cssi/SciSciGPT-SciSciNet huggingface dataset:
Targeting Liver Fibrosis with a Cell-penetrating Protease-activated Receptor-2 (PAR2) Pepducin.

Chronic liver inflammation and fibrosis in nonalcoholic steatohepatitis can lead to cirrhosis and liver failure for which there are currently no approved treatments. Protease-activated receptor-2 (PAR2) is an emerging new target expressed on liver stellate cells and hepatocytes that regulates the response to liver injury and inflammation. Here, we identified a pepducin to block the deleterious actions of PAR2 in promoting liver fibrosis. Non-alcoholic fatty liver disease and early fibrosis were induced by the methionine-choline-deficient diet in mice. Fibrotic liver disease was induced by administering carbon tetrachloride for 8 weeks. Mice were treated with the pepducin PZ-235 either from onset of the experiment or after fibrosis was established. Hepatic fibrosis, collagen content, inflammatory cytokines, steatosis, triglycerides, and NAFLD activity score were assessed as primary outcome parameters depending on the model. The activity of the PAR2 pepducin on cultured stellate cell activation and hepatocyte reactive oxygen species production was evaluated. PZ-235 significantly suppressed liver fibrosis, collagen deposition, inflammatory cytokines, NAFLD activity score, steatosis, triglycerides, aspartate transaminase, alanine transaminase, and stellate cell proliferation by up to 50–100%. The PAR2 inhibitor afforded significant protective effects against hepatocellular necrosis and attenuated PAR2-mediated reactive oxygen species production in hepatocytes. PZ-235 was distributed to liver and other mouse tissues and was found to form a well structured α-helix that closely resembles the juxtamembrane helical region of the analogous TM6 and third intracellular region of the intact receptor that is critical for coupling to internal G proteins. The ability of PZ-235 to effectively suppress fibrosis, hepatocellular necrosis, reactive oxygen species production, steatosis, and inflammation indicates the potential for PAR2 pepducin inhibitors to be broadly efficacious in the treatment of liver fibrosis.
Correlation between the number of allergen sensitizations and immunoglobulin E: monosensitization vs polysensitization.

Background The purpose of this study was to determine if total serum immunoglobulin E (IgE) could predict monosensitization compared to polysensitization in patients with allergic rhinitis (AR). Methods This was a retrospective study of a cohort of 1073 patients who underwent allergy testing. Differences in total IgE level between unsensitized, monosensitized, and polysensitized subjects were calculated. Pearson correlation coefficient was calculated to determine whether there was a relationship between total IgE level and the number of positive allergen sensitizations. In addition, allergen sensitization class was calculated for each allergen sensitization and totaled for each patient. Pearson correlation coefficient was calculated to determine the relationship between total IgE level and weighted allergen sensitization by class. Results There were 159 patients who were monosensitized compared to 492 patients who were polysensitized. Of the monosensitized patients, almost 50% (74) were sensitized to one or both dust mites. Total IgE was higher in polysensitized patients compared to monosensitized compared to controls (p < 0.001). Pearson correlation coefficient between total IgE and number of positive allergen sensitizations was 0.465 (p ≤ 0.001). Pearson correlation coefficient between total IgE and allergen class–weighted sensitizations was 0.529 (p ≤ 0.001). Conclusion IgE level can be used to predict monosensitization vs polysensitization. There is a moderate correlation between total IgE sensitization and the number of positive allergen sensitizations, as well as allergen class–weighted sensitizations.
Coherence and probability: A probabilistic account of coherence

I develop a probabilistic account of coherence, and argue that at least in certain respects it is preferable to (at least some of) the main extant probabilistic accounts of coherence: (i) Igor Douven and Wouter Meijs’s account, (ii) Branden Fitelson’s account, (iii) Erik Olsson’s account, and (iv) Tomoji Shogenji’s account. Further, I relate the account to an important, but little discussed, problem for standard varieties of coherentism, viz., the “Problem of Justified Inconsistent Beliefs.”
Derisking drug-induced liver injury from bench to bedside

Abstract In the world of translational biomarkers, the bar is high for qualification of improved indicators of liver injury. A ‘holy grail’ of translational biomarkers with respect to drug-induced liver injury (DILI) will be the discovery, evaluation, and qualification of those that provide accurate prognoses regarding individuals that will go on to experience liver failure from those that recover given modest increases in ALT, AST and total bilirubin (TBL). The performance of these well-established liver function tests (LFT) is quite good in terms of sensitivity for diagnosing liver injury, but opportunities exist for developing specific indicators of injury and better prognostic biomarkers of liver failure. Presently, in the absence of novel qualified translational biomarkers, the challenge for drug discovery is to minimize, and ideally eliminate, late stage drug failures due to DILI signals that may or may not indicate life threatening injury. This will be achieved through the application of novel in vitro and in vivo models utilized early in the drug development process. Predictive structure activity relationship (SAR) models are being developed by leveraging data from these novel tools with clinical outcomes. Mechanistic insights to the underlying biological processes that initiate adverse clinical DILI are being elucidated and used to design better molecules with a higher probability of success while decreasing cost and time to market. In addition to the near term gains of acquiring these mechanistic insights, this enhanced understanding could result in novel translational biomarkers with improved diagnostic and prognostic power over ALT/AST and TBL alone resulting in safer drugs while ensuring patient safety.
Heat stress causes dysfunctional autophagy in oxidative skeletal muscle

Abstract We have previously established that 24 h of environmental hyperthermia causes oxidative stress and have implicated mitochondria as likely contributors to this process. Given this, we hypothesized that heat stress would lead to increased autophagy/mitophagy and a reduction in mitochondrial content. To address this hypothesis pigs were housed in thermoneutral (TN; 20°C) or heat stress (35°C) conditions for 1‐ (HS1) or 3‐ (HS3) days and the red and white portions of the semitendinosus collected. We did not detect differences in glycolytic muscle. Counter to our hypothesis, upstream activation of autophagy was largely similar between groups as were markers of autophagosome nucleation and elongation. LC3A/B‐I increased 1.6‐fold in HS1 and HS3 compared to TN ( P P P P α signaling. In total, these data suggest heat‐stress‐mediated suppression of activation of autophagy and autophagosomal degradation, which may enable the persistence of damaged mitochondria in muscle cells and promote a dysfunctional intracellular environment.
XRD-473 (AN EXPERIMENTAL BENZOYLPHENYLUREA): RATES AND OPTIMAL TIME OF APPLICATION TO WESTERN SPRUCE BUDWORM

XRD-473 (N-(((3,5-Dichloro-4-(1,1,2,2-tetrafluoroethoxy) phenyl-amino) carbonyl)-2, 6-difluorobenzamide), a benzoylphenylurea (BPU), was tested in a series of experiments to estimate the optimal ti...
Inexpensive multigram-scale synthesis of cyclic enamines and 3-N spirocyclopropyl systems

Cyclic enamines are important synthons for many synthetic and pharmacological targets. Here, we report an inexpensive, catalyst-free, multigram-scale synthesis for cyclic enamines with exocyclic double bonds and four- to seven-membered rings. This strategy is more conducive to scale up, permissive of functionalization around the cyclic system, and less sensitive to the nature of the N-protecting group than previously-described methods for cyclic enamine synthesis. Further, we explore application of these enamines to the synthesis of highly-strained spirocyclic 3N-cyclopropyl scaffolds.
Examination of pesticide exposure in Burrowing Owls nesting in agricultural and nonagricultural areas in the Morley Nelson Snake River Birds of Prey National Conservation Area, Idaho.

Western Burrowing Owls (Athene cunicularia hypugaea) frequently nest near agricultural lands. In southwestern Idaho, greater population density in agricultural landscapes appears to be driven in part by reliable and abundant prey populations. However, these potential benefits may be offset if agricultural land use increases pesticide exposure, especially during the sensitive reproduction period. Thus, we investigated the extent to which Burrowing Owls nesting near croplands within the Morley Nelson Snake River Birds of Prey National Conservation Area (NCA), Idaho, were exposed to organophosphate (OP), carbamate (CB), and/or organochlorine (OC) pesticides. We examined plasma cholinesterase activity, OP and CB residues in foot-wash samples, and OCs in soils and whole egg contents collected from owls and their nests along a distance gradient from agricultural fields. We further measured eggshell thickness to assess potential for thinning from OC exposure. There was no inhibition of cholinesterase activities in adult or nestling owls near agriculture, and foot-wash samples from adults tested negative for OP and CB pesticides. The OC p,p′-DDE, a metabolite of DDT, occurred in eggs at 27 of 58 nests, but there was some evidence that concentrations increased with increasing distance from agriculture. Concentrations of p,p′-DDE in eggs were relatively low compared to harmful levels in other avian species, were not correlated with eggshell thickness, and did not appear to reduce nesting success. Neither DDT, its metabolites, nor any other OCs were detected in soil samples from local owl breeding areas. These results indicate that p,p′-DDE, organophosphate, and carbamate exposure were not causing toxicity or reproductive impairment of Burrowing Owls in the NCA during our study years.
Role of atypical antipsychotics in rapid cycling bipolar disorder: a review of the literature.

Background The role of atypical antipsychotics in the management of bipolar disorder continues to expand. This review summarizes the literature on use of atypicals in rapid cycling bipolar disorder in clinical practice and highlights areas for future study. Methods A PubMed search was done using keywords rapid cycling, atypical antipsychotics, refractory bipolar, aripiprazole, clozapine, olanzapine, risperidone, quetiapine, and ziprasidone. Reference lists from original peer-reviewed articles, review articles, and book chapters were reviewed and articles were extracted. Results Data on the use of atypical antipsychotics in rapid cycling bipolar disorder are sparse. Atypical antipsychotics may be effective as anti-manic agents during acute mania and may reduce depressive symptoms when used for short and intermediate durations. Their efficacy as mood stabilizers in maintenance therapy has not been demonstrated. Conclusions The study of atypical antipsychotics in rapid cycling bipolar disorder is in its infancy. Although atypical antipsychotics are useful in acute mania, current data do not support their use as maintenance agents. Future double-blind, randomized studies are needed to establish their efficacy relative to traditional mood stabilizers and their utility as adjuvant agents in this subset of patients.
Covalent "Click Chemistry"-Based Attachment of DNA onto Solid Phase Enables Iterative Molecular Analysis.

Molecular analysis of DNA samples with limited quantities can be challenging. Repeatedly sequencing the original DNA molecules from a given sample would overcome many issues related to accurate genetic analysis and mitigate issues with processing small amounts of DNA analyte. Moreover, an iterative, replicated analysis of the same DNA molecule has the potential to improve genetic characterization. Herein, we demonstrate that the use of “click”-based attachment of DNA sequencing libraries onto an agarose bead support enables repetitive primer extension assays for specific genomic DNA targets such as gene exons. We validated the performance of this assay for evaluating specific genetic alterations in both normal and cancer reference standard DNA samples. We demonstrate the stability of conjugated DNA libraries and related sequencing results over the course of independent serial assays spanning several months from the same set of samples. Finally, we finally applied this method to DNA derived from a tumor sa...
Human Papillomavirus Vaccine Interventions in the U.S.: A Systematic Review and Meta-analysis.

Context Despite current recommendations, human papillomavirus vaccine uptake remains low. A systematic review and meta-analysis assessed the effectiveness of interventions targeting human papillomavirus vaccine initiation and completion among children, adolescents, and young adults aged 9–26 years. Evidence acquisition Three electronic databases (CINAHL, OVID, and Web of Science) were searched for articles published in English peer-reviewed journals between January 2006 and January 2017 of U.S. studies that evaluated intervention strategies and reported post-intervention human papillomavirus vaccine initiation or completion rates among individuals aged 9–26 years. Study characteristics and outcomes were extracted. Data were collected in 2016 and analyzed in 2017. Evidence synthesis Reviewers screened 983 unique titles and abstracts, read 241 full-text articles, and extracted data from 30 articles meeting the inclusion criteria (12 behavioral, ten environmental, four informational, and four combination strategies). Published EQUATOR (Enhancing the Quality and Transparency of Health Research) guidelines were used to assess study quality. Random effects meta-analyses were conducted. The meta-analyses included 17 RCTs and quasi-experiments involving 68,623 children, adolescents, and young adults. The pooled relative incidence estimates were 1.84 (95% CI=1.36, 2.48) for human papillomavirus vaccine initiation and 1.50 (95% CI=1.23, 1.83) for completion. Behavioral and informational interventions doubled human papillomavirus vaccine initiation (relative incidence estimate=2.04, 95% CI=1.36, 3.06 and relative incidence estimate=1.92, 95% CI=1.27, 2.91, respectively). Behavioral interventions increased completion by 68% (relative incidence estimate=1.68, 95% CI=1.25, 2.27). Conclusions Evidence supports behavioral interventions for increasing human papillomavirus vaccine initiation and completion. Future studies are needed to assess the effectiveness of interventions in reaching diverse populations and reducing missed opportunities for human papillomavirus vaccination.
Students Adding Value: Improving Patient Care Measures While Learning Valuable Population Health Skills:

Medical students are potential resources for ambulatory primary care practices if learning goals can align with clinical needs. The authors introduced a quality improvement (QI) curriculum in the ambulatory clinical rotation that matched student learning expectations with practice needs. In 2016-2017, 128 students were assigned to academic, university affiliated, community health, and private practices. Student project measures were matched with appropriate outcome measures on monthly practice dashboards. Binomial mixed effects models were used to model QI measures. For university collaborative practices with student involvement, the estimated odds of a patient being screened for breast cancer in March 2017 was approximately 2 times greater than in 2016. This odds ratio was 36.2% greater than the comparable odds ratio for collaborative practices without student involvement (95% confidence interval = 22.7% to 51.2% greater). When student curriculum and assignments align with practice needs, practice metrics improve and students contribute to improvements in real-world settings.
The Effect of Light Quality and Fertility on Long Term Interior Maintenance of Selected Foliage Plants

Ficus benjamina, F. stricta, Dieffenbachia amoena and Brassaia arboricola were used to determine the effects of light quality and fertility on long-term maintenance of foliage plants in low light. ...
Cholinergic plasticity in hippocampus of individuals with mild cognitive impairment: correlation with Alzheimer's neuropathology.

Several recent studies indicate that activity of cholinergic enzymes in the cortex of people with mild cognitive impairment (MCI) and early Alzheimer's disease (AD) are preserved. We correlated levels of hippocampal choline acetyltransferase (ChAT) activity with the extent of AD lesions in subjects from the Religious Order Study, including cases with no cognitive impairment (NCI), MCI, and with mild to moderate AD. Hippocampal ChAT activity levels were also determined in a group of end-stage AD patients who were enrolled in the University of Pittsburgh Alzheimer's Disease Research Center. MCI subjects were characterized with increased hippocampal ChAT activity. This elevation was no longer present in mild AD cases, which were not different from NCI subjects. Severe AD cases showed markedly depleted hippocampal ChAT levels. In NCI, MCI, and mild-moderate AD, there was a positive correlation between hippocampal ChAT activity levels and progression of neuritic plaque pathology in entorhinal cortex and hippocampus. A significant elevation of hippocampal ChAT in the MCI group was found selectively in the limbic (i.e., entorhinal-hippocampal, III/IV) Braak stages. We hypothesize that cholinergic changes in the hippocampus of MCI subjects reflect a compensatory response to the progressive denervation of the hippocampus by lost entorhinal cortex input. Moreover, the present findings suggest that the short-term memory loss observed in MCI is not caused by cholinergic deficits; it more likely relates to disrupted entorhinal-hippocampal connectivity.
Acceptability and Feasibility of a Telehealth Intervention for Sexually Transmitted Infection Testing Among Male Couples: Protocol for a Pilot Study.

Background: Gay, bisexual, and other men who have sex with men (MSM) are at elevated risk for acquiring sexually transmitted infections (STIs) in the United States, especially chlamydia and gonorrhea. While research has indicated main partners over casual partners may play a central role in STI risk, the frequency of STI screening among MSM couples is particularly low. Self-sample collection for chlamydia and gonorrhea screening has been shown to be highly accurate, and at-home STI testing has been shown to be highly acceptable among diverse populations. However, there is little research exploring the feasibility and acceptability of at-home chlamydia and gonorrhea screening among MSM couples. Our pilot study aims to help evaluate the viability of this screening modality as an intervention tool for MSM couples Objective: The objective of this study was to assess the feasibility and acceptability of an at-home chlamydia and gonorrhea sample collection and remote lab testing program among a sample of 50 MSM couples living in the United States. Methods: This pilot study enrolled 50 MSM couples, ranging from 18-40 years old and living in the United States, who participated in a larger at-home HIV testing randomized controlled trial. Participating couples completed a pretest instructional video call and then had the option of completing at-home sample collection across three bodily sites (rectal swab, pharyngeal swab, and urine sample) for remote chlamydia and gonorrhea lab testing. For participants who completed any sample collection, they received their results via a posttest video call. All participants completed an online survey examining satisfaction and acceptability of the home testing process, experience with logistics, willingness to test at home in the future, recent sexual risk behavior, STI testing history, and linkage to care. A subset of 10 couples completed an in-depth interview about their attitudes towards the sample collection process, different decisions they made while collecting their samples, and their experience accessing treatment (for those who received a positive result). Results: Recruitment began in September 2017, and as of March 2019 a total of 50 couples have been enrolled. Overall, 49/50 couples have returned their samples and completed the posttest delivery call, and 10 in-depth interviews have been completed and transcribed. Conclusions: Screening MSM couples at home for chlamydia and gonorrhea and providing video-facilitated results delivery may offer a tailored approach to address the increasing prevalence of these STIs. By collecting data on how MSM couples experience at-home STI screening, this project will provide valuable insight into the utility of such a service delivery program to public health interventionists and researchers alike.
Rényi Differential Privacy of the Sampled Gaussian Mechanism.

The Sampled Gaussian Mechanism (SGM)---a composition of subsampling and the additive Gaussian noise---has been successfully used in a number of machine learning applications. The mechanism's unexpected power is derived from privacy amplification by sampling where the privacy cost of a single evaluation diminishes quadratically, rather than linearly, with the sampling rate. Characterizing the precise privacy properties of SGM motivated development of several relaxations of the notion of differential privacy. This work unifies and fills in gaps in published results on SGM. We describe a numerically stable procedure for precise computation of SGM's R\'enyi Differential Privacy and prove a nearly tight (within a small constant factor) closed-form bound.
Technology Adoption in Spectrum Sharing: Estimating the Impact on Incumbents in the 3.5GHz Band

In spectrum sharing, incumbents are concerned about interference to their operations caused by spectrum entrants. Technical approaches, such as cognitive radios, spectrum databases, etc. have been developed in an attempt to minimize this interference. Whether the interference is co-channel or adjacent-channel, the power level of the interfering signal depends on the number of entrant radios and their spatial relationship to the incumbent operations. In this paper, we report on a modelling approach that is based on technology adoption literature and uses a tool that was developed for epidemiology to empirically estimate received signal power in a particular geographic location for a particular sharing framework (CBRS). Using this tool, we can estimate the received signal strength a particular points in space (US Naval base, in particular) under different technology adoption profiles, and allow these to change over time.
The pain of weight gain: self-experimentation with overfeeding

The Vermont overfeeding studies were published 50 y ago and began a change in the acceptance of obesity as a bona fide area of academic interest. This article chronicles the experience of the author with acute weight gain while overfeeding, in the context of current obesity research, and presents a glimpse of things to come. The pain associated with acute overeating is illustrated by the firsthand experience of the author. The rapid return to normal weight contrasts with the difficulty that almost all people with obesity experience when they attempt to lose and maintain weight loss. Contrasting the response to overfeeding of individuals who are "resistant" to obesity with those who are obesity prone provides an avenue for unraveling the difficulties people with obesity face when they try to lose weight.
Exogenous GDF11, but not GDF8, reduces body weight and improves glucose homeostasis in mice

Insulin resistance is associated with aging in mice and humans. We have previously shown that administration of recombinant GDF11 (rGDF11) to aged mice alters aging phenotypes in the brain, skeletal muscle, and heart. While the closely related protein GDF8 has a role in metabolism, limited data are available on the potential metabolic effects of GDF11 or GDF8 in aging. To determine the metabolic effects of these two ligands, we administered rGDF11 or rGDF8 protein to young or aged mice fed a standard chow diet, short-term high-fat diet (HFD), or long-term HFD. Under nearly all of these diet conditions, administration of exogenous rGDF11 reduced body weight by 3–17% and significantly improved glucose tolerance in aged mice fed a chow (~30% vs. saline) or HF (~50% vs. saline) diet and young mice fed a HFD (~30%). On the other hand, exogenous rGDF8 showed signifcantly lesser effect or no effect at all on glucose tolerance compared to rGDF11, consistent with data demonstrating that GFD11 is a more potent signaling ligand than GDF8. Collectively, our results show that administration of exogenous rGDF11, but not rGDF8, can reduce diet-induced weight gain and improve metabolic homeostasis.
Crack nucleation and growth during dynamic indentation of chemically-strengthened glass

Abstract Dynamic point impact loading is a primary cause of fracture of glass screens on mobile devices. An improved understanding of crack initiation and evolution under high-speed indentation could contribute to the development of materials with better performance, but experimental observations are challenging due to the short timescales and limited depth-of-field of optical microscopy. To address this need, we have observed fracture of a chemically-strengthened glass during dynamic indentation using in situ x-ray phase-contrast imaging (XPCI). Median cracks initiate below the surface of the glass, at a depth approximately corresponding to the depth at which the surface residual compressive stress diminishes to zero. These cracks initially propagate at ∼ 10 m s − 1 , rapidly accelerating to > 100 m s − 1 . We also observe some evidence for rate-dependent behavior, in that indentation at the lowest rates studied here (below about ∼ 0 . 15 m s − 1 ) fails to initiate cracks regardless of the depth of the indentation (up to 18 μ m ), while indentation at higher rates produces median cracks that either arrest or cause complete fracture, depending on the depth of indentation.
PopPhy-CNN: A Phylogenetic Tree Embedded Architecture for Convolutional Neural Networks to Predict Host Phenotype From Metagenomic Data

Accurate prediction of the host phenotype from a metagenomic sample and identification of the associated microbial markers are important in understanding potential host-microbiome interactions related to disease initiation and progression. We introduce PopPhy-CNN, a novel convolutional neural network (CNN) learning framework that effectively exploits phylogenetic structure in microbial taxa for host phenotype prediction. Our approach takes an input format of a 2D matrix representing the phylogenetic tree populated with the relative abundance of microbial taxa in a metagenomic sample. This conversion empowers CNNs to explore the spatial relationship of the taxonomic annotations on the tree and their quantitative characteristics in metagenomic data. We show the competitiveness of our model compared to other available methods using nine metagenomic datasets of moderate size for binary classification. With synthetic and biological datasets, we show the superior and robust performance of our model for multi-class classification. Furthermore, we design a novel scheme for feature extraction from the learned CNN models and demonstrate improved performance when the extracted features. PopPhy-CNN is a practical deep learning framework for the prediction of host phenotype with the ability of facilitating the retrieval of predictive microbial taxa.
Optimal experimental designs for ordinal models with mixed factors for industrial and healthcare applications

Models with ordinal outcomes are an important part of generalized linear models and design issues for them are less studied, especially when the model has discrete and continuous factors. We propos...
In situ monitoring of dislocation, twinning, and detwinning modes in an extruded magnesium alloy under cyclic loading conditions

Abstract This work investigates the microscopic deformation mechanisms of an extruded, precipitation-strengthened AZ80 magnesium (Mg) alloy subjected to strain-controlled low-cycle fatigue using in situ neutron diffraction measurements. Results demonstrate that the plastic deformation during cyclic loading is dominated by the alternating {10.2} extension twinning and detwinning mechanisms. The observed deformation mode is strongly texture and precipitate dependent. For the initial texture, the tested material has two major texture components which result in the occurrence of extension twinning during both compression and reverse tension in the first two cycles. The prolonged detwinning process in the following cycles is proposed to relieve the shear stress field of {00.2} grains, leading to the disappearance of twinning. The precipitation strengthening results in an increase of the critical resolved shear stress (CRSS) by ~33 MPa for the extension twinning in this AZ80 alloy. The synergistic effects of the initial texture, precipitation strengthening, and load sharing of various grain families and phases contribute to the complicated evolution of dominant deformation mechanisms, among which elevated dislocation activities are believed to be responsible for the relatively poor low-cycle-fatigue lifetime when compared to other Mg alloys.
Rapid high-resolution volumetric T1 mapping using a highly accelerated stack-of-stars Look Locker technique.

Abstract Purpose To develop a fast volumetric T1 mapping technique. Materials and methods A stack-of-stars (SOS) Look Locker technique based on the acquisition of undersampled radial data (>30× relative to Nyquist) and an efficient multi-slab excitation scheme is presented. A principal-component based reconstruction is used to reconstruct T1 maps. Computer simulations were performed to determine the best choice of partitions per slab and degree of undersampling. The technique was validated in phantoms against reference T1 values measured with a 2D Cartesian inversion-recovery spin-echo technique. The SOS Look Locker technique was tested in brain (n = 4) and prostate (n = 5). Brain T1 mapping was carried out with and without kz acceleration and results between the two approaches were compared. Prostate T1 mapping was compared to standard techniques. A reproducibility study was conducted in brain and prostate. Statistical analyses were performed using linear regression and Bland Altman analysis. Results Phantom T1 values showed excellent correlations between SOS Look Locker and the inversion-recovery spin-echo reference (r2 = 0.9965; p Conclusion A rapid volumetric T1 mapping technique was developed. The technique enables high-resolution T1 mapping with adequate anatomical coverage in a clinically acceptable time.
On products of consonant spaces

Abstract We establish some results about countable products of spaces that are either consonant or whose complement in some compactification has the Menger Property. We use our results to answer some questions of A. Bouziad.
Broadband 2DES detection of vibrational coherence in the Sx state of canthaxanthin.

The nonadiabatic mechanism that mediates nonradiative decay of the bright S2 state to the dark S1 state of carotenoids involves population of a bridging intermediate state, Sx, in several examples. The nature of Sx remains to be determined definitively, but it has been recently suggested that Sx corresponds to conformationally distorted molecules evolving along out-of-plane coordinates of the isoprenoid backbone near a low barrier between planar and distorted conformations on the S2 potential surface. In this study, the electronic and vibrational dynamics accompanying the formation of Sx in toluene solutions of the ketocarotenoid canthaxanthin (CAN) are characterized with broadband two-dimensional electronic spectroscopy (2DES) with 7.8 fs excitation pulses and detection of the linear polarization components of the third-order nonlinear optical signal. A stimulated-emission cross peak in the 2DES spectrum accompanies the formation of Sx in <20 fs following excitation of the main absorption band. Sx is prepared instantaneously, however, with excitation of hot-band transitions associated with distorted conformations of CAN’s isoprenoid backbone in the low frequency onset of the main absorption band. Vibrational coherence oscillation maps and modulated anisotropy transients show that Sx undergoes displacements from the Franck–Condon S2 state along out-of-plane coordinates as it passes to the S1 state. The results are consistent with the conclusion that CAN’s carbonyl-substituted β-ionone rings impart an intramolecular charge-transfer character that frictionally slows the passage from Sx to S1 compared to carotenoids lacking carbonyl substitution. Despite the longer lifetime, the S1 state of CAN is formed with retention of vibrational coherence after passing through a conical intersection seam with the Sx state.
Quantifying Age-Related Changes in Brain and Behavior: A Longitudinal versus Cross-Sectional Approach.

Cross-sectional versus longitudinal comparisons of age-related change have often revealed differing results. In the current study, we employed within-subject task-based fMRI to investigate changes in voxel-based activations and behavioral performance across the lifespan in the Reference Ability Neural Network (RANN) cohort, at both baseline and 5-year follow-up. We analyzed fMRI data from between 127 and 159 participants (20-80 years), on a battery of tests relating to each of four cognitive reference abilities (RAs). We applied a Gaussian age kernel to capture continuous change across the lifespan using a 5-year sliding window centered on each age in our participant sample, with a subsequent division into young, middle, and old age brackets. This method was applied separately to both cross-sectional approximations of change and real longitudinal changes adopting a comparative approach. We then focused on longitudinal measurements of neural change to identify regions expressing peak changes and fluctuations of sign change across our sample. Our results revealed several regions expressing divergence between cross-sectional and longitudinal measurements in each domain and age bracket; behavioral comparisons between measurements showed differences in change curves for all four domains, with processing speed displaying the steepest declines. In the longitudinal change measurement, we found lack of support for age-related frontal increases across analyses types, instead finding more posterior regions displaying peak increases in activation, particularly in the old age bracket. Our findings encourage greater focus on longitudinal measurements of age-related changes, which display appreciable differences from cross-sectional approximations. Significance Statement Knowledge of the aging process is mostly informed by cross-sectional studies. The fewer studies that have looked at longitudinal aging trajectories display variable consensus with cross-sectional findings. The current study provides a direct comparison between cross-sectional and longitudinal measurements of change in both neural activation and behavioral performance across several cognitive domains, providing insight into similarities versus discrepancies. Furthermore, it adopts a method of analysis used in the MRI 4D atlas literature to quantify continuous change across the lifespan through construction of neural activation “templates” that are generated from age-weighted averaging across the entire sample. Longitudinal measurements of change could then further be probed for characteristics such as peaks and change fluctuations, enabling a better understanding of true age-related changes.
Structuring Training Goals for Psychodynamic Psychotherapy

A multiaxial model that structures educational goals for psychodynamic psychotherapy has been developed. It specifies core aspects of psychodynamic psychotherapy, clusters them in categories that further define and link related areas, and presents a sequence that enables educators and students to focus on training goals in a consistent progression. This model has been used by the Director of Education as a basis for developing the curriculum, by students as a way of focusing learning and giving perspective to current work, and by supervisors to link individual teaching to the goals of the training program. This method has enhanced consistency, clarity, and efficiency in the psychotherapy program.
UTBiome: citizen science and campus community engagement

The University of Texas main campus is located at the heart of the city of Austin. The university campus can be used as “living” laboratory to engage students, faculty, and the public in general, in science. The UTBiome (aka “Mapping the UTBiome”) project, is a cross-disciplinary educational, research and outreach effort to (1) engage the community in the collection and analysis of environmental samples from campus environment, and (2) to create an open access web-based mapping platform to disseminate the environmental and microbiological data obtained. In this project, both indoor and outdoor environments are being interrogated to answer diverse scientific questions. Over 250 citizens from the university community have been involved to date in the collection of biological samples and environment metadata associated with key water quality metrics including temperature, nitrate, phosphate, dissolved oxygen, alkalinity, pH, turbidity and fecal indicator bacteria. A data management system was designed and implemented for both, ‘online’ data input through student’s mobile phones and to facilitate sample tracking. In order to fully engage the students and the UT community, we envisioned an interactive and innovative workflow, involving technology, automation, and social media. The interactive mapping platform we have created allow users within and outside the university to access and download the results and associated environmental data by simply clicking on the interactive map. The comprehensive UTBiome map created in ArcGIS can be found in this website http://crwr-utbiome.austin.utexas.edu/utb_webapp/utbiome.html (or just http://tinyurl.com/UTBiomeMap). The online platform design offers access to the environmental information, providing resources for students, faculty and the general public to learn more about the environment that surrounds us.
Architectural challenges of an electrical distribution system in prototype HEVs

Hybrid Electric Vehicle (HEV) prototypes are based off production platforms. Several new systems are added to the vehicle, either to perform hybrid functions or to support them and enhance vehicle performance and fuel economy. All these systems are electrically connected in the vehicle with overlay wiring harnesses. Architecture of overlay wiring harness for the HEV requires identification of new systems and working out their electrical connectivity requirements. This dictates the level of changes required in the vehicle electrical system. Harnesses are built based on the circuit design and location of these systems in the vehicle. EMI requirements, routing and packaging challenges are resolved during the overlay process and testing of the prototype. This paper presents the process of harness design, its architecture and integration challenges in the vehicle.
Not in My Backyard Pash v HPC: The Clash between Native Hawaiian Gathering Rights and Western Concepts of Property in Hawaii

This article examines the uneasy truce that exists between Western property law and the original Hawaiian native gathering practices that existed before the arrival of Europeans. The author traces the development of Hawaiian law from early cases that severely restricted gathering rights to more permissive results. The article demonstrates both the strengths and weaknesses of the present system of land tenure in Hawaii and argues for the continued expansion of native Hawaiian gather rights providing such expansion takes place within, not outside of, the dominant fee simple land tenure system now in place in Hawaii.
Effects of spinal anesthesia on maternal circulating catecholamines.

Abstract This study evaluated the effects of spinal anesthesia on maternal circulatinq catecholamines. Spinal anesthesia was administered to two groups of patients undergoing cesarean section. Nine patients were in labor; 14 were not in labor. Spinal anesthesia was followed by a significant reduction in norepinephrine (NE) in patients in labor (p
The Superconducting Flux Flow Transistor: Models and Applications

The superconducting flux flow transistor (SFFT) is a single film, active device generally made from high temperature superconducting (HTS) materials. The device is based on the magnetic control of flux motion, has gain and can operate to over 40 GHz with 3 µm feature size. Existing models are reviewed along with the latest equivalent circuit values derived from S-parameter measurements. Noise performance is compared to that predicted by a relatively simple flux noise model and recent amplifier performance is discussed.
To test or not to test? An updated evidence-based assessment of the value of screening and monitoring tests when using systemic biologic agents to treat psoriasis and psoriatic arthritis.

Background Safety profiles of systemic biologic agents for the treatment of psoriasis and psoriatic arthritis (PsA) encompass a wide spectrum of adverse events. To date, no uniform evidence-based guidelines exist regarding screening and monitoring patients who are undergoing biologic therapy. Objective We sought to identify studies evaluating screening and monitoring tests in the treatment of psoriasis and PsA with systemic biologic agents, and to propose evidence-based practical guidelines. Methods The MEDLINE database was searched to identify data on risks associated with adalimumab, etanercept, infliximab, and ustekinumab. Articles were reviewed and graded according to methods developed by the US Preventative Services Task Force. Results Evidence was strongest (grade B) for tuberculosis screening. Interferon-gamma release assay was preferable to tuberculin skin testing. Among known hepatitis B virus carriers, the evidence grade was C for monitoring liver function tests and viral load. Limitations This study was limited by the lack of high-quality controlled trials evaluating screening and monitoring tests in patients treated with biologic agents. Conclusions Baseline tuberculosis testing remains the only screening test with strong evidence to support its practice. Other screening and monitoring tests commonly performed in patients who are taking biologic agents are supported only in certain clinical settings or lack evidence to support or recommend against their practice.
The Structure of Stockholder Litigation: When Do the Merits Matter?

This Article investigates a question that has preoccupied corporate law scholarship for nearly 75 years: Do the merits matter in stockholder litigation? We exploit variation in the remedies available to stockholders at merger to show that classic stockholder litigation seems driven largely by factors unrelated to legal merit. Two unique features make the merger setting an especially apt setting to study this question. First, in merger litigation, the merits of the legal claims are uniquely easy to perceive. Prior work has relied on proxies for litigation merit — the presence of an accounting restatement, a parallel SEC inquiry, and so forth. A merger, however, is an end-period transaction, and the only issue of genuine consequence to a typical stockholder will be the adequacy of the merger consideration. The second unique advantage of studying mergers is that stockholders have two distinct types of legal remedies available to them — filing a class action alleging fiduciary breach or seeking stockholder appraisal. The fiduciary class action shares the same basic structure as other forms of stockholder litigation like federal securities suits and derivative claims: a class comprised of all shareholders, lead plaintiffs with small holdings, and plaintiffs’ attorneys who control of the claims. Appraisal litigation, by contrast, has none of these features. If the fiduciary class actions differ from appraisal in the incidence and intensity of litigation, we can thus conclude that the difference is attributable to the difference in structure. We analyze over 1,000 mergers from 2004 through 2013, investigating what factors are associated with fiduciary class actions and with appraisal filings. Fiduciary duty class actions challenging mergers are strongly associated with deal size, a variable that has far greater explanatory power than the merger premium. Our findings suggest that the merits count for little in the decision to bring a fiduciary suit and that such suits are brought for their nuisance value. By contrast, appraisal claims appear strongly related to legal merit. We argue that this difference demonstrates that litigation structure has a marked effect on the merits of claims. We also sketch out some preliminary reforms designed to restructure conventional stockholder litigation in ways that will reduce meritless claims and improve the incentive to prosecute strong claims.
Novel treatment of a central type, primitive neuroectodermal tumor of the ovary with postoperative pediatric medulloblastoma chemotherapy regimen: A case report and review of the literature

•Central type primitive neuroectodermal tumor (cPNET) of the ovary is difficult to treat.•Etoposide, cisplatin and cyclophosphamide is a pediatric medulloblastoma regimen.•Our case with cPNET responded to this combination chemotherapy.
The scavenging ratio normalized to remove the effect of humidity

Abstract The range of magnitude of mean observed scavenging (or washout) ratios is shown to be significantly decreased by removing the effect of humidity. This effect must be considered when concentrations and ratios are compared between events or locations, and even within a single event. An equation is derived that permits the calculation of ratios as the sum of three terms—nucleation, postnucleation and below-cloud scavenging. The equation is shown to be consistent with a variety of past observations and empirical relations. Parameters are identified that should be measured in monitoring and during experiments so as to improve upon ability to specify values of scavenging ratios for practical applications.
Spontaneous gastroduodenal perforation in patients with cancer receiving chemotherapy and steroids. Report of four cases combining 5‐fluorouracil infusion and cisplatin with antiemetics dexamethasone

Background. Spontaneous gastroduodenal perforation is an uncommon but life-threatening complication of systemic chemotherapy and/or steroids. Here, the authors reported four cases of gastroduodenal perforation following combined chemotherapy with steroids. Methods. The chemotherapeutic regimens all included 5-fluorouracil (5-FU) by continuous infusion and cisplatin. The authors used dexamethasone as an antiemetic. All patients took analgesics for pain relief. No patient had a history of peptic ulcer disease. Results. Severe epigastralgia occurred 3–5 days after the start of chemotherapy. The peptic ulcer perforations were diagnosed within 3 days of onset of symptoms. All patients had an emergency laparotomy. Three of the perforations were located in the duodenum and one was located in the stomach. Pathologic examination of one patient revealed a chronic peptic ulcer. Two patients with preoperative shock died in the postoperative period. Conclusions. The cause of spontaneous gastroduodenal perforation is not known, but the etiology can be complex. Either 5-FU or steroids can induce the perforation. An asymptomatic peptic ulcer may be aggravated by 5-FU, cisplatin, or dexamethasone. The authors suggest that patients receiving 5-FU infusion and cisplatin with dexamethasone for antiemesis who complain of epigastric pain should be mentioned for a gastroduodenal ulcer or even a perforation.