gebhart/patrepeval huggingface dataset:
Two-Component Signal Transduction (2000)

Most prokaryotic signal-transduction systems and a few eukaryotic pathways use phosphotransfer schemes involving two conserved components, a histidine protein kinase and a response regulator protein. The histidine protein kinase, which is regulated by environmental stimuli, autophosphorylates at a histidine residue, creating a high-energy phosphoryl group that is subsequently transferred to an aspartate residue in the response regulator protein. Phosphorylation induces a conformational change in the regulatory domain that results in activation of an associated domain that effects the response. The basic scheme is highly adaptable, and numerous variations have provided optimization within specific signaling systems. The domains of two-component proteins are modular and can be integrated into proteins and pathways in a variety of ways, but the core structures and activities are maintained. Thus detailed analyses of a relatively small number of representative proteins provide a foundation for understanding this large family of signaling proteins.
Beta-blocking agents in heart failure Should they be used and how? (1996)

Experience accumulated from several large trials strongly suggests that beta-blockers should be used for the management of chronic heart failure[87]. It is appropriate to add beta-blockade to conventional therapy such as diuretics, ACE inhibitors and digoxin, as this was the approach used in the major trials. It is appropriate to treat patients with mild, moderate and, when stable, severe chronic heart failure. The benefits obtained include improvements in left ventricular function, reductions in symptoms and morbidity, improvement of quality of life, and delay of clinical progression, reflected in a reduced need for cardiac transplantation and, probably, a reduction in mortality. beta-blockers are much better tolerated, when used appropriately in selected patients, than was previously supposed. To confirm the improvement in survival recently reported with carvedilol, further prospective trials using different beta-blockers are warranted. No major comparative trials have been carried out between beta-blockers in chronic heart failure, therefore it is not known whether the differences between them are clinically significant. The optimal dose of beta-blocker and the effect in patient groups excluded from or poorly represented in the clinical trials (e.g. elderly patients) have yet to be determined. Placebo-controlled mortality trials with bucindolol (BEST) and bisoprolol (CIBIS-II) are under way[89,90]. A large study of carvedilol versus metoprolol (COMET), added to conventional treatment, is planned.
A novel mutation in YARS2 causes myopathy with lactic acidosis and sideroblastic anemia (2012)

Mutations in the mitochondrial aminoacyl-tRNA synthetases (ARSs) are associated with a strikingly broad range of clinical phenotypes, the molecular basis for which remains obscure. Here, we report a novel missense mutation (c.137G>A, p.Gly46Asp) in the catalytic domain of YARS2, which codes for the mitochondrial tyrosyl-tRNA synthetase, in a subject with myopathy, lactic acidosis, and sideroblastic anemia (MLASA). YARS2 was undetectable by immunoblot analysis in subject myoblasts, resulting in a generalized mitochondrial translation defect. Retroviral expression of a wild-type YARS2 complementary DNA completely rescued the translation defect. We previously demonstrated that the respiratory chain defect in this subject was only present in fully differentiated muscle, and we show here that this likely reflects an increased requirement for YARS2 as muscle cells differentiate. An additional, heterozygous mutation was detected in TRMU/MTU1, a gene encoding the mitochondrial 2-thiouridylase. Although subject myoblasts and myotubes contained half the normal levels of TRMU, thiolation of mitochondrial tRNAs was normal. YARS2 eluted as part of high-molecular-weight complexes of ∼250 kDa and 1 MDa by gel filtration. This study confirms mutations in YARS2 as a cause of MLASA and shows that, like some of the cytoplasmic ARSs, mitochondrial ARSs occur in high-molecular-weight complexes.
The Search for Unrecognized Pathogens (1999)

The distribution and diversity of microorganisms in the world are far greater than have been previously appreciated. Molecular, cultivation-independent methods have played a key role in this insight. To what extent do humans remain ignorant of microbial diversity within the human body and the settings in which microorganisms cause human disease? In addition to implicating microbial agents in nontraditional infectious diseases, the use of methods such as broad-range polymerase chain reaction, representational difference analysis, expression library screening, and host gene expression profiling may force a reassessment of the concepts of microbial disease causation.
Insulin-Degrading Enzyme as a Downstream Target of Insulin Receptor Signaling Cascade: Implications for Alzheimer's Disease Intervention (2004)

Insulin-degrading enzyme (IDE) is one of the proteins that has been demonstrated to play a key role in degrading beta-amyloid (Abeta) monomer in vitro and in vivo, raising the possibility of upregulating IDE as an approach to reduce Abeta. Little is known, however, about the cellular and molecular regulation of IDE protein. Because one of the main functions of IDE is to degrade insulin, we hypothesized that there is a negative feedback mechanism whereby stimulation of insulin receptor-mediated signaling upregulates IDE to prevent chronic activation of the pathway. We show that treatment of primary hippocampal neurons with insulin increased IDE protein levels by approximately 25%. Insulin treatment also led to phosphatidylinositol-3 (PI3) kinase activation evidenced by Akt phosphorylation, which was blocked by PI3 kinase inhibitors, wortmannin and LY 294002. Inhibition of PI3 kinase abolished the IDE upregulation by insulin, indicating a cause-effect relationship between insulin signaling and IDE upregulation. Further support for this link was provided by the findings that deficient insulin signaling (decreased PI3 kinase subunit P85) was correlated with reduced IDE in Alzheimer's disease (AD) brains and in Tg2576 Swedish amyloid precursor protein transgenic mice fed a safflower oil-enriched ("Bad") diet used to accelerate pathogenesis. Consistent with IDE function in the degradation of Abeta monomer, the IDE decrease in the Bad diet-fed Tg2576 mice was associated with increased Abeta monomer levels. These in vitro and in vivo analyses validate the use of enhanced CNS insulin signaling as a potential strategy for AD intervention to correct the IDE defects occurring in AD.
Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma (2015)

The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice.
Oxygen requirements of yeasts (1990)

Type species of 75 yeast genera were examined for their ability to grow anaerobically in complex and mineral media. To define anaerobic conditions, we added a redox indicator, resazurin, to the media to determine low redox potentials. All strains tested were capable of fermenting glucose to ethanol in oxygen-limited shake-flask cultures, even those of species generally regarded as nonfermentative. However, only 23% of the yeast species tested grew under anaerobic conditions. A comparative study with a number of selected strains revealed that Saccharomyces cerevisiae stands out as a yeast capable of rapid growth at low redox potentials. Other yeasts, such as Torulaspora delbrueckii and Candida tropicalis, grew poorly mu max, 0.03 and 0.05 h-1, respectively) under anaerobic conditions in mineral medium supplemented with Tween 80 and ergosterol. The latter organisms grew rapidly under oxygen limitation and then displayed a high rate of alcoholic fermentation. It can be concluded that these yeasts have hitherto-unidentified oxygen requirements for growth.
Theoretical studies of a simulcast digital radio paging system using a carrier frequency offset strategy (1980)

In a multistation simulcast digital radio paging system, each base station transmits the same RF signal simultaneously with the resulting efficient frequency utilization and simplified receiver design. In this system a paging receiver in the overlapping area receives several RF signals transmitted from different base stations. When frequency-shift keying (FSK) is used as a modulation method, experimental test results have already shown that the timing of each RF signal should be synchronized as closely as possible, but that the carrier frequency of each transmitter should be set following a certain offset assignment. The signal transmission performance in a multipath fading environment can then be markedly improved. The cause of this improvement effect is theoretically analyzed. It is clarified that the improvement effect is caused by transforming the probability distribution of time-averaged signal power.
Stem cells as therapeutics for neurodegenerative disorders? (2001)

Aging is associated with a progressive increase in the risk of several prominent neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke and amyotrophic lateral sclerosis. In each of these disorders specific populations of neurons become dysfunctional, then die and are not replaced. The adult brain and spinal cord contain populations of so-called neural stem cells (self-renewing and multipotent) and neural precursor cells (specified to a certain fate, but still mitotic) that may provide a continuing source of new neurons and glial cells during successful aging and after injury to the nervous system. Recent studies have shown that stem cells from embryos and adults can be transplanted into the nervous system, differentiate into neurons and glia and restore lost function in experimental models of neurodegenerative diseases. Embryonic stem cells may be a particularly effective donor cell type for transplantation-based therapies. Efficacy of stem cell therapies remains to be established in clinical trials in humans. Another approach is to mobilize endogenous neural stem cells. Animals studies have shown that dietary and behavioral modifications can indeed stimulate neurogenesis. Molecular and cellular mechanisms that regulate the proliferation, differentiation and survival of neural stem cells and neural precursor cells are being elucidated and are revealing novel targets for the development of pharmaceuticals that promote neurogenesis.
Remission in rheumatoid arthritis: agreement of the disease activity score (DAS28) with the ARA preliminary remission criteria (2004)

DAS28 <2.6 corresponds to fulfilment of the preliminary ARA criteria for clinical remission in RA.
Organization and expression of the human myelin basic protein gene (1988)

The human brain contains four isoforms of myelin basic protein (MBP), previously identified by cDNA cloning. We have now isolated and characterized genomic clones encoding the human MBP gene. The gene is 45 kb in extent and consists of seven exons. Alternative splicing of the primary MBP transcript can account for all four human MBP isoforms. The intron-exon boundaries of the gene have also been determined, and all conform to the known consensus splice sequences. These sequences, however, do not explain the alternative splicing pattern found in human brain. Transcription of the human MBP gene begins at a single site within the MBP promoter, and all four MBP isoforms are transcribed from this same site. The promoter region does not contain any known sequence elements, but does have a 12-bp sequence also found in the JC virus 98-bp tandem repeat. A relative gradient of MBP transcription is found from caudal to rostral within the developing human brain, which parallels the known sequence of myelination found in these areas. RNase protection of brain RNA demonstrates more of the 21.5-kD and 20.5-kD MBP mRNAs in neonatal brain than in the adult frontal cortex, which suggests that alternative splicing of the primary MBP transcript is also regulated temporally during myelin development. These data show that regulation of myelination is complex, involving regional cellular interactions and trans activation of transcription, as well as modulation of alternative splicing. Comparison of the human and mouse data also suggests that alternative splicing plays an important role in myelin biogenesis.
EVIDENCE FOR MECHANOSENSITIVE TRANSMEMBRANE ION CHANNELS OF SMALL CONDUCTANCE IN MAGNETOTACTIC BACTERIA (2000)

To determine whether or not mechanosensitive (MS) ion channels are present in the magnetotactic bacterium Magnetospirillum magnetotacticum, techniques for spheroplast preparation in Escherichia coli were adapted for this bacterium. This resulted in the formation of 2–3-μm spheroplasts, which were used for patch clamp analysis. Ion channel activity in M. magnetotacticum was compared with that of the MS of small conductance (MscS) in E. coli. This comparison reveals the presence of MscS-like channels in M. magnetotacticum and, as this bacterium produces intracellular magnetite (Fe3O4) particles similar to those found in the human brain, provides a model for investigation of the effects of magnetic fields on MS ion channels in magnetite-bearing cells.
A Spectrally Efficient PMR System Utilizing Broadcast Service (2005)

Different trunked Private Mobile Radio (PMR) systems have been designed over the last several decades, all of which have symmetric downlink and uplink channel capacities. Due to this symmetry, these systems may not be spectrally efficient in case of different types of services, which are specific to PMR systems, such as group and broadcast calls. In this study, a new asymmetric trunked PMR system comprising a broadband, wide-area downlink and a narrowband cellular uplink, is proposed to achieve a higher spectral efficiency than current digital trunked PMR systems. This system is spectrally more efficient because in group and broadcast calls only a single downlink channel has to be allocated in the downlink part. However, as the number of clusters in the system increases, this advantage relative to PMR systems is lost, since the latter can employ frequency reuse. Spectral efficiency of the proposed asymmetric system (a-PMR) system and a standard TETRA system are compared using numerical case studies against different traffic loads and number of clusters. The optimum point, with respect to number of clusters, up to which the proposed a-PMR system is more efficient, is determined. It is shown that a very large PMR user population can be efficiently served using the proposed a-PMR system. The issues related to implementing such a system are discussed.
Spreading sequence selection scheme for NBI suppression IN DS-UWB systems (2010)

Interference suppression is important for the ultra-wideband (UWB) systems to operate over spectrum occupied by pre-existing narrowband systems. In this paper, a spreading sequence selection scheme is proposed for code-aided interference suppression in direct-sequence UWB (DS-UWB) systems. Compared with a randomly selected spreading sequence, the presented scheme can ensure the system achieves suboptimal performance. Compared with our recently proposed eigenvector sign (EVS) spreading sequence, an equalizer can be avoided for high speed application by using the selected spreading sequence, which reduces the complexity of system implementation.
Activity tracking (2015)

Activity trackers are increasingly popular, but they have high levels of abandonment and little evidence exists to suggest why this is. This paper explores barriers to engagement with activity trackers. We extend previous research by not only characterising the barriers users experienced, such as tracking accuracy and device aesthetics, but also by reporting the workarounds they created. We discuss implications for the design of activity tracking systems by reflecting on these workarounds, the potential for activity tracker design to help overcome existing barriers, and how customisation could play a role.
Electrophilic Perfluoroalkylating Agents (1996)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrophilic Perfluoroalkylating AgentsTeruo UmemotoView Author Information MEC Laboratory, Daikin Industries, Ltd., Miyukigaoka 3, Tsukuba, Ibaraki 305, Japan Cite this: Chem. Rev. 1996, 96, 5, 1757–1778Publication Date (Web):August 1, 1996Publication History Received21 December 1995Revised9 May 1996Published online1 August 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/cr941149uhttps://doi.org/10.1021/cr941149uresearch-articleACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views7145Altmetric-Citations531LEARN 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 SUBJECTS:Alkyls,Anions,Aromatic compounds,Reagents,Salts Get e-Alerts
High‐dose cytarabine induction is well tolerated and active in patients with de novo acute myeloid leukemia older than 60 years (2011)

The modified HiDAC regimen was well tolerated in patients aged >60 years with AML and was associated with low induction mortality and high rates of CR. Nevertheless, these high remissions still were associated with poor overall outcomes.
Neuroimmunomodulation in medical oncology: application of psychoneuroimmunology with subcutaneous low-dose IL-2 and the pineal hormone melatonin in patients with untreatable metastatic solid tumors. (2008)

The administration of IL-2 and the pineal hormone MLT may induce control of neolplastic growth and a prolonged survival time in patients with metastatic solid tumors, for whom no other conventional anticancer therapy is available.
DNA−TiO2 Nanoconjugates Labeled with Magnetic Resonance Contrast Agents (2007)

Recent efforts have shown that nanoscale materials, specifically, metal-based nanoparticles, hold particular promise for the development of multifunctional imaging probes. These new materials provide the means to chaperone and concentrate both drugs and contrast agents in specific organs, tissues, and cells. Therefore, we have prepared a Gd(III)-modified DNA-TiO2 semiconducting nanoparticle that is detectable in cells by MR imaging. These labeled particles are retained at specific subcellular locations via DNA hybridization to intracellular targets, hence creating the first nanoparticle system capable of targeting specific DNA sequences while being simultaneously detected via MR imaging.
Lymphocyte membrane potential and Ca2+‐sensitive potassium channels described by oxonol dye fluorescence measurements (1985)

A method is described for quantitative measurement of lymphocyte transmembrane electrical potential difference (psi) by flow cytometric recording of the oxonol dye fluorescence of single cells. Both the simultaneous collection and analysis of multiple optical parameters and the use of a negatively charged oxonol probe allowed more accurate measurement of psi than may be obtained by bulk cell suspension techniques employing cationic voltage indicators. Mouse spleen and human blood lymphocyte psi was calculated to be -70 mV. T and B lymphocytes maintain a constant psi as extracellular K+ is varied from 2 to 10 mM and the deviation from K+ equilibrium potentials (EK) is shown to result from Na+ permeability. At [K+]o values greater than 10 mM, lymphocytes behave as K+ electrodes. Examination of lymphocyte subsets showed that hyperpolarization induced by the Ca2+ ionophore A23187 occurs only in T cells. This response was identified as activation of a Ca2+-sensitive K+ channel by pharmacologic manipulations. Hence, T cells depolarized by 4-aminopyridine (4-AP, 10 mM) were observed to return to resting psi by A23187-induced elevation of [Ca2+]i. Cells depolarized by quinine (100 microM) were unaffected by A23187. The Ca2+-activated channel does not contribute to resting psi in T cells since it may be selectively blocked by quinine (20 microM) or modulated by calmodulin antagonists (5 microM trifluperazine) without affecting resting psi.
Genomic and bioinformatic profiling of mutational neoepitopes reveals new rules to predict anticancer immunogenicity (2014)

The mutational repertoire of cancers creates the neoepitopes that make cancers immunogenic. Here, we introduce two novel tools that identify, with relatively high accuracy, the small proportion of neoepitopes (among the hundreds of potential neoepitopes) that protect the host through an antitumor T cell response. The two tools consist of (a) the numerical difference in NetMHC scores between the mutated sequences and their unmutated counterparts, termed the differential agretopic index, and (b) the conformational stability of the MHC I-peptide interaction. Mechanistically, these tools identify neoepitopes that are mutated to create new anchor residues for MHC binding, and render the overall peptide more rigid. Surprisingly, the protective neoepitopes identified here elicit CD8-dependent immunity, even though their affinity for K(d) is orders of magnitude lower than the 500-nM threshold considered reasonable for such interactions. These results greatly expand the universe of target cancer antigens and identify new tools for human cancer immunotherapy.
Cellular Control of the Synthesis and Activity of the Bacterial Luminescent System (1970)

In bioluminescent bacteria growing in shake flasks, the enzyme luciferase has been shown to be synthesized in a relatively short burst during the period of exponential growth. The luciferase gene appears to be completely inactive in a freshly inoculated culture; the pulse of preferential luciferase synthesis which occurs later is the consequence of its activation at the level of deoxyribonucleic acid transcription which is attributed to an effect of a "conditioning" of the medium by the growing of cells. Although cells grown in a minimal medium also exhibit a similar burst of synthesis of the luminescent system, the amount of synthesis is quantitatively less, relative to cell mass. Under such conditions, added arginine results in a striking stimulation of bioluminescence. This is attributed to a stimulation of existing patterns of synthesis and not to induction or derepression per se.
Cardiovascular disease and long-chain omega-3 fatty acids (2003)

Current evidence suggests that individuals with coronary artery disease may reduce their risk of sudden cardiac death by increasing their intake of long-chain omega-3 fatty acids by approximately 1 g per day.
Expression of glial cell line‐derived neurotrophic factor correlates with perineural invasion of bile duct carcinoma (2001)

The results suggest that GDNF expression in tumor cells and GFRalpha1 and RET expression in peripheral nerve tissues may play a role in perineural invasion in patients with bile duct carcinoma through chemoattraction among these molecules.