR pathway to prohibit their shell formation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Further characterization of diabetes mellitus and body weight loss in males of the congenic mouse strain DDD.Cg-A(y.).

PubMed

Suto, Jun-ichi; Satou, Kunio

2015-02-01

The A(y) allele at the agouti locus causes obesity and promotes linear growth in mice. However, body weight gain stops between 16 and 17 weeks after birth, and then, body weight decreases gradually in DDD.Cg-A(y) male mice. Body weight loss is a consequence of diabetes mellitus, which is genetically controlled mainly by a quantitative trait locus (QTL) on chromosome 4. This study aimed to further characterize diabetes mellitus and body weight loss in DDD.Cg-A(y) males. The number of β-cells was markedly reduced, and plasma insulin levels were very low in the DDD.Cg-A(y) males. Using a backcross progeny of DDD × (B6 × DDD.Cg-A(y)) F1-A(y), we identified one significant QTL for plasma insulin levels on distal chromosome 4, which was coincidental with QTL for hyperglycemia and lower body weight. The DDD allele was associated with decreased plasma insulin levels. When the DDD.Cg-A(y) males were housed under three different housing conditions [group housing (4 or 5 DDD.Cg-A(y) and DDD males), individual housing (single DDD.Cg-A(y) male) and single male housing with females (single DDD.Cg-A(y) male with DDD.Cg-A(y) or DDD females)], diabetes mellitus and body weight loss were most severely expressed in individually housed mice. Thus, the severity of diabetes and body weight loss in the DDD.Cg-A(y) males was strongly influenced by the housing conditions. These results demonstrate that both genetic and nongenetic environmental factors are involved in the development of diabetes mellitus and body weight loss in the DDD.Cg-A(y) males.

Further characterization of diabetes mellitus and body weight loss in males of the congenic mouse strain DDD.Cg-Ay

PubMed Central

SUTO, Jun-ichi; SATOU, Kunio

2014-01-01

The Ay allele at the agouti locus causes obesity and promotes linear growth in mice. However, body weight gain stops between 16 and 17 weeks after birth, and then, body weight decreases gradually in DDD.Cg-Ay male mice. Body weight loss is a consequence of diabetes mellitus, which is genetically controlled mainly by a quantitative trait locus (QTL) on chromosome 4. This study aimed to further characterize diabetes mellitus and body weight loss in DDD.Cg-Ay males. The number of β-cells was markedly reduced, and plasma insulin levels were very low in the DDD.Cg-Ay males. Using a backcross progeny of DDD × (B6 × DDD.Cg-Ay) F1-Ay, we identified one significant QTL for plasma insulin levels on distal chromosome 4, which was coincidental with QTL for hyperglycemia and lower body weight. The DDD allele was associated with decreased plasma insulin levels. When the DDD.Cg-Ay males were housed under three different housing conditions [group housing (4 or 5 DDD.Cg-Ay and DDD males), individual housing (single DDD.Cg-Ay male) and single male housing with females (single DDD.Cg-Ay male with DDD.Cg-Ay or DDD females)], diabetes mellitus and body weight loss were most severely expressed in individually housed mice. Thus, the severity of diabetes and body weight loss in the DDD.Cg-Ay males was strongly influenced by the housing conditions. These results demonstrate that both genetic and nongenetic environmental factors are involved in the development of diabetes mellitus and body weight loss in the DDD.Cg-Ay males. PMID:25373882

Multilinear approach to the precipitation-lightning relationship: a case study of summer local electrical storms in the northern part of Spain during 2002-2009 period

NASA Astrophysics Data System (ADS)

Herrero, I.; Ezcurra, A.; Areitio, J.; Diaz-Argandoña, J.; Ibarra-Berastegi, G.; Saenz, J.

2013-11-01

Storms developed under local instability conditions are studied in the Spanish Basque region with the aim of establishing precipitation-lightning relationships. Those situations may produce, in some cases, flash flood. Data used correspond to daily rain depth (mm) and the number of CG flashes in the area. Rain and lightning are found to be weakly correlated on a daily basis, a fact that seems related to the existence of opposite gradients in their geographical distribution. Rain anomalies, defined as the difference between observed and estimated rain depth based on CG flashes, are analysed by PCA method. Results show a first EOF explaining 50% of the variability that linearly relates the rain anomalies observed each day and that confirms their spatial structure. Based on those results, a multilinear expression has been developed to estimate the rain accumulated daily in the network based on the CG flashes registered in the area. Moreover, accumulates and maximum values of rain are found to be strongly correlated, therefore making the multilinear expression a useful tool to estimate maximum precipitation during those kind of storms.

A neuropsychological rehabilitation program for patients with Multiple Sclerosis based on the model of the ICF.

PubMed

Pusswald, Gisela; Mildner, Christa; Zebenholzer, Karin; Auff, Eduard; Lehrner, Johann

2014-01-01

Forty to sixty percent of MS patients suffer from cognitive impairments. Cognitive deficits are a great burden for patients affected. In particular they may lead to a reduced quality of life, loss of work and problems with the social environment. The aim of this study was to evaluate a specific neuropsychological rehabilitation program for MS patients according to the ICF to be able to meet more properly individual requirements on the therapy level of function as well as of activities and participation. Forty patients with MS were randomised in an intervention (IG) - and a control group (CG). The outcome measure of the IG, who started an intensive computer based home training of attention and attended psychological counselling was compared to the untrained CG. In specific domains of attention (simple and cued alertness and divided attention) significant group differences between CG and IG could be found. The IG reported an improvement of mental fatigue and retardation. These findings support the idea that a neuropsychological rehabilitation program, which based on the model of ICF, could improve cognitive impairment and could also have a positive influence of activities and participation.

Double sac sign and intradecidual sign in early pregnancy: interobserver reliability and frequency of occurrence.

PubMed

Doubilet, Peter M; Benson, Carol B

2013-07-01

To assess the interobserver agreement, frequency of occurrence, and prognostic importance of the double sac sign (DSS), intradecidual sign (IDS), and other sonographic findings in early intrauterine pregnancies. We retrospectively identified all sonograms obtained between January 1, 2006, and December 31, 2011, in which: (1) the scan demonstrated an intrauterine fluid collection without a yolk sac or embryo; (2) a follow-up scan confirmed an intrauterine pregnancy; and (3) the first-trimester outcome was known. Each coinvestigator characterized the 199 study sonograms as demonstrating or not demonstrating a DSS or an IDS, based on judgment about whether the scan met published criteria defining these signs. Interobserver agreement was poor for the DSS (κ= 0.24) and IDS (κ= 0.23). Scans frequently demonstrated neither sign: 150 cases (75.4%) if we considered a sign to be present when both investigators graded it as present and 69 cases (34.7%) using the looser criterion that either graded it as present. The presence of a DSS or an IDS was unrelated to the β-human chorionic gonadotropin (β-hCG) value (P > .05, t test, all comparisons). An inner echogenic ring was present in 158 cases (79.4%), and the decidua was brighter peripherally than centrally in 102 (51.3%). The first-trimester outcome was unrelated to the presence of a DSS or an IDS, presence of an inner echogenic ring, or decidual appearance (P > .05, χ(2), all comparisons). The sonographic appearance of early gestational sacs, before visualization of a yolk sac or embryo, is highly variable. The DSS and IDS are often absent; there is poor interobserver agreement regarding these signs; and the prognosis is unrelated to their presence or absence. A round or oval intrauterine fluid collection in a woman with positive β-hCG should be treated as a gestational sac until proven otherwise, regardless of whether it demonstrates a DSS or an IDS.

Oral Progestin Priming Increases Ovarian Sensitivity to Gonadotropin Stimulation and Improves Luteal Function in the Cat1

PubMed Central

Stewart, Rosemary A.; Pelican, Katharine M.; Crosier, Adrienne E.; Pukazhenthi, Budhan S.; Wildt, David E.; Ottinger, Mary Ann; Howard, JoGayle

2012-01-01

ABSTRACT As the only domesticated species known to exhibit both induced and spontaneous ovulation, the cat is a model for understanding the nuances of ovarian control. To explore ovarian sensitivity to exogenous gonadotropins and the influence of progestin priming, we conducted a study of queens that were down-regulated with oral progestin or allowed to cycle normally, followed by low or high doses of equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG). Our metrics included 1) fecal steroid metabolite profiles before and after ovulation induction, 2) laparoscopic examination of ovarian follicles and corpora lutea (CL) on Days 2 and 17 (Day 0 = hCG administration), and 3) ovariohysterectomy (Day 17) to assess CL progesterone concentrations, morphometrics, and histology. Reproductive tracts from time-matched, naturally mated queens (n = 6) served as controls. Every progestin-primed cat (n = 12) produced the desired response of morphologically similar, fresh CL (regardless of eCG/hCG dose) by Day 2, whereas 41.7% of unprimed counterparts (n = 12) failed to ovulate or had variable-aged CL suggestive of prior spontaneous ovulation (P < 0.05). The ovarian response to low, but not high, eCG/hCG was improved (P < 0.05) in primed compared to unprimed cats, indicating increased sensitivity to gonadotropin in the progestin-primed ovary. Progestin priming prevented hyperelevated fecal steroid metabolites and normalized CL progesterone capacity, but only when combined with low eCG/hCG. However, priming failed to prevent ancillary CL formation, smaller CL mass, or abnormal luteal cell density, which were common to all eCG/hCG-treated cats. Thus, the domestic cat exposed to eCG/hCG produces CL with structural and functional aberrations. These anomalies can be partially mitigated by progestin priming, possibly due to a protective effect of progestin associated with enhanced ovarian sensitivity to gonadotropins. PMID:23100619

A regulatory network of two galectins mediates the earliest steps of avian limb skeletal morphogenesis

PubMed Central

2011-01-01

Background The skeletal elements of vertebrate embryonic limbs are prefigured by rod- and spot-like condensations of precartilage mesenchymal cells. The formation of these condensations depends on cell-matrix and cell-cell interactions, but how they are initiated and patterned is as yet unresolved. Results Here we provide evidence that galectins, β-galactoside-binding lectins with β-sandwich folding, play fundamental roles in these processes. We show that among the five chicken galectin (CG) genes, two, CG-1A, and CG-8, are markedly elevated in expression at prospective sites of condensation in vitro and in vivo, with their protein products appearing earlier in development than any previously described marker. The two molecules enhance one another's gene expression but have opposite effects on condensation formation and cartilage development in vivo and in vitro: CG-1A, a non-covalent homodimer, promotes this process, while the tandem-repeat-type CG-8 antagonizes it. Correspondingly, knockdown of CG-1A inhibits the formation of skeletal elements while knockdown of CG-8 enhances it. The apparent paradox of mutual activation at the gene expression level coupled with antagonistic roles in skeletogenesis is resolved by analysis of the direct effect of the proteins on precartilage cells. Specifically, CG-1A causes their aggregation, whereas CG-8, which has no adhesive function of its own, blocks this effect. The developmental appearance and regulation of the unknown cell surface moieties ("ligands") to which CG-1A and CG-8 bind were indicative of specific cognate- and cross-regulatory interactions. Conclusion Our findings indicate that CG-1A and CG-8 constitute a multiscale network that is a major mediator, earlier-acting than any previously described, of the formation and patterning of precartilage mesenchymal condensations in the developing limb. This network functions autonomously of limb bud signaling centers or other limb bud positional cues. PMID:21284876

Total variation superiorized conjugate gradient method for image reconstruction

NASA Astrophysics Data System (ADS)

Zibetti, Marcelo V. W.; Lin, Chuan; Herman, Gabor T.

2018-03-01

The conjugate gradient (CG) method is commonly used for the relatively-rapid solution of least squares problems. In image reconstruction, the problem can be ill-posed and also contaminated by noise; due to this, approaches such as regularization should be utilized. Total variation (TV) is a useful regularization penalty, frequently utilized in image reconstruction for generating images with sharp edges. When a non-quadratic norm is selected for regularization, as is the case for TV, then it is no longer possible to use CG. Non-linear CG is an alternative, but it does not share the efficiency that CG shows with least squares and methods such as fast iterative shrinkage-thresholding algorithms (FISTA) are preferred for problems with TV norm. A different approach to including prior information is superiorization. In this paper it is shown that the conjugate gradient method can be superiorized. Five different CG variants are proposed, including preconditioned CG. The CG methods superiorized by the total variation norm are presented and their performance in image reconstruction is demonstrated. It is illustrated that some of the proposed variants of the superiorized CG method can produce reconstructions of superior quality to those produced by FISTA and in less computational time, due to the speed of the original CG for least squares problems. In the Appendix we examine the behavior of one of the superiorized CG methods (we call it S-CG); one of its input parameters is a positive number ɛ. It is proved that, for any given ɛ that is greater than the half-squared-residual for the least squares solution, S-CG terminates in a finite number of steps with an output for which the half-squared-residual is less than or equal to ɛ. Importantly, it is also the case that the output will have a lower value of TV than what would be provided by unsuperiorized CG for the same value ɛ of the half-squared residual.

Effect of Changing the Center of Gravity on Human Performance in Simulated Lunar Gravity

NASA Technical Reports Server (NTRS)

Chappell, Steven P.; Norcross, Jason R.; Gernhardt, Michael L.

2010-01-01

The presentation slides include: Moving Past Apollo, Testing in Analog Environments, NEEMO/NBL CG (center of gravity) Studies, Center of Gravity Test Design and Methods, CG Suited Locations and Results, CG Individual Considerations, CG Shirt-Sleeve Locations and Results.

46 CFR 1.01-10 - Organization.

Code of Federal Regulations, 2014 CFR

2014-10-01

... resources; plans, acquires, develops, and allocates resources for development and execution of the Coast... Assistant Commandant for Prevention Policy (CG-5P), and the Director of Operations Resource Management (CG... Standards Evaluation and Development (CG-REG); and (ii) The Director of Inspections and Compliance (CG-5PC...

Long-Term, Low-Frequency Cluster of a German-Imipenemase-1-Producing Enterobacter hormaechei ssp. steigerwaltii ST89 in a Tertiary Care Hospital in Germany.

PubMed

Wendel, Andreas F; Meyer, Sebastian; Deenen, René; Köhrer, Karl; Kolbe-Busch, Susanne; Pfeffer, Klaus; Willmann, Matthias; Kaasch, Achim J; MacKenzie, Colin R

2018-05-11

Enterobacter cloacae complex is a common cause of hospital outbreaks. A retrospective and prospective molecular analysis of carbapenem-resistant clinical isolates in a tertiary care center demonstrated an outbreak of a German-imipenemase-1 (GIM-1) metallo-beta-lactamase-producing Enterobacter hormaechei ssp. steigerwaltii affecting 23 patients between 2009 and 2016. Thirty-three isolates were sequence type 89 by conventional multilocus sequence typing (MLST) and displayed a maximum difference of 49 out of 3,643 targets in the ad-hoc core-genome MLST (cgMLST) scheme (SeqSphere+ software; Ridom, Münster, Germany). The relatedness of all isolates was confirmed by further maximum-likelihood phylogeny. One clonal complex of highly related isolates (≤15 allele difference in cgMLST) contained 17 patients, but epidemiological data only suggested five transmission events. The bla GIM-1 -gene was embedded in a class-1-integron (In770) and the Tn21-subgroup transposon Tn6216 (KC511628) on a 25-kb plasmid. Environmental screening detected one colonized sink trap in a service room. The outbreak was self-limited as no further bla GIM-1 -positive E. hormaechei has been isolated since 2016. Routine molecular screening of carbapenem-nonsusceptible gram-negative isolates detected a long-term, low-frequency outbreak of a GIM-1-producing E. hormaechei ssp. steigerwaltii clone. This highlights the necessity of molecular surveillance.

Conjugate gradient method for phase retrieval based on the Wirtinger derivative.

PubMed

Wei, Zhun; Chen, Wen; Qiu, Cheng-Wei; Chen, Xudong

2017-05-01

A conjugate gradient Wirtinger flow (CG-WF) algorithm for phase retrieval is proposed in this paper. It is shown that, compared with recently reported Wirtinger flow and its modified methods, the proposed CG-WF algorithm is able to dramatically accelerate the convergence rate while keeping the dominant computational cost of each iteration unchanged. We numerically illustrate the effectiveness of our method in recovering 1D Gaussian signals and 2D natural color images under both Gaussian and coded diffraction pattern models.

The Zur regulon of Corynebacterium glutamicum ATCC 13032

PubMed Central

2010-01-01

Background Zinc is considered as an essential element for all living organisms, but it can be toxic at large concentrations. Bacteria therefore tightly regulate zinc metabolism. The Cg2502 protein of Corynebacterium glutamicum was a candidate to control zinc metabolism in this species, since it was classified as metalloregulator of the zinc uptake regulator (Zur) subgroup of the ferric uptake regulator (Fur) family of DNA-binding transcription regulators. Results The cg2502 (zur) gene was deleted in the chromosome of C. glutamicum ATCC 13032 by an allelic exchange procedure to generate the zur-deficient mutant C. glutamicum JS2502. Whole-genome DNA microarray hybridizations and real-time RT-PCR assays comparing the gene expression in C. glutamicum JS2502 with that of the wild-type strain detected 18 genes with enhanced expression in the zur mutant. The expression data were combined with results from cross-genome comparisons of shared regulatory sites, revealing the presence of candidate Zur-binding sites in the mapped promoter regions of five transcription units encoding components of potential zinc ABC-type transporters (cg0041-cg0042/cg0043; cg2911-cg2912-cg2913), a putative secreted protein (cg0040), a putative oxidoreductase (cg0795), and a putative P-loop GTPase of the COG0523 protein family (cg0794). Enhanced transcript levels of the respective genes in C. glutamicum JS2502 were verified by real-time RT-PCR, and complementation of the mutant with a wild-type zur gene reversed the effect of differential gene expression. The zinc-dependent expression of the putative cg0042 and cg2911 operons was detected in vivo with a gfp reporter system. Moreover, the zinc-dependent binding of purified Zur protein to double-stranded 40-mer oligonucleotides containing candidate Zur-binding sites was demonstrated in vitro by DNA band shift assays. Conclusion Whole-genome expression profiling and DNA band shift assays demonstrated that Zur directly represses in a zinc-dependent manner the expression of nine genes organized in five transcription units. Accordingly, the Zur (Cg2502) protein is the key transcription regulator for genes involved in zinc homeostasis in C. glutamicum. PMID:20055984

BRCA1 regulation on β-hCG: a mechanism for tumorigenicity in BRCA1 defective breast cancer.

PubMed

Sengodan, S K; Nadhan, R; Nair, R S; Hemalatha, S K; Somasundaram, V; Sushama, R R; Rajan, A; Latha, N R; Varghese, G R; Thankappan, R K; Kumar, J M; Chil, A; Anilkumar, T V; Srinivas, P

2017-09-04

Human chorionic gonadotropin β (β-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of β-hCG in breast cancer. We identified for the first time that β-hCG expression is linked to BRCA1 status and its overexpression is seen in BRCA1 mutated breast cancer cells, BRCA1 conditional knockout mouse breast cancer tissues and BRCA1 floxed basal cell carcinoma (BCC) tissues. An analysis of three large, transcriptomic data sets from TCGA (The Cancer Genome Atlas) expression profile confirmed the inverse correlation between BRCA1 and β-hCG in human breast cancer. Using ChIP and luciferase assays, we also demonstrated that the cancer cells with wild-type but not mutant BRCA1 directly repress the expression of β-hCG by binding to its promoter. Further, β-hCG promotes migration and invasion predominantly in BRCA1 mutant breast cancer cells. Interestingly, stable overexpression of β-hCG in BRCA1 mutant but not wild-type breast cancer cells results in the formation of spheres even on monolayer cultures. The cells of these spheres show high expression of both EMT and stem cell markers. Since β-hCG belongs to a cysteine knot family of proteins like TGFβ and TGFβ signaling is deregulated in BRCA1 defective tumors, we checked whether β-hCG can mediate signaling through TGFβRII in BRCA1 mutated cells. We found for the first time that β-hCG can bind and phosphorylate TGFβRII, irrespective of LHCGR status and induce proliferation in BRCA1 defective cells. Our results confirmed that there exists a transcriptional regulation of BRCA1 on β-hCG and BRCA1 mutation promotes β-hCG mediated tumorigenesis through TGFβRII signaling. Thus inhibiting β-hCG-TGFβRII could prove an effective treatment strategy for BRCA1 mutated tumors.

LH and hCG Action on the Same Receptor Results in Quantitatively and Qualitatively Different Intracellular Signalling

PubMed Central

Casarini, Livio; Lispi, Monica; Longobardi, Salvatore; Milosa, Fabiola; La Marca, Antonio; Tagliasacchi, Daniela; Pignatti, Elisa; Simoni, Manuela

2012-01-01

Human luteinizing hormone (hLH) and chorionic gonadotropin (hCG) act on the same receptor (LHCGR) but it is not known whether they elicit the same cellular and molecular response. This study compares for the first time the activation of cell-signalling pathways and gene expression in response to hLH and hCG. Using recombinant hLH and recombinant hCG we evaluated the kinetics of cAMP production in COS-7 and hGL5 cells permanently expressing LHCGR (COS-7/LHCGR, hGL5/LHCGR), as well as cAMP, ERK1/2, AKT activation and progesterone production in primary human granulosa cells (hGLC). The expression of selected target genes was measured in the presence or absence of ERK- or AKT-pathways inhibitors. In COS-7/LHCGR cells, hCG is 5-fold more potent than hLH (cAMP ED50: 107.1±14.3 pM and 530.0±51.2 pM, respectively). hLH maximal effect was significantly faster (10 minutes by hLH; 1 hour by hCG). In hGLC continuous exposure to equipotent doses of gonadotropins up to 36 hours revealed that intracellular cAMP production is oscillating and significantly higher by hCG versus hLH. Conversely, phospho-ERK1/2 and -AKT activation was more potent and sustained by hLH versus hCG. ERK1/2 and AKT inhibition removed the inhibitory effect on NRG1 (neuregulin) expression by hLH but not by hCG; ERK1/2 inhibition significantly increased hLH- but not hCG-stimulated CYP19A1 (aromatase) expression. We conclude that: i) hCG is more potent on cAMP production, while hLH is more potent on ERK and AKT activation; ii) hGLC respond to equipotent, constant hLH or hCG stimulation with a fluctuating cAMP production and progressive progesterone secretion; and iii) the expression of hLH and hCG target genes partly involves the activation of different pathways depending on the ligand. Therefore, the LHCGR is able to differentiate the activity of hLH and hCG. PMID:23071612

BRCA1 regulation on β-hCG: a mechanism for tumorigenicity in BRCA1 defective breast cancer

PubMed Central

Sengodan, S K; Nadhan, R; Nair, R S; Hemalatha, S K; Somasundaram, V; Sushama, R R; Rajan, A; Latha, N R; Varghese, G R; Thankappan, R k; Kumar, J M; Chil, A; Anilkumar, T V; Srinivas, P

2017-01-01

Human chorionic gonadotropin β (β-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of β-hCG in breast cancer. We identified for the first time that β-hCG expression is linked to BRCA1 status and its overexpression is seen in BRCA1 mutated breast cancer cells, BRCA1 conditional knockout mouse breast cancer tissues and BRCA1 floxed basal cell carcinoma (BCC) tissues. An analysis of three large, transcriptomic data sets from TCGA (The Cancer Genome Atlas) expression profile confirmed the inverse correlation between BRCA1 and β-hCG in human breast cancer. Using ChIP and luciferase assays, we also demonstrated that the cancer cells with wild-type but not mutant BRCA1 directly repress the expression of β-hCG by binding to its promoter. Further, β-hCG promotes migration and invasion predominantly in BRCA1 mutant breast cancer cells. Interestingly, stable overexpression of β-hCG in BRCA1 mutant but not wild-type breast cancer cells results in the formation of spheres even on monolayer cultures. The cells of these spheres show high expression of both EMT and stem cell markers. Since β-hCG belongs to a cysteine knot family of proteins like TGFβ and TGFβ signaling is deregulated in BRCA1 defective tumors, we checked whether β-hCG can mediate signaling through TGFβRII in BRCA1 mutated cells. We found for the first time that β-hCG can bind and phosphorylate TGFβRII, irrespective of LHCGR status and induce proliferation in BRCA1 defective cells. Our results confirmed that there exists a transcriptional regulation of BRCA1 on β-hCG and BRCA1 mutation promotes β-hCG mediated tumorigenesis through TGFβRII signaling. Thus inhibiting β-hCG-TGFβRII could prove an effective treatment strategy for BRCA1 mutated tumors. PMID:28869585

Establishing reference intervals for hCG in postmenopausal women.

PubMed

Patel, Khushbu K; Qavi, Abraham J; Hock, Karl G; Gronowski, Ann M

2017-03-01

Plasma concentrations of human chorionic gonadotropin (hCG) have been shown to increase with age due to pituitary secretion. We previously recommended that an hCG cutoff of 14.0IU/L be used for women ≥55years of age. However, it remains unknown whether concentrations >14.0IU/L can be expected in women with advanced age. Our objectives were to establish plasma hCG reference intervals and correlate follicle stimulating hormone (FSH) and hCG concentrations in postmenopausal females ≥55years. Residual plasma samples from 798 women ≥55years were utilized with 303, 269, and 226 samples belonging to the age groups 55-69, 70-84, and ≥85years, respectively. FSH and hCG were measured using the Abbott ARCHITECT. All positive hCG samples (hCG ≥5IU/L) were analyzed for potential heterophile antibody interference and 3 were excluded. Electronic medical records were reviewed and patients with malignancy were excluded. 8% (56/666) of women age≥55years had plasma hCG ≥5IU/L. There were 19, 16, and 21 patients with hCG ≥5IU/L in the age groups 55-69, 70-84, and ≥85years, respectively. The highest hCG concentrations observed in each age group were: 55-69years maximum=11.7IU/L and 97.5th percentile=9.6IU/L; 70-84years maximum=18.09IU/L, 97.5th percentile=6.2IU/L; ≥85years maximum=11.1IU/L and 97.5th percentile=10.0IU/L, and the overall 97.5th percentile=8.5IU/L for all women ≥55years of age. Neither hCG nor FSH concentrations continued to increase with age in women ≥55years. The prevalence of positive hCG in women ≥55years is 8%. This study confirms our previously recommended cutoff of 14IU/L for women ≥55years of age. In women ≥55years of age, FSH concentrations do not predict hCG concentrations. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

The use of altrenogest to avoid hyperestrogenism after eCG-hCG ovulation induction in southern tigrina (Leopardus guttulus).

PubMed

Micheletti, Tatiane; Brown, Janine L; Walker, Susan L; Cubas, Zalmir S; Furtado, Priscila V; Putman, Sarah B; de Moraes, Wanderlei; de Oliveira, Marcos J; de Oliveira, Claudio A; Moreira, Nei

2015-09-01

The goal of this study was to optimize an ovulation induction protocol for use with artificial insemination in the southern tigrina (Leopardus guttulus). The specific aims were to report the efficacy of using altrenogest, an oral progestin (Regumate, MSD Animal Health, Merck Animal Health), to suppress ovarian activity and prevent follicular hyperstimulation and hyperestrogenism after the administration of exogenous eCG and hCG. To monitor ovarian responses, fecal estrogen and progestogen metabolites were quantified by enzyme immunoassay in females before and after intramuscular administration of 200-IU eCG and 150-IU hCG in two trials, 4 months apart. During the first trial, there was no use of altrenogest, only the eCG-hCG ovulation induction protocol. In the second trial, the ovulation induction protocol was preceded by the administration of oral altrenogest for 14 days (minimum of 0.192 mg per kg per day). Altrenogest administration resulted in a suppression of follicular activity in three out of six females before eCG-hCG administration on the basis of lower mean estrogen concentrations (P < 0.05). It also resulted in four out of six females presenting lower fecal estrogen metabolite concentrations (P < 0.05) after ovulation induction, and two out of six individuals showed a reduction (P < 0.05) in postovulatory fecal progestogen metabolite concentrations, all when compared to the same female's cycles without the progestin. Fecal estrogen metabolite concentrations were closer to baseline in 50% of these individuals after altrenogest and eCG-hCG treatments when compared to basal concentrations before gonadotropins without the use of altrenogest. This study reported that use of altrenogest in southern tigrina can suppress ovarian activity and avoid hyperestrogenism after administration of eCG and hCG treatment. However, not all females responded uniformly, so more studies are needed to increase the efficacy of ovulation induction for use with artificial insemination in this species. Copyright © 2015 Elsevier Inc. All rights reserved.

Sensor-based balance training with motion feedback in people with mild cognitive impairment.

PubMed

Schwenk, Michael; Sabbagh, Marwan; Lin, Ivy; Morgan, Pharah; Grewal, Gurtej S; Mohler, Jane; Coon, David W; Najafi, Bijan

2016-01-01

Some individuals with mild cognitive impairment (MCI) experience not only cognitive deficits but also a decline in motor function, including postural balance. This pilot study sought to estimate the feasibility, user experience, and effects of a novel sensor-based balance training program. Patients with amnestic MCI (mean age 78.2 yr) were randomized to an intervention group (IG, n = 12) or control group (CG, n = 10). The IG underwent balance training (4 wk, twice a week) that included weight shifting and virtual obstacle crossing. Real-time visual/audio lower-limb motion feedback was provided from wearable sensors. The CG received no training. User experience was measured by a questionnaire. Postintervention effects on balance (center of mass sway during standing with eyes open [EO] and eyes closed), gait (speed, variability), cognition, and fear of falling were measured. Eleven participants (92%) completed the training and expressed fun, safety, and helpfulness of sensor feedback. Sway (EO, p = 0.04) and fear of falling (p = 0.02) were reduced in the IG compared to the CG. Changes in other measures were nonsignificant. Results suggest that the sensor-based training paradigm is well accepted in the target population and beneficial for improving postural control. Future studies should evaluate the added value of the sensor-based training compared to traditional training.

Estimating glomerular filtration rate in diabetes: a comparison of cystatin-C- and creatinine-based methods.

PubMed

Macisaac, R J; Tsalamandris, C; Thomas, M C; Premaratne, E; Panagiotopoulos, S; Smith, T J; Poon, A; Jenkins, M A; Ratnaike, S I; Power, D A; Jerums, G

2006-07-01

We compared the predictive performance of a GFR based on serum cystatin C levels with commonly used creatinine-based methods in subjects with diabetes. In a cross-sectional study of 251 consecutive clinic patients, the mean reference (plasma clearance of (99m)Tc-diethylene-triamine-penta-acetic acid) GFR (iGFR) was 88+/-2 ml min(-1) 1.73 m(-2). A regression equation describing the relationship between iGFR and 1/cystatin C levels was derived from a test population (n=125) to allow for the estimation of GFR by cystatin C (eGFR-cystatin C). The predictive performance of eGFR-cystatin C, the Modification of Diet in Renal Disease 4 variable formula (MDRD-4) and Cockcroft-Gault (C-G) formulas were then compared in a validation population (n=126). There was no difference in renal function (ml min(-1) 1.73 m(-2)) as measured by iGFR (89.2+/-3.0), eGFR-cystatin C (86.8+/-2.5), MDRD-4 (87.0+/-2.8) or C-G (92.3+/-3.5). All three estimates of renal function had similar precision and accuracy. Estimates of GFR based solely on serum cystatin C levels had the same predictive potential when compared with the MDRD-4 and C-G formulas.

Cheilitis Glandularis: Two Case Reports of Asian-Japanese Men and Literature Review of Japanese Cases

PubMed Central

Yanagawa, Toru; Yamaguchi, Akira; Harada, Hiroyuki; Yamagata, Kenji; Ishibashi, Naomi; Noguchi, Masayuki; Onizawa, Kojiro; Bukawa, Hiroki

2011-01-01

Cheilitis glandularis (CG) is a rare disorder characterized by swelling of the lip with hyperplasia of the labial salivary glands. CG is most frequently encountered in the lower lip, in middle-aged to older Caucasian men; however Asian cases were rarely reported. In this paper we present two cases of CG in Asian-Japanese men. One was a 23-year-old male with CG of the superficial suppurative type. The other was a 54-year-old male with deep suppurative type. We also reviewed the Japanese cases of CG in the literature and discussed about clinical feature of Japanese CG. PMID:21991474

46 CFR 1.01-10 - Organization.

Code of Federal Regulations, 2013 CFR

2013-10-01

... resource issues in support of the Standards and Operations Directorates; and oversees the development and... Assistant Commandant for Prevention Policy (CG-5P), and the Director of Operations Resource Management (CG... Standards Evaluation and Development (CG-REG); and (ii) The Director of Inspections and Compliance (CG-5PC...

Multigrid accelerated simulations for Twisted Mass fermions

NASA Astrophysics Data System (ADS)

Bacchio, Simone; Alexandrou, Constantia; Finkerath, Jacob

2018-03-01

Simulations at physical quark masses are affected by the critical slowing down of the solvers. Multigrid preconditioning has proved to deal effectively with this problem. Multigrid accelerated simulations at the physical value of the pion mass are being performed to generate Nf = 2 and Nf = 2 + 1 + 1 gauge ensembles using twisted mass fermions. The adaptive aggregation-based domain decomposition multigrid solver, referred to as DD-αAMG method, is employed for these simulations. Our simulation strategy consists of an hybrid approach of different solvers, involving the Conjugate Gradient (CG), multi-mass-shift CG and DD-αAMG solvers. We present an analysis of the multigrid performance during the simulations discussing the stability of the method. This significant speeds up the Hybrid Monte Carlo simulation by more than a factor 4 at physical pion mass compared to the usage of the CG solver.

Psychological stress evaluation of patients with bronchial asthma based on the chromogranin a level in saliva.

PubMed

Hoshino, Ken; Suzuki, Jun; Yamauchi, Kohei; Inoue, Hiroshi

2008-09-01

To evaluate the involvement of stress in asthmatics we measured the concentration of chromogranin A (CgA) in saliva as an indicator of psychological stress and investigated its correlation with peak expiratory flow (PEF), a visual analog scale (VAS) score of symptoms, and the score of the Short-form 36 health survey questionnaire (SF-36) in 62 adult asthmatics. CgA had a significant correlation with role physical (RP) (r = -0.298, p < 0.05), role emotional (RE) (r = -0.294, p < 0.05) and the physical component summary (PCS) (r = -0.310, p < 0.05) of SF-36, and VAS score (r = -0.435, p < 0.01). We concluded that the concentration of CgA reflects the stress in asthmatics caused by work or daily life limitations.

Serum chromogranin A concentration in hyperthyroidism before and after medical treatment.

PubMed

Al-Shoumer, Kamal A S; Vasanthy, Bagavathy A

2009-07-01

The aim was to evaluate changes in chromogranin A (CgA) concentration in hyperthyroidism and to assess its metabolic correlations. We studied CgA levels in hyperthyroidism. First, 38 hyperthyroid patients matched with 86 normal controls were studied after an overnight fast. Second, 30 if the 38 patients were followed up for 6 months with medical antithyroid drug therapy (carbimazole). In the first study, after 10-12 h overnight fasting, blood was collected for measurement of CgA, glucose, insulin, intact proinsulin, and thyroid function. These variables were remeasured in the second study for the patients after attainment of euthyroidism with the antithyroid drug carbimazole for 6 months. Pretreatment CgA level was significantly higher in patients compared with controls. CgA levels dropped significantly to levels similar to those of controls after antithyroid therapy. Although baseline and follow-up fasting glucose, insulin, and intact proinsulin demonstrated similar pattern of CgA changes before and after medical treatment, CgA did not correlate with any of them. However, CgA levels demonstrated a significant positive correlation with free T(3) and free T(4) only. These studies demonstrate that untreated hyperthyroidism is associated with elevated CgA level that changes in parallel to thyroid status. It is therefore possible to use CgA concentration as a potential marker of disease activity in hyperthyroidism.

Effects of a single administration of different gonadotropins on day 7 post-insemination on pregnancy outcomes of rabbit does.

PubMed

Hashem, N M; Aboul-Ezz, Z R

2018-01-01

This study aimed to investigate the effects of a single administration of one of three different gonadotropins on Day 7 post-insemination on ovarian activity, progesterone (P 4 ) concentration and pregnancy outcomes of rabbit does. Multiparous, non-lactating, V-line does were artificially inseminated after synchronization and ovulation induction with equine chorionic gonadotropin (eCG; 25 IU im) and gonadotropin releasing hormone (GnRH; 0.8  μg buserelin im) 48 h later. On Day 7 post-inseminarion, does were randomly allocated into four groups (n = 40/group). Does of each group were intramuscularly injected with a single dose of one of physiological saline (placebo; control), GnRH (0.8  μg buserelin), human chorionic gonadotropin (hCG; 25 IU) or eCG (25 IU). Concentration of serum P 4 was determined on Days 6, 9, 11 and 18 post-insemination. On Day 14 post-insemination, the ovaries and reproductive tracts of pregnant does were removed and weighed. Also, numbers of visible follicles, hemorrhagic follicles, corpora lutea of pregnancy (pCLs), new CLs (nCLs; formed after Day 7 post-insemination) and implantation sites were recorded. Conception rate, parturition rate, abortion rate, litter size/weight and litter viability were recorded. The highest (P < 0.05) reproductive tract and ovary weights were for eCG. The highest (P < 0.05) number of visible ovarian follicles was for eCG, whereas the lowest (P < 0.05) was for GnRH. Treatment with eCG increased (P < 0.05) numbers of pCLs and total implantation sites compared to the other groups. Treatment with GnRH or hCG increased (P < 0.05) number of nCLs compared to control and eCG. The highest rate of fetal loss was in does treated with GnRH. The concentration of serum P 4 decreased (P < 0.05) following the treatment with GnRH and continued low until Day 18. However, it remained in line for control, hCG and eCG groups up to Day 11, then decreased (P < 0.05) for control and hCG on Day 18, being lower for hCG than control, while continued to increase for eCG up to Day 18. Compared to control, treatment with eCG improved (P < 0.05) conception and parturition rates by 24 and 22%; respectively, while GnRH and hCG treatments decreased (P < 0.05) them by 57 and 47.6%; respectively. Litter size and litter weight at birth were improved by eCG, but were adversely affectd by GnRH and hCG. In conclusion, a single administration of eCG 7 Days post-insemination could be recommended for improving pregnancy outcomes in rabbits. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictive value of serum β-hCG for early pregnancy outcomes among women with recurrent spontaneous abortion.

PubMed

Liu, Yinglin; Liu, Yukun; Li, Xuejiao; Jiao, Xuedan; Zhang, Rui; Zhang, Jianping

2016-10-01

To examine peak serum levels of the β-subunit of human chorionic gonadotropin (β-hCG) for prediction of early pregnancy outcomes among women with recurrent spontaneous abortion (RSA). In a retrospective study, the medical records of pregnant women with a history of RSA treated at Sun Yat-sen Memorial Hospital, China, between January 2011 and July 2013 were reviewed. Serum β-hCG had been measured twice weekly from 5 to 13weeks of pregnancy, and pregnancy was monitored by transvaginal ultrasonography to 13(+6)weeks. Optimal cutoff for peak β-hCG level was determined by receiver operator characteristic curve analysis and Youden index. Women were divided into four groups on the basis of optimal peak β-hCG cutoff and pregnancy outcome (pregnancy at 13weeks or spontaneous abortion). Peak β-hCG levels and length of pregnancy at this peak were examined. Overall, 1240 patients were included. The optimal cutoff value of peak β-hCG was 88 468IU/L, with a sensitivity, specificity, positive predictive value, and negative predictive value for successful pregnancy of 95.6%, 88.0%, 95.6%, and 89.0%, respectively. A faster rise in β-hCG, higher peak β-hCG, and longer pregnancy length at peak β-hCG were associated with successful early pregnancy. A cutoff value of serum β-hCG of 88 000IU/L could be used to predict early pregnancy outcomes for women with a history of RSA. Copyright © 2016. Published by Elsevier Ireland Ltd.

Chicken galectin-1B inhibits Newcastle disease virus adsorption and replication through binding to hemagglutinin-neuraminidase (HN) glycoprotein.

PubMed

Sun, Junfeng; Han, Zongxi; Qi, Tianming; Zhao, Ran; Liu, Shengwang

2017-12-08

Galectin-1 is an important immunoregulatory factor and can mediate the host-pathogen interaction via binding glycans on the surface of various viruses. We previously reported that avian respiratory viruses, including lentogenic Newcastle disease virus (NDV), can induce up-regulation of chicken galectin (CG)-1B in the primary target organ. In this study, we investigated whether CG-1B participated in the infectious process of NDV in chickens. We demonstrated that velogenic NDV induced up-regulation of CG-1B in target organs. We also found that CG-1B directly bound to NDV virions and inhibited their hemagglutination activity in vitro We confirmed that CG-1B interacted with NDV hemagglutinin-neuraminidase (HN) glycoprotein, in which the specific G4 N -glycans significantly contributed to the interaction between CG-1B and HN glycoprotein. The presence of extracellular CG-1B, rather than the internalization process, inhibited adsorption of NDV. The interaction between intracellular CG-1B and NDV HN glycoproteins inhibited cell-surface expression of HN glycoprotein and reduced the titer of progeny virus in NDV-infected DF-1 cells. Significantly, the replication of parental and HN glycosylation mutant viruses in CG-1B knockdown and overexpression cells demonstrated that the replication of NDV was correlated with the expression of CG-1B in a specific glycan-dependent manner. Collectively, our results indicate that CG-1B has anti-NDV activity by binding to N -glycans on HN glycoprotein. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of two physical education programmes on health- and skill-related physical fitness of Albanian children.

PubMed

Jarani, J; Grøntved, A; Muca, F; Spahi, A; Qefalia, D; Ushtelenca, K; Kasa, A; Caporossi, D; Gallotta, M C

2016-01-01

This study aims to evaluate the effectiveness of two school-based physical education (PE) programmes (exercise-based and games-based) compared with traditional PE, on health- and skill-related physical fitness components in children in Tirana, Albania. Participants were 378 first-grade (6.8 years) and 389 fourth-grade (9.8 years) children attending four randomly selected schools in Tirana. Twenty-four school classes within these schools were randomly selected (stratified by school and school grade) to participate as exercise group (EG), games group (GG) and control group (CG). Both EG and GG intervention programmes were taught by professional PE teachers using station/circuit teaching framework while CG referred to traditional PE school lessons by a general teacher. All programmes ran in parallel and lasted 5 months, having the same frequency (twice weekly) and duration (45 min). Heart rate (HR) monitoring showed that intensity during PE lessons was significantly higher in the intervention groups compared with control (P < 0.001). Both PE exercise- and games programmes significantly improved several health- and skill-related fitness indicators compared with traditional PE lessons (e.g. gross motor skill summary score: 9.4 (95% CI 7.9; 10.9) for exercise vs. control and 6.5 (95% CI 5.1; 8.1) for games vs. control, cardiorespiratory fitness: 2.0 ml O2 · min(-1) · kg(-1) (95% CI 1.5; 2.4) for exercise vs. control and 1.4 ml O2 · min(-1) · kg(-1) (95% CI 1.0; 1.8) for games vs. control). Furthermore, compared to games-based PE, exercise-based PE showed more positive changes in some gross motor coordination skills outcomes, coordination skills outcomes and cardiorespiratory fitness. The results from this study show that exercise- and games-based PE represents a useful strategy for improving health- and skill-related physical fitness in Albanian elementary school children. In addition, the study shows that exercise-based PE was more effective than games-based PE in improving gross motor function and cardiorespiratory fitness.

46 CFR 147.5 - Commandant (CG-522); address.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Commandant (CG-522); address. 147.5 Section 147.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES HAZARDOUS SHIPS' STORES General Provisions § 147.5 Commandant (CG-522); address. Commandant (CG-522) is the Office of Operating...

46 CFR 147.5 - Commandant (CG-OES); address.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Commandant (CG-OES); address. 147.5 Section 147.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES HAZARDOUS SHIPS' STORES General Provisions § 147.5 Commandant (CG-OES); address. Commandant (CG-ENG) is the Office of Design and...

46 CFR 147.5 - Commandant (CG-522); address.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Commandant (CG-522); address. 147.5 Section 147.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES HAZARDOUS SHIPS' STORES General Provisions § 147.5 Commandant (CG-522); address. Commandant (CG-522) is the Office of Operating...

46 CFR 147.5 - Commandant (CG-OES); address.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Commandant (CG-OES); address. 147.5 Section 147.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES HAZARDOUS SHIPS' STORES General Provisions § 147.5 Commandant (CG-OES); address. Commandant (CG-ENG) is the Office of Design and...

46 CFR 147.5 - Commandant (CG-OES); address.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Commandant (CG-OES); address. 147.5 Section 147.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES HAZARDOUS SHIPS' STORES General Provisions § 147.5 Commandant (CG-OES); address. Commandant (CG-OES) is the Office of Operating...

75 FR 34114 - Pesticide Products; Registration Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... & 16); vegetables, legume, including soybeans (CG 6 & 7); canola, borage, crambe, cuphea, echium, flax... use as seed treatment on alfalfa, beans and peas including soybean and legume (CG 6 & 7); cotton... treatment on alfalfa, beans and peas including soybean and legume (CG 6 & 7); cotton, cereal grains (CG 15...

46 CFR 1.01-10 - Organization.

Code of Federal Regulations, 2012 CFR

2012-10-01

... coordinates the activities of the Operations Resource Management Directorate (CG-DCO-R), consisting of the Office of Workforce Management (CG-DCO-R-1), the Office of Budget Development (CG-DCO-R-2), the Office of... administrative control over the NMC detachments. (iii) The Director of Operations Resource Management (CG-DCO-R...

PERIOD2 variants are associated with abdominal obesity, psycho-behavioral factors, and attrition in the dietary treatment of obesity.

PubMed

Garaulet, Marta; Corbalán-Tutau, M Dolores; Madrid, Juan A; Baraza, Juan C; Parnell, Laurence D; Lee, Yu-Chi; Ordovas, Jose M

2010-06-01

The purpose of this research was to test for association between polymorphisms in the circadian clock-related gene PERIOD2 (PER2) and attrition in patients prone to withdrawal from a behavioral weight-reduction program based on the Mediterranean diet. A total of 454 overweight/obese participants (women=380, men=74), aged 20 to 65 years, who attended outpatient clinics specializing in obesity between January and December 2008, were studied. Anthropometric, biochemical, and dietary-intake variables were analyzed. Effectiveness of the program was assessed, and a questionnaire of barriers to weight loss was considered. Multivariate analysis and logistic regression models were performed. Results indicate that PER2 polymorphisms rs2304672C>G and rs4663302C>T were associated with abdominal obesity (P<0.05). Participants who withdrew from treatment were significantly more obese and had more barriers to lose weight (P<0.05). They also displayed a lower likelihood of planning eating in advance and experiencing stress with dieting than those who completed treatment. Frequency of rs4663307 minor allele was significantly greater in withdrawers than in those who successfully completed treatment (P<0.05). Logistic regression analysis showed that rs2304672 C>G minor allele carriers had a greater probability of dropping out, displaying extreme snacking, experiencing stress with dieting, eating when bored, and skipping breakfast than noncarriers. PER2 is implicated in attrition in weight-loss treatment and may modulate eating-behavior-related phenotypes. These findings could represent a step toward personalized health care and nutrition based on a combination of genotyping and psycho-behavioral characterization. 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

Refining the role of PMS2 in Lynch syndrome: germline mutational analysis improved by comprehensive assessment of variants.

PubMed

Borràs, Ester; Pineda, Marta; Cadiñanos, Juan; Del Valle, Jesús; Brieger, Angela; Hinrichsen, Inga; Cabanillas, Ruben; Navarro, Matilde; Brunet, Joan; Sanjuan, Xavier; Musulen, Eva; van der Klift, Helen; Lázaro, Conxi; Plotz, Guido; Blanco, Ignacio; Capellá, Gabriel

2013-08-01

The majority of mismatch repair (MMR) gene mutations causing Lynch syndrome (LS) occur either in MLH1 or MSH2. However, the relative contribution of PMS2 is less well defined. The aim of this study was to evaluate the role of PMS2 in LS by assessing the pathogenicity of variants of unknown significance (VUS) detected in the mutational analysis of PMS2 in a series of Spanish patients. From a cohort of 202 LS suspected patients, 13 patients showing loss of PMS2 expression in tumours were screened for germline mutations in PMS2, using a long range PCR based strategy and multiplex ligation dependent probe amplification (MLPA). Pathogenicity assessment of PMS2 VUS was performed evaluating clinicopathological data, frequency in control population and in silico and in vitro analyses at the RNA and protein level. Overall 25 different PMS2 DNA variants were detected. Fourteen were classified as polymorphisms. Nine variants were classified as pathogenic: seven alterations based on their molecular nature and two after demonstrating a functional defect (c.538-3C>G affected mRNA processing and c.137G>T impaired MMR activity). The c.1569C>G variant was classified as likely neutral while the c.384G>A remained as a VUS. We have also shown that the polymorphic variant c.59G>A is MMR proficient. Pathogenic PMS2 mutations were detected in 69% of patients harbouring LS associated tumours with loss of PMS2 expression. In all, PMS2 mutations account for 6% of the LS cases identified. The comprehensive functional analysis shown here has been useful in the classification of PMS2 VUS and contributes to refining the role of PMS2 in LS.

Activated Carbon Fibers with Hierarchical Nanostructure Derived from Waste Cotton Gloves as High-Performance Electrodes for Supercapacitors.

PubMed

Wei, Chao; Yu, Jianlin; Yang, Xiaoqing; Zhang, Guoqing

2017-12-01

One of the most challenging issues that restrict the biomass/waste-based nanocarbons in supercapacitor application is the poor structural inheritability during the activating process. Herein, we prepare a class of activated carbon fibers by carefully selecting waste cotton glove (CG) as the precursor, which mainly consists of cellulose fibers that can be transformed to carbon along with good inheritability of their fiber morphology upon activation. As prepared, the CG-based activated carbon fiber (CGACF) demonstrates a surface area of 1435 m 2  g -1 contributed by micropores of 1.3 nm and small mesopores of 2.7 nm, while the fiber morphology can be well inherited from the CG with 3D interconnected frameworks created on the fiber surface. This hierarchically porous structure and well-retained fiber-like skeleton can simultaneously minimize the diffusion/transfer resistance of the electrolyte and electron, respectively, and maximize the surface area utilization for charge accumulation. Consequently, CGACF presents a higher specific capacitance of 218 F g -1 and an excellent high-rate performance as compared to commercial activated carbon.

Temperature and mineral dust variability recorded in two low-accumulation Alpine ice cores over the last millennium

NASA Astrophysics Data System (ADS)

Bohleber, Pascal; Erhardt, Tobias; Spaulding, Nicole; Hoffmann, Helene; Fischer, Hubertus; Mayewski, Paul

2018-01-01

Among ice core drilling sites in the European Alps, Colle Gnifetti (CG) is the only non-temperate glacier to offer climate records dating back at least 1000 years. This unique long-term archive is the result of an exceptionally low net accumulation driven by wind erosion and rapid annual layer thinning. However, the full exploitation of the CG time series has been hampered by considerable dating uncertainties and the seasonal summer bias in snow preservation. Using a new core drilled in 2013 we extend annual layer counting, for the first time at CG, over the last 1000 years and add additional constraints to the resulting age scale from radiocarbon dating. Based on this improved age scale, and using a multi-core approach with a neighbouring ice core, we explore the time series of stable water isotopes and the mineral dust proxies Ca2+ and insoluble particles. Also in our latest ice core we face the already known limitation to the quantitative use of the stable isotope variability based on a high and potentially non-stationary isotope/temperature sensitivity at CG. Decadal trends in Ca2+ reveal substantial agreement with instrumental temperature and are explored here as a potential site-specific supplement to the isotope-based temperature reconstruction. The observed coupling between temperature and Ca2+ trends likely results from snow preservation effects and the advection of dust-rich air masses coinciding with warm temperatures. We find that if calibrated against instrumental data, the Ca2+-based temperature reconstruction is in robust agreement with the latest proxy-based summer temperature reconstruction, including a Little Ice Age cold period as well as a medieval climate anomaly. Part of the medieval climate period around AD 1100-1200 clearly stands out through an increased occurrence of dust events, potentially resulting from a relative increase in meridional flow and/or dry conditions over the Mediterranean.

Benchtop quantification of gutter formation and compression of chimney stent grafts in relation to renal flow in chimney endovascular aneurysm repair and endovascular aneurysm sealing configurations.

PubMed

Boersen, Johannes T; Donselaar, Esme J; Groot Jebbink, Erik; Starreveld, Roeliene; Overeem, Simon P; Slump, Cornelis H; de Vries, Jean-Paul P M; Reijnen, Michel M P J

2017-11-01

The chimney technique has been successfully used to treat juxtarenal aortic aneurysms. The two main issues with this technique are gutter formation and chimney graft (CG) compression, which induce a risk for type Ia endoleaks and stent thrombosis, respectively. In this benchtop study, the geometry and renal artery flow of chimney endovascular aneurysm repair configurations were compared with chimney configurations with endovascular aneurysm sealing (ch-EVAS). Seven flow phantoms were constructed, including one control and six chimney endovascular aneurysm repairs (Endurant [Medtronic Inc, Minneapolis, Minn] and AFX [Endologix Inc, Irvine, Calif]) or ch-EVAS (Nellix, Endologix) configurations, combined with either balloon-expandable or self-expanding CGs with an intended higher positioning of the right CG in comparison to the left CG. Geometric analysis was based on measurements at three-dimensional computed tomography angiography and included gutter volume and CG compression, quantified by the ratio between maximal and minimal diameter (D-ratio). In addition, renal artery flow was studied in a physiologic flow model and compared with the control. The average gutter volume was 343.5 ± 142.0 mm 3 , with the lowest gutter volume in the EVAS-Viabahn (W. L. Gore & Associates, Flagstaff, Ariz) combination (102.6 mm 3 ) and the largest in the AFX-Advanta V12 (Atrium Medical Corporation, Hudson, NH) configuration (559.6 mm 3 ). The maximum D-ratio was larger in self-expanding CGs than in balloon-expandable CGs in all configurations (2.02 ± 0.34 vs 1.39 ± 0.13). The CG compression had minimal influence on renal volumetric flow (right, 390.7 ± 29.4 mL/min vs 455.1 mL/min; left, 423.9 ± 28.3 mL/min vs 410.0 mL/min in the control). This study showed that gutter volume was lowest in ch-EVAS in combination with a Viabahn CG. CG compression was lower in configurations with the Advanta V12 than with Viabahn. Renal flow is unrestricted by CG compression. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

[The influence of high fluoride exposure in drinking water on endocrine hormone in female].

PubMed

Hou, Jia-xiang; Yang, Yue-jin; Gong, Biao; Li, Shi-hong; Ding, Zhong; Wen, Shi-bao; Li, Shi-qun; Cheng, Xue-min; Cui, Liu-xin; Ba, Yue

2013-02-01

To explore the influence of water fluoride exposure on reproductive hormones in female. Cross-sectional study was conducted in seven villages of a county in Henan province by using simple random sampling including high fluoride area, defluoridation project area and control area on April, 2011 based on the preliminary study results of fluoride concentration in drinking water. Women who were born and growth or lived in the village at least 5 years and aged 18-48 years old were recruited using cluster sampling. They were divided into high fluoride group (HFG, 116 subjects), defluoridation project group (DFPG, 132 subjects) and control group (CG, 227 subjects) in accordance with the above areas. All subjects accepted questionnaire and physical checkup. Fasting blood and morning urine samples were collected. The concentration of fluoride in urine was determined by fluoride ion selective electrode method. The serum level of GnRH was detected using enzyme linked immunosorbent assay (ELISA). The serum level of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) were determined by chemiluminesence immunoassay (CLIA). The average age was (39.44 ± 7.34), (38.84 ± 8.03), (37.45 ± 7.70) years old in female from DFPG, HFG and CG respectively, there were no significant differences among the three groups (F = 3.02, P = 0.05). The urine fluoride levels were (1.34 ± 1.07), (2.59 ± 1.57), (0.92 ± 0.46) mg/ml in female from DFPG, HFG and CG respectively, there was a significant difference among three groups (F = 105.38, P < 0.01). No significant differences were observed of serum GnRH, LH, T, FSH and E2 among three groups in follicular phase (P > 0.05). The serum levels of E2 in Ovulatory period were 67.73, 58.09, 84.96 pg/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in CG (H = 4.00, P < 0.05). The serum levels of T in Ovulatory period were 0.55, 0.45, 0.55 ng/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 6.47, P < 0.05), but no significant difference was observed between HFG and CG (H = 2.41, P > 0.05). The serum levels of GnRH in Luteal phase were 24.09, 20.16, 23.50 ng/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 14.14, P < 0.05) and CG (H = 12.53, P < 0.05). The serum level of E2 in luteal phase were 81.47, 64.60, 74.55 pg/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 5.69, P < 0.05). As for LH, FSH and T, no significant differences were observed among the three groups (P > 0.05 respectively). The abnormal rates of E2 level were 22.73 (30/102), 37.93 (44/72), 20.26 (46/181) in female from DFPG, HFG and CG respectively. The E2 abnormal rate in female from HFG was higher that from DFPG (χ(2) = 6.82, P < 0.05) and CG (χ(2) = 12.38, P < 0.05). Fluoride exposure may influence reproductive hormones in female, especially in ovulatory and luteal phase of menstrual cycle.

Obstetrical complications associated with abnormal maternal serum markers analytes.

PubMed

Gagnon, Alain; Wilson, R Douglas

2008-10-01

To review the obstetrical outcomes associated with abnormally elevated or decreased level of one or more of the most frequently measured maternal serum marker analytes used in screening for aneuploidy. To provide guidance to facilitate the management of pregnancies that have abnormal levels of one of more markers and to assess the usefulness of these markers as a screening test. Perinatal outcomes associated with abnormal levels of maternal serum markers analytes are compared with the outcomes of pregnancies with normal levels of the same analytes or the general population. The Cochrane Library and Medline were searched for English-language articles published from 1966 to February 2007, relating to maternal serum markers and perinatal outcomes. Search terms included PAPP-A (pregnancy associated plasma protein A), AFP (alphafetoprotein), hCG (human chorionic gonadotropin), estriol, unconjugated estriol, inhibin, inhibin-A, maternal serum screen, triple marker screen, quadruple screen, integrated prenatal screen, first trimester screen, and combined prenatal screen. All study types were reviewed. Randomized controlled trials were considered evidence of the highest quality, followed by cohort studies. Key individual studies on which the recommendations are based are referenced. Supporting data for each recommendation are summarized with evaluative comments and references. The evidence was evaluated using the guidelines developed by the Canadian Task Force on Preventive Health Care. The evidence collected was reviewed by the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada. The benefit expected from this guideline is to facilitate early detection of potential adverse pregnancy outcomes when risks are identified at the time of a maternal serum screen. It will help further stratification of risk and provide options for pregnancy management to minimize the impact of pregnancy complications. The potential harms resulting from such practice are associated with the so called false positive (i.e., uncomplicated pregnancies labelled at increased risk for adverse perinatal outcomes), the potential stress associated with such a label, and the investigations performed for surveillance in this situation. No cost-benefit analysis is available to assess costs and savings associated with this guideline. SUMMARY STATEMENTS: 1. An unexplained level of a maternal serum marker analyte is defined as an abnormal level after confirmation of gestational age by ultrasound and exclusion of maternal, fetal, or placental causes for the abnormal level. (III) 2. Abnormally elevated levels of serum markers are associated with adverse pregnancy outcomes in twin pregnancies, after correction for the number of fetuses. Spontaneous or planned mutifetal reductions may result in abnormal elevations of serum markers. (II-2) RECOMMENDATIONS: 1. In the first trimester, an unexplained low PAPP-A (< 0.4 MoM) and/or a low hCG (< 0.5 MoM) are associated with an increased frequency of adverse obstetrical outcomes, and, at present, no specific protocol for treatment is available. (II-2A) In the second trimester, an unexplained elevation of maternal serum AFP (> 2.5 MoM), hCG (> 3.0 MoM), and/or inhibin-A (> or =2.0 MoM) or a decreased level of maternal serum AFP (< 0.25 MoM) and/or unconjugated estriol (< 0.5 MoM) are associated with an increased frequency of adverse obstetrical outcomes, and, at present, no specific protocol for treatment is available. (II-2A) 2. Pregnant woman with an unexplained elevated PAPP-A or hCG in the first trimester and an unexplained low hCG or inhibin-A and an unexplained elevated unconjugated estriol in the second trimester should receive normal antenatal care, as this pattern of analytes is not associated with adverse perinatal outcomes. (II-2A) 3. The combination of second or third trimester placenta previa and an unexplained elevated maternal serum AFP should increase the index of suspicion for placenta accreta, increta, or percreta. (II-2B) An assessment (ultrasound, MRI) of the placental-uterine interface should be performed. Abnormal invasion should be strongly suspected, and the planning of delivery location and technique should be done accordingly. (III-C) 4. A prenatal consultation with the medical genetics department is recommended for low unconjugated estriol levels (<0.3 MoM), as this analyte pattern can be associated with genetic conditions. (II-2B) 5. The clinical management protocol for identification of potential adverse obstetrical outcomes should be guided by one or more abnormal maternal serum marker analyte value rather than the false positive screening results for the trisomy 21 and/or the trisomy 18 screen. (II-2B) 6. Pregnant woman who are undergoing renal dialysis or who have had a renal transplant should be offered maternal serum screening, but interpretation of the result is difficult as the level of serum hCG is not reliable. (II-2A) 7. Abnormal maternal uterine artery Doppler in association with elevated maternal serum AFP, hCG, or inhibin-A or decreased PAPP-A identifies a group of women at greater risk of IUGR and gestational hypertension with proteinuria. Uterine artery Doppler measurements may be used in the evaluation of an unexplained abnormal level of either of these markers. (II-2B) 8. Further research is recommended to identify the best protocol for pregnancy management and surveillance in women identified at increased risk of adverse pregnancy outcomes based on an abnormality of a maternal serum screening analyte. (III-A) 9. In the absence of evidence supporting any specific surveillance protocol, an obstetrician should be consulted in order to establish a fetal surveillance plan specific to the increased obstetrical risks (maternal and fetal) identified. This plan may include enhanced patient education on signs and symptoms of the most common complications, increased frequency of antenatal visits, increased ultrasound (fetal growth, amniotic fluid levels), and fetal surveillance (biophysical profile, arterial and venous Doppler), and cervical length assessment. (III-A) 10. Limited information suggests that, in women with elevated hCG in the second trimester and/or abnormal uterine artery Doppler (at 22-24 weeks), low-dose aspirin (60-81 mg daily) is associated with higher birthweight and lower incidence of gestational hypertension with proteinuria. This therapy may be used in women who are at risk. (II-2B) 11. Further studies are recommended in order to assess the benefits of low-dose aspirin, low molecular weight heparin, or other therapeutic options in pregnancies determined to be at increased risk on the basis of an abnormal maternal serum screening analyte. (III-A) 12. Multiple maternal serum markers screening should not be used at present as a population-based screening method for adverse pregnancy outcomes (such as preeclampsia, placental abruption, and stillbirth) outside an established research protocol, as sensitivity is low, false positive rates are high, and no management protocol has been shown to clearly improve outcomes. (II-2D) When maternal serum screening is performed for the usual clinical indication (fetal aneuploidy and/or neural tube defect), abnormal analyte results can be utilized for the identification of pregnancies at risk and to direct their clinical management. (II-2B) Further studies are recommended to determine the optimal screening method for poor maternal and/or perinatal outcomes. (III-A).

Opportunity for academic research in a low-gravity environment - Crystal growth

NASA Technical Reports Server (NTRS)

Matthiesen, D. H.; Wargo, M. J.; Witt, A. F.

1986-01-01

The history of basic and applied research on crystal growth (CG), especially of semiconductor materials, is reviewed, stressing the dominance (at least in the U.S.) of industrial R&D projects over academic programs and the need for more extensive fundamental investigations. The NASA microgravity research program and the recommendations of the University Space Research Association are examined as they affect the availability of space facilities for academic CG research. Also included is a report on ground experiments on the effectiveness of magnetic fields in controlling vertical Bridgman CG and melt stability, using the apparatus employed in the Apollo-Soyuz experiments (Witt et al., 1978); the results are presented in graphs and briefly characterized. The role of NASA's microgravity CG program in stimulating academic work on CG, the importance of convection effects, CG work on materials other than semiconductors, and NSF support of CG research are discussed in a comment by R. F. Sekerka.

Sequence analysis of laci mutations obtained from lung cells of radon-exposed big blue{trademark} transgenic mice

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

Layton, A.D.; Cross, F.T.; Steigler, G.L.

1994-12-31

We have exposed Big Blue{trademark} transgenic mice by inhalation to 320, 640 and 960 Working Level Months (WLM) of radon progeny. Mice were sacrificed after 3, 6 and 9 days; the time periods required to obtain the exposures. Control mice were also sacrificed at each time interval. In each case all tissues were excised, flash frozen in liquid nitrogen, and stored at -80{degrees}C for further analysis. Twelve lacI mutations have been isolated from the lung tissue of a mouse from the 960-WLM exposure group; the lacI genes from these mutants have been sequenced. Sequence data indicate that three of themore » mutants have a C;G deletion at BP 978 and are possibly clonal in origin. Two mutants have multiple events within the gene: one has a an A:T to C:G transversion and a C:G insertion separated by 291 BPs; the second has a G:C to A:T transition as well as an A:T deletion followed by 6 base pairs downstream by a T:A insertion. Other mutations include a single G:C to A:T transition, a two base pair deletion, and a C:G to T:A transition. Mutant plaques are being evaluated from individual mice at other dose levels. Time course experiments are also planned. These studies will help define the molecular fine structure of mutations induced by high-LET radiation exposure.« less

[Influence of water fluoride exposure on sex hormone binding globulin and testosterone in adult male].

PubMed

Zhou, Tong; Yang, Rupu; Li, Shihong; Zheng, Guoqing; Xi, Yu; Cheng, Xuemin; Hou, Jiaxiang; Cui, Liuxin; Ba, Yue

2013-03-01

To explore the influence of water fluoride exposure on sex hormone binding globulin (SHBG) and testosterone in adult male. Cross-sectional study was conducted in three villages of Tongxu county including high fluoride group (HFG), defluoridation project group (DFPG) and control group (CG) based on the fluoride concentration in drinking water. Adult male who were born and raised in the village and aged 18 - 50 years old were recruited using cluster sampling. Fasting blood and morning urine samples were collected. The fluoride levels in drinking water and urine were detected by fluoride-ion selective electrode method. Serum SHBG level was determined using enzyme-linked immunosorbent assay (ELISA). The chemical luminescence immune analysis method was used to detect serum testosterone content. Serum SHBG level was 47.85 nmol/L in CG, 31.37 nmol/L in DFPG and 24.52 nmol/L in HFG respectively. There were significant difference among of three groups (P < 0.05). Serum testosterone level was 3.69 ng/ml in CG, 4.61 ng/ml in DFPG and 4.83 ng/ml in HFG respectively. Serum testosterone level in HFG was significantly higher than that in CG (P < 0.05). Serum SHBG level in HFG has positive correlation with serum testosterone (r = 0.230, P = 0.049), which has not been observed in DFPG and CG. Long-time fluorine exposure may affect serum SHBG and testosterone level in adult male.

Glucose Prediction Algorithms from Continuous Monitoring Data: Assessment of Accuracy via Continuous Glucose Error-Grid Analysis.

PubMed

Zanderigo, Francesca; Sparacino, Giovanni; Kovatchev, Boris; Cobelli, Claudio

2007-09-01

The aim of this article was to use continuous glucose error-grid analysis (CG-EGA) to assess the accuracy of two time-series modeling methodologies recently developed to predict glucose levels ahead of time using continuous glucose monitoring (CGM) data. We considered subcutaneous time series of glucose concentration monitored every 3 minutes for 48 hours by the minimally invasive CGM sensor Glucoday® (Menarini Diagnostics, Florence, Italy) in 28 type 1 diabetic volunteers. Two prediction algorithms, based on first-order polynomial and autoregressive (AR) models, respectively, were considered with prediction horizons of 30 and 45 minutes and forgetting factors (ff) of 0.2, 0.5, and 0.8. CG-EGA was used on the predicted profiles to assess their point and dynamic accuracies using original CGM profiles as reference. Continuous glucose error-grid analysis showed that the accuracy of both prediction algorithms is overall very good and that their performance is similar from a clinical point of view. However, the AR model seems preferable for hypoglycemia prevention. CG-EGA also suggests that, irrespective of the time-series model, the use of ff = 0.8 yields the highest accurate readings in all glucose ranges. For the first time, CG-EGA is proposed as a tool to assess clinically relevant performance of a prediction method separately at hypoglycemia, euglycemia, and hyperglycemia. In particular, we have shown that CG-EGA can be helpful in comparing different prediction algorithms, as well as in optimizing their parameters.

Implementing clinical governance in Isfahan hospitals: Barriers and solutions, 2014.

PubMed

Ferdosi, Masoud; Ziyari, Farhad Bahman; Ollahi, Mehran Nemat; Salmani, Amaneh Rahim; Niknam, Noureddin

2016-01-01

In the new approach, all health care providers have been obligated to maintain and improve the quality and have been accountable for it. One of the ways is the implementation of clinical governance (CG). More accurate understanding of its challenges can help to improve its performance. In this study, barriers of CG implementation are investigated from the perspective of the hospitals involved. Besides, some solutions are suggested based on stakeholders' opinions. This study used combined method (qualitative content analysis and questionnaire) in hospitals affiliated to Isfahan University of Medical Sciences in 2014. First, experts, and stakeholders talked about CG implementation obstacles in a semi-structured interview. Interviews were confirmed by the interviewee (double check). After analyzing the interviews using reduction coding the questionnaire was drawn up. The questionnaire "validity was confirmed by Cronbach's alpha (0/891)" and its reliability was obtained using experts confirmation. Data analyzing was performed using SPSS (18) software. According to results staffing and management factors were the main obstacles. After them, were factors related to organizational culture, infrastructure elements, information, sociocultural and then process factors. The learning barriers were in final rank. Thirty-four solutions was proposed by experts and divided into subset of eight major barriers. Most solutions were offered on modifying processes and minimal solutions about modifying of organizational culture, sociocultural, and educational factors. Removing the obstacles, especially management and human resource factors can be effective by facilitating and accelerating CG. Furthermore, use of experts and stakeholders opinions can help to remove CG barriers.

bZIP transcription factor CgAP1 is essential for oxidative stress tolerance and full virulence of the poplar anthracnose fungus Colletotrichum gloeosporioides.

PubMed

Sun, Yingjiao; Wang, Yonglin; Tian, Chengming

2016-10-01

Yeast AP1 transcription factor is a regulator of oxidative stress response. Here, we report the identification and characterization of CgAP1, an ortholog of YAP1 in poplar anthracnose fungus Colletotrichum gloeosporioides. The expression of CgAP1 was highly induced by reactive oxygen species. CgAP1 deletion mutants displayed enhanced sensitivity to oxidative stress compared with the wild-type strain, and their poplar leaf virulence was obviously reduced. However, the mutants exhibited no obvious defects in aerial hyphal growth, conidia production, and appressoria formation. CgAP1::eGFP fusion protein localized to the nucleus after TBH (tert-Butyl hydroperoxide) treatment, suggesting that CgAP1 functions as a redox sensor in C. gloeosporioides. In addition, CgAP1 prevented the accumulation of ROS during early stages of biotrophic growth. CgAP1 also acted as a positive regulator of several ROS-related genes (i.e., Glr1, Hyr1, and Cyt1) involved in the antioxidative response. These results highlight the key regulatory role of CgAP1 transcription factor in oxidative stress response and provide insights into the function of ROS detoxification in virulence of C. gloeosporioides. Copyright © 2016 Elsevier Inc. All rights reserved.

Biochemical markers of trisomy 21 in amniotic fluid.

PubMed

Spencer, K; Muller, F; Aitken, D A

1997-01-01

In a study of amniotic fluid from 91 Down's syndrome cases and 240 controls, we have shown that the median values of four biochemical markers (AFP, total hCG, free beta hCG, and unconjugated oestriol) in the amniotic fluid of pregnancies affected by Down's syndrome on the whole reflect those observed in the maternal serum of affected cases. The median MOM for AFP was lower than average (0.56), as was that for unconjugated oestriol (0.55), whilst those for total hCG (1.82) and free beta hCG (2.10) were increased on average. The width of the distribution of marker levels in amniotic fluid is similar to that in serum for free beta hCG and total hCG but between 1.5 and 2 times wider for unconjugated oestriol and AFP. Analysis of data by fetal sex showed a significantly higher median MOM in female control cases compared with male controls for the analytes free beta hCG, total hCG, and unconjugated oestriol, but not for AFP. Amongst the Down's syndrome cases, this trend was not statistically significant and we cannot confirm a previous study which reported that elevated levels of amniotic fluid total and free beta hCG were associated only with female fetuses.

Molecular Characterization of Voltage-Gated Sodium Channels and Their Relations with Paralytic Shellfish Toxin Bioaccumulation in the Pacific Oyster Crassostrea gigas

PubMed Central

Boullot, Floriane; Castrec, Justine; Bidault, Adeline; Dantas, Natanael; Payton, Laura; Perrigault, Mickael; Tran, Damien; Amzil, Zouher; Boudry, Pierre; Soudant, Philippe; Hégaret, Hélène; Fabioux, Caroline

2017-01-01

Paralytic shellfish toxins (PST) bind to voltage-gated sodium channels (Nav) and block conduction of action potential in excitable cells. This study aimed to (i) characterize Nav sequences in Crassostrea gigas and (ii) investigate a putative relation between Nav and PST-bioaccumulation in oysters. The phylogenetic analysis highlighted two types of Nav in C. gigas: a Nav1 (CgNav1) and a Nav2 (CgNav2) with sequence properties of sodium-selective and sodium/calcium-selective channels, respectively. Three alternative splice transcripts of CgNav1 named A, B and C, were characterized. The expression of CgNav1, analyzed by in situ hybridization, is specific to nervous cells and to structures corresponding to neuromuscular junctions. Real-time PCR analyses showed a strong expression of CgNav1A in the striated muscle while CgNav1B is mainly expressed in visceral ganglia. CgNav1C expression is ubiquitous. The PST binding site (domain II) of CgNav1 variants possess an amino acid Q that could potentially confer a partial saxitoxin (STX)-resistance to the channel. The CgNav1 genotype or alternative splicing would not be the key point determining PST bioaccumulation level in oysters. PMID:28106838

Dual triggering with GnRH agonist plus hCG versus triggering with hCG alone for IVF/ICSI outcome in GnRH antagonist cycles: a systematic review and meta-analysis.

PubMed

Chen, Chi-Huang; Tzeng, Chii-Ruey; Wang, Peng-Hui; Liu, Wei-Min; Chang, Heng-Yu; Chen, Huang-Hui; Chen, Ching-Hui

2018-03-29

To summarize available evidence from randomized-controlled trials which have evaluated triggering of final oocyte maturation with concomitant GnRH agonists and hCG in patients undergoing IVF, and to analyze whether dual triggering is as efficacious as hCG triggering in terms of oocyte and pregnancy outcomes. A comprehensive literature search was performed to identify randomized-controlled trials comparing IVF outcomes between women receiving combined administration of hCG with GnRH agonists and those receiving hCG alone for triggering of final oocyte maturation. Four studies including 527 patients eligible for inclusion in meta-analysis were identified. No significant difference in the number of mature oocytes or fertilized oocytes retrieved was found between groups. Clinical pregnancy rate with dual triggering was significantly higher as compared with hCG-alone triggering (pooled OR = 0.48, 95% CI 0.31-0.77, P = 0.002), but there was no significant difference in the ongoing pregnancy rate between groups. Results of meta-analysis indicate comparable or significantly improved outcomes with the use of GnRH agonists plus hCG as compared with hCG alone for triggering of final oocyte maturation.

Senior managers' viewpoints toward challenges of implementing clinical governance: a national study in iran.

PubMed

Ravaghi, Hamid; Heidarpour, Peigham; Mohseni, Maryam; Rafiei, Sima

2013-11-01

Quality improvement should be assigned as the main mission for healthcare providers. Clinical Governance (CG) is used not only as a strategy focusing on responding to public and government's intolerance of poor healthcare standards, but also it is implemented for quality improvement in a number of countries. This study aims to identify the key contributing factors in the implementation process of CG from the viewpoints of senior managers in curative deputies of Medical Universities in Iran. A quantitative method was applied via a questionnaire distributed to 43 senior managers in curative deputies of Iran Universities of Medical Sciences. Data were analyzed using SPSS. Analysis revealed that a number of items were important in the successful implementation of CG from the senior managers' viewpoints. These items included: knowledge and attitude toward CG, supportive culture, effective communication, teamwork, organizational commitment, and the support given by top managers. Medical staff engagement in CG implementation process, presence of an official position for CG officers, adequate resources, and legal challenges were also regarded as important factors in the implementation process. Knowledge about CG, organizational culture, managerial support, ability to communicate goals and strategies, and the presence of effective structures to support CG, were all related to senior managers' attitude toward CG and ultimately affected the success of quality improvement activities.

Development and evaluation of an automatically adjusting coarse-grained force field for a β-O-4 type lignin from atomistic simulations

NASA Astrophysics Data System (ADS)

Li, Wenzhuo; Zhao, Yingying; Huang, Shuaiyu; Zhang, Song; Zhang, Lin

2017-01-01

This goal of this work was to develop a coarse-grained (CG) model of a β-O-4 type lignin polymer, because of the time consuming process required to achieve equilibrium for its atomistic model. The automatic adjustment method was used to develop the lignin CG model, which enables easy discrimination between chemically-varied polymers. In the process of building the lignin CG model, a sum of n Gaussian functions was obtained by an approximation of the corresponding atomistic potentials derived from a simple Boltzmann inversion of the distributions of the structural parameters. This allowed the establishment of the potential functions of the CG bond stretching and angular bending. To obtain the potential function of the CG dihedral angle, an algorithm similar to a Fourier progression form was employed together with a nonlinear curve-fitting method. The numerical potentials of the nonbonded portion of the lignin CG model were obtained using a potential inversion iterative method derived from the corresponding atomistic nonbonded distributions. The study results showed that the proposed CG model of lignin agreed well with its atomistic model in terms of the distributions of bond lengths, bending angles, dihedral angles and nonbonded distances between the CG beads. The lignin CG model also reproduced the static and dynamic properties of the atomistic model. The results of the comparative evaluation of the two models suggested that the designed lignin CG model was efficient and reliable.

Concomitant use of FSH and low-dose recombinant hCG during the late follicular phase versus conventional controlled ovarian stimulation for intracytoplasmic sperm injection cycles.

PubMed

Iaconelli, Carla Andrade Rebello; Setti, Amanda Souza; Braga, Daniela Paes Almeida Ferreira; Maldonado, Luiz Guilherme Louzada; Iaconelli, Assumpto; Borges, Edson; Aoki, Tsutomu

2017-12-01

The objective of this study was to investigate the effects of low-dose hCG supplementation on ICSI outcomes and controlled ovarian stimulation (COS) cost. Three hundred and thirty patients undergoing ICSI were split into groups according to the COS protocol: (i) control group (n = 178), including patients undergoing conventional COS treatment; and (ii) low-dose hCG group (n = 152), including patients undergoing COS with low-dose hCG supplementation. Lower mean total doses of FSH administered and higher mean oestradiol level and mature oocyte rates were observed in the low-dose hCG group. A significantly higher fertilization rate, high-quality embryo rate and blastocyst formation rate were observed in the low-dose hCG group as compared to the control group. The miscarriage rate was significantly higher in the control group compared to the low-dose hCG group. A significantly lower incidence of OHSS was observed in the low-dose hCG group. There was also a significantly lower gonadotropin cost in the low-dose hCG group as compared to the control group ($1235.0 ± 239.0×$1763.0 ± 405.3, p < 0.001). The concomitant use of low-dose hCG and FSH results in a lower abortion rate and increased number of mature oocytes retrieved, as well as improved oocyte quality, embryo quality and blastocyst formation and reduced FSH requirements.

Hyperglycosylated hCG and Placenta Accreta Spectrum.

PubMed

Einerson, Brett D; Straubhar, Alli; Soisson, Sean; Szczotka, Kathryn; Dodson, Mark K; Silver, Robert M; Soisson, Andrew P

2018-02-28

 We aimed to evaluate the relationship between hyperglycosylated human chorionic gonadotropin (hCG-H) and placenta accreta spectrum (PAS) in the second and third trimesters of pregnancy.  This was a case-control study of PAS and controls. hCG-H was measured in the second and third trimesters of pregnancy in women with pathologically confirmed cases of PAS and in gestational age-matched controls without PAS. We compared serum hCG-H levels in cases and controls, calculated summary statistics for diagnostic accuracy, and used receiver operating characteristic (ROC) curves to define an optimal cut-point for diagnosis of PAS using hCG-H.  Thirty case samples and 30 control samples were evaluated for hCG-H. Mean hCG-H was lower in the case compared with control group (7.8 ± 5.9 μg/L vs. 11.8 ± 8.8 μg/L, p  = 0.03). At an optimal cut-point for hCG-H of ≤7.6 μg/L, the sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and area under the ROC curve were 66.7%, 69.7%, 2.20%, 0.48%, and 0.68%, respectively.  Hyperglycosylated hCG levels in the second and third trimesters of pregnancy were lower in patients with PAS than in controls, but hCG-H showed only modest capability as a diagnostic test for PAS. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Mechanistic insights into the recognition of 5-methylcytosine oxidation derivatives by the SUVH5 SRA domain.

PubMed

Rajakumara, Eerappa; Nakarakanti, Naveen Kumar; Nivya, M Angel; Satish, Mutyala

2016-02-04

5-Methylcytosine (5 mC) is associated with epigenetic gene silencing in mammals and plants. 5 mC is consecutively oxidized to 5-hydroxymethylcytosine (5 hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) by ten-eleven translocation enzymes. We performed binding and structural studies to investigate the molecular basis of the recognition of the 5 mC oxidation derivatives in the context of a CG sequence by the SET- and RING-associated domain (SRA) of the SUVH5 protein (SUVH5 SRA). Using calorimetric measurements, we demonstrate that the SRA domain binds to the hydroxymethylated CG (5hmCG) DNA duplex in a similar manner to methylated CG (5mCG). Interestingly, the SUVH5 SRA domain exhibits weaker affinity towards carboxylated CG (5caCG) and formylated CG (5fCG). We report the 2.6 Å resolution crystal structure of the SUVH5 SRA domain in a complex with fully hydroxymethyl-CG and demonstrate a dual flip-out mechanism, whereby the symmetrical 5hmCs are simultaneously extruded from the partner strands of the DNA duplex and are positioned within the binding pockets of individual SRA domains. The hydroxyl group of 5hmC establishes both intra- and intermolecular interactions in the binding pocket. Collectively, we show that SUVH5 SRA recognizes 5hmC in a similar manner to 5 mC, but exhibits weaker affinity towards 5 hmC oxidation derivatives.

Minimally-aggressive gestational trophoblastic neoplasms.

PubMed

Cole, Laurence A

2012-04-01

We have previously defined a new syndrome "Minimally-aggressive gestational trophoblastic neoplasms" in which choriocarcinoma or persistent hydatidiform mole has a minimal growth rate and becomes chemorefractory. Previously we described a new treatment protocol, waiting for hCG rise to >3000 mIU/ml and disease becomes more advanced, then using combination chemotherapy. Initially we found this treatment successful in 8 of 8 cases, here we find this protocol appropriate in a further 16 cases. Initially we used hyperglycosylated hCG, a limited availability test, to identify this syndrome. Here we propose also using hCG doubling rate to detect this syndrome. Minimally aggressive gestational trophoblastic disease can be detected by chemotherapy resistance or low hyperglycosylated hCG, <40% of total hCG. It can also be identified by hCG doubling rate, with doubling time greater than 2 weeks. Nineteen new cases were identified as having minimally aggressive gestational trophoblastic disease by hyperglycosylated hCG and by hCG doubling test. All were recommended to hold off further chemotherapy until hCG >3000mIU/ml. One case died prior to the start of the study, one case withdrew because of a lung nodule and one withdrew refusing the suggested combination chemotherapy. The remaining 16 women were all successfully treated. A total of 8 plus 16 or 24 of 24 women were successfully treated using the proposed protocol, holding back on chemotherapy until hCG >3000mIU/ml. Copyright © 2011 Elsevier Inc. All rights reserved.

Chromogranin A promotes peptide hormone sorting to mobile granules in constitutively and regulated secreting cells: role of conserved N- and C-terminal peptides.

PubMed

Montero-Hadjadje, Maité; Elias, Salah; Chevalier, Laurence; Benard, Magalie; Tanguy, Yannick; Turquier, Valérie; Galas, Ludovic; Yon, Laurent; Malagon, Maria M; Driouich, Azeddine; Gasman, Stéphane; Anouar, Youssef

2009-05-01

Chromogranin A (CgA) has been proposed to play a major role in the formation of dense-core secretory granules (DCGs) in neuroendocrine cells. Here, we took advantage of unique features of the frog CgA (fCgA) to assess the role of this granin and its potential functional determinants in hormone sorting during DCG biogenesis. Expression of fCgA in the constitutively secreting COS-7 cells induced the formation of mobile vesicular structures, which contained cotransfected peptide hormones. The fCgA and the hormones coexpressed in the newly formed vesicles could be released in a regulated manner. The N- and C-terminal regions of fCgA, which exhibit remarkable sequence conservation with their mammalian counterparts were found to be essential for the formation of the mobile DCG-like structures in COS-7 cells. Expression of fCgA in the corticotrope AtT20 cells increased pro-opiomelanocortin levels in DCGs, whereas the expression of N- and C-terminal deletion mutants provoked retention of the hormone in the Golgi area. Furthermore, fCgA, but not its truncated forms, promoted pro-opiomelanocortin sorting to the regulated secretory pathway. These data demonstrate that CgA has the intrinsic capacity to induce the formation of mobile secretory granules and to promote the sorting and release of peptide hormones. The conserved terminal peptides are instrumental for these activities of CgA.

Medical comorbidity in complicated grief: Results from the HEAL collaborative trial.

PubMed

Robbins-Welty, Gregg; Stahl, Sarah; Zhang, Jun; Anderson, Stewart; Schenker, Yael; Shear, M Katherine; Simon, Naomi M; Zisook, Sidney; Skritskaya, Natalia; Mauro, Christina; Lebowitz, Barry D; Reynolds, Charles F

2018-01-01

To describe medical comorbidity in persons with Complicated Grief (CG) and to test whether medical comorbidity in individuals with CG is associated with the severity and duration of CG, after adjusting for age, sex, race, and current depressive symptoms. In exploratory analyses, we compared data from participants in an NIMH-sponsored multisite clinical trial of CG ("HEAL": "Healing Emotions After Loss") to archival data from participants matched on age, gender, and race/ethnicity, stratified by the presence or absence of current major depression. We used the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) as a measure of medical polymorbidity. We investigated the association between CG and medical comorbidity via multiple linear regression, adjusting for sociodemographic and clinical variables, including severity of depressive symptoms. Chronological age and severity of co-occurring symptoms of major depression correlated with cumulative medical polymorbidity in persons with Complicated Grief. The severity of CG and the time since loss did not correlate with global medical polymorbidity (CIRS-G score). Nor was there an interaction between severity of depressive symptoms and severity of CG symptoms in predicting global CIRS-G score. Cumulative medical comorbidity, as measured by CIRS-G scores, was greater in subjects with current major depression ("DEPRESSED") than in CG subjects, and both DEPRESSED and CG subjects had greater medical morbidity than CONTROLS. Medical comorbidity is prevalent in Complicated Grief, associated with increasing age and co-occurring depressive symptoms but apparently not with chronicity and severity of Complicated Grief per se. This observation suggests that treating depression in the context of CG may be important to managing medical conditions in individuals with Complicated Grief to attenuate or prevent the long-term medical sequelae of CG. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reproductive performance of seasonally anovular mixed-bred dairy goats induced to ovulate with a combination of progesterone and eCG or estradiol.

PubMed

Contreras-Villarreal, Viridiana; Meza-Herrera, César A; Rivas-Muñoz, Raymundo; Angel-Garcia, Oscar; Luna-Orozco, Juan R; Carrillo, Evaristo; Mellado, Miguel; Véliz-Deras, Francisco G

2016-06-01

Adult goats (n = 32) were randomly assigned to one of four treatments (n = 8, each): (i) progesterone (P4 ) + equine chorionic gonadotropin (eCG), treated with 25 mg progesterone intramuscularly (i.m.) + 250 IU eCG 24 h later; (ii) cronolone + eCG, treated with vaginal sponges - 20 mg cronolone × 7 days + 250 IU eCG at pessary removal; (ii) P4 + estradiol (E2 ), treated with 25 mg progesterone i.m. + 1 mg estradiol 24 h later; (iv) cronolone + E2 , treated with vaginal sponges - 20 mg cronolone × 7 days + 1 mg of estradiol i.m. at pessary removal. Goats were tested for estrus throughout the presence of a buck. Seven days prior and after treatment, an ovarian ultrasonographic scanning was performed to determine ovarian function and structures. An ultrasonographic pregnancy diagnosis was performed on day 30 post-service. In all groups, 100% estrus response was observed within 96 h post-treatment. While ovulation occurred in 100% of P4 + eCG and cronolone + eCG treated goats, the other groups only depicted 50% ovulatory activity (P < 0.05). Pregnancy rate was higher (P <0.05) in the P4 + eCG and cronolone + eCG groups (88 and 100%, respectively), compared with 38% in P4 + E2 and cronolone + E2 groups. The best treatments were those in which eCG was applied. The P4 + eCG treatment was a pessary-free, cheaper and effective protocol to induce ovulation in goats during the seasonal anovulatory period. © 2015 Japanese Society of Animal Science.

Concordance between results of somatostatin receptor scintigraphy with 111In-DOTA-DPhe 1-Tyr 3-octreotide and chromogranin A assay in patients with neuroendocrine tumours.

PubMed

Rodrigues, Margarida; Gabriel, Michael; Heute, Dirk; Putzer, Daniel; Griesmacher, Andrea; Virgolini, Irene

2008-10-01

Somatostatin receptor scintigraphy (SRS) and chromogranin A (CgA) assay have successfully been implemented in the clinical work-up and management of neuroendocrine tumour (NET) patients. However, there is still a lack of studies comparing results in these patients. Our aim was to compare directly in NET patients SRS and CgA assay results with special regard to tumour features such as grade of malignancy, primary origin, disease extent and function. One hundred twenty consecutive patients with histological confirmed NETs were investigated with (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide ((111)In-DOTA-TOC) SRS and CgA immunoradiometric assay. Tumours were classified by cell characteristics [well-differentiated NETs, well-differentiated neuroendocrine carcinomas, poorly differentiated neuroendocrine carcinomas (PDNECs)], primary origin (foregut, midgut, hindgut, undetermined), disease extent (limited disease, metastases, primary tumour and metastases) and functionality (secretory, nonsecretory). SRS was positive in 107 (89%) patients; CgA levels were increased in 95 (79%) patients. Overall, concordance between SRS and CgA results was found in 84 patients. Positive SRS but normal CgA level were found in 24 patients, with higher prevalence (p<0.05) in patients with nonsecretory tumours. Conversely, negative SRS but CgA level increased were seen in 12 patients, with higher proportion (p<0.05) in patients with PDNECs and tumours of hindgut origin. Overall, (111)In-DOTA-TOC SRS proved to be more sensitive than CgA in NETs patients. Tumour differentiation, disease extent and presence of liver metastases impact both SRS and CgA results, whereas nonsecretory activity is a negative predictor of only CgA increase. PDNECs and hindgut origin of tumours predispose to discrepancies with negative SRS but increased CgA levels.

Regulation of gonadotropin receptors, gonadotropin responsiveness, and cell multiplication by somatomedin-C and insulin in cultured pig Leydig cells

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

Bernier, M.; Chatelain, P.; Mather, J.P.

1986-11-01

The author have investigated the effects of insulin and somatomedin-C/insulin like growth factor I(Sm-C) in purified porcine Leydig cells in vitro on gonadotrophins (hCG) receptor number, hCG responsiveness (cAMP and testosterone production), and thymidine incorporation into DNA. Leydig cells cultured in a serum-free medium containing transferrin, vitamin E, and insulin (5 ..mu..g/ml) maintained fairly constant both hCG receptors and hCG responsiveness. When they were cultured for 3 days in the same medium without insulin, there was a dramatic decline (more than 80%) in both hCG receptor number and hCG responsiveness. However the cAMP but not the testosterone response to forskolinmore » was normal. Both insulin and Sm-C at nanomolar concentrations prevent the decline of both hCG receptors and hCG-induced cAMP production. At nanomolar concentrations, Sm-C and insulin enhanced hCG-induced testosterone production but the effect of Sm-C was significantly higher than that of insulin. However, the effect of insulin at higher concentrations (5 ..mu..g/ml) was significantly higher than that of Sm-C at 50 ng/ml. In contrast, at nanomolar concentrations only Sm-C stimulated (/sup 3/H)-thymidine incorporation into DNA and cell multiplication, the stimulatory effect of insulin on these parameters, was seen only at micromolar concentrations. These results indicate that both Sm-C and insulin acting through the receptors increase Leydig cell steroidogenic responsiveness to hCG by increasing hCG receptor number and improving some step beyond cAMP formation. In contrast, the mitogenic effects of insulin are mediated only through Sm-C receptors.« less

Evaluation of preventive and therapeutic activity of novel non-steroidal anti-inflammatory drug, CG100649, in colon cancer: Increased expression of TNF-related apoptosis-inducing ligand receptors enhance the apoptotic response to combination treatment with TRAIL.

PubMed

Woo, Jong Kyu; Kang, Ju-Hee; Jang, Yeong-Su; Ro, Seonggu; Cho, Joong Myung; Kim, Hwan-Mook; Lee, Sang-Jin; Oh, Seung Hyun

2015-04-01

Non-steroidal anti-inflammatory drugs (NSAIDs) have been suggested as the potential new class of preventive or therapeutic antitumor agents. The aim of the present study was to evaluate the antitumor activity of the novel NSAID, CG100649. CG100649 is a novel NSAID dual inhibitor for COX-2 and carbonic anhydrase (CA)-I/-II. In the present study, we investigated the alternative mechanism by which CG100649 mediated suppression of the colon cancer growth and development. The anchorage‑dependent and -independent clonogenic assay showed that CG100649 inhibited the clonogenicity of human colon cancer cells. The flow cytometric analysis showed that CG100649 induced the G2/M cell cycle arrest in colon cancer cells. Animal studies showed that CG100649 inhibited the tumor growth in colon cancer xenograft in nude mice. Furthermore, quantitative PCR and FACS analysis demonstrated that CG100649 upregulated the expression of TNF-related apoptosis-inducing ligand (TRAIL) receptors (DR4 and DR5) but decreased the expression of decoy receptors (DcR1 and DcR2) in colon cancer cells. The results showed that CG100649 treatment sensitized TRAIL‑mediated growth suppression and apoptotic cell death. The combination treatment resulted in significant repression of the intestinal polyp formation in APCmin/+ mice. Our data clearly demonstrated that CG100649 contains preventive and therapeutic activity for colon cancer. The present study may be useful for identification of the potential benefit of the NSAID CG100649, for the achievement of a better treatment response in colon cancer.

The B-cell translocation gene 1 (CgBTG1) identified in oyster Crassostrea gigas exhibit multiple functions in immune response.

PubMed

Liu, Rui; Cheng, Qi; Wang, Xiudan; Chen, Hao; Wang, Weilin; Zhang, Huan; Wang, Lingling; Song, Linsheng

2017-02-01

B-cell translocation gene 1 (BTG1) is a member of the anti-proliferative gene family, which plays important roles in regulation of cell cycle. In the present study, a B-cell translocation gene 1 molecule homologue (designed CgBTG1) are identified and characterized in oyster Crassostrea gigas. CgBTG1 contains a conserved BTG domain with Box A and Box B motifs, and it shares high similarities with both BTG1 and BTG2 proteins in vertebrates. CgBTG1 mRNA is predominantly expressed in hemocytes, and its expression level in hemocytes is significantly up-regulated at 6 h (5.40-fold, p < 0.01) post Vibrio splendidus stimulation. The apoptosis rate of oyster hemocytes is significantly decreased (p < 0.05) after CgBTG1 interfered by dsRNA (dsCgBTG1). This is indicated that CgBTG1 participated in the regulation of oyster hemocytes apoptosis. Furthermore, CgBTG1 could also induce the apoptosis of cancer cells (HeLa, A549 and BEL7402) in vitro. Compared with normal oysters, both vessel-like structures and muscle fibers in CgBTG1 interfered oysters are severely damaged after V. splendidus challenge in paraffin section, considering that CgBTG1 possessed an analogous feature of angiogenesis for maintenance of vessel-like structures in adductor muscle of oyster. The results suggests that CgBTG1 is a multi-functional molecule involved in the immune response of C. gigas against pathogen infection, which provides more clues for intensive studies of BTG family proteins in invertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Novel histone deacetylase inhibitor CG200745 induces clonogenic cell death by modulating acetylation of p53 in cancer cells.

PubMed

Oh, Eun-Taex; Park, Moon-Taek; Choi, Bo-Hwa; Ro, Seonggu; Choi, Eun-Kyung; Jeong, Seong-Yun; Park, Heon Joo

2012-04-01

Histone deacetylase (HDAC) plays an important role in cancer onset and progression. Therefore, inhibition of HDAC offers potential as an effective cancer treatment regimen. CG200745, (E)-N(1)-(3-(dimethylamino)propyl)-N(8)-hydroxy-2-((naphthalene-1-loxy)methyl)oct-2-enediamide, is a novel HDAC inhibitor presently undergoing a phase I clinical trial. Enhancement of p53 acetylation by HDAC inhibitors induces cell cycle arrest, differentiation, and apoptosis in cancer cells. The purpose of the present study was to investigate the role of p53 acetylation in the cancer cell death caused by CG200745. CG200745-induced clonogenic cell death was 2-fold greater in RKO cells expressing wild-type p53 than in p53-deficient RC10.1 cells. CG200745 treatment was also cytotoxic to PC-3 human prostate cancer cells, which express wild-type p53. CG200745 increased acetylation of p53 lysine residues K320, K373, and K382. CG200745 induced the accumulation of p53, promoted p53-dependent transactivation, and enhanced the expression of MDM2 and p21(Waf1/Cip1) proteins, which are encoded by p53 target genes. An examination of CG200745 effects on p53 acetylation using cells transfected with various p53 mutants showed that cells expressing p53 K382R mutants were significantly resistant to CG200745-induced clonogenic cell death compared with wild-type p53 cells. Moreover, p53 transactivation in response to CG200745 was suppressed in all cells carrying mutant forms of p53, especially K382R. Taken together, these results suggest that acetylation of p53 at K382 plays an important role in CG200745-induced p53 transactivation and clonogenic cell death.

Docking and free energy simulations to predict conformational domains involved in hCG-LH receptor interactions using recombinant antibodies.

PubMed

Majumdar, Ritankar; Railkar, Reema; Dighe, Rajan R

2011-11-01

Single chain fragment variables (ScFvs) have been extensively employed in studying the protein-protein interactions. ScFvs derived from phage display libraries have an additional advantage of being generated against a native antigen, circumventing loss of information on conformational epitopes. In the present study, an attempt has been made to elucidate human chorionic gonadotropin (hCG)-luteinizing hormone (LH) receptor interactions by using a neutral and two inhibitory ScFvs against hCG. The objective was to dock a computationally derived model of these ScFvs onto the crystal structure of hCG and understand the differential roles of the mapped epitopes in hCG-LH receptor interactions. An anti-hCG ScFv, whose epitope was mapped previously using biochemical tools, served as the positive control for assessing the quality of docking analysis. To evaluate the role of specific side chains at the hCG-ScFv interface, binding free energy as well as residue interaction energies of complexes in solution were calculated using molecular mechanics Poisson-Boltzmann/surface area method after performing the molecular dynamic simulations on the selected hCG-ScFv models and validated using biochemical and SPR analysis. The robustness of these calculations was demonstrated by comparing the theoretically determined binding energies with the experimentally obtained kinetic parameters for hCG-ScFv complexes. Superimposition of hCG-ScFv model onto a model of hCG complexed with the 51-266 residues of LH receptor revealed importance of the residues previously thought to be unimportant for hormone binding and response. This analysis provides an alternate tool for understanding the structure-function analysis of ligand-receptor interactions. Copyright © 2011 Wiley-Liss, Inc.

[Risk-benefit analysis of a hCG-500 kcal reducing diet (cura romana) in females].

PubMed

Rabe, T; Richter, S; Kiesel, L; Runnebaum, B

1987-05-01

The British physician A.T.W. Simeons described in 1954 a new method for dieting. He combined a reduction diet (500 kcal per day) with daily injections of the pregnancy hormone human chorionic gonadotropin (hCG) (125 IU i.m.). According to Simeons the patient should not lose more weight during a 4-to-6 weeks' diet than without hCG, but the injections should facilitate to maintain the diet and to lose body weight at specific parts of the body (e.g. hip, belly, thigh). After the first publication various studies conducted with male and female patients analysed the efficacy of the "Cura romana". 10 of these studies showed positive and another 10 studies negative results with regard to hCG-related weight reduction. Two of these studies with positive results were double-blind studies (hCG vs. placebo). Most of them were reports on therapeutical experiences and were not controlled studies. According to these reports the body proportions normalized and the feeling of hunger was tolerable. Four out of 10 studies with negative results were controlled studies (hCG vs. control without hCG), whereas 6 were double-blind studies. These studies showed a significant weight reduction during dieting, but no differences between treatment groups in respect of body weight, body proportions and feeling of hunger. One of them is the only German study conducted by Rabe et al. in 1981 in which 82 randomised premenopausal volunteers had been dieting either with hCG or without hCG injections. In recent publications describing mostly well-documented double-blind studies authors largely reject hCG administration in dieting. Supporters of the hCG diet must prove the efficacy of this method in controlled studies according to the German Drug Law. Until then the opinion of the German steroid toxicology panel is still valid, that hCG is ineffective in dieting and should not be used (Bolt 1982 a, 1982 b).

Sliding scale HCG trigger yields equivalent pregnancy outcomes and reduces ovarian hyperstimulation syndrome: Analysis of 10,427 IVF-ICSI cycles.

PubMed

Gunnala, Vinay; Melnick, Alexis; Irani, Mohamad; Reichman, David; Schattman, Glenn; Davis, Owen; Rosenwaks, Zev

2017-01-01

To evaluate pregnancy outcomes and the incidence of ovarian hyperstimulation syndrome (OHSS) using a sliding scale hCG protocol to trigger oocyte maturity and establish a threshold level of serum b-hCG associated with optimal oocyte maturity. Retrospective cohort. Academic medical center. Fresh IVF cycles from 9/2004-12/2011. 10,427 fresh IVF-ICSI cycles met inclusion criteria. hCG was administered according to E2 level at trigger: 10,000IU vs. 5,000IU vs. 4,000IU vs. 3,300IU vs. dual trigger (2mg leuprolide acetate + 1,500IU hCG). Serum absorption of hCG was assessed according to dose and BMI. Oocyte maturity was analyzed according to post-trigger serum b-hCG. Fertilization, clinical pregnancy, live birth and OHSS rates were examined by hCG trigger dose. Post-trigger serum b-hCG 20-30, 30-40, and 40-50 mIU/mL was associated with reduced oocyte maturity as compared b-hCG >50 (67.8% vs. 71.4% vs. 73.3% vs. 78.9%, respectively, P<0.05). b-hCG 20-50 mIU/mL was associated with a 40.1% reduction in live birth (OR 0.59, 95% CI 0.41-0.87). No differences in IVF outcomes per retrieval were seen for varying doses of hCG or dual trigger when controlling for patient age. The incidence of moderate to severe OHSS was 0.13% (n = 14) and severe OHSS was 0.03% (n = 4) of cycles. Moderate stimulation with sliding scale hCG at trigger and fresh transfer is associated with low rates of OHSS and favorable pregnancy rates. Doses as low as 3,300IU alone or dual trigger with 1,500IU are sufficient to facilitate oocyte maturity.

Topographic antigenic determinants recognized by monoclonal antibodies on human choriogonadotropin beta-subunit

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

Bidart, J.M.; Troalen, F.; Salesse, R.

1987-06-25

We describe a first attempt to study the antibody-combining sites recognized by monoclonal antibodies raised against the beta-subunit of human choriogonadotropin (hCG). Two groups of antibodies were first defined by their ability to recognize only the free beta-subunit or the free and combined subunit. Antibodies FBT-11 and FBT-11-L bind only to hCG beta-subunit but not to hCG, whereas antibodies FBT-10 and D1E8 bind to both the beta-subunit and the hormone. In both cases, the antigenic determinants were localized to the core of the protein (residues 1-112), indicating the weak immunogenicity of the specific carboxyl-terminal extension of hCG-beta. Nine synthetic peptidesmore » spanning different regions of hCG-beta and lutropin-beta were assessed for their capacity to inhibit antibody binding. A synthetic peptide inclusive of the NH2-terminal region (residues 1-7) of the hCG beta-subunit was found to inhibit binding to the radiolabeled subunit of a monoclonal antibody specific for free hCG-beta (FBT-11). Further delineation of the antigenic site recognized by this antibody provided evidence for the involvement of fragment 82-92. Moreover, monoclonal antibody FBT-11 inhibited the recombination of hCG-beta to hCG-alpha, indicating that its antigenic determinant might be located nearby or in the hCG-beta portion interacting with the alpha-subunit. Binding of monoclonal antibody FBT-10, corresponding to the second antigenic determinant, was weakly inhibited by fragment 82-105 and did not impair the recombination of the hCG beta-subunit to the hCG alpha-subunit. Its combining site appeared to be located in a region of the intact native choriogonadotropin present at the surface of the hormone-receptor complex.« less

Sliding scale HCG trigger yields equivalent pregnancy outcomes and reduces ovarian hyperstimulation syndrome: Analysis of 10,427 IVF-ICSI cycles

PubMed Central

Schattman, Glenn; Davis, Owen; Rosenwaks, Zev

2017-01-01

Objective To evaluate pregnancy outcomes and the incidence of ovarian hyperstimulation syndrome (OHSS) using a sliding scale hCG protocol to trigger oocyte maturity and establish a threshold level of serum b-hCG associated with optimal oocyte maturity. Design Retrospective cohort. Setting Academic medical center. Patients Fresh IVF cycles from 9/2004–12/2011. Intervention 10,427 fresh IVF-ICSI cycles met inclusion criteria. hCG was administered according to E2 level at trigger: 10,000IU vs. 5,000IU vs. 4,000IU vs. 3,300IU vs. dual trigger (2mg leuprolide acetate + 1,500IU hCG). Serum absorption of hCG was assessed according to dose and BMI. Main outcome measures Oocyte maturity was analyzed according to post-trigger serum b-hCG. Fertilization, clinical pregnancy, live birth and OHSS rates were examined by hCG trigger dose. Results Post-trigger serum b-hCG 20–30, 30–40, and 40–50 mIU/mL was associated with reduced oocyte maturity as compared b-hCG >50 (67.8% vs. 71.4% vs. 73.3% vs. 78.9%, respectively, P<0.05). b-hCG 20–50 mIU/mL was associated with a 40.1% reduction in live birth (OR 0.59, 95% CI 0.41–0.87). No differences in IVF outcomes per retrieval were seen for varying doses of hCG or dual trigger when controlling for patient age. The incidence of moderate to severe OHSS was 0.13% (n = 14) and severe OHSS was 0.03% (n = 4) of cycles. Conclusions Moderate stimulation with sliding scale hCG at trigger and fresh transfer is associated with low rates of OHSS and favorable pregnancy rates. Doses as low as 3,300IU alone or dual trigger with 1,500IU are sufficient to facilitate oocyte maturity. PMID:28441461

Lowered reference limits for hCG improve follow-up of patients with hCG-producing tumors.

PubMed

Nome, Ragnhild V; Bjøro, Trine; Paus, Elisabeth; Bjerner, Johan; Fosså, Sophie D; Steen, Rita; Nustad, Kjell; Bolstad, Nils

2018-02-01

Human Chorionic Gonadotropin (hCG) is produced by germ cell tumors, but can also be elevated in benign conditions such as primary hypogonadism, where hCG is produced by the pituitary gland. In our experience, the reference limits for hCG (Elecsys hCG+β-assay, Roche Diagnostics), were unnecessarily high and did not reflect levels encountered in clinical practice. We wanted to establish new reference limits to increase the clinical utility of the hCG-assay. We analysed hCG in serum samples from a healthy adult population and in a cohort of testicular cancer survivors. The gonadotropins LH and FSH were measured in the cohort and in a selection of the reference population to assess gonadal function. We found low hCG levels for all men and women <45years (97.5 percentiles 0.1 and 0.2IU/L, respectively) from the healthy population (n=795) having normal FSH and LH. Due to assay limitations, we suggest a common reference limit of <0.3IU/L. For the age group ≥45, the 97.5 percentiles in the healthy population were 0.5IU/L for men and 6.0IU/L for women. In all subjects from both the reference population and the cohort (n=732), hCG levels exceeding the reference limit could be fully explained by reduced gonadal function indicated by elevated LH and FSH levels. The Elecsys hCG+β-assay should have lower reference limits than recommended by the manufacturer, with important implications for tumor follow-up. Elevated hCG is rare with intact gonadal function, both in a normal population and among survivors of testicular cancer, and should lead to further investigations when encountered in clinical practice. Copyright © 2017 Oslo University Hospital. Published by Elsevier Inc. All rights reserved.

Expression of the dopaminergic D1 and D2 receptors in the anterior cingulate cortex in a model of neuropathic pain

PubMed Central

2011-01-01

Background The anterior cingulate cortex (ACC) has been related to the affective component of pain. Dopaminergic mesocortical circuits, including the ACC, are able to inhibit neuropathic nociception measured as autotomy behaviour. We determined the changes in dopamine D1 and D2 (D1R and D2R) receptor expression in the ACC (cg1 and cg2) in an animal model of neuropathic pain. The neuropathic group had noxious heat applied in the right hind paw followed 30 min. later by right sciatic denervation. Autotomy score (AS) was recorded for eight days and subsequently classified in low, medium and high AS groups. The control consisted of naïve animals. A semiquantitative RT-PCR procedure was done to determine mRNA levels for D1R and D2R in cg1 and cg2, and protein levels were measured by Western Blot. Results The results of D1R mRNA in cg1 showed a decrease in all groups. D2R mRNA levels in cg1 decreased in low AS and increased in medium and high AS. Regarding D1R in cg2, there was an increase in all groups. D2R expression levels in cg2 decreased in all groups. In cg1, the D2R mRNA correlated positively with autotomy behaviour. Protein levels of D2R in cg1 increased in all groups but to a higher degree in low AS. In cg2 D2R protein only decreased discretely. D1R protein was not found in either ACC region. Conclusions This is the first evidence of an increase of inhibitory dopaminergic receptor (D2R) mRNA and protein in cg1 in correlation with nociceptive behaviour in a neuropathic model of pain in the rat. PMID:22171983

Predictive value of modeled AUC(AFP-hCG), a dynamic kinetic parameter characterizing serum tumor marker decline in patients with nonseminomatous germ cell tumor.

PubMed

You, Benoit; Fronton, Ludivine; Boyle, Helen; Droz, Jean-Pierre; Girard, Pascal; Tranchand, Brigitte; Ribba, Benjamin; Tod, Michel; Chabaud, Sylvie; Coquelin, Henri; Fléchon, Aude

2010-08-01

The early decline profile of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) in patients with nonseminomatous germ cell tumors (NSGCT) treated with chemotherapy may be related to the risk of relapse. We assessed the predictive values of areas under the curve of hCG (AUC(hCG)) and AFP (AUC(AFP)) of modeled concentration-time equations on progression-free survival (PFS). Single-center retrospective analysis of hCG and AFP time-points from 65 patients with IGCCCG intermediate-poor risk NSGCT treated with 4 cycles of bleomycin-etoposide-cisplatin (BEP). To determine AUC(hCG) and AUC(AFP) for D0-D42, AUCs for D0-D7 were calculated using the trapezoid rule and AUCs for D7-D42 were calculated using the mathematic integrals of equations modeled with NONMEM. Combining AUC(AFP) and AUC(hCG) enabled us to define 2 predictive groups: namely, patients with favorable and unfavorable AUC(AFP-hCG). Survival analyses and ROC curves assessed the predictive values of AUC(AFP-hCG) groups regarding progression-free survival (PFS) and compared them with those of half-life (HL) and time-to-normalization (TTN). Mono-exponential models best fit the patterns of marker decreases. Patients with a favorable AUC(AFP-hCG) had a significantly better PFS (100% vs 71.5%, P = .014). ROC curves confirmed the encouraging predictive accuracy of AUC(AFP-hCG) against HL or TTN regarding progression risk (ROC AUCs = 79.6 vs 71.9 and 70.2 respectively). Because of the large number of patients with missing data, multivariate analysis could not be performed. AUC(AFP-hCG) is a dynamic parameter characterizing tumor marker decline in patients with NSGCT during BEP treatment. Its value as a promising predictive factor should be validated. Copyright 2010 Elsevier Inc. All rights reserved.

"Hook-like effect" causes false-negative point-of-care urine pregnancy testing in emergency patients.

PubMed

Griffey, Richard T; Trent, Caleb J; Bavolek, Rebecca A; Keeperman, Jacob B; Sampson, Christopher; Poirier, Robert F

2013-01-01

Failure to detect pregnancy in the emergency department (ED) can have important consequences. Urine human chorionic gonadotropin (uhCG) point-of-care (POC) assays are valued for rapidly detecting early pregnancy with high sensitivity. However, under certain conditions, POC uhCG tests can fail to detect pregnancy. In investigating a series of late first-trimester false-negative pregnancy tests in our ED, a novel and distinct causative phenomenon was recently elucidated in our institution. We discuss uhCG POC tests, review our false-negative rate, and describe mechanisms for false negatives and potential remedies. The false-negative POC uhCG rate is very low, but in the setting of a large volume of tests, the numbers are worth consideration. In positive uhCG POC tests, free and fixed antibodies bind hCG to form a "sandwich"; hCG is present in several variant forms that change in their concentrations at different stages of pregnancy. When in excess, intact hCG can saturate the antibodies, preventing sandwich formation (hook effect phenomenon). Some assays may include an antibody that does not recognize certain variants present in later stages of pregnancy. When this variant is in excess, it can bind one antibody avidly and the other not at all, resulting in a false-negative test (hook-like phenomenon). In both situations, dilution is key to an accurate test. Manufacturers should consider that uhCG tests are routinely used at many stages of pregnancy. Characterizing uhCG variants recognized by their tests and eliminating lot-to-lot variability may help improve uhCG test performance. Clinicians need to be aware of and familiarize themselves with the limitations of the specific type of uhCG POC tests used in their practice, recognizing that under certain circumstances, false-negative tests can occur. Copyright © 2013 Elsevier Inc. All rights reserved.

A novel junctional adhesion molecule A (CgJAM-A-L) from oyster (Crassostrea gigas) functions as pattern recognition receptor and opsonin.

PubMed

Liu, Conghui; Wang, Mengqiang; Jiang, Shuai; Wang, Lingling; Chen, Hao; Liu, Zhaoqun; Qiu, Limei; Song, Linsheng

2016-02-01

Junctional adhesion molecule (JAM), a subfamily of immunoglobulin superfamily (IgSF) with a couple of immunoglobulin domains, can act as regulator in homeostasis and inflammation of vertebrates. In the present study, a structural homolog of JAM-A (designated CgJAM-A-L) was screened out from oyster, Crassostrea gigas, through a search of JAM-A D1 domain (N-terminal Ig domain in JAM-A). The cDNA of CgJAM-A-L was of 1188 bp encoding a predicted polypeptide of 395 amino acids. The immunoreactive area of CgJAM-A-L mainly distributed over the plasma membrane of hemocytes. After Vibro splendidus or tumor necrosis factor (CgTNF-1) stimulation, the mRNA transcripts of CgJAM-A-L in hemocytes increased significantly by 4.46-fold and 9.00-fold (p < 0.01) of those in control group, respectively. The recombinant CgJAM-A-L protein (rCgJAM-A-L) could bind multiple PAMPs including lipopolysaccharides (LPS), peptidoglycan (PGN), lipoteichoic acid (LTA), mannose (MAN), β-glucan (GLU) and poly(I:C), and various microorganisms including Micrococcus luteus, Staphylococcus aureus, Escherichia coli, Vibro anguillarum, V. splendidus, Pastoris pastoris and Yarrowia lipolytica. The phagocytic rates of oyster hemocytes towards Gram-negative bacteria V. anguillarum and yeast P. pastoris were significantly enhanced after the incubation of rCgJAM-A-L, and even increased more significantly after the pre-incubation of rCgJAM-A-L with microbes (p < 0.01). The results collectively indicated that CgJAM-A-L functioned as an important pattern recognition receptor (PRR) and opsonin in the immune defense against invading pathogen in oyster. Moreover, as the most primitive specie with homolog of JAMs, the information of CgJAM-A-L in oyster would provide useful clues for the evolutionary study of JAMs and immunoglobulins. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regulation of the CgPdr1 Transcription Factor from the Pathogen Candida glabrata ▿

PubMed Central

Paul, Sanjoy; Schmidt, Jennifer A.; Moye-Rowley, W. Scott

2011-01-01

Candida glabrata is an opportunistic human pathogen that is increasingly associated with candidemia, owing in part to the intrinsic and acquired high tolerance the organism exhibits for the important clinical antifungal drug fluconazole. This elevated fluconazole resistance often develops through gain-of-function mutations in the zinc cluster-containing transcriptional regulator C. glabrata Pdr1 (CgPdr1). CgPdr1 induces the expression of an ATP-binding cassette (ABC) transporter-encoding gene, CgCDR1. Saccharomyces cerevisiae has two CgPdr1 homologues called ScPdr1 and ScPdr3. These factors control the expression of an ABC transporter-encoding gene called ScPDR5, which encodes a homologue of CgCDR1. Loss of the mitochondrial genome (ρ0 cell) or overexpression of the mitochondrial enzyme ScPsd1 induces ScPDR5 expression in a strictly ScPdr3-dependent fashion. ScPdr3 requires the presence of a transcriptional Mediator subunit called Gal11 (Med15) to fully induce ScPDR5 transcription in response to ρ0 signaling. ScPdr1 does not respond to either ρ0 signals or ScPsd1 overproduction. In this study, we employed transcriptional fusions between CgPdr1 target promoters, like CgCDR1, to demonstrate that CgPdr1 stimulates gene expression via binding to elements called pleiotropic drug response elements (PDREs). Deletion mapping and electrophoretic mobility shift assays demonstrated that a single PDRE in the CgCDR1 promoter was capable of supporting ρ0-induced gene expression. Removal of one of the two ScGal11 homologues from C. glabrata caused a major defect in drug-induced expression of CgCDR1 but had a quantitatively minor effect on ρ0-stimulated transcription. These data demonstrate that CgPdr1 appears to combine features of ScPdr1 and ScPdr3 to produce a transcription factor with chimeric regulatory properties. PMID:21131438

Pharmacokinetics and pharmacodynamics of human chorionic gonadotropin (hCG) after rectal administration of hollow-type suppositories containing hCG.

PubMed

Kowari, Kouji; Hirosawa, Iori; Kurai, Hirono; Utoguchi, Naoki; Fujii, Makiko; Watanabe, Yoshiteru

2002-05-01

To determine the effectiveness of human chorionic gonadotropin (hCG) administered rectally, we studied the pharmacokinetics and pharmacodynamics of hCG using a hollow-type suppository. HCG was not detected in plasma when only hCG was administered rectally, even at a higher dose (4,000 IU/kg body weight) than intravenous injection, because of its low bioavailability due to high molecular weight or degradation by proteolytic activity. To enhance the rectal absorption of hCG, the effectiveness of its coadministration with alpha-cyclodextrin (alpha-CyD), an absorption-enhancing agent, was investigated in male rabbits. HCG was detected in plasma following coadministration of hCG and alpha-CyD (10 mg/kg body weight) into the rectum. The plasma hCG concentration increased with increasing dose of alpha-CyD. The AUC(0-48) observed after coadministration of hCG and alpha-CyD at 30 mg/kg body weight was approximately four times higher than that of hCG and alpha-CyD at 10mg/kg body weight. HCG at a high concentration induced a rapid increase in the plasma testosterone concentration (74.2 +/- 3.4 ng/ml) 2 h after intravenous administration. However, the testosterone concentration 24 h after intravenous administration decreased to the physiological level (approximately 20 ng/ml) which had been observed before such administration. On the other hand, the maximum level of testosterone concentration (40.0 +/- 12.6 ng/ml) was observed 24 h after rectal administration of hCG (400 IU/kg body weight) in combination with alpha-CyD (30 mg/kg body weight). Moreover, the plasma testosterone concentration (31.0 +/- 11.4 ng/ml) obtained 72 h after rectal administration tended to be maintained at a higher level than that (14.4 +/- 0.9ng/ml) observed before the administration. These results suggest that the hollow-type suppository as a rectal delivery system of hCG is promising as a new mode of hCG therapy.

Hydrodynamic properties of the gonadotropin receptor from a murine Leydig tumor cell line are altered by desensitization

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

Rebois, R.V.; Bradley, R.M.; Titlow, C.C.

1987-10-06

The murine Leydig tumor cell line 1 (MLTC-1) contains gonadotropin receptors (GR) that are coupled to adenylate cyclase through the stimulatory guanine nucleotide binding protein (G/sub s/). The binding of human choriogonadotropin (hGC) causes MLTC-1 cells to accumulate cAMP. With time, the ability of MLTC-1 cells to respond to hCG is attenuated by a process called desensitization. The hydrodynamic properties of GR from control and desensitized MLTC-1 cells were studied. Sucrose density gradient sedimentation in H/sub 2/O and D/sub 2/O and gel filtration chromatography were used to estimate the Stokes radius (a), partial specific volume (v/sub c/), sedimentation coefficient (s/submore » 20,w/), and molecular weight (M/sub r/) of the detergent-solubilized hormone-receptor complex (hCG-GR). (/sup 125/I)hCG was bound to MLTC-1 cells under conditions that allow (37/sup 0/C) or prevent (0/sup 0/C) desensitization, and hCG-GR was solubilized in Triton X-100. In the absence of desensitization, control hCG-GR had a M/sub r/ of 213,000, whereas desensitized hCG-GR had a M/sub r/ of 158,000. Deglycosylated hCG (DG-HCG) is an antagonist that binds to GR with high affinity but fails to stimulate adenylate cyclase or cause desensitization. (/sup 125/I)DG-hCG was bound to MLTC-1 cells and DG-hCG-GR solubilized in Triton X-100. The hydrodynamic properties of DG-hCG-GR were the same as that for control hCG-GR. There was no evidence for the association of adenylate cyclase or G/sub s/ with GR in Triton X-100 solubilized preparations. When hCG was cross-linked to GR and solubilized with sodium dodecyl sulfate (SDS), the M/sub r/ was found to be 116,000, which was similar to that determined by SDS-polyacrylamide gel electrophoresis and less than that of the Triton X-100 solubilized control hCG-GR.« less