gebhart/patrepeval huggingface dataset:
Blockade of Programmed Death-1 Pathway Rescues the Effector Function of Tumor-Infiltrating T Cells and Enhances the Antitumor Efficacy of Lentivector Immunization (2010)

Despite intensive effort, the antitumor efficacy of tumor vaccines remains limited in treating established tumors regardless of the potent systemic tumor-specific immune response and the increases of tumor infiltration of T effector cells. In the current study, we demonstrated that although lentivector (lv) immunization markedly increased Ag-dependent tumor infiltration of CD8 and CD4 T cells and generated Ag-specific antitumor effect, it simultaneously increased the absolute number of myeloid-derived suppressor cells and regulatory T cells in the tumor lesions. In addition, lv immunization induced expression of programmed death-ligand 1 in the tumor lesions. Furthermore, the tumor-infiltrating CD8 T cells expressed high levels of programmed death-1 and were partially dysfunctional, producing lower amounts of effector cytokines and possessing a reduced cytotoxicity. Together, these immune-suppression mechanisms in the tumor microenvironment pose a major obstacle to effective tumor immunotherapy and may explain the limited antitumor efficacy of lv immunization. The loss of effector function in the tumor microenvironment is reversible, and the effector function of CD8 T cells in the tumor could be partially rescued by blocking programmed death-1 and programmed death-ligand 1 pathway in vitro and in vivo, resulting in enhanced antitumor efficacy of lv immunization. These data suggest that immunization alone may exacerbate immune suppression in the tumor lesions and that methods to improve the tumor microenvironment and to rescue the effector functions of tumor-infiltrating T cells should be incorporated into immunization strategies to achieve enhanced antitumor efficacy.
Role for Nucleotide Excision Repair in Virulence of Mycobacterium tuberculosis (2005)

Mutations in Mycobacterium tuberculosis uvrB result in severe sensitivity to acidified nitrite, a source of nitric oxide (6). In this study, we show that a uvrB mutant is exquisitely sensitive to UV light but not to several sources of reactive oxygen species in vitro. Furthermore, a uvrB mutant was attenuated in mice as judged by an extension of life span. Attenuation in mice was partially reversed by genetic inactivation of nitric oxide synthase 2 (iNOS) and almost completely reversed in mice lacking both iNOS and phagocyte oxidase. Thus, a gene predicted to encode a key element of DNA repair is required for resistance of M. tuberculosis to both reactive nitrogen and reactive oxygen species in mice.
A new method for converting oxiranes to allylic alcohols by an organosilicon reagent (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA new method for converting oxiranes to allylic alcohols by an organosilicon reagentS. Murata, M. Suzuki, and R. NoyoriCite this: J. Am. Chem. Soc. 1979, 101, 10, 2738–2739Publication Date (Print):May 1, 1979Publication History Published online1 May 2002Published inissue 1 May 1979https://pubs.acs.org/doi/10.1021/ja00504a045https://doi.org/10.1021/ja00504a045research-articleACS PublicationsRequest reuse permissionsArticle Views1268Altmetric-Citations87LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
INTERACTIONS OF HORMONAL STEROIDS WITH NUCLEIC ACIDS, I. A SPECIFIC REQUIREMENT FOR GUANINE (1969)

Under equilibrium conditions testosterone, progesterone, estradiol, and corticosterone bind to denatured but not to native DNA. Among synthetic polynucleotides, steroids bind only to guanine containing polymers:poly dG, poly G, poly UG, poly AG, and "denatured" poly dG:dC; however, they do not bind to rRNA, sRNA, TMV-RNA, poly CG, or native poly dG:dC. These data indicate a preferential affinity for guanine residues and for single-stranded regions of polynucleotides. That different functional groups of the purine are involved in the associations with different steroids is indicated by the observation that only estradiol binds to poly I. Restrictions are also imposed by structural attributes of the steroids: an alpha-substitution at C-17 reduces binding, polyhydroxylated steroids bind poorly or not at all.
Meningoencephalitis associated with passive immunization of a transgenic murine model of Alzheimer's amyloidosis (2005)

Immunization against the Abeta peptide reverses the pathologic and behavioral manifestations of Alzheimer's disease in murine models. Since active immunization is associated with an autoimmune meningoencephalitis in a subset of humans, passive transfer of anti-Abeta immunoglobulin is being pursued as a potentially safer alternative. We have identified cases of meningoencephalitis subsequent to peripheral and intracerebral passive immunization of Tg2576 mice. The vasocentric mononuclear infiltrate localized only to brain regions affected by Abeta amyloid deposits suggesting that the inflammatory reaction was Abeta specific. This report indicates that current passive immunization in humans should proceed with careful regard for autoimmune complications.
Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (2006)

clinicaltrials.gov Identifier: NCT00006206.
Pharmacokinetics and absolute bioavailability of intramuscular tranexamic acid in man. (1985)

The bioavailability of tranexamic acid after the administration of a single intramuscular dose was estimated in three healthy male volunteers. 500 mg tranexamic acid were given intramuscularly and intravenously, as a bolus injection, to each subject on separate occasions. Following intramuscular administration, the peak plasma concentrations were attained after approximately one hour and the apparent elimination half-life was about two hours. The absolute bioavailability was 105.2 +/- 10.7% (mean +/- SD). At the dose given, the bioavailability of tranexamic acid after intramuscular administration is fast and complete.
Protein kinase C is activated in glomeruli from streptozotocin diabetic rats. Possible mediation by glucose. (1989)

Glomerular inositol content and the turnover of polyphosphoinositides was reduced by 58% in 1-2 wk streptozotocin diabetic rats. Addition of inositol to the incubation medium increased polyphosphoinositide turnover in glomeruli from diabetic rats to control values. Despite the reduction in inositol content and polyphosphoinositide turnover, protein kinase C was activated in glomeruli from diabetic rats, as assessed by an increase in the percentage of enzyme activity associated with the particulate cell fraction. Total protein kinase C activity was not different between glomeruli from control and diabetic rats. Treatment of diabetic rats with insulin to achieve near euglycemia prevented the increase in particulate protein kinase C. Moreover, incubation of glomeruli from control rats with glucose (100-1,000 mg/dl) resulted in a progressive increase in labeled diacylglycerol production and in the percentage of protein kinase C activity which was associated with the particulate fraction. These results support a role for hyperglycemia per se in the enhanced state of activation of protein kinase C seen in glomeruli from diabetic rats. Glucose did not appear to increase diacylglycerol by stimulating inositol phospholipid hydrolysis in glomeruli. Other pathways for diacylglycerol production, including de novo synthesis and phospholipase C mediated hydrolysis of phosphatidylcholine or phosphatidyl-inositol-glycan are not excluded.
Achieving the nitrite pathway using aeration phase length control and step‐feed in an SBR removing nutrients from abattoir wastewater (2008)

Aeration phase length control and step-feed of wastewater are used to achieve nitrogen removal from wastewater via nitrite in sequencing batch reactors (SBR). Aeration is switched off as soon as ammonia oxidation is completed, which is followed by the addition of a fraction of the wastewater that the SBR receives over a cycle to facilitate denitrification. The end-point of ammonia oxidation is detected from the on-line measured pH and oxygen uptake rate (OUR). The method was implemented in an SBR achieving biological nitrogen and phosphorus removal from anaerobically pre-treated abattoir wastewater. The degree of nitrite accumulation during the aeration period was monitored along with the variation in the nitrite oxidizing bacteria (NOB) population using fluorescence in situ hybridization (FISH) techniques. It is demonstrated that the nitrite pathway could be repeatedly and reliably achieved, which significantly reduced the carbon requirement for nutrient removal. Model-based studies show that the establishment of the nitrite pathway was primarily the result of a gradual reduction of the amount of nitrite that is available to provide energy for the growth of NOB, eventually leading to the elimination of NOB from the system.
Tracking interacting people (2002)

A computer vision system for tracking multiple people in relatively unconstrained environments is described. Tracking is performed at three levels of abstraction: regions, people and groups. A novel, adaptive background subtraction method that combines colour and gradient information is used to cope with shadows and unreliable colour cues. People are tracked through mutual occlusions as they form groups and part from one another. Strong use is made of colour information to disambiguate occlusions and to provide qualitative estimates of depth ordering and position during occlusion. Some simple interactions with objects can also be detected. The system is tested using indoor and outdoor sequences. It is robust and should provide a useful mechanism for bootstrapping and reinitialisation of tracking using more-specific but less-robust human models.
The genetic mediation of individual differences in sensitivity to pain and its inhibition (1999)

The underlying bases of the considerable interindividual variability in pain-related traits are starting to be revealed. Although the relative importance of genes versus experience in human pain perception remains unclear, rodent populations display large and heritable differences in both nociceptive and analgesic sensitivity. The identification and characterization of particularly divergent populations provides a powerful initial step in the genetic analysis of pain, because these models can be exploited to identify genes contributing to the behavior-level variability. Ultimately, DNA sequence differences representing the differential alleles at pain-relevant genes can be identified. Thus, by using a combination of "top-down" and "bottom-up" strategies, we are now able to genetically dissect even complex biological traits like pain. The present review summarizes the current progress toward these ends in both humans and rodents.
Simple Methods to Detect Triacylglycerol Biosynthesis in a Yeast‐Based Recombinant System (2009)

Standard methods to quantify the activity of triacylglycerol (TAG) synthesizing enzymes DGAT and PDAT (TAG-SE) require a sensitive but rather arduous laboratory assay based on radio-labeled substrates. Here we describe two straightforward methods to detect TAG production in baker's yeast Saccharomyces cerevisiae. First we demonstrate that a quadruple knockout yeast strain deficient in storage lipids has a reduced growth rate in a medium supplemented with fatty acids. This phenotype is rescued by restoring TAG biosynthesis and can be thus used to select yeast cells expressing a recombinant TAG-SE. In the second method, the activity of the recombinant enzyme is measured in a fluorescent in situ assay using Nile red dye that is specific for neutral lipids. Correlation between Nile red fluorescence and enzyme activity is demonstrated with several mutants of a TAG synthesizing enzyme. This yeast live-cell-based assay is rapid, inexpensive, sensitive, and is amenable to high-throughput applications. The methods can be used for a variety of applications such as isolation of novel genes, directed evolution, gene-specific drug screening and will facilitate novel approaches in the research of TAG-SE.
Herbicide Resistance and World Grains (2001)

Introduction and Review of Resistance, I. Heap and H. LeBaron Biochemical Mechanisms, Inheritance, and Molecular Genetics of Herbicide, Resistance in Weeds, C. Preston and C.A. Mallory-Smith The Population Dynamics and Genetics of Herbicide Resistance: A Modeling Approach, A.Diglle and P. Neve Herbicide Resistance and Its Management in World Maize and Soybean Ecosystems, M.D.K. Owen Herbicide Resistance and Its Management in World Wheat and Canola Ecosystems, D. Lemerle and D. Thill Herbicide Resistance and Its Management in World Rice Ecosystems, B.E. Valverde and K. Itoh Economic and Sociological Factors Affecting Growers Decision Making on Herbicide Resistance, D.J. Pannell and D. Zilberman Regulatory Aspects of Herbicide Resistance Management, D.L. Shaner and P. Leonard
Physical activity, skeletal health and fractures in a long term perspective. (2004)

Exercise during adolescence, especially during the pre-pubertal years, builds a skeleton with a high bone mineral density (BMD) and possibly a larger skeleton with a different skeletal architecture. This would lead to a stronger skeleton more resistant to trauma. These changes could be of biological significance for fracture reduction, if they were maintained into old age where fragility fractures exponentially rise. The Achilles heel of exercise is its cessation. Most BMD benefits achieved by exercise appear to be eroded with cessation of exercise. Reduced exercise intensity after a period of high activity, may maintain some residual BMD benefits into old age. A decreased fracture rate in the population could perhaps be achieved by promoting a physically active life style with lifelong high activity. But what happens if the activity in former athletes is reduced to the same level as in individuals who never exercised? The null hypothesis that exercise has no effect on fracture rates in old age cannot be rejected on the basis of any published, randomised, prospective data. Instead we have to rely on retrospective observational and case control studies, all hypothesis-generating, not hypothesis-testing. Existing data suggest that there could be a reduced fracture risk in former athletes. This notion may be correct, but consistently replicated sampling bias may produce the same observation and any biological explanation for this fracture reduction is unclear. Residual structural skeletal benefits, improved muscle strength, coordination and balance are all traits possibly maintained in former athletes after their active career. These traits may possibly reduce the number of fractures in later life.
A 50-Gb/s High-Sensitivity (−9.2 dBm) Low-Power (7.9 pJ/bit) Optical Receiver Based on 0.18-<inline-formula> <tex-math notation="LaTeX">$\mu$ </tex-math> </inline-formula>m SiGe BiCMOS Technology (2018)

A 50-Gb/s optical receiver (RX) based on 0.18-μm SiGe BiCMOS technology was fabricated and evaluated. To improve the horizontal eye opening and sensitivity of the RX without degrading its power efficiency, it is configured with a two-stage pre-amplifier with high gain (56 dBQ) and high bandwidth (35 GHz), a high-accuracy automatic decision-threshold control (ATC) consisting of power-supply variation and offset cancellers for improving sensitivity, and a jitter-reduction packaging structure for improving transimpedance flatness. The RX achieves high sensitivity of -9.2 dBm, while its power consumption is 7.9 pJ/bit at a data rate of 50 Gb/s. In 50and 56-Gb/s transmission tests through a 100-m multi-mode fiber (MMF), it demonstrated error-free operation at the bit error rate (BER) of less than 10-12 with the sensitivities of -9 and -6.1 dBm optical modulation amplitude (OMA). It also demonstrated 300-m error-free MMF transmission (at 50 Gb/s) with the practical sensitivity of -7.6 dBm OMA.
Soluble Biomarkers May Differentiate Psoriasis from Psoriatic Arthritis (2012)

Patients with psoriatic arthritis (PsA) have a higher inflammatory burden and poorer quality of life compared to patients with psoriasis without PsA. Early identification of PsA may prevent joint damage progression and improve quality of life. Soluble biomarkers have the potential to be useful for screening patients with psoriasis for underlying PsA so that appropriate referral to a rheumatologist is made. Pilot studies have shown that C-reactive protein, interleukin 6, cartilage oligomeric matrix protein (COMP), Dickkopf-1, and macrophage-colony stimulating factor may differentiate PsA from psoriasis without PsA. Compared with controls, increased serum levels of receptor activator of nuclear factor-κB ligand, tumor necrosis factor superfamily member 14, matrix metalloproteinase-3 (MMP-3), and COMP are independently associated with psoriatic disease. Increased levels of high-sensitivity CRP (hsCRP), osteoprotegerin (OPG), MMP-3, and the ratio of C-propeptide of type II collagen (CPII) to collagen fragment neoepitopes Col2-3/4 C(long mono) (C2C) are independently associated with PsA. A combination of hsCRP, OPG, MMP-3, and the ratio CPII of C2C was able to distinguish patients with PsA from those with psoriasis alone in a receiver-operating characteristic curve analysis, with area under the curve 0.904. Therefore, a combination of the above biomarkers may at least have a role in screening patients with psoriasis for PsA. These findings need to be validated in prospective studies.
Tissue‐specific expression of the human receptor for glucagon‐like peptide‐I: brain, heart and pancreatic forms have the same deduced amino acid sequences (1995)

Glucagon-like peptide-I(GLP-I), encoded by the glucagon gene and released from the gut in response to nutrients, is a potent stimulator of glucose-induced insulin secretion. In human subjects GLP-I exerts its physiological effect as an incretin. The incretin effect of GLP-I is preserved in patients with Type II diabetes mellitus (NIDDM), suggesting that GLP-I receptor agonist can be used therapeutically in this group of patients. In these studies we addressed the question of whether GLP-I has broader actions in human physiology. To investigate this issue we examined the tissue distribution of GLP-I receptor using RNAse protection assay in order to avoid the cross-reactivities with structurally related receptors and to increase the sensitivity of detection. The riboprobe was synthesized from the human pancreatic GLP-I receptor cDNA and used in hybridization experiments with total RNA isolated from different human tissues. In addition to the pancreas, we found expression of GLP-I receptor mRNA in lung, brain, kidney, stomach and heart. Peripheral tissues which are the major sites of glucose turnover, such as liver, skeletal muscle and adipose did not express the pancreatic form of the GLP-I receptor. We also cloned and sequenced GLP-I receptor cDNA from human brain and heart. The deduced amino acid sequences are the same as the sequence found in the pancreas. These results indicate that GLP-I might have effects beyond the pancreas, including the cardiovascular and central nervous systems where a receptor with the same ligand binding specificity is found.
Dynamic Fluorescence Spectroscopy on Single Tryptophan Mutants of EIImtl in Detergent Micelles. Effects of Substrate Binding and Phosphorylation on the Fluorescence and Anisotropy Decay (1997)

The effects of substrate and substrate analogue binding and phosphorylation on the conformational dynamics of the mannitol permease of Escherichia coli were investigated, using time-resolved fluorescence spectroscopy on mutants containing five single tryptophans situated in the membrane-embedded C domain of the enzyme [Swaving Dijkstra et al. (1996) Biochemistry 35, 6628-6634]. Since no fluorescent impurities are present in these mutants, the changes in fluorescence and anisotropy could be related with changes in the tryptophan microenvironment. Tryptophans at positions 30 and 42 showed changes in fluorescence intensity decay upon binding mannitol, which were reflected in the changes in lifetime distribution patterns. The disappearance of the shortest-lived decay component in these mutants, as well as in the mutant with a single tryptophan at position 109, indicates a change in the local environment such that quenching via neighboring side chains or solvent is reduced. Phosphorylation at histidine 554 and cysteine 384, located in the cytoplasmatic A and B domains of EII(mtl), respectively, induced an increase in the average fluorescence lifetimes of all of the tryptophans. The effect was most pronounced for tryptophans 30 and 109 which show large increases in the average fluorescence lifetime mainly due to loss of short-lived decay components. A correlation time distribution of the individual tryptophans deduced from an analysis of the anisotropy decay showed that they differed in their rotational mobility with tryptophan 30 showing the least local flexibility. Phosphorylation resulted in immobilization of W109 which, together with changes in the average fluorescence lifetime, is evidence for a conformational coupling between the phosphorylated B domain and the C domain. The influence of mannitol binding on the rotational behavior of the tryptophans is limited; it induces more internal flexibility at all tryptophan positions. A rotational correlation time of 30 ns was resolved for tryptophan 30, which probably represents a rotational mode of the micelle-embedded C-domain of EII(mtl) or a portion thereof. Upon phosphorylation, this rotational correlation time increases to 50 ns, probably reflecting a changed spatial orientation of W30 with respect to the C domain. Although kinetic experiments have shown that none of the tryptophans is essential for the catalytic activity of EII(mtl), it is significant that the residues most sensitive to mannitol binding, W30 and W42, are both located in the first membrane-spanning alpha-helix, a portion of which is highly conserved among mannitol-specific EII's of different bacteria.
Progress in use of carbon-black-polymer composite vapor detector arrays for land mine detection (2000)

Thin films of carbon black-organic polymer composites have been deposited across two metallic leads, with swelling- induced resistance changes of the films signaling the presence of vapors. To identify and classify vapors, arrays of such vapor sensing elements have been constructed. Each element contained a different organic polymer as the insulating phase. The differing gas-solid partition coefficients for the various polymers of the detector array produced a pattern of resistance changes that was used to classify vapors and vapor mixtures. The performance of this system towards DNT, the predominant signature in the vapor phase above land miens, has been evaluated in detail, with robust detection demonstrated in the laboratory in less than 5 s in air at DNT levels in the low ppb range.