cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract B17: ADGRB3 is a novel tumor suppressor epigenetically silenced in WNT medulloblastoma

Medulloblastoma (MB) is the most aggressive primary malignant brain tumor in children and arises from neural progenitor cells in the developing cerebellum. Although some subtypes of MB show a favorable prognosis with treatment, still one third of patients succumb to this disease and the children who survive suffer from long-term side effects of the aggressive treatments. ADGRB3 (formerly called BAI3) is a member of the ADGRB1-3 subfamily of adhesion GPCR transmembrane proteins, which are highly expressed in the brain specially in cerebellum and hippocampal neurons. The ADGRB3 gene was recently found to undergo somatic mutations in several cancers, but nothing is known about the functional role of ADGRB3 in medulloblastoma. Our recent findings based on analysis of a published microarray dataset and RT-PCR experiments showed that ADGRB3 mRNA expression was selectively repressed in WNT-MB tumor tissue compared to other three molecular subgroups and normal human cerebellar tissue. Using bisulfite sequencing we have detected hypermethylation of the ADGRB3 promoter exclusively in WNT-MB subgroup of human MB tissue but not in the other three molecular subgroups and normal human cerebellar tissue. These results clearly indicate that ADGRB3 is epigenetically silenced in WNT-MB via promoter hypermethylation. In vitro experiments showed that restoration of ADGRB3 expression in ADGRB3-silenced MB cell lines slows cell growth and inhibits WNT signaling targets. We further analyzed whether methyl CpG binding proteins and histone modifications modulate transcriptional repression of ADGRB3 in WNT-MB. ChIP assays revealed enrichment of repressive MBD2 protein in the ADGRB3 promoter region. siRNA mediated knockdown of ADGRB3 in ADGRB3-silent MB cell line (UW288-1) was found to reactivate ADGRB3 expression. We found that in vitro treatment with KCC-07, a recently discovered MBD2 inhibitor, reactivates ADGRB3 mRNA expression in ADGRB3-silent but not expressing MB cells. We are currently investigating whether ADGRB3 can negatively regulate the WNT/beta-catenin pathway or acts via an independent pathway that synergizes with it to facilitate transformation. Altogether, our findings define an epigenetic mechanism for ADGRB3 silencing in WNT-MB and indicate a novel role of ADGRB3 as a potent suppressor of oncogenic cerebellar transformation. Our findings also highlight the potential of epigenetic reactivation of ADGRB3 as a less toxic therapeutic intervention for the children suffering from WNT-MB. Citation Format: Debanjan Bhattacharya, Dan Zhu, Narra Devi, Erwin G. Van Meir. ADGRB3 is a novel tumor suppressor epigenetically silenced in WNT medulloblastoma [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr B17.
Sex-Based Predictors of Male and Female Property Crime Arrest Rates: Disadvantage and Drug Use

A large body of research has considered the relationship between crime and structural indicators. However, despite trends in the gender gap in offending, fewer studies have separately examined the ...
Cultures of anyone: studies on cultural democratization in the Spanish neoliberal crisis

In many respects, the economic crisis that began in Spain in 2008 – also known as, simply, la crisis – is still not over. Despite the mild recovery of the Spanish economy and a dip in unemployment ...
52. MICROAGGRESSIONS IN ROTATION EVALUATIONS BY RESIDENTS

Background There seems to be an increasing sense of hostility or harshness in comments of rotation evaluations submitted by residents. There seems to be an emergence of microaggressions and even hostile comments recently. Millennials are now the largest generation in the US labor force and the prevalent generation of medical learners. This generation grew up in a digital world where expressing their opinion as online comments was the norm. When comments are anonymous, they are more likely to be uncivil, and the lack accountability contributes to writing simplistic evaluations of complicated issues. Microaggressions are “brief and commonplace verbal, behavioral, and environmental indignities, whether intentional or unintentional, that communicate hostile, derogatory, or negative...slights and insults.” Similar to online comments are online evaluations completed by residents. Methods We conducted a qualitative study of all free-form answers in written, electronic, anonymous resident evaluations of rotations and the program from 2 academic years: 2007-2008 and 2017-2018. Rotation evaluations asked for the (a) strengths of the rotation, (b) in what ways the rotation did not meet one's expectations, and (c) suggestions to improve the rotation. In 2007-2008, there were 2934 comments and in 2017-2018, there were 3717. A constant comparison method was used to identify codes and themes within the comments, including a focus on constructive criticism versus microaggressions. Results The majority of negative comments were constructive criticism directed at characteristics of or, more rarely, specific behavior of personnel on the rotation. There were few microaggressions noted in 2007-2008 with the majority found in 2017-2018. Three types of microaggressions were identified. First, an insult was seen as a personal attack that ascribed a negative attribute to the person as opposed to the person's behavior. Second, the use of sarcasm was seen as a hostile response. Third, the use of powerful words that elevated the intensity of the comment (e.g. rabid, horrible, miscreant) or made generalized or absolute statements, for example, using terms like “everyone”, “everywhere”, and “all”. Conclusions Microaggressions have emerged in anonymous, online resident evaluations. The types of microaggressions may inform future research on the implications and impact of microaggressions in medical education.
Proceedings of the 2006 annual meeting of the Fetal Alcohol Spectrum Disorders Study Group

This article describes the proceedings of the 2006 Annual Meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG), which was held in Baltimore, Maryland on June 24, 2006. The meeting was held in conjunction with the annual meeting of the Research Society on Alcoholism and was supported by a grant from the National Institute on Alcohol Abuse and Alcoholism. The 2005-2006 FASDSG officers, Daniel J. Bonthius (President), Heather Carmichael Olson (Vice-President), and Jennifer Thomas (Secretary-Treasurer), organized the meeting. Nationally prominent speakers delivered plenary lectures on topics of newborn screening, ethics, and neuroscience. Selected members of the FASDSG provided brief scientific data (FASt) reports, describing new research findings. Representatives from national agencies involved in fetal alcohol syndrome (FAS) research, treatment, and prevention provided updates regarding priorities, funding, and agency activities. Presentations were also made by the 2006 Student Merit Award recipient and by the 2006 Rosett Award recipient. The meeting served as a forum for clinicians, neuroscientists, psychologists, social scientists, and other professionals to discuss recent advances in FAS research and to identify the most important gaps in the understanding of alcohol-induced teratology.
Engineering of a novel subnanomolar affinity fibronectin III domain binder targeting human programmed death-ligand 1.

The programmed death-ligand 1 (PD-L1) is a major checkpoint protein that helps cancer cells evade the immune system. A non-invasive imaging agent with rapid clearance rate would be an ideal tool to predict and monitor the efficacy of anti-PD-L1 therapy. The aim of this research was to engineer a subnanomolar, high-affinity fibronectin type 3 domain (FN3)-based small binder targeted against human PD-L1 (hPD-L1) present on tumor cells. A naive yeast G4 library containing the FN3 gene with three binding loop sequences was used to isolate high-affinity binders targeted to purified full-length hPD-L1. The selected binder clones displayed several mutations in the loop regions of the FN3 domain. One unique clone (FN3hPD-L1-01) with a 6x His-tag at the C-terminus had a protein yield of >5 mg/L and a protein mass of 12 kDa. In vitro binding assays on six different human cancer cell lines (MDA-MB-231, DLD1, U87, 293 T, Raji and Jurkat) and murine CT26 colon carcinoma cells stably expressing hPD-L1 showed that CT26/hPD-L1 cells had the highest expression of hPD-L1 in both basal and IFN-γ-induced states, with a binding affinity of 2.38 ± 0.26 nM for FN3hPD-L1-01. The binding ability of FN3hPD-L1-01 was further confirmed by immunofluorescence staining on ex vivo CT26/hPD-L1 tumors sections. The FN3hPD-L1-01 binder represents a novel, small, high-affinity binder for imaging hPD-L1 expression on tumor cells and would aid in earlier imaging of tumors. Future clinical validation studies of the labeled FN3hPD-L1 binder(s) have the potential to monitor immune checkpoint inhibitors therapy and predict responders.
Multidimensional analysis and detection of informative features in diffusion MRI measurements of human white matter

The white matter contains long-range connections between different brain regions and the organization of these connections holds important implications for brain function in health and disease. Tractometry uses diffusion-weighted magnetic resonance imaging (dMRI) data to quantify tissue properties (e.g. fractional anisotropy (FA), mean diffusivity (MD), etc.), along the trajectories of these connections. Statistical inference from tractometry usually either (a) averages these quantities along the length of each bundle in each individual, or (b) performs analysis point-by-point along each bundle, with group comparisons or regression models computed separately for each point along every one of the bundles. These approaches are limited in their sensitivity, in the former case, or in their statistical power, in the latter. In the present work, we developed a method based on the sparse group lasso (SGL) that takes into account tissue properties measured along all of the bundles, and selects informative features by enforcing sparsity, not only at the level of individual bundles, but also across the entire set of bundles and all of the measured tissue properties. The sparsity penalties for each of these constraints is identified using a nested cross-validation scheme that guards against over-fitting and simultaneously identifies the correct level of sparsity. We demonstrate the accuracy of the method in two settings: i) In a classification setting, patients with amyotrophic lateral sclerosis (ALS) are accurately distinguished from matched controls. Furthermore, SGL automatically identifies FA in the corticospinal tract as important for this classification -- correctly finding the parts of the white matter known to be affected by the disease. ii) In a regression setting, dMRI is used to accurately predict "brain age." In this case, the weights are distributed throughout the white matter indicating that many different regions of the white matter change with development and contribute to the prediction of age. Thus, SGL makes it possible to leverage the multivariate relationship between diffusion properties measured along multiple bundles to make accurate predictions of subject characteristics while simultaneously discovering the most relevant features of the white matter for the characteristic of interest.
A Single Enzyme Mediates the “Quasi-Living” Formation of Multiblock Copolymers with a Broad Biomedical Potential

This study describes a unique “quasi-living” block copolymerization method based on an initiation by a single enzyme. We use this term to describe a process where a preformed polymer chain can be r...
Measurements of deposited aerosol dose in infants and small children

Pediatric patients are very dependent on inhaled aerosol medications. There are significant differences in how these aerosols deposit in the lungs of children vs. adults that may affect the efficacy of the therapies. Inefficient aerosol delivery to children, caused by factors such as high mouth and throat deposition during oral inhalation, significant losses within adjunct devices such as masks, and high rates of nasal deposition during cannula delivery, can lead to dosing that is difficult to control. Here we discuss the methods, such as deposition scintigraphy, that are used to assess inhaled dose in vivo and review previous studies where these techniques have been applied to measure dosing in children. This includes studies of nebulizers and metered dose inhalers and delivery through adjuncts such as facemasks and nasal cannulas. We discuss the factors that can lead to inefficient inhaled drug delivery and high levels of mouth and throat deposition in children. Finally, we propose areas of innovation to improve inhaled drug delivery to this population. There is a need for child-specific technologies for inhaled drug delivery. This includes the use of smart devices that can guide pediatric breathing patterns and better engage children during treatments, the use of smaller aerosols which are less likely to deposit in the upper airways after inhalation, and the design of better nasal cannula interfaces for aerosol delivery to infants.
Animal personality shapes evolutionary trajectories via conserved genetic architecture

Abstract Consistent individual differences in behavior, i.e. animal personality, are often correlated within broader syndromes1 that can cause evolution in one trait to drive correlated changes in other behaviors via genetic correlations2. Despite abundant demonstration that these behavioral syndromes are common across taxa3,4, it has not been clear whether syndromes arise due to genetic and cellular mechanisms or because particular combinations of behavioral responses are favored. Here we show that populations of field crickets (Gryllus integer) exhibit a genetically conserved behavioral syndrome structure despite differences in average behaviors. We found that the distribution of genetic variation and covariance among behavioral traits was consistent with genes and cellular mechanisms underpinning behavioral syndromes rather than historic correlated selection. Moreover, divergence among populations’ average behaviors was constrained by the genetically conserved behavioral syndrome. By constraining the divergence of populations, animal personality may therefore also affect the ability of species to behaviorally diverge and therefore speciation. This suggests important ways in which labile traits—traits that are highly plastic, like behavior, physiology, and life-history traits—might affect evolutionary outcomes.
On Removing Algorithmic Priority Inversion from Mission-critical Machine Inference Pipelines

The paper discusses algorithmic priority inversion in mission-critical machine inference pipelines used in modern neural-network-based cyber-physical applications, and develops a scheduling solution to mitigate its effect. In general, priority inversion occurs in real-time systems when computations that are of lower priority are performed together with or ahead of those that are of higher priority.1 In current machine intelligence software, significant priority inversion occurs on the path from perception to decision-making, where the execution of underlying neural network algorithms does not differentiate between critical and less critical data. We describe a scheduling framework to resolve this problem, and demonstrate that it improves the system’s ability to react to critical inputs, while at the same time reducing platform cost.
Purple in a Black & White World: Self-Determination Theory and Transgender Military Service

We offer a theoretical framework to advance our understanding of the psychology of transgender service members—the most understudied and mysterious class of US military personnel. Using grounded theory methods with interview data collected from clandestinely-serving active-duty, guard and reserve military members from the US Army, Navy, Air Force and Marine Corps who self-identified as transgender or transsexual, we reveal a latent structure of Self Determination Theory (Deci & Ryan, 1985; Deci & Ryan, 2000; Ryan & Deci, 2000). The variance in our data heavily centers around the concepts of autonomy, competence and relatedness, illustrating how post-DADT military personnel policy, which excludes open transgender service, impacts the mental well-being of transgender service members.
SOE Reform Discourse Under Jiang Zemin

This chapter discusses the first case study: the policy discourse over the ownership restructuring of state-owned enterprises under Jiang Zemin (1992–1997). The analysis focuses on how party ideology—ideological lines, slogans, and directives of Deng Xiaoping and Jiang Zemin—were operationalized by major groups and influential figures as political rhetoric for persuasion and examines its effects on the dynamics of the discourse and policy outcomes. Through the qualitative analysis and coding of nearly 500 periodical articles, the chapter identifies major rhetoric, their central claims, discursive strategies, rhetorical appeals, and interactions. The chapter concludes that despite the highly contentious nature of the debate, Deng’s ideological line was skillfully operationalized by reformist groups to promote party initiatives and performed a compliance-inducing function in the discourse.
Measurement Equivalence across Multiple Administrations of the Massachusetts Youth Screening Instrument

Multiple studies have shown that the Massachusetts Youth Screening Instrument-2nd Version (MAYSI-2) has strong validity and reliability. Justice involved youth are often administered the MAYSI-2 on repeated occasions. The purpose of the current study was to test the equivalence of measurement properties over time for males who were administered the MAYSI-2 on multiple occasions. Archived data were drawn from the Utah Juvenile Justice Services administration, which consisted of all administrations of the MAYSI-2 between 2007 to 2018. Among these, 909 males completed the MAYSI-2 three or more times. Single and multiple group longitudinal invariance tests were conducted using a weighted least squares mean and variance adjusted estimation in order to determine measurement equivalence across multiple administrations. Increasingly restrictive constraints for configural, metric, and scalar invariance models across Time 1 and Time 3 as well as models constraining latent means and variances to be equal across Time 1 and Time 3 all fit these data well. The established seven factor structure for the MAYSI-2 fit the data as well. However, some differences were noted in item level functioning across multiple administrations. The results of the current study suggest that multiple administrations of the MAYSI-2 may not exhibit equivalent measurement properties over time. Consistency of the measurement properties of the MAYSI-2 over time is essential for evaluating changes in mental health. Given that contact with the juvenile justice system has the potential to worsen symptoms of mental illness, caution is warranted when using the MAYSI-2 to assess change.
Phosphine/Photoredox Catalyzed anti-Markovnikov Hydroamination of Olefins with Primary Sulfonamides via a-Scission from Phosphoranyl Radicals

New strategies to access radicals from common feedstock chemicals hold the potential to broadly impact synthetic chemistry. We report a dual phosphine and photoredox catalytic system that enables direct formation of sulfonamidyl radicals from primary sulfonamides. The method is proposed to proceed via -scission of the sulfonamidyl radical from a phosphoranyl radical intermediate, generated upon sulfonamide nucleophilic addition to a phosphine radical cation. As compared to the recently well-explored β-scission chemistry of phosphoranyl radicals, this strategy is applicable to activation of N-based nucleophiles and is catalytic in phosphine. We highlight application of this activation strategy to an intermolecular anti-Markovnikov hydroamination of unactivated olefins with primary sulfonamides. A range of structurally diverse secondary sulfonamides can be prepared in good to excellent yields under mild conditions.
Outcomes of Severe Alcohol-Related Hepatitis with or without Early Liver Transplantation.

We read with great interest the article by Musto et al. in a recent issue of "Hepatology".(1) Evaluation of severe alcohol-related hepatitis (AH) demonstrated that 34 out of 144 patients (23.6%) recovered without liver transplantation (LT). Most recovered patients, however, continue to experience end-stage complications. The authors concluded that only LT was associated with improved survival.
295 Tumor cell- intrinsic expression of FGFR3 drives anti-PDL-1 immunotherapy resistance in a murine bladder cancer model

Background Immune checkpoint blockade therapy has recently shown efficacy in treating advanced urothelial bladder cancer and anti-PD-1/PD-L1 therapy is currently the standard of care. However, most patients do not respond to these drugs and resistance mechanisms remain elusive. The non-T cell-inflamed tumor microenvironment phenotype correlates with poor prognosis and immunotherapy resistance. We previously found that activating mutations in Fibroblast Growth Factor Receptor 3 (FGFR3) were exclusive to non-T cell-inflamed bladder cancers. We investigated the impact of tumor cell-intrinsic FGFR3 activation on T cell infiltration and tumor responsiveness to anti-PD-1/PD-L1 in a murine model. Methods We developed a syngeneic transplantable murine bladder cancer model using the MB49 cell line engineered to express FGFR3 with either the activating G370C mutation (FGFR3-G370C), a kinase-dead mutation K508M (FGFR3-K508M), a truncating mutation resulting in a secreted receptor (FGFR3-sec), or control. Mice were injected subcutaneously into flank and size was measured every 3 days along with PD-L1 therapy (BioXcell clone 10F.9G2). Tumors, draining lymph nodes, and spleens were harvested at endpoint for flow cytometry. Results Tumors from mice inoculated with MB49-FGFR3-G370C cells showed diminished CD8+ T cell accumulation within the tumor and were resistant to anti-PD-L1 checkpoint blockade compared to MB49 controls. To determine if FGFR3-mediated immune resistance was dependent on FGFR3 kinase activity, MB49-FGFR3-K508M tumors were evaluated and unexpectedly found to be resistant to anti-PD-L1 treatment. Tumors with a secreted FGFR3 receptor (FGFR3-sec) retained responsiveness to anti-PD-L1 therapy. Conclusions In a murine bladder cancer model, FGFR3 activation led to relative T cell exclusion and resistance to immune checkpoint blockade. The mechanism of resistance was not dependent on receptor kinase activity. Further studies are ongoing to determine the biochemical mechanisms of FGFR3-mediated immunotherapy resistance in bladder cancer.
Replication of non-repetitive DNA during early, middle and late S phase. The general class and the subset transcribed.

Abstract Synchronized cultures of Chinese hamster ovary cells were pulse-labelled with 5-bromodeoxyuridine (BrdU) during early (0–2.0 h), middle (2.5–4.0 h) and late (4.5–6.0 h) S phase in two successive cell cycles. In each case, the DNA containing BrdU in both strands was duplicated at the same time in both cycles and was isolated for further characterization by centrifugation in CsCl gradients. These DNAs were then radiolabelled by nick-translation and used in either DNA-DNA or RNA-DNA hybridization experiments. In the DNA-DNA experiments, advantage was taken of the substantial rate increases attainable in high concentrations of dextran sulfate to obtain complete reassociation curves with relatively small amounts of material. Assuming that no unresolved low repetition frequency components exist, renaturation kinetics suggest that early replicating DNA contains a greater proportion of non-repetitive sequences than DNA synthesized at later times, the order being early>middle>late. However, in terms of complexity the non-repeated DNA duplicated early had only 74% of the diverse sequences present in logphase cells, whereas that replicated in middle and late S phase had 82 and 79.5%, respectively. It therefore appears that while DNA synthesized at different times in S phase may contain varying proportions of non-repetitive sequences, when their diversity is taken into account very few of these sequences (25% or less) exhibit temporal control of replication. Finally, measurements with total cell RNA indicated that the transcribed fraction of non-repeated DNA showed a slight preference for replication in early S phase.
Research Review: Independent living programmes: the influence on youth ageing out of care (YAO)

Independent living programmes (ILPs) aid in promoting productive outcomes for youth ageing out of care (YAO). This narrative review aimed to determine if sufficient evidence exists to substantiate statements regarding the effectiveness of ILPs based upon outcome studies published from January 2006 through December 2012. Are current ILPs effectively promoting independent living and productive outcomes among youth leaving foster care, relative to similar youth who do not participate in an ILP? Six studies published in English, in the USA and in peer-reviewed journals included non-experimental design (n = 1), quantitative designs (n = 2), mixed methods design (n = 2) and randomized design (n = 1). Five outcomes addressing education, employment, housing, mental health, and living skills emerged. Weak evidence that ILPs effectively aid YAO exists. Additionally, inconsistencies exist in methodology. Finally, differences in important components in the ILPs exist, making comparisons difficult.
Design of a cosecant square-shaped beam pattern SAR antenna array fed with square coaxial feeder network

This paper presents the design and simulation of a high power wide band cosecant squared pattern Synthetic Aperture Radar (SAR) array antenna with low side lobe level. A multilayer stacked radiating array of 8×8 elements at C band with center frequency of 5.2 GHz and 500 MHz bandwidth for a peak power 6KW and PRF 1.2% is fed with 1∶8 square coaxial feeder network. Mixed Electromagnetic simulation approach is used to reduce design cycle by 50–60%. Radiating array has been designed with 3D-planar solver (Momentum) and high power Square Coaxial Line (SCL) feeder network of antenna design has been designed using Finite Element Method (FEM) based 3D electromagnetic solver. Complete integrated antenna simulation has been performed with FDTD solver.
A reference model for mass storage systems

Publisher Summary This chapter discusses the development of the mass storage systems from a large peripheral device to integration into the distributed computing architectures as multiple storage service nodes. As a peripheral, the success of a mass storage system is as dependent on the operational procedures and operating system of the site as it is on the design of the device. The integration of distributed computing and multiple storage service nodes can readily incorporate large peripherals as mass storage subsystems. This can be done by operational procedures and distributed operating systems. Version 2.0 of the IEEE-computer society (CS) mass storage system reference model has a structure that fits almost entirely into the application layer of the ISO Open Systems Interconnection (OSI) reference model. The IEEE-CS mass storage system bitfile server defines an alternate set of objects and commands from the OSI model of Virtual Filestore (DIS 8571).
Improved growth of lipoprotein lipase deficient kittens by feeding a low-fat, highly digestible diet

Adult domestic cats homozygous with a naturally occurring Gly412Arg LPL gene mutation are good models for the study of LPL deficiency. Previous studies report that homozygous LPL deficient kittens have reduced growth rates and develop subnormal body fat mass. It was hypothesized in the present study that homozygote kittens would have normal growth if provided a standard low fat, highly digestible diet at weaning and that their body fat would be increased by provision of a diet high in protein. When fed a nutritionally complete, 10% fat, purified or commercial extruded diet, the body weights of homozygous (n = 24), heterozygous (n = 25) and normal (n = 16) kittens were determined at birth, 2, 3, 4, 6, 12 and 18 weeks of age. Male homozygote kittens from homozygote dams had reduced weight gains (p < 0.05) compared to normal males at 2, 3 and 4 weeks. Female heterozygotes and homozygotes from homozygote and heterozygote dams had reduced weight gains (p < 0.05) compared to normal females at 2, 3, 4 and 6 weeks. By 6 weeks for males and 18 weeks for females, genotype related differences in weight gain were not observed. At 30 weeks, homozygotes and heterozygotes were given either a 60 or 30% (dry matter) protein diet for two months. As indicated by deuterium dilution estimation of body composition, cats eating the 30% protein diet (n = 12) tended to have a lower increase in lean body mass (p = 0.057) and a greater increase in fat mass (p = 0.092) compared to cats eating the 60% protein diet (n = 12). Increase in lean body mass among homozygotes tended to be not as great as that observed in heterozygotes (p = 0.057). Poor postweaning gains previously reported in homozygotes probably reflected inappropriate selection of diet for this genotype. The high protein diet increased the rate of lean body mass development but not body fat mass.
HYDRODYNAMIC SIMULATIONS OF 16O+208Pb COLLISIONS AT 200 GeV/N

We investigate collisions of 16O with 208Pb at a bombarding energy of 200 GeV/N in the lab frame. Our basis is an ideal, one-fluid 3-D hydrodynamics model. Several equations of state are used to study the qualitative relation between final baryon rapidity distributions and the stiffness of the EOS. We find that 75% of the baryonic matter lies within one unit of the initial target rapidity, in qualitative agreement with recent experimental data. In addition, our calculation is able to reproduce the integrated value of the dET/dy distribution that is observed experimentally.
When It Is Better to Regress: Dynamics of Vascular Pruning

Blood vascular networks in vertebrates are essential to tissue survival. Establishment of a fully functional vasculature is complex and requires a number of steps including vasculogenesis and angiogenesis that are followed by differentiation into specialized vascular tissues (i.e., arteries, veins, and lymphatics) and organ-specific differentiation. However, an equally essential step in this process is the pruning of excessive blood vessels. Recent studies have shown that pruning is critical for the effective perfusion of blood into tissues. Despite its significance, vessel pruning is the least understood process in vascular differentiation and development. Two recently published PLOS Biology papers provide important new information about cellular dynamics of vascular regression.
New insights into uremic toxicity.

Purpose of reviewOur concept of uremia has expanded to encompass the illness patients begin to suffer as glomerular filtration rate declines long before the onset of end-stage renal disease (ESRD) not explained by known derangements in volume status or metabolic parameters. New insights into the acc
Small comets: Naked‐eye visibility

We investigate an obvious consequence of the small-comet hypothesis. We find that the 30-ton cloud of water-ice particles formed by a small comet would survive long enough to be an unmistakably bright object. The visual magnitude of such clouds would be between that of a bright star and the full Moon. A whole-Earth small-comet flux of 20/min implies the sudden appearance of at least two bright patches of light every five minutes. The two-hour periods after sunset and before sunrise ought to produce the most spectacular sightings—intermittent punctuations of bright rapidly-moving points of light. Because such events are not reported, we conclude that this class of object does not exist in detectable numbers.
Primary neurons maintain their central axonal arbors in the spinal dorsal horn following peripheral nerve injury: an anatomical analysis using transganglionic transport of horseradish peroxidase.

Abstract This study in adult cats demonstrates that primary neurons of all sizes survive following the transection and capping with a polyethylene tube of their peripheral processes in the superficial radial nerve. The central axonal arbors of these injured primary neurons remain intact and maintain their normal topographic position across laminae I–VI of the cervical (C6–C8) dorsal horn. In addition, they maintain their synaptic vesicles, some of their synaptic connections and their ability to transport horseradish peroxidase transganglionically.
Chemical and electrochemical behavior of metallic technetium in acidic media

The chemical and electrochemical properties of technetium metal were studied in 1–6 M HX and in 1 M NaX (pH 1 and 2.5), X = Cl, NO3. The chemical dissolution rates of Tc metal were higher in HNO3 than in HCl (i.e. 8.63 × 10−5 mol cm−2 h−1 in 6 M HNO3 versus 2.05 × 10−9 mol cm−2 h−1 in 6 M HCl). The electrochemical dissolution rates in HNO3 and HCl were similar and mainly depended on the electrochemical potential and the acid concentration. The optimum dissolution of Tc metal was obtained in 1 M HNO3 at 1 V/AgAgCl (1.70 × 10−3 mol cm−2 h−1). The dissolution potentials of Tc metal in nitric acid were in the range of 0.596–0.832 V/AgAgCl. Comparison of Tc behavior with Mo and Ru indicated that in HNO3, the dissolution rate followed the order: Mo > Tc > Ru, and for dissolution potential the order: E diss(Ru) > E diss(Tc) > E diss(Mo). The corrosion products of Tc metal were analyzed in HCl solution by UV–Visible spectroscopy and showed the presence of TcO4 −. The surface of the electrode was characterized by microscopic techniques; it indicated that Tc metal preferentially corroded at the scratches formed during the polishing and no oxide layer was observed.
Arylesterases in blood: effect of calcium and inhibitors.

Abstract (1) The normal functioning of human serum arylesterase requires the presence of calcium. An enzyme in human plasma fraction IV-I is probably identical with serum arylesterase. The activity of arylesterase is accelerated by calcium, inhibited by various chelating agents, metal ions, SH-reagents, and competitively and reversibly inhibited by the ionized form of 1-phenyl-2-hydrazinopropane. The d -isomer of this compound is more effective than the L-isomer. In contrast to results with arylesterase, the racaemic form of this agent accelerated the hydrolysis of phenyl acetate by human plasma cholinesterase. The best inhibitors of arylesterase were the rare earths, some of them active in the order of 10 −8 M. Under the experimental conditions used calcium chloride protected the enzyme partially or fully against the inhibition and against loss of activity during dialysis. (2) Swine serum contains an arylesterase with properties similar to those of human serum. (3) The human red blood cell and serum arylesterase are not identical.
The Human Nuclear Xenobiotic Receptor PXR: Structural Determinants of Directed Promiscuity

The human nuclear pregnane X receptor (hPXR) activates cytochrome P450-3A expression in response to a wide variety of xenobiotics and plays a critical role in mediating dangerous drug-drug interactions. We present the crystal structures of the ligand-binding domain of hPXR both alone and in complex with the cholesterol-lowering drug SR12813 at resolutions of 2.5 and 2.75 angstroms, respectively. The hydrophobic ligand-binding cavity of hPXR contains a small number of polar residues, permitting SR12813 to bind in three distinct orientations. The position and nature of these polar residues were found to be critical for establishing the precise pharmacologic activation profile of PXR. Our findings provide important insights into how hPXR detects xenobiotics and may prove useful in predicting and avoiding drug-drug interactions.
Sample sizes for medical trials with special reference to long-term therapy

AN IMPORTANT step in planning a medical trial involving a control group and an experimental group is to determine the total number of subjects required. The study end-point may be the occurrence of an “event”, such as death or a new case of disease. We assume this to be the case so that the results of the medical trial are to be evaluated by comparing the incidence of events in the control and experimental groups. With sampling as the only consideration, the total number needed will in general depend, for a T-yr study, on the anticipated T-yr event rate in the control group (PC), the anticipated T-yr event rate in the experimental group (pi), the Type I error (a, the probability of rejecting the null hypothesis when the null hypothesis is true), and the Type II error (p, the probability of accepting the null hypothesis when the null hypothesis is false). This is well known as is the asymptotic formula for total sample size, assuming equal size groups and a one-tailed normal deviate test of significance:
Effectiveness of an Acetabular Positioning Device in Primary Total Hip Arthroplasty

To evaluate the efficacy of a commercially available acetabular positioning device, we performed a prospective evaluation of 40 consecutive patients undergoing primary total hip arthroplasty. All surgery was performed by the same surgeon, in the same operating room, and on the same operating table. The acetabular positioning device was designed to place the component in 45° of abduction. At 6 weeks, all radiographs were evaluated by 3 investigators not involved with the surgery. Each radiograph was evaluated by each reviewer on 3 separate occasions, blinded to the findings of the other reviewer to assess interobserver and intraobserver variability. The mean cup abduction angle was 42.1°, with a range from 23° to 57° (SD 8.3°). Intraobserver and interobserver variability were 0.2 and 0.3°, respectively. The findings of this study demonstrate a wide variability in acetabular cup placement in primary total hip arthroplasty. We believe this is due to movement of the pelvis, which may occur during preparation, draping, and retracting during surgery. We feel surgeons should not rely solely on positioning devices when implanting the acetabular component in total hip arthroplasty. Identification of bone landmarks and determination of superolateral implant coverage noted on preoperative templating is advocated to improve the precision of component position.
Isolation of Campylobacter Coli from a Proliferative Intestinal Lesion in a Ferret

The domestic ferret (Mustela putorius furo) is commonly used in biomedical research and is becoming increasingly popular as a pet. An estimated 5 million ferrets are kept in 1 million homes in the United States. Therefore, it is likely that diagnostic laboratories are or will be involved in diagnosing ferret diseases. This report describes the clinical, histologic, and bacteriologic aspects of an intestinal disease that may cause significant morbidity and mortality in domestic ferrets. A live 1 16-week-old female ferret was presented to the Iowa State University Veterinary Diagnostic Laboratory on September 9, 1988, for examination. The owner stated that it was one of approximately 50 animals out of a total population of 1,000 on his commercial ferret farm that were suffering from a “watery scour,” anorexia, and weight loss. The owner also stated that another 30 ferrets had died during the previous 3 weeks after exhibiting similar clinical signs. Some of those ferrets had a mucoid or mucohemorrhagic diarrhea. Observation of the ferret prior to euthanasia failed to disclose abnormal behavior. At necropsy, the gastointestinal tract was empty, and the large intestine was slightly thickened. The thickening was subtle and could have been easily overlooked. There were no lesions in the small intestine or in the other organs. A fecal sample collected by the owner approximately 4 hours prior to arrival at the laboratory was evaluated by routine sugar flotation technique and was negative for parasites. A fecal sample can also be utilized to obtain a quick, presumptive diagnosis of campylobacteriosis by microscopic examination of a Gram-stained (use carbol-fuchsin as the counterstain) fecal smear. Best results are obtained from a very fresh fecal sample collected from a ferret with acute diarrhea. This technique was not used in the present case. Sections of large and small intestine were placed in neutral buffered 10% formalin, embedded in paraffin, sectioned at 5 μm thickness, and stained with hematoxylin and eosin (HE) and War-thin-Starry stains. Histologically, there was a purulent exudate in the colon lumen and on segments of the colon mucosa. The majority of lamina propria was infiltrated with sheets of lymphocytes, but some focal areas also contained neutrophils, plasma cells, and macrophages. There was focal exfoliation of epithelium from the mucosal surface. The majority of mucosal glands were branching, irregular in shape, and lined by crowded and multilayered polymorphic epithelial cells (Fig. 1). Clusters of curved or S-shaped organisms were observed in the apical portions of many of
Using metal complex-labeled peptides for charge transfer-based biosensing with semiconductor quantum dots

Luminescent colloidal semiconductor quantum dots (QDs) have unique optical and photonic properties and are highly sensitive to charge transfer in their surrounding environment. In this study we used synthetic peptides as physical bridges between CdSe-ZnS core-shell QDs and some of the most common redox-active metal complexes to understand the charge transfer interactions between the metal complexes and QDs. We found that QD emission underwent quenching that was highly dependent on the choice of metal complex used. We also found that quenching traces the valence or number of metal complexes brought into close proximity of the nanocrystal surface. Monitoring of the QD absorption bleaching in the presence of the metal complex provided insight into the charge transfer mechanism. The data suggest that two distinct charge transfer mechanisms can take place. One directly to the QD core states for neutral capping ligands and a second to surface states for negatively charged capping ligands. A basic understanding of the proximity driven charge-transfer and quenching interactions allowed us to construct proteolytic enzyme sensing assemblies with the QD-peptide-metal complex conjugates.
Heat Transfer Enhancement by Acoustic Streaming in an Enclosure

Thermal convection in a differentially heated shallow enclosure due to acoustic excitations induced by the vibration of a vertical side wall is investigated numerically. The fully compressible form of the Navier-Stokes equations is considered and an explicit time-marching algorithm is used to track the acoustic waves. Numerical solutions are obtained by employing a highly accurate flux corrected transport algorithm. The frequency of the wall vibration is chosen such that an acoustic standing wave forms in the enclosure. The interaction of the acoustic standing waves and the fluid properties trigger steady secondary streaming flows in the enclosure. Simulations were also carried out for “off-design” vibration frequency where no standing waves were formed. The effects of steady second order acoustic streaming structures are found to be more significant than the main oscillatory flow field on the heat transfer rates. The model developed can be used for the analysis of flow and temperature fields driven by acoustic transducers and in the design of high performance resonators for acoustic compressors.
AFLATOXIN PRODUCTION AS AFFECTED BY ENVIRONMENTAL CONDITIONS

SUMMARY— The effects of controlled atmosphere (CA) (10% CO2, 1.8% O2 and 88.2% N2 and air were noted on the growth of aflatoxin production of Aspergillus flavus incubated at several temperatures on 2 substrates. In liquid medium, the mold grew well and produced toxin in both air and CA at room temperature. At 60°F, growth and toxin were substantial in air but minimal in CA. At temperatures of 54°F and below. toxin was inhibited; growth was minimal in air and inhibited in CA. Cracked corn of 16.6, 18.8, 23.6 and 31.2% moisture content (dry basis) also was studied. At 31.2% moisture and 60°F, growth was reduced in CA to a greater extent than in air. whereas sporulation and toxin in CA showed a longer lag period at both 84 and 60°F.
Subacromial anatomy and biomechanics related to the impingement syndrome

Abstract Shoulder girdle evolution, anatomy, biomechanics, and potential etiologies of impingement are reviewed. It is apparent that shoulder impingement can occur as a secondary phenomenon in the presence of certain intrinsic shoulder pathology. Rotator cuff lesions frequently involve tendon degeneration. Subacromial impingement is believed to play a major role in this degenerative process. In addition, it is postulated that cuff degeneration precedes subacromial impingement more frequently than is commonly believed. A multifactorial etiology in which the relative importance of a specific element varies from case to case best explains tendon degeneration.
Fluctuations and patterns in nanoscale surface reaction systems: Influence of reactant phase separation during CO oxidation

A realistic atomistic model is used to assess spatiotemporal behavior in nanoscale CO oxidation systems at higher pressures than for traditional ultrahigh vacuum studies. The strong influence of adspecies interactions in this regime of high reactant coverages leads to phase separation between oxygen-rich and CO-rich reactive states. Time-series studies reveal fluctuation-induced transitions between these states, as well as transitions between reactive and inactive states. In addition, we observe flickering spatial patterns with sharp boundaries.
OCCURRENCE OF ACTIVE 80 S RIBOSOMES IN SUBCELLULAR PARTICLES IN THE MITOCHONDRIAL FRACTION OF FETAL BOVINE LIVER

In the course of studies on protein synthesis by unidentified subcellular particle in the mitochonmitochondria isolated from fetal calves liver, we drial fraction . Because these ribosomes incorporate found active' 80 S ribosomes associated with an leucine-'H under conditions that label only intramitochondrial ribosomes in adult mammalian sys1 Active under incubation conditions that support tems, we considered the possibility that they might mitochondrial, but not microsomal, protein synthereside within mitochondria, perhaps occurring as sis . dimers of the mammalian 55 S mitochondrial ribo-
Immunomodulatory effects of interferon beta-1a in multiple sclerosis

Several studies have established a role for interferon beta (IFNbeta) as a treatment for relapsing-remitting multiple sclerosis (MS). IFNbeta has been reported to decrease the relapse rate, relapse severity, progression of disability and development of new brain lesions. Its mechanisms of action, however, remain unclear. We hypothesize that immunomodulatory effects of IFNbeta may underlie its clinical efficacy. We used intracellular cytokine flow cytometry to analyze the effects of IFNbeta-1a on expression of the anti-inflammatory cytokine, IL-10, and its effects on major co-stimulatory molecules in MS patients. We found that peripheral blood mononuclear cells (PBMC) produced more IL-10 following in vitro or in vivo treatment with IFNbeta-1a. The primary cellular sources of IL-10 were monocytes and CD4(+) T lymphocytes. IL-10 production in response to IFNbeta-1a was increased in unseparated PBMC compared to purified lymphocyte cultures, indicating that interaction between monocytes and lymphocytes may influence IL-10 production in response to IFNbeta-1a. Using flow cytometry, we monitored the ex vivo expression of two major co-stimulatory pairs-B7/CD28 and CD40/CD40L-before and after intramuscular IFNbeta-1a treatment of MS patients. IFNbeta-1a lowered the expression of B7.1 on circulating B cells and increased B7.2 expression on monocytes. CD40 expression on B cells was down-regulated, but CD40 on monocytes was up-regulated by IFNbeta-1a treatment. These data suggest that co-stimulatory molecules are modulated by IFNbeta, providing a possible mechanism for its in vivo immune regulatory effects.