gebhart/patrepeval huggingface dataset:
A hybrid pipelined path-searching architecture for multiple communications applications (1992)

A high-throughput architecture that can search for the shortest path within a graph is proposed. The architecture can decode any data encoded with a finite state machine or data encrypted in a dynamic trellis code, and also serve as a specialized processor for other searching and matching applications. The proposed retargetable architecture is suitable for futuristic workstations equipped with wireless access, basic voice recognition, and high speed data services. Balance between flexibility and hardware efficiency is achieved by an integrated design of architecture, in-place scheduling, and concurrent algorithms.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
FUNCTION OF RETINOID NUCLEAR RECEPTORS: Lessons from Genetic and Pharmacological Dissections of the Retinoic Acid Signaling Pathway During Mouse Embryogenesis (2005)

Retinoic acid (RA) is involved in vertebrate morphogenesis, growth, cellular differentiation, and tissue homeostasis. The use of in vitro systems initially led to the identification of nuclear receptor RXR/RAR heterodimers as possible transducers of the RA signal. To unveil the physiological functions of RARs and RXRs, genetic and pharmacological studies have been performed in the mouse. Together, their results demonstrate that (a) RXR/RAR heterodimers in which RXR is either transcriptionally active or silent are involved in the transduction of the RA signal during prenatal development, (b) specific RXRalpha/RAR heterodimers are required at many distinct stages during early embryogenesis and organogenesis, (c) the physiological role of RA and its receptors cannot be extrapolated from teratogenesis studies using retinoids in excess. Additional cell type-restricted and temporally controlled somatic mutagenesis is required to determine the functions of RARs and RXRs during postnatal life.
In Vitro Efficient Transfection by CM18-Tat11 Hybrid Peptide: A New Tool for Gene-Delivery Applications (2013)

Cell penetrating peptides (CPPs) are actively researched as non-viral molecular carriers for the controlled delivery of nucleic acids into cells, but widespread application is severely hampered by their trapping into endosomes. Here we show that the recently introduced endosomolytic CM18-Tat11 hybrid peptide (KWKLFKKIGAVLKVLTTG-YGRKKRRQRRR, residues 1-7 of Cecropin-A, 2-12 of Melittin, and 47-57 of HIV-1 Tat protein) can be exploited to obtain a self-assembled peptide-DNA vector which maintains the CM18-Tat11 ability to enter cells and destabilize vesicular membranes, concomitantly yielding high DNA transfection efficiency with no detectable cytotoxic effects. Different peptide-DNA stoichiometric ratios were tested to optimize vector size, charge, and stability characteristics. The transfection efficiency of selected candidates is quantitatively investigated by the luciferase-reporter assay. Vector intracellular trafficking is monitored in real time and in live cells by confocal microscopy. In particular, fluorescence resonant energy transfer (FRET) between suitably-labeled peptide and DNA modules was exploited to monitor complex disassembly during endocytosis, and this process is correlated to transfection timing and efficiency. We argue that these results can open the way to the rational design and application of CM18-Tat11-based systems for gene-delivery purposes.
Discovery of AMG 232, a Potent, Selective, and Orally Bioavailable MDM2–p53 Inhibitor in Clinical Development (2014)

We recently reported the discovery of AM-8553 (1), a potent and selective piperidinone inhibitor of the MDM2–p53 interaction. Continued research investigation of the N-alkyl substituent of this series, focused in particular on a previously underutilized interaction in a shallow cleft on the MDM2 surface, led to the discovery of a one-carbon tethered sulfone which gave rise to substantial improvements in biochemical and cellular potency. Further investigation produced AMG 232 (2), which is currently being evaluated in human clinical trials for the treatment of cancer. Compound 2 is an extremely potent MDM2 inhibitor (SPR KD = 0.045 nM, SJSA-1 EdU IC50 = 9.1 nM), with remarkable pharmacokinetic properties and in vivo antitumor activity in the SJSA-1 osteosarcoma xenograft model (ED50 = 9.1 mg/kg).
Joshua Retold: Synoptic Perspectives (2000)

Joshua Retold: Synoptic Perspectives, by A. Graeme AuId. Old Testament Studies. Edinburgh: T&T Clark, 1998. 179 pp. $39.95 (c). This volume is a collection of thirteen essays on the book of Joshua by Professor AuId spanning his career from 1975 to the present. Most of them have been previously published or read at professional meetings. Most have been revised for this volume. The final one is new. After a brief Orientation the essays are organized into four sections. The first five come under the heading Texts and deal with text-critical issues in Joshua concerning particularly the relationship between the Masoretic text (MT) and the Septuagint (LXX). There are also essays here dealing specifically with the lists of cities in Joshua 20 and 21 and the importance of textual evidence for determining their literary relationship and development vis-a-vis parallel biblical texts, especially the one in 1 Chronicles 6. The next three essays are grouped under Words and are studies of the place name Bet Anat (Josh 15:59 MT), the term kbs, and the words for tribe. These studies overlap with or follow from the text-critical essays in the previous section as they warn against uncritical acceptance of the MT or argue for the discernment of distinct literary traditions in word choices of the variant textual witnesses. The third section, entitled Connections, contains four essays that deal with literary connections between Joshua and otiier biblical books. AuId here questions consensus views about the dependence of 1 Chronicles 2-7 on Joshua 13-22, suggesting mutual influence, and about the existence of Deuteronomistic History, the theory that the books of Deuteronomy, Joshua, Judges, 1-2 Samuel, 1-2 Kings were originally a unit. The fourth section, Interpretations, contains a single essay on the history of interpretation of the book of Joshua. The book concludes with what is really a fourteenth essay called Re-orientation, that further updates this history of interpretation, particularly in dialogue witii Auld's earlier book, Joshua, Moses and the Land (1980). This essay also offers a kind of prospectus for the direction that AuId believes further study of Joshua should take. This collection is useful for laying out the trajectory of thought of one of the leading scholars on Joshua. Auld's work has been and remains revisionist in the best sense. He is at his best when reexamining widely accepted conclusions (or assumptions) of scholars, pointing out their weaknesses and turning them on their heads to find out whether they actually stand better upside down. …
Functional Testing of Human Dopamine D 1 And D 5 Receptors Expressed in Stable camp-Responsive Luciferase Reporter Cell Lines (1993)

A large number of G-protein coupled receptors are known to modulate adenylyl cyclase activity. In order to find new compounds modulating the activity of specific receptor subtypes we developed a cellular screening system that measures the biological activity of drugs acting on receptors rather than merely their binding characteristics. The activity of the receptor coupling to the cAMP signal transduction pathway was measured via transcriptional activation of a reporter gene. A chinese hamster ovary cell line was stably transformed with a reporter plasmid containing the firefly luciferase gene under the transcriptional control of multiple cAMP responsive elements (CRE). This CRE reporter cell line exhibited 20 to 30-fold induction of luciferase activity upon stimulation of adenylyl cyclase with forskolin, but did not respond to dopamine agonists. Stable test cell lines were developed by transfecting reporter cell lines with human dopamine D1 and D5 receptor genes, respectively. Treatment of these test cell lines with dopamine receptor agonists and antagonists modulated the luciferase expression in a dose-dependent manner. The rank of potency of dopamine receptor agonists and antagonists was in agreement with reported data obtained from binding studies. The non-isotopic assay can be performed in microtiter plate format and is far less work intensive than the determination of adenylyl cyclase activity by direct cAMP measurement. This technology could also be utilized for discovery of new classes of compounds, e.g. allosteric effectors or non competitive ligands.
Shear stress analysis of mammalian cell suspensions for prediction of industrial centrifugation and its verification (2006)

This article describes the use of ultra scale-down studies requiring milliliter quantities of process material to study the clarification of mammalian cell culture broths using industrial-scale continuous centrifuges during the manufacture of a monoclonal antibody for therapeutic use. Samples were pretreated in a small high-speed rotating-disc device in order to mimic the effect on the cells of shear stresses in the feed zone of the industrial scale centrifuges. The use of this feed mimic was shown to predict a reduction of the clarification efficiency by significantly reducing the particle size distribution of the mammalian cells. The combined use of the rotating-disc device and a laboratory-scale test tube centrifuge successfully predicted the separation characteristics of industrial-scale, disc stack centrifuges operating with different feed zones. A 70% reduction in flow rate in the industrial-scale centrifuge was shown to arise from shear effects. A predicted 2.5-fold increase in throughput for the same clarification performance, achieved by the change to a centrifuge using a feed zone designed to give gentler acceleration of the bioprocess fluid, was also verified at large-scale.
Novel Biomarkers of Acute Kidney Toxicity (2009)

Novel biomarkers of kidney toxicity are powerful tools not only with respect to their clinical applications but also because of their impact on drug development. These biomarkers can influence the assessment of efficacy of new drugs for kidney diseases as well as the risk management for new drugs. The science behind these novel biomarkers reflects the evolution over the past decade of genomic and proteomic platforms that have transformed the discovery and development of new biomarkers for preclinical and clinical applications in drug development. Several of these biomarkers are in use as transcriptomic biomarkers in animal models as well as translational proteomic biomarkers in animal models and in humans. Their ability to detect kidney damage earlier than is possible with currently accessible biomarkers is being given qualification through regulatory biomarker-qualification programs, which will help establish consensus for their widespread use.
Transcytosis of Albumin in Endothelial Cells is Brefeldin A—Independent (1997)

To determine whether in endothelial cells (EC) the pathways of endocytosis and transcytosis of macromolecules interconnect, the effect of Brefeldin A (BFA) on these processes was tested. To this purpose EC were grown to confluence on plastic culture dishes or on cell culture chamber inserts placed into corresponding wells, so as to obtain a dual chamber system. The cells maintained the typical characteristics of EC and had an electrical resistance in the range of 30-60 Ohm.cm2. Transendothelial transport of albumin conjugated to the fluorochrom Texas Red (Alb-TR) and of horseradish peroxidase (HRP) added to the upper compartment, in the absence or presence of BFA (0-25 micrograms/ml), was evaluated in aliquots collected from the lower compartment. At different time intervals, quantitative data were obtained by fluorimetry and spectrophotometry. In other experiments transcytosis of Alb-TR was examined in the presence of 100 microM forskolin (an inhibitor of BFA effect). The endocytosis of Alb-TR and HRP was evaluated by incubating EC with the probes, and the internalized tracers determined in the cell lysate using the methods described above. The results showed that BFA has no significant effect on transcytosis of albumin and HRP. In contradistinction, BFA (5 micrograms/ml) reduced markedly endocytosis of HRP (by 47%). Forskolin has no effect on transcytosis. The data indicate that the BFA-induced perturbance in the endocytic route does not affect the transcytotic pathway of albumin, and suggest that in EC, transcytosis of macromolecules may represent a shortcut for rapid and direct transport of some plasma molecules across the cell.
Analyzing network coding gossip made easy (2011)

We introduce projection analysis - a new technique to analyze the stopping time of gossip protocols that are based on random linear network coding (RLNC). Projection analysis drastically simplifies, extends and strengthens previous results. We analyze RLNC gossip in a general framework for network and communication models that encompasses and unifies the models used previously in this context. We show, in most settings for the first time, that the RLNC gossip converges with high probability in optimal time. Most stopping times are of the form O(k + T), where k is the number of messages to be distributed and T is the time it takes to disseminate one message. This means RLNC gossip achieves perfect pipelining. Our analysis directly extends to highly dynamic networks in which the topology can change completely at any time. This remains true, even if the network dynamics are controlled by a fully adaptive adversary that knows the complete network state. Virtually nothing besides simple O(kT) sequential flooding protocols was previously known for such a setting.While RLNC gossip works in this wide variety of networks our analysis remains the same and extremely simple. This contrasts with more complex proofs that were put forward to give less strong results for various special cases.
A new receptor protein kinase from chick embryo related to type II receptor for TGF-β (1993)

We have isolated cDNA encoding a new member of protein kinase family from chicken embryo cDNA library. The deduced amino acid sequence comprises a cysteine-rich extracellular domain, a single hydrophobic transmembrane domain, and a cytoplasmic serine/threonine kinase domain. Two short inserts are contained in the kinase domain. The primary structure shows that it belongs to the receptor-type serine/threonine kinase subfamily and is most similar to Daf-1. Conserved cysteine residues in the ectodomain suggest the protein as a receptor for a peptide growth factor of TGF-beta family.
Effect of Oral Gavage Treatment with ZnAL42 and other Metallo-Ion Formulations on Influenza a H5N1 and H1N1 Virus Infections in Mice (2007)

Avian influenza H5N1 infections can cause severe, lethal human infections. Whether influenza A virus treatments effectively ameliorate avian influenza H5N1 human infections is uncertain. The research objective was to evaluate the efficacy of novel zinc and other metallo-ion formulations in two influenza A mouse models. Mice infected with influenza A/Duck/MN/1525/81 (H5N1) virus were treated orally 48 h before virus exposure and then twice daily for 13 days with ZnAL42. The optimal dosing regimen for ZnAL42 was achieved at 17.28 mg/kg 48 h prior to virus exposure, twice daily for 7 days. The survival rate was 80% compared with 10% in the untreated control group and a 100% survival rate with ribavirin (75 mg/kg/day, twice a day for 5 days, beginning 4 h before virus exposure). ZnAL42 treatment significantly lessened the decline in arterial oxygen saturation (SaO2; P < 0.001). This regimen was also well tolerated by the mice. Manganese and selenium formulations were not inhibitory to virus replication when given therapeutically. Mice were also infected with influenza A/NWS/33 (H1N1) virus and were treated 48 h before virus exposure with three dosages of ZnAL42 (8.64, 1.46 or 0.24 mg/kg/day). Treatment was by oral gavage twice daily for 13 days. The highest dose of ZnAL42 was significantly inhibitory to the virus infection as seen by prevention of deaths and lessening of decline in SaO2. The data suggest that the prophylactic use of ZnAL42 is effective against avian influenza H5N1 or H1N1 virus infection in mice and should be further explored as an option for treating human influenza virus infections.
Scrambling query plans to cope with unexpected delays (2002)

Accessing data from numerous widely distributed sources poses significant new challenges for query optimization and execution. Congestion and failures in the network can introduce highly variable response times for wide area data access. The paper is an initial exploration of solutions to this variability. We introduce a class of dynamic, run time query plan modification techniques that we call query plan scrambling. We present an algorithm that modifies execution plans on-the-fly in response to unexpected delays in obtaining initial requested tuples from remote sources. The algorithm both reschedules operators and introduces new operators into the query plan. We present simulation results that demonstrate how the technique effectively hides delays by performing other useful work while waiting for missing data to arrive.
Design of high-power ultrashort pulse amplifiers by expansion and recompression (1987)

A system that expands and recompresses an ultrashort pulse by means of diffraction gratings is described. The expansion can be large enough to broaden the pulse to several nanoseconds. In this manner, as the signal and pump pulses have similar lengths, high-efficiency amplifiers can be designed. The expansion avoids inefficient energy storage in high-gain amplifiers and nonlinear effects in the amplifier medium, and the amplified spontaneous emission is drastically reduced by working in a saturated amplifier regime.
Ralbp1 In Stress Resistance (2007)

Ralbp1 is a multi-specific transporter of glutathione conjugates as well as unconjugated amphiphilic toxins. Because glutathione conjugates are major metabolites of toxic lipid peroxidation products generated as a consequence of oxidant and radiant stress, the hypothesis is put forth that the function of Ralbp1 in-vivo and in vitro should be to protect organisms from chemical stress by removing toxic chemicals. Studies described in this dissertation were designed to prove this hypothesis. We tested the hypothesis by examining whether the inhibition or augmentation of Ralbp1 would sensitize or protect cells and whole animals from the toxic effects of chemicals and radiation. These studies establish that Ralbp1 is a primary determinant of resistance to chemical stressors by the direct transport of these toxins.
Aptamers Switch on Fluorescence of Triphenylmethane Dyes (2003)

MG and SRB aptamers, which are short RNA sequences originally selected only for binding to malachite green or sulforhodamine B, can greatly enhance the fluorescence of normally nonfluorescent triphenylmethane dyes. MG aptamer enhances the quantum yields of malachite green (MG) and a novel rigidized derivative, indolinyl malachite green (IMG) by >2000-fold. SRB aptamer brightens patent blue V and VF by >90-fold. These enhancements are specific because MG aptamer has no effect on patent blue dyes and SRB aptamer has little or no effect on MG and IMG. Such sequence-specific fluorescence labeling of short RNA motifs is a first step toward genetically encodable fusion tags for imaging selected RNAs in vitro and in cells.
A missense mutation in hepatocyte nuclear factor-4 alpha, resulting in a reduced transactivation activity, in human late-onset non-insulin-dependent diabetes mellitus. (1998)

Non-insulin-dependent diabetes mellitus (NIDDM) is a heterogeneous disorder characterized by hyperglycemia resulting from defects in insulin secretion and action. Recent studies have found mutations in the hepatocyte nuclear factor-4 alpha gene (HNF-4alpha) in families with maturity-onset diabetes of the young (MODY), an autosomal dominant form of diabetes characterized by early age at onset and a defect in glucose-stimulated insulin secretion. During the course of our search for susceptibility genes contributing to the more common late-onset NIDDM forms, we observed nominal evidence for linkage between NIDDM and markers in the region of the HNF-4alpha/MODY1 locus in a subset of French families with NIDDM diagnosed before 45 yr of age. Thus, we screened these families for mutations in the HNF-4alpha gene. We found a missense mutation, resulting in a valine-to-isoleucine substitution at codon 393 in a single family. This mutation cosegregated with diabetes and impaired insulin secretion, and was not present in 119 control subjects. Expression studies showed that this conservative substitution is associated with a marked reduction of transactivation activity, a result consistent with this mutation contributing to the insulin secretory defect observed in this family.
Divalent Metal Ion-Catalyzed Hydrolysis of Phosphorothionate Ester Pesticides and Their Corresponding Oxonates (1997)

The divalent metal ion-catalyzed hydrolysis of thionate (PS) and oxonate (PO) organophosphorus pesticides has been examined in light of three possible catalysis mech anisms: (1) metal ion coordination of the thionate sulfur or oxonate oxygen to enhance the electrophilicity of the phosphorus electrophilic site; (2) metal ion coordination and induced deprotonation of water to create a reactive nucleophile; and (3) metal ion coordination of the leaving group to facilitate its exit. The effect of the following metals at a concentration of 1 mM was examined: CoII, NiII, CuII, ZnII, and PbII. These metal ions were chosen for their ability to complex organic ligands and inorganic nucleophiles. Of these metal ions, CuII possesses properties most suitable for all three catalytic mechanisms and serves as the most effective catalyst for the five thionate esters (chlorpyrifos-methyl, zinophos, diazinon, parathion-methyl, and ronnel) and the two oxonate esters (chlorpyrifos-methyl oxon and paraoxon) included in this study. A decrease in the degree of CuII catalysis at high pH arises from solubility limitations. PbII nearly matches CuII as a catalyst for oxonate esters, but is a less effective catalyst for thionate esters. Catalysis by CoII, NiII, and ZnII is negligible. Phenolate product analysis indicates that metal catalysis in some instances shifts hydrolysis from alkyl carbon-centered pathways to phosphorus-centered pathways.
Resveratrol, a remarkable inhibitor of ribonucleotide reductase (1998)

Resveratrol, a natural phytoalexin found in grapes, is well known for its presumed role in the prevention of heart disease, associated with red wine consumption. We show here that it is a remarkable inhibitor of ribonucleotide reductase and DNA synthesis in mammalian cells, which might have further applications as an antiproliferative or a cancer chemopreventive agent in humans.
The high efficiency hyperspectral imager - A new instrument for measurements of the arctic surface (2005)

Throughout the Polar Regions the surface heat budget is dominated by the radiative terms; this is the case not only where the surface is frozen (Persson et al., 2002) but also for summertime conditions over open