gebhart/patrepeval huggingface dataset:
Localization of the Heparin Binding Exosite of Factor IXa (2002)

Factor IXa (FIXa) is known to have a binding site for heparin that has not been mapped by a mutagenesis study. By homology modeling based on structural data, we identified eight basic residues in the catalytic domain of FIXa that can potentially bind to heparin. These residues, Lys(98), Lys(126), Arg(165), Arg(170), Lys(173), Lys(230), Arg(233), and Lys(239) (chymotrypsin numbering) were substituted with Ala in separate constructs in Gla-domainless forms. Following activation, it was found that all FIXa derivatives cleaved the chromogenic substrate CBS 31.39 with near normal catalytic efficiencies. Similarly, antithrombin inactivated FIXa derivatives with a similar second-order association rate constant (k(2)) in both the absence and presence of pentasaccharide. In the presence of a full-length heparin, however, k(2) values were dramatically impaired with certain mutants. Direct binding studies revealed that the same mutants lost their affinities for binding to heparin-Sepharose. Both kinetic and direct binding data indicated that five basic residues of FIXa in the following order of importance, Arg(233) > Arg(165) > Lys(230) > Lys(126) > Arg(170) are critical for binding to heparin. Consistent with these results, examination of the crystal structure of the catalytic domain of FIXa indicated that all five basic residues are spatially aligned in a manner optimal for interaction with heparin.
A simplified expression of the dyadic Green's function for a conducting half-sheet (1981)

Simple analytical expressions of the dyadic Green's function for a conducting half-sheet have been derived. These expressions involve some finite integrals which can be easily calculated by a digital computer and are much simpler than those involving the vector mode function expansion. Input impedances of monopole antennas on and near an edge of a conducting half-sheet and the impedance of a notch antenna have been obtained, and the usefulness of these simplified expressions has been proved. The present results can be applied to check the limits of the applicability of the asymptotic theories, e.g., the geometrical theory of diffraction (GTD) and the uniform asymptotic theory of diffraction (UAT).
Vascular endothelial growth factor receptor expression during embryogenesis and tissue repair suggests a role in endothelial differentiation and blood vessel growth. (1993)

Vascular endothelial growth factor (VEGF) is a polypeptide mitogen that stimulates the growth of endothelial cells in vitro and promotes the growth of blood vessels in vivo. We have recently shown that the fms-like receptor tyrosine kinase (flt) is a receptor for VEGF. Here we used in situ hybridization to show that, in adult mouse tissues, the pattern of flt expression was consistent with localization in endothelium. We also show that flt was expressed in endothelium during neovascularization of healing skin wounds and during early vascular development in mouse embryos. Moreover, flt was expressed in populations of embryonic cells from which endothelium is derived such as early yolk sac mesenchyme. The expression of flt in the endothelium of both developing and mature blood vessels suggests that VEGF might regulate endothelial differentiation, blood vessel growth, and vascular repair.
Toward Realistic Image Compositing With Adversarial Learning (2019)

Compositing a realistic image is a challenging task and usually requires considerable human supervision using professional image editing software. In this work we propose a generative adversarial network (GAN) architecture for automatic image compositing. The proposed model consists of four sub-networks: a transformation network that improves the geometric and color consistency of the composite image, a refinement network that polishes the boundary of the composite image, and a pair of discriminator network and a segmentation network for adversarial learning. Experimental results on both synthesized images and real images show that our model, Geometrically and Color Consistent GANs (GCC-GANs), can automatically generate realistic composite images compared to several state-of-the-art methods, and does not require any manual effort.
Identification of a Novel Subpopulation of Human Cord Blood CD34−CD133−CD7−CD45+Lineage− Cells Capable of Lymphoid/NK Cell Differentiation After In Vitro Exposure to IL-15 (2003)

The hemopoietic stem cell (HSC) compartment encompasses cell subsets with heterogeneous proliferative and developmental potential. Numerous CD34(-) cell subsets that might reside at an earlier stage of differentiation than CD34(+) HSCs have been described and characterized within human umbilical cord blood (UCB). We identified a novel subpopulation of CD34(-)CD133(-)CD7(-)CD45(dim)lineage (lin)(-) HSCs contained within human UCB that were endowed with low but measurable extended long-term culture-initiating cell activity. Exposure of CD34(-)CD133(-)CD7(-)CD45(dim)lin(-) HSCs to stem cell factor preserved cell viability and was associated with the following: 1) concordant expression of the stem cell-associated Ags CD34 and CD133, 2) generation of CFU-granulocyte-macrophage, burst-forming unit erythroid, and megakaryocytic aggregates, 3) significant extended long-term culture-initiating cell activity, and 4) up-regulation of mRNA signals for myeloperoxidase. At variance with CD34(+)lin(-) cells, CD34(-)CD133(-)CD7(-)CD45(dim)lin(-) HSCs maintained with IL-15, but not with IL-2 or IL-7, proliferated vigorously and differentiated into a homogeneous population of CD7(+)CD45(bright)CD25(+)CD44(+) lymphoid progenitors with high expression of the T cell-associated transcription factor GATA-3. Although they harbored nonclonally rearranged TCRgamma genes, IL-15-primed CD34(-)CD133(-)CD7(-)CD45(dim)lin(-) HSCs failed to achieve full maturation, as manifested in their CD3(-)TCRalphabeta(-)gammadelta(-) phenotype. Conversely, culture on stromal cells supplemented with IL-15 was associated with the acquisition of phenotypic and functional features of NK cells. Collectively, CD34(-)CD133(-)CD7(-)CD45(dim)lin(-) HSCs from human UCB displayed an exquisite sensitivity to IL-15 and differentiated into lymphoid/NK cells. Whether the transplantation of CD34(-)lin(-) HSCs possessing T/NK cell differentiation potential may impact on immunological reconstitution and control of minimal residual disease after HSC transplantation for autoimmune or malignant diseases remains to be determined.
The utilization of next-generation sequencing to detect somatic mutations and predict clinical prognosis of Chinese non-small cell lung cancer patients (2018)

We demonstrated that NGS can be used in multiple applications to effectively identify potential oncogenic driver mutations, guide mutation-targeted therapy decisions, and predict clinical outcomes in Chinese NSCLC patients.
Autonomous 3-d positioning of surgical instruments in robotized laparoscopic surgery using visual servoing (2003)

This paper presents a robotic vision system that automatically retrieves and positions surgical instruments during robotized laparoscopic surgical operations. The instrument is mounted on the end-effector of a surgical robot which is controlled by visual servoing. The goal of the automated task is to safely bring the instrument at a desired three-dimensional location from an unknown or hidden position. Light-emitting diodes are attached on the tip of the instrument, and a specific instrument holder fitted with optical fibers is used to project laser dots on the surface of the organs. These optical markers are detected in the endoscopic image and allow localizing the instrument with respect to the scene. The instrument is recovered and centered in the image plane by means of a visual servoing algorithm using feature errors in the image. With this system, the surgeon can specify a desired relative position between the instrument and the pointed organ. The relationship between the velocity screw of the surgical instrument and the velocity of the markers in the image is estimated online and, for safety reasons, a multistages servoing scheme is proposed. Our approach has been successfully validated in a real surgical environment by performing experiments on living tissues in the surgical training room of the Institut de Recherche sur les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France.
Identification of Novel Genes Coding for Small Expressed RNAs (2001)

In Caenorhabditis elegans, lin-4 and let-7 encode 22- and 21-nucleotide (nt) RNAs, respectively, which function as key regulators of developmental timing. Because the appearance of these short RNAs is regulated during development, they are also referred to as small temporal RNAs (stRNAs). We show that many 21- and 22-nt expressed RNAs, termed microRNAs, exist in invertebrates and vertebrates and that some of these novel RNAs, similar to let-7 stRNA, are highly conserved. This suggests that sequence-specific, posttranscriptional regulatory mechanisms mediated by small RNAs are more general than previously appreciated.
Triangulation-based fusion of sonar data with application in robot pose tracking (2000)

In this paper a sensor fusion scheme, called triangulation-based fusion (TBF) of sonar data, is presented. This algorithm delivers stable natural point landmarks, which appear in practically all indoor environments, i.e., vertical edges like door posts, table legs, and so forth. The landmark precision is in most cases within centimeters. The TBF algorithm is implemented as a voting scheme, which groups sonar measurements that are likely to have hit the same object in the environment. The algorithm has low complexity and is sufficiently fast for most mobile robot applications. As a case study, we apply the TBF algorithm to robot pose tracking. The pose tracker is implemented as a classic extended Kalman filter, which use odometry readings for the prediction step and TBF data for measurement updates. The TBF data is matched to pre-recorded reference maps of landmarks in order to measure the robot pose. In corridors, complementary TBF data measurements from the walls are used to improve the orientation and position estimate. Experiments demonstrate that the pose tracker is robust enough for handling kilometer distances in a large scale indoor environment containing a sufficiently dense landmark set.
Tau phosphorylation in neuronal cell function and dysfunction (2004)

Tau is a group of neuronal microtubule-associated proteins that are formed by alternative mRNA splicing and accumulate in neurofibrillary tangles in Alzheimer's disease (AD) brain. Tau plays a key role in regulating microtubule dynamics, axonal transport and neurite outgrowth, and all these functions of tau are modulated by site-specific phosphorylation. There is significant evidence that a disruption of normal phosphorylation events results in tau dysfunction in neurodegenerative diseases, such as AD, and is a contributing factor to the pathogenic processes. Indeed, the abnormal tau phosphorylation that occurs in neurodegenerative conditions not only results in a toxic loss of function (e.g. decreased microtubule binding) but probably also a toxic gain of function (e.g. increased tau-tau interactions). Although tau is phosphorylated in vitro by numerous protein kinases, how many of these actually phosphorylate tau in vivo is unclear. Identification of the protein kinases that phosphorylate tau in vivo in both physiological and pathological processes could provide potential therapeutic targets for the treatment of AD and other neurodegenerative diseases in which there is tau pathology.
Isolation of the bile canalicular actin-myosin II motor. (1994)

Cytoskeleton-rich canalicular membranes (CCMs) with preserved cytoskeleton and demembranated CCMs, consisting only of cytoskeletal elements, were used to examine the relationship of pericanalicular microfilaments, myosin II phosphorylation, and canalicular contraction. The components of CCMs were visualized by fluorescence microscopy using the filamentous actin probe rhodamine-phalloidin and by electron microscopy, before and after incubation in 1 microM Ca2+/1 mM ATP (contraction solution). Canalicular contraction (luminal closure) was evaluated by morphometric analysis. Myosin II was extracted from CCMs, purified by immunoprecipitation, and analyzed on Western blots. In sequential experiments, autoradiographs of gels from [gamma-32P]-ATP-treated CCMs in the presence or absence of Ca2+ were examined after 0.25, 0.50, 1, 2, 3, 5, and 10 min, and the effects of W7 (a calmodulin antagonist) and ML9 (a myosin light chain kinase inhibitor) were evaluated. The results showed that phosphorylation of the 20-kDa protein was low in controls but enhanced beginning 0.25-0.50 min after addition of contraction solution. Both W7 and ML9 significantly inhibited this reaction and inhibited canalicular contraction. The results indicate that phosphorylation of the regulatory 20-kDa myosin light chain of canaliculus-associated myosin II coincides with or precedes contraction of the canaliculus. We conclude that the canalicular contractile apparatus is composed of actin filaments and a myosin II motor.
Morphine Activates Opioid Receptors without Causing Their Rapid Internalization (1996)

We have examined the endocytic trafficking of epitope-tagged delta and mu opioid receptors expressed in human embryonic kidney (HEK) 293 cells. These receptors are activated by peptide agonists (enkephalins) as well as by the alkaloid agonist drugs etorphine and morphine. Enkephalins and etorphine cause opioid receptors to internalize rapidly (t1/2 approximately 6 min) by a mechanism similar to that utilized by a number of other classes of receptor, as indicated by localization of internalized opioid receptors in transferrin-containing endosomes and inhibition of opioid receptor internalization by hypertonic media. Remarkably, morphine does not stimulate the rapid internalization of either delta or mu opioid receptors, even at high concentrations that strongly inhibit adenylyl cyclase. These data indicate that agonist ligands, which have similar effects on receptor-mediated signaling, can have dramatically different effects on the intracellular trafficking of a G protein-coupled receptor.
Initial testing of dasatinib by the pediatric preclinical testing program (2007)

Dasatinib was active at low nanomolar concentrations against a small subset of the PPTP's in vitro panel. Dasatinib had limited in vivo activity against the PPTP solid tumor xenografts, but was highly active against a Ph(+) ALL xenograft and also had anti-leukemia activity against two other xenografts.
Normal and leukaemic stem cells (2005)

The blood-related cancer leukaemias were the first diseases where human cancer stem cells, or leukaemic stem cells (LSC), were isolated. The haematopoietic system is one of the best tissues for investigating cancer stem cells, because the developmental hierarchy of normal blood formation is well defined. Leukaemias can now be viewed as aberrant haematopoietic processes initiated by rare LSC that have maintained or reacquired the capacity for indefinite proliferation through accumulated mutations and/or epigenetic changes. Yet, despite their critical importance, much remains to be learned about the developmental origin of LSC and the mechanisms responsible for their emergence in the course of the disease. This report will review our current knowledge on normal and LSC development and examine the impact of these discoveries may have clinically and in our understanding of the leukaemogenic process.
Why interaction is more powerful than algorithms (1997)

article Free Access Share on Why interaction is more powerful than algorithms Author: Peter Wegner Brown Univ. Brown Univ.View Profile Authors Info & Claims Communications of the ACMVolume 40Issue 5May 1997 pp 80–91https://doi.org/10.1145/253769.253801Published:01 May 1997Publication History 466citation5,543DownloadsMetricsTotal Citations466Total Downloads5,543Last 12 Months316Last 6 weeks61 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
A Plasmablast Biomarker for Nonresponse to Antibody Therapy to CD20 in Rheumatoid Arthritis (2011)

An important goal for personalized health care is the identification of biomarkers that predict the likelihood of treatment responses. Here, we tested the hypothesis that quantitative mRNA assays for B lineage cells in blood could serve as baseline predictors of therapeutic response to B cell depletion therapy in subjects with rheumatoid arthritis (RA). In samples from the REFLEX trial of rituximab in inadequate responders to antibodies to tumor necrosis factor-α, a 25% subgroup of treated subjects with elevated baseline mRNA levels of IgJ, a marker for antibody-secreting plasmablasts, showed reduced clinical response rates. There were no significant efficacy differences in the placebo arm subjects stratified by this marker. Prospective testing of the IgJ biomarker in the DANCER and SERENE rituximab clinical trial cohorts and the SCRIPT ocrelizumab cohort confirmed the utility of this marker to predict nonresponse to anti-CD20 therapy. A combination mRNA biomarker, IgJhiFCRL5lo, showed improved test performance over IgJhi alone. This study demonstrates that baseline blood levels of molecular markers for late-stage B lineage plasmablasts identify a ~20% subgroup of active RA subjects who are unlikely to gain substantial clinical benefit from anti-CD20 B cell depletion therapy.
Synthesis of Various 3-Substituted 1,2,4-Oxadiazole-Containing Chiral β3- and α-Amino Acids from Fmoc-Protected Aspartic Acid (2003)

Various 3-substituted chiral 1,2,4-oxadiazole-containing Fmoc-beta(3)- and -alpha-amino acids were synthesized from Fmoc-(l or d)-Asp(OtBu)-OH and Fmoc-l-Asp-OtBu, respectively, in three steps (i.e., condensation of an aspartyl derivative with differentially substituted amidoximes, formation of the 1,2,4-oxadiazole, and cleavage of the tert-butyl ester). These compounds represent new series of nonnatural amino acids, which could be used in combinatorial synthesis. A simple protocol has been developed to generate the 1,2,4-oxadiazole ring. Indeed, common methods resulted in cleavage of the Fmoc group or required long reaction times. We found that sodium acetate in refluxing ethanol/water (86 degrees C) was a convenient and efficient catalyst to promote conversion of Fmoc-amino acyl amidoximes to 1,2,4-oxadiazoles, and this procedure proved to be compatible with Fmoc protection. It is shown that these compounds can be prepared without significant loss of enantiomerical purity. Furthermore, the alkaline conditions used to cleave the Fmoc protecting group from these compounds did not induce epimerization of their chiral center.
A monoclonal antibody (B724) to von Willebrand factor recognizing an epitope within the Al disulphide loop (Cys509‐Cys695) discriminates between type 2A and type 2B von Willebrand disease (1995)

Monoclonal antibody (MoAb) B724 to von Willebrand factor (vWF) completely inhibits its interaction with heparin, sulphatides and botrocetin and consequently botrocetin-induced binding of vWF to platelets. MoAb B724 has no effect on the binding of vWF to collagen or to ristocetin-treated platelets nor on vWF-dependent platelet aggregation induced with ristocetin and asialo-vWF-mediated platelet aggregation. MoAb B724 preferentially recognizes a conformation of native vWF, in solution, or immobilized through a coated antibody. It exhibits a markedly lower affinity for vWF immobilized onto collagen or plastic surfaces. Using proteolytic fragments of vWF, B724 epitope was localized within the 512-673 sequence of the A1 disulphide loop of vWF, MoAb B724 was used as second antibody in a two-site ELISA to test a series of patients with type 1, 2A, 2B and 2N vWD or haemophilia A and recombinant wild type or mutated vWFs. Results were compared with those obtained by control ELISAs performed using polyclonal antibodies. Using MoAb B724, strikingly lower levels of vWFAg were observed in plasma from most patients with type 2B vWD, and in seven out of the eight rvWF mutated close to or within the A1 disulphide loop. Therefore MoAb B724, which interferes with this loop involved in the function of vWF, appears to be a useful tool for rapid screening of conformational changes in this region.
Nonatheromatous Ischemic Heart Disease following Withdrawal from Chronic Industrial Nitroglycerin Exposure (1972)

This report describes the clinical, angiographic, and hemodynamic findings in nine patients who manifested nonatheromatous ischemic heart disease induced by chronic industrial exposure to nitroglycerin and subsequent withdrawal. They represent nearly 5% incidence in the group of 200 workers with similar exposure. One patient died suddenly, and the disease was commonly without premonitory symptoms. Of the eight survivors, five were studied and none showed evidence of significant organic obstructive disease. However, in one studied during the withdrawal state, coronary and digital arteriospasm was demonstrated, and was readily reversed by nitroglycerin. Survivors exhibited exercise symptomatology and hemodynamic impairment similar to other patients with myocardial dysfunction from ischemic heart disease. Complete left bundle-branch block with late sudden death occurred in one, and chronic recurrent atrial fibrillation is present in a second. An attractive hypothesis suggests that chronic vasodilatation evokes homeostatic vasoconstriction, the latter persisting during the withdrawal period with cardiac ischemia. A more detailed study of the vasodilator action of organic nitrate and the homeostatic reaction is warranted. In addition, the effect of chronic administration of potent, longacting organic nitrate-based drugs should be examined in the light of this industrial experience.
Long-Term Effects of Donepezil on P300 Auditory Event-Related Potentials in Patients with Alzheimer’s Disease (2003)

The P300, one of the cognitive event-related potentials (ERPs) of the cerebral cortex, reflects the functioning of the neurochemical system involved in cognitive processes. We investigated clinical significance of the components of auditory P300 ERPs, in comparison with neuropsychologic tests including the Mini-Mental State Examination and the Japanese version of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-J cog), for evaluating of the effect of donepezil (DPZ) (5 mg daily for 6 months), an acetylcholinesterase inhibitor, in patients with Alzheimer's disease (AD). Reduction of P300 latency associated with a parallel improvement of ADAS-J cog scores was observed after administration of 5 mg/day of DPZ in patients with AD. P300 latency gives very useful information on the progression of AD, especially in the longitudinal follow-up of patients with AD during treatment with DPZ acting on cholinergic pathways.