gebhart/patrepeval huggingface dataset:
Synthesis and Conformational Analysis of a Non-Amidine Factor Xa Inhibitor That Incorporates 5-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine as S4 Binding Element (2004)

Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expected to be S4 binding element. Among this series, 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine type 61 displayed orally potent anti-fXa activity and evident prolongation of prothrombin time (PT) with the moderate bioavailability in rats. The X-ray crystal analysis afforded an obvious binding mode that 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine and 6-chloronaphthalene respectively bound to S4 and S1 subsites. In this X-ray study, we discovered a novel intramolecular S-O close contact. Ab initio energy calculations of model compounds deduced that conformers with the most close S-O proximity were most stable. The Mulliken population analysis proposed that this energy profile was caused by both of electrostatic S-O affinity and N-O repulsion. The results of these calculations and X-ray analysis suggested a possibility that the restricted conformation effected the affinity to S4 subsite of fXa.
Symptoms and Signs of Chronic Fatigue Syndrome (1991)

This review summarizes the symptoms and signs seen in patients with chronic fatigue syndrome (CFS). It is based on the authors' experience with two cohorts of approximately 510 patients with chronic debilitating fatigue and on the reported experience of other investigators with similar patients. The most characteristic symptoms of CFS are the sudden onset of an infectious-type illness, the subsequent chronic and debilitating fatigue, and postexertional malaise; many patients also have recurrent fevers, pharyngitis, adenopathy, myalgias, sleep disorders, and cognitive impairment.
Early detection of disease outbreaks using the Internet (2009)

Rapidly identifying an infectious disease outbreak is critical, both for effective initiation of public health intervention measures and timely alerting of government agencies and the general public. Surveillance capacity for such detection can be costly, and many countries lack the public health
Assessment of self‐selection bias in a pediatric unilateral hearing loss study (2010)

Self-selection bias may jeopardize both internal and external validity of study results and should be evaluated whenever possible. Methods to minimize self-selection bias should be considered and implemented during the planning stages of clinical studies.
"Son-Go-Ku": A dream of automated library. (1989)

図書館を自動化する過程で, 本を眺め見て検索することが見落とされている。テレマティーク図書館は, 眺め見るプロセスをまねることによって, 本の内容までサービスできる本のDBMSである。検索は, 実際に人が本物の図書館で本を選ぶときのプロセスをまねた, グラフィックディスプレイに表示された映像で表される。1988年に試作した実験的検索システム「孫悟空」の特徴について述べる。
Neuregulin-1 attenuated doxorubicin-induced decrease in cardiac troponins (2009)

Neuregulin-1 (NRG1) is a potential therapeutic agent for the treatment of doxorubicin (Dox)-induced heart failure. NRG1, however, activates the erbB2 receptor, which is frequently overexpressed in breast cancers. It is, therefore, important to understand how NRG1, via erbB2, protects the heart against Dox cardiotoxicity. Here, we studied NRG1-erbB2 signaling in Dox-treated mice hearts and in isolated neonatal rat ventricular myocytes (NRVM). Male C57BL/6 mice were treated with recombinant NRG1 before and daily after a single dose of Dox. Cardiac function was determined by catheterization. Two-week survival was analyzed by the Kaplan-Meier method. Cardiac troponins [cardiac troponin I (cTnI) and cardiac troponin T (cTnT)] and phosphorylated Akt protein levels were determined in mice hearts and in NRVM by Western blot analysis. Activation of caspases and ubiquitinylation of troponins were determined in NRVM by caspase assay and immunoprecipitation. NRG1 significantly improved survival and cardiac function in Dox-treated mice. NRG1 reduced the decrease in cTnI, cTnT, and cardiac troponin C (cTnC) and maintained Akt phosphorylation in Dox-treated mice hearts. NRG1 reduced the decrease in cTnI and cTnT mRNA and proteins in Dox-treated NRVM. Inhibition of erbB2, phosphoinositide 3-kinase (PI3K), Akt, and mTOR blocked the protective effects of NRG1 on cTnI and cTnT in NRVM. NRG1 significantly reduced Dox-induced caspase activation, which degraded troponins, in NRVM. NRG1 reduced Dox-induced proteasome degradation of cTnI. NRG1 attenuates Dox-induced decrease in cardiac troponins by increasing transcription and translation and by inhibiting caspase activation and proteasome degradation of troponin proteins. NRG1 maintains cardiac troponins by the erbB2-PI3K pathway, which may lessen Dox-induced cardiac dysfunction.
Dendritic Cells Accumulate in Human Fibrotic Interstitial Lung Disease (2007)

These findings suggest that resident cells in pulmonary fibrosis can sustain chronic inflammation by driving the accumulation of DCs with the potential to mature locally within ectopic lymphoid follicles. Future strategies should consider DCs or chemokines as therapeutic targets in the treatment of pulmonary fibrosis.
ChemInform Abstract: Reaction of Triafulvenes with Isonitriles. A Simple Synthesis of Diphenyl Substituted Functionalized Cyclobutene Derivatives and Related Products. (1987)

Abstract Reaction of the triafulvenes (I) with the isonitriles (II) yields the cyclobuteneimines (III) which are hydrolyzed to give the cyclobutenones (IV).
Standardized image interpretation and post processing in cardiovascular magnetic resonance: Society for Cardiovascular Magnetic Resonance (SCMR) Board of Trustees Task Force on Standardized Post Processing (2013)

With mounting data on its accuracy and prognostic value, cardiovascular magnetic resonance (CMR) is becoming an increasingly important diagnostic tool with growing utility in clinical routine. Given its versatility and wide range of quantitative parameters, however, agreement on specific standards for the interpretation and post-processing of CMR studies is required to ensure consistent quality and reproducibility of CMR reports. This document addresses this need by providing consensus recommendations developed by the Task Force for Post-Processing of the Society for Cardiovascular Magnetic Resonance (SCMR). The aim of the Task Force is to recommend requirements and standards for image interpretation and post-processing enabling qualitative and quantitative evaluation of CMR images. Furthermore, pitfalls of CMR image analysis are discussed where appropriate. It is an update of the original recommendations published 2013.
Beyond bottom-up: Incorporating task-dependent influences into a computational model of spatial attention (2007)

A critical function in both machine vision and biological vision systems is attentional selection of scene regions worthy of further analysis by higher-level processes such as object recognition. Here we present the first model of spatial attention that (1) can be applied to arbitrary static and dynamic image sequences with interactive tasks and (2) combines a general computational implementation of both bottom-up (BU) saliency and dynamic top-down (TD) task relevance; the claimed novelty lies in the combination of these elements and in the fully computational nature of the model. The BU component computes a saliency map from 12 low-level multi-scale visual features. The TD component computes a low-level signature of the entire image, and learns to associate different classes of signatures with the different gaze patterns recorded from human subjects performing a task of interest. We measured the ability of this model to predict the eye movements of people playing contemporary video games. We found that the TD model alone predicts where humans look about twice as well as does the BU model alone; in addition, a combined BU*TD model performs significantly better than either individual component. Qualitatively, the combined model predicts some easy-to-describe but hard-to-compute aspects of attentional selection, such as shifting attention leftward when approaching a left turn along a racing track. Thus, our study demonstrates the advantages of integrating BU factors derived from a saliency map and TD factors learned from image and task contexts in predicting where humans look while performing complex visually-guided behavior.
Sufentanil Citrate: A New Opioid Analgesic for Use in Anesthesia (1984)

Sufentanil citrate is a potent analogue of fentanyl that has been evaluated primarily for use in opioid anesthesia. It is a pure mu receptor agonist and produces the typical spectrum of opioid effects. The major side effects are truncal rigidity and prolonged respiratory depression. In doses of 4-30 micrograms/kg sufentanil produces hypnosis and suppresses most hemodynamic and hormonal responses to surgery without producing significant cardiovascular depression. In this respect sufentanil and fentanyl have clear advantages over morphine, meperidine and potent inhalation anesthetics. Compared to fentanyl, sufentanil has a more rapid onset and shorter duration of action. The relatively high concentration of commercially available sufentanil injection will make it much more convenient for its intended application than fentanyl injection. This new agent will be used primarily for open-heart surgery and major operations in patients with severe cardiovascular compromise.
Hsp70 Reduces α-Synuclein Aggregation and Toxicity (2004)

Aggregation and cytotoxicity of misfolded alpha-synuclein is postulated to be crucial in the disease process of neurodegenerative disorders such as Parkinson's disease and DLB (dementia with Lewy bodies). In this study, we detected misfolded and aggregated alpha-synuclein in a Triton X-100 insoluble fraction as well as a high molecular weight product by gel electrophoresis of temporal neocortex from DLB patients but not from controls. We also found similar Triton X-100 insoluble forms of alpha-synuclein in an alpha-synuclein transgenic mouse model and in an in vitro model of alpha-synuclein aggregation. Introducing the molecular chaperone Hsp70 into the in vivo model by breeding alpha-synuclein transgenic mice with Hsp70-overexpressing mice led to a significant reduction in both the high molecular weight and detergent-insoluble alpha-synuclein species. Concomitantly, we found that Hsp70 overexpression in vitro similarly reduced detergent-insoluble alpha-synuclein species and protected cells from alpha-synuclein-induced cellular toxicity. Taken together, these data demonstrate that the molecular chaperone Hsp70 can reduce the amount of misfolded, aggregated alpha-synuclein species in vivo and in vitro and protect it from alpha-synuclein-dependent toxicity.
Proteomics studies of pancreatic cancer (2007)

Pancreatic cancer is the fourth leading cause of cancer death in the United States, with 4% survival 5 years after diagnosis. Biomarkers are desperately needed to improve earlier, more curable cancer diagnosis and to develop new effective therapeutic targets. The development of quantitative proteomics technologies in recent years offers great promise for understanding the complex molecular events of tumorigenesis at the protein level, and has stimulated great interest in applying the technology for pancreatic cancer studies. Proteomic studies of pancreatic tissues, juice, serum/plasma, and cell lines have recently attempted to identify differentially expressed proteins in pancreatic cancer to dissect the abnormal signaling pathways underlying oncogenesis, and to detect new biomarkers. It can be expected that the continuing evolution of proteomics technology with better resolution and sensitivity will greatly enhance our capability in combating pancreatic cancer.
MANNING THE ROYAL NAVY: THE REFORM OF THE RECRUITING SYSTEM, 1852–1862 (1958)

(1958). MANNING THE ROYAL NAVY: THE REFORM OF THE RECRUITING SYSTEM, 1852–1862. The Mariner's Mirror: Vol. 44, No. 4, pp. 302-313.
Negative Refraction Makes a Perfect Lens (2000)

With a conventional lens sharpness of the image is always limited by the wavelength of light. An unconventional alternative to a lens, a slab of negative refractive index material, has the power to focus all Fourier components of a 2D image, even those that do not propagate in a radiative manner. Such ``superlenses'' can be realized in the microwave band with current technology. Our simulations show that a version of the lens operating at the frequency of visible light can be realized in the form of a thin slab of silver. This optical version resolves objects only a few nanometers across.
A Nearly Planar Water Sheet Sandwiched between Strontium−Imidazolium Carboxylate Coordination Polymers (2005)

The crystal structure of a strontium-imidazolium polymeric material obtained from the reaction of zwitterionic 1,3-bis(carboxymethyl)imidazolium with SrCO(3) (2:1) in water is reported. The compound crystallized in the orthorhombic space group Pcc2 with a = 14.545(3) A, b = 8.514(5) A, c = 8.5619(14) A, V = 1060.2(6) A(3), and Z = 2. The macromolecular structure is constructed from 8-coordinate strontium, which binds to six different imidazolium carboxylate molecules. The two-dimensional polymer is separated by water sheets in which the water molecules form near-planar hexagons.
Five‐year experience with incobotulinumtoxinA (Xeomin®): the first botulinum toxin drug free of complexing proteins (2011)

In 2005, incobotulinumtoxinA (Xeomin ® ), a new botulinum toxin (BT) type A drug without complexing proteins (CPs), became available. This paper reviews the specific features of Xeomin ® and the experience gathered with it during the last 5 years. Compared with conventional BT drugs, Xeomin ® ’s extended shelf live and its simplified temperature restrictions indicate that CPs are not necessary for BT drug stability. Its reduced molecular size does not translate into diffusion differences, and its potency labelling is identical to that of onabotulinumtoxinA (Botox ® ). With a reduced content of inactivated botulinum neurotoxin, Xeomin ® should have reduced antigenicity. Lack of CP’s may further reduce antigenicity. Xeomin ® ’s therapeutic efficacy against cervical dystonia, blepharospasm and spasticity has been proven in large randomised, double‐blind and placebo‐controlled studies leading to registrations in many countries. Additional successful clinical use in axillary hyperhidrosis, hemifacial spasm, re‐innervation synkinesias and hypersalivation as well as in dystonia and spasticity in extended doses and throughout extended observation periods has been documented meanwhile. Lack of reported cases of antibody‐induced therapy failure (ABF), as to date, support the hypothesis of an improved antigenicity.
Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors (1989)

A novel class of low molecular weight protein tyrosine kinase inhibitors is described. These compounds constitute a systematic series of molecules with a progressive increase in affinity toward the substrate site of the EGF receptor kinase domain. These competitive inhibitors also effectively block the EGF-dependent autophosphorylation of the receptor. The potent EGF receptor kinase blockers examined were found to competitively inhibit the homologous insulin receptor kinase at 10(2)-10(3) higher inhibitor concentrations in spite of the significant homology between these protein tyrosine kinases. These results demonstrate the ability to synthesize selective tyrosine kinase inhibitors. The most potent EGF receptor kinase inhibitors also inhibit the EGF-dependent proliferation of A431/clone 15 cells with little or no effect on EGF independent cell growth. These results demonstrate the potential use of protein tyrosine kinase inhibitors as selective antiproliferative agents for proliferative diseases caused by the hyperactivity of protein tyrosine kinases. We have suggested the name "tyrphostins" for this class of antiproliferative compounds which act as protein tyrosine kinase blockers.
Complex cardiac Nkx2-5 gene expression activated by noggin-sensitive enhancers followed by chamber-specific modules (2005)

We previously reported that an Nkx2-5-GFP bacterial artificial chromosome in transgenic mice recapitulated the endogenous gene activity in the heart. Here, we identified three additional previously uncharacterized distal enhancer modules of Nkx2-5: UH6, which directed transgene expression in the right ventricle, interventricular septum, and atrial ventricular canal; UH5, which directed expression in both atria; and UH4, which directed transgene expression in tongue muscle. Nkx2-5 enhancers drive cardiogenic gene activity from the earliest progenitors to the late-stage embryonic heart, reside within its 27 kb of 5' flanking sequences, organized in a tandem array. Nkx2-5 enhancers involved with stomach-, tongue-, and chamber-restricted expression displayed lacZ transgene activity and chromatin histone acetylation patterns consistent with tissue-specific expression. An examination of Nkx2-5 gene activity in murine embryonic stem cells converted to beating embryoid bodies showed that only the proximal active region 2 and GATA-Smad enhancers were chromatin-remodeled. Chromatin remodeling of active region 2 and GATA-Smad enhancers were blunted by noggin coexpression, which indicated dependence on bone morphogenetic protein signaling for their chromatin activation during activation of Nkx2-5 expression.
Rational Design of Cesium‐Selective Ionophores: Dihydrocalix[4]arene Crown‐6 Ethers (2003)

Abstract Molecular mechanics calculations performed on calix[4]arene crown‐6 ethers predict that the 1,3‐dihydro derivatives will exhibit greater complementarity for potassium and cesium ions than the parent 1,3‐bis(alkyloxy) calixcrowns. The X‐ray crystal structures of 1,3‐ alt ‐bis(octyloxy)calix[4]arene benzocrown‐6 ether, dihydrocalix[4]arene benzocrown‐6 ether, and the cesium nitrate complex of dihydrocalix[4]arene benzocrown‐6 ether were determined. The structure of the cesium complex corresponds closely to the structure predicted by molecular mechanics. The dihydrocalix[4]arene crown‐6 ethers exhibit enhanced cesium selectivity in the extraction of alkali‐metal salts. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)
Interleukin‐4 but not interleukin‐10 inhibits the production of leukemia inhibitory factor by rheumatoid synovium and synoviocytes (1994)

The expression of the proinflammatory cytokine leukemia inhibitory factor (LIF) has been reported in the cartilage and synovium of rheumatoid arthritis (RA) patients. Here, we show that high levels of LIF were constitutively produced by cultures of synovium pieces. Low levels of LIF were produced spontaneously by isolated synoviocytes, but interleukin (IL)-1 beta caused a fourfold enhancement of this secretion. The anti-inflammatory cytokine IL-4 reduced the production of LIF by synovium pieces by 75%, as observed earlier with IL-6, IL-1 beta and tumor necrosis factor (TNF)-alpha. IL-4 had a direct effect since it inhibited LIF production by unstimulated and IL-1 beta- or TNF-alpha-stimulated synoviocytes. Conversely, IL-4 enhanced the production of IL-6, which shares with LIF biological activities and receptor components. The inhibitory effect of IL-4 was dose dependent and was reversed using a blocking anti-IL-4 receptor antibody. Similar inhibitory action of IL-4 on LIF production was observed on synovium pieces from patients with osteoarthritis and on normal synoviocytes. IL-10, another anti-inflammatory cytokine acting on monocytes, had no effect on LIF production by either synovium pieces or isolated synoviocytes. Thus, the production of LIF by synovium tissue was inhibited by IL-4 through both a direct effect on synoviocytes and an indirect effect by inhibition of the production of LIF-inducing cytokines.
Structural Study of the Li–Mn–Ni Oxide Pseudoternary System of Interest for Positive Electrodes of Li-Ion Batteries (2013)

Solution-based combinatorial samples of lithium manganese nickel oxide were synthesized and studied by X-ray diffraction in order to map out the entire pseudoternary system. The samples were made by heating to 800 °C in an oxygen atmosphere, and two cooling methods were tested: quenching and a slower cooling rate. This article focuses on the areas of the Gibbs triangle that lie between the layered and spinel structures as well as the single-phase layered region. The layered region is much larger than previously reported in the literature, and lattice parameters throughout the solid solution are reported. The complex coexistence region includes a two-phase region as well as two 3-phase regions. Supporting evidence demonstrating the 3-phase regions and careful identification of their corners is included here. The 3-phase regions also undergo a transformation during slow cooling that can be attributed to high entropy phases no longer being favored. In order to confirm that the findings for the small combinatorial samples are relevant to bulk samples, we present XRD patterns from a few bulk samples synthesized in oxygen as well as some heated in air. The results show that though the boundaries in the phase diagram move with synthesis conditions, the main features of the coexistence regions remain the same.
Complete Electrolysis Using a Microflow Cell with an Oil/Water Interface (2002)

A novel microflow cell with a nitrobenzene (NB)/water (W) interface was developed. A poly(tetrafluoroethylene) membrane filter was employed to prepare the NB/W interface which was formed over a thin channel (0.1 mm thick, 48 cm long) on a silver plate. The silver plate was electrolyzed in advance and served as an Ag/AgCl electrode for controlling the Galvani potential difference across the NB/W interface as well as detecting the current flowing through the interface. Using the microflow cell, complete electrolysis was accomplished for the interfacial transfer of a representative ion (i.e., tetramethylammonium ion). Thus, the present microflow cell was shown to be promising for coulometric (i.e., absolute quantitative) analysis of ions. Also, the microflow cell was shown to be useful for determination of the number of electrons for complicated charge-transfer processes at the oil/water interface.
Competition for p300 Regulates Transcription by Estrogen Receptors and Nuclear Factor-κB in Human Coronary Smooth Muscle Cells (2000)

Previous studies suggest that estrogen may prevent expression of cell adhesion molecules implicated in vascular inflammation associated with atherosclerosis. We demonstrate the interaction and reciprocal interference of estrogen receptors (ERs) with p65, the nuclear factor-kappaB component, in smooth muscle cells that express ERalpha and ERss after exposure to 17ss-estradiol for 48 to 72 hours. ER and p65 do not associate directly, as shown by lack of coprecipitation, but instead compete for limiting amounts of p300, a close relative of the CREB-binding protein. Overexpressed p300 significantly reduced the inhibitory effect of ER on p65-dependent transcription as well as the inhibitory effect of p65 on ER-dependent transcription. These actions were ligand-dependent. The expression of both ER and nuclear factor-kappaB-dependent reporter genes was partially rescued from ER/p65 mutual inhibition by transient transfection of smooth muscle cells with a p300 expression vector. These actions of 17ss-estradiol may play an important role in the cytokine-induced expression of immune and inflammatory genes implicated in atherogenesis.