gebhart/patrepeval huggingface dataset:
Comprehensive analysis of two Shank3 and the Cacna1c mouse models of autism spectrum disorder (2017)

To expand, analyze and extend published behavioral phenotypes relevant to autism spectrum disorder (ASD), we present a study of three ASD genetic mouse models: Feng's Shank3<sup>tm2Gfng</sup> model, hereafter Shank3/F, Jiang's Shank3<sup>tm1Yhj</sup> model, hereafter Shank3/J and the Cacna1c deletion model. The Shank3 models mimick gene mutations associated with Phelan-McDermid Syndrome and the Cacna1c model recapitulates the deletion underlying Timothy syndrome. This study utilizes both standard and novel behavioral tests with the same methodology used in our previously published companion report on the Cntnap2 null and 16p11.2 deletion models. We found that some but not all behaviors replicated published findings and those that did replicate, such as social behavior and overgrooming in Shank3 models, tended to be milder than reported elsewhere. The Shank3/F model, and to a much lesser extent, the Shank3/J and Cacna1c models, showed hypoactivity and a general anxiety-like behavior triggered by external stimuli which pervaded social interactions. We did not detect deficits in a cognitive procedural learning test nor did we observe perseverative behavior in these models. We did, however, find differences in exploratory patterns of Cacna1c mutant mice suggestive of a behavioral effect in a social setting. In addition, only Shank3/F showed differences in sensory-gating. Both positive and negative results from this study will be useful in identifying the most robust and replicable behavioral signatures within and across mouse models of autism. Understanding these phenotypes may shed light of which features to study when screening compounds for potential therapeutic interventions.
Accelerated first-in-human clinical trial of EIDD-2801/MK-4482 (molnupiravir), a ribonucleoside analog with potent antiviral activity against SARS-CoV-2 (2021)

A recently published article described the safety, tolerability, and pharmacokinetic profile of molnupiravir (Painter et al. 2021), a novel antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Here, we report an unprecedented collaboration between sponsor, contract research organization (CRO), and regulatory authorities that enabled accelerated generation of these phase I data, including administration of the first-in-human (FIH) dose of molnupiravir within 5 days of receiving regulatory approval in the United Kingdom (UK). Single and multiple ascending dose (SAD and MAD, respectively) cohorts were dosed in randomized, double-blind, and placebo-controlled fashion, with a 6:2 active-to-placebo ratio in each cohort. A food-effect (FE) cohort included 10 subjects who were randomized to receive drug in the fasted or fed state followed by the fed or fasted state to complete a fed and fasted sequence for each subject. Dose escalation decisions were accelerated and MAD cohorts were initiated prior to completion of all SAD cohorts with the provision that the total daily dose in a MAD cohort would not exceed a dose proven to be safe and well-tolerated in a SAD cohort. Dosing in healthy volunteers was completed for eight single ascending dose (SAD) cohorts, seven multiple ascending dose (MAD) cohorts, and one food-effect (FE) cohort within approximately 16 weeks of initial protocol submission to the Research Ethics Committee (REC) and Medicines and Healthcare products Regulatory Agency (MHRA). Working to standard industry timelines, the FIH study would have taken approximately 46 weeks to complete and 33 weeks to enable phase 2 dosing. Data from this study supported submission of a phase 2/3 clinical trial protocol to the US Food and Drug Administration (FDA) within 8 weeks of initial protocol submission, with FDA comments permitting phase 2 study initiation within two additional weeks. In the setting of a global pandemic, this model of collaboration allows for accelerated generation of clinical data compared to standard processes, without compromising safety.
PS-R04-8: DIFFERENTIAL RECOVERY OF IMPAIRED ENDOTHELIAL AND RENAL FUNCTION IN A CASE OF MALIGNANT HYPERTENSION (2023)

A 37-year-old man with no past history of hypertension presented with no symptoms but with acutely elevated blood pressure (230/140mmHg) and proteinuria (&gt; 300 mg/dL). Fundoscopic appearance represented grade IV hypertensive retinopathy with papilledema, flamed-shaped hemorrhages, exudates and arteriovenous nipping, indicating typical features of the malignant hypertension. The laboratory tests at admission indicated the possible organ damages in kidney and heart (eGFR 21 mL/min/1.73m2, BNP 263pg/mL). The other examinations are normal. After 20 days of treatments with amlodipine, azilsartan and carvedilol, the average of multiple blood pressure measurements and BNP showed almost normal levels (146/87mmHg, BNP &lt; 10pg/mL), although eGFR level was still under 30. In addition, at this time point, flow mediated dilation (FMD), a noninvasive index of vascular endothelial function measured in forearm, showed significant impairment of endothelial function (%FMD 2.6). At 60 days, fundoscopic images represented entire restoration of retinopathy with disappearance of papilledema, hemorrhage and exudates. In contrast, however, both endothelial and renal function were still under normal levels (%FMD 3.2, eGFR 28.2 mL/min/1.73m2). Notably, FMD showed improvement of sustained endothelial dysfunction at day 90 (% FMD 7.5), while a little recovery of renal function was observed at 360 days (eGFR 35.4 mL/min/1.73m2). This case represents the possibility that damaged endothelial and renal function in acute severe hypertension seem to be still reversal with appropriate anti-hypertensive treatment, while differential time-course recovery in each organ might be existed.
Elliptic Curve Cryptography (ECC) Support for Public Key Cryptography for Initial Authentication in Kerberos (PKINIT) (2008)

This document describes the use of Elliptic Curve certificates,
Elliptic Curve signature schemes and Elliptic Curve Diffie-Hellman
(ECDH) key agreement within the framework of PKINIT -- the Kerberos
Version 5 extension that provides for the use of public key
cryptography. This memo provides information for the Internet
community.
Single microfilaments mediate the early steps of microtubule bundling during preprophase band formation in onion cotyledon epidermal cells (2016)

The preprophase band (PPB) is a cytokinetic apparatus that determines the site of cell division in plants. It originates as a broad band of microtubules (MTs) in G2 and narrows to demarcate the future division site during late prophase. Studies with fluorescent probes have shown that PPBs contain F-actin during early stages of their development but become actin depleted in late prophase. Although this suggests that actins contribute to the early stages of PPB formation, how actins contribute to PPB-MT organization remains unsolved. To address this question, we used electron tomography to investigate the spatial relationship between microfilaments (MFs) and MTs at different stages of PPB assembly in onion cotyledon epidermal cells. We demonstrate that the PPB actins observed by fluorescence microscopy correspond to short, single MFs. A majority of the MFs are bound to MTs, with a subset forming MT-MF-MT bridging structures. During the later stages of PPB assembly, the MF-mediated links between MTs are displaced by MT-MT linkers as the PPB MT arrays mature into tightly packed MT bundles. On the basis of these observations, we propose that the primary function of actins during PPB formation is to mediate the initial bundling of the PPB MTs.
Multi-View Matching Network for 6D Pose Estimation (2019)

Applications that interact with the real world such as augmented reality or robot manipulation require a good understanding of the location and pose of the surrounding objects. In this paper, we present a new approach to estimate the 6 Degree of Freedom (DoF) or 6D pose of objects from a single RGB image. Our approach can be paired with an object detection and segmentation method to estimate, refine and track the pose of the objects by matching the input image with rendered images.
A Novel Method for the In situ Generation of Alkoxydialkylboranes and Their Use in the Selective Preparation of 1,3-syn Diols (1987)

Abstract An in situ method for generating Et2BOCH3 from triethylborane and methanol without using any other catalysts is described. Using the Et2BOCH3 thus generated as a chelating agent, syn 1,3-diols are prepared in ≥ 98% stereochemical purity by reducing β-hydroxyketones with sodium borohydride.
The functional role of the precuneus (2023)

Recent advancements in computational approaches and neuroimaging techniques have refined our understanding of the precuneus. While previously believed to be largely a visual processing region, the importance of the precuneus in complex cognitive functions has been previously less familiar due to a lack of focal lesions in this deeply seated region, but also a poor understanding of its true underlying anatomy. Fortunately, recent studies have revealed significant information on the structural and functional connectivity of this region, and this data has provided a more detailed mechanistic understanding of the importance of the precuneus in healthy and pathologic states. Through improved resting-state functional MRI analyses, it has become clear that the function of the precuneus can be better understood based on its functional association with large scale brain networks. Dual default mode network systems have been well explained in recent years in supporting episodic memory and theory of mind; however, a novel 'para-cingulate' network, which is a subnetwork of the larger central executive network, with likely significant roles in self-referential processes and related psychiatric symptoms is introduced here and requires further clarification. Importantly, detailed anatomic studies on the precuneus structural connectivity inside and beyond the cingulate cortex has demonstrated the presence of large structural white matter connections, which provide an additional layer of meaning to the structural-functional significance of this region and its association with large scale brain networks. Together, the structural-functional connectivity of the precuneus has provided central elements which can model various neurodegenerative diseases and psychiatric disorders, such as Alzheimer's disease and depression.
Activation of serpins and their cognate proteases in muscle after crush injury (1994)

Direct muscle injury was induced in rats in order to evaluate alterations in the balance of serine proteases and inhibitors (serpins) as a response to tissue damage. It was previously found that certain proteases, specifically urokinase-like plasminogen activator (uPA) and others, required activation in order to effect regeneration. We hypothesized that the magnitude and temporal sequence of serpin activation would follow, pari passu, activation of their cognate proteases. In addition to uPA, tissue PA (tPA) and tissue kallikrein were the proteases studied. The serpins we analyzed were protease nexin I (PNI), PA inhibitor 1 (PAI-1, and the kallikrein-binding protein (KBP). uPA nearly doubled 48 h after injury, while there was no change in amidolytic activity after addition of fibrin monomer as an estimation of tPA activity. Tissue kallikrein activity, barely detectable in normal muscle, slowly increased, nearly tripling at 7 days after injury. Greater magnitude and more rapid changes in muscle serpins occurred over the same post-injury time course. By 24 h PNI increased threefold, while PAI-1 increased more slowly, reaching double the control values by 5 days after injury. Surprisingly, KBP, the serpin-class inhibitor of tissue kallikrein, had the most robust response, increasing tenfold over control 48 h after crush injury of muscle. These results further implicate the serpin:protease balance in tissue injury. Participation of complex receptors, such as the alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP), various growth factors, cytokines, and other molecules, in regulating this balance is implicated by these data.
Abstract 14390: The Cardiac Myosin Inhibitor, Ck-3772271, Attenuates Cardiac Fibrosis and Diastolic Dysfunction in the Dahl/salt Sensitive Rat Model of Heart Failure With Preserved Ejection Fraction (2020)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is characterized by underlying contractile dysfunction and progressive myocardial fibrosis and stiffness. CK-3772271 (CK-271) is a novel small molecule cardiac myosin inhibitor that reduces cardiac myosin ATPase activity and reduces cardiac contractility in unloaded isolated cardiomyocytes in vitro and in healthy rats and dogs in vivo . The effect of chronic CK-271 treatment on cardiac function and morphology was evaluated in the Dahl/Salt Sensitive (DSS) rat hypertension model of HFpEF. Methods: DSS male rats were fed either a control low salt (LS, 0.3% NaCl) or high salt (HS, 4% NaCl) diet to induce a hypertension-driven HFpEF disease phenotype. 6 weeks after HS diet treatment, DSS rats were randomized into two sub-groups: continued HS diet or a HS diet formulated with CK-271 (100 ppm) for an additional 6 weeks. Body mass, systolic blood pressure, and cardiac function were measured longitudinally. After 12 weeks of HS treatment, hearts were collected to assess cardiac fibrosis. Results: HS diet treatment increased systolic blood pressure (LS:132.2 ± 4.7 mm Hg vs. HS: 163.5 ± 4.0 mm Hg, mean ± SEM, p&lt; 0.001) and caused cardiac hypercontractility as evidenced by an increase in the end-systolic pressure-volume relationship (LS: 0.8 ± 0.17 vs. HS: 2.1 ± 0.46 mm Hg/ml). HS diet also increased isovolumic relaxation time (IVRT) (LS: 16.8 ± 0.6 vs. HS: 22.8 ± 0.6 ms, p&lt;0.0001), left atrial area (LS: 30.3 ± 0.8 vs. HS: 42.5 ± 2.2 mm 2 , p&lt;0.0001) and cardiac fibrosis (LS: 3.4 ± 0.4 vs. HS: 5.0 ± 0.6 %). 6 weeks of CK-271 treatment reduced fractional shortening (HS: 53.8 ± 1.4 vs. HS+CK-271: 42.7 ± 1.0 %, p&lt;0.0001) and reduced HS diet-induced diastolic dysfunction, including IVRT (HS: 22.8 ± 0.6 vs. HS+CK-271: 19.5 ± 0.5 ms, p&lt;0.0001) and left atrial area (HS: 42.5 ± 2.2 vs. HS+CK-271: 35.4 ± 0.8 mm 2 , p&lt;0.0001). Furthermore CK-271 reduced the development of cardiac fibrosis (HS: 5.0 ± 0.6 vs. HS+CK-271: 3.5 ± 0.3 %, p&lt;0.05) induced by HS diet. Conclusion: The small molecule cardiac myosin inhibitor, CK-3772271, attenuated the development of cardiac hypercontractility, diastolic dysfunction and fibrosis in the DSS rat model of HFpEF. Cardiac myosin inhibition may be a novel approach to mitigate the development of HFpEF.
Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis (2021)

Abstract Background Colorectal cancer (CRC) is the third-leading cause of cancer-related deaths in the United States and worldwide. Obesity - a worldwide public health concern - is a known risk factor for cancer including CRC. However, the mechanisms underlying the link between CRC and obesity have yet to be fully elucidated in part because of the molecular heterogeneity of CRC. We hypothesized that obesity modulates CRC in a consensus molecular subtype (CMS)-dependent manner. Methods RNA-seq data and associated tumor and patient characteristics including body weight and height data for 232 patients were obtained from The Cancer Genomic Atlas – Colon Adenocarcinoma (TCGA-COAD) database. Tumor samples were classified into the four CMSs with the CMScaller R package; Body mass index (BMI) was calculated and categorized as normal, overweight, and obese. Results We observed a significant difference in CMS categorization between BMI categories. Differentially expressed genes (DEGs) between obese and overweight samples and normal samples differed across the CMSs, and associated prognostic analyses indicated that the DEGs had differing effects on survival. Using Gene Set Enrichment Analysis, we found differences in Hallmark gene set enrichment between obese and overweight samples and normal samples across the CMSs. We constructed Protein-Protein Interaction networks and observed differences in obesity-regulated hub genes for each CMS. Finally, we analyzed and found differences in predicted drug sensitivity between obese and overweight samples and normal samples across the CMSs. Conclusions Thus, we conclude that obesity has CMS-specific effects on the CRC tumor transcriptome.
<title>PRIISM: an integrated system for display and analysis of 3-D microscope images</title> (1992)

Recent advances in a number of technologies, including digital data acquisition and image processing, have caused a revolution in light and electron microscopy. One important result of this revolution has been that it is now possible to investigate directly the structure of cells and cell components in three dimensions. For some time our laboratory has been developing the hardware and software required for high resolution three-dimensional imaging, utilizing both light and electron microscopy. This development effort has been driven by our desire to understand the three-dimensional structure and organization of chromosomes within the cell nucleus. Due to the vast amount of information contained in the three-dimensional data sets (typically 10 - 50 Mbytes each) and the complexity of the biological samples, data visualization plays a critical role. Without powerful display and analysis tools, it would be essentially impossible to extract useful information. Toward this end, we have spent considerable effort in developing software to aid the biologist in comprehending his three-dimensional data. A key aspect of this has been the utilization of multiple display windows that readily allow the comparison of different data or simultaneous viewing of data from multiple directions (PRISM, Chen et al, 1990). With the advancement of our research project, we require a parallel evolution in the visualization methods used to examine and understand the volumetric data. Consequently, a project was begun one year ago to develop a new image visualization system which will meet the future data visualization and image analysis requirements of our research.
Clouds and their discontents (2011)

Cloud computing has become increasingly popular and important. Many companies have policy initiatives encouraging or even mandating the use of "cloud" computing. The popularity of cloud computing stems primarily from the hope for significant cost savings but also from the ability to scale quickly without large capital expenditures and efficient sharing and curation of very large data sets (for example, search indexes). Clouds, like distributed computing generally, also offers the ability to access data and resources from any connected device (increasingly mobile devices like smart phones and lightweight tablets like iPads). However, cloud computing in all its incarnations (Infrastructure as a Service, Software as a Service, Platform as a Service) raises a number of security questions that current providers have not addressed (or remain ominously silent about): increased susceptibility to insider attacks due to concentration of valuable data, "fate-sharing" and other vulnerabilities due to multi-tenancy, policy issues arising from multi-jurisdictional siting, vulnerabilities arising from scale operations, the opacity of cloud operators security practices and disclosure of interruption of operations or attacks. Despite these potential issues, cloud computing can be beneficial with judicial and transparent application of some simple security principles. We discuss cloud infrastructure, economics, operations and security infrastructure desiderata.
Characteristics of microwave power GaN HEMTs on 4-inch Si wafers (2003)

We present the design and development of AlGaN/GaN high electron mobility transistors (HEMTs) fabricated on a 4-inch Si wafer. The GaN HEMT devices demonstrate a maximum drain current of 900 mA/mm, a peak g/sub m/ of 300 mS/mm, and a microwave output power density of 1.5 W/mm. To the best of the authors' knowledge, these are the best results reported on GaN HEMTs on 4-inch Si wafers.
Scheduling with preemption for incident management: when interrupting tasks is not such a bad idea (2012)

Large IT service providers comprise hundreds or even thousands of system administrators to handle customers' IT infrastructure. As part of the Information Systems that support the decision making of this environment, Incident Management Systems are used and usually provide human resource assignment functionalities. However, the assignment poses several challenges, such as establishing priorities to tasks and defining when and how tasks are allocated to available system administrators. This paper describes a set of incident dispatching policies that can be used, and by using workloads from different departments of an IT service provider, this work evaluates the impact of task preemption on incident resolution and service level agreement attainment.
ChemInform Abstract: Odoamide, a Cytotoxic Cyclodepsipeptide from the Marine Cyanobacterium Okeania sp. (2016)

Abstract The structure of the 26‐membered cyclodepsipeptide odoamide (I) is established by spectroscopic analysis, HPLC analysis, and synthetic methods.
Heterogeneous Segmental Dynamics during Creep and Constant Strain Rate Deformations of Rod-Containing Polymer Nanocomposites (2012)

The state of a glassy material can be altered considerably through the application of stress. The origins of this effect, and its relation to molecular mobility, are not well understood. Recent experimental, theoretical, and simulation studies have examined molecular mobility under deformation for different classes of materials, ranging from colloidal suspensions to polymeric glasses. While such studies indicate that dynamic heterogeneity, one of the hallmarks of glasses, decreases with the onset of flow, less is known about the effects of stress on polymer nanocomposites, whose mechanical and rheological properties can be significantly different from those of pure polymers. In this work, molecular simulations of multistep creep deformations and constant strain rate tensile deformations are used to examine dynamic heterogeneity in entangled, rod-containing nanocomposites. It is found that polymer nanocomposites, like polymers, experience reduced dynamic heterogeneity due to deformation, but some intrinsic heterogeneity of nonglassy origin persists. A connection between the segmental relaxation time and dynamic heterogeneity, suggested on the basis of an activated barrier-hopping model that includes local density fluctuations, is found to describe pure polymer behavior over a wide range of applied stresses, material compliances, and deformation histories. Additionally, segment displacements during postyield deformation are found to agree with a simple diffusional model across 2 orders of magnitude in strain rate for both pure polymer and nanocomposite systems.