gebhart/patrepeval huggingface dataset:
Cytokines (IL-6, TNF-alpha, IL-1alpha) and soluble interleukin-2 receptor as serum tumor markers in multiple myeloma. (1996)

The serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble interleukin-2 receptor (sIL-2r), and interleukin-1alpha (IL-1alpha) were measured in 30 healthy subjects, 22 patients with monoclonal gammopathy of undetermined significance (MGUS), five patients with smoldering multiple myeloma (SMM), and 46 with multiple myeloma (MM). Serum levels of IL-6, TNF-alpha, and sIL-2r were significantly increased in patients with active MM when compared with normal controls. Furthermore, MM patients with advanced aggressive disease had significantly higher levels of IL-6, TNF-alpha, and sIL-2r than those with MM in plateau phase. In conclusion, our data support the involvement of IL-6, TNF-alpha, and sIL-2r in MM. This confirms recent in vitro studies suggesting that these cytokines may play a central role in the pathogenesis of MM. Our data also show that serum levels of TNF-alpha, sIL-2r, and, particularly, IL-6 could be useful in the clinical management of patients with MM.
Three-dimensional optical holography using a plasmonic metasurface (2013)

Abstract Benefitting from the flexibility in engineering their optical response, metamaterials have been used to achieve control over the propagation of light to an unprecedented level, leading to highly unconventional and versatile optical functionalities compared with their natural counterparts. Recently, the emerging field of metasurfaces, which consist of a monolayer of photonic artificial atoms, has offered attractive functionalities for shaping wave fronts of light by introducing an abrupt interfacial phase discontinuity. Here we realize three-dimensional holography by using metasurfaces made of subwavelength metallic nanorods with spatially varying orientations. The phase discontinuity takes place when the helicity of incident circularly polarized light is reversed. As the phase can be continuously controlled in each subwavelength unit cell by the rod orientation, metasurfaces represent a new route towards high-resolution on-axis three-dimensional holograms with a wide field of view. In addition, the undesired effect of multiple diffraction orders usually accompanying holography is eliminated.
The Activation of Metabotropic Glutamate Receptors Protects Nerve Cells from Oxidative Stress (1998)

Metabotropic glutamate receptors (mGluRs) have been implicated in a variety of cellular responses to glutamic acid. The work described in this manuscript extends the role of mGluRs to include protection from oxidative stress-induced programmed cell death. Glutamate analogs regulate inositol-1,4,5 triphosphate mass accumulation in accordance with their ability to protect cells from oxidative glutamate toxicity, and protection appears to take place at the level of glutathione metabolism. Short-term exposure of cells to low concentrations of glutamate desensitizes cells to a subsequent challenge from glutamate. Glutamate exposure upregulates the expression of mGluR5 in hippocampal HT-22 cells and mGluR1 in cortical primary cultures. Finally, group I mGluR agonists also protect cells from death programs initiated by glucose starvation and cystine deprivation.
An Antisense Oligonucleotide to 1-cys Peroxiredoxin Causes Lipid Peroxidation and Apoptosis in Lung Epithelial Cells (2002)

1-cys peroxiredoxin (1-cysPrx), a member of the peroxiredoxin superfamily, reduces phospholipid hydroperoxides as well as organic peroxides and H(2)O(2). To determine the physiological function(s) of 1-cysPrx, we have used an antisense strategy to suppress endogenous 1-cysPrx in L2 cells, a rat lung epithelial cell line. A 25-base antisense morpholino oligonucleotide was designed to bind a complementary sequence overlapping the translational start site (-18 to +7) in the rat 1-cysPrx mRNA, blocking protein synthesis. Treatment with an antisense oligonucleotide for 48 h resulted in approximately 60% suppression of the 1-cysPrx protein content as measured by immunoblot analysis and an approximately 44% decrease of glutathione peroxidase activity as compared with random oligonucleotide treated and control (vehicle only) cells. Accumulation of phosphatidylcholine hydroperoxide in plasma membranes was demonstrated by high pressure liquid chromatography assay for conjugated dienes (260 pmol/10(6) cells for antisense versus 70 pmol/10(6) cells for random oligonucleotide and control cells) and by fluorescence of diphenyl-1-pyrenylphosphine, a probe for lipid peroxidation. The percentage of cells showing positive staining for annexin V and propidium iodide after antisense treatment was 40% at 28 h and 80% at 48 h. TdT-mediated dUTP nick end labeling assay at 48 h indicated DNA fragmentation in antisense-treated cells that was blocked by prior infection with adenovirus encoding 1-cysPrx or by pretreatment with a vitamin E analogue. The results indicate that 1-cysPrx can function in the intact cell as an antioxidant enzyme to reduce the accumulation of phospholipid hydroperoxides and prevent apoptotic cell death.
De novo germline mutation in the serine–threonine kinase STK11/LKB1 gene associated with Peutz–Jeghers syndrome (2004)

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease, characterized phenotypically by mucocutaneous pigmentation and hamartomatous polyposis. Affected patients are at an increased risk of developing gastrointestinal and other malignancies. Mutations in the STK11/LKB1 (LKB1) gene, which encodes for a serine-threonine kinase, have been identified as a genetic cause of PJS. Molecular analysis of the LKB1 gene in a simplex case of PJS revealed a substitution of cytosine (C) for guanine (G) at codon 246 in exon 6, resulting in the Tyr246X mutation. The nucleotide substitution leads to a premature stop codon at the 246 residue, predicting a truncated protein and presumed loss of kinase activity. Analysis of DNA from both parents of the PJS patient did not show this mutation, which is therefore a de novo mutation. We isolated DNA from microdissected gastrointestinal hamartomatous polyps in the PJS patient and investigated the loss of heterozygosity (LOH) at the LKB1 locus by real-time fluorescence polymerase chain reaction genotyping using a fluorescent resonance energy transfer technique. The results suggest a different mechanism from LOH in the formation of hamartomatous polyps.
The role of temporal cortical areas in perceptual organization (1997)

The visual areas of the temporal lobe of the primate are thought to be essential for the representation of visual objects. To examine the role of these areas in the visual awareness of a stimulus, we recorded the activity of single neurons in monkeys trained to report their percepts when viewing ambiguous stimuli. Visual ambiguity was induced by presenting incongruent images to the two eyes, a stimulation condition known to instigate binocular rivalry, during which one image is seen at a given time while the other is perceptually suppressed. Previous recordings in areas V1, V2, V4, and MT of monkeys experiencing binocular rivalry showed that only a small proportion of striate and early extrastriate neurons discharge exclusively when the driving stimulus is seen. In contrast, the activity of almost all neurons in the inferior temporal cortex and the visual areas of the cortex of superior temporal sulcus was found to be contingent upon the perceptual dominance of an effective visual stimulus. These areas thus appear to represent a stage of processing beyond the resolution of ambiguities--and thus beyond the processes of perceptual grouping and image segmentation--where neural activity reflects the brain's internal view of objects, rather than the effects of the retinal stimulus on cells encoding simple visual features or shape primitives.
Physiological and immunopathological consequences of active immunization of spontaneously hypertensive and normotensive rats against murine renin. (1990)

Spontaneously hypertensive Okamoto-strain rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were actively immunized with mouse renin to investigate the effect on blood pressure of blocking the renin-angiotensinogen reaction. Ten male SHR and 10 male WKY rats were immunized with purified mouse submandibular gland renin. Control rats were immunized with bovine serum albumin. Antirenin antibodies were produced by both SHR and WKY rats, but renin-immunized SHR had higher titers of circulating renin antibodies after three injections. The increase in renin antibody in renin-immunized SHR was associated with a significant drop in blood pressure (tail-cuff method) that became similar to that of the WKY control rats after four injections. The blockade by antirenin immunoglobulins of the renin-angiotensinogen reaction also decreased the blood pressure of normotensive rats. Perfusion of renin-immunized rats with mouse submandibular renin (10 micrograms) in vivo caused no increase in blood pressure. Perfusion of renin-immunized, salt-depleted SHR with converting enzyme inhibitor caused no further decrease in blood pressure but significantly decreased blood pressure in salt-depleted control rats. The presence of circulating renin antibodies was associated with low plasma renin activity (0.31 +/- 0.23 ng angiotensin I [Ang I]/ml/hr). Plasma renin activity was unchanged in control animals (13.1 +/- 3.9 ng Ang I/ml/hr in control SHR, 13.9 +/- 3.2 ng Ang I/ml/hr in control WKY rats). Renin antibody-rich serum produced a dose-dependent inhibition of rat renin enzymatic activity in vitro. The chronic blockade of the renin-angiotensinogen reaction in renin-immunized SHR produced an almost-complete disappearance of Ang II (0.8 %/- 7 fmol/ml; control SHR, 30.6 +/- 15.7 fmol/ml) and a 50% reduction in urinary aldosterone. Renin immunization was never associated with a detectable loss of sodium after either 10 or 24 weeks. The glomerular filtration rate was not decreased 10 weeks after renin immunization, whereas blood pressure was significantly decreased, plasma renin activity was blocked, and renal plasma flow was increased. The ratio of left ventricular weight to body weight after 24 weeks was significantly below control levels in renin-immunized WKY rats and SHR. Histological examination of the kidney of renin-immunized SHR showed a chronic autoimmune interstitial nephritis characterized by the presence of immunoglobulins, mononuclear cell infiltration, and fibrosis around the juxtaglomerular apparatus. These experiments demonstrate that chronic specific blockade of renin decreases blood pressure in a genetic model of hypertension in which the renin-angiotensin system is not directly involved.(ABSTRACT TRUNCATED AT 400 WORDS)
Flap endonucleases pass 5′-flaps through a flexible arch using a disorder-thread-order mechanism to confer specificity for free 5′-ends (2012)

Flap endonucleases (FENs), essential for DNA replication and repair, recognize and remove RNA or DNA 5'-flaps. Related to FEN specificity for substrates with free 5'-ends, but controversial, is the role of the helical arch observed in varying conformations in substrate-free FEN structures. Conflicting models suggest either 5'-flaps thread through the arch, which when structured can only accommodate single-stranded (ss) DNA, or the arch acts as a clamp. Here we show that free 5'-termini are selected using a disorder-thread-order mechanism. Adding short duplexes to 5'-flaps or 3'-streptavidin does not markedly impair the FEN reaction. In contrast, reactions of 5'-streptavidin substrates are drastically slowed. However, when added to premixed FEN and 5'-biotinylated substrate, streptavidin is not inhibitory and complexes persist after challenge with unlabelled competitor substrate, regardless of flap length or the presence of a short duplex. Cross-linked flap duplexes that cannot thread through the structured arch react at modestly reduced rate, ruling out mechanisms involving resolution of secondary structure. Combined results explain how FEN avoids cutting template DNA between Okazaki fragments and link local FEN folding to catalysis and specificity: the arch is disordered when flaps are threaded to confer specificity for free 5'-ends, with subsequent ordering of the arch to catalyze hydrolysis.
Binaural cue coding: a novel and efficient representation of spatial audio (2002)

We present a novel concept for representing multi-channel audio signals: Binaural Cue Coding (BCC). BCC aims at separating the basic audio content and the information relevant for spatial perception. A multi-channel audio signal is represented as a mono signal and BCC parameters. We present two types of applications of BCC. Firstly, a number of separate sound source signals are reduced to a mono signal and BCC parameters. In this case, the decoder has control over the location of each source in auditory space. In other words, the decoder can render spatial images as if the separate source signals were given. Secondly, a multi-channel audio signal is reduced to a mono signal and BCC parameters. In this case the decoder generates a multi-channel signal with a spatial image similar to the spatial image of the input signal of the encoder. Results from a subjective test suggest that BCC, combined with existing mono audio coders, offers better quality than conventional stereo and multi-channel perceptual transform audio coders for a wide range of bitrates.
Amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease: phylogenetic disorders of the human neocortex sharing many characteristics. (1992)

Features common to amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD) are reviewed. Shared epidemiological aspects include an increasing frequency which is proportional for each disease. We draw attention to geographic non-uniform distribution which, for ALS and PD, correlates positively with latitude. Clinical and pathological overlap occurs in the same patients, and in members of the same family. A high early morning plasma cysteine/sulphate ratio possibly related to the development of proteinacious inclusions, as well as ubiquinated neuronal inclusions, characterize ALS, PD and AD. HLA-DR (the human group II major histocompatibility class) staining is marked in ALS, PD and AD and may represent autoimmunity-incited by-products of neuronal degeneration. Based upon demonstrated glutaminergic connections between the neocortex and anterior horn cells, the entorhinal cortex and the basal ganglia we hypothesize that ALS, AD and PD are phylogenetic disturbances of the neocortical cell. The postsynaptic neuron may degenerate secondarily to anterograde effects of deranged glutamate metabolism. Future therapeutic strategies should be directed to agents that decrease transmission induced by excitatory amino-acids.
An In Vitro Model of the Glomerular Capillary Wall Using Electrospun Collagen Nanofibres in a Bioartificial Composite Basement Membrane (2011)

The filtering unit of the kidney, the glomerulus, contains capillaries whose walls function as a biological sieve, the glomerular filtration barrier. This comprises layers of two specialised cells, glomerular endothelial cells (GEnC) and podocytes, separated by a basement membrane. Glomerular filtration barrier function, and dysfunction in disease, remains incompletely understood, partly due to difficulties in studying the relevant cell types in vitro. We have addressed this by generation of unique conditionally immortalised human GEnC and podocytes. However, because the glomerular filtration barrier functions as a whole, it is necessary to develop three dimensional co-culture models to maximise the benefit of the availability of these cells. Here we have developed the first two tri-layer models of the glomerular capillary wall. The first is based on tissue culture inserts and provides evidence of cell-cell interaction via soluble mediators. In the second model the synthetic support of the tissue culture insert is replaced with a novel composite bioartificial membrane. This consists of a nanofibre membrane containing collagen I, electrospun directly onto a micro-photoelectroformed fine nickel supporting mesh. GEnC and podocytes grew in monolayers on either side of the insert support or the novel membrane to form a tri-layer model recapitulating the human glomerular capillary in vitro. These models will advance the study of both the physiology of normal glomerular filtration and of its disruption in glomerular disease.
The delta (argF-lacZ)205(U169) deletion greatly enhances resistance to hydrogen peroxide in stationary-phase Escherichia coli (1994)

In this study, we demonstrate that a strain bearing the delta (argF-lacZ)205(U169) deletion exhibits a high level of resistance to hydrogen peroxide compared with its undeleted parent. Our initial investigation of the mechanism behind the observed differences in peroxide resistance when parent and mutant strains are compared indicates that the parent strain carries a region near argF that is responsible for the H2O2-sensitive phenotype, which we have named katC. The H2O2 resistance phenotype of the delta katC [delta (argF-lacZ)205(U169)] mutant strain can be duplicated by Tn9 insertion in a specific locus (katC5::Tn9) which maps near argF. The increased H2O2 resistance of the delta katC and katC5::Tn9 mutant strains can be seen only when cells are grown to stationary phase; exponential-phase cells are unaffected by the presence or absence of katC. This H2O2 resistance mechanism requires functional katE and katF genes, which suggests that the mechanism of H2O2 resistance may involve the activity of the stationary-phase-specific catalase HPII. Cloning, DNA sequencing, and analysis of the katC5::Tn9 insertion allele in comparison with its parent allele implicate two insertion elements, IS1B and IS30B, and suggest that their presence sensitizes parent cells to H2O2.
Continuous-wave mode-locked Cr^4+:YAG laser (1993)

A cw room-temperature Cr(4+):YAG laser, tuning from 1.37 to 1.51 microm, is described. Mode locking of this novel laser is reported for what is to our knowledge the first time.
5-Aryl-2,3-dihydro-5H-imidazo[2,1-a]isoindol-5-ols. Novel class of anorectic agents (1975)

A series of 5-aryl-2,3-dihydro-5H-imidazo[2,1-a]isoindol-5-ols (IV), prepared by the LiA1H4 reduction of the corresponding 9b-aryl-1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones (II), was evaluated for suppression of food consumption in rats. One member of this series, 5-p-chlorophenyl-2,3-dihydro-5H-imidazo[2,1-a]isoindol-5-ol (6, mazindol), was evaluated in squirrel and capuchin monkeys and found to have anorexic activity approximately equal to d-amphetamine.
How Does Internal Motion Influence the Relaxation of the Water Protons in LnIIIDOTA-like Complexes? (2002)

Taking advantage of the Curie contribution to the relaxation of the protons in the Tb(III) complex, and the quadrupolar relaxation of the 17O and 2H nuclei on the Eu(III) complex, the effect of the internal motion of the water molecule bound to [Ln(DOTAM)(H2O)]3+ complexes was quantified. The determination of the quadrupolar coupling constant of the bound water oxygen chi(Omicron)(1 + eta(Omicron)2/3)1/2 = 5.2 +/- 0.5 MHz allows a new analysis of the 17O and 1H NMR data of the [Gd(DOTA)(H2O)]- complex with different rotational correlation times for the Gd(III)-O(water) and Gd(III)-H(water) vectors. The ratio of the rotational correlation times for the Ln(III)-H(water) vector and the overall rotational correlation time is calculated tau(RH)/tau(RO) = 0.65 +/- 0.2. This could have negative consequences on the water proton relaxivity, which we discuss in particular for macromolecular systems. It appears that the final effect is actually attenuated and should be around 10% for such large systems undergoing local motion of the chelating groups.
The molecular role of the common gamma c subunit in signal transduction reveals functional asymmetry within multimeric cytokine receptor complexes. (1996)

The specific signal transduction function of the gamma c subunit in the interleukin (IL) 2, IL-4, IL-7, IL-9, and IL-15 receptor complexes remains undefined. The present structure-function analyses demonstrated that the entire cytoplasmic tail of gamma c could be functionally replaced in the IL-2 receptor (IL-2R) signaling complex by a severely truncated erythropoietin receptor cytoplasmic domain lacking tyrosine residues. Heterodimerization of IL-2R beta with either gamma c or the truncated erythropoietin receptor chain led to an array of specific signals normally derived from the native IL-2R despite the substitution of Janus kinase JAK2 for JAK3 in the receptor complex. These findings thus suggest a model in which the gamma c subunit serves as a common and generic "trigger" chain by providing a nonspecific Janus kinase for signaling program initiation, while signal specificity is determined by the unique "driver" subunit in each of the gamma c- containing receptor complexes. Furthermore, these results may have important functional implications for the asymmetric design of many cytokine receptor complexes and the evolutionary design of receptor subfamilies that share common trigger or driver subunits.
Progressive Familial Intrahepatic Cholestasis (PFIC) Type 1, 2, and 3: A Review of the Liver Pathology Findings (2011)

Progressive familial intrahepatic cholestatic diseases encompass a group of autosomal recessive hereditary diseases, which usually present in infancy or childhood, with cholestasis of hepatocellular origin. The currently preferred nomenclature for the three PFIC disorders that have been characterized to date is FIC1 deficiency, BSEP deficiency, and MDR3 deficiency, relating to mutations in the specific genes involved in bile acid formation and transport. Since the first description of these diseases, extensive clinical, biochemical, and molecular studies have increased our understanding of the features specific to each one of them. This review focuses mainly on the liver histology, summarizing their characteristic pathologic features, the correlation to specific genotypes, and complications arising with disease progression.