gebhart/patrepeval huggingface dataset:
Three-dimensional brain growth abnormalities in childhood-onset schizophrenia visualized by using tensor-based morphometry (2008)

Earlier studies revealed progressive cortical gray matter (GM) loss in childhood-onset schizophrenia (COS) across both lateral and medial surfaces of the developing brain. Here, we use tensor-based morphometry to visualize white matter (WM) growth abnormalities in COS throughout the brain. Using high-dimensional elastic image registration, we compared 3D maps of local WM growth rates in COS patients and healthy children over a 5-year period, based on analyzing longitudinal brain MRIs from 12 COS patients and 12 healthy controls matched for age, gender, and scan interval. COS patients showed up to 2.2% slower growth rates per year than healthy controls in WM (P = 0.02, all P values corrected). The greatest differences were in the right hemisphere (P = 0.006). This asymmetry was attributable to a right slower than left hemisphere growth rate mapped in COS patients (P = 0.037) but not in healthy controls. WM growth rates reached 2.6% per year in healthy controls (P = 0.0002). COS patients showed only a 1.3% per year trend for growth in the left hemisphere (P = 0.066). In COS, WM growth rates were associated with improvement in the Children's Global Assessment Scale (R = 0.64, P = 0.029). Growth rates were reduced throughout the brain in COS, but this process appeared to progress in a front-to-back (frontal-parietal) fashion, and this effect was not attributable to lower IQ. Growth rates were correlated with functional prognosis and were visualized as detailed 3D maps. Finally, these findings also confirm that the progressive GM deficits seen in schizophrenia are not the result of WM overgrowth.
Transfection of AtT-20ins cells with GLUT-2 but not GLUT-1 confers glucose-stimulated insulin secretion. Relationship to glucose metabolism (1993)

Glucose is thought to stimulate insulin release from islet beta-cells through generation of metabolic signals. In the current study we have introduced the genes encoding the facilitated glucose transporters known as GLUT-1 and GLUT-2 into AtT-20ins cells to assess their impact on glucose-stimulated insulin release and glucose metabolism. We find that transfection of AtT-20ins cells with GLUT-2, but not GLUT-1, confers glucose-stimulated insulin release in both static incubation and perifusion studies. Cells transfected with GLUT-1 have a Km for 3-O-methyl glucose uptake of 4 mM and a Vmax of 5-6 mmol/min/liter cell space. These values are increased compared to untransfected AtT-20ins cells (Km = 2 mM; Vmax = 0.5 mmol/min/liter cell space), but are less than observed in GLUT-2-transfected lines (Km = 16-17 mM; Vmax = 17-25 mmol/min/liter cell space). Despite these dramatic differences in glucose transport affinity and capacity, the rates of [5-3H]glucose usage are not different in the control and transfected lines over a range of glucose concentrations from 10 microM to 20 mM. We conclude that the specific effect of GLUT-2 on glucose-stimulated insulin release in AtT-20ins cells is not related to changes in the overall rate of glucose metabolism and may instead involve physical coupling of GLUT-2 with cellular proteins and/or structures involved in glucose signaling.
Thresholdless switching induced by polar anchoring in antiferroelectric liquid crystals (1999)

We present a novel thresholdless switching mode in an antiferroelectric liquid crystal cell which is stabilized by the presence of polar anchoring at the cell surfaces and the antiferroelectric nature of the material. We also suggest other possible configurations which are induced by strong polar anchoring and possess quite different director structures and optical characteristics.
Cognitive Impairment in the Euthymic Phase of Chronic Unipolar Depression (1997)

Cognitive functioning in the nonsymptomatic phase and the long-term cognitive outcome of patients with mood disorders are both heuristic and important clinical issues in the study of mood disorders. Literature findings are inconsistent because of design confounds. We tried to address these issues while controlling for several confounds including age, education, gender differences in neurobehavioral functioning, and diagnosis. Nonsymptomatic patients with a history of chronic unipolar depression and bipolar affective disorder and healthy male individuals were administered neuropsychological tests to assess attention, visual-motor tracking, executive abilities, and immediate verbal memory. Subjects had comparable depression scores at the time of testing. Disease duration was 7.5 years (SD 5.1) for unipolar and 11 years (SD 7.3) for bipolar patients. Unipolar patients were more impaired than healthy normal comparison subjects on measures of visual-motor sequencing (Trail Making Test A, p < .05), executive function (Trail Making Test B, Stroop Test Color/Word Trial, p < .05), and immediate memory and attention (CERAD 1st trial, WAIS Digit Symbol subtest, p < .05). Differences between bipolar patients and normal comparison subjects did not reach significance in any of the selected measures. Male patients with a history of chronic unipolar disorder are at risk for cognitive impairment in the nonsymptomatic phase of their disease. Cognitive disturbance is the type seen with prefrontal dysfunction and may be assessed with standard neuropsychological assessments.
Extracellular matrix 4: The elastic fiber (1993)

The elastic properties of many tissues such as the lung, dermis, and large blood vessels are due to the presence of elastic fibers in the extracellular space. These fibers have been shown by biochemical and ultrastructural analysis to be composed of two distinct components, a more abundant amorphous component and a 10-12 nm microfibrillar component, which is located primarily around the periphery of the amorphous component. The protein elastin makes up the highly insoluble amorphous component and is responsible for the elastic properties. Elastin is found throughout the vertebrate kingdom and possesses an unusual chemical composition rich in glycine, proline, and hydrophobic amino acids, consonant with its characteristic physical properties. The 72-kDa biosynthetic precursor, tropoelastin, is secreted into the extracellular space where it becomes highly cross-linked into a rubber-like network through the activity of the copper-requiring enzyme lysyl oxidase. Analysis of the elastin gene has demonstrated that hydrophobic and cross-linking domains are encoded in separate exons and that there is significant alternative splicing, resulting in multiple isoforms of tropoelastin. The elastin gene promoter contains many potential binding sites for various modulating factors indicative of a complex pattern of transcriptional regulation. The microfibrils contain several proteins, including fibrillin, and probably act as an organizing scaffold in the formation of the elastin network. There appears to be a fibrillin gene family in which each protein contains multiple repeats of a motif previously found in epidermal growth factor and a second motif observed in transforming growth factor beta 1-binding protein. Mutations in the fibrillin gene located on human chromosome 15 have been strongly implicated as the cause of the Marfan syndrome.
Checkpoint Inhibitors and Their Application in Breast Cancer (2016)

Immune checkpoints are crucial for the maintenance of self-tolerance and for the modulation of immune responses in order to minimize tissue damage. Tumor cells take advantage of these mechanisms to evade immune recognition. A significant proportion of tumors, including breast cancers, can express co-inhibitory molecules that are important formediating the escape from T cell-mediated immune surveillance. The interaction of inhibitory receptors with their ligands can be blocked by specific molecules. Monoclonal antibodies (mAbs) directed against the cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and, more recently, against the programmed cell death protein 1 (PD1), have been approved for the therapy of melanoma (anti-CTLA4 and anti-PD1 mAbs) and non-small cell lung cancer (anti-PD1 mAbs). Moreover, inhibition of PD1 signaling has shown extremely promising signs of activity in breast cancer. An increasing number of molecules directed against other immune checkpoints are currently under clinical development. In this review, we summarize the evidence supporting the implementation of checkpoint inhibition in breast cancer by reviewing in detail data on PD-L1 expression and its regulation. In addition, opportunities to boost anti-tumor immunity in breast cancer with checkpoint inhibitor-based immunotherapies alone and in combination with other treatment options will be discussed.
Production of Organic Acids by Probiotic Lactobacilli Can Be Used to Reduce Pathogen Load in Poultry (2012)

Probiotic Lactobacillus can be used to reduce the colonization of pathogenic bacteria in food animals, and therefore reduce the risk of foodborne illness to consumers. As a model system, we examined the mechanism of protection conferred by Lactobacillus species to inhibit C. jejuni growth in vitro and reduce colonization in broiler chickens. Possible mechanisms for the reduction of pathogens by lactobacilli include: 1) stimulation of adaptive immunity; 2) alteration of the cecal microbiome; and, 3) production of inhibitory metabolites, such as organic acids. The Lactobacillus species produced lactic acid at concentrations sufficient to kill C. jejuni in vitro. We determined that lactic acid produced by Lactobacillus disrupted the membrane of C. jejuni, as judged by biophotonics. The spectral features obtained using Fourier-transform infrared (FT-IR) and Raman spectroscopy techniques were used to accurately predict bacterial viability and differentiate C. jejuni samples according to lactic acid treatment. FT-IR spectral features of C. jejuni and Lactobacillus grown in co-culture revealed that the metabolism was dominated by Lactobacillus prior to the killing of C. jejuni. Based on our results, the development of future competitive exclusion strategies should include the evaluation of organic acid production.
Platelet-Derived Serotonin, the Endothelium, and Cardiovascular Disease (1991)

The endothelial cells can release both relaxing and contracting substances. The former include prostacyclin and endothelium-derived relaxing factor (EDRF, which most likely is nitric oxide, or a nitrosoderivative releasing nitric oxide, derived from L-arginine). Candidates as endothelium-derived contracting factors (EDCF) include superoxide anions thromboxane A2 and the peptide endothelin. Endothelium-derived relaxing factor causes relaxation of vascular smooth muscle by activation of the soluble form of guanylate cyclase which leads to an accumulation of cyclic GMP; it also reduces platelet adhesion and aggregation. The latter effect is synergistic with the inhibition evoked by prostacyclin. The release of EDRF and prostacyclin plays a key role in the protective role of the endothelium against vasospasm and the unwanted coagulation of blood. Indeed, thrombin and aggregating platelets are potent stimuli for the release of EDRF. The platelet-products responsible are the adenine nucleotides, ADP and ATP, which activate P2y-purinergic receptors on the endothelial cells and 5-hydroxytryptamine (serotonin) that stimulates 5-HT1-like serotonergic receptors. The response to serotonin, but not that to the adenine nucleotides, is mediated by a pertussis toxin-sensitive mechanism. When endothelial cells regenerate, or are cultured, they selectively lose the pertussis toxin-sensitive mechanism of release, which results in a marked decrease in sensitivity to exogenous and platelet-released serotonin. As a consequence, the endothelial cells exhibit a considerably reduced response to aggregating platelets. This phenomenon, which can be exacerbated by hypercholesterolemia, favors ongoing platelet aggregation and vasospasm, and constitutes a first step toward atherosclerosis.
Lexical normalization for social media text (2013)

Twitter provides access to large volumes of data in real time, but is notoriously noisy, hampering its utility for NLP. In this article, we target out-of-vocabulary words in short text messages and propose a method for identifying and normalizing lexical variants. Our method uses a classifier to detect lexical variants, and generates correction candidates based on morphophonemic similarity. Both word similarity and context are then exploited to select the most probable correction candidate for the word. The proposed method doesn't require any annotations, and achieves state-of-the-art performance over an SMS corpus and a novel dataset based on Twitter.
Physiological Roles of Dietary Free Glutamate in Gastrointestinal Functions (2008)

The appropriate recognition of nutrients in gastrointestinal tract has an important role in the maintenance of healthy body functions. Perception of nutrients in gastrointestinal tract influences not only the regulation of gastrointestinal functions such as digestion and absorption, but also the subsequent formation of ingestive behaviors and food preferences. Glutamate is widely distributed amino acids, approximately 15—45% in the dietary protein as the total of free- and bound-forms. To note is that, glutamate is implicated in numerous physiological and metabolic functions in the body as a nutrient, in addition, free glutamate in the food is also known as the source of umami, one of the five basic taste. Taste is basically percepted on the tongue in the oral cavity via the specific taste sensors (receptors and/or transporters), however, the recent studies suggest the functional roles of taste sensors in the regulation of gastrointestinal tract. Interestingly, we recently found the presence of specific glutamate-sensing systems in the lumen of the stomach. In addition, we have been vigorously studying the physiological roles of dietary free glutamate in the body through experimental animals and human. In this topic, we review the beneficial roles of dietary free glutamate in the regulation of gastrointestinal functions and propose some application of the benefits for the clinical gastrointestinal disorders.
A STUDY OF RECOMBINANT ALVAC-CEA IN PATIENTS WITH ADVANCED CEA-BEARING CANCERS (1996)

Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.
β‐Carbolin‐Alkaloide, II Tributyl(1‐ethoxyvinyl)stannan als C2‐Baustein für die Synthese von β‐Carbolin‐Alkaloiden (1993)

β‐Carboline Alkaloids, II. – Tributyl(1‐ethoxyvinyl)stannane as a C 2 ‐Building Block in the Syntheses of β‐Carboline Alkaloids 1‐Acetyl‐β‐carboline ( 4 ) is prepared by palladium‐catalyzed coupling of 1‐chloro‐β‐carboline ( 1 ) with tributyl(1‐ethoxyvinyl)stannane ( 3 ) and subsequent hydrolysis with aqueous acid. Reduction of 4 with NaBH 4 gives the alkaloid 5 . Nitramarine ( 7 ) and annomontine ( 9 ) are prepared from 4 by one‐pot conversions of the acetyl group to a quinoline or an aminopyrimidine ring, respectively.
How Antigen Quantity and Quality Determine T-Cell Decisions in Lymphoid Tissue (2008)

T lymphocytes (T cells) express T-cell receptor (TCR) molecules on their surface that can recognize peptides (p) derived from antigenic proteins bound to products of the major histocompatibility complex (MHC) genes. The pMHC molecules are expressed on the surface of antigen-presenting cells, such as dendritic cells (DCs). T cells first encounter antigen on DCs in lymph nodes (LN). Intravital microscopy experiments show that upon entering the LN containing antigen, CD8+ T cells first move rapidly. After a few hours, they stop and make extended contacts with DCs. The factors that determine when and how this transition occurs are not well understood. We report results from computer simulations that suggest that the duration of phase one is related to the low probability of productive interactions between T cells and DCs. This is demonstrated by our finding that the antigen dose and type determine when such a transition occurs. These results are in agreement with experimental observations. TCR-pMHC binding characteristics and the antigen dose determine the time required for a productive T-cell-DC encounter (resulting in sustained contact). We find that the ratio of this time scale and the half-life of the pMHC complex itself provide a consolidated measure of antigen quantity and type. Results obtained upon varying different measures of antigen quantity and type fall on one curve when graphed against this ratio of time scales. Thus, we provide a mechanism for how the effects of varying one set of parameters are influenced by other prevailing conditions. This understanding should help guide future experimentation.
MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors (2012)

Neurofibromatosis type 1 (NF1) patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras signaling. Activated Ras controls numerous downstream effectors, but specific pathways mediating the effects of hyperactive Ras in NF1 tumors are unknown. We performed cross-species transcriptome analyses of mouse and human neurofibromas and MPNSTs and identified global negative feedback of genes that regulate Ras/Raf/MEK/ERK signaling in both species. Nonetheless, ERK activation was sustained in mouse and human neurofibromas and MPNST. We used a highly selective pharmacological inhibitor of MEK, PD0325901, to test whether sustained Ras/Raf/MEK/ERK signaling contributes to neurofibroma growth in a neurofibromatosis mouse model (Nf1(fl/fl);Dhh-Cre) or in NF1 patient MPNST cell xenografts. PD0325901 treatment reduced aberrantly proliferating cells in neurofibroma and MPNST, prolonged survival of mice implanted with human MPNST cells, and shrank neurofibromas in more than 80% of mice tested. Our data demonstrate that deregulated Ras/ERK signaling is critical for the growth of NF1 peripheral nerve tumors and provide a strong rationale for testing MEK inhibitors in NF1 clinical trials.
A transformation method for the reconstruction of functions from nonuniformly spaced samples (1985)

The reconstruction of functions from their samples at nonuniformly distributed locations is an important task for many applications. This paper presents a sampling theory which extends the uniform sampling theory of Whittaker et al. [11] to include nonuniform sample distributions. This extension is similar to the analysis of Papoulis [15], who considered reconstructions of functions that had been sampled at positions deviating slightly from a uniform sequence. Instead of treating the sample sequence as deviating from a uniform sequence, we show that a more general result can be obtained by treating the sample sequence as the result of applying a coordinate transformation to the uniform sequence. It is shown that the class of functions reconstructible in this manner generally include nonband-limited functions. The two-dimensional uniform sampling theory of Petersen and Middle ton [16] can be similarly extended as is shown in this paper. A practical algorithm for performing reconstructions of two-dimensional functions from nonuniformly spaced samples is described, as well as examples illustrating the performance of the algorithm.
Cannabidiol reduced frequency of convulsive seizures in drug resistant Dravet syndrome (2017)

Design: Multinational double-blinded placebo-controlled trial. Patients randomised in 1:1 ratio to receive cannabidiol or placebo, in addition to stable antiepileptic treatment regime.

Setting: Twenty-three centres in Europe and USA.

Patients: Patients aged 2 years to 18 years with established diagnosis of Dravet syndrome having at least four convulsive seizures during the 28-day baseline period despite regular antiepileptic medication.

Intervention: Adjunctive cannabidiol or placebo oral solution at 20 mg per kilogram of body weight per day.

Primary outcome: Percentage change in median frequency of convulsive seizures per month.

Follow-up period: Outcome measured over a 14-week treatment period in comparison to a 4-week baseline period.

Patient follow-up: One hundred and eight (90%) completed the trial: 85% (52/61) in the cannabidiol group and …
Case studies of survivable ring, mesh and mesh-arc hybrid networks (2003)

A quantitative comparison of pure ring and pure mesh survivable network alternatives in a metropolitan study network is provided. The results lead to the development of B-DCS technology to convert the capacity efficiency of mesh restoration methods into economic advantages. An architecture for cooperative interworking between ADM and DCS nodes to realize a survivable access and transport network is introduced. The concept of a survivable arc (as opposed to a pure ring) for cooperative interworking between ADM-based ring and DCS-based mesh restoration technologies is illustrated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
B Cell Development Pathways (2001)

B cell development is a highly regulated process whereby functional peripheral subsets are produced from hematopoietic stem cells, in the fetal liver before birth and in the bone marrow afterward. Here we review progress in understanding some aspects of this process in the mouse bone marrow, focusing on delineation of the earliest stages of commitment, on pre-B cell receptor selection, and B cell tolerance during the immature-to-mature B cell transition. Then we note some of the distinctions in hematopoiesis and pre-B selection between fetal liver and adult bone marrow, drawing a connection from fetal development to B-1/CD5(+) B cells. Finally, focusing on CD5(+) cells, we consider the forces that influence the generation and maintenance of this distinctive peripheral B cell population, enriched for natural autoreactive specificities that are encoded by particular germline V(H)-V(L) combinations.
Computerized diagnostic setups and simulations. (1970)

Abstract No Abstract Available. Supported in part by P.H.S. Grants DE-02506-01, FR-15 and DE-0087-14 and the Elementary Particles Group of the Physics department at the University of Pennsylvania.
Graphene Bragg gratings on microfiber (2014)

Graphene Bragg gratings (GBGs) on microfiber are proposed and investigated in this paper. Numerical analysis and simulated results show that the mode distribution, transmission loss, and central wavelength of the GBG are controllable by changing the diameter of the microfiber or the refractive index of graphene. Such type of GBGs with tunability may find important applications in optical fiber communication and sensing as all-fiber in-line devices.