gebhart/patrepeval huggingface dataset:
Prognostic significance of signal transducer and activator of transcription 1 activation in breast cancer. (2002)

Our study reveals a favorable and independent prognostic significance of STAT1 activation in mammary carcinoma, and is in accordance with the documented role of STAT1 in growth arrest, and in pro-apoptotic signaling pathways.
Expression of the <i>met</i> receptor tyrosine kinase in muscle progenitor cells in somites and limbs is absent in <i>Splotch</i> mice (1996)

Hepatocyte growth factor/scatter factor (HGF/SF) stimulates proliferation, dissociation, migration and morphogenesis of cells in culture. To investigate a possible role for HGF/SF and its receptor, the Met tyrosine kinase, in embryonic development, we have analyzed their expression in mouse embryos from day 7.5 of gestation by whole-mount in situ hybridization. Met expression is first detected in the ventral portion of somites at day 9.25 of gestation (22 somite embryo) at the level of fore limb buds. As somites mature, met expression is detected in caudal somites, and is confined to the lateral and media] tips of the dermomyotome and dermomyotome/myotome respectively. In contrast, HGF/SF is expressed exclusively in the mesodermal core of the limb bud. As the dermomyotome elongates ventrolaterally, the met-expressing cells at the lateral tip appear to detach from the somite, invade the limb bud and localize at the dorsal and ventral limb sides in close proximity to HGF/SF-expressing cells. At later stages, both met- and HGF/SF-expressing cells appear to migrate distally and localize to the digit forming area of the developing hand plate. Met expression in the lateral dermomyotome and limb bud coincides with expression of Pax-3, a marker for migrating muscle precursor cells in the somite and limb. Splotch-2H and Splotch-delayed mice, which harbor mutations in Pax-3, show major disruptions in early limb muscle development. Significantly, no met-expressing cells were observed in the limbs of homozygous Splotch-2H and Splotch-delayed animals, whereas HGF/SF expression was not affected. The restricted expression of met to a sub-population of Pax-3-expressing cells in the lateral tip of the dermomyotome, demonstrates that met represents a unique molecular marker for this migratory cell population. From these observations, together with the biological activities of HGF/SF, we propose that in homozygous Splotch embryos the failure of muscle precursors to migrate into and populate the limb bud results from a loss of met expression in the cells at the ventrolateral edge of the somitic dermomyotome.
Acute hypotension episode prediction using information divergence for feature selection, and non-parametric methods for classification (2009)

Acute hypotension is a critical event that can lead to irreversible organ damage and death. When detected in time, an appropriate intervention can significantly lower the risks for the patient. The objective of this work is to describe an automated statistical method that produces an automated method to predict acute hypotension episodes, using the least data possible. We first detailed the problem of having more features than samples in the PhysioNet/CinC Challenge 2009 training set. We constrained our analysis to the largest common subset of features available for all patients (arterial blood pressure measurements). We then used information divergence (or Kullback-Liebler divergence) between two distributions to identify the most discriminative features. We used these features in each training set to classify the samples in the test sets using a nearest neighbors (NN) algorithm. With this method, we obtained a score of 9/10 for event 1, and 32/40 for event 2 compared to a control method which gives us 10/10 for event 1, and 35/40 for event 2. Our preliminary results showed that our method leads to significantly better than random results, therefore it increases our information about the samples in the test sets.
Total Synthesis of Bistramide A (2006)

An asymmetric synthesis of the marine metabolite bistramide A is reported. The synthesis relies on the utility of three different organosilane reagents to construct all principle fragments and 8 of the 11 stereogenic centers of the natural product. [structure: see text].
A dual grating alignment method insensitive to mask-wafer gap variation. (1988)

This paper presents an X-ray lithography alignment method insensitive to mask-wafer gap variation, using dual gratings. Diffraction light beam intensities for various dual gratings were calculated on the assumption that each grating is a sinusoidal amplitude grating. As a result, if dual gratings, consisting of a linear grating on the mask and a checkerboard grating on the wafer, are used as a alignment key, it was found that the diffraction beam intensity I (0, 1), zero order in x (displacement) direction and first order in y direction, is independent from mask-wafer gap variation. The fact was confirmed by more detail calculations and experiments. Alignment experiments were carried out using intensity difference ΔI = I1 (0, 1) -I2 (0, 1) between two pairs of the dual gratings, which were arranged to have 180° phase shifted signal with reference to each other. A resolution better than 0.01 μm and 0.03 μm (3σ) alignment repeatability have been achieved among 25 μm and 55 μm gap variations.
The effect of some β‐lactam antibiotics on escherichia coli studied by flow cytometry (1982)

The effects of three beta-lactam antibiotics on Escherichia coli were studied by means of flow cytometry. Since these agents block bacterial cell wall synthesis in such manner as to prevent septal formation without appreciably affecting nucleic acid synthesis, the resulting cell elongation caused by these agents can be assessed by nucleic acid fluorescent staining. It was shown by this technique that the somatic effects of cefazolin, cefamandole and moxalactam were related both to the antibiotic concentration and time of exposure to the drugs and were observable within 30 minutes of the initial exposure of the cultures to these agents. These results demonstrate that fluorescent cytometry can provide accurate assessment of the effects of compounds that inhibit cell wall formation. This technology could be a useful tool for comparing antibiotic somatic effects on bacteria and for rapidly and reliably determining their sensitivity and resistance to these agents.
PEGylation of microbead surfaces reduces unspecific antibody binding in glycan-based suspension array (2014)

Glycan-based suspension array (SGA) is an "in-house" developed multi-target immunoassay, employing commercially available fluorescent microbeads as a solid support for unique chemically synthesized glycopolymers which capture naturally occurring human anti-glycan antibodies. SGA is a sensitive and reliable tool for the high-throughput screening of anti-glycan antibody alterations characteristic for a vast number of human diseases including cancer. However, unspecific background binding, for instance binding of non-target antibodies, is a common obstacle in such immunoassays. In an attempt to reduce unspecific background binding of serum (or plasma) antibodies, we prepared glycosylated microbeads modified with linear poly(ethylene glycols) (PEGs) of different lengths. We compared several kinds of PEG modifications: (a) partial side-chain substitution of glycopolymers by PEGs of different lengths, (b) end-point addition of biotin-linked PEGs to glycopolymer-coupled beads, and (c) linking of heterobifunctional PEGs to the bead surface prior to glycopolymer immobilization. Among the various modifications investigated, the direct modification of the bead surface with linear heterobifunctional PEGs, consisting of 23- and 60PEG-units significantly reduced the background binding. The end-point addition of biotin-linked PEGs, especially in the case of PEG consisting from 50PEG-units, helped to repel non-target binding caused by endogenous biotin. We observed unspecific binding predominantly for antibodies of IgG but of IgM class. The novel design of fluorescent microbeads allows the detection of human anti-glycan antibodies with increased specificity and opens new horizons for practical application of SGA as a diagnostic tool.
Algorithms for Rewriting Aggregate Queries Using Views (2000)

Queries involving aggregation are typical in database applications. One of the main ideas to optimize the execution of an aggregate query is to reuse results of previously answered queries. This leads to the problem of rewriting aggregate queries using views. Due to a lack of theory, algorithms for this problem were rather ad-hoc. They were sound, but were not proven to be complete. Recently we have given syntactic characterizations for the equivalence of aggregate queries and applied them to decide when there exist rewritings. However, these decision procedures do not lend themselves immediately to an implementation. In this paper, we present practical algorithms for rewriting queries with $\COUNT$ and $\SUM$. Our algorithms are sound. They are also complete for important cases. Our techniques can be used to improve well-known procedures for rewriting non-aggregate queries. These procedures can then be adapted to obtain algorithms for rewriting queries with $\MIN$ and $\MAX$. The algorithms presented are a basis for realizing optimizers that rewrite queries using views.
An IL-17 Peptide-Based and Virus-Like Particle Vaccine Enhances the Bioactivity of IL-17 <i>in Vitro</i> and <i>in Vivo</i> (2012)

The IL-17 peptide-based vaccine enhances the bioactivity of IL-17 in vitro and in vivo, providing a potential immunotherapy for treatment of diseases associated with insufficient IL-17 production, such as hyper-IgE syndrome.
Airway pharmacology: treatment options and algorithms to treat patients with chronic obstructive pulmonary disease (2019)

Pharmacological treatment of patients with chronic obstructive pulmonary disease (COPD) aims to reduce disease burden and prevent future risk, especially exacerbations, hospitalizations, decline of lung function and quality of life, and mortality. This review will describe the basic pharmacology of the different classes of agents, followed by the effects they exert in patients with COPD, and the side effects. Targets for pharmacological treatments include airway smooth muscle contraction, inflammation, mucus production, alpha-1-antitrypsin deficiency and respiratory infection. Inhaled bronchodilators are the mainstay, with methylxanthines as secondary choice agents. Anti-inflammatory therapy can be administered as corticosteroids, phosphodiesterase inhibitor, and long-term macrolides such as azithromycin. Mucus production is addressed by use of mucolytics. In some countries, alpha-1-antitrypsin augmentation therapy is available for severe alpha-1-antitrypsin deficiency. The treatment of bacterial infection and/or colonization can be attempted with antibiotics; there is a dire need for effective anti-viral agents for the common viruses causing exacerbations of COPD. Since clinicians need to choose medications for their individual patients, algorithms for how to choose and change medication are increasingly being presented with more elements of treatable traits and personalized medicine.
The performance of a hybrid videoconferencing coder using displacement estimation in the transform domain (2005)

In this paper we extend the transform domain oriented estimation algorithm introduced in [1] in which the calculation of the displacement vector was obtained from the transform domain coefficients. The performance of the algorithm is verified within a hybrid coding configuration. In this paper only transform domain block matching algorithms are considered. The block-match procedure makes use of the displacement matrix H defined in [1]. A matrix decomposition method is described in order to show that a practical implementation is very well possible. The properties of the translation invariant matrices are explained by using the ordered Walsh Hadamard transform as an example. The procedure however enables the use any other orthogonal transform. An important issue with respect to the hardware complexity of this motion compensated hybrid coder is the use of only one transform. The performance of the proposed new algorithm is shown and a video tape containing a very critical videoconferencing scene (i.e. split screen and a hard switch to full screen with heavy motion) will be presented. The sequences are coded at a bitrate of 384 kbit/s and 64 kbit/s respectively. Results of the compensation in the pixel domain and in the transform domain are compared and it is shown that the latter approach results in an improved performance of the estimation procedure.
IL-6 as a target in inflammation. (2015)

Interleukin-6 (IL-6) has a unique feature of its own signaling pathway. IL-6 can act on various types of cells because there are abundant amounts of soluble IL-6 receptor in peripheral blood and can mediate signaling into cells. IL-6 participates in a broad spectrum of biological events, such as immune responses, hematopoiesis, and acute-phase reactions. In contrast, overproduction of IL-6 has been implicated in the pathogenesis of a variety of diseases, including several chronic inflammatory diseases. Future studies to clarify the molecular mechanisms of IL-6 functions as well as studies in which inhibitors of IL-6 signaling are used should provide information critical to a better understanding of the molecular mechanisms of diseases and the development of new therapeutic methods.
Effects of the central analgesic tramadol and its main metabolite, O‐desmethyltramadol, on rat locus coeruleus neurones (1993)

1. Tramadol is a centrally acting analgesic with low opioid receptor affinity and, therefore, presumably additional mechanisms of analgesic action. Tramadol and its main metabolite O-desmethyltramadol were tested on rat central noradrenergic neurones of the nucleus locus coeruleus (LC), which are involved in the modulation of nociceptive afferent stimuli. 2. In pontine slices of the rat brain the spontaneous discharge of action potentials of LC cells was recorded extracellularly. (-)-Tramadol (0.1-100 microM), (+)-tramadol (0.1-100 microM), (-)-O-desmethyl-tramadol (0.1-100 microM) and (+)-O-desmethyltramadol (0.01-1 microM) inhibited the firing rate in a concentration-dependent manner. (+)-O-desmethyltramadol had the highest potency, while all other agonists were active at a similar range of concentrations. 3. (-)-Tramadol (10, 100 microM) was less inhibitory in brain slices of rats pretreated with reserpine (5 mg kg-1, 5 h before decapitation) than in controls. 4. The effect of (-)-tramadol (10 microM) was abolished in the presence of the alpha 2-adrenoceptor antagonist, rauwolscine (1 microM), whilst that of (+)-O-desmethyltramadol (0.3 microM) virtually disappeared in the presence of the opioid antagonist, naloxone (0.1 microM). (+)-Tramadol (30 microM) and (-)-O-desmethyl-tramadol (10 microM) became inactive only in the combined presence of naloxone (0.1 microM) and rauwolscine (1 microM). 5. In another series of experiments, the membrane potential of LC neurones was determined with intracellular microelectrodes. (-)-Tramadol (100 microM) inhibited the spontaneous firing and hyper-polarized the cells; this effect was abolished by rauwolscine (1 microM). (+)-O-desmethyltramadol (10 microM)had a similar but somewhat larger effect on the membrane potential than (-)-tramadol. The (+)-O-desmethyltramadol-(10 microM) induced hyperpolarization was abolished by naloxone (0.1 microM).6. The hyperpolarizing effect of noradrenaline (30 microM) was potentiated in the presence of (-)-tramadol(100 microM), but not in the presence of (+)-O-desmethyltramadol (10 microM). There was no potentiation of the noradrenaline (30 microM) effect, when the cells were hyperpolarized by current injection to an extent similar to that produced by (-)-tramadol (100 microM).7. Both noradrenaline (100 microM) and (- )-tramadol (100 microM) decreased the input resistance.8. The results confirm that the analgesic action of tramadol involves both opioid and non-opioid components. It appears that (-)-tramadol inhibits the uptake of noradrenaline and via a subsequent increase in the concentration of endogenous noradrenaline indirectly stimulates alpha2-adrenoceptors. (+)-0-desmethyltramadol seems to stimulate directly opioid micro-receptors. The effects of (+)-tramadol and(-)-O-desmethyltramadol consist of combined micro-opioid and alpha2-adrenergic components.
Nanoliter Homogenous Ultra-High Throughput Screening Microarray for Lead Discoveries and IC <sub>50</sub> Profiling (2005)

Microfluidic technologies offer the potential for highly productive and low-cost ultra-high throughput screening and high throughput selectivity profiling. Such technologies need to provide the flexibility of plate-based assays as well as be less expensive to operate. Presented here is a unique microarray system (the Reaction Biology [Malvern, PA] DiscoveryDot), which runs over 6,000 homogeneous reactions per 1" x 3" microarray using chemical libraries or compound dilutions printed in 1-nl volumes. A simple and rapid piezo-activation method delivers from 30 to 300 pl of biochemical targets and detector chemistries to each reaction. The fluorescent signals are detected and analyzed with conventional microarray scanners and software. The DiscoveryDot platform is highly customizable, and reduces consumption of targets and reaction chemistries by >40-fold and the consumption of compounds by >10,000-fold, compared to 384-well plate assay. We demonstrate here that the DiscoveryDot platform is compatible with conventional large-volume well-based reactions, with a Z' factor of >0.6 for many enzymes, such as the caspase family enzymes, matrix metalloproteinase, serine proteases, kinases, and histone deacetylases. The platform is well equipped for 50% inhibitory concentration (IC50) profiling studies of enzyme inhibitors, with up to 10 dilution conditions of each test compound printed in duplicate, and each microarray chip can generate over 300 IC50 measurements against a given target.
Bone Anchors in Urogynecology (2000)

Louisiana State University Medical Center, New Orleans, Louisiana Correspondence: Carol Glowacki, MD, Department of Obstetrics and Gynecology, Division of Urogynecology, Harbor-University of California Los Angeles Medical Center, 1000 West Carson Street, Torrance, CA 90509.
Identification and Characterization of Mutations Conferring Resistance to d-Amino Acids in Bacillus subtilis (2015)

Proteins are composed of L-amino acids. Mischarging of tRNAs with D-amino acids or the misincorporation of D-amino acids into proteins causes toxicity. This work reports on mutations that confer resistance to D-amino acids and their mechanisms of action.
Exosome-mediated shuttling of microRNA-29 regulates HIV Tat and morphine-mediated Neuronal dysfunction (2012)

Neuronal damage is a hallmark feature of HIV-associated neurological disorders (HANDs). Opiate drug abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Opiates such as morphine have been shown to enhance HIV transactivation protein Tat-mediated toxicity in both human neurons and neuroblastoma cells. In the present study, we demonstrate reduced expression of the tropic factor platelet-derived growth factor (PDGF)-B with a concomitant increase in miR-29b in the basal ganglia region of the brains of morphine-dependent simian immunodeficiency virus (SIV)-infected macaques compared with the SIV-infected controls. In vitro relevance of these findings was corroborated in cultures of astrocytes exposed to morphine and HIV Tat that led to increased release of miR-29b in exosomes. Subsequent treatment of neuronal SH-SY5Y cell line with exosomes from treated astrocytes resulted in decreased expression of PDGF-B, with a concomitant decrease in viability of neurons. Furthermore, it was shown that PDGF-B was a target for miR-29b as evidenced by the fact that binding of miR-29 to the 3'-untranslated region of PDGF-B mRNA resulted in its translational repression in SH-SY5Y cells. Understanding the regulation of PDGF-B expression may provide insights into the development of potential therapeutic targets for neuronal loss in HIV-1-infected opiate abusers.
Visualization Tools for Clustering, Trees and Ordered Trees (1992)

Consider the situation of a set of individuals visiting a library and browsing through a collection. Each individual will, of course, select different books to browse depending on the original purpose of the visit. In addition, the order in which they search through a catalog will differ. The order is often ignored, yet might provide interesting cues as to the importance of certain books or topics. This scenario is not limited to browsing physical collections, but rather is repeated almost continually in other information-seeking behaviors including searching of on-line databases and hypenext/hypermedia systems.
Pulsed-Field Capillary Electrophoresis Separation of Large DNA Fragments (2003)

Field-inversion capillary electrophoresis (FICE) provides many of the same benefits as the more familiar, field-inversion gel electrophoresis (FIGE). In the capillary format, field inversion allows size separation of linear dsDNA into the megabase region. Whereas FIGE separation of megabase pair (Mb) DNA takes 24 h or more, the most rapid FICE separations are complete within 4 min (,). As with any capillary electroseparation, the technique is rapid and provides high resolution, but is analytical scale only. Preparative scale use of capillary electrophoresis (CE) is not very practical, although apparatus capable of the collection of CE fractions have been developed ().
RNA-seq analysis of 2 closely related leukemia clones that differ in their self-renewal capacity (2010)

The molecular mechanisms regulating self-renewal of leukemia stem cells remain poorly understood. Here we report the generation of 2 closely related leukemias created through the retroviral overexpression of Meis1 and Hoxa9. Despite their apparent common origin, these clonal leukemias exhibit enormous differences in stem cell frequency (from 1 in 1.4, FLA2; to 1 in 347, FLB1), suggesting that one of these leukemias undergoes nearly unlimited self-renewal divisions. Using next-generation RNA-sequencing, we characterized the transcriptomes of these phenotypically similar, but biologically distinct, leukemias, identifying hundreds of differentially expressed genes and a large number of structural differences (eg, alternative splicing and promoter usage). Focusing on ligand-receptor pairs, we observed high expression levels of Sdf1-Cxcr4; Jagged2-Notch2/1; Osm-Gp130; Scf-cKit; and Bmp15-Tgfb1/2. Interestingly, the integrin beta 2-like gene (Itgb2l) is both highly expressed and differentially expressed between our 2 leukemias (∼ 14-fold higher in FLA2 than FLB1). In addition, gene ontology analysis indicated G-protein-coupled receptor had a much higher proportion of differential expression (22%) compared with other classes (∼ 5%), suggesting a potential role regulating subtle changes in cellular behavior. These results provide the first comprehensive transcriptome analysis of a leukemia stem cell and document an unexpected level of transcriptome variation between phenotypically similar leukemic cells.