gebhart/patrepeval huggingface dataset:
Neuronal cell damage in the brain: possible involvement of oxidative mechanisms. (1980)

Neuronal lesions in the brain occur in conditions associated with a reduced supply of oxygen (hypoxia and ischemia) and glucose (hypoglycemia) as well as in those associated with a pathologically enhanced neuronal activity (status epilepticus). In only two of these conditions (hypoxia and ischemia) are the lesions correlated to cellular oxygen lack, and gross energy failure is absent in one condition (status epilepticus). Although anaerobic mechanisms seem responsible for the cell injury in hypoxia and ischemia, oxidative mechanisms could operate in hypoglycemia and status epilepticus. Since the supply of oxygen has not ceased altogether in hypoxia and incomplete ischemia, and since reoxygenation/recirculation leads to a transient increase in tissue oxygen tensions, one cannot exclude the possibility that oxidative mechanisms contribute to the final damage following all types of cellular oxygen lack. We have failed to obtain evidence that peroxidative degradation of cellular constituents occurs in hypoglycemia and status epilepticus. Thus, there is neither a perturbation of the redox state of the glutathione pool of the tissue nor a measurable degradation of polyenoic phospholipid-bound fatty acids. It is emphasized that the cascade of events triggered by an accumulation of free polyenoic fatty acids, mainly arachidonic acid, may contribute to cell lesions by leading to cell edema and/or microcirculatory changes. During seizures, such an accumulation occurs even though energy failure is moderate and it may conceivably contribute to cell damage. In general, though, mechanisms of cell damage in the brain remain partly elusive.
VTX-2337 Is a Novel TLR8 Agonist That Activates NK Cells and Augments ADCC (2011)

VTX-2337 is a novel small-molecule TLR8 agonist that activates monocytes, DCs, and NK cells. Through the activation of NK cells, it has the potential to augment the effectiveness of monoclonal antibody treatments where a polymorphism in FcγR3A limits clinical efficacy.
Sequence of a cysteine-rich galactose-specific lectin of Entamoeba histolytica. (1991)

Entamoeba histolytica trophozoites adhere to human colonic mucins and epithelial cells by a cell surface galactose-specific lectin. This lectin, which is composed of two subunits linked by disulfide bonds, has been shown to be a protective antigen in an animal model of amebiasis. We have determined the sequence of the mature form of the 170-kDa heavy subunit from cDNA clones and PCR-amplified fragments. The heavy subunit sequence consisted of a putative extracellular domain containing 1209 amino acids with 16 potential sites for N-linked glycosylation, a 26-amino acid hydrophobic region, and a 41-amino acid cytoplasmic tail. The presence of N-linked oligosaccharides was confirmed by culturing amebae with tunicamycin, which resulted in a decrease in the heavy subunit molecular mass to 160 kDa and a loss of lectin activity. The extracellular domain was remarkable for an extensive cysteine-rich domain that shared identify with similar regions of several other cell surface proteins and appeared to confer protease resistance to the subunit.
The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of the primary demyelinating lesion (1997)

Tissues from 13 exceptionally early cases of multiple sclerosis were studied to identify and characterize the primary demyelinating lesion, using a variety of histological and immunocytochemical methods. Multifactorial cluster analysis identified five significantly distinct lesion groups, which showed histological progression from simple microglial lesions, predominating in tissues from the earliest cases, to complex hypercellular fully demyelinated plaques, chiefly associated with cases of intermediate duration. Quiescent lesions showing evidence of remyelination were found at all stages of the disease studied, but hypocellular inactive plaques, were associated with older cases. Evidence is presented that initial demyelination is effected by activated resident microglia. Undegraded myelin is initially enveloped by membranes bearing fixed complexes of immunoglobulin and complement. In contrast with perivenous encephalomyelitis, in which demyelination was dominated by T-cell infiltration, multiple sclerosis lesions of comparable duration and maturity exhibited humoral immune reactions. Parenchymal CD4+ T-cell infiltration developed in association with subsequent plaque maturation. These results emphasize the need for lesion staging when multiple sclerosis tissues are being used in the investigation of pathogenic mechanisms, and suggest that further analysis of the oligoclonal B-cell response may be productive in the search for primary provoking antigens.
Distribution of dipeptide repeat proteins in cellular models and C9orf72 mutation cases suggests link to transcriptional silencing (2015)

A massive expansion of a GGGGCC repeat upstream of the C9orf72 coding region is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. Despite its intronic localization and lack of a canonical start codon, both strands are translated into aggregating dipeptide repeat (DPR) proteins: poly-GA, poly-GP, poly-GR, poly-PR and poly-PA. To address conflicting findings on the predominant toxicity of the different DPR species in model systems, we compared the expression pattern of the DPR proteins in rat primary neurons and postmortem brain and spinal cord of C9orf72 mutation patients. Only poly-GA overexpression closely mimicked the p62-positive neuronal cytoplasmic inclusions commonly observed for all DPR proteins in patients. In contrast, overexpressed poly-GR and poly-PR formed nucleolar p62-negative inclusions. In patients, most of the less common neuronal intranuclear DPR inclusions were para-nucleolar and p62 positive. Neuronal nucleoli in C9orf72 cases showed normal size and morphology regardless of the presence of poly-GR and poly-PR inclusions arguing against widespread nucleolar stress, reported in cellular models. Colocalization of para-nucleolar DPR inclusions with heterochromatin and a marker of transcriptional repression (H3K9me2) indicates a link to gene transcription. In contrast, we detected numerous intranuclear DPR inclusions not associated with nucleolar structures in ependymal and subependymal cells. In patients, neuronal inclusions of poly-GR, poly-GP and the poly-GA interacting protein Unc119 were less abundant than poly-GA inclusions, but showed similar regional and subcellular distribution. Regardless of neurodegeneration, all inclusions were most abundant in neocortex, hippocampus and thalamus, with few inclusions in brain stem and spinal cord. In the granular cell layer of the cerebellum, poly-GA and Unc119 inclusions were significantly more abundant in cases with FTLD than in cases with MND and FTLD/MND. Poly-PR inclusions were rare throughout the brain but significantly more abundant in the CA3/4 region of FTLD cases than in MND cases. Thus, although DPR distribution is not correlated with neurodegeneration spatially, it correlates with neuropathological subtypes.
Characterization of the genomic structure, chromosomal location, promoter, and development expression of the alpha-globin transcription factor CP2 (1994)

We recently cloned murine and human cDNAs that encode CP2, a cellular transcription factor that interacts with the alpha-globin promoter as well as with additional cellular and viral promoter elements. We have now characterized the genomic structure, chromosome location, promoter, and expression pattern of the factor. Genes for the murine and human mRNAs contained 16 and 15 exons, respectively. Both genes spanned approximately 30 kilobases of chromosomal DNA, and among coding exons, all exon/intron boundaries were conserved. The human gene for CP2 was found to reside on chromosome 12 while the murine gene mapped to the distal end of chromosome 15, near Gdc-1, Wnt-1, and Rarg, a region syntenic with human chromosome 12. The murine and human promoters initiated mRNAs at multiple start sites in a conserved region that spanned more than 450 nucleotides. Lastly, a study of the pattern of CP2 gene expression showed that the factor was expressed in all adult and fetal murine tissues examined from at least day 9.5 of development.
Webgalaxy - integrating spoken language and hypertext navigation (1997)

The growth in the quantity of information and services offered online has been phenomenal. Nevertheless, access mechanisms have remained relatively primitive, requiring users to primarily point and click their way through a forest of Web links and to expend valuable cognitive capacities to track the geography of the Web space. Conversational systems can provide an intuitive, flexible multi-modal interface to online resources. The explosive growth of the World Wide Web, the continuing standardization of Web related technologies, and the growing penetration of Internet access enable us to embed a very thin client inside a standard Web browser, making conversational interfaces available to a much wider audience. This paper presents WebGALAXY, a conversational spoken language system for access to selected online resources from within a typical browser. A thin Java based client is employed as the front end with much of the speech and natural language processing occuring on remote servers.
Molecular cloning, functional expression and chromosomal localization of an amiloride‐sensitive Na+ channel from human small intestine (2000)

Amiloride-sensitive Na(+) channels belonging to the recently discovered NaC/DEG family of genes have been found in several human tissues including epithelia and central and peripheral neurons. We describe here the molecular cloning of a cDNA encoding a novel human amiloride-sensitive Na(+) channel subunit that is principally expressed in the small intestine and has been called hINaC (human intestine Na(+) channel). This protein is similar to the recently identified rodent channel BLINaC and is relatively close to the acid sensing ion channels (ASICs) (79 and 29% amino acid identity, respectively). ASICs are activated by extracellular protons and probably participate in sensory neurons to nociception linked to tissue acidosis. hINaC is not activated by lowering the external pH but gain-of-function mutations can be introduced and reveal when expressed in Xenopus oocytes, an important Na(+) channel activity which is blocked by amiloride (IC(50)=0.5 microM). These results suggest the existence of a still unknown physiological activator for hINaC (e.g. an extracellular ligand). The presence of this new amiloride-sensitive Na(+) channel in human small intestine probably has interesting physiological as well as physiopathological implications that remain to be clarified. The large activation of this channel by point mutations may be associated with a degenerin-like behavior as previously observed for channels expressed in nematode mechanosensitive neurons. The hINaC gene has been mapped on the 4q31.3-q32 region of the human genome.
Treatment of diffuse large B-cell lymphoma. (2005)

A review of new or emerging ideas concerning diffuse large B-cell lymphomas (DLBCL) is presented with particular emphasis on histologic classification, genetic prognostic factors, and first-line treatments. This lymphoma rests the most heterogeneous of all lymphomas for its clinical characteristics and outcome. This heterogeneity is probably secondary to the fact that a large proportion seems to occur from a transformation of an unknown indolent lymphoma. Current treatment is based on the combination of chemotherapy including cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) or dose-intense CHOP-like regimen, and rituximab (R-CHOP).
HPLC micromethod for amrinone and metabolites in patients receiving concurrent cephalosporin therapy (1996)

Amrinone (AMR), a bipyridine derivative, is receiving increasing use in postoperative cardiac patients as an inotrope and vasodilator. The hemodynamic response to amrinone in adults is linearly related to AMR concentrations, warranting therapeutic drug monitoring. We report a rapid microsample HPLC method for monitoring AMR and its principal metabolites, N-acetyl (N-ac) and N-glycolyl (N-gly) AMR. Serum was precipitated with acetonitrile, and the supernatant fluid was then injected into a C18 narrow-bore column. The mobile phase consisted of a 0.1 mol/L sodium phosphate buffer (pH 6) with a gradient of acetonitrile going from 50 to 100 mL/L of eluent. Detection with a diode-array detector (DAD) concurrently monitored the absorbances at 320 and 345 nm. Monitoring 320 nm allows optimal quantification of AMR, N-gly, and N-ac. Patients often receive concurrent cephalosporin therapy, which is detectable at 320 nm but not 345 nm. Because cephalosporins coelute with AMR or metabolites, monitoring at 345 nm allows separation of these antibiotics from AMR and metabolites while retaining a detection limit of 0.5 mg/L.
Real‐Time Rendering Techniques with Hardware Tessellation (2015)

Abstract Graphics hardware has progressively been optimized to render more triangles with increasingly flexible shading. For highly detailed geometry, interactive applications restricted themselves to performing transforms on fixed geometry, since they could not incur the cost required to generate and transfer smooth or displaced geometry to the GPU at render time. As a result of recent advances in graphics hardware, in particular the GPU tessellation unit, complex geometry can now be generated on the fly within the GPU's rendering pipeline. This has enabled the generation and displacement of smooth parametric surfaces in real‐time applications. However, many well‐established approaches in offline rendering are not directly transferable due to the limited tessellation patterns or the parallel execution model of the tessellation stage. In this survey, we provide an overview of recent work and challenges in this topic by summarizing, discussing, and comparing methods for the rendering of smooth and highly detailed surfaces in real time.
Gaussian networks for direct adaptive control (1992)

A direct adaptive tracking control architecture is proposed and evaluated for a class of continuous-time nonlinear dynamic systems for which an explicit linear parameterization of the uncertainty in the dynamics is either unknown or impossible. The architecture uses a network of Gaussian radial basis functions to adaptively compensate for the plant nonlinearities. Under mild assumptions about the degree of smoothness exhibit by the nonlinear functions, the algorithm is proven to be globally stable, with tracking errors converging to a neighborhood of zero. A constructive procedure is detailed, which directly translates the assumed smoothness properties of the nonlinearities involved into a specification of the network required to represent the plant to a chosen degree of accuracy. A stable weight adjustment mechanism is determined using Lyapunov theory. The network construction and performance of the resulting controller are illustrated through simulations with example systems.
Interorgan ammonia and amino acid metabolism in metabolically stable patients with cirrhosis and a TIPSS (2002)

Ammonia is central to the pathogenesis of hepatic encephalopathy. This study was designed to determine the quantitative dynamics of ammonia metabolism in patients with cirrhosis and previous treatment with a transjugular intrahepatic portosystemic stent shunt (TIPSS). We studied 24 patients with cirrhosis who underwent TIPSS portography. Blood was sampled and blood flows were measured across portal drained viscera, leg, kidney, and liver, and arteriovenous differences across the spleen and the inferior and superior mesenteric veins. The highest amount of ammonia was produced by the portal drained viscera. The kidneys also produced ammonia in amounts that equaled total hepatosplanchnic area production. Skeletal muscle removed more ammonia than the cirrhotic liver. The amount of nitrogen that was taken up by muscle in the form of ammonia was less than the glutamine that was released. The portal drained viscera consumed glutamine and produced ammonia, alanine, and citrulline. Urea was released in the splenic and superior mesenteric vein, contributing to whole-body ureagenesis in these cirrhotic patients. In conclusion, hyperammonemia in metabolically stable, overnight-fasted patients with cirrhosis of the liver and a TIPSS results from portosystemic shunting and renal ammonia production. Skeletal muscle removes more ammonia from the circulation than the cirrhotic liver. Muscle releases excessive amounts of the nontoxic nitrogen carrier glutamine, which can lead to ammonia production in the portal drained viscera (PDV) and kidneys. Urinary ammonia excretion and urea synthesis appear to be the only way to remove ammonia from the body.
Production of endogenous antibiotics in articular cartilage (2004)

This study demonstrated a previously unrecognized function of human chondrocytes. In addition to its biomechanical properties, articular cartilage has the ability to produce antimicrobial substances when challenged with microorganisms. The expression of HBD-2 in microbicidal doses suggests that antimicrobial peptides may contribute to host defense mechanisms in articular joints.
Single L‐type calcium channel conductance with physiological levels of calcium in chick ciliary ganglion neurons. (1996)

1. Single L-type calcium channels in chick ciliary ganglion neurons were studied at high current resolution in cell-attached patch recordings using quartz-glass micropipettes. 2. A single open-channel current amplitude was observed when Ba2+ was the charge carrier with a conductance of 26 pS at 110 mM barium. However, with 110 mM calcium two current fluctuation amplitudes were observed. These were termed low and high fluctuation amplitudes, CaL and CaH, and had conductances of 8.8 and 12 pS, respectively. These two levels probably reflect two different channel species. CaL was identified as an L-type calcium channel on the basis of resistance to inactivation, conductance, and dihydropyridine sensitivity. 3. Single-channel current fluctuations could be detected with calcium concentrations as low as 1.0 mM. Although the unitary conductance (gamma) was much greater with barium than calcium at every concentration tested, the concentration dependence of conductance was similar for gamma Ba, gamma CaH and gamma CaL. Fitting the concentration dependencies of these conductances with a Langmuir isotherm gave KD estimates of 4.7, 5.6 and 5.0 mM for barium, CaL and CaH, respectively 4. The single-channel conductance of the L-type channel (gamma L) can be described by the relation: conductance (in pS) = 9.2/(1 + 5.6/[Ca]) where [Ca] is the external calcium concentration in the 1.0-110 mM range. Thus, at a physiological external calcium concentration of 2 mM the conductance is 2.4 pS. 5. Ca2+ transport through the L-type calcium channel is particularly sensitive to changes in external calcium concentration in the physiological range but approaches saturation at about 10 mM. this characteristic may optimize the responsiveness of the cell to small changes in ambient calcium concentrations while limiting excess entry in the presence of abnormally high calcium levels.
Minimal Residual Disease Monitoring with High-Throughput Sequencing of T Cell Receptors in Cutaneous T Cell Lymphoma (2013)

Mycosis fungoides (MF) and the leukemic presentation Sézary syndrome (SS) are clonal T cell lymphomas arising from the skin and are considered noncurable with standard therapies. To develop a specific and sensitive monitoring tool, we tested the ability of high-throughput sequencing (HTS) of T cell receptors (TCRB) to monitor minimal residual disease (MRD) after allogeneic hematopoietic cell transplantation. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) or skin samples. The rearranged TCRβ loci were amplified using Vβ- and Jβ-specific primers, followed by HTS, to generate up to 1,000,000 reads spanning the CDR3 region of individual cells. Malignant clones were identified in diagnostic samples in all cases by a dominant CDR3 sequence. Before transplant, four patients had circulating Sézary cells by the routine flow cytometry, which was confirmed by TCRB HTS. Although the flow cytometry found no detectable Sézary cells, malignant clones were detected by TCRB HTS in all other six cases. Five patients achieved "molecular remission" in blood between +30 and +540 days after transplant. Four of these patients also achieved molecular clearance in skin after transplant. Experiments using blood samples spiked with purified Sézary cells demonstrated that TCRB HTS can detect Sézary cells at the level of 1 in 50,000 PBMCs, which is more sensitive than standard diagnostics. We have thus demonstrated the utility of TCRB HTS to assess MRD with increased sensitivity and specificity compared to other current methodologies, and to monitor response to therapy in this MF/SS patient population.
The primate subthalamic nucleus. III. Changes in motor behavior and neuronal activity in the internal pallidum induced by subthalamic inactivation in the MPTP model of parkinsonism (1994)

1. The effects of reversible and irreversible pharmacological manipulations of the neuronal activity in the subthalamic nucleus (STN) on parkinsonian motor signs and neuronal activity in the internal segment of the globus pallidus (GPi) were studied in African green monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 2. Muscimol injections (< or = 1 microliter, 1 microgram/microliter) into STN reduced neuronal activity recorded at the injection site within minutes. This was immediately followed by reduced akinesia, tremor, and rigidity, as well as the emergence of dyskinesias in contralateral limbs. The motor effects were accompanied by generalized behavioral activation, lasted between 10 and 60 min, and were strongly dependent on the site of injection, with injections into the lateral "arm area" of STN first affecting contralateral arm movements and injections into the "leg" area affecting leg movements first. 3. Bicuculline injections (< or = 1 microliter, 1 microgram/microliter) into STN marginally increased the neuronal activity and induced neuronal discharge in bursts. Rigidity, akinesia, and tremor in the contralateral limbs were not changed. 4. Injections of ibotenic acid in two animals (2 and 7 microliters, 10 micrograms/microliters) resulted in 70 and 51% destruction of STN, respectively. Similarly to the muscimol injections, this resulted in a reduction of the neuronal activity, a reversal of parkinsonian motor signs, and the development of dyskinesias in the contralateral limbs. 5. Although tremor was significantly reduced after STN lesions, periodic oscillatory neuronal activity in GPi persisted. The strength of modulation of the neuronal oscillation was not significantly changed after STN lesion. 6. The percentage of cells in GPi exhibiting increases in discharge in response to torque application was significantly reduced after STN lesion. The magnitude and duration of the responses with increase in firing rate were reduced after STN lesioning. 7. These results support the hypothesis that abnormally increased tonic and phasic activity in STN leads to abnormal GPi activity and is a major factor in the development of parkinsonian motor signs. Furthermore they imply that cells in the basal ganglia have the intrinsic property of discharging in periodic bursts, which is unmasked under parkinsonian conditions.