gebhart/patrepeval huggingface dataset:
Non-neuronal cell outgrowth in<i>C</i><i>. elegans</i> (2017)

Cell outgrowth is a hallmark of some non-migratory developing cells during morphogenesis. Understanding the mechanisms that control cell outgrowth not only increases our knowledge of tissue and organ development, but can also shed light on disease pathologies that exhibit outgrowth-like behavior. <i>C. elegans</i> is a highly useful model for the analysis of genes and the function of their respective proteins. In addition, <i>C. elegans</i> also has several cells and tissues that undergo outgrowth during development. Here we discuss the outgrowth mechanisms of nine different <i>C. elegans</i> cells and tissues. We specifically focus on how these cells and tissues grow outward and the interactions they make with their environment. Through our own identification, and a meta-analysis, we also identify gene families involved in multiple cell outgrowth processes, which defined potential <i>C. elegans</i> core components of cell outgrowth, as well as identify a potential stepwise cell behavioral cascade used by cells undergoing outgrowth.
Current-density centric logical effort delay model for high-speed current-mode logic circuits (2011)

A simple yet accurate delay model based on the method of logical effort is presented for the analysis of high-speed current-mode logic (CML) circuits. The model describes the logical effort of a CML gate in terms of its operating current density normalised to the characteristic current density that yields peak transistor cutoff frequency (fT). Since the latter remains largely invariant over technology nodes as a result of constant-field scaling, the proposed logical effort model quantifies the effect of gate sizing, biasing and loading to simplify delay analysis for CML gates.
Highly Specific Coordination-Driven Self-Assembly of 2D Heterometallic Metal–Organic Frameworks with Unprecedented Johnson-type (<i>J</i><sub>51</sub>) Nonanuclear Zr-Oxocarboxylate Clusters (2021)

The quest for new and unique polynuclear metal-oxocarboxylate clusters has led to a continual boom of highly connected and robust metal-organic frameworks (MOFs) with intriguing properties. In this work, by virtue of a highly specific coordination-driven cluster rearrangement process of a presynthesized trinuclear zirconocene-based tripodal metallo-pyridine ligand, we realized the preparation of the first two 2D heterometallic MOFs incorporating unprecedented Johnson-type (<i>J</i><sub>51</sub>) nonanuclear Zr-oxocarboxylate clusters, as unambiguously uncovered by single-crystal X-ray crystallography. The resultant two charged frameworks feature counteranion-dependent 3,6-c kgd (JMOF-1) and 3,12-c 3,12L4 (JMOF-2) nets that are formed by octahedral and hexagonal prismatic Zr<sub>9</sub> molecular building blocks (MBBs), respectively. In addition, JMOF-2 shows promise for the purification of acetylene from CO<sub>2</sub> and C<sub>2</sub>H<sub>4</sub>, with IAST selectivities of about 12 and 8, respectively, at 298 K and 1 bar, as well as remarkable iodine capture capacity of up to 2.4 g g<sup>-1</sup>.
Differential Effects of Traumatic Brain Injury on the Cytochrome P450 System: A Perspective into Hepatic and Renal Drug Metabolism (2003)

Traumatic brain injury is known to cause several secondary effects, one of which is altered drug clearance. Given the fact that patients who sustain TBI are subsequently treated with a variety of pharmacological agents for the purpose of either neuroprotection or physiological support, it is imperative to clarify changes in expression and/or activities of enzymes involved in clearing drugs. The mixed function oxidase system, which consists of cytochrome P450 and cytochrome P450 reductase, plays a vital role in phase I drug metabolism. This paper addresses the issue as to what extent TBI affects the levels and activity of various rat CYP450 subfamilies. Our results show that TBI induces tissue-specific and time-dependent alterations. Total hepatic CYP450 content showed a biphasic response with a decrease seen at 24 h followed by an increase at 2 weeks. CYP450 reductase, in contrast, showed an opposite temporal profile. Immunoblot analyses and marker substrate metabolism demonstrated a clear decrease in hepatic CYP1A levels while a significant increase in kidney was seen at both 24 h and 2 weeks. A dramatic induction of CYP3A was evident at 2 weeks in liver, while no changes were noticed in CYP2B or CYP2D subfamilies. CYP4F subfamily showed induction in kidney only. Collectively, the data reveal the differential effects of TBI on hepatic and renal drug metabolism.
Hierarchical Multialgorithm Parallel Circuit Simulation (2010)

The emergence of multicore and many-core processors has introduced new opportunities and challenges to electronic design automation research and development. While the availability of increasing parallel computing power holds new promise to address many challenges in computer-aided design (CAD), the leverage of hardware parallelism can only be possible with a new generation of parallel CAD applications. In this paper, we propose a novel hierarchical multialgorithm (MA) parallel circuit simulation approach and its multicore implementation to expedite one of the most fundamental CAD applications: transistor-level transient circuit simulation. In our parallel circuit simulation approach, we create two levels of parallelism. At the higher level of parallelism, we start multiple simulation algorithms in parallel for a given simulation task. Interalgorithm communication is established to enable simulation algorithms to exchange useful information so that they could advance faster than without doing so. At the lower level of parallelism, each algorithm within the MA framework utilizes fine-grained parallel techniques such as parallel device evaluation and parallel matrix solve to fully harness the available hardware resources. By combining the two levels of parallelism, the computing power of the multicore or many-core processor platforms can be fully utilized to achieve superlinear speedup in circuit simulation.
Synthèse de ligands de l'acétylcholinestérase humaine : application à l'étude des réactions de click in situ (2010)

La click in est une technique recente proposee pour accelerer la decouverte de molecules biologiquement actives. Elle repose sur un test de « criblage » utilisant deux chimiotheques de ligands dotes d'une fonction reactive complementaire par click et de la biomolecule cible. Celle-ci serait alors capable de selectionner parmi le melange de une(des) combinaison(s) adequate(s) pour former des ligands couples tres actifs. Le principe de cette technique a d'ores et deja ete valide par ses concepteurs en utilisant les acetylcholinesterases (AChE) de souris et d'anguille et a permis la decouverte de molecules puissamment inhibitrices de ces enzymes. Le cadre de ce projet se place dans une optique d'investigation de la chimie click in situ via sa transposition a l'AChE humaine, dont l'inhibition comporte des interets medicinaux importants comme le traitement palliatif de la maladie d'Alzheimer. Le travail presente dans ce manuscrit porte principalement sur la synthese de ligands de l'AChE humaine comportant une fonction reactive en tant que fragments pouvant etre assembles par chimie click in situ. Plus precisement, la synthese a ete focalisee sur des ligands de type 4-aminoquinoline de la famille des tacrines et huprines, mais des derives de tetrahydroisoquinolines, de l'indole, de tetrahydropyrido[3,4,b]indole et de coumarine ont egalement ete prepares. Au cours de ces travaux, une methode alternative d'amination palladocatalysee a ete developpee pour obtenir des tacrines et huprines N-alkylees en position 12 et une voie d'acces aux huprines fonctionnalisees en position 9 a ete decouverte et exploitee pour obtenir in fine plus de 60 inhibiteurs mono- ou heterodimeriques. Les molecules synthetisees presentent un interet double. Dans le cadre de l'application de la click in a l'AChE humaine, elles ont constitue des outils qui ont permis non seulement d'observer le premier produit de click in avec cette enzyme mais aussi de clarifier certaines interrogations sur la methode et d'en esquisser les limitations. D'autre part, certains de ces ligands ont ete utilises pour des applications emergentes dans des domaines varies de la bio-organique telles que l’imagerie TEP ou par florescence, des etudes cristallographiques ou la purification de biomolecules.
High-Quality Torque Control at Zero and Very High Speed Operation (1995)

This article focuses on the design and analysis of a direct field orientation (DFO) approach based upon a closed-loop loop rotor flux observer. The approach is ideally suited for applications requiring both zero and very high (i.e., several times base) speed operation. Such applications are common in manufacturing automation where both zero speed position control and high traverse rates with controlled position trajectories are required. Examples include robot motion control systems as used for assembly and the more traditional machining center axis control. The quality of the proposed approach is largely based on the unique structure of its flux observer. The observer effectively combines the best accuracy attributes of rotor flux indirect (feedforward) field orientation (IFO) and stator flux DFO. The parameter sensitivity is similar to IFO at low and zero speeds and to stator flux DFO at high speeds. The closed-loop structure of the observer provides a smooth transition between two open-loop rotor flux observers referred to as the current and voltage models in a deterministic manner set by the closed-loop bandwidth (eigenvalues). The proposed DFO approach is analytically evaluated in comparison with both IFO and stator flux DFO. Experimental results verify the viability of this approach.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
LONG TERM DYNAMIC COMPRESSION OF THE INTERVERTEBRAL DISC CAUSES REMODELING IN VIVO (2008)

Spine is an international, peer-reviewed, bi-weekly periodical that considers for publication original articles in the field of spine. It is the leading subspecialty journal for the treatment of spinal disorders. Only original papers are considered for publication with the understanding that they are contributed solely to Spine. The Journal does not publish articles reporting material that has been reported at length elsewhere.
Kindler syndrome: Extension of FERMT1 mutational spectrum and natural history (2011)

Mutations in the FERMT1 gene (also known as KIND1), encoding the focal adhesion protein kindlin-1, underlie the Kindler syndrome (KS), an autosomal recessive skin disorder with an intriguing progressive phenotype comprising skin blistering, photosensitivity, progressive poikiloderma with extensive skin atrophy, and propensity to skin cancer. Herein we review the clinical and genetic data of 62 patients, and delineate the natural history of the disorder, for example, age at onset of symptoms, or risk of malignancy. Although most mutations are predicted to lead to premature termination of translation, and to loss of kindlin-1 function, significant clinical variability is observed among patients. There is an association of FERMT1 missense and in-frame deletion mutations with milder disease phenotypes, and later onset of complications. Nevertheless, the clinical variability is not fully explained by genotype-phenotype correlations. Environmental factors and yet unidentified modifiers may play a role. Better understanding of the molecular pathogenesis of KS should enable the development of prevention strategies for disease complications.
A Virtual Frame Buffer Abstraction for Parallel Rendering of Large Tiled Display Walls (2020)

We present dw2, a flexible and easy-to-use software infrastructure for interactive rendering of large tiled display walls. Our library represents the tiled display wall as a single virtual screen through a display "service", which renderers connect to and send image tiles to be displayed, either from an on-site or remote cluster. The display service can be easily configured to support a range of typical network and display hardware configurations; the client library provides a straightforward interface for easy integration into existing renderers. We evaluate the performance of our display wall service in different configurations using a CPU and GPU ray tracer, in both on-site and remote rendering scenarios using multiple display walls.
Therapeutic Induction of Collateral Flow (2022)

Therapeutic induction of collateral flow as a means to salvage tissue and improve outcome from acute ischemic stroke is a promising approach in the era in which endovascular therapy is no longer time-dependent but collateral-dependent. The importance of collateral flow enhancement as a therapeutic for acute ischemic stroke extends beyond those patients with large amounts of salvageable tissue. It also has the potential to extend the time window for reperfusion therapies in patients who are ineligible for endovascular thrombectomy. In addition, collateral enhancement may be an important adjuvant to neuroprotective agents by providing a more robust vascular route for which treatments can gain access to at risk tissue. However, our understanding of collateral hemodynamics, including under comorbid conditions that are highly prevalent in the stroke population, has hindered the efficacy of collateral flow augmentation for improving stroke outcome in the clinical setting. This review will discuss our current understanding of pial collateral function and hemodynamics, including vasoactivity that is critical for enhancing penumbral perfusion. In addition, mechanisms by which collateral flow can be increased during acute ischemic stroke to limit ischemic injury, that may be different depending on the state of the brain and vasculature prior to stroke, will also be reviewed.
Local Gene Transduction of Cyclooxygenase-1 Increases Blood Flow in Injured Atherosclerotic Rabbit Arteries (2005)

The effectiveness of COX-1 in preventing restenosis and preserving normal blood flow 28 days after injury results from increased lumen area caused by durable vasodilation. COX-1 efficacy correlates with an early increase in the production of PGI2, PGE2, PGE1 (known to cause vasodilation), and cAMP. These results demonstrate for the first time that COX-1 gene transduction is an effective treatment for the prevention of postangioplasty restenosis of atherosclerotic arteries under clinically relevant conditions.
Alosetron Improves Quality of Life in Women With Diarrhea-Predominant Irritable Bowel Syndrome (2001)

These results in women with diarrhea-predominant IBS demonstrate that alosetron significantly improves health-related quality of life.
Copper-Catalyzed Nitroso-Diels–Alder Reaction (2016)

Key words nitroso-Diels–Alder reaction - cyclic dienes - narciclasine - copper catalysis
Monoallelic <i>CRMP1</i> gene variants cause neurodevelopmental disorder (2022)

Abstract Collapsing response mediator proteins (CRMPs) are key for brain development and function. Here, we link CRMP1 to a neurodevelopmental disorder. We report heterozygous de novo variants in the CRMP1 gene in three unrelated individuals with muscular hypotonia, intellectual disability and/or autism spectrum disorder. Based on in silico analysis these variants are predicted to affect the CRMP1 structure. We further analyzed the effect of the variants on the protein structure/levels and cellular processes. We showed that the human CRMP1 variants are dominant-negative and impact the oligomerization of CRMP1 proteins. Moreover, overexpression of mutant- CRMP1 variants affect neurite outgrowth of murine cortical neurons. While altered CRMP1 levels have been reported in psychiatric diseases, genetic mutation in CRMP1 gene has never been linked to human disease. We report for the first-time mutations in the CRMP1 gene and emphasize its key role in brain development and function by linking directly to a human neurodevelopmental disease.
Comparative gene expression analysis between coronary arteries and internal mammary arteries identifies a role for the TES gene in endothelial cell functions relevant to coronary artery disease (2011)

Coronary artery disease (CAD) is the leading cause of death worldwide. It has been established that internal mammary arteries (IMA) are resistant to the development of atherosclerosis, whereas left anterior descending (LAD) coronary arteries are athero-prone. The contrasting properties of these two arteries provide an innovative strategy to identify the genes that play important roles in the development of atherosclerosis. We carried out microarray analysis to identify genes differentially expressed between IMA and LAD. Twenty-nine genes showed significant differences in their expression levels between IMA and LAD, which included the TES gene encoding Testin. The role of TES in the cardiovascular system is unknown. Here we show that TES is involved in endothelial cell (EC) functions relevant to atherosclerosis. Western blot analysis showed higher TES expression in IMA than in LAD. Reverse transcription polymerase chain reaction and western blot analyses showed that TES was consistently and markedly down-regulated by more than 6-fold at both mRNA and protein levels in patients with CAD compared with controls without CAD (P= 0.000049). The data suggest that reduced TES expression is associated with the development of CAD. Knockdown of TES expression by small-interfering RNA promoted oxidized-LDL-mediated monocyte adhesion to ECs, EC migration and the transendothelial migration of monocytes, while the over-expression of TES in ECs blunted these processes. These results demonstrate association between reduced TES expression and CAD, establish a novel role for TES in EC functions and raise the possibility that reduced TES expression increases susceptibility to the development of CAD.
Electron Deficient Monomers that Optimize Nucleation and Enhance the Photocatalytic Redox Activity of Carbon Nitrides (2019)

Abstract Polymeric carbon nitride (PCN) is usually synthesized from nitrogen‐rich monomers such as cyanamide, melamine, and urea, but is rather disordered in many cases. Now, a new allotrope of carbon nitride with internal heterostructures was obtained by co‐condensation of very electron poor monomers (for example, 5‐amino‐tetrazole and nucleobases) in the presence of mild molten salts (for example, NaCl/KCl) to mediate the polymerization kinetics and thus modulate the local structure, charge carrier properties, and most importantly the HOMO and LUMO levels. Results reveal that the as‐prepared NaK‐PHI‐A material shows excellent photo‐redox activities because of a nanometric hetero‐structure which enhances visible light absorption and promotes charge separation in the different domains.
P-1080 - Quetiapine fumarate extended release (XR) in bipolar depression and major depressive disorder (2012)

Quetiapine extended release (XR) was developed to provide convenient, once-daily dosing and rapid dose escalation when compared to the immediate-release (IR) formulation. To review preclinical and clinical study data on the efficacy and safety of quetiapine XR in bipolar depression and major depressive disorder (MDD). Review of published studies and presentations at scientific congresses. Quetiapine fumarate demonstrates a broad spectrum of efficacy in psychotic and mood disorders. In pharmacologic studies, quetiapine and its major active metabolite, norquetiapine, have actions on 5-HT2A receptors and D2 receptors, considered to explain efficacy in psychosis and mania. Norquetiapine, unlike quetiapine and other atypical antipsychotics at relevant doses, has affinity for the norepinephrine transporter in-vitro and demonstrates binding in-vivo, which may contribute to antidepressant efficacy. Quetiapine XR as monotherapy (300 mg/day) was significantly more effective than placebo in a study of patients with acute bipolar depression, with onset of effect as early as 1 week. In large, placebo-controlled studies, quetiapine XR as monotherapy (50-300 mg/day), or adjunct therapy (150-300 mg/day) to antidepressants, has demonstrated efficacy against depressive and comorbid symptoms in MDD, with rapid onset of effect. The safety profile of quetiapine XR in these studies was broadly consistent with quetiapine IR. Sedation intensity during initial dose escalation was significantly lower with quetiapine XR than IR in 1 study in patients with bipolar depression. Quetiapine XR is effective in bipolar depression and MDD and has a safety profile consistent with quetiapine IR. By funding from AstraZeneca Pharmaceuticals LP.
Abstract WP125: Relationships Of Hemoglobin With Ischemic Lesions After Intracerebral Hemorrhage (2023)

Introduction: Hemoglobin concentrations and diffusion weighted imaging (DWI) lesions are separately known to be associated with poor intracerebral hemorrhage (ICH) outcomes. Though hemoglobin concentrations are related to both hypoxia and thrombosis at their extremes, it is unknown whether hemoglobin concentrations relate to DWI lesions after ICH. Methods: Spontaneous, supratentorial ICH patients with available baseline hemoglobin and hospitalized MRI data enrolled into a multicenter cohort study between 2010-2016 were analyzed. Baseline hemoglobin was assessed as both a continuous variable (g/dL) and categorical variable (&lt;11, 11 to &lt;13, 13 to &lt;15, &gt;/=15 g/dL). Primary analyses assessed relationships of baseline hemoglobin with MRI DWI lesions. Secondary analyses assessed independent relationships of hemoglobin and DWI lesions with poor 3-month outcomes (modified Rankin Scale [mRS] 4-6). Separate multivariable regression models assessed these relationships after adjusting for relevant covariates. Results: Of 917 ICH patients analyzed, the mean baseline hemoglobin was 13.8 g/dL (+/-1.9), 60% were deep ICH, and DWI lesions were identified in 27% of the cohort. In our primary analyses, increased hemoglobin, defined as a continuous variable, was associated with DWI lesions (adjusted OR 1.21, 95% CI: 1.07-1.37) after adjusting for sex, race, ICH severity, time to MRI, and blood pressure treatment change. In secondary analyses, DWI lesions were associated with poor 3-month outcomes (adjusted OR 1.83, 95% CI: 1.24-2.69) adjusting for similar covariates. We identified associations of low hemoglobin categories, when referenced to hemoglobin 13 to &lt;15 g/dL, with poor outcomes (&lt;11 g/dL: adjusted OR 1.99, 95% CI: 1.05-3.79; 11 to &lt;13 g/dL: adjusted OR 1.62, 95% CI: 1.04-2.52). Effect estimates of high hemoglobin (&gt;/=15 g/dL) with poor outcomes were smaller and imprecise (adjusted OR 1.39, 95% CI: 0.89-2.17). Conclusions: We identified novel relationships between higher baseline hemoglobin concentrations and DWI lesions in ICH patients. Further studies are required to clarify the role of hemoglobin concentrations on both cerebral small vessel disease pathophysiology and ICH outcomes.