cssi/SciSciGPT-SciSciNet huggingface dataset:
Solid State Carbon-13 NMR Studies of Elastomers. XL N-t-Butyl Benzothiazole Sulfenimide Accelerated Sulfur Vulcanization of cis-Polyisoprene at 75 MHz

Abstract The network structure of TBSI-accelerated vulcanization of cis-polyisoprene was studied using C-13 solid-state NMR. The initial crosslink products consisted of A1c (cis) and A2c (cis) polysulfides. As the percent cure is increased, the A1c and A2c structures reduce in rank to monosulfides, and polysulfidic B1c (cis) and B1t (trans) structures are formed. During the maturation period C1c (cis) polysulfidic structures are also formed. The percent of sulfurization was shown to vary directly with sulfur concentration, while the efficiency of sulfurization (crosslink/cyclic-structure ratio) was shown to vary with accelerator content. TBSI-accelerated vulcanization was found to be more inefficient (lower crosslink/cyclic-structure ratio) than TBBS-accelerated vulcanization during the initial cure region. However, this results in shorter sulfur chains, which decreases the reactivity of TBSI vulcanizates as compared to TBBS vulcanizates during the reversion regime.
The effects of beta-adrenergic blocking agents on atherosclerosis and its complications.

Epidemiologic and experimental data are reviewed to determine whether treatment with beta-adrenergic blocking agents (‘beta blockers’) is likely to be antiatherogenic. Both indirect and direct evidence are considered. Indirect evidence is derived from studies of the effects of beta blockers on the risk factors for atherosclerosis, or on the disease sequelae of atherosclerosis. Direct evidence refers to studies in which atherosclerosis is an endpoint. Regarding indirect evidence, the data generally are consistent with a retarding or neutral effect of beta blockers on atherosclerosis. For example stroke incidence is reduced when hypertension is treated with beta blockers. About half of these same studies also show a reduction in the incidence of myocardial infarction, a complication that may be more closely related to atherosclerosis extent and severity than is stroke, which can have a nonatherosclerosis origin. The most important potential negative effect of beta blockers occurs with respect to serum lipid concentrations. However, there is no evidence that atherosclerosis is worsened as a result of pharmacologically induced alterations of serum lipids. The direct evidence more clearly indicates a retarding effect of beta blockers on atherosclerosis, with 11 of 13 studies having outcomes in this direction. However, interpretation of these studies is complicated by the fact that all of the data are derived from animal models, some of which are not similar to human beings in the development of atherosclerosis. Also, the studies are diverse, not only in the research designs and species utilized, but also in the type of beta blocker employed, the degree of beta blockade acheived, and the anatomic location of lesions. In summary. the data suggest that treatment with beta blockers may retard atherosclerosis. A more definitive answer requires efforts in two directions: (a) studies on atherosclerosis in selected populations of human beings, using cineangiography or autopsy material; and (b) additional, well-controlled studies in appropriate animal models.
Circadian Rhythms, Sleep, and Disorders of Aging.

Sleep–wake cycles are known to be disrupted in people with neurodegenerative disorders. These findings are now supported by data from animal models for some of these disorders, raising the question of whether the disrupted sleep/circadian regulation contributes to the loss of neural function. As circadian rhythms and sleep consolidation also break down with normal aging, changes in these may be part of what makes aging a risk factor for disorders like Alzheimer's disease (AD). Mechanisms underlying the connection between circadian/sleep dysregulation and neurodegeneration remain unclear, but several recent studies provide interesting possibilities. While mechanistic analysis is under way, it is worth considering treatment of circadian/sleep disruption as a means to alleviate symptoms of neurodegenerative disorders.
Interhemispheric subdural hematoma secondary to hemorrhage from a calloso-marginal artery aneurysm

This report documents two unusual consequencies of bleeding from an aneurysm located on the callosomarginal artery; the development of an acute interhemispheric subdural hematoma which was removed at operation six days after hemorrhage and the angiographic delineation of spontaneous thrombosis of the aneurysm two weeks after the initial ictus.
The Influence of Extracts of Anchylostoma Caninum on the Coagulation of the Blood and on Hemolysis

In former experiments, one of us (Loeb, with A. J. Smith) had found that in the anterior part of Anchylostoma caninum a substance is present that has a distinctly inhibiting action upon the coagulation of the blood.1 At that time we did not carry out experiments concerning the hemolytic action of such extracts, but we noticed that in the mixtures used for the determination of the coagulationtime no distinct hemolytic influence of the extract could be observed. In the posterior part of anchylostoma little of the substance inhibiting the coagulation was present in one experiment, while in the other experiments it was absent. Boiling the extract during a period of 15 minutes caused a marked weakening of its activity, without, however, destroying it entirely. At that time Loeb had assumed that the substance present in anchylostomum would in all probability be found to be similar to hirudin, the substance of the leech which inhibits coagulation, in fact the analogy which at that time appeared to exist between the behavior of the leech and of anchylostomum induced one of us to undertake these experiments. In order to test this hypothesis we carried out new experiments. For some time past we searched for specimens of Anchylostoma caninum in all the dogs upon which we performed an autopsy. The anchylostoma found were carefully washed and afterward dried with filter-paper. The worms thus freed from adhering intestinal contents were ground up in a porcelain mortar and the ground up material was dried at a temperature varying between approximately 420 and 500 C. The dried material was scraped off and collected in a bottle for further use. In this way approximately 170 mgm. dried substance of Anchylostoma caninum were obtained, which enabled us to carry out a limited number of experiments.
Memory Disruption Following Traumatic Brain Injury

Traumatic brain injury (TBI) is a major public health concern worldwide, and is the leading cause of disability and death in children and young adults. One of the most common consequences of TBI is cognitive impairment, including deficits in memory and executive function. Although some recovery of function is typical after injury, many individuals are left with lifelong memory problems. Therefore, it is important to understand how the brain’s memory systems are affected by various types of TBI. Such knowledge will improve our ability to understand what memory functions are most vulnerable to injury and then to use this information to develop more effective treatments and rehabilitation strategies to improve cognitive outcome. This chapter reviews studies of memory loss following TBI, with a focus on studies in animal models of brain injury and how results from these studies have shaped our understanding of the mechanisms and consequences of TBI on the brain’s memory systems. The chapter also considers how understanding the organization of multiple memory systems is shaping current research in the field, and describes recent studies based on the Kesner attribute model that provide new insights into how TBI affects memory and cognition.
Reversible Dopamine Transporter Modifications in Response to Methylphenidate Treatment of ADHD

Single-photon emission computed tomography (SPECT) was used to monitor the dopamine transporter activity in 5 males, ages 8 to 10, with ADHD, after cessation of methylphenidate (MPH) treatment, in a study at the University Hospital Maastricht, The Netherlands.
17β-Hydroxy-18-acetoxywithanolides from Aeroponically Grown Physalis crassifolia and Their Potent and Selective Cytotoxicity for Prostate Cancer Cells

When cultivated under aeroponic growth conditions, Physalis crassifolia produced 11 new withanolides (1–11) and seven known withanolides (12–18) including those obtained from the wild-crafted plant. The structures of the new withanolides were elucidated by the application of spectroscopic techniques, and the known withanolides were identified by comparison of their spectroscopic data with those reported. Withanolides 1–11 and 16 were evaluated for their potential anticancer activity using five tumor cell lines. Of these, the 17β-hydroxy-18-acetoxywithanolides 1, 2, 6, 7, and 16 showed potent antiproliferative activity, with some having selectivity for prostate adenocarcinoma (LNCaP and PC-3M) compared to the breast adenocarcinoma (MCF-7), non-small-cell lung cancer (NCI-H460), and CNS glioma (SF-268) cell lines used. The cytotoxicity data obtained for 12–15, 17, and 19 have provided additional structure–activity relationship information for the 17β-hydroxy-18-acetoxywithanolides.
Introduction: Defining Sustainable Electricity

There are many definitions of sustainability and company examples of how to meet social, environmental, and economic goals simultaneously. However, how can such approaches apply to the electric power industry, which is subject to heavy regulation and unable to forgo safe, affordable, and constantly reliable power? In Sustainable Electricity companies discuss some of the most hotly debated challenges of today: renewable energy, water use, species impacts, employee engagement, stakeholder communication, resiliency and climate change, distributed energy, energy efficiency, greenhouse gas emissions, consumer preferences, and business vitality. Unless we are satisfied with vague business commitments, the current definitions of sustainability to protect future generations are too nebulous to set goals, measure progress, and inform balanced outcomes in the electric power industry. This book provides concrete examples of what “sustainable electricity” will encompass in the next decade.
Social Business Planning: Management and Financial Issues

This chapter reviews some of the most well-known social business cases as well as social business literature, complemented with qualitative interviews with social business entrepreneurs and practitioners to identify common challenges, risks and opportunities from a management and financial perspective. An analysis of that literature and these interviews allows us to identify issues faced by social business practitioners that are not unique to them, along with others arising from the very concept of the social nature of their ventures.
Differential Expression of Ccn4 and Other Genes Between Metastatic and Non-metastatic EL4 Mouse Lymphoma Cells

Background Previous work characterized variants of the EL4 murine lymphoma cell line. Some are non-metastatic, and others metastatic, in syngenic mice. In addition, metastatic EL4 cells were stably transfected with phospholipase D2 (PLD2), which further enhanced metastasis. Materials and methods Microarray analyses of mRNA expression was performed for non-metastatic, metastatic, and PLD2-expressing metastatic EL4 cells. Results Many differences were observed between non-metastatic and metastatic cell lines. One of the most striking new findings was up-regulation of mRNA for the matricellular protein WNT1-inducible signaling pathway protein 1 (CCN4) in metastatic cells; increased protein expression was verified by immunoblotting and immunocytochemistry. Other differentially expressed genes included those for reproductive homeobox 5 (Rhox5; increased in metastatic) and cystatin 7 (Cst7; decreased in metastatic). Differences between PLD2-expressing and parental cell lines were limited but included the signaling proteins Ras guanyl releasing protein 1 (RGS18; increased with PLD2) and suppressor of cytokine signaling 2 (SOCS2; decreased with PLD2). Conclusion The results provide insights into signaling pathways potentially involved in conferring metastatic ability on lymphoma cells.
Wideband dual-mode monostatic simultaneous transmit and receive antenna system

A novel wideband monostatic simultaneous transmit and receive (STAR) antenna system based on eight-arm equiangular spiral aperture is proposed. The eight-arm STAR spiral is configured such that four arms are used for transmitting and the other four arms for receiving. The multi-mode characteristics of the four-arm spiral aperture along with applied excitation enable high TX/RX isolation for diverse circular-polarization modes of radiation (i.e. broadside and split-beam modes). The operational principles of the proposed system are discussed and the feasibility thereof is demonstrated computationally and experimentally. System isolation >40dB is obtained over 8:1 bandwidth for different modes of operation while maintaining similar high-quality TX/RX radiation characteristics.
Multiparametric Assessment of Gold Nanoparticle Cytotoxicity in Cancerous and Healthy Cells: The Role of Size, Shape, and Surface Chemistry

In recent years, we and others have become interested in evaluating the use of surface-enhanced Raman scattering (SERS) tags for early cancer detection and in designing new approaches to demonstrate the applicability of this spectroscopic technique in the clinic. SERS-based imaging in particular offers ultra sensitivity up to the single molecule, multiplexing capability, and increased photostability and has been shown to outperform fluorescence. However, to employ SERS tags for early cancer detection, it is important to understand their interaction with cells and determine their cytotoxicity. We have been particularly interested for quite some time in determining if and how gold nanostars, which have been demonstrated as outstanding SERS enhancing substrates, can be safely employed in living systems and translated to the clinic. In this study, we carried out a multiparametric in vitro study to look at the cytotoxicity and cellular uptake of gold nanoparticles on human glioblastoma and human dermal fibrobl...
Acquisition of accurate data from intramolecular quenched fluorescence protease assays

The Intramolecular Quenched Fluorescence (IQF) protease assay utilizes peptide substrates containing donor-quencher pairs that flank the scissile bond. Following protease cleavage, the dequenched donor emission of the product is subsequently measured. Inspection of the IQF literature indicates that rigorous treatment of systematic errors in observed fluorescence arising from inner-filter absorbance (IF) and non-specific intermolecular quenching (NSQ) is incompletely performed. As substrate and product concentrations vary during the time-course of enzyme activity, iterative solution of the kinetic rate equations is, generally, required to obtain the proper time-dependent correction to the initial velocity fluorescence data. Here, we demonstrate that, if the IQF assay is performed under conditions where IF and NSQ are approximately constant during the measurement of initial velocity for a given initial substrate concentration, then a simple correction as a function of initial substrate concentration can be derived and utilized to obtain accurate initial velocity data for analysis.
Unexpected Aphasia following Right Temporal Lobectomy as Treatment of Recurrent Super-Refractory Status Epilepticus

Background Super-refractory status epilepticus (SRSE) is a critical neurological condition with a high mortality rate. There are only limited data to direct the treatment in SRSE, and surgery has been reported to successfully stop SRSE. We present a case of recurrent SRSE treated with urgent right temporal lobectomy in a right-handed woman which potentially saved her life but resulted in crossed sensory aphasia. Case description A 61-year-old woman with a recent episode of prolonged focal SRSE due to right frontotemporal meningioma and hyperkalemia was admitted for recurrence of seizures that evolved to SRSE despite aggressive treatment with multiple fosphenytoin antiepileptic drugs (AEDs) and anesthetics. The patient underwent a right temporal lobectomy to remove the encephalomalacic and gliotic tissue around the meningioma that had been resected during a previous admission. Postoperatively the patient had a protracted course with modest improvement after stepwise reduction in her AEDs; however, her recovery unveiled a severe crossed aphasia. Conclusion Resective surgery is an effective treatment option in the treatment of SRSE, although the recovery period can be protracted. Crossed aphasia after right temporal lobectomy should be considered in patients where it is not possible to complete a presurgical evaluation of higher cortical functions.
The Relevance of Brain-Behavior Relationships for Rehabilitation

In order to assess the implications of brain-behavior relationships for rehabilitation, two separate yet related issues will be considered: (1) How can recovery be understood in terms of the capacity of the central nervous system to respond to injury? Specifically, what mechanisms have been proposed to account for recovery?; and (2) To what extend may a role for environmental influence in the recovery process be defended?
Callous-Unemotional Traits Modulate Brain Drug Craving Response in High-Risk Young Offenders

Adults with psychopathy have a high propensity for substance abuse, generally starting from a young age. This investigation tested hypotheses about differences in the neural responses associated with drug craving among high-risk young offenders with histories of abuse of stimulants and other drugs as a function of psychopathic traits. Fifty-four male adolescents (44 with a history of stimulant abuse and 10 controls) incarcerated at a maximum-security facility (M age = 17.08 years) completed a drug-cue exposure task while brain hemodynamic activity was monitored using functional magnetic resonance imaging (fMRI) with a mobile MRI scanner stationed at the facility. Psychopathic traits were assessed using the Hare Psychopathy Checklist: Youth Version (PCL:YV). In the stimulant abuser group, drug cues elicited activity in classic reward circuitry. Consistent with studies of adult psychopathic traits and substance abuse, there was a negative association between PCL-YV scores and hemodynamic response related to drug craving in the amygdala and ACC in youth with a history of stimulant abuse. However, there were considerably more negative associations between the PCL:YV and hemodynamic response among youth than adults and this was primarily due to callous-unemotional traits rather than interpersonal or behavioral traits. The implications for how personality traits modulate motivations for drug-seeking behavior among adolescent offenders are discussed.
Opportunities and challenges in converting a pharmacy curriculum elective course from a live to an online teaching environment

Objective: Discuss the strengths and limitations regarding creating and implementing an asynchronous online elective course on drug discovery within an accredited college of pharmacy’s Pharm.D. curriculum. Methods: Students enrolled in the first two iterations of the course were surveyed before and after course completion. Results: All liked the convenience of self-paced online learning with the first offering. Despite student satisfaction, most (63%) students watched half or fewer lectures. In the second offering, course satisfaction was comparable to the first. Implementation of short post-lecture quizzes substantially increased lecture viewership. Lower satisfaction rates were noted across both course iterations when students were asked whether interaction with faculty and peers was sufficient. Conclusion: Our experience demonstrates that the flexibility of online education comes at the potential cost of additional work and reduced interaction among students and faculty. However, overall student approval was high with this course style and all students reported they would recommend it to others.
DIRECT ORAL ANTICOAGULANTS COMPARED TO WARFARIN FOR LEFT VENTRICULAR THROMBI: A SINGLE CENTER EXPERIENCE

Off-label use of direct oral anticoagulants (DOACs) has outpaced evidence of efficacy, including for left ventricular thrombi (LVT). We hypothesized that utilization of DOACs for LVT may be approaching that of more established agents and that differences in efficacy may exist. We reviewed all LVT
Neutron Transmutation Doping of p-Type Czochralski-Grown Gallium Arsenide

We have studied the neutron transmutation doping process in bulk GaAs grown by the liquid encapsulated Czochralski technique. By choosing undoped, but initially p-type samples for irradiation, we observed the effects of transmutation doping with Se and Ge donors both at low doping levels as added compensation in p-type samples, and at higher doping levels as added donors in n-type samples. We found that a measurable fraction of NTD-produced Ge atoms act as acceptors rather than donors in our material.
MOLECULAR TARGETS FOR METHOTREXATE

Publisher Summary This chapter discusses molecular targets for methotrexate (MTX). Two targets for MTX have been identified in eukaryotic cells. The first is dihydrofolate eductase. This enzyme is involved in thymidylate synthesis and plays a key role in DNA formation and cell replication. The drug binds tightly to, and inactivates, dihydrofolate reductase; under certain conditions, however, this interaction may induce a conformational change in the enzyme that leads to the production of a form having a reduced affinity for the drug. Prevention of this sequence would presumably maximize the effectiveness of the drug. The second target is the cAMP-regulated, 5-methyltetrahydrofolate transport system whose components have not yet been isolated from membranes of eukaryotic cells. However, a study of the folate transport system in L. casei has revealed some mechanistic details which may be relevant to the eukaryotic counter-part. Both dihydrofolate reductase and the binding protein contain specific sites for interaction with MTX, and information about the topography of these sites should facilitate the design of drug analogs capable of maximum interaction with these targets.
A behavior-theoretic evaluation of values clarification on parental beliefs and intentions toward genomic sequencing for newborns

Abstract Decision aids commonly include values clarification exercises to help people consider which aspects of a choice matter most to them, and to help them make decisions that are congruent with their personal values and preferences. Using a randomized online experiment, we examined the influence of values clarification on parental beliefs and intentions about having genomic sequencing for newborns. We recruited 1186 women and men ages 18–44 who were pregnant or whose partner was pregnant or planning to become pregnant in the next two years. Participants (N = 1000) completed one of two versions of an online decision aid developed as part of a larger project examining the technical, clinical, and social aspects of using exome sequencing to screen newborns for rare genetic conditions. The education-only version provided information about using genomic sequencing to screen newborns for medically treatable conditions. The education-plus-values-clarification version included the same information, along with a values clarification exercise in which participants classified as important or unimportant five reasons in support of having and five reasons against having their newborn undergo genomic sequencing. We conducted partial correlations, regression analysis, and MANCOVAs with sex, health literacy, and experience with genetic testing as covariates. Participants who completed the decision aid with the values clarification exercise agreed less strongly with four of the five statements against sequencing compared to participants who viewed the education-only decision aid. The groups did not differ on agreement with reasons in support of sequencing. Agreement with four of five reasons against genomic sequencing was negatively associated with intentions to have their newborn sequenced, whereas agreement with all five reasons in support of sequencing were positively associated with intentions.
Mapping the microbial interactome: Statistical and experimental approaches for microbiome network inference.

Advances in high-throughput sequencing have ushered in a new era of research into the gut microbiome and its role in human health and disease. However, due to the unique characteristics of microbio...
A computational approach for evaluating post-disaster transportation network resilience

The comprehension of transportation network resilience is of prime interest to transportation agencies. Thus, this study seeks to complement the ongoing discussion by (i) extending a traffic assign...
The second rational homology group of the moduli space of curves with level structures

Abstract Let Γ be a finite-index subgroup of the mapping class group of a closed genus g surface that contains the Torelli group. For instance, Γ can be the level L subgroup or the spin mapping class group. We show that H 2 ( Γ ; Q ) ≅ Q for g ⩾ 5 . A corollary of this is that the rational Picard groups of the associated finite covers of the moduli space of curves are equal to Q . We also prove analogous results for surface with punctures and boundary components.
How to Ask Questions

Questions focus creative sparks onto a problem. The right question lies at the heart of innovations. Indeed, to achieve out-of-the-box thinking, one needs to perform out-of-the-box questioning. Closed questions have constricted answers, whether yes/no, true/false, or multiple choice. They are suitable for rapid-fire feedback and confirmation of ideas. Open questions have long-form answers. They invite respondents to elaborate on their ideas, conveying the contextual nuance of a situation. Cleverly crafted questions contain within them a frame of reference that guides the respondent’s analysis and answer. Energy strategists need to constantly probe for gaps in knowledge, opportunities to chase, and unknowns to learn. Nurturing a culture of inquiry can help open the team’s minds to ideas beyond one’s experiences.
eHealth in kidney care

eHealth is gaining momentum in nephrology, although evidence for its efficacy remains unclear and challenges to its widespread adoption persist. Successful integration of eHealth into kidney care will require patient engagement to develop effective interventions and issues such as data validity, regulation, oversight and adequate infrastructure to be addressed.
Enhancement of homology-directed repair with chromatin donor templates in cells

A key challenge in precise genome editing is the low efficiency of homology-directed repair (HDR). Here we describe a strategy for increasing the efficiency of HDR in cells by using a chromatin donor template instead of a naked DNA donor template. The use of chromatin, which is the natural form of DNA in the nucleus, increases the frequency of HDR-edited clones as well as homozygous editing. In addition, transfection of chromatin results in negligible cytotoxicity. These findings suggest that a chromatin donor template should be useful for a wide range of HDR applications such as the precise insertion or replacement of DNA fragments that contain the coding regions of genes.
The Definitive Diagnosis of Mycoplasma Infections

Mycoplasma pneumoniae is no longer the only mycoplasma recognized as a pathogen for humans. The emergence of Mycoplasma hominis and Ureaplasma urealyticum as genitourinary tract pathogens in adults (1), as well as for the fetus in utero and the neonate (2), makes isolation of these organisms no longer a research exercise but an essential diagnostic laboratory test. It is for this reason that the methodology for isolation and identification of these organisms must be reviewed. Another area of major import has been the development of a reproducible antibiotic susceptibility test which has relevance to attainable serum levels of the different antibiotics. This is critical for instituting appropriate and effective therapy.
Modeling mesoscale energy localization in shocked HMX, part I: machine-learned surrogate models for the effects of loading and void sizes

This work presents the procedure for constructing a machine-learned surrogate model for hot-spot ignition and growth rates in pressed HMX materials. A Bayesian kriging algorithm is used to assimilate input data obtained from high-resolution mesoscale simulations. The surrogates are built by generating a sparse set of training data using reactive mesoscale simulations of void collapse by varying loading conditions and void sizes. Insights into the physics of void collapse and ignition and growth of hot spots are obtained. The criticality envelope for hot spots is obtained as the function $$ \varSigma_{\text{cr}} = f\left( {P_{\text{s}} ,D_{\text{void}} } \right) $$ where $$ P_{\text{s}} $$ is the imposed shock pressure and $$ D_{\text{void}} $$ is the void size. Criticality of hot spots is classified into the plastic collapse and hydrodynamic jetting regimes. The information obtained from the surrogate models for hot-spot ignition and growth rates and the criticality envelope can be utilized in meso-informed ignition and growth models to perform multi-scale simulations of pressed HMX materials.
Use of Machine Learning to Screen for Acute Respiratory Distress Syndrome Using Raw Ventilator Waveform Data.

To develop and characterize a machine learning algorithm to discriminate acute respiratory distress syndrome from other causes of respiratory failure using only ventilator waveform data. Design Retrospective, observational cohort study. Setting Academic medical center ICU. Patients Adults admitted to the ICU requiring invasive mechanical ventilation, including 50 patients with acute respiratory distress syndrome and 50 patients with primary indications for mechanical ventilation other than hypoxemic respiratory failure. Interventions None. Measurements and main results Pressure and flow time series data from mechanical ventilation during the first 24-hours after meeting acute respiratory distress syndrome criteria (or first 24-hr of mechanical ventilation for non-acute respiratory distress syndrome patients) were processed to extract nine physiologic features. A random forest machine learning algorithm was trained to discriminate between the patients with and without acute respiratory distress syndrome. Model performance was assessed using the area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value. Analyses examined performance when the model was trained using data from the first 24 hours and tested using withheld data from either the first 24 hours (24/24 model) or 6 hours (24/6 model). Area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value were 0.88, 0.90, 0.71, 0.77, and 0.90 (24/24); and 0.89, 0.90, 0.75, 0.83, and 0.83 (24/6). Conclusions Use of machine learning and physiologic information derived from raw ventilator waveform data may enable acute respiratory distress syndrome screening at early time points after intubation. This approach, combined with traditional diagnostic criteria, could improve timely acute respiratory distress syndrome recognition and enable automated clinical decision support, especially in settings with limited availability of conventional diagnostic tests and electronic health records.
Initial Validation Evidence for Clinical Case Presentations by Student Pharmacists.

Objective: There is a paucity of validation evidence for assessing clinical case-presentations by Doctor of Pharmacy (PharmD) students. Within Kane’s Framework for Validation, evidence for inferences of scoring and generalization should be generated first. Thus, our objectives were to characterize and improve scoring, as well as build initial generalization evidence, in order to provide validation evidence for performance-based assessment of clinical case-presentations. Design: Third-year PharmD students worked up patient-cases from a local hospital. Students orally presented and defended their therapeutic care-plan to pharmacist preceptors (evaluators) and fellow students. Evaluators scored each presentation using an 11-item instrument with a 6-point rating-scale. In addition, evaluators scored a global-item with a 4-point rating-scale. Rasch Measurement was used for scoring analysis, while Generalizability Theory was used for generalization analysis. Findings: Thirty students each presented five cases that were evaluated by 15 preceptors using an 11-item instrument. Using Rasch Measurement, the 11-item instrument’s 6-point rating-scale did not work; it only worked once collapsed to a 4-point rating-scale. This revised 11-item instrument also showed redundancy. Alternatively, the global-item performed reasonably on its own. Using multivariate Generalizability Theory, the g-coefficient (reliability) for the series of five case-presentations was 0.76 with the 11-item instrument, and 0.78 with the global-item. Reliability was largely dependent on multiple case-presentations and, to a lesser extent, the number of evaluators per case-presentation. Conclusions: Our pilot results confirm that scoring should be simple (scale and instrument). More specifically, the longer 11-item instrument measured but had redundancy, whereas the single global-item provided measurement over multiple case-presentations. Further, acceptable reliability can be balanced between more/fewer case-presentations and using more/fewer evaluators.
Enhancing Subject and Keyword Access to Periodical Abstracts and Indexes

Bibliographic records in an online catalog for periodical abstracts and indexes lack adequate subject and keyword access. Access can be improved by adding L.C. subject headings, and by expanding the use of the contents note. However, no good methodology currently exists to provide optimum access given the constraints of the bibliographic record and of online catalogs.
Experiences with Dihedral Angle Space Monte Carlo Search for Small Protein Structures

In this article, we describe the experiences we had in trying to find the native conformation of polypeptides and a small protein molecule, crambin, by means of the Monte Carlo (MC) sampling procedure.
PHF-Tau from Alzheimer Brain is Rapidly Dephosphorylated and Degraded When Injected into Neurons in situ

Accumulation of abnormally modified tau protein (PHF-tau) is the principal intracellular lesion in a variety of neurodegenerative diseases, including Alzheimer's Disease (AD), but the cellular mechanisms underlying this accumulation are unknown. In this study, the cellular metabolism of PHF-tau purified from AD brain was investigated by microinjecting it into identified central neurons of the lamprey, a lower vertebrate. Dephosphorylation of 2 critical epitopes (the PHF-1 and TAU-1 sites), occurred within a few hours of PHF-tau microinjection, while proteolysis was complete by 2 days. These results constitute the first demonstration of the intracellular degradation of PHF-tau in an experimental in vivo system and suggest that the degradation of PHF-tau in situ is preceded by dephosphorylation. They also suggest that intracellular PHF-tau accumulation is primarily due to the failure of normal dephosphorylation and/or proteolytic mechanisms during neurofibrillary degenerative disease.
Distinct Control of the Frequency and Allelic Exclusion of the Vβ Gene Rearrangement at the TCRβ Locus

Ag receptor gene loci contain many V gene segments, each of which is recombined and expressed at a different frequency and is subject to allelic exclusion. To probe the parameters that mediate the different levels of regulation of V gene rearrangement, a Vβ gene segment together with 3.6-kb 5′ and 0.7-kb 3′ flanking sequences was inserted 6.8 kb upstream of the Dβ1 gene segment in the murine TCRβ locus. Despite its proximity to the Dβ gene segments and the Eβ enhancer, the inserted Vβ segment underwent VDJ recombination at the same frequency as the natural copy located 470 kb upstream. However, the inserted Vβ segment was no longer under allelic exclusion control as it recombined at a similar frequency in the presence of a TCRβ transgene. These results suggest that while the inserted fragment contains the necessary cis -regulatory elements for determining the frequency of Vβ rearrangement, additional cis -regulatory elements are required for mediating Vβ allelic exclusion. Interestingly, most of the inserted Vβ rearrangements were not transcribed and expressed in the presence of a TCRβ transgene, suggesting that TCRβ allelic exclusion can also be achieved by blocking the transcription of the rearranged gene segments. These findings provide strong evidence for distinct control of the frequency and allelic exclusion of Vβ gene rearrangement.
The Significance of Sprint/United Management Company v. Mendelsohn: A Reply to Professors Gregory and Secunda

In this Essay I reply to Professor David Gregory and Paul Secunda's comments about my principal article, Sprint/United Management Co. vs. Mendelsohn: The Supreme Court Appears To Have Punted On The Admissibility of Me Too Evidence Of Discrimination. But Did it? 102 Nw. U. L. Rev. 264 (2008). Both of these articles are important pieces of scholarship. David Gregory, Sprint/United Management Company v. Mendelsohn and Case-by-Case Adjudication of Me Too Evidence of Discrimination, 102 Nw. U. L. Rev. Colloquy 382 (2008); Paul M. Secunda, The Many Mendelsohn Me Too Missteps: An Alliterative Response To Professor Rubinstein, 102 Nw. U. L. Rev. Colloquy 264 (2008). I primarily focused this response on my disagreement with Professor Secunda's argument that the Court had to punt the issue of the admissibility of me too evidence and with his claim that the Court made a mistake in granting certiorari. While I agree that the Court correctly remanded the case, a remand does not require a judicial punt. I believe that the Court had the opportunity to provide such guidance and simply blew it. I also disagree with Professor Secunda's view that the Court incorrectly granted certiorari. I believe that Professor Secunda reads too much into what he admits are oral argument tea leaves. As I demonstrated in my principle article, the state of the law was in a complete disarray prior to Sprint being granted review. Therefore, the Supreme Court had good reason to review this important issue. As Professor Gregory and I both noted, post Sprint lower courts are already divided over how to treat the admissibility of me too evidence. Therefore, there is no reason why the Court should not take this issue up again.
Nonserologic Assays for Detection of Bacteria and Other Nonviral Infections

Many of the old microbiology techniques continue to play an integral part in the laboratory diagnosis of infectious diseases. However, in the past several years advances in technology enabled the clinical microbiology laboratory to respond rapidly to the needs of patients and clinicians for the identification of possible infections. Three topic areas are discussed in this chapter. The first outlines specimen collection guidelines, various culture protocols for the isolation of organisms, identification protocols, and the value of antimicrobial susceptibility testing. The second broad category covers methods for the immunological detection of nonviral infectious processes. The final section introduces the expanding area of molecular microbiology.
Contacts to group III nitride semiconductor alloys

In group III nitride semiconductor alloys, such as Al/sub x/Ga/sub 1-x/N, most contacts are very similar to those for GaN. In this presentation, we have explored a special consideration of the contact metallurgy alloy semiconductors and how interfacial reactions with metals can lead to compositional shifts in the semiconductor alloys beneath the contacts. High temperature annealing of the late transition Ni and Pd on Al/sub x/Ga/sub 1-x/N leads to compositional shift in the semiconductor immediately beneath the contact metal, as determined by X-ray photoelectron spectroscopy and scanning transmission electron microscopy. It has also been reported that a significant reduction in the resistance of ohmic contacts to n-type Al/sub x/Ga/sub 1-x/N with x>0.4 takes place using a contact metallurgy. In addition to describing these contacts, we offer a possible explanation for the advantage of using V-based contacts, developed by considering the metallurgy of contacts to the Al/sub x/Ga/sub 1-x/N semiconductor alloy.
Enhancement of Antiviral Immunity by Small Molecule Antagonist of Suppressor of Cytokine Signaling

Suppressors of cytokine signaling (SOCSs) are negative regulators of both innate and adaptive immunity via inhibition of signaling by cytokines such as type I and type II IFNs. We have developed a small peptide antagonist of SOCS-1 that corresponds to the activation loop of JAK2. SOCS-1 inhibits both type I and type II IFN activities by binding to the kinase activation loop via the kinase inhibitory region of the SOCS. The antagonist, pJAK2(1001–1013), inhibited the replication of vaccinia virus and encephalomyocarditis virus in cell culture, suggesting that it possesses broad antiviral activity. In addition, pJAK2(1001–1013) protected mice against lethal vaccinia and encephalomyocarditis virus infection. pJAK2(1001–1013) increased the intracellular level of the constitutive IFN-β, which may play a role in the antagonist antiviral effect at the cellular level. Ab neutralization suggests that constitutive IFN-β may act intracellularly, consistent with recent findings on IFN-γ intracellular signaling. pJAK2(1001–1013) also synergizes with IFNs as per IFN-γ mimetic to exert a multiplicative antiviral effect at the level of transcription, the cell, and protection of mice against lethal viral infection. pJAK2(1001–1013) binds to the kinase inhibitory region of both SOCS-1 and SOCS-3 and blocks their inhibitory effects on the IFN-γ activation site promoter. In addition to a direct antiviral effect and synergism with IFN, the SOCS antagonist also exhibits adjuvant effects on humoral and cellular immunity as well as an enhancement of polyinosinic-polycytidylic acid activation of TLR3. The SOCS antagonist thus presents a novel and effective approach to enhancement of host defense against viruses.
A confirmatory study of violence risk assessment tool (M55) and demographic predictors of patient violence.

ideker k., todicheeney-mannes d. & kim s.c. (2011) A confirmatory study of Violence Risk Assessment Tool (M55) and demographic predictors of patient violence. Journal of Advanced Nursing67(11), 2455–2462. Abstract Aim. The aims of this study were to confirm the usefulness of Violence Risk Assessment Tool (M55) for prospectively identifying violent patients in medical–surgical units and to explore predictors of Code-55 activation for violent behaviour or physical attack. Background. A previous retrospective case-controlled study claimed moderate sensitivity and high specificity of the M55 in identifying potentially violent patients. However, the usefulness of M55 needs to be confirmed in a prospective study before wide adoption. Methods. A prospective cohort study of patients in medical–surgical units of a hospital in southern California was conducted from August 2009 to December 2009. A checklist containing the M55 was completed on admission. Following a violent event or just prior to discharge, the violent event outcome section of the data collection tool was completed. The sensitivity and specificity of M55 for identifying the violent patients were calculated using the original M55 flagging criteria. Results. Of 2063 patients, 32 (1·6%) had a violent event of Code-55 activation (12), physical attack (26) or both (6). The M55 showed a low sensitivity (41%) and acceptable specificity (99%) for prospectively identifying violent patients. The multivariate logistic regression model indicated higher odds of violent events for patients ≥70 years of age [odds ratio (OR) = 2·3; 95% confidence interval (CI): 0·9–5·7], males (OR = 2·7; 95% CI: 1·2–6·1) or Caucasian (OR = 3·4; 95% CI: 0·8–14·7). Conclusion. The M55 does not appear to be useful for prospectively identifying violent patients in medical–surgical units because of low sensitivity. Older, male or Caucasian patients had higher odds of becoming violent.
Profiling the Essential Nature of Lipid Metabolism in Asexual Blood and Gametocyte Stages of Plasmodium falciparum

During its life cycle, Plasmodium falciparum undergoes rapid proliferation fueled by de novo synthesis and acquisition of host cell lipids. Consistent with this essential role, Plasmodium lipid synthesis enzymes are emerging as potential drug targets. To explore their broader potential for therapeutic interventions, we assayed the global lipid landscape during P. falciparum sexual and asexual blood stage (ABS) development. Using liquid chromatography-mass spectrometry, we analyzed 304 lipids constituting 24 classes in ABS parasites, infected red blood cell (RBC)-derived microvesicles, gametocytes, and uninfected RBCs. Ten lipid classes were previously uncharacterized in P. falciparum, and 70%-75% of the lipid classes exhibited changes in abundance during ABS and gametocyte development. Utilizing compounds that target lipid metabolism, we affirmed the essentiality of major classes, including triacylglycerols. These studies highlight the interplay between host and parasite lipid metabolism and provide a comprehensive analysis of P. falciparum lipids with candidate pathways for drug discovery efforts.
An algorithm for early breast cancer detection in mammograms

Presents a novel algorithm specifically designed for detecting clusters of microcalcifications that are early mammographic signs of breast cancer. The algorithm, which can be implemented in a general-purpose computer, is intended to assist the radiologist by indicating the location of suspicious clusters. A small number of parameters (features) are extracted from the mammogram and used in a decision-making process that requires no human supervision. >
Computational Studies: B12 Cofactors and their Interaction with Enzyme Active Sites

Cyanocobalamin, commonly known as vitamin B12, and its biologically active derivatives, 5′-deoxyadenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl), have long fascinated scientists with their elaborate structures and intriguing reactivities in enzymatic systems. While the large size and complex electronic structures of these cofactors have posed a major challenge for theoretical chemists, recent insights gained from kinetic, spectroscopic, and X-ray crystallographic studies have established an excellent foundation for validating computational investigations of the geometric, electronic, and reactivity properties of the isolated cofactors and the molecular details of the catalytic cycles of B12-dependent enzymes. This review—which is by no means exhaustive—summarizes salient information that has been obtained from experimentally validated computational studies of the following: (i) the free B12 cofactors in their Co3+, Co2+, and Co1+ oxidation states; (ii) the mechanism by which enzymes involved in the biosynthesis of AdoCbl overcome the large thermodynamic barrier associated with the Co2+ Co1+ reduction; (iii) plausible strategies by which AdoCbl-dependent enzymes achieve a trillion-fold rate of acceleration for the homolytic cleavage of the cofactor's CoC(Ado) bond; and (iv) the means by which MeCbl-dependent methyltransferases regenerate the active MeCbl cofactor and accelerate the rate of methyl transfer via heterolytic CoC(Me) bond cleavage by as many as 6 orders of magnitude. Keywords: adenosylcobalamin; ATP:corrinoid adenosyltransferases; coenzyme B12; density functional theory; isomerases; methylcobalamin; methyltransferases; quantum mechanics/molecular mechanics; time-dependent density functional theory