gebhart/patrepeval huggingface dataset:
Review of research leading to new anti-herpesvirus agents in clinical development: Valaciclovir hydrochloride (256u, the L-valyl ester of acyclovir) and 882c, a specific agent for varicella zoster virus (1993)

Research leading to the new anti-herpesvirus compounds discussed here has come from three approaches. The first approach was directed towards improving the bioavailability of acyclovir by examining the potential of a variety of prodrugs, leading to the new compound valaciclovir hydrochloride. The second approach was to examine a large number of 5-substituted pyrimidines for activity against those viruses which were not as potently inhibited by acyclovir as are herpes simplex viruses, i.e., varicella zoster virus (VZV) and human cytomegalovirus (HCMV). This research led to the new chemical entity 882C for VZV. A third approach has been to examine drug combinations with acyclovir. This research led to the compound 348U, an inhibitor of herpes simplex virus ribonucleotide reductase which acts synergistically in combination with acyclovir. This manuscript will focus on the first two approaches leading to new compounds valaciclovir hydrochloride and 882C since Dr. Safrin details such background for 348U/acyclovir. Attempts to improve the bioavailability of acyclovir began a decade ago. Early prodrugs were compounds with alterations in the 6-substituent of the purine ring of acyclovir. The 6-amino congener required the cellular enzyme adenosine deaminase for conversion to acyclovir and the 6-deoxycongener was dependent on cellular xanthine oxidase for conversion. Neither of these prodrugs had a chronic toxicity profile in laboratory animals as good as acyclovir. Efforts were directed towards simpler esters and 18 amino acid esters were made. The pharmacokinetic profile of each prodrug was determined in rats by measuring the recovery of acyclovir in urine after oral dosing.(ABSTRACT TRUNCATED AT 250 WORDS)
Erratum (1991)

Centromere and kinetochoreThe terms 'centromere' and 'kinetochore' were originallycoined to describe the region(s) of each chromosome withwhich the spindle microtubules become associated (Riegeret al. 1976). In recent years, the term 'centromere' haslargely come to be used by morphologists to describe theprimary constriction of mitotic chromosomes. The termTunetochore' has been used to refer to the circular plaquestructure that rests on the surface of the centromericchromatin and into which microtubules are inserted(Jokelainen, 1967; Brinkley and Stubblefield, 1966). Thiscommentary is concerned with development of a rationalefor assignment of newly identified antigens to specificcentromere domains and, in particular, to the kinetochoredomain.The distributions of a number of centromere-associatedantigens that have been described in recent years are mostconveniently classified if the centromere is subdivided intothree principle domains, which we have previouslydesignated the kinetochore, central and pairing domains(Earnshaw and Rattner, 1989). Under this nomenclature,the kinetochore domain consists of both the kinetochoreand the subjacent chromatin upon which it rests (Earn-shaw and Rattner, 1989). The kinetochore is a small(0.4-0.6 urn diameter in PtKl cells; Roos, 1973) button-like structure that rests on the surface of the centromericchromatin. The most extensive mammalian kinetochoresare seen in the fusion chromosomes of the Indian muntjac,where they may be up 1.45/a to inn length (Comings andOkada, 1971).At metaphase, the kinetochore consists of a denseosmophilic outer plate 0.025-0.040 ^m thick that isseparated from the surface of the centromeric chromatinby an electron-lucent zone of similar thickness (Roos,1973; Rieder, 1982). The surface of the subjacent chroma-tin is often compacted into a second dense plate. A fibrouscorona is seen to radiate outward from the outer platewhenever microtubules are absent (Rieder, 1982).Much recent interest has been focussed on the kineto-chore outer plate, since this is where the majority ofmicrotubules are inserted. The detailed structure of thisplate is not known, although a variety of evidence suggeststhat it may contain a special form of chromatin. Thisevidence includes the presence of a fibrous substructureseen by electron microscopy (Ris and Witt, 1981; Rattner,1986; Rattner and Bazett-Jones, 1989), the susceptibilityof the structure to digestion with DNase (Pepper andBrinkley, 1980) and the presence of phosphate as revealed
Application of two‐dimensional gel electrophoresis in the study of cytoskeletal protein regulation during growth activation and differentiation (1990)

Two-dimensional gel electrophoresis was used to study the regulation of cytoskeletal protein synthesis during growth activation and development of the differentiated phenotype. We demonstrated a correlation between the state of organization and the expression of the respective cytoskeletal protein by showing that depolymerization of microtubules leads to a rapid decrease in new tubulin synthesis. We found that the synthesis of vimentin in both fibroblasts and epithelial cells correlates with extensive cell spreading on the substrate, while cytokeratin synthesis is maximal when cell to cell contacts are abundant. The analysis of cytoskeletal elements, involved directly in the formation of cell contacts, revealed that the level of vinculin synthesis is dependent on the extent of adherent type of cell contacts formed. Moreover, we found that the transient disappearance of vinculin from adhesion plaques of quiescent fibroblasts in response to serum factors was followed by an induction of vinculin mRNA and protein synthesis. The morphological changes associated with establishment of the differentiated phenotype were also found to include changes in the expression of the cytoskeletal-extracellular matrix complex. This was demonstrated in several differentiating systems: in 3T3 preadipocytes which change their shape from a fibroblastic to a spherical shape when stimulated to differentiate with adipogenic medium, we observed a decrease in mRNA levels and in the synthesis of fibronectin, beta-integrin, and the microfilament proteins, vinculin, alpha-actinin, tropomyosin and actin. The culturing of these cells on a certain extracellular matrix prevented the morphological changes occurring in the presence of adipogenic medium and blocked the shifts in cytoskeletal- and differentiation-related gene expression. Similar changes in the organization and expression of cytoskeletal proteins were identified during maturation of primary ovarian granulosa cell cultures, stimulated with gonadotropic hormones to form highly steroidogenic cells. The cell rounding and aggregation occurring during this process were associated with a decreased synthesis of vinculin, alpha-actinin, actin and the nonmuscle tropomyosins. The physiological relevance of these changes was suggested by the observation that the level of tropomyosin mRNA was lower in follicles of animals at late stages of granulosa cell maturation when compared to earlier stages. The expression of tissue-specific and cytoskeletal proteins was also determined in primary cultures of liver hepatocytes, maintained under conditions either favorable for growth or for expression of liver-specific functions. When DNA synthesis was elevated, cytoskeletal protein synthesis was high and that of liver-specific proteins was low.(ABSTRACT TRUNCATED AT 400 WORDS)
WISPCam: A battery-free RFID camera (2015)

Energy-scavenging devices with general-purpose microcontrollers can support arbitrarily complex sensing tasks in theory, but in practice, energy limitations impose severe constraints on the application space. Richer sensing such as image capture would enable many new applications to take advantage of energy scavenging. Richer sensing faces two key challenges: efficiently retaining the necessary amount of harvested energy, and storing and communicating large units of sensor data. This paper presents the WISPCam, a passive UHF RFID camera tag based on the Wireless Identification and Sensing Platform that overcomes these two challenges to support reliable image capture and transmission while powered by an RFID reader. The WISPCam uses a novel charge-storage scheme designed specifically to match the image sensor's needs. This scheme optimally balances capacitance and leakage to improve the sensitivity and efficiency of the power harvester. The WISPCam also uses a novel data storage and communication scheme to reliably support the transfer of complete images to an RFID reader application. The WISPCam makes battery-free image capture practical for applications such as mechanical gauge reading and surveillance, both demonstrated in this paper, and opens the door to richer sensing applications on battery-free devices.
Occurrence of QoI Fungicide Resistance in Cercospora sojina from Mississippi Soybean (2015)

Frogeye leaf spot, caused by Cercospora sojina Hara, is a foliar disease affecting soybean (Glycine max (L.) Merr.), often managed by applications of quinone outside inhibitor (QoI) fungicides. In 2013 and 2014, 634 C. sojina monoconidial isolates were collected from soybean fields throughout Mississippi. Initially, in vitro bioassays were performed to evaluate the sensitivity of 14 of 634 isolates plus a baseline. Resistant and sensitive isolates were characterized by determining the effective fungicide concentrations at which 50% of conidial germination was inhibited (EC<sub>50</sub>). The molecular mechanism of resistance was determined for all 634 isolates, using a PCR-RFLP method and comparing nucleotide sequences of the cytochrome b gene. The state of Mississippi was divided into five distinct geographical regions (the Hills, Delta, Pines, Capital, and Coast) based on estimates of total soybean hectares. The greatest proportion (16.7%) of QoI-sensitive isolates was collected in the Hills while the Coast had no QoI-sensitive isolates. QoI-sensitive isolates from the Pines, Capital, and Delta ranged from 1.6 to 7.0%. Results of this study determined that more than 93% of C. sojina isolates collected in Mississippi carried the G143A amino acid substitution, indicating a shift to a QoI-resistant population throughout Mississippi soybean fields.
Development and evaluation of a radioimmunoassay for Arg8-vasopressin, after extraction with Sep-Pak C18. (1985)

We describe a specific double-antibody radioimmunoassay for measuring arginine vasopressin (AVP) in human plasma. Antisera of high avidity were obtained from rabbits that had been injected with AVP coupled to bovine thyroglobulin. The antibody reacts with both the tripeptide tail and the pentapeptide ring of the molecule, thereby eliminating cross reaction with oxytocin. Synthetic AVP was labeled with 125I by a modification of the Chloramine-T technique. The specific activity of the labeled hormone was 29 MBq/micrograms of AVP, as estimated by self-displacement analysis. The assay involves Sep-Pak C18 extraction of acidified (pH 4) plasma. Recovery of [3H]AVP added to plasma averaged 86.6 (SD 6.1)% (n = 14). Dilution curves for plasma showed linearity of response with concentration. The overall sensitivity was 0.3 ng/L when 2-mL plasma samples were extracted. The intra-assay CV was 7.8% at 4.8 ng/L (n = 12) and the interassay CV was 12.3% (n = 16) and 6.3% (n = 14) at 2.7 and 4.1 ng/L concentrations, respectively.
The Oxidative Stressor Arsenite Activates Vascular Endothelial Growth Factor mRNA Transcription by an ATF4-dependent Mechanism (2005)

Aberrant retinal expression of vascular endothelial growth factor (VEGF) leading to neovascularization is a central feature of age-related macular degeneration and diabetic retinopathy, two leading causes of vision loss. Oxidative stress is suggested to occur in retinal tissue during age-related macular degeneration and diabetic retinopathy and is suspected in the mechanism of VEGF expression in these diseases. Arsenite, a thiol-reactive oxidative stressor, induces VEGF expression by a HIF-1alpha-independent mechanism. Previously, we demonstrated that homocysteine, an endoplasmic reticulum stressor, increases VEGF transcription by a mechanism dependent upon activating transcription factor ATF4. Because ATF4 is expressed in response to oxidative stress, we hypothesized that ATF4 was also responsible for increased VEGF transcription in response to arsenite. We now show that arsenite increased steady state levels of VEGF mRNA and activated transcription from a VEGF promoter construct. Arsenite induced eIF2alpha phosphorylation, resulting in increased ATF4 protein levels. Inactivation or loss of ATF4 greatly diminished the VEGF response to arsenite treatment. Overexpression of ATF4 was sufficient to activate the VEGF promoter, and arsenite cooperated with exogenous ATF4 to further activate the promoter. A complex containing ATF4 binds a DNA element at +1767 bp relative to the VEGF transcription start site, and DNA binding activity is increased by arsenite treatment. In addition, the ability of a thiol antioxidant, N-acetylcysteine, to inhibit the effect of arsenite on VEGF expression coincided with its ability to inhibit phosphorylation of eIF2alpha and ATF4 protein expression. Thus, arsenite-induced up-regulation of VEGF gene transcription occurs by an ATF4-dependent mechanism.
Synthesis and characterisation of poly(arylene sulfides), 9. Optimisation of the solvent composition for solution polymerisation of copper(I) 4‐bromobenzenethiolate at atmospheric pressure and structural investigations of low molar mass poly(1,4‐phenylene sulfide) (1987)

Abstract Solution polymerisation of copper(I) 4‐bromobenzenethiolate (CBT) was effected at atmospheric pressure using a range of quinoline/pyridine solvent mixtures. Yields of poly(1,4‐phenylene sulfide) (PPS) were evaluated and PPS fractionated into toluene soluble (TS) and 1‐chloronaphthalene soluble (CNS) material. The fractions were characterised by end‐group analysis, viscometry and differential scanning calorimetry. The yield of CNS PPS is optimum for solvent mixtures comprising 70–80 vol.‐% quinoline, whereas the molar mass of this fraction is at a maximum for 95 vol.‐% quinoline. Results are discussed in terms of the effects of reaction temperature, complexing of CBT by quinoline and pyridine, and copper(I) bromide‐catalysed debromination. A low molar mass TS PPS fraction prepared in pyridine was subjected to detailed structural analysis by IR, 1 H NMR and Raman spectroscopy. Evidence is presented to show that this material contains disulfide linkages and that thiol end‐groupings are absent. These results are discussed relative to possible structures for poly(arylene sulfides). The relevance of this observation to high molar mass samples of PPS and their chain extension and degradative behaviour is also discussed.
Regulation of Formyl Peptide Receptor Agonist Affinity by Reconstitution with Arrestins and Heterotrimeric G Proteins (2001)

Although heptahelical chemoattractant and chemokine receptors are known to play a significant role in the host immune response and the pathophysiology of disease, the molecular mechanisms and transient macroassemblies underlying their activation and regulation remain largely uncharacterized. We report herein real time analyses of molecular assemblies involving the formyl peptide receptor (FPR), a well described member of the chemoattractant subfamily of G protein-coupled receptors (GPCRs), with both arrestins and heterotrimeric G proteins. In our system, the ability to define and discriminate distinct, in vitro receptor complexes relies on quantitative differences in the dissociation rate of a fluorescent agonist as well as the guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) sensitivity of the complex, as recently described for FPR-G protein interactions. In the current study, we demonstrate a concentration- and time-dependent reconstitution of liganded, phosphorylated FPR with exogenous arrestin-2 and -3 to form a high agonist affinity, nucleotide-insensitive complex with EC(50) values of 0.5 and 0.9 microm, respectively. In contrast, neither arrestin-2 nor arrestin-3 altered the ligand dissociation kinetics of activated, nonphosphorylated FPR. Moreover, we demonstrated that the addition of G proteins was unable to alter the ligand dissociation kinetics or induce a GTP gamma S-sensitive state of the phosphorylated FPR. The properties of the phosphorylated FPR were entirely reversible upon treatment of the receptor preparation with phosphatase. These results represent to our knowledge the first report of the reconstitution of a detergent-solubilized, phosphorylated GPCR with arrestins and, furthermore, the first demonstration that phosphorylation of a nonvisual GPCR is capable of efficiently blocking G protein binding in the absence of arrestin. The significance of these results with respect to receptor desensitization and internalization are discussed.
Semantic segmentation using regions and parts (2012)

We address the problem of segmenting and recognizing objects in real world images, focusing on challenging articulated categories such as humans and other animals. For this purpose, we propose a novel design for region-based object detectors that integrates efficiently top-down information from scanning-windows part models and global appearance cues. Our detectors produce class-specific scores for bottom-up regions, and then aggregate the votes of multiple overlapping candidates through pixel classification. We evaluate our approach on the PASCAL segmentation challenge, and report competitive performance with respect to current leading techniques. On VOC2010, our method obtains the best results in 6/20 categories and the highest performance on articulated objects.
The Role of Surfactant Adsorption during Ultrasonication in the Dispersion of Single-Walled Carbon Nanotubes (2003)

The ionic surfactant-assisted dispersion of single-walled carbon nanotubes in aqueous solution has been studied by Raman and fluorescent spectroscopy during ultrasonic processing. During the process, an equilibrium is established between free individuals and aggregates or bundles that limits the concentration of the former that is possible. This equilibrium is a function of free sodium dodecyl sulfate concentration. At surfactant concentrations below this value, fluorescence is shifted to a lower energy due to an increase in micropolarity from water association at the nanotube surface. The mechanism of dispersion is postulated as the formation of gaps or spaces at the bundle ends in the high shear environment of the ultrasonicated solution. Surfactant adsorption and diffusion then propagate this space along the bundle length, thereby separating the individual nanotube. The former is found to be controlling, with the use of a derived kinetic model for the dispersion process and extraction of the characteristic rate of nanotube isolation.
The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expression (2012)

Cell cycle progression is dependent on two major waves of gene expression. Early cell cycle gene expression occurs during G1/S to generate factors required for DNA replication, while late cell cycle gene expression begins during G2 to prepare for mitosis. Here we demonstrate that the MuvB complex-comprised of LIN9, LIN37, LIN52, LIN54, and RBBP4-serves an essential role in three distinct transcription complexes to regulate cell cycle gene expression. The MuvB complex, together with the Rb-like protein p130, E2F4, and DP1, forms the DREAM complex during quiescence and represses expression of both early and late genes. Upon cell cycle entry, the MuvB complex dissociates from p130/DREAM, binds to B-Myb, and reassociates with the promoters of late genes during S phase. MuvB and B-Myb are required for the subsequent recruitment of FoxM1 to late gene promoters during G2. The MuvB complex remains bound to FoxM1 during peak late cell cycle gene expression, while B-Myb binding is lost when it undergoes phosphorylation-dependent, proteasome-mediated degradation during late S phase. Our results reveal a novel role for the MuvB complex in recruiting B-Myb and FoxM1 to promote late cell cycle gene expression and in regulating cell cycle gene expression from quiescence through mitosis.
Clinical manual of electrophysiology (1993)

Basic mechanisms clinical approach to arrhythmias pacing for brady-arrhythmias electrical therapy for tachy-arrhythmias ablative therapy: surgery and catheter ablation - cardiopulmonary resuscitation.
Heteromeric NMDA Receptors: Molecular and Functional Distinction of Subtypes (1992)

The N-methyl D-aspartate (NMDA) receptor subtype of glutamate-gated ion channels possesses high calcium permeability and unique voltage-dependent sensitivity to magnesium and is modulated by glycine. Molecular cloning identified three complementary DNA species of rat brain, encoding NMDA receptor subunits NMDAR2A (NR2A), NR2B, and NR2C, which are 55 to 70% identical in sequence. These are structurally related, with less than 20% sequence identity, to other excitatory amino acid receptor subunits, including the NMDA receptor subunit NMDAR1 (NR1). Upon expression in cultured cells, the new subunits yielded prominent, typical glutamate- and NMDA-activated currents only when they were in heteromeric configurations with NR1. NR1-NR2A and NR1-NR2C channels differed in gating behavior and magnesium sensitivity. Such heteromeric NMDA receptor subtypes may exist in neurons, since NR1 messenger RNA is synthesized throughout the mature rat brain, while NR2 messenger RNA show a differential distribution.
A unifying approach to hard and probabilistic clustering (2005)

We derive the clustering problem from first principles showing that the goal of achieving a probabilistic, or "hard", multi class clustering result is equivalent to the algebraic problem of a completely positive factorization under a doubly stochastic constraint. We show that spectral clustering, normalized cuts, kernel K-means and the various normalizations of the associated affinity matrix are particular instances and approximations of this general principle. We propose an efficient algorithm for achieving a completely positive factorization and extend the basic clustering scheme to situations where partial label information is available.
Synthetic exfoliative toxin A and B DNA probes for detection of toxigenic Staphylococcus aureus strains (1989)

Two methods for the detection of exfoliative toxin (ET) from Staphylococcus aureus were compared: (i) a phenotypic assay, electrosyneresis, and (ii) a genotypic assay, staphylococcal DNA hybridization with oligodeoxynucleotide probes. The probes were chosen from the previously determined sequences of serotype A and B of ET, one probe for serotype A and another for serotype B. Strains exhibiting ET production in electrosyneresis always possessed the ET gene(s). Conversely, some strains not exhibiting ET production in electrosyneresis harbored the ET gene(s). The latter strains produced levels of ET. ET-negative phage group 2 strains of S. aureus as well as tested coagulase-negative staphylococci did not possess the ET gene(s). The sensitivity of the DNA hybridization technique was 10(6) bacteria or 100 ng of genomic DNA.
Etanercept: a new era in the treatment of psoriatic arthritis. (2002)

Psoriatic arthritis (PsA) can exact a devastating physical and emotional toll from its sufferers. For decades, patients have been understandably dismayed by the shortcomings of the therapeutic approaches that have been available. Now, equipped with a greater understanding of the role of cytokines such as tumor necrosis factor in the origins of PsA, researchers have been able to develop cytokine inhibitors aimed precisely at the mechanisms of cutaneous and articular inflammation. When used in combination with physical rehabilitation, pharmacologic therapy can slow or arrest the progression of PsA and profoundly improve the quality of life of PsA patients.