cssi/SciSciGPT-SciSciNet huggingface dataset:
New Insights into the Molecular Basis of T Cell Anergy: Anergy Factors, Avoidance Sensors, and Epigenetic Imprinting

The vertebrate immune system has evolved to deal with invasive pathogens, but this adaptation comes at the expense of immunopathology. Among a number of mechanisms that coevolved to control adaptive immunity is anergy, the functional inactivation of T lymphocytes that respond to Ag in the absence of inflammation. In this review, I highlight a series of intracellular proteins in quiescent T cells that function to integrate signals from Ag, costimulatory, and growth factor receptors. These factors ensure that cells that fail to engage all three pathways are shunted into an alternative transcriptional program designed to dissuade them from participating in subsequent immune responses. Recent studies indicate that anergy is the combined result of factors that negatively regulate proximal TCR-coupled signal transduction, together with a program of active transcriptional silencing that is reinforced through epigenetic mechanisms.
Acrosin Inhibitors as Vaginal Contraceptives in the Primate and their Acute Toxicity

The contraceptive activity of Delfen vaginal cream in the stumptailed macaque (macaca arctoides) tends to be enhanced by the addition of p-nitrophenyl-p’-guanidino benzoate (NPGB. 9 mg/ ml) but not by N-o-p-tosyl-L-lysine chloromethylketone (TLCK, 3 mg/mI). Both compounds are synthetic inhibitors of acrosin, a sperm proteinase involved in the union of the male and female gametes. The addition of NPGB (0.09 mg/mI) to K-Y jelly made this neutral suppository equally or slightly more effective than Delfen vaginal cream. The addition of TLCK (3 mg/mI) or antipain (0.9 mg/mI), a naturally occurring inhibitor of acrosin, did not cause K-V jelly to have contraceptive activity but 10 mg/mI TLCK did. The inhibitors had little or no effect on the postcoital motility of the spermatozoa, did not influence the length of pregnancy and had no toxic effects in the primates. NPGB and 2 other low molecular weight acrosin inhibitors, aminobenzamidine and benzamidine, were evaluated for acute toxicity by intraperitoneal injection into mice. The 3 compounds had LD50 values of 180, 240 and 580 mg/kg BW, respectively. Thus, the toxic dose of these compounds is 1,000-10,000 times greater than the concentration at which they exert antifertility activity. The results encourage the continued development and evaluation of acrosin inhibitors as contraceptive agents for human use.
Application of Continuous Automatic Colorimetry in Medical Research

A recent development of interest in analytical instrumentation provides a system for the continuous automatic determination of a wide variety of biochemically important compounds by colorimetry. The system is controlled by a multichannel, peristaltic proportioning pump which accurately delivers fixed volume ratios of samples and reagents to other components. Purification or separation of the constituent to be analyzed is effected by continuous dialysis and, after appropriate chemical treatment, optical density is measured in a ratio-recording dual beam colorimeter fitted with a flow curette. The system can analyze different samples on a continuous basis or monitor changes in a continuous sample stream. Operations require a minimum of technical attendance. The system has application in many areas of medical research: routine determination of classical clinical constituents for diagnosis and treatment; study of chemical pharmacology in vivo and in vitro; biochemical aspects of proteins, amino acids, and enzymes; organ and tissue perusal studies in physiology; microbial metabolism and assay; screening of experimental pharmacodynamic agents. The design and operation of the instrument system will be treated in general terms and the application and results in the aforementioned fields of research will be discussed. Economies in time and financial expenditure will be summarily noted.
Light as a reinforcer of pecking in tube-fed leghorn chicks

Chicks maintained in dim light developed high peck rates for 10 sec. of bright light on a CRF schedule. Controls given 10 sec. of bright light arbitrarily every 15 min. pecked reliably less.
Liposomes in drug delivery: Progress and limitations

Liposomes are microparticulate lipoidal vesicles which are under extensive investigation as drug carriers for improving the delivery of therapeutic agents. Due to new developments in liposome technology, several liposome-based drug formulations are currently in clinical trial, and recently some of them have been approved for clinical use. Reformulation of drugs in liposomes has provided an opportunity to enhance the therapeutic indices of various agents mainly through alteration in their biodistribution. This review discusses the potential applications of liposomes in drug delivery with examples of formulations approved for clinical use, and the problems associated with further exploitation of this drug delivery system.
Self-Affine Fractal Characterization of a TNT Fracture Surface

A trinitrotoluene (TNT) fracture surface image is characterized in terms of a self-affine fractal structure. The fracture surface was produced by high acceleration in an ultracentrifuge when the TNT strength was exceeded. An atomic force microscope (AFM) captured the topography of a 4 micron square region on the fracture surface. The present analysis supports a self-affine description of the TNT fracture surface (wavelengths of 0.016 micron to 4.0 micron) and provides a new prespective on fracture processes in TNT. An essential step in self-affine fractal characterization of surfaces is the determination of reference surfaces. A self-affine fracture surface can be described in terms of a single-valued height function. In the TNT fracture surface, single-valued height functions, which describe surface texture can only be defined with respect to curved reference surfaces. By employing curved reference surfaces, we have demonstrated that self-affine fractal scaling can be used to characterize the TNT fracture surface. This provides important information that is not evident in the analysis of individual surface scans.
Analysis of electromagnetic scattering from a cavity with a complex termination by means of a hybrid ray-FDTD method

The electromagnetic modeling of engine cavities is a very difficult task because the electrical size of the cavity is very large, while the engine termination is geometrically complex. High-frequency techniques can adequately model the cavity, but perform poorly when applied to the termination. Low-frequency techniques are currently infeasible for such large geometries because of the large memory and computation time requirements. The authors present a hybrid method which combines the most attractive features of the lowand high-frequency techniques. The finite-difference time-domain (FDTD) method is applied to the small region surrounding the termination. The remainder of the cavity is modeled with ray methods. To validate this method, they consider two-dimensional cavities with complex terminations. Their results are compared against those found from a hybrid combination of the modal method and the method of moments. >
The Effect of Processing on the Nitrogen Distribution in Milk

Summary 1.Semimicro methods have been described and used to study the N distribution in milk. These methods are efficient, well adapted to routine analyses and results compare very favorably with those obtained by the Official Methods. 2.The homogenization of milk at normal and abnormal pressures produced no significant changes in the N distribution. 3.The coagulation of albumin and globulin was the most significant change that occurred in the N distribution of evaporated milk. There is evidence to indicate that some hydrolysis of the proteins takes place in this milk as a result of the processing. 4.Condensing skim milk produced only minor changes in the N distribution of the product. 5.The addition of Steapsin, Trypsin and Enzylac to milk at a temperature of 145° F. for 30 minutes produced definite hydrolysis of the milk proteins. 6.Pasteurization of milk at 145° F. for 30 minutes produced no significant changes in N distribution.
Toughening Behavior of a Two‐Dimensional SiC/SiC Woven Composite at Ambient Temperature: II, Stress‐Displacement Relationship in the Crack Process Zone

In this paper insight into the origin of the JR-curve of a SiC/SiC woven composite was obtained by experimental characterization of the closure stress-crack opening displacement, sigma(u), relationship in the process zone of the crack. This process zone included both a crack frontal zone and a crack wake damage zone so that quantitative estimates could be obtained of the magnitudes of toughening associated with these two separate zones. The research indicated that the closure stress-crack opening displacement curve has a positive slope in the crack frontal zone and a negative slope in the wake zone with a maximum stress capability on the order of 350 MPa. The toughness contributions from the crack wake and from the crack front were consistent with the JR-curve results obtained in the previous paper. The stresses supported locally in the crack frontal zone were almost twice as large as those supported by tensile specimens even though this zone was considerably damaged by matrix cracks. This appears to be the result of stabilization of matrix cracks by arrest at fiber bundles. Application of a previously derived theoretical function, sigmab(u), solely based on crack bridging by continuous unidirectional fibers, suggested that the efficacy of bridging in the woven composite may in part be related to the woven fiber architecture. Such an architecture apparently induces greater sliding resistance of the SiC bundles against the surrounding SiC matrix.
Analysis of a mathematical model for transport of 131I-albumin

Abstract The hypotheses and results given are motivated by the study of the distribution of albumin in man which represents a class of delay-differential systems. The approach used is to study the behavior of the solutions of nonlinear delay-differential systems with variable coefficients under the assumptions of continuity and boundedness of coefficients. The criterions are conditions on the roots of a certain “quasi-polynomial”, i.e., a polynomial in a variable and exponential of that variable. These criterions bear a resemblance to the ones in the case of constant coefficients and retardations and are applicable to this case also. The method is based on Lyapunov type functional with appropriate properties.
Concise Review: Personalized Human Bone Grafts for Reconstructing Head and Face

Regeneration of normal shape, architecture, and function of craniofacial tissues following congenital abnormality, trauma, or surgical treatment presents special problems to tissue engineering. Because of the great variations in properties of these tissues, currently available treatment options fall short of adequate care. We propose that the engineering of personalized bone graft customized to the patient and the specific clinical condition would revolutionize the way we currently treat craniofacial defects and discuss some of the current and emerging treatment modalities.
Assessing reliability of microsatellite genotypes from kit fox faecal samples using genetic and GIS analyses

Noninvasive faecal DNA sampling has the potential to provide a wealth of information necessary for monitoring and managing endangered species while eliminating the need to capture, handle or observe rare individuals. However, scoring problems, and subsequent genotyping errors, associated with this monitoring method remain a great concern as they can lead to misidentification of individuals and biased estimates. We examined a kit fox scat data set (353 scats; 80 genotypes) for genotyping errors using both genetic and GIS analyses, and evaluated the feasibility of combining both approaches to assess reliability of the faecal DNA results. We further checked the appropriateness of using faecal genotypes to study kit fox populations by describing information about foxes that we could deduce from the 'acceptable' scat genotypes, and comparing it to information gathered with traditional field techniques. Overall, genetic tests indicated that our data set had a low rate of genotyping error. Furthermore, examination of distributions of scat locations confirmed our data set was relatively error free. We found that analysing information on sex primer consistency and scat locations provided a useful assessment of scat genotype error, and greatly limited the amount of additional laboratory work that was needed to identify potentially 'false' scores. 'Acceptable' scat genotypes revealed information on sex ratio, relatedness, fox movement patterns, latrine use, and size of home range. Results from genetic and field data were consistent, supporting the conclusion that our data set had a very low rate of genotyping error and that this noninvasive method is a reliable approach for monitoring kit foxes.
Methods for a Life-Span Developmental Approach to Women in the Middle Years

The central thesis of this chapter1 is that the study of women in midlife can be enriched if it is placed in a change-oriented, life-span framework. This message is conveyed by the title of this book—Women in Midlife—which places middle age in the context of the life span. The book’s title also conveys a message about the current state of the field of life-span human development. Until recently, researchers have focused primarily on the young and the old. Thus, there is a gap in our knowledge about the middle of the life-span. This neglect of the middle years is particularly true with regard to the study of women, but the situation is slowly being rectified (see Baruch, Barnett, and Rivers, 1983; Eichorn, Clausen, Haan, Honzik, and Mussen, 1981; Giele, 1982; Lowenthal, Thurnher, and Chiriboga, 1975; Rossi, 1980; Rubin, 1979; Stewart and Platt, 1982; as well as this volume).
Crystal Structure of the Simian Virus 40 Large T-Antigen Origin-Binding Domain

The origins of replication of DNA tumor viruses have a highly conserved feature, namely, multiple binding sites for their respective initiator proteins arranged as inverted repeats. In the 1.45-A crystal structure of the simian virus 40 large T-antigen (T-ag) origin-binding domain (obd) reported herein, T-ag obd monomers form a left-handed spiral with an inner channel of 30 A having six monomers per turn. The inner surface of the spiral is positively charged and includes residues known to bind DNA. Residues implicated in hexamerization of full-length T-ag are located at the interface between adjacent T-ag obd monomers. These data provide a high-resolution model of the hexamer of origin-binding domains observed in electron microscopy studies and allow the obd's to be oriented relative to the hexamer of T-ag helicase domains to which they are connected.
Three-body recombination with mixed sign light particles

Using a classical trajectory Monte Carlo method, we have computed the threebody recombination (two free positrons and an anti-proton scattering into one free positron and an anti-hydrogen atom: e + +e + + ¯ p → ¯ H+e + ) in the presence of electrons. By simply reversing the sign of all of the particles, these results can be applied to three-body recombination of matter in the presence of positrons. An important parameter is the fraction of light particles which are of the opposite sign; we performed calculations for several values of this parameter and find a substantial effect even for small fractions. We have also included a strong magnetic field in the calculation since this seems the most likely way to have mixed sign light particles in the same region of space. Our results will be useful for future anti-hydrogen experiments. We identify the main mechanisms controlling the recombination process.
Low cost AM/AM and AM/PM distortion measurement using distortion-to-amplitude transformations

Amplitude-to-amplitude (AM-AM) and amplitude-to-phase (AM-PM) distortion are two significant effects in power amplifiers at high output power levels. Traditional measurement of amplitude and phase distortion in RF power amplifiers requires the use of expensive vector network analyzers (VNAs). This paper proposes a low cost and accurate test methodology for AM-AM and AM-PM measurement using distortion-to-amplitude conversion using simple load board test circuitry along with the use of hardware and software based difference generation and peak detection mechanisms. It is seen that both distortion effects can be measured with high accuracy while allowing significant reduction in test cost.
Cytologic Analysis of Papillary Renal Cell Carcinoma

BACKGROUND The papillary variant of renal cell carcinoma has distinctive pathologic and clinical features. Because the prognosis of patients with papillary renal cell carcinoma differs from that of patients with other variants of renal cell carcinoma, accurate diagnosis based on cytologic material may be important for appropriate clinical disease management. METHODS A retrospective analysis of cytologic material from 17 papillary renal cell carcinomas and 52 other renal neoplasms with histologic follow-up was performed to identify the relative sensitivity and specificity of different cytologic criteria for papillary carcinoma. RESULTS Foamy macrophages and intracytoplasmic hemosiderin were the most sensitive and most specific criteria for the diagnosis of papillary renal cell carcinoma. Foamy macrophages were present in 14 of 17 cases (82%), and intracytoplasmic hemosiderin was present in 13 of 17 cases (76%). Foamy macrophages and intracellular hemosiderin were each present in only 2 of 52 (4%) of nonpapillary tumors examined. Malignant cells were arranged in papillary groups with fibrovascular cores in only 6 of 17 cases (35%), including only 1 of 7 high grade tumors. Nuclear grooves were present in 9 of 17 cases (53%) but were common in only 2 cases. Psammoma bodies were present in only 1 case. Nucleoli and pleomorphism were prominent in high grade tumors. These features, in association with frequent abundant vacuolated cytoplasm, made it difficult to distinguish high grade papillary carcinoma from the clear cell variant of renal cell carcinoma. However, as with low grade tumors, the presence of intracytoplasmic hemosiderin and foamy macrophages were important clues to the diagnosis of 6 of 7 high grade tumors (86%). CONCLUSIONS Intracytoplasmic hemosiderin and foamy macrophages are the most sensitive and specific markers for both high and low grade papillary renal cell carcinoma, and they allow for the correct diagnosis in most cases. Cancer (Cancer Cytopathol) 1998;84:303-308. © 1998 American Cancer Society.
Evolution in the practice of primary angioplasty: effect of adjunctive coronary stenting and glycoprotein IIb/IIIa inhibitors on long-term outcomes.

Primary angioplasty strategies have evolved dramatically, including increasing adjunctive use of stents and glycoprotein (GP) IIb/IIIa inhibitors. The purpose of this study was to examine the specific effects of these adjunctive therapies on long-term outcomes after primary angioplasty. From 1996 to 1998, 257 unselected, consecutive patients underwent primary PTCI at our institution. In-hospital mortality was 5.4% (2.9% for patients without cardiogenic shock). The remaining 243 patients were followed for 2.0 ± 0.7 years. Adjunctive stenting was associated with increased late mortality (8.7% vs. 2.3%, P = 0.02). GP IIb/IIIa inhibitors were associated with reduced late mortality among patients receiving stents (6.9% vs. 21.4%, P = 0.07), but not in those patients treated with balloon angioplasty alone (2.9% vs. 0%, P > 0.20). Coronary stenting remained a significant predictor of late mortality (hazard ratio 5.6, 95% CI 1.5–21.2) after adjustment for other established risk factors. In this unselected series, adjunctive coronary stenting was associated with higher late mortality among hospital discharge survivors. Concomitant GP IIb/IIIa inhibitors partially corrected for this increase. These results are limited by the small sample size and retrospective design of this study. Additional long-term studies are required to test these findings and evaluate for possible mechanisms. Cathet Cardiovasc Intervent 2001;54:327–332. © 2001 Wiley-Liss, Inc.
Adaptive Optical Sensing in an Object Tracking DDDAS

The generalized optical remote sensing tracking problem for an object moving in a dynamic urban environment is complex. Two emerging capabilities that can help solve this problem are adaptive multimodal sensing and modeling with data assimilation. Adaptive multimodal sensing describes sensor hardware systems that can be rapidly reconfigured to collect the appropriate data as needed. Imaging of a moving target implies some ability to forecast where to image next so as to keep the object in the scene. Forecasts require models and to help solve this prediction problem, data assimilation techniques can be applied to update executing models with sensor data and thereby dynamically minimize forecast errors. The direct combination of these two capabilities is powerful but does not answer the questions of how or when to change the imaging modality. The Dynamic DataDriven Applications Systems (DDDAS) paradigm is well-suited for solving this problem, where sensing must be adaptive to a complex changing environment and where the prediction of object movement and its interaction with the environment will enhance the ability of the sensing system to stay focused on the object of interest. Here we described our work on the creation of a modeling system for optical tracking in complex environments, with a focus on integrating an adaptive imaging sensor within the system framework.
Nonholonomic path planning of space robots via a bidirectional approach

The path planning of nonholonomic motion of space robot systems is discussed. A space vehicle with a 6-DOF (degrees of freedom) manipulator is described as a nine-variable system with six inputs. It is shown that, by carefully utilizing the nonholonomic mechanical structure, the vehicle orientation in addition to the joint variables of the manipulator can be controlled by actuating only the joint variables. The nonholonomic mechanical structure of space robot systems is shown. A rigorous mathematical proof of the nonholonomic nature of the free-flying space robot systems is provided using Frobenius's theorem. A method for nonholonomic motion planning for space robot systems is established by using a Lyapunov function. >
A technique for delineating defects in silicon

A decoration and etching technique was developed to delineate several types of defects in silicon wafers, slugs and slabs. The technique was originally developed to detect interstitial type (A) defects but it has proved highly effective in decorating all kinds of other defects. Being fast, and requiring no special equipment except an inexpensive muffle furnace and a dedicated etch bench the technique has quickly become an integral part of our characterization portfolio. We discuss below how we have used this technique and its advantages over other methods used to detect A- defects.
Reconsidering Self Care

In light of diminishing resources in service settings, and the subsequent high risk for worker burnout, self care remains an important vehicle for promoting worker well-being. However, traditional definitions of self care are based in formulations about the nature of the self that don’t reflect paradigmatic shifts in social work practice that place increased emphasis on the multiplicity of workers’ selves, use of self and a collaborative frame for the worker–client relationship. Thus, a reconsidered definition of self care is proposed that reflects intersubjective, relational, and recovery-oriented frames for practice and posits strategies for self care that make the self appear.
Psychological screening in the surgical treatment of lumbar disc herniation.

Abstract:The specific use of psychological screenings to determine appropriateness for lumbar discectomy surgery and predict outcomes is not well understood. Data from spine surgery as a whole are not likely generalizable to the patient with a significant disc herniation considering surgery. As oppo
Susceptibility of Syrian Hamster (Cricetus auratus) to Viruses of St. Louis and Japanese B Encephalitis

ConclusionsThe Syrian hamster (Cricetus auratus) is highly susceptible to cerebral infection with the viruses of St. Louis and of Japanese B encephalitis and should prove valuable in certain types of investigation where the use of mice or monkeys is not feasible. Both viruses easily propagate in the brain of this host and attain a titer comparable to that achieved in mouse-brain.
P4.079 Sexual Behaviors and Safety Strategies of Women Who Have Sex with Men and Women

Background Women who have sex with women and men (WSWM) are at an increased risk for STI. Yet, knowledge regarding the behaviours associated with infection remains limited, with most studies focused on the experiences of women who have sex with only men or women. The diversity of sexual behaviours WSWM engage in may be limited by comparing WSWM to other groups. Instead, focusing on their experiences exclusively may provide a more comprehensive understanding of the sexual lives of WSWM. Methods Local (Indianapolis, IN, US) women who had engaged in recent genital contact with a male and female partner were invited to complete an on-line survey followed by an interview. Participants were asked to indicate the most recent time they had participated in a variety of behaviours with a male and/or female partner. Results Eighty participants ranging in age from 18 to 51 (M = 26.74, SD = 7.97) completed the survey. The most commonly reported sexual behaviours were similar for male and female partners, including kissing, cuddling, external genital rubbing, vaginal fingering, cunnilingus/fellatio and penile-vaginal intercourse. While less commonly reported, a sizable minority of participants reported vaginal fisting, anal fingering and analingus. Toy use was reported by the majority of the participants with vibrator use reported as the most commonly used toy. Approximately 75% of participants indicated sexual behaviour with more than one person at one time. The percentage of participants who reported barrier use varied by behaviour and partner gender with the lowest percentage of participants reporting use during oral sex or genital-on-genital rubbing with a female partner (> 90% never) and the highest percentage reporting use during penile-vaginal intercourse (> 25% always). Conclusion Participants reported engaging in a variety of sexual behaviours that may facilitate STI transmission. Further knowledge about the types of behaviours WSWM engage in may help inform risk reduction strategies.
Restoration of β-galactosidase to Escherichia coli M15. Complementation studies

Carboxymethylated beta-galactosidase from Escherichia coli was dissociated at 100 degrees C to form carboxymethylated fragments A and B. The mol.wts. of carboxymethylated fragments A and B were determined by gel filtration to be 64300 and 22400 respectively. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of carboxymethylated fragments A and B that had been pretreated with 2-mercaptoethanol and sodium dodecyl sulphate yielded mol.wts. of 64000 and 22100 respectively. Carboxymethylated fragments A and B had arginine as their C-terminal amino acid. When a crude extract of E. coli M15 was filtered through a column of Sepharose 6B, it was found that carboxymethylated fragment B could restore beta-galactosidase activity when added to fractions having mol.wts. estimated to be 123000, 262000 and 506000. These fractions are referred to as ;complementable fractions'. Similarly, it was found that carboxymethylated fragment A could restore enzyme activity to tractions having mol.wts. estimated to be 63000, 253000 and 506000. Estimates of the molecular weights of the beta-galactosidase activity obtained by restoration with carboxymethylated fragments A and B were made by filtering the active enzyme through another column of Sepharose 6B. The enzyme obtained by complementation with carboxymethylated fragment B, i.e. the complemented enzyme, had mol.wt. 525000, and that obtained with carboxymethylated fragment A had mol.wts. of 525000, 646000 and 2000000. The latter finding suggests that multiple forms of complemented beta-galactosidase can exist.
Improving Power Density of Free-Piston Stirling Engines

Analyses and experiments demonstrate the potential benefits of optimizing piston and displacer motion in a free-piston Stirling Engine. Isothermal analysis shows the theoretical limits of power density improvement due to ideal motion in ideal Stirling engines. More realistic models based on nodal analysis show that ideal piston and displacer waveforms are not optimal, often producing less power than engines that use sinusoidal piston and displacer motion. Constrained optimization using nodal analysis predicts that Stirling engine power density can be increased by as much as 58 percent using optimized higher harmonic piston and displacer motion. An experiment is conducted in which an engine designed for sinusoidal motion is forced to operate with both second and third harmonics, resulting in a piston power increase of as much as 14 percent. Analytical predictions are compared to experimental data and show close agreement with indirect thermodynamic power calculations, but poor agreement with direct electrical power measurements.
Arguments with Peers: Negotiating the Past in the Present

How do youth2 produce and negotiate the meanings of the past when interacting within their generation? What discourses about the past do they draw on in order to construct their positioning vis-a-vis their peers? How is the past used to construct their identities as youth? In this chapter, we explore youth-centered interactions to capture a glimpse of peer-to-peer discursive processes of transmission of the recent past. This allows us to focus on youth as cultural agents in the process of transmitting the recent past.
Influence of Study Design on Developmental and Reproductive Toxicology Study Outcomes.

Regulatory studies of developmental and reproductive toxicity (DART) studies have remained largely unchanged for decades, with exposures occurring at various phases of the reproductive cycle and toxicity evaluations at different ages/times depending on the study purpose. The National Toxicology Program has conducted studies examining the power to detect adverse effects where there is a prenatal exposure, but evaluations occur postnatally. In these studies, examination is required of only 1 male and female pup from each litter beyond weaning. This provides poor resolving power to detect rare events (e.g., reproductive tract malformations). If an adverse effect is detected, there is little confidence in the shape of the dose–response curve (and the Benchmark Dose or No Observed Adverse Effect Level [NOAEL]). We have developed a new protocol to evaluate DART, the modified one generation study, with exposure commencing with pregnant animals and retention of 4 males and females from each litter beyond weaning ...
Photolysis of 2,4,6-trinitrotoluene in seawater and estuary water: Impact of pH, temperature, salinity, and dissolved organic matter.

Abstract The influence of salinity, pH, temperature, and dissolved organic matter on the photolysis rate of 2,4,6-trinitrotoluene (TNT) in marine, estuary, and laboratory-prepared waters was studied using a Suntest CPS +® solar simulator equipped with optical filters. TNT degradation rates were determined using HPLC analysis, and products were identified using LC/MS. Minimal or no TNT photolysis occurred under a 395-nm long pass filter, but under a 295-nm filter, first-order TNT degradation rate constants and apparent quantum yields increased with increasing salinity in both natural and artificial seawater. TNT rate constants increased slightly with increasing temperature (10 to 32 °C) but did not change significantly with pH (6.4 to 8.1). The addition of dissolved organic matter (up to 5 mg/L) to ultrapure water, artificial seawater, and natural seawater increased the TNT photolysis rate constant. Products formed by TNT photolysis in natural seawater were determined to be 2,4,6-trinitrobenzaldehyde, 1,3,5-trinitrobenzene, 2,4,6-trinitrobenzoic acid, and 2-amino-4,6-dinitrobenzoic acid.
Rapid shift in substrate utilization driven by hypothalamic Agrp neurons

Agrp neurons drive feeding. To what extend these neurons participate in the regulation of other homeostatic processes is not well understood. We investigated the role of Agrp neurons in substrate utilization in mice. Activation of Agrp neurons was sufficient to rapidly increase RER and carbohydrate utilization, while decreasing fat utilization. These metabolic changes were linearly correlated with carbohydrates ingested, but not protein or fat ingestion. However, even in the absence of ingestive behaviors, activation of Agrp neurons led to changes in substrate utilization in well-fed mice. These effects were coupled to metabolic shifts towards lipogenesis. Inhibition of fatty acid synthetase (FAS) blunted the effects of Agrp neurons on substrate utilization. Finally, Agrp neurons controlled peripheral metabolism, but not food intake, via β3-adrenergic receptor signaling in fat tissues. These results reveal a novel component of Agrp neuron-mediate metabolism regulation that involves sympathetic activity on fat compartments to shift metabolism towards lipogenesis.
Gene–Environment Interaction in the Behavioral Sciences: Findings, Challenges, and Prospects

We review gene × environment interaction (G×E) research in behavioral and psychiatric genetics. Two approaches to G×E are contrasted: a latent-variable approach that seeks to determine whether the heritability of a behavioral outcome varies by environmental exposure, and a candidate-gene × environment approach that seeks to determine whether genotypes are differentially sensitive to environmental conditions. Three major challenges to current G×E research are identified: (1) most published G×E findings are based on small samples and thus a high proportion are likely to be false-positive reports; (2) imprecision in the assessment of the phenotype, environment, and the genotype can significantly attenuate the power of a G×E study; and (3) a G×E is not an inherent property of the organism but rather a feature of a statistical model and so its identification depends on the structure of that model. The promise of genomic medicine is that interventions can be tailored to individual treatments, a form of G×E. Nonetheless, there is currently limited evidence of gene × intervention interactions in behavioral and psychiatric genetics. Future gene × intervention research will benefit from what we have learned from earlier G×E research and especially the need for large samples and the standardization of assessments to enable pooling of data across multiple studies.
Hybrid cathode catalyst with synergistic effect between carbon composite catalyst and Pt for ultra-low Pt loading in PEMFCs

Abstract Due to the high cost of Pt catalyst, reducing the amount of Pt in electrodes is one of the primary issues in polymer electrolyte membrane fuel cells. In this study, the hybrid cathode catalyst using the electrochemically active carbon composite catalyst and Pt catalyst is developed in order to reduce the amount of Pt and increase the overall catalytic performance. The carbon composite catalyst (CCC) is synthesized by pyrolysis of Fe-Co chelate compound followed by acid leaching. The current density of Pt/CCC is 1.5–6-fold higher than that of Pt/CB when employing ultra-low Pt loading (0.04 mgPt cm−2). It is found that the Pt/CCC with the ultra-low Pt loading at tuned operating conditions exhibits a higher fuel cell performance than the Pt/CB and commercial Pt/C with four times higher Pt loading (0.16 mgPt cm−2). The extensive activity of Pt/CCC is ascribed to the synergistic effect through (1) the combined activity of catalytic sites present in the CCC support and Pt, (2) the well-distributed nanoparticles and (3) the increased metallic Pt0 concentration which indicated that the pyridinic-N played a role of oxide-cleanser.
Impact of recombination on the base composition of Bacteria and Archaea

The mutational process in bacteria is biased toward A and T, and most species are GC-rich relative to the mutational input to their genome. It has been proposed that the shift in base composition is an adaptive process-that natural selection operates to increase GC-contents-and there is experimental evidence that bacterial strains with GC-rich versions of genes have higher growth rates than those strains with AT-rich versions expressing identical proteins. Alternatively, a nonadaptive process, GC-biased gene conversion (gBGC), could also increase the GC-content of DNA due to the mechanistic bias of gene conversion events during recombination. To determine what role recombination plays in the base composition of bacterial genomes, we compared the spectrum of nucleotide polymorphisms introduced by recombination in all microbial species represented by large numbers of sequenced strains. We found that recombinant alleles are consistently biased toward A and T, and that the magnitude of AT-bias introduced by recombination is similar to that of mutations. These results indicate that recombination alone, without the intervention of selection, is unlikely to counteract the AT-enrichment of bacterial genomes.
Acetaminophen Toxicity: Novel Insights Into Mechanisms and Future Perspectives

Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the US, and decades of intense study of its pathogenesis resulted in the development of the antidote N-acetylcysteine, which facilitates scavenging of the reactive metabolite and is the only treatment in clinical use. However, the narrow therapeutic window of this intervention necessitates a better understanding of the intricacies of APAP-induced liver injury for the development of additional therapeutic approaches that can benefit late-presenting patients. More recent investigations into APAP hepatotoxicity have established the critical role of mitochondrial dysfunction in mediating liver injury as well as clarified mechanisms of APAP-induced hepatocyte cell death. Thus, it is now established that mitochondrial oxidative and nitrosative stress is a key mechanistic feature involved in downstream signaling after APAP overdose. The identification of specific mediators of necrotic cell death further establishes the regulated nature of APAP-induced hepatocyte cell death. In addition, the discovery of the role of mitochondrial dynamics and autophagy in APAP-induced liver injury provides additional insight into the elaborate cell signaling mechanisms involved in the pathogenesis of this important clinical problem. In spite of these new insights into the mechanisms of liver injury, significant controversy still exists on the role of innate immunity in APAP-induced hepatotoxicity.
Estimating the Cost of Providing Foundational Public Health Services

Objective To estimate the cost of resources required to implement a set of Foundational Public Health Services (FPHS) as recommended by the Institute of Medicine. Study design A stochastic simulation model was used to generate probability distributions of input and output costs across 11 FPHS domains. We used an implementation attainment scale to estimate costs of fully implementing FPHS. Data collection/extraction methods We use data collected from a diverse cohort of 19 public health agencies located in three states that implemented the FPHS cost estimation methodology in their agencies during 2014-2015. Principal findings The average agency incurred costs of $48 per capita implementing FPHS at their current attainment levels with a coefficient of variation (CV) of 16 percent. Achieving full FPHS implementation would require $82 per capita (CV=19 percent), indicating an estimated resource gap of $34 per capita. Conclusions Substantial variation in costs exists across communities in resources currently devoted to implementing FPHS, with even larger variation in resources needed for full attainment. Reducing geographic inequities in FPHS may require novel financing mechanisms and delivery models that allow health agencies to have robust roles within the health system and realize a minimum package of public health services for the nation.
Characteristics of corneal xenograft rejection in a discordant species combination.

PURPOSE To characterize the fate of Lewis rat corneas transplanted to Hartley guinea pigs. METHODS Full-thickness Lewis rat corneal buttons were grafted orthotopically to Hartley guinea pigs (xenografts), ACI rats (allografts), or Lewis rats (isografts). Two panels of recipients were presensitized with xenogeneic skin grafts or allogeneic skin grafts. Serum samples were collected pre- and post-transplant and analyzed by flow cytometry and indirect immunofluorescence. RESULTS Unlike vascularized xenografts that reject within 30 min, corneal xenografts had a mean survival time of 8 days. Presensitization with guinea pig skin grafts increased recipient IgM and IgG xenoantibody levels, as measured by flow cytometry on guinea pig hematopoietic cells, and significantly accelerated corneal xenograft rejection with a mean survival time of 5 days. Presensitization with allogeneic ACI skin grafts had no effect on xenoantibody levels or xenogeneic corneal graft survival. Guinea pig corneas stained by indirect immunofluorescence with normal rat serum exhibited low (1+) but significant binding of IgG and IgM, primarily on epithelium and stroma. Serum from Lewis rats that rejected a corneal xenograft had elevated IgG and IgM xenoantibodies that reacted strongly (4+) with guinea pig cornea and heart. CONCLUSIONS In the discordant guinea pig-to-rat species combination, donor corneas express xenoantigens; rejection of corneal xenografts stimulates IgM and IgG xenoantibody production; sensitization to xenoantigens can accelerate corneal xenograft rejection; and discordant corneal xenografts, unlike vascularized organs, are not hyperacutely rejected.
The effects of exercise on transdiagnostic treatment targets: A meta-analytic review.

Abstract Background The present study meta-analytically reviewed the effects of exercise on four transdiagnostic treatment targets: anxiety sensitivity (AS), distress tolerance (DT), stress reactivity (SR), and general self-efficacy (GSE). Methods We conducted systematic searches of peer-reviewed studies in bibliographical databases (Cochrane Library, psychINFO, PubMed) before April 1, 2018. Only randomized controlled trials (RCT) evaluating the effect of exercise on AS, DT, SR, or GSE using at least one validated outcome instrument in a sample of adolescents (≥13 years old) or adults were selected. We employed a meta-analysis of effects using random-effects pooling modeling for each treatment target. Results The systematic search yielded 28 RCTs meeting eligibility criteria. Exercise interventions had a large effect on reducing AS (six studies, Hedges's g = 0.72, p = .001), a medium effect on increasing GSE (eight studies, Hedges's g = 0.59, p Conclusions This meta-analysis provides preliminary evidence exercise can engage certain transdiagnostic targets. Further research is required to optimize exercise intervention parameters to achieve the strongest effects on these important mechanistic variables.
A role for peripheral GDNF signaling in ischemic myalgia development

Abstract Group III/IV muscle afferents transduce nociceptive signals and modulate exercise pressor reflexes (EPR). However, the mechanisms governing afferent responsiveness to dually modulate these processes are not well characterized. Peripheral ischemia/reperfusion (I/R) injury provides an opportunity to study both processes simultaneously. We recently showed that ischemic injury induced increased pain-related behaviors and exacerbated EPRs in the same mice. After I/R, ischemic-myalgia-like behaviors correlated with primary muscle afferent sensitization and increased expression of glial cell line-derived neurotrophic factor (GDNF) in injured muscle and increased expression of GDNF family receptor α1 (GFRα1) in DRGs. Here we report that increased GDNF/GFRα1 signaling to sensory neurons from I/R affected muscle modulated pain-related behaviors, increased EPRs, and group III/IV muscle afferent sensitization. This appeared to have taken effect through increased CREB/CREB-binding protein (CBP) mediated expression of the purinergic receptor P2X5 in the DRGs. Inhibition of GFRα1, P2X5, or CREB/CBP signaling each inhibited the development of pain-related behaviors and altered EPRs post I/R. Anti-GDNF antibodies injected into affected muscle also successfully prevented development of observed ischemic-myalgia-like behaviors. Muscle GDNF signaling to neurons may play an important dual role in nociception and sympathetic reflexes and could provide a novel therapeutic target for treating complications from I/R injuries.
Quality and quantity: The association of state-level educational policies with later life cardiovascular disease.

Abstract Education is a powerful predictor of cardiovascular morbidity and mortality. While the majority of the literature has focused on years of educational attainment or degree attainment, fewer studies examine the role of educational quality in the prevention of cardiovascular disease (CVD). We tested the hypothesis that average state-level educational quality was associated with CVD, linking state-level data on educational quality with individual demographic and health data from multiple waves of the National Health and Nutrition Examination Survey (N = 34,770). We examined thirteen CVD-related outcomes—including blood pressure, cholesterol, and heart attack—to understand the multiple pathways through which educational quality may influence CVD. The primary predictor was a composite index of educational quality, combining state-level measures of student-teacher ratios, per-pupil expenditures, and school term length. We fit multivariable models, regressing each outcome on the educational quality composite index and adjusting for individual- and state-level covariates. We also assessed whether the association between state educational quality and CVD differed for less educated individuals. Overall, higher educational quality was associated with less smoking (OR = 0.86, 95%CI: 0.77, 0.97), but there was no statistically significant association for the other 12 outcomes. Interaction tests indicated that less educated individuals benefited less from higher educational quality relative to those with more education for several outcomes. Our study suggests that state-level educational quality is not strongly associated with CVD, and that this null association overall may mask heterogeneous benefits that accrue disproportionately to those with higher levels of education.