gebhart/patrepeval huggingface dataset:
A Potential Role for Erythropoietin in Focal Permanent Cerebral Ischemia in Mice (1999)

The present study describes, for the first time, a temporal and spatial cellular expression of erythropoietin (Epo) and Epo receptor (Epo-R) with the evolution of a cerebral infarct after focal permanent ischemia in mice. In addition to a basal expression of Epo in neurons and astrocytes, a postischemic Epo expression has been localized specifically to endothelial cells (1 day), microglia/macrophage-like cells (3 days), and reactive astrocytes (7 days after occlusion). Under these conditions, the Epo-R expression always precedes that of Epo for each cell type. These results support the hypothesis that there is a continuous formation of Epo, with its corresponding receptor, during the active evolution of a focal cerebral infarct and that the Epo/Epo-R system might be implicated in the processes of neuroprotection and restructuring (such as angiogenesis and gliosis) after ischemia. To support this hypothesis, a significant reduction in infarct volume (47%; P < 0.0002) was found in mice treated with recombinant Epo 24 hours before induction of cerebral ischemia. Based on the above, we propose that the Epo/Epo-R system is an endogenous mechanism that protects the brain against damages consequent to a reduction in blood flow, a mechanism that can be amplified by the intracerebroventricular application of exogenous recombinant Epo.
Phase I evaluation of humanized OKT3: toxicity and immunomodulatory effects of hOKT3gamma4. (1999)

Murine anti-CD3 (OKT3, Muromonab-CD3) is a potent human T-lymphocyte mitogen. A previous clinical Phase I trial examined OKT3 as an immunomodulator for the treatment of cancer. However, the murine monoclonal antibody triggered a potent humoral response that neutralized the antibody activity during subsequent administration. Thus, a "humanized" form of OKT3 (hOKT3gamma4) was developed to minimize immunogenicity. The genetically engineered human anti-CD3 retained its binding activity and effectively activated T cells in vitro. Therefore, we evaluated the safety and activity of hOKT3gamma4 in a Phase I clinical trial. hOKT3gamma4 was administered as a 10-min i.v. infusion every 2 weeks for three injections (one course of therapy). Six dose levels ranging from 50 to 1600 microg/injection were evaluated. Headache and fever were common, transient toxicities but were not dose limiting. The dose-limiting toxicities were rigors and dyspnea at the 1600-microg dose level, which defined 800 microg as the maximally tolerated dose in this trial. A dose-dependent in vivo T-lymphocyte activation was produced by this treatment, and the most significant T-lymphocyte activation occurred in patients treated at the two highest dose levels (800 and 1600 microg). Persistent CD3 modulation occurred after administration of 1600 microg of hOKT3gamma4. Anti-idiotypic antibodies were detected in only 6 of 24 patients after multiple injections and were not associated with attenuation of T-lymphocyte activation. Malignant ascites resolved in three patients, one each with peritoneal mesothelioma, pancreatic adenocarcinoma, and ovarian adenocarcinoma. hOKT3gamma4 can induce T-lymphocyte activation in patients with cancer, and the immunogenicity of the "humanized" antibody is sufficiently reduced relative to its murine "parent" to permit immunostimulation by repetitive i.v. administration. The therapeutic potential of biweekly i.v. hOKT3gamma4 at a dose of 800 microg should be further evaluated.
A spatial dissection of the Arabidopsis floral transcriptome by MPSS (2008)

This extensive MPSS analysis confirms and supplements prior microarray floral expression studies and illustrates the utility of sequence survey-based expression analysis in functional genomics. Spatial floral expression data accrued by MPSS and similar methods will be advantageous in the elucidation of more comprehensive genetic regulatory networks governing floral development.
Crescendo in Depolarization and Repolarization Heterogeneity Heralds Development of Ventricular Tachycardia in Hospitalized Patients With Decompensated Heart Failure (2011)

This investigation is the first clinical demonstration of the potential utility of tracking depolarization and repolarization heterogeneity to detect crescendos in electrical instability that could forewarn of impending nonsustained VT. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00270400.
Modern Coating and Drying Technology (1992)

Part 1 Choosing the coating method: coating components and structures coating technologies coating methods selecting a coating method - basic considerations choosing the coating method information sources. Part 2: purpose of fluid handling and preparation fluid displacement flow measurement gas removal filtration online injection and homogenization temperature control system perturbations residence time systems cleaning. Part 3 Roll coating: classification of roll coating flows analysis of roll coating flows forward roll coating ribbing instability reverse roll coating deformable rolls gravure coating. Part 4 Premetered coatings: review of premetered coaters surface tension and wettability shear and elongation rates contact angles and spreading low flow limits of coatability instabilities in slide coating. Part 5 Air knife coating: overview typical operating range mechanism a coating thickness correlation defects and flow stability. Part 6 Drive systems for off-machine coaters: writing specifications selecting a winding machine for a coating operation the master or lead section and factors that reduce its effectiveness on a coating machine influence of unwind and winder on web control a speed monitoring system tension in a coating machine effects of wiring practices on tension control when to use pure speed control types of tension control sytems isolation sections that can control tension integral versus proportional control the need for motoring and regeneration sizing power supplied for off-machine coater drives web web guides and web spreaders defects - sources and solutions application considerations for off-machine coater sections summary. Part 7 Thin film drying: basic principles drying regimes hardware dryer control drying defects.
Mutant Lrp1 Knock-In Mice Generated by Recombinase-Mediated Cassette Exchange Reveal Differential Importance of the NPXY Motifs in the Intracellular Domain of LRP1 for Normal Fetal Development (2005)

Lrp1 knock-in mice carrying either a wild-type allele or three different mutated alleles encoding the multifunctional endocytic receptor LRP1 were generated by recombinase-mediated cassette exchange (RMCE). Reinsertion by RMCE of a wild-type allele led to a normal pattern and level of gene expression and a completely normal phenotype, indicating that the RMCE procedure itself is neutral with respect to the function of the gene locus. In contrast, reinsertion of mutated LRP1 alleles carrying either inactivating mutations in the proximal NPXY motif (NPTY-->AATA) of the cytoplasmic domain or in the furin cleavage site (RHRR-->AHAA) caused distinctive liver phenotypes: respectively, either a late fetal destruction of the organ causing perinatal death or a selective enlargement of von-Kupffer cell lysosomes reminiscent of a mild lysosomal storage without an apparent negative effect on animal survival. Notably, mutation of the distal NPXY motif overlapping with an YXXL motif (NPVYATL-->AAVAATL) did not cause any obvious pathological effect. The mutations showed no effect on the LRP1 expression level; however, as expected, the proteolytic maturation of LRP1 into its two subunits was significantly impaired, although not completely abolished, in the furin cleavage mutant. These data demonstrate that RMCE is a reliable and efficient approach to generate multiple mutant knock-in alleles for in vivo functional analysis of individual domains or motifs of large multidomain proteins. Its application in Lrp1 reveals dramatically variant phenotypes, of which further characterization will definitively contribute to our understanding of the biology of this multifunctional receptor.
14C‐labeling of a tetrahydroacridine, a novel CNS‐selective cholinesterase inhibitor (1992)

Abstract 9‐Amino‐8‐fluoro‐2, 4‐methano‐1,2,3,4‐tetrahydroacridine citrate (SM‐10888), a novel cholinesterase inhibitor, was labeled with carbon‐14 at C9 of the tetrahydroacridine ring for use in metabolic studies. Carbonation of 2,6‐difluorophenyllithium ( 3 ) with [ 14 C]carbon dioxide gave the acid ( 4 ). Chlorination of 4 followed by treatment of the resulting acid chloride with ammonia afforded the amide ( 5 ). Dehydration of 5 with thionyl chloride and subsequent displacement reaction with ammonia gave the aminobenzonitrile ( 7 ). Condensation of 7 with the ketone ( 8 ) in the presence of anhydrous zinc chloride yielded the aminoacridine ( 9 ), which was treated with citric acid to afford [9‐ 14 C]SM‐10888 ( 1 ). The overall yield of 1 was 37% from 2 , and the specific activity was 1.35 GBq/mmol.
Brain anatomy and sensorimotor gating in Asperger's syndrome (2002)

Asperger's syndrome (an autistic disorder) is characterized by stereotyped and obsessional behaviours, and pervasive abnormalities in socio-emotional and communicative behaviour. These symptoms lead to social exclusion and a significant healthcare burden; however, their neurobiological basis is poorly understood. There are few studies on brain anatomy of Asperger's syndrome, and no focal anatomical abnormality has been reliably reported from brain imaging studies of autism, although there is increasing evidence for differences in limbic circuits. These brain regions are important in sensorimotor gating, and impaired 'gating' may partly explain the failure of people with autistic disorders to inhibit repetitive thoughts and actions. Thus, we compared brain anatomy and sensorimotor gating in healthy people with Asperger's syndrome and controls. We included 21 adults with Asperger's syndrome and 24 controls. All had normal IQ and were aged 18-49 years. We studied brain anatomy using quantitative MRI, and sensorimotor gating using prepulse inhibition of startle in a subset of 12 individuals with Asperger's syndrome and 14 controls. We found significant age-related differences in volume of cerebral hemispheres and caudate nuclei (controls, but not people with Asperger's syndrome, had age-related reductions in volume). Also, people with Asperger's syndrome had significantly less grey matter in fronto-striatal and cerebellar regions than controls, and widespread differences in white matter. Moreover, sensorimotor gating was significantly impaired in Asperger's syndrome. People with Asperger's syndrome most likely have generalized alterations in brain development, but this is associated with significant differences from controls in the anatomy and function of specific brain regions implicated in behaviours characterizing the disorder. We hypothesize that Asperger's syndrome is associated with abnormalities in fronto-striatal pathways resulting in defective sensorimotor gating, and consequently characteristic difficulties inhibiting repetitive thoughts, speech and actions.
EXAMINATION OF DISLOCATIONS IN LATTICE-MISMATCHED GaInAs/BUFFER LAYER/GaAs FOR III-V PHOTOVOLTAICS (2007)

Dislocations act as sites for nonradiative electron/hole pair recombination, which reduces the effi ciency of photovoltaics. Lattice-matched materials can be grown on top of one another without forming a high density of dislocations. However, when the growth of lattice-mismatched (LMM) materials is attempted, many dislocations result from the relaxation of strain in the crystal structure. In an attempt to reduce the number of dislocations that propagate into a solar device when using LMM materials, a compositionally step-graded buffer is placed between the two LMM materials. In order to confi ne the dislocations to the buffer layer and therefore increase material quality and device effi ciency, the growth temperature and thickness of the buffer layer were varied. A GaInP compositionally graded buffer and GaInAs p-n junction were grown on a GaAs substrate in a metal-organic chemical vapor deposition (MOCVD) system. A multibeam optical stress sensor (MOSS) and X-ray diffraction (XRD) were used to characterize the strain in the epilayers. Electrical and optoelectronic properties were measured using a probe station and multimeter setup, solar simulator, and a quantum effi ciency instrument. It was determined that device functionality was highly dependent on the growth temperature of the graded buffer. As growth temperature increased, so did the dislocation density in the device despite an increase in the dislocation velocity, which should have increased the dislocation annihilation rate and the diffusion of dislocations to the edge of the crystal. The thickness of the graded buffer also affected device effi ciency with thinner samples performing poorly. The thinner graded buffer layers had high internal resistances from reduced carrier concentrations. In terms of effi ciency, the empirically derived recipe developed by the scientists at the National Renewable Energy Laboratory (NREL) produced the highest quality cells.
CD4 and CD8 molecules can physically associate with the same T-cell receptor. (1989)

The expression of the cell-surface glycoproteins CD4 and CD8 on functionally mature T cells is usually mutually exclusive and correlates with class II and class I major histocompatibility complex (MHC) restriction, respectively. CD4 and CD8 function by binding to class II and class I MHC molecules on the antigen-presenting cell (APC), thereby increasing the adhesion between the T cell and the APC. From antibody-blocking studies and from cocapping and comodulation experiments, CD4 and CD8 come into close physical contact with their appropriately restricted T-cell receptor (TCR) at the time of antigen recognition. By the use of affinity chromatography followed by two-dimensional diagonal gel electrophoresis, we have identified a Mr 43,000 disulfide-bonded heterodimer copurifying with CD4. This protein was identified as the TCR by its removal after preclearing with the anti-TCR antibody F23.1 and by its generation after protease digestion of the same peptides as the TCR from this clone. When CD4 and CD8 were similarly isolated from an unusual CD4+ CD8+ class II-restricted T-cell clone, the TCR was identified as associating with either accessory molecule in the absence of activation. Therefore, CD4 and CD8 do not distinguish between class I- and class II-restricted TCRs in their ability to form membrane complexes, indicating a need for both the TCR and its associated accessory molecule to recognize the same individual MHC molecule on the APC to optimize TCR triggering.
Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications (2003)

There is substantial evidence that oxidative stress participates in the pathophysiology of cardiovascular disease. Biochemical, molecular and pharmacological studies further implicate xanthine oxidoreductase (XOR) as a source of reactive oxygen species in the cardiovascular system. XOR is a member of the molybdoenzyme family and is best known for its catalytic role in purine degradation, metabolizing hypoxanthine and xanthine to uric acid with concomitant generation of superoxide. Gene expression of XOR is regulated by oxygen tension, cytokines and glucocorticoids. XOR requires molybdopterin, iron-sulphur centres, and FAD as cofactors and has two interconvertible forms, xanthine oxidase and xanthine dehydrogenase, which transfer electrons from xanthine to oxygen and NAD(+), respectively, yielding superoxide, hydrogen peroxide and NADH. Additionally, XOR can generate superoxide via NADH oxidase activity and can produce nitric oxide via nitrate and nitrite reductase activities. While a role for XOR beyond purine metabolism was first suggested in ischaemia-reperfusion injury, there is growing awareness that it also participates in endothelial dysfunction, hypertension and heart failure. Importantly, the XOR inhibitors allopurinol and oxypurinol attenuate dysfunction caused by XOR in these disease states. Attention to the broader range of XOR bioactivity in the cardiovascular system has prompted initiation of several randomised clinical outcome trials, particularly for congestive heart failure. Here we review XOR gene structure and regulation, protein structure, enzymology, tissue distribution and pathophysiological role in cardiovascular disease with an emphasis on heart failure.
Hyperphosphorylation induces self-assembly of τ into tangles of paired helical filaments/straight filaments (2001)

The microtubule-associated protein tau is a family of six isoforms that becomes abnormally hyperphosphorylated and accumulates in the form of paired helical filaments (PHF) in the brains of patients with Alzheimer's disease (AD) and patients with several other tauopathies. Here, we show that the abnormally hyperphosphorylated tau from AD brain cytosol (AD P-tau) self-aggregates into PHF-like structures on incubation at pH 6.9 under reducing conditions at 35 degrees C during 90 min. In vitro dephosphorylation, but not deglycosylation, of AD P-tau inhibits its self-association into PHF. Furthermore, hyperphosphorylation induces self-assembly of each of the six tau isoforms into tangles of PHF and straight filaments, and the microtubule binding domains/repeats region in the absence of the rest of the molecule can also self-assemble into PHF. Thus, it appears that tau self-assembles by association of the microtubule binding domains/repeats and that the abnormal hyperphosphorylation promotes the self-assembly of tau into tangles of PHF and straight filaments by neutralizing the inhibitory basic charges of the flanking regions.
Some α-Arylsulfonamido Acids and Amides (1952)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSome α-Arylsulfonamido Acids and AmidesRichard H. Wiley, Newton R. Smith, and Joseph P. JohansenCite this: J. Am. Chem. Soc. 1952, 74, 24, 6298–6299Publication Date (Print):December 1, 1952Publication History Published online1 May 2002Published inissue 1 December 1952https://doi.org/10.1021/ja01144a524RIGHTS & PERMISSIONSArticle Views43Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (309 KB) Get e-Alerts Get e-Alerts
Large single-mode rib waveguides in GeSi-Si and Si-on-SiO/sub 2/ (1991)

Mode-matching and beam-propagation methods are used to analyze single-mode operation of optical GeSi-Si and Si-SiO/sub 2/ semiconductor rib waveguides. The waveguide dimensions that allow only the fundamental HE/sub 00/ or EH/sub 00/ mode to propagate have been determined. For both material systems, it is found that the rib can be several microns wide and several microns high, thus allowing efficient coupling to single-mode fibers. Numerical examples are given for monomode guiding group-IV materials, but the results apply to III-V rib waveguides. It is shown that single-mode rib guides with large cross sections are feasible as long as the waveguide is at least several millimeters long.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Serum disposition of exogenous progesterone after intramuscular administration in bitches (1990)

Progesterone was administered IM to 6 adult anestrous bitches at a dosage of 2 mg/kg of body weight. Serum progesterone concentrations were measured prior to progesterone administration and for 72 hours thereafter. The serum progesterone concentration time data were analyzed by use of a pharmacokinetics modeling computer program. The mean (+/- SD) peak serum progesterone concentration (34.3 +/- 7.8 ng/ml) was reached at 1.8 +/- 0.2 hours after progesterone administration. The mean serum progesterone concentration was 6.9 +/- 1.4 ng/ml at 24 hours and 2.0 +/- 0.4 ng/ml at 48 hours after progesterone administration. By 72 hours after administration, mean serum progesterone concentration was 0.9 +/- 0.2 ng/ml, which was comparable to serum progesterone concentrations prior to injection. The mean half-life of the absorption phase was 0.5 hours (range, 0.3 to 0.7 hours). The mean half-life of elimination was 12.1 hours (range, 9.5 to 13.8 hours). By analysis of the data, it was established that a dosage of 3 mg/kg, when the hormone was given IM to dogs once a day, would maintain serum progesterone concentration greater than 10 ng/ml.
Human SHMT inhibitors reveal defective glycine import as a targetable metabolic vulnerability of diffuse large B-cell lymphoma (2017)

The enzyme serine hydroxymethyltransferse (SHMT) converts serine into glycine and a tetrahydrofolate-bound one-carbon unit. Folate one-carbon units support purine and thymidine synthesis, and thus cell growth. Mammals have both cytosolic SHMT1 and mitochondrial SHMT2, with the mitochondrial isozyme strongly up-regulated in cancer. Here we show genetically that dual SHMT1/2 knockout blocks HCT-116 colon cancer tumor xenograft formation. Building from a pyrazolopyran scaffold that inhibits plant SHMT, we identify small-molecule dual inhibitors of human SHMT1/2 (biochemical IC<sub>50</sub> ∼ 10 nM). Metabolomics and isotope tracer studies demonstrate effective cellular target engagement. A cancer cell-line screen revealed that B-cell lines are particularly sensitive to SHMT inhibition. The one-carbon donor formate generally rescues cells from SHMT inhibition, but paradoxically increases the inhibitor's cytotoxicity in diffuse large B-cell lymphoma (DLBCL). We show that this effect is rooted in defective glycine uptake in DLBCL cell lines, rendering them uniquely dependent upon SHMT enzymatic activity to meet glycine demand. Thus, defective glycine import is a targetable metabolic deficiency of DLBCL.
Swing-leg retraction: a simple control model for stable running (2003)

In running, the spring-like axial behavior of stance limbs is a well-known and remarkably general feature. Here we consider how the rotational behavior of limbs affects running stability. It is commonly observed that running animals retract their limbs just prior to ground contact, moving each foot rearward towards the ground. In this study, we employ a conservative spring-mass model to test the effects of swing-leg retraction on running stability. A feed-forward control scheme is applied where the swing-leg is retracted at constant angular velocity throughout the second half of the swing phase. The control scheme allows the spring-mass system to automatically adapt the angle of attack in response to disturbances in forward speed and stance-limb stiffness. Using a return map to investigate system stability, we propose an optimal swing-leg retraction model for the stabilization of flight phase apex height. The results of this study indicate that swing-leg retraction significantly improves the stability of spring-mass running, suggesting that swing-phase limb dynamics may play an important role in the stabilization of running animals.