cssi/SciSciGPT-SciSciNet huggingface dataset:
D-dimer levels in VTE patients with distal and proximal clots.

Abstract Objectives There is growing evidence that venous thromboembolism (VTE) patients with distal clots (distal calf deep vein thrombosis [DVT] and sub-segmental pulmonary embolism [PE]) may not routinely benefit from anticoagulation. We compared the D-dimer levels in VTE patients with distal and proximal clots. Methods We conducted a multinational, prospective observational study of low-to-intermediate risk adult patients presenting to the emergency department (ED) with suspected VTE. Patients were classified as distal (calf DVT or sub-segmental PE) or proximal (proximal DVT or non-sub-segmental PE) clot groups and compared with univariate and multivariate analyses. Results Of 1752 patients with suspected DVT, 1561 (89.1%) had no DVT, 78 (4.4%) had a distal calf DVT, and 113 (6.4%) had a proximal DVT. DVT patients with proximal clots had higher D-dimer levels (3760 vs. 1670 mg/dL) than with distal clots. Sensitivity and negative predictive value (NPV) for proximal DVT at an optimal D-dimer cutoff of 5770 mg/dL were 40.7% and 52.1% respectively. Of 1834 patients with suspected PE, 1726 (94.1%) had no PE, 7 (0.4%) had isolated sub-segmental PE, and 101 (5.5%) had non-sub-segmental PE. PE patients with proximal clots had higher D-dimer levels (4170 vs. 2520 mg/dL) than those with distal clots. Sensitivity and NPV for proximal PE at an optimal D-dimer cutoff of 3499 mg/dL were 57.4% and 10.4% respectively. Conclusions VTE patients with proximal clots had higher D-dimer levels than patients with distal clots. However, D-dimer levels cannot be used alone to discriminate between VTE patients with distal or proximal clots.
Effect of hot carrier stress on device junctions measured by electron holography and scanning capacitance microscopy

The effect of hot carrier injection on the FET's junction properties has been investigated for CMOS NFET devices. Junction profiles and carrier concentration of stressed and unstressed devices are measured and compared by dual lens electron holography and scanning capacitance microscopy, respectively. The measurements reveal that the width of the junction on the drain side of the device that undergoes hot carrier stressing decreases, indicating a reduction in active carrier concentration. These results are consistent with the hypothesis of phosphorous dopant passivation by the hot carrier induced release of hydrogen into the drain side extension region.
Iatrogenic Facial Palsy: The Cost:

The cost of iatrogenic facial paralysis can be high. Ways to avoid facial nerve injury during surgery and, should it occur, ways to minimize the disability and cost are discussed. These include adequate preparation and training by the surgeon, the exercise of sound judgment, the presence of high morals by the surgeon, adequate preoperative diagnosis and surgical instrumentation and thorough preoperative oral and written informed consent. Should facial nerve injury occur, immediate consultation and reparative decompression, anastomosis or grafting should be performed to obtain the best ultimate result. The value of prompt, competent, sympathetic and continuing concern offered by the surgeon to the patient cannot be over emphasized.
Medical Management of Radiation Effects on the Intestines

Despite advances in the delivery of pelvic radiotherapy, radiation-related injuries of the small and large intestines remain one of the most prominent acute and chronic toxicities of treatment. Management of acute toxicity is mainly symptomatic. Options for chronic radiation enteropathy include low-residue diet, nutritional supplementation, hyperbaric oxygen (HBO) therapy, and total parenteral nutrition. Chronic radiation proctopathy can be managed using either nonendoscopic methods including sucralfate enemas, oral vitamin A and HBO therapy, and/or endoscopic methods for rectal bleeding, including bipolar electrocautery, heater probe, and argon plasma coagulation. Several preventive options are available, including amifostine, a scavenger of radiation-induced free radicals.
Characterizing user-perceived impairment events using end-to-end measurements

SUMMARY Measures of quality of service (QoS) must correlate to end-user experience. For multimedia services, these metrics should focus on the phenomena that are observable by the end-user. Metrics such as delay and loss may have little direct meaning to the end-user because knowledge of specific coding and/or adaptive techniques is required to translate delay and loss to the user-perceived performance. Impairment events, as defined in this paper, are observable by the end-users independent of coding, adaptive playout or packet loss concealment techniques employed by their multimedia applications. Time between impairments and duration of impairments are metrics that are easily understandable by a network user. Methods to detect these impairment events using end-to-end measurements are developed here. In addition, techniques to identify Layer 2 route changes and congestion events using end-to-end measurements are also developed. These are useful in determining what caused the impairments. End-to-end measurements were conducted for about 26 days on 9 different node pairs to evaluate the developed techniques. Impairments occurred at a high rate on the two paths on which congestion events were detected. On these two paths, congestion occurred for 6–8 hours during the day on weekdays. Impairments caused by route changes were rare but lasted for several minutes. Copyright # 2005 John Wiley & Sons, Ltd.
Portfolio analysis on preeclampsia and pregnancy-associated hypertension research funded by the National Heart, Lung, and Blood Institute.

Chronic hypertension and preeclampsia are the most common complications of pregnancy. To clarify the contributions of the National Heart, Lung, and Blood Institute (NHLBI) to the field and identify...
Emergency department patient payer status after implementation of the Affordable Care Act: A nationwide analysis using NHAMCS data

Abstract Objective To evaluate changes in insurance status among emergency department (ED) patients presenting in the two years immediately before and after full implementation of the Affordable Care Act (ACA). Methods We evaluated National Hospital Ambulatory Medical Care Survey (NHAMCS) Emergency Department public use data for 2012–2015, categorizing patients as having any insurance (private; Medicare; Medicaid; workers' compensation) or no insurance. We compared the pre- and post-ACA frequency of insurance coverage—overall and within the older (≥65), working-age (18–64) and pediatric ( Results Overall, the proportion of ED patients with any insurance did not significantly change from 2012 to 2013 to 2014–2015 (74.2% vs 77.7%) but the proportion of working-age adult patients with at least one form of insurance increased significantly, from 66.0% to 71.8% (OR 1.31, CI: 1.13–1.52). The difference-in-differences analysis confirmed the change in insurance coverage among working-age adults was greater than that seen in the reference population of Medicare-eligible adults (AOR 1.70, CI: 1.29–2.23). The increase was almost entirely attributable to increased Medicaid coverage. Conclusion In the first two years following full implementation of the ACA, there was a significant increase in the proportion of working-age adult ED patients who had at least one form of health insurance. The increase appeared primarily associated with expansion of Medicaid.
Serious Ethical Violations by Physicians: What’s the Solution?

These are trying times in regard to public trust. In an era when the Catholic Church chose to protect pedophilic priests rather than young congregants, many traditionally trusted figures in our soc...
Clinical data quality: a data life cycle perspective

Clinical data is the staple of modern learning health systems. It promises to accelerate biomedical discovery and improves the efficiency of clinical and translational research but is also fraught with significant data quality issues. This paper aims to provide a life cycle perspective of clinical data quality issues along with recommendations for establishing appropriate expectations for research based on real-world clinical data and best practices for reusing clinical data as a secondary data source.
FEVER OF UNKNOWN ORIGIN POST-CARDIAC TRANSPLANTATION

The differential diagnosis for fever of unknown origin in solid organ transplantation is vast and includes rejection, malignancy, adrenal insufficiency, drug fever, and infection. A 64 year-old man's post-cardiac transplantation course was complicated by 6 weeks of fevers and failure to thrive. He
Legal authorized representative experience with smartphone-based electronic informed consent in an acute stroke trial.

Background The pilot use of a smartphone platform for electronic informed consent (e-Consent) in large vessel occlusion acute stroke (LVOS) trials has recently been reported. The degree of satisfaction from Legal Authorized Representatives (LARs) with regard to this process remains to be established. Methods A single-center study evaluating the experience of LARs with the use of e-Consent in a LVOS randomized trial of an investigational drug administered within 12 hours of last known normal was carried out. A structured survey was used to evaluate the experience of the LARs with the e-consenting process. Results From February to November 2018, 60 consecutive patients were e-Consented. Of these, 53 LARs completed the survey. The median (IQR) age of the patients was 63 (53–70) years, baseline/discharge National Institutes of Health Stroke Scale score was 17 (12–20)/3(1–12), and 45% were independent at discharge. The survey was applied in person in 43% of cases and via telephone in 57%. Median LAR age was 48 (39–59) years, 64% were female, and a multi-ethnic composition was observed. Forty percent of LARs had less than tertiary level of education (high-school or less). Regarding the e-Consent, 98% of LARs reported to be ‘clear’ and 83% felt ‘very comfortable’ in signing. The overall experience was ‘excellent/good’ in 91%. Despite the positive general impression regarding the use of e-Consent, 12 LARs (22%) would have preferred paper consent. Multivariable regression indicated that lower educational status (tertiary education or less: OR 5.09, 95% CI 1.02 to 25.48; p=0.04) and lower baseline ASPECTS score (OR 0.63, 95% CI 0.41 to 0.96; p=0.03) were independently associated with preference for paper consent. Conclusions e-Consent was overall very well perceived by LARs in a randomized clinical trial of LVOS. A minority of proxies, who were more commonly less formally educated, would have preferred paper consenting.
tRNA functional signatures classify plastids as late-branching cyanobacteria

Eukaryotes acquired the trait of oxygenic photosynthesis through endosymbiosis of the cyanobacterial progenitor of plastid organelles. Despite recent advances in the phylogenomics of Cyanobacteria, the phylogenetic root of plastids remains controversial. Although a single origin of plastids by endosymbiosis is broadly supported, recent phylogenomic studies are contradictory on whether plastids branch early or late within Cyanobacteria. One underlying cause may be poor fit of evolutionary models to complex phylogenomic data. Using Posterior Predictive Analysis, we show that recently applied evolutionary models poorly fit three phylogenomic datasets curated from cyanobacteria and plastid genomes because of heterogeneities in both substitution processes across sites and of compositions across lineages. To circumvent these sources of bias, we developed CYANO-MLP, a machine learning algorithm that consistently and accurately phylogenetically classifies (“phyloclassifies”) cyanobacterial genomes to their clade of origin based on bioinformatically predicted function-informative features in tRNA gene complements. Classification of cyanobacterial genomes with CYANO-MLP is accurate and robust to deletion of clades, unbalanced sampling, and compositional heterogeneity in input tRNA data. CYANO-MLP consistently classifies plastid genomes into a late-branching cyanobacterial sub-clade containing single-cell, starch-producing, nitrogen-fixing ecotypes, consistent with metabolic and gene transfer data. Phylogenomic data of cyanobacteria and plastids exhibit both site-process heterogeneities and compositional heterogeneities across lineages. These aspects of the data require careful modeling to avoid bias in phylogenomic estimation. Furthermore, we show that amino acid recoding strategies may be insufficient to mitigate bias from compositional heterogeneities. However, the combination of our novel tRNA-specific strategy with machine learning in CYANO-MLP appears robust to these sources of bias with high accuracy in phyloclassification of cyanobacterial genomes. CYANO-MLP consistently classifies plastids as late-branching Cyanobacteria, consistent with independent evidence from signature-based approaches and some previous phylogenetic studies.
Experience with same-day placement of the 52 mg levonorgestrel-releasing intrauterine system.

Abstract Background Prescribing information for the levonorgestrel-releasing intrauterine system allows placement when the clinician is reasonably certain the patient is not pregnant. A six-item checklist aids clinicians in determining pregnancy risk, but may be too restrictive, resulting in delaying placement for many women. Same-day placement, however, may risk placement during an unrecognized luteal-phase pregnancy, that is, a pre-implantation fertilized ovum not yet detectable by urine pregnancy test. Objective We assessed the applicability of pregnancy checklist criteria in two gynecology practices that routinely provide same-day placements following a negative urine pregnancy test. Study design In this retrospective cohort study, we reviewed electronic medical records of all women who underwent levonorgestrel-releasing intrauterine system placement from July 2009 to August 2012. We evaluated each record to identify whether the woman met any of the checklist criteria to exclude pregnancy. We ascertained luteal-phase pregnancies and other outcomes within 12 months following placement. Results Of 885 placements, 293 (33%) were immediately post-abortion. Of the remaining 592 placements, 353 (60%) met at least one pregnancy checklist criterion to rule out pregnancy but 239 (40%) met none. Two percent received levonorgestrel emergency contraception at the time of placement. One luteal-phase pregnancy occurred in the group not meeting pregnancy checklist criteria. Removals and expulsions were rare and similar whether or not patients met checklist criteria. Conclusions In two practices that provide same-day intrauterine system placements, strict adherence to pregnancy checklist criteria would have resulted in 239 (40%) patients not receiving a same-day intrauterine system. Twelve-month outcomes were similar whether or not patients met pregnancy checklist criteria. Providers need not withhold intrauterine system placement based on the pregnancy checklist criteria.
Investigating Augmented Reality Animals as Companions

Human-animal interaction has been studied in a variety of settings and for a range of populations, with some findings pointing towards its benefits for physical, mental and social human health. Technological advances opened up new opportunities for researchers to replicate human-animal interactions with robotic and graphical animals, and to investigate human-animal relationships for different applications such as mental health and education. Although graphical animals have been studied in the past in the physical health and education domains, most of the time, their realizations were bound to computer screens, limiting their full potential, especially in terms of companionship and the provision of support. In this work, we describe past research efforts investigating influences of human-animal interaction on mental health and different realization of such animals. We discuss the idea that augmented reality could offer potential for human-animal interaction in terms of mental and social health, and propose several aspects of augmented reality animals that warrant further research for such interactions.
Kernel Tests for One, Two, and K-Sample Goodness-of-Fit: State of the Art and Implementation Considerations

In this article, we first discuss the fundamental role of statistical distances in the problem of goodness-of-fit and review various existing multivariate two-sample goodness-of-fit tests from both statistics and machine learning literature. The review conducted delivers the fact that there does not exist a satisfactory multivariate two-sample goodness-of-fit test. We introduce a class of one and two-sample tests constructed using the kernel-based quadratic distance, and briefly touch upon their asymptotic properties. We discuss the practical implementation of these tests, with emphasis on the kernel-based two-sample test. Finally, we use simulations and real data to illustrate the application of the kernel-based two-sample test, and compare this test with tests existing in the literature.
Macrophage fusion caused by particle instillation.

Abstract Background Multinucleated giant cells (MGC) are formed by fusion of macrophages in pathological conditions. These are often studied in the context of the foreign body response to biomaterial implants, but MGC formation is rarely assessed in response to inorganic particles in the lungs. Therefore, a major objective of this study was to quantitatively compare in vivo macrophage fusion resulting from exposure to a spectrum of micron- and nano-sized particles from both environmental and engineered origin, including crystalline silica, multiwalled carbon nanotubes, titanium nanobelts, and crocidolite asbestos. Methods Groups of C57Bl/6 mice were instilled with inorganic particles or PBS control. Lung cells were collected by lavage after one week for cell differentials, quantification of macrophage fusion, and microscopic observation of particle uptake. Results MGC were present in lungs of all mice exposed to particles; no MGC were found in control mice. Asbestos exposure resulted in significant macrophage fusion, which coincided with significantly increased total lavage cells and percent neutrophils. Microscopic observations show particle internalization in MGC and a unique case of potential heterotypic fusion of macrophages with neutrophils. Conclusion MGC can form in the lungs of mice within a relatively short one-week time period after particle exposure. The number of MGC was sufficient for quantification and statistical analysis, indicating that MGC formation was more than simply a rare chance occurrence. Observations of particles within MGC warrants further investigation of MGC involvement in inflammation and particle clearance.
Natural Product-Based Nanomedicine in Treatment of Inflammatory Bowel Disease

Many synthetic drugs and monoclonal antibodies are currently in use to treat Inflammatory Bowel Disease (IBD). However, they all are implicated in causing severe side effects and long-term use results in many complications. Numerous in vitro and in vivo experiments demonstrate that phytochemicals and natural macromolecules from plants and animals reduce IBD-related complications with encouraging results. Additionally, many of them modify enzymatic activity, alleviate oxidative stress, and downregulate pro-inflammatory transcriptional factors and cytokine secretion. Translational significance of natural nanomedicine and strategies to investigate future natural product-based nanomedicine is discussed. Our focus in this review is to summarize the use of phytochemicals and macromolecules encapsulated in nanoparticles for the treatment of IBD and IBD-associated colorectal cancer.
Health-related and sociodemographic correlates of meeting the muscle strengthening exercise recommendations in middle-aged and older adults with and without disabilities

To identify sociodemographic and health correlates of meeting the muscle strengthening (MS) exercise recommendations in middle-aged and older adults by disability status. Respondents from the 2011 Behavioral Risk Factor Surveillance System were stratified by disability status (with disability, without disability), age [ages 45–64 (middle-aged), 65 + years of age (older adults)] and whether they met MS recommendations (yes, no). Two logistic regression models were run to evaluate whether perceived health status and sociodemographic characteristics were associated with meeting the MS recommendations by disability status. The sample included 477,662. Middle-aged persons were 20% more likely than older adults to meet the MS recommendations. Persons with a disability were less likely to meet muscle strengthening recommendations compared with those without. Persons with a disability who reported having poor health were ~ 65% less likely to meet the MS recommendation than those reporting excellent health. Furthermore, those with a disability and with one or more chronic diseases were nearly 40% less likely to meet the MS recommendation than no disability. Among respondents without disability, being Black and being a healthy weight or underweight increased the odds of meeting the MS recommendations. Several health and sociodemographic factors were associated with not meeting MS recommendations. Persons with disability and poor health, had the lowest likelihood of participation. Studies are needed to understand whether improving MS exercise behavior may attenuate functional limitations associated with chronic diseases and aging.
Three Approaches to Take the User Perspective into Account During New Product Design

This paper addresses three different approaches which can be employed to adequately answer different questions faced by product developers. These approaches differ in the ways users themselves are involved in developing the "real" user perspective. In participatory design, products and product concepts are developed together with users so that they fit better with what the users do and want to do. The modelling of product adoption quantifies the likely market adoption of products, based on user characteristics and product attributes. The evaluation of user experience describes a way to evaluate products in terms of their users' interaction with the product daily life. These approaches have originated from different areas and are often seen as competing viewpoints. This paper shows that the three approaches be seen as complementary to each other and suggests a method for to choose the right approach.
Medication Management of Anxiety and Depression by Primary Care Pediatrics Providers: A Retrospective Electronic Health Record Study

Abstract Objectives To describe medication management of children diagnosed with anxiety and depression by primary care providers. Study Design/Methods We performed a retrospective cross-sectional analysis of electronic health record (EHR) structured data. All visits for pediatric patients seen at least twice during a four-year period within a network of primary care clinics in Northern California were included. Descriptive statistics summarized patient variables and most commonly prescribed medications. For each subcohort (anxiety, depression, and both (anxiety+depression)), logistic regression models examined the variables associated with medication prescription. Results Of all patients (N=93,025), 2.8% (n=2635) had a diagnosis of anxiety only, 1.5% (n=1433) depression only, and 0.79% (n=737) both anxiety and depression (anxiety+depression); 18% of children with anxiety and/or depression had comorbid ADHD. A total of 14.0% with anxiety (n=370), 20.3% with depression (n=291), and 47.5% with anxiety+depression (n=350) received a psychoactive non-stimulant medication. For anxiety only and depression only, sertraline, citalopram, and fluoxetine were most commonly prescribed. For anxiety+depression, citalopram, sertraline, and escitalopram were most commonly prescribed. The top prescribed medications also included benzodiazepines. Logistic regression models showed that older age and having developmental or mental health comorbidities were independently associated with increased likelihood of medication prescription for children with anxiety, depression, and anxiety+depression. Insurance type and sex were not associated with medication prescription. Conclusions PCPs prescribe medications more frequently for patients with anxiety+depression than for patients with either diagnosis alone. Medication choices generally align with current recommendations. Future research should focus on the use of benzodiazepines due to safety concerns in children.
The role of high-risk HPV testing in cervical cancer surveillance.

ABSTRACT Objectives While high-risk HPV (hrHPV) testing is not formally recommended as a surveillance modality in patients with a history of cervical cancer, it is often performed in routine practice. It is unclear whether the presence of hrHPV infection after cervical cancer treatment is associated with recurrent disease. Methods Patients with a cervical cancer diagnosis who were seen in a single institution between May 2012 and December 2019 were retrospectively identified. Squamous cell, adenocarcinoma, adenosquamous, and neuroendocrine histologies were included. Those with cancer progression within 3 months of treatment or Results Of the 262 patients meeting inclusion criteria, 58 (22%) recurrences were diagnosed, and recurrence was most commonly detected by a surveillance imaging study (71%). Among the 169 patients that were tested for hrHPV during the surveillance period, 41 (24%) had at least one positive hrHPV test. Recurrent disease was diagnosed in 24 (14%). Of the 24 patients with recurrent disease, 5 (21%) had at least one positive hrHPV test during surveillance, versus 36 (24%) of 145 patients without recurrent disease (p = 0.67). No recurrences were detected by hrHPV testing. Conclusions Positive hrHPV testing in the surveillance setting was not associated with cervical cancer recurrence but did lead to additional studies and procedures. Our findings do not support the routine use of hrHPV testing for the evaluation of cervical cancer recurrence.
Assessing the Pcrit in relation to temperature and the expression of hypoxia associated genes in the mayfly, Neocloeon triangulifer.

Hypoxia is a growing concern in aquatic ecosystems. Historically, scientists have used the Pcrit (the dissolved oxygen level below which an animal can no longer oxyregulate) to infer hypoxia tolerance across species. Here, we tested the hypothesis that the Pcrit is positively correlated with temperature in the mayfly, Neocloeon triangulifer. Cross-temperature comparisons showed a modest (r = 0.47), but significant (p < 0.0001) association between temperature and Pcrit despite relatively large interindividual variability (Coefficient of Variance (CV) = 39.9% at 18 °C). We used the expression of hypoxia-responsive genes EGL-9 (an oxygen sensing gene and modulator of HIF-1a activity) and LDH (a hypoxia indicator) to test whether oxygen partial pressure near the Pcrit stimulates expression of hypoxia-responsive genes. Neither gene was upregulated at oxygen levels above the estimated Pcrit, however, at or below the Pcrit estimates, expression of both genes was stimulated (~20- and ~3-fold change for EGL-9 and LDH, respectively). Finally, we evaluated the influence of hypoxic exposure time and pretreatment conditions on the mRNA expression levels of hypoxia-responsive genes. When larvae were exposed to a gradual reduction of DO, hypoxic gene expression was more robust than during instantaneous exposure to hypoxia. Our data provide modest support for traditional interpretation of the Pcrit as a physiologically meaningful shift from aerobic to anaerobic metabolism in N. triangulifer. However, we also discuss limitations of the Pcrit as a proxy measure of hypoxia tolerance at the species level.
Care for Patients Dying with a Left Ventricular Assist Device

Left ventricular assist devices (LVADs) are increasingly being used to support patients with advanced heart failure, both as a bridge to heart transplantation and as a final or ‘destination’ therapy. Compared with continued medical therapy alone, these devices prolong survival and improve overall patient functional status and quality of life – as such LVADs are not a strictly palliative therapy. However, life with LVAD support is frequently accompanied by device-related complications such as bleeding, ventricular arrhythmias, infection, stroke, renal failure, and right ventricular failure. Management of the LVAD-supported patient who has experienced device-related complications requires both a focus on the underlying pathophysiology and the patient’s overall goals of care. Palliative or supportive care approaches serve an important complementary role in the management of these patients and may also be used to inform decision-making prior to device implantation. We present a review of the complications of LVAD support and their treatment, describe a role for palliative care in the management of these patients, and consider future directions for research to improve the care of LVAD-supported patients.
Chapter 2 Structure and function of muscarinic receptors

Publisher Summary This chapter describes the structure and function of muscarinic receptors (mAchR). The results from several laboratories regarding the structure and function of the five mAChR subtypes, specific examples, particularly concerning physical characterization of the receptor protein, utilizing the M 2 subtype from porcine atria are discussed in the chapter. Depending on the particular system under consideration, muscarinic receptors can couple to physiological responses, which are either excitatory or inhibitory in nature. In heart preparations, addition of ACh caused a reduction in the level of adenosine 3’,5’-cyclic monophosphate (CAMP). Muscarinic inhibition of adenylyl cyclase require guanosine triphosphate (GTP) and is known to be mediated by one or more of a class of signal-transducing proteins called “guanine nucleotide binding proteins” (G-proteins). G-proteins that regulate adenylyl cyclase are heterotrimers consisting of differing G α subunits and similar G βγ , subunits. The role of the hormone-receptor complex is to promote the release of a tightly bound molecule of guanosine diphosphate (GDP) from the G α subunit of the heterotrimer.
Abstract 113: Nuclear Translocation of Neuronal Histone Deacetylase 4 (HDAC4) is Detrimental in Stroke

HDAC4 has been identified as a transcriptional corepressor that catalyzes local histone deacetylation. It is highly expressed in neurons and usually trapped in cytosol. In vitro, translocation of HDAC4 from cytosol into nucleus induced neuronal death in response to glutamate toxicity. Here we assessed the hypothesis that accumulation of nuclear HDAC4 occurs after stroke, this translocation is detrimental in stroke outcome and regulated by calcium/calmodulin-dependent protein kinase IV (CaMK IV). Wild type (WT) and CaMK IV knockout (KO) mice were subjected to transient middle cerebral artery occlusion and were sacrificed 6 hours for molecule assessments or 72 hours post stroke for outcome assessments. Primary cortical neurons underwent oxygen-glucose deprivation (OGD) and viability was measured 24 hours after OGD. Lentiviral vectors were utilized in culture and mice. Stroke induced HDAC4 nuclear translocation in WT mice as assessed by both Western blots and immunohistochemistry. Knockdown of HDAC4 improved cell viability after OGD (HDAC4 SiRNA: 87.19±7.57% vs. control: 68.09±3.83%, p<0.05, n=6). Expression of a nuclear restricted HDAC4 mutant (Nuc) reduced cell viability after OGD (p<0.05), in contrast, no effect was seen for a cytoplasmic mutant HDAC4 (Cyto) (Nuc: 50.32±1.36% and Cyto: 68.95±2.17% vs. GFP control: 73.25±1.28%, n=6). In vivo nuclear HDAC4 mutant expression increased hemispheric infarcts (Nuc: 57.54±1.67% vs. Cyto: 36.98±3.26%) and worsened mice performance in rotarod test (Nuc: 12.38±3.50 seconds vs. Cyto: 33.65±2.98 seconds) compared with expression of cytoplasmic HDAC4 mutant after stroke (p<0.05, n=8-10). Percentage of nuclear HDAC4 positive neurons in penumbra was increased in CaMK IV KO mice (KO: 66.28±4.28% vs. WT: 37.08±2.44%, p<0.05, n=4) when compared to WT after stroke. Finally, overexpression of CaMK IV increased neuronal viability after OGD; however, this effect was lost when HDAC4 was inhibited by SiRNA. In conclusion, we showed that ischemia induces HDAC4 nuclear shuttling in neurons and this translocation is deleterious in stroke outcome. Our data suggested CaMK IV inhibits HDAC4 nuclear accumulation in stroke.
Mutations affecting genetic recombination in bacteriophage T4D. I. Pathway analysis.

Abstract The nature of DNA synthesis and recombination has been examined in bacteriophage T4D mutants deficient in recombination and repair. The interactions of several of these mutations have been assessed by measuring DNA synthesis, uv sensitivity, and genetic recombination in multiply mutant strains. Certain multiple mutants exhibited a 60-fold reduction in recombination frequency. Gene x - and gene y -deficient strains each exhibited an arrest in DNA synthesis and a concomitant interruption of concatemer formation as measured by alkaline sucrose density gradient centrifugation. The arrest in DNA synthesis was suppressed by the presence of a second mutation in gene 55. Strains carrying x and y mutations failed to complement mutants fds A and fds B, respectively. A gene w mutation was found to suppress the arrest in DNA synthesis caused by mutations in genes 46–47 and in gene 59. In the case of genes 46–47, genetic recombination was not restored, while for gene 59 mutants genetic recombination and uv resistance were partially restored. A gene w mutation did not suppress the DNA arrest phenotype produced by mutations in the x or y genes. The T4B strain 1206 was found to contain a mutation in gene w , along with several uncharacterized mutations.
Light-cone physics and duality

In this paper we make an attempt to grasp some features of hadron physics in terms of light-cone properties. Hadrons are considered, in the light-cone asymptotism, as aggregates of free massless quarks, aligned on the same direction (collinearity). The hadron states are classified by a representation of anO 2.1 algebra, constructed from the generators of the conformal group. Deep inelastic structure functions are evaluated and discussed. Analogies between duality and light-cone physics are stressed.
Synthesis, structure and physical properties of YbNi3Al9.23.

The physical properties of YbNi{sub 3}Al{sub 9.23}, including the crystal structure, magnetization, specific heat, valence, and electrical resistivity, are reported. Single crystal X-ray diffraction reveals that the compound crystallizes with the rhombohedral space group R32 and has unit cell parameters a=7.2443(3) A and c=27.251(3) A with some crystallographic disorder on an Al site. The compound orders antiferromagnetically at T{sub N}=3 K despite the presence of strong ferromagnetic correlations, accompanied by a spin flop-like transition to a moment-aligned rate above 0.1 T. X-ray absorption spectroscopy and magnetic susceptibility measurements indicate a localized Yb{sup 3+} electronic configuration, while the Sommerfeld coefficient in the magnetically ordered state was determined to be approximately 135 mJ/mol-K{sup 2}, suggesting moderately heavy fermion behavior. Therefore, these data indicate a balance between competing Ruderman-Kittel-Kasuya-Yosida (RKKY) and Kondo interactions in YbNi{sub 3}Al{sub 9.23} with a somewhat dominant RKKY interaction that leads to a relatively high ordering temperature.
Abstract 198: Familial Hypercholesterolemia and Intra-Cranial Aneurysm: A Novel Phenotypic and Genetic Association

Background: Autosomal dominant familial hypercholesterolemia (FH) is characterized by elevated levels of low density lipoprotein (LDL) cholesterol. Mutations in LDLR, APOB, and PCSK9 genes are established causes of this condition. However, in up to 20-40% of cases, the genetic cause has not been defined. FH is associated with coronary ectasias, but extra-cardiac vascular malformations have not been described. Methods: A subject with hypercholesterolemia was evaluated, and a three generation pedigree was constructed. Whole exome sequencing (WES) was performed (Illumina HiSeq 2500, 100x avg coverage) and reads were aligned to a human reference genome (hg19) using BWA. Variants were called with GATK Unified Genotyper and annotated using SeattleSeq. Results: Pedigree analysis suggested an autosomal dominant mode of inheritance of the hypercholesterolemia trait (Fig 1). Multiple family members also had intracranial aneurysms. Targeted analysis of the classical genes associated with FH (LDLR, APOB, and PCSK9) d...
Comparison of deep-ocean finescale shear at two sites along the Mid-Atlantic Ridge

Abstract Four drifting floats were used to measure the magnitude of the vertical derivative of horizontal velocity in waters above the rough bathymetry of the Mid-Atlantic Ridge. This derivative is typically the dominant component of the velocity gradient (the shear). Two floats were at the site of the Brazil Basin Tracer Release Experiment (BBTRE) in the South Atlantic, and two were near the site of the Guiana Abyssal Gyre Experiment (GAGE) in the North Atlantic. Floats operated for 1 year except for one BBTRE float, which operated for 100 days. Shear was measured over a vertical span of 9.5 m using drag elements that caused the floats to rotate slowly in response to shear. For each float, the first, second and fourth moments of shear were elevated above levels associated with the Garrett–Munk model internal-wave spectrum. Three of the four floats were tracked as they moved over mountainous terrain, allowing shear intensity to be measured as a function of height above the bottom. A deep BBTRE float showed enhancement of rms shear near the bottom. Floats at both areas provided measurements at 2000 m above the bottom, with differing results: the GAGE site had a lower fourth moment of shear (diapycnal diffusivity proxy) than the BBTRE site. However, application of normalization factors accounting for differences between the sites in bottom roughness, latitude-dependent internal-wave dynamics, and tidal current speeds brings the results into agreement.
STUDIES ON THE MOLECULAR STRUCTURE OF RAT LIVER CARDIOLIPIN.

Abstract Rat liver cardiolipin, isolated by silicic acid column chromatography, has been resolved into five subfractions by discontinuous gradient elution from a silicic acid column. Comparison of these lipids with authentic beef heart cardiolipin established theis essential identity; the beef heart lipid differed only in having a more unsaturated fatty acid composition. A comparison between the five subfractions with regard to phosphorus and amino nitrogen content, ester/phosphorus ratios, fatty acid composition, infrared spectra, presence of salt forms, extent of peroxidation, component glycerphosphoric esters, and hydrolysis characteristics failed to explain the molecular basis for the fractionation. The presence of a free hydroxyl group in cardiolipin could not be confirmed by accetylation or acetonation. These observations were not consistent with the generally accepted diphosphatidyl glycerol structure for cardiolipin and lead to consideration of some additional possibilities.
A giant Ordovician anomalocaridid

The anomalocaridids were the giant, jointed-legged predators of the Cambrian seas. Well known as one of the oddities from the mid-Cambrian Burgess Shales of Canada, anomalocaridids have been found in Cambrian strata worldwide, but it was widely thought that they and their kin did not survive beyond the Cambrian. Peter Van Roy and Derek Briggs now extend the record of these bizarre creatures to the Ordovician, with a report of anomalocaridids from the Ordovician of Morocco. They join an assemblage of relic Cambrian animals recently described from that country. One of the Ordovician anomalocaridids was a metre or so in length, perhaps capable of challenging predators such as nautiloids for dominance of the seas. Anomalocaridids, giant lightly sclerotized invertebrate predators, occur in a number of exceptionally preserved early and middle Cambrian (542–501 million years ago) biotas and have come to symbolize the unfamiliar morphologies displayed by stem organisms in faunas of the Burgess Shale type. They are characterized by a pair of anterior, segmented appendages, a circlet of plates around the mouth, and an elongate segmented trunk lacking true tergites with a pair of flexible lateral lobes per segment1,2. Disarticulated body parts, such as the anterior appendages and oral circlet, had been assigned to a range of taxonomic groups—but the discovery of complete specimens from the middle Cambrian Burgess Shale showed that these disparate elements all belong to a single kind of animal3. Phylogenetic analyses support a position of anomalocaridids in the arthropod stem, as a sister group to the euarthropods4,5,6. The anomalocaridids were the largest animals in Cambrian communities. The youngest unequivocal examples occur in the middle Cambrian Marjum Formation of Utah7 but an arthropod retaining some anomalocaridid characteristics is present in the Devonian of Germany5. Here we report the post-Cambrian occurrence of anomalocaridids, from the Early Ordovician (488–472 million years ago) Fezouata Biota8 in southeastern Morocco, including specimens larger than any in Cambrian biotas. These giant animals were an important element of some marine communities for about 30 million years longer than previously realized. The Moroccan specimens confirm the presence of a dorsal array of flexible blades attached to a transverse rachis on the trunk segments; these blades probably functioned as gills.
MagnifiSense: inferring device interaction using wrist-worn passive magneto-inductive sensors

The different electronic devices we use on a daily basis produce distinct electromagnetic radiation due to differences in their underlying electrical components. We present MagnifiSense, a low-power wearable system that uses three passive magneto-inductive sensors and a minimal ADC setup to identify the device a person is operating. MagnifiSense achieves this by analyzing near-field electromagnetic radiation from common components such as the motors, rectifiers, and modulators. We conducted a staged, in-the-wild evaluation where an instrumented participant used a set of devices in a variety of settings in the home such as cooking and outdoors such as commuting in a vehicle. MagnifiSense achieves a classification accuracy of 82.6% using a model-agnostic classifier and 94.0% using a model-specific classifier. In a 24-hour naturalistic deployment, MagnifiSense correctly identified 25 of the total 29 events, while achieving a low false positive rate of 0.65% during 20.5 hours of non-activity.
The morphology of dorsal column postsynaptic spinomedullary neurons in the cat.

Dorsal column postsynaptic (DCPS) spinomedullary neurons from the cat's lumbosacral enlargement were identified by antidromic stimulation of the cervical dorsal columns and stained intracellularly with horseradish peroxidase. The cell bodies were located in laminae III-IV. Their dendritic arbors were elongated rostrocaudally but narrow mediolaterally. On the average, the arbors were ×5 longer than they were wide. Most of the neurons had nearly all of their dendrites in laminae III-IV and some of the neurons had, in addition, a considerable amount of dendritic surface area in lamina V. Only one neuron had more than a very small amount of dendritic surface area dorsal to lamina III. Seven of the neurons had unmyelinated axon collaterals that arborized extensively and issued varicosity-bearing terminal branches in laminae III-V, both within and beneath their dendritic territories. All of the neurons were excited by myelinated, low-threshold mechanoreceptors. Since the rostrocaudally elongated and mediolaterally narrow dendritic arbors of DCPS neurons are in register with the laminae III-IV terminal distributions of myelinated, low-threshold mechanoreceptors, it is probable that this excitation arises from a monosynaptic and topographically discrete innervation. About one-half of the DCPS neurons were also excited by noxious stimuli. It is probable that this excitation is accomplished by a polysynaptic distributions are largely or completely separate.
Chronic cocaine administration causes extensive white matter damage in brain: Diffusion tensor imaging and immunohistochemistry studies

Abstract The effect of chronic cocaine exposure on multiple white matter structures in rodent brain was examined using diffusion tensor imaging (DTI), locomotor behavior, and end point histology. The animals received either cocaine at a dose of 100mg/kg ( N =19), or saline ( N =17) for 28 days through an implanted osmotic minipump. The animals underwent serial DTI scans, locomotor assessment, and end point histology for determining the expressions of myelin basic protein (MBP), neurofilament-heavy protein (NF-H), proteolipid protein (PLP), Nogo-A, aquaporin-4 (AQP-4), and growth associated protein-43 (GAP-43). Differences in the DTI measures were observed in the splenium (scc) and genu (gcc) of the corpus callosum (cc), fimbria (fi), and the internal capsule (ic). A significant increase in the activity in the fine motor movements and a significant decrease in the number of rearing events were observed in the cocaine-treated animals. Reduced MBP and Nogo-A and increased GAP-43 expressions were most consistently observed in these structures. A decrease in the NF-H expression was observed in fi and ic. The reduced expression of Nogo-A and the increased expression of GAP-43 may suggest destabilization of axonal connectivity and increased neurite growth with aberrant connections. Increased GAP-43 suggests drug-induced plasticity or a possible repair mechanism response. The findings indicated that multiple white matter tracts are affected following chronic cocaine exposure.
Data structured programming: Program design without arrays and pointers

Structured programming introduced a new discipline for accessing the instructions of a program. In suitable programming languages, this discipline can be described in terms of program design without gotos. It can be shown, for example, that any functional result achievable in a programming language with gotos can be achieved in that same language without gotos if sequence, selection, and iteration control constructs are present. The gotos permit random access to the instructions while sequence, selection, and iteration provide much more limited and disciplined access. The authors introduce a new discipline for accessing the data of a program. Any functional result achievable in a programming language with arrays and pointers can be achieved in that same language without arrays and pointers if set, stack, and queue data types are present. The arrays and pointers permit random access to the data while sets, stacks, and queues provide much more limited and disciplined access.