gebhart/patrepeval huggingface dataset:
Progressive multifocal leukoencephalopathy diagnosed by amplification of JC virus-specific DNA from cerebrospinal fluid (1994)

PML can be diagnosed by PCR analysis of CSF. The sensitivity and specificity of the method depends on the sensitivity of the primers used for amplification. Using a primer pair from the large T gene, JCV-specific DNA was amplified in three cases with PML as early as the day of presentation with the first neurological symptom of PML.
Excitation of the Intrinsic Conduction System Through His and Interventricular Septal Pacing (2006)

This study has shown that LV activation patterns similar to sinus rhythm may be achieved without direct activation of the His bundle, while maintaining acceptable pacing and sensing performance. These data indicate that pacing systems designed to stimulate the tissues below the point at which the His bundle penetrates the central fibrous body may provide improved system efficiency and LV performance in comparison to both direct His bundle pacing and traditional pacing sites.
Novel SN-38–Incorporating Polymeric Micelles, NK012, Eradicate Vascular Endothelial Growth Factor–Secreting Bulky Tumors (2006)

7-Ethyl-10-hydroxy-camptothecin (SN-38), a biological active metabolite of irinotecan hydrochloride (CPT-11), has potent antitumor activity but has not been used clinically because it is a water-insoluble drug. For delivery by i.v. injection, we have successfully developed NK012, a SN-38-releasing nanodevice. The purpose of this study is to investigate the pharmacologic character of NK012 as an anticancer agent, especially in a vascular endothelial growth factor (VEGF)-secreting tumor model. The particle size of NK012 was approximately 20 nm with a narrow size distribution. NK012 exhibited a much higher cytotoxic effect against lung and colon cancer cell lines as compared with CPT-11. NK012 showed significantly potent antitumor activity against a human colorectal cancer HT-29 xenograft as compared with CPT-11. Enhanced and prolonged distribution of free SN-38 in the tumor was observed after the injection of NK012. NK012 also had significant antitumor activity against bulky SBC-3/Neo (1,533.1 +/- 1,204.7 mm(3)) and SBC-3/VEGF tumors (1,620.7 +/- 834.0 mm(3)) compared with CPT-11. Furthermore, NK012 eradicated bulky SBC-3/VEGF tumors in all mice but did not eradicate SBC-3/Neo tumors. In the drug distribution analysis, an increased accumulation of SN-38 in SBC-3/VEGF tumors was observed as compared with that in SBC-3/Neo tumors. NK012 markedly enhanced the antitumor activity of SN-38, especially in highly VEGF-secreting tumors, and could be a promising SN-38-based formulation.
Direct Analysis of CYP21B Genes in 21-Hydroxylase Deficiency using Polymerase Chain Reaction Amplification (1990)

Steroid 21-hydroxylase deficiency is the leading cause of impaired cortisol synthesis in congenital adrenal hyperplasia (CAH). We have studied the structure of the CYP21B gene in 30 unrelated CAH patients using the polymerase chain reaction (PCR) to differentiate the active CYP21B gene from its highly related CYP21A pseudogene. The PCR approach obviates the need to distinguish the CYP21A and CYP21B genes by restriction endonuclease digestion and electrophoresis before analysis with labeled probes. Furthermore, direct nucleotide sequence analysis of CYP21B genes is demonstrated on the PCR-amplified DNA. Gene deletion of CYP21B, gene conversion of the entire CYP21B gene to CYP21A, frame shift mutations in exon 3, an intron 2 mutation that causes abnormal RNA splicing, and a mutation leading to a stop codon in exon 8 appear to be the major abnormalities of the CYP21B gene in our patients. These mutations appear to account for 21-hydroxylase deficiency in 22 of 26 of our salt-wasting CAH patients.
Witnessing the truth (1996)

‘A camera in the right hands at the right time in the right place can be more powerful than tanks and guns’ Peter Gabriel announcing the ‘Witness Program’
Pathophysiology and diagnostic value of urinary trypsin inhibitors (2005)

Inflammation is an important indicator of tissue injury. In the acute form, there is usually accumulation of fluids and plasma components in the affected tissues. Platelet activation and the appearance in blood of abnormally increased numbers of polymorphonucleocytes, lymphocytes, plasma cells and macrophages usually occur. Infectious disorders such as sepsis, meningitis, respiratory infection, urinary tract infection, viral infection, and bacterial infection usually induce an inflammatory response. Chronic inflammation is often associated with diabetes mellitus, acute myocardial infarction, coronary artery disease, kidney diseases, and certain auto-immune disorders, such as rheumatoid arthritis, organ failures and other disorders with an inflammatory component or etiology. The disorder may occur before inflammation is apparent. Markers of inflammation such as C-reactive protein (CRP) and urinary trypsin inhibitors have changed our appraisal of acute events such as myocardial infarction; the infarct may be a response to acute infection and (or) inflammation. We describe here the pathophysiology of an anti-inflammatory agent termed urinary trypsin inhibitor (uTi). It is an important anti-inflammatory substance that is present in urine, blood and all organs. We also describe the anti-inflammatory agent bikunin, a selective inhibitor of serine proteases. The latter are important in modulating inflammatory events and even shutting them down.
Heterocyclic steroids: Synthesis of androsteno[17,16‐d]pyrazoles and androsteno[17,16‐e]pyrimidines (1995)

Abstract The Vilsmeier‐Haack reaction of 3β‐acetoxyandost‐5‐en‐17‐one ( 1 ) with phosporous oxychloride and dimethylformamide gave 3β‐acetoxy‐17‐chloro‐16‐formylandrosta‐5,16‐diene ( 2 ). Reaction of 2 with hydrazine and phenylhydrazine provided substituted 5‐androsteno[17,16‐ d ]pyrazoles 3 and 4 respectively. Similarly, condensation of 2 with urea and guanidine hydrochloride revealed the formation of the corresponding substituted pyrimidines 5 and 6 respectively.
Lagging strand maturation factor Dna2 is a component of the replication checkpoint initiation machinery (2013)

Initiation of the DNA replication checkpoint in yeast is mainly mediated by Mec1 protein kinase, the ortholog of human ATR, while its homolog Tel1, the ortholog of human ATM, has a minor replication checkpoint function. Checkpoint initiation requires stimulation of Mec1 kinase activity by specific activators. Saccharomyces cerevisiae Dna2, a nuclease-helicase that is essential for Okazaki fragment maturation, is employed specifically during S phase to stimulate Mec1 kinase and initiate the replication checkpoint. Mutations (W128A and Y130A) in the unstructured N terminus of Dna2 abrogate its checkpoint function in vitro and in vivo. Dna2 shows partial redundancy for the replication checkpoint with checkpoint initiators 9-1-1 (S. cerevisiae Ddc1-Mec3-Rad17 and human Rad9-Rad1-Hus1) and Dpb11, the ortholog of human TopBP1. A triple mutant that eliminates the checkpoint functions of all three initiators abrogates the Mec1-dependent checkpoint.
An Autoinhibitory Tyrosine Motif in the Cell-Cycle-Regulated Nek7 Kinase Is Released through Binding of Nek9 (2009)

Mitosis is controlled by multiple protein kinases, many of which are abnormally expressed in human cancers. Nek2, Nek6, Nek7, and Nek9 are NIMA-related kinases essential for proper mitotic progression. We determined the atomic structure of Nek7 and discovered an autoinhibited conformation that suggests a regulatory mechanism not previously described in kinases. Additionally, Nek2 adopts the same conformation when bound to a drug-like molecule. In both structures, a tyrosine side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix. Tyrosine mutants of Nek7 and the related kinase Nek6 are constitutively active. The activity of Nek6 and Nek7, but not the tyrosine mutant, is increased by interaction with the Nek9 noncatalytic C-terminal domain, suggesting a mechanism in which the tyrosine is released from its autoinhibitory position. The autoinhibitory conformation is common to three Neks and provides a potential target for selective kinase inhibitors.
Deep Blue: One Small Step for a Computer (1997)

Can a machine beat the human World Chess Champion in a match? This question had been around even before the existence of electronic computers, and the problem of creating such a computer had been one of the toughest problem in computer science. In 1996, Deep Blue proved that computers can beat the human World Chess Champion in a single game, and in May 1997, Deep Blue finally proved that computers can defeat the human World Chess Champion in a match. In this talk, we will go under the hood, and discuss the advances that make such a feat possible.
Notes (1942)

W. O. Kermack, A. P. Weatherhead, E. O. Walsh, F. E. King and T. J. King, J. Chem. Soc., 1942, 726 DOI: 10.1039/JR9420000726
Application of robust control to sustained oscillations in power systems (1992)

Transient control of the sustained oscillations that can occur after a major disturbance to a power system is investigated. A control scheme for an n-generator system is first developed using a classical machine model, and then extended to a machine model that includes governor/turbine dynamics. The proposed control strategies are linear and require only local relative angle and velocity measurements for the classical model case, plus the measurement of mechanical power if governor/turbine dynamics are included. Using Lyapunov's direct method, the control is shown to be robust with respect to parameter and load variations, and topology changes in the power system. The overall power system is shown to be exponentially stable in the main so that any oscillation, anywhere in the system, can be damped efficiently. The results are obtained without any linearization of the power system model. Simulation results for the 30-bus New England system demonstrate the effectiveness of the proposed control.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Selection of views to materialize in a data warehouse (2004)

A data warehouse stores materialized views of data from one or more sources, with the purpose of efficiently implementing decision-support or OLAP queries. One of the most important decisions in designing a data warehouse is the selection of materialized views to be maintained at the warehouse. The goal is to select an appropriate set of views that minimizes total query response time and the cost of maintaining the selected views, given a limited amount of resource, e.g., materialization time, storage space, etc. In This work, we have developed a theoretical framework for the general problem of selection of views in a data warehouse. We present polynomial-time heuristics for a selection of views to optimize total query response time under a disk-space constraint, for some important special cases of the general data warehouse scenario, viz.: 1) an AND view graph, where each query/view has a unique evaluation, e.g., when a multiple-query optimizer can be used to general a global evaluation plan for the queries, and 2) an OR view graph, in which any view can be computed from any one of its related views, e.g., data cubes. We present proofs showing that the algorithms are guaranteed to provide a solution that is fairly close to (within a constant factor ratio of) the optimal solution. We extend our heuristic to the general AND-OR view graphs. Finally, we address in detail the view-selection problem under the maintenance cost constraint and present provably competitive heuristics.
Specific Recruitment of Antigen-presenting Cells by Chemerin, a Novel Processed Ligand from Human Inflammatory Fluids (2003)

Dendritic cells (DCs) and macrophages are professional antigen-presenting cells (APCs) that play key roles in both innate and adaptive immunity. ChemR23 is an orphan G protein-coupled receptor related to chemokine receptors, which is expressed specifically in these cell types. Here we present the characterization of chemerin, a novel chemoattractant protein, which acts through ChemR23 and is abundant in a diverse set of human inflammatory fluids. Chemerin is secreted as a precursor of low biological activity, which upon proteolytic cleavage of its COOH-terminal domain, is converted into a potent and highly specific agonist of ChemR23, the chemerin receptor. Activation of chemerin receptor results in intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of p42-p44 MAP kinases, through the Gi class of heterotrimeric G proteins. Chemerin is structurally and evolutionary related to the cathelicidin precursors (antibacterial peptides), cystatins (cysteine protease inhibitors), and kininogens. Chemerin was shown to promote calcium mobilization and chemotaxis of immature DCs and macrophages in a ChemR23-dependent manner. Therefore, chemerin appears as a potent chemoattractant protein of a novel class, which requires proteolytic activation and is specific for APCs.
Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. (1978)

MRL/1 and BXSB male mice have a systemic lupus erythematosus (SLE)-like disease similar to but more acute than that occurring in NZB X W mice. The common elements of lymphoid hyperplasia, B-cell hyperactivity, autoantibodies, circulating immune complex (IC), complement consumption, IC glomerulonephritis with gp70 deposition, and thymic atrophy were found in all three kinds of SLE mice. On the basis of these common elements, SLE seen in these mice can be considered a single disease in the same sense that human SLE is one disease. The differences in the SLE expressed in the different mice are no greater than those found in an unselected series of humans with SLE. However, the significant quantitative and qualitative variations in abnormal immunologic expression suggest that different constellations of factors, genetic and/or pathophysiologic, may operate in the three murine strains and that each constellation is capable of leading, via its particular abnormal immunologic consequences, to the activation of common immunopathologic effector mechanisms that cause quite similar SLE-like syndromes. From an experimental point of view, the availability of several inbred murine strains of commonplace histocompatibility types that express an SLE-like syndrome makes possible innumerable manipulations which should help to elucidate the nature and cause(s) of this disorder.
Cellular effects of acute direct current stimulation: somatic and synaptic terminal effects (2013)

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique to modulate cortical excitability. Although increased/decreased excitability under the anode/cathode electrode is nominally associated with membrane depolarization/hyperpolarization, which cellular compartments (somas, dendrites, axons and their terminals) mediate changes in cortical excitability remains unaddressed. Here we consider the acute effects of DCS on excitatory synaptic efficacy. Using multi-scale computational models and rat cortical brain slices, we show the following. (1) Typical tDCS montages produce predominantly tangential (relative to the cortical surface) direction currents (4-12 times radial direction currents), even directly under electrodes. (2) Radial current flow (parallel to the somatodendritic axis) modulates synaptic efficacy consistent with somatic polarization, with depolarization facilitating synaptic efficacy. (3) Tangential current flow (perpendicular to the somatodendritic axis) modulates synaptic efficacy acutely (during stimulation) in an afferent pathway-specific manner that is consistent with terminal polarization, with hyperpolarization facilitating synaptic efficacy. (4) Maximal polarization during uniform DCS is expected at distal (the branch length is more than three times the membrane length constant) synaptic terminals, independent of and two-three times more susceptible than pyramidal neuron somas. We conclude that during acute DCS the cellular targets responsible for modulation of synaptic efficacy are concurrently somata and axon terminals, with the direction of cortical current flow determining the relative influence.
Cellular and molecular mechanisms in kidney fibrosis (2014)

Fibrosis is a characteristic feature of all forms of chronic kidney disease. Deposition of pathological matrix in the interstitial space and within the walls of glomerular capillaries as well as the cellular processes resulting in this deposition are increasingly recognized as important factors amplifying kidney injury and accelerating nephron demise. Recent insights into the cellular and molecular mechanisms of fibrogenesis herald the promise of new therapies to slow kidney disease progression. This review focuses on new findings that enhance understanding of cellular and molecular mechanisms of fibrosis, the characteristics of myofibroblasts, their progenitors, and molecular pathways regulating both fibrogenesis and its resolution.
A single-chip multiprocessor for multimedia: the MVP (1992)

The multimedia video processor (MVP) architecture, which incorporates a variety of parallel processing techniques to deliver very high performance to a wide range of imaging and graphics applications, is described. The MVP combines, on a single semiconductor chip, multiple fully programmable processors with multiple data streams connected to shared RAMs through a crossbar network. Each of the independent processors can execute many operations in parallel every cycle. The architecture is scalable and supports different numbers of processors to meet the cost and performance requirements of different markets. MVP's target environment and the development of MVP are outlined.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Enamel matrix proteins; old molecules for new applications (2009)

Emdogain (enamel matrix derivative, EMD) is well recognized in periodontology, where it is used as a local adjunct to periodontal surgery to stimulate regeneration of periodontal tissues lost to periodontal disease. The biological effect of EMD is through stimulation of local growth factor secretion and cytokine expression in the treated tissues, inducing a regenerative process that mimics odontogenesis. The major (>95%) component of EMD is Amelogenins (Amel). No other active components have so far been isolated from EMD, and several studies have shown that purified amelogenins can induce the same effect as the complete EMD. Amelogenins comprise a family of highly conserved extracellular matrix proteins derived from one gene. Amelogenin structure and function is evolutionary well conserved, suggesting a profound role in biomineralization and hard tissue formation. A special feature of amelogenins is that under physiological conditions the proteins self-assembles into nanospheres that constitute an extracellular matrix. In the body, this matrix is slowly digested by specific extracellular proteolytic enzymes (matrix metalloproteinase) in a controlled process, releasing bioactive peptides to the surrounding tissues for weeks after application. Based on clinical and experimental observations in periodontology indicating that amelogenins can have a significant positive influence on wound healing, bone formation and root resorption, several new applications for amelogenins have been suggested. New experiments now confirm that amelogenins have potential for being used also in the fields of endodontics, bone regeneration, implantology, traumatology, and wound care.
Comprehensive Survey of Combinatorial Library Synthesis:  1999 (2000)

ADVERTISEMENT RETURN TO ISSUEReviewNEXTComprehensive Survey of Combinatorial Library Synthesis: 1999Roland E. DolleView Author Information Department of Chemistry, Pharmacopeia, Inc., P.O. Box 5350, Princeton, New Jersey 08543-5350 Cite this: J. Comb. Chem. 2000, 2, 5, 383–433Publication Date (Web):September 12, 2000Publication History Received30 June 2000Published online12 September 2000Published inissue 1 September 2000https://pubs.acs.org/doi/10.1021/cc000055xhttps://doi.org/10.1021/cc000055xreview-articleACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views1116Altmetric-Citations143LEARN 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 options SUBJECTS:Inhibitors,Optimization,Organic polymers,Peptides and proteins,Receptors Get e-Alerts
Characterization of a newly identified ETV6-NTRK3 fusion transcript in acute myeloid leukemia (2011)

We have characterized a novel ETV6-NTRK3 fusion transcript which has not been previously described in AML FAB M0 by FISH and RACE PCR. ETV6-NTRK3 rearrangements have been described in secretory breast carcinoma and congenital fibrosarcoma.
Differential expression of microRNAs during melanoma progression: miR-200c, miR-205 and miR-211 are downregulated in melanoma and act as tumour suppressors (2012)

We have identified a series of differentially expressed miRNAs that could be useful as diagnostic or prognostic markers for melanoma and have shown that three miRNAs (namely miR-200c, miR-205 and miR-211) act as tumour suppressors.
A phase 1, randomized, placebo‐controlled, dose‐escalation study of an anti‐IL‐13 monoclonal antibody in healthy subjects and mild asthmatics (2012)

GSK679586 demonstrated dose-dependent pharmacological activity in the lungs of mild intermittent asthmatics. These findings, together with the favourable safety profile and advantageous PK characteristics of a monoclonal antibody (e.g. a long half-life supporting less frequent dosing), warrant further investigation of GSK679586 in a broader asthma patient population.