gebhart/patrepeval huggingface dataset:
Prevention of Inflammation-Mediated Neurotoxicity by Rg3 and Its Role in Microglial Activation (2008)

Considering the importance of inflammation and apoptosis in neurodegenerative conditions, the potential suppressive effects of the Rg3, a by-product obtained during the steaming of red ginseng, may indicate that Rg3 could provide a beneficial therapeutic approach to treating or preventing neurodegenerative disease. We investigated the effect of Rg3 on Abeta42-mediated microglial activation and inflammation-mediated neurotoxicity in murine BV-2 microglial and Neuro-2a neuroblastoma cells, respectively. Rg3 effectively reduced inflammatory cytokine expression in Abeta42-treated BV-2, and inhibited the binding of NF-kappaB p65 to its DNA consensus sequences, and significantly reduced the expression of TNF-alpha in activated microglia. Pretreatment with Rg3 increased the survival rate of Neuro-2a exposed to TNF-alpha. These observations suggest that Rg3 reduced neurotoxicity by inhibiting chronic inflammation through the suppression of activated microglia. In addition, the expression of pro-inflammatory cytokines in BV-2 stimulated by Abeta42 was decreased but not eliminated by Rg3 when binding to the macrophage scavenger receptor type A (MSRA) was blocked with fucoidan. This implies that the inflammatory response may not be exclusively triggered via MSRA. More interestingly, iNOS was almost completely inhibited in the presence of Rg3 when MSRA binding was blocked with fucoidan. Moreover, Rg3 increased the expression of MSRA in BV-2 transfected with siRNA targeting MSRA mRNA, and this increased MSRA expression may play a role in the phagocytosis of Abeta42 peptides. Our results indicate that inhibition of the inflammatory repertoire of microglia, neuroprotection, and increased MSRA expression induced by Rg3 may at least partly explain its therapeutic effects in chronic neurodegenerative diseases.
A simple method to combine multiple molecular biomarkers for dichotomous diagnostic classification (2006)

The proposed algorithm can be used for accurate diagnosis in the setting of dichotomous classification of disease states.
Peripheral blood mononuclear cells produce normal amounts of defective Vif- human immunodeficiency virus type 1 particles which are restricted for the preretrotranscription steps (1995)

Previous studies have demonstrated the absence of viral replication of Vif- mutants in stimulated primary blood mononuclear cells (PBMC). Human immunodeficiency virus type 1 strain NDK Vif- mutants were propagated on the semipermissive CEM cell line, and the viral stock obtained was compared with the wild-type virus during a single cycle in PBMC. The Vif- virus was able to enter PBMC with the same efficiency as the wild type, as demonstrated by quantification of the strong-stop cDNA, and retrotranscription was observed for both viruses within 4 h postinfection. Using a PCR assay with an Alu-long terminal repeat pair of primers, we detected integration for both the wild-type and Vif- viruses. We then used qualitative and quantitative reverse transcription-mediated PCR techniques to study the steady-state level of intracellular and extracellular viral RNAs. All mRNA species were detected in PBMC infected with the wild-type virus or with the Vif- virus 36 h postinfection. Furthermore, quantification of viral RNA released from infected cells demonstrated similar levels of virus produced after a unique cycle of replication. However, the Vif- virus obtained after one replication cycle in PBMC was unable to initiate retrotranscription in permissive target cells. These data strongly suggest that the failure to infect target cells is due to a defect in the formation of the viral particle in PBMC.
Picosecond optoelectronic switching and gating in silicon (1975)

Quasimetallic photoconductivity produced by the absorption of picosecond optical pulses in silicon transmission line structures has been used to devise electronic switches and gates which can be turned on and off in a few picoseconds. Electrical signals as large as 100 V can be switched by a few microjoules of optical energy. The switching speed was measured by correlating the response of two transmission gates in tandem, each having an aperture time of 15 psec.
Fabrication and lateral electronic transport measurements of gold nanowires (2001)

A technique for fabrication of gold nanowires on a Si(111) surface in ultrahigh vacuum and their electronic transport properties are presented. Gold wires with widths as small as 4 nm are produced by using a gold-coated piezoresistive cantilever in atomic force microscope contact mode. This technique allows patterns to be written at will. In situ electronic transport measurements of a gold wire as long as 7 μm and 4 nm wide show unambiguous metallic behavior. This fabrication method could become pivotal within the next generation of nanoscale microprocessors.
A class of balanced binary sequences with optimal autocorrelation properties (1977)

The construction of a class of balanced binary sequences with optimal autocorrelation properties is described. Given any odd prime <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</tex> and any positive integer <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</tex> , a balanced <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">( \pm 1)</tex> binary sequence of length <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p^{m} - 1</tex> whose cyclic autocorrelation function <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c (\tau)</tex> satisfies <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c (0) = p^{m} - 1</tex> , and, for <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\tau \neq 0, c (\tau) = +2</tex> or <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-2</tex> when <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(p^{m} - 1)/2</tex> is odd, and <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c(\tau) = 0</tex> or <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-4</tex> when <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(p^{m} - 1)/2</tex> is even is constructed. Optimality is proved by showing that every balanced binary sequence has at least two distinct out-of-phase correlation values which are at least as large as those obtained here.
Candida and candidosis (1979)

A comprehensive and critical review of the medical and scientific literature on Candida infections by a leading authority in the field. Covers all aspects of the subject, including epidemiology, pathogensis and treatment, as well as the properties of the fungi that cause infections.
Dorsal root entry zone lesions for pain relief (1979)

✓ Arm pain due to avulsion of the cervical dorsal roots of the brachial plexus may become intractable, ameliorated little, if at all, by contemporary medical or surgical treatment. Severe and sudden trauma to the neck, shoulder, or arm is the usual cause of avulsion of the cervical rootlets. The injury may result in complete sensorimotor paralysis of the involved extremity, or a partial deficit if only a few rootlets are involved. Previous therapies have included stellate block, sympathectomy, high cervical cordotomy, rhizotomy, transcutaneous stimulation, dorsal column stimulation, mesencephalic tractotomy, cingulotomy, and the use of narcotics. The extent of the pathological change in the spinal cord following root avulsion is not completely known; at the time of operation, abnormalities frequently noted included ipsilateral atrophy of the dorsal aspect of the cord, dense arachnoid scarring, microcyst formation, and loss of both dorsal and ventral roots. The cervical myelogram is abnormal, although not necessarily pathognomonic of the extent of injury. The surgical technique of coagulation of the dorsal root entry zone is discussed, and the results and morbidity in 21 patients are reviewed. Thirteen patients (67%) continue to have good pain relief, with follow-up periods ranging from 6 months to 3½ years. Three patients with extremity pain from other causes are included in the series. Clinical observations suggest the possibility that pain resulting from brachial plexus avulsion originates from pathophysiological changes in the injured dorsal horn of the spinal cord. This report is a discussion of a new technique aimed at destruction of the dorsal root entry zone for relief of chronic extremity pain.
Autocrine PDGFR signaling promotes mammary cancer metastasis (2006)

Metastasis is the major cause of cancer morbidity, but strategies for direct interference with invasion processes are lacking. Dedifferentiated, late-stage tumor cells secrete multiple factors that represent attractive targets for therapeutic intervention. Here we show that metastatic potential of oncogenic mammary epithelial cells requires an autocrine PDGF/PDGFR loop, which is established as a consequence of TGF-beta-induced epithelial-mesenchymal transition (EMT), a faithful in vitro correlate of metastasis. The cooperation of autocrine PDGFR signaling with oncogenic Ras hyperactivates PI3K and is required for survival during EMT. Autocrine PDGFR signaling also contributes to maintenance of EMT, possibly through activation of STAT1 and other distinct pathways. Inhibition of PDGFR signaling interfered with EMT and caused apoptosis in murine and human mammary carcinoma cell lines. Consequently, overexpression of a dominant-negative PDGFR or application of the established cancer drug STI571 interfered with experimental metastasis in mice. Similarly, in mouse mammary tumor virus-Neu (MMTV-Neu) transgenic mice, TGF-beta enhanced metastasis of mammary tumors, induced EMT, and elevated PDGFR signaling. Finally, expression of PDGFRalpha and -beta correlated with invasive behavior in human mammary carcinomas. Thus, autocrine PDGFR signaling plays an essential role during cancer progression, suggesting a novel application of STI571 to therapeutically interfere with metastasis.
CpG DNA Induces Sustained IL-12 Expression In Vivo and Resistance to Listeria monocytogenes Challenge (1998)

Vertebrates have evolved innate immune defense mechanisms that recognize and respond to structural patterns that are specific to microbial molecules. One such pattern recognition system is based on unmethylated CpG dinucleotides in particular sequence contexts (CpG motifs); these motifs are common in bacterial DNA but are under-represented ("CpG suppression") and methylated in vertebrate DNA. Mice that are injected with bacterial DNA or synthetic oligodeoxynucleotides (ODNs) containing CpG motifs respond with a rapid production of IL-12 and IFN-gamma. The serum levels of IL-12 were increased for at least 8 days after a single injection of CpG ODNs, but IFN-gamma levels returned to baseline within 24 h. This Th1-like cytokine response to CpG motifs induces a state of resistance to infection by Listeria monocytogenes in susceptible specific pathogen-free BALB/c mice. Resistance developed within 48 h of pretreatment with CpG ODNs, persisted for at least 2 wk, and was dependent upon IFN-gamma secretion. These data support the hypothesis that CpG DNA motifs are a "danger signal" that activates protective innate immune defenses and may have therapeutic potential.
Serum Free Light Chains: An Alternative to the Urine Bence Jones Proteins Screening Test for Monoclonal Gammopathies (2006)

Additional diagnostic information is gained by adding serum FLCs to SPEP as first-line tests for investigating possible B-cell disorders. The quality of the diagnostic service is enhanced by more confident exclusion of light chain disorders and improved interpretive assessment of SPEP and immunofixation electrophoresis.
Loss of peroxisome proliferator–activated receptor γ in mouse fibroblasts results in increased susceptibility to bleomycin‐induced skin fibrosis (2009)

These results indicate that PPARgamma suppresses fibrogenesis. Specific agonists of PPARgamma may therefore alleviate the extent of the development of cutaneous sclerosis.
The multistable charge controlled memory effect in SOI-transistors at low temperatures (2003)

The operation of nMOS-transistors, made in SOI material, is investigated at low temperatures. A new phenomenon, the MCCM (multistable charge controlled memory) effect, is observed. Measurements demonstrating this MCCM effect are presented on nMOS transistors made in ZMR-SOI material. A physical model and an analytical model are given. Finally, some very promising applications of the MCCM-effect are highlighted, such as its use as a visible light sensor and as a very dense memory cell, with refresh times on the order of several hours.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Regional Brain Concentrations of Neuropeptides in Huntington's Chorea and Schizophrenia (1983)

To ascertain whether Huntington's chorea and schizophrenia are associated with specific regional alterations in neurotensin, somatostatin, and thyrotropin-releasing hormone, the concentrations of these putative neurotransmitters were measured by radioimmunoassay in postmortem brain samples from patients with Huntington's chorea or schizophrenia. Compared to 50 patients without psychiatric or neurological disease, the patients with Huntington's chorea showed significantly elevated concentrations of all three neuropeptides in the nucleus caudatus. In the nucleus accumbens somatostatin levels were increased threefold, while in the amygdala thyrotropin-releasing hormone levels were elevated. In contrast, the schizophrenics exhibited reduced levels of thyrotropin-releasing hormone in two frontal cortical regions, reduced somatostatin levels in one frontal cortical area, and increased neurotensin levels in one frontal cortical area. None of the differences between the diseased brains and the controls could be accounted for by differences in age, sex, or time between death and autopsy.
Signal Transfer from GPCRs to G Proteins (2006)

Catalysis of nucleotide exchange in heterotrimeric G proteins (Galphabetagamma) is a key step in cellular signal transduction mediated by G protein-coupled receptors. The Galpha N terminus with its helical stretch is thought to be crucial for G protein/activated receptor (R(*)) interaction. The N-terminal fatty acylation of Galpha is important for membrane targeting of G proteins. By applying biophysical techniques to the rhodopsin/transducin model system, we studied the effect of N-terminal truncations in Galpha. In Galphabetagamma, lack of the fatty acid and Galpha truncations up to 33 amino acids had little effect on R(*) binding and R(*)-catalyzed nucleotide exchange, implying that this region is not mandatory for R(*)/Galphabetagamma interaction. However, when the other hydrophobic modification of Galphabetagamma, the Ggamma C-terminal farnesyl moiety, is lacking, R(*) interaction requires the fatty acylated Galpha N terminus. This suggests that the two hydrophobic extensions can replace each other in the interaction of Galphabetagamma with R(*). We propose that in native Galphabetagamma, these two terminal regions are functionally redundant and form a microdomain that serves both to anchor the G protein to the membrane and to establish an initial docking complex with R(*). Accordingly, we find that the native fatty acylated Galpha is competent to interact with R(*) even in the absence of Gbetagamma, whereas nonacylated Galpha requires Gbetagamma for interaction. Experiments with N-terminally truncated Galpha subunits suggest that in the second step of the catalytic process, the receptor binds to the alphaN/beta1-loop region of Galpha to reduce nucleotide affinity and to make the Galpha C terminus available for subsequent interaction with R(*).
The Hotdog fold: wrapping up a superfamily of thioesterases and dehydratases (2004)

The HotDog domain is both an ancient and ubiquitous motif, with members found in the three branches of life.
Use of a bacterial expression vector to map the varicella-zoster virus major glycoprotein gene, gC (1985)

The genome of varicella-zoster virus (VZV) encodes at least three major glycoprotein genes. Among viral gene products, the gC gene products are the most abundant glycoproteins and induce a substantial humoral immune response (Keller et al., J. Virol. 52:293-297, 1984). We utilized two independent approaches to map the gC gene. Small fragments of randomly digested VZV DNA were inserted into a bacterial expression vector. Bacterial colonies transformed by this vector library were screened serologically for antigen expression with monoclonal antibodies to gC. Hybridization of the plasmid DNA from a gC antigen-positive clone revealed homology to the 3' end of the VZV Us segment. In addition, mRNA from VZV-infected cells was hybrid selected by a set of VZV DNA recombinant plasmids and translated in vitro, and polypeptide products were immunoprecipitated by convalescent zoster serum or by monoclonal antibodies to gC. This analysis revealed that the mRNA encoding a 70,000-dalton polypeptide precipitable by anti-gC antibodies mapped to the HindIII C fragment, which circumscribes the entire Us region. We conclude that the VZV gC glycoprotein gene maps to the 3' end of the Us region and is expressed as a 70,000-dalton primary translational product. These results are consistent with the recently reported DNA sequence of Us (A.J. Davison, EMBO J. 2:2203-2209, 1983). Furthermore, glycosylation appears not to be required for a predominant portion of the antigenicity of gC glycoproteins. We also report the tentative map assignments for eight other VZV primary translational products.
Role of outer ring carboxylates of the rat skeletal muscle sodium channel pore in proton block (2002)

Voltage-gated Na+ current is reduced by acid solution. Protons reduce peak Na+ conductance by lowering single channel conductance and shift the voltage range of gating by neutralizing surface charges. Structure-function studies identify six carboxyls and a lysine in the channel's outer vestibule. We examined the roles of the superficial ring of carboxyls in acid block of Na(v)1.4 (the rat skeletal muscle Na+ channel isoform) by measuring the effects of their neutralization or their substitution by lysine on sensitivity to acid solutions, using the two-micropipette voltage clamp in Xenopus oocytes. Alteration of the outer ring of carboxylates had little effect on the voltage for half-activation of Na+ current, as if they are distant from the channels' voltage sensors. The mutations did not abolish proton block; rather, they all shifted the pK(a) (-log of the dissociation constant) in the acid direction. Effects of neutralization on pK(a) were not identical for different mutations, with E758Q > D1241A > D1532N > E403Q. E758K showed double the effect of E758Q, and the other lysine mutations all produced larger effects than the neutralizing mutations. Calculation of the electrostatic potential produced by these carboxylates using a pore model showed that the pK(a) values of carboxylates of Glu-403, Glu-758, and Asp-1532 are shifted to values similar to the experimentally measured pK(a). Calculations also predict the experimentally observed changes in pK(a) that result from mutational neutralization or introduction of a positive charge. We propose that proton block results from partial protonation of these outer ring carboxylates and that all of the carboxylates contribute to a composite Na+ site.
QUINOLINIC ACID AND KYNURENINE PATHWAY METABOLISM IN INFLAMMATORY AND NON-INFLAMMATORY NEUROLOGICAL DISEASE (1992)

Neurological dysfunction, seizures and brain atrophy occur in a broad spectrum of acute and chronic neurological diseases. In certain instances, over-stimulation of N-methyl-D-aspartate receptors has been implicated. Quinolinic acid (QUIN) is an endogenous N-methyl-D-aspartate receptor agonist synthesized from L-tryptophan via the kynurenine pathway and thereby has the potential of mediating N-methyl-D-aspartate neuronal damage and dysfunction. Conversely, the related metabolite, kynurenic acid, is an antagonist of N-methyl-D-aspartate receptors and could modulate the neurotoxic effects of QUIN as well as disrupt excitatory amino acid neurotransmission. In the present study, markedly increased concentrations of QUIN were found in both lumbar cerebrospinal fluid (CSF) and post-mortem brain tissue of patients with inflammatory diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases and septicaemia) independent of breakdown of the blood-brain barrier. The concentrations of kynurenic acid were also increased, but generally to a lesser degree than the increases in QUIN. In contrast, no increases in CSF QUIN were found in chronic neurodegenerative disorders, depression or myoclonic seizure disorders, while CSF kynurenic acid concentrations were significantly lower in Huntington's disease and Alzheimer's disease. In inflammatory disease patients, proportional increases in CSF L-kynurenine and reduced L-tryptophan accompanied the increases in CSF QUIN and kynurenic acid. These responses are consistent with induction of indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway which converts L-tryptophan to kynurenic acid and QUIN. Indeed, increases in both indoleamine-2,3-dioxygenase activity and QUIN concentrations were observed in the cerebral cortex of macaques infected with retrovirus, particularly those with local inflammatory lesions. Correlations between CSF QUIN, kynurenic acid and L-kynurenine with markers of immune stimulation (neopterin, white blood cell counts and IgG levels) indicate a relationship between accelerated kynurenine pathway metabolism and the degree of intracerebral immune stimulation. We conclude that inflammatory diseases are associated with accumulation of QUIN, kynurenic acid and L-kynurenine within the central nervous system, but that the available data do not support a role for QUIN in the aetiology of Huntington's disease or Alzheimer's disease. In conjunction with our previous reports that CSF QUIN concentrations are correlated to objective measures of neuropsychological deficits in HIV-1-infected patients, we hypothesize that QUIN and kynurenic acid are mediators of neuronal dysfunction and nerve cell death in inflammatory diseases. Therefore, strategies to attenuate the neurological effects of kynurenine pathway metabolites or attenuate the rate of their synthesis offer new approaches to therapy.
[Electronic cigarette--a safe substitute for tobacco cigarette or a new threat?]. (2012)

The aim of this paper was to summarize up-to-date data on the new emerging nicotine containing product 'electronic cigarette', commonly referred as e-cigarette. We presented data on prevalence and popularity of various brands and models on domestic markets. Development of the new products with technical and chemical modifications was also described. We reviewed studies on chemical composition and efficacy of nicotine delivery from e-cigarettes and discussed its potential use as nicotine replacement for tobacco cigarettes. Regulatory policies on e-cigarette sale as nicotine containing product were also discussed. We concluded that e-cigarette might be an effective harm reduction tool but little is known about its safety, especially when used for a long time. Despite many positive findings from surveys among e-cigarettes users, there is need for comprehensive state-of-the-at clinical trials to show efficacy of e-cigarette as smoking cessation tool.