gebhart/patrepeval huggingface dataset:
Methionine sulfoximine shows excitotoxic actions in rat cortical slices (1999)

Methionine sulfoximine (MSO) is a rare amino acid. It occurs in nature or as a by-product of some forms of food processing. A notable example of the latter was a former method for bleaching wheat flour, using nitrogen trichloride, the "agene process," in use for most of the first 50 years of this century. "Agenized" flour was found to be responsible for various neurological disorders in animals, and MSO was identified as the toxic factor. The agene process was subsequently discontinued in the United States and the United Kingdom circa 1950. MSO inhibits the synthesis of both glutathione and glutamine, and it is possible that its actions on the nervous system arise from alterations in the amount or distribution of these molecules. Structurally, MSO resembles glutamate, an observation that has also raised the possibility that it might have more direct glutamate-like actions on neurons. In the present investigation, we report excitatory and toxic actions of MSO in an in vitro preparation of adult rat cortex. Field potential recordings in this preparation show that MSO application evokes a sustained depolarization, which can be blocked by the N-methyl-D-aspartate (NMDA) antagonist L-(+)-2-amino-5-phosphonovalerate (AP5). However, competition assays using MSO on [ 3 H]CGP-39653 (DL-(E)-2-amino-4-propyl-1-phosphono-3-pentenoate) binding in rat cortical homogenates show only 20% displacement of total binding, suggesting that MSO is acting indirectly, perhaps by releasing glutamate. To investigate this possibility, we measured glutamate release during MSO application. Time course and dose-response experiments with MSO showed significant [ 3 H]glutamate release, which was partially attenuated by AP5. To assess cellular toxicity, we measured lactate dehydrogenase (LDH) release from cortical sections exposed to MSO. MSO treatment led to a rapid increase in LDH activity, which could be blocked by AP5. These data suggest that MSO acts by increasing glutamate release, which then activates NMDA receptors, leading to excitotoxic cell death. These data suggest the possibility that MSO in processed flour had excitotoxic actions that may have been contributing factors to some human neuronal disorders.Key words: agene process, glutamate release, lactate dehydrogenase, methionine sulfoximine, N-methyl-D-aspartate (NMDA) receptor, neurological disorders.
Analyzing the forces binding a restriction endonuclease to DNA using a synthetic nanopore (2009)

Restriction endonucleases are used prevalently in recombinant DNA technology because they bind so stably to a specific target sequence and, in the presence of cofactors, cleave double-helical DNA specifically at a target sequence at a high rate. Using synthetic nanopores along with molecular dynamics (MD), we have analyzed with atomic resolution how a prototypical restriction endonuclease, EcoRI, binds to the DNA target sequence--GAATTC--in the absence of a Mg(2+) ion cofactor. We have previously shown that there is a voltage threshold for permeation of DNA bound to restriction enzymes through a nanopore that is associated with a nanonewton force required to rupture the complex. By introducing mutations in the DNA, we now show that this threshold depends on the recognition sequence and scales linearly with the dissociation energy, independent of the pore geometry. To predict the effect of mutation in a base pair on the free energy of dissociation, MD is used to qualitatively rank the stability of bonds in the EcoRI-DNA complex. We find that the second base in the target sequence exhibits the strongest binding to the protein, followed by the third and first bases, with even the flanking sequence affecting the binding, corroborating our experiments.
Epigenetic mechanisms of gene regulation (1996)

Historical overview of epigenetic mechanisms DNA methylation paramutation, imprinting and X inactivation repeated genes and gene silencing nuclear organization and chromatin structure transposable elements and viruses. Appendices.
Characterization of a novel Rochalimaea species, R. henselae sp. nov., isolated from blood of a febrile, human immunodeficiency virus-positive patient (1992)

Isolation of a Rochalimaea-like organism from a febrile patient infected with human immunodeficiency virus was confirmed. Analysis of 16S rRNA gene sequences, together with polymerase chain reaction and restriction endonuclease length polymorphism analysis of a portion of the citrate synthase gene, demonstrated that the agent is closely related to members of the genus Rochalimaea and that the isolate is genotypically identical to the presumptive etiologic agent of bacillary angiomatosis. However, the same genotypic analyses readily differentiated the new isolate from isolates of other recognized Rochalimaea species as well as other genera of bacteria previously suggested as putative etiologic agents of bacillary angiomatosis and related syndromes. We propose that the novel species be referred to as Rochalimaea henselae sp. now.
A 90nm CMOS 16Gb/s Transceiver for Optical Interconnects (2007)

An optical interconnect transceiver incorporates a 4-tap FIR TX to reduce VCSEL average current and an integrating/double-sampling RX to eliminate the need for a bit-rate TIA. A dual-loop CDR with baud-rate phase detection further reduces power and area. Fabricated in a 1V 90nm CMOS process, the transceiver achieves 16Gb/s operation while consuming 129mW and occupying 0.105mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup>
Amelioration of acute graft vs host disease due to minor histocompatibility antigens by in vivo administration of anti-interleukin 2 receptor antibody. (1986)

Lethal acute graft vs host disease (GVHD) elicited by minor histocompatibility antigens was studied in a murine model of bone marrow transplantation (B10.BR----CBA). The severity of GVHD was reduced by both clinical and histologic parameters when transplant recipients received injections of a monoclonal antibody directed against the interleukin 2 receptor. This study suggests that anti-interleukin 2 receptor antibodies may be useful in clinical marrow transplantation and provides additional evidence that monoclonal antibodies that block T cell function in vitro may be of therapeutic value in vivo.
Biological activity of recombinant human ZP3 produced in vitro: potential for a sperm function test (1996)

The human zona binding test is the most predictive test of sperm function yet the availability of human zona severely restricts its clinical use. The primary aim of this study was to use a commercially available in-vitro transcription and translation system to produce immobilized recombinant human ZP3 (rhuZP3) on agarose beads. The biological activity of this preparation was examined using sperm binding and the acrosome reaction. Significantly higher levels of sperm binding to rhuZP3 beads (n = 12, P < 0.05) compared with controls were observed and there was a significant induction (n = 12, P < 0.01) in the acrosome reaction after overnight incubation at 37 degrees C in 5% CO2 in air. In conclusion, the in-vitro transcription and translation system can produce sufficient quantities of purified immobilized biologically active rhuZP3. These preliminary experiments will enable further refinements to be made so that a solid-phase sperm function test based on rhuZP3 coated beads is likely to be developed in the near future.
E2 polypeptides encoded by bovine papillomavirus type 1 form dimers through the common carboxyl-terminal domain: transactivation is mediated by the conserved amino-terminal domain. (1989)

The E2 open reading frame (ORF) of bovine papillomavirus type 1 (BPV-1) encodes positive- and negative-acting factors that regulate viral gene expression. The full-length ORF encodes a transactivator, and two transcriptional repressors are expressed from the 3' half of the ORF. Previous analysis has shown that a conserved C-terminal region of 101 amino acids, which is shared by E2 transactivator and repressor proteins, contains the specific DNA binding activity. Further analysis of the E2 transactivator shows that a conserved N-terminal domain of approximately 220 amino acids is crucial for the transcriptional activation function, whereas the variable internal region is not required. The E2 proteins bind to a sequence, ACCGN4CGGT, several copies of which are sufficient to constitute an E2-dependent enhancer. By using a gel retardation assay and proteins derived by in vitro transcription and translation, we were able to show that the E2 polypeptides bind as dimers to a single DNA binding site. The dimeric E2 proteins are stable in the absence of DNA and dimerization is mediated through the DNA binding domain. This may reveal an additional mechanism of repression that could potentially result from the formation of inactive heterodimers between transactivator and repressor species.
Photoreceptor Guanylate Cyclases: A Review (1997)

Almost three decades of research in the field of photoreceptor guanylate cyclases are discussed in this review. Primarily, it focuses on the members of membrane-bound guanylate cyclases found in the outer segments of vertebrate rods. These cyclases represent a new guanylate cyclase subfamily, termed ROS-GC, which distinguishes itself from the peptide receptor guanylate cyclase family that it is not extracellularly regulated. It is regulated, instead, by the intracellularly-generated Ca2+ signals. A remarkable feature of this regulation is that ROS-GC is a transduction switch for both the low and high Ca2+ signals. The low Ca2+ signal transduction pathway is linked to phototransduction, but the physiological relevance of the high Ca2+ signal transduction pathway is not yet clear; it may be linked to neuronal synaptic activity. The review is divided into eight sections. In Section I, the field of guanylate cyclase is introduced and the scope of the review is briefly explained; Section II covers a brief history of the investigations and ideas surrounding the discovery of rod guanylate cyclase. The first five subsections of Section III review the experimental efforts to quantify the guanylate cyclase activity of rods, including in vitro and in situ biochemistry, and also the work done since 1988 in which guanylate cyclase activity has been determined. In the remaining three subsections an analytical evaluation of the Ca2+ modulation of the rod guanylate cyclase activity related to phototransduction is presented. Section IV deals with the issues of a biochemical nature: isolation and purification, subcellular localization and functional properties of rod guanylate cyclase. Section V summarizes work on the cloning of the guanylate cyclases, analysis of their primary structures, and determination of their location with in situ hybridization. Section VI summarizes studies on the regulation of guanylate cyclases, with a focus on guanylate cyclases activating proteins. In Section VII, the evidence about the localization and functional role of guanylate cyclases in other retinal cells, especially in "on-bipolar" cells, in which guanylate cyclase most likely plays a critical role in electrical signaling, is discussed. The review concludes with Section VIII, with remarks about the future directions of research on retinal guanylate cyclases.
Activity‐dependent regulation of voltage‐gated Na+ channel expression in Mat‐LyLu rat prostate cancer cell line (2006)

We have shown previously that voltage-gated Na(+) channels (VGSCs) are up-regulated in human metastatic disease (prostate, breast and small-cell lung cancers), and that VGSC activity potentiates metastatic cell behaviours. However, the mechanism(s) regulating functional VGSC expression in cancer cells remains unknown. We investigated the possibility of activity-dependent (auto)regulation of VGSC functional expression in the strongly metastatic Mat-LyLu model of rat prostate cancer. Pretreatment with tetrodotoxin (TTX) for 24-72 h subsequently suppressed peak VGSC current density without affecting voltage dependence. The hypothesis was tested that the VGSC auto-regulation occurred via VGSC-mediated Na(+) influx and subsequent activation of protein kinase A (PKA). Indeed, TTX pretreatment reduced the level of phosphorylated PKA, and the PKA inhibitor KT5720 decreased, whilst the adenylate cyclase activator forskolin and the Na(+) ionophore monensin both increased the peak VGSC current density. TTX reduced the mRNA level of Nav1.7, predominant in these cells, and VGSC protein expression at the plasma membrane, although the total VGSC protein level remained unchanged. TTX pretreatment eliminated the VGSC-dependent component of the cells' migration in Transwell assays. We concluded that the VGSC activity in Mat-LyLu rat prostate cancer cells was up-regulated in steady-state via a positive feedback mechanism involving PKA, and this enhanced the cells' migratory potential.
Low-Dimensional Non-Rigid Image Registration Using Statistical Deformation Models From Semi-Supervised Training Data (2015)

Accurate and robust image registration is a fundamental task in medical image analysis applications, and requires non-rigid transformations with a large number of degrees of freedom. Statistical deformation models (SDMs) attempt to learn the distribution of non-rigid deformations, and can be used both to reduce the transformation dimensionality and to constrain the registration process. However, high-dimensional SDMs are difficult to train given orders of magnitude fewer training samples. In this paper, we utilize both a small set of annotated imaging data and a large set of unlabeled data to effectively learn an SDM of non-rigid transformations in a semi-supervised training (SST) framework. We demonstrate results applying this framework towards inter-subject registration of skull-stripped, magnetic resonance (MR) brain images. Our approach makes use of 39 labeled MR datasets to create a set of supervised registrations, which we augment with a set of over 1200 unsupervised registrations using unlabeled MRIs. Through leave-one-out cross validation, we show that SST of a non-rigid SDM results in a robust registration algorithm with significantly improved accuracy compared to standard, intensity-based registration, and does so with a 99% reduction in transformation dimensionality.
Rapid Diagnosis of Germline p53 Mutation Using the Enzyme Mismatch Cleavage Method (1996)

The p53 tumor suppressor gene is the most commonly altered gene in human cancers. Germline mutations in p53 are the genetic alteration underlying predisposition to multiple cancers in Li-Fraumeni syndrome and Li-Fraumeni-like syndrome. We describe a patient who presented with developed adrenocortical carcinoma at age 19 months and a cerebral primitive neuroectodermal tumor at age 5 years. The patient did not have a family history of cancer. We used the enzyme mismatch cleavage (EMC) method to screen for mutations in the p53 gene and found a germline mutation in exon 7 (codon 248). Loss of heterozygosity analysis in one tumor revealed loss of the wild-type p53 allele. In our report we demonstrate the EMC method to be a rapid and sensitive method for mutation detection.
MooM -- A Prototype Framework for Management of Ontology Mappings (2011)

The heterogeneity of ontologies is a major obstacle to the promised interoperability of knowledge in the Semantic Web. Ontology mappings can help to mitigate the effects by specifying the correspondences between related ontologies. However, the creation of mappings is still complex and time-consuming and therefore it is appealing to discover existing mappings and to reuse them. For reuse, it is essential to understand how a mapping was created and applied. Thus meta-data documenting the lifecycle of an ontology mapping is essential to facilitate management and reuse. Currently the mapping lifecycle is only fragmentary documented and in general the reuse of ontology mappings is insufficiently supported by applications and formats. This paper addresses the question to what extent a semantically expressive ontology-based meta-data model can aid in the discovery, management and reuse of ontology mappings. In particular, experimental results collected from a use-case study on mapping discovery are presented. Based on findings derived, it is shown that semantic rich and effective meta-data describing the ontology mapping lifecycle are crucial for management of ontology mappings. Finally, to address the identified challenges, a framework for management of ontology mappings is outlined.
Activity of PXD101, a histone deacetylase inhibitor, in preclinical ovarian cancer studies (2006)

Histone deacetylase inhibitors represent a promising new class of anticancer agents. In the current investigation, we examined the activity of PXD101, a potent histone deacetylase inhibitor, used alone or in combination with clinically relevant chemotherapeutics (docetaxel, paclitaxel, and carboplatin), in preclinical in vitro and in vivo models of ovarian cancer. In vitro activity was examined in ovarian cancer and multidrug-resistant cell lines grown in monolayer culture, and in primary clinical ovarian cancer specimens grown in three-dimensional organoid culture. PXD101 was found to inhibit in vitro cancer cell growth at sub- to low micromolar IC(50) potency, exhibited synergistic activity when used in combination with relevant chemotherapeutics, and effectively inhibited the growth of multidrug-resistant cells. In vivo, PXD101 displayed single-agent antitumor activity on human A2780 ovarian cancer s.c. xenografts which was enhanced via combination therapy with carboplatin. In support of these findings, PXD101 was shown to increase the acetylation of alpha-tubulin induced by docetaxel and the phosphorylation of H2AX induced by carboplatin. Taken together, these results support the clinical evaluation of PXD101 used alone or in combination therapy for the treatment of ovarian cancer.
The detachment strength and morphology of bone cells contacting materials modified with a peptide sequence found within bone sialoprotein (1997)

Adhesion, spreading, and focal contact formation of primary bone-derived cells on quartz surfaces grafted with a 15 amino acid peptide that contained a -RGD-(-Arg-Gly-Asp-) sequence unique to bone sialoprotein was investigated. The peptide surfaces were fabricated by using a heterbifunctional crosslinker, sulfosuccinimidyal 4-(N-maleimidomethyl)cyclohexane-1-carboxylate, to link the peptide to amine functionalized quartz surfaces. Contact angle measurements, spectroscopic ellipsometry, and X-ray photoelectron spectroscopy were used to confirm the chemistry and thickness of the overlayers. A radial flow apparatus was used to characterize cell detachment from peptide-grafted surfaces. After 20 min of cell incubation, the strength of cell adhesion was significantly (p < 0.05) higher on the -RGD- compared to -RGE- (control) surfaces. Furthermore, the mean area of cells contacting the -RGD- was significantly (p < 0.05) higher than -RGE- surfaces. Vinculin staining showed formation of small focal contact patches on the periphery of bone cells incubated for 2 h on the -RGD- surfaces; however, few or no focal contacts were formed by cells seeded on the -RGE-grafted surfaces. The methods of peptide immobilization utilized in this study can be applied to implants, biosensors, and diagnostic devices that require specificity in cell adhesion.
Intraabdominal Pressure Rise During Weight Lifting as an Objective Measure of Low-Back Pain (1980)

Twenty-three male patients who had chronic nonspecific low-back pain were asked to record the amount of pain they felt on an arbitrary scale while lifting light weights in different directions. During the lifts their intraabdominal pressures were recorded with an intragastric transducer. The patients who experienced extra pain during the lift had higher rises of pressure than both normal controls and those patients who did not experience extra pain. The available evidence suggests that this pressure rise may be a response to low-back pain and may be used as a method of objectively measuring that pain.
Mammalian Sirt1: insights on its biological functions (2011)

Sirt1 (member of the sirtuin family) is a nicotinamide adenosine dinucleotide (NAD)-dependent deacetylase that removes acetyl groups from various proteins. Sirt1 performs a wide variety of functions in biological systems. The current review focuses on the biological functions of Sirt1 in obesity-associated metabolic diseases, cancer, adipose tissue, aging, cellular senescence, cardiac aging and stress, prion-mediated neurodegeneration, inflammatory signaling in response to environmental stress, development and placental cell survival.
Conserved nucleotide sequences in the open reading frame and 3' untranslated region of selenoprotein P mRNA. (1993)

Rat liver selenoprotein P contains 10 selenocysteine residues in its primary structure (deduced). It is the only selenoprotein characterized to date that has more than one selenocysteine residue. Selenoprotein P cDNA has been cloned from human liver and heart cDNA libraries and sequenced. The open reading frames are identical and contain a signal peptide, indicating that the protein is secreted by both organs and is therefore not exclusively produced in the liver. Ten selenocysteine residues (deduced) are present. Comparison of the open reading frame of the human cDNA with the rat cDNA reveals a 69% identity of the nucleotide sequence and 72% identity of the deduced amino acid sequence. Two regions in the 3' untranslated portion have high conservation between human and rat. Each of these regions contains a predicted stable stem-loop structure similar to the single stem-loop structures reported in 3' untranslated regions of type I iodothyronine 5'-deiodinase and glutathione peroxidase. The stem-loop structure of type I iodothyronine 5'-deiodinase has been shown to be necessary for incorporation of the selenocysteine residue at the UGA codon. Because only two stem-loop structures are present in the 3' untranslated region of selenoprotein P mRNA, it can be concluded that a separate stem-loop structure is not required for each selenocysteine residue.
Estado metodológico de las tesis doctorales en torno a ELE defendidas en 2017 (2019)

"Este trabajo realiza una investigación del tipo Meta Análisis (MA) y analiza, pormenorizadamente, las distintas categorías partiendo de una taxonomía establecida previamente para ofrecer una radiografía del estado metodológico de las tesis doctorales relacionadas con la enseñanza de Español como Lengua Extranjera (ELE) defendidas en universidades españolas a lo largo de 2017. Para ello, abordamos el estado de la cuestión mediante estudios precedentes que nos permiten contextualizar y situar la trayectoria investigadora de ELE. Posteriormente, establecemos las definiciones de lo que se entiende en cada categoría, y se conduce el MA mediante los datos primarios que aportan las 65 Tesis doctorales disponibles en cuatro bases de datos: Dialnet, TESEO, TDX y Portal del Hispanismo. Tras el análisis de dichos datos, presentamos las conclusiones donde, por un lado, se observa la trayectoria investigadora en ELE en 2017 y, por otro lado, se perfilan las posibles líneas de investigación futuras."
Verisimilitude (or “truthlikeness”) as an alternative to pro and cons: migraine and cluster headache mechanisms (2010)

Calculating verisimilitude (or "truthlikeness") ad modum Popper is a quantitative alternative to the usual pros and cons in migraine and cluster headache mechanisms. The following items were evaluated: dilation of large cranial arteries during migraine; CGRP increase during migraine; migraine as a brain disorder; aura and migraine headache; brain stem activation during migraine; rCBF in migraine without aura; NO and pathophysiology of migraine; neurogenic inflammation and migraine; aura in cluster headache; and hypothalamic activation in cluster headache. It is concluded that verisimilitude calculations can be helpful when judging pathophysiological problems in migraine and cluster headache.