gebhart/patrepeval huggingface dataset:
Cross Talk between Nucleotide Synthesis Pathways with Cellular Immunity in Constraining Hepatitis E Virus Replication (2016)

Viruses are solely dependent on host cells to propagate; therefore, understanding virus-host interaction is important for antiviral drug development. Since de novo nucleotide biosynthesis is essentially required for both host cell metabolism and viral replication, specific catalytic enzymes of these pathways have been explored as potential antiviral targets. In this study, we investigated the role of different enzymatic cascades of nucleotide biosynthesis in hepatitis E virus (HEV) replication. By profiling various pharmacological inhibitors of nucleotide biosynthesis, we found that targeting the early steps of the purine biosynthesis pathway led to the enhancement of HEV replication, whereas targeting the later step resulted in potent antiviral activity via the depletion of purine nucleotide. Furthermore, the inhibition of the pyrimidine pathway resulted in potent anti-HEV activity. Interestingly, all of these inhibitors with anti-HEV activity concurrently triggered the induction of antiviral interferon-stimulated genes (ISGs). Although ISGs are commonly induced by interferons via the JAK-STAT pathway, their induction by nucleotide synthesis inhibitors is completely independent of this classical mechanism. In conclusion, this study revealed an unconventional novel mechanism of cross talk between nucleotide biosynthesis pathways and cellular antiviral immunity in constraining HEV infection. Targeting particular enzymes in nucleotide biosynthesis represents a viable option for antiviral drug development against HEV. HEV is the most common cause of acute viral hepatitis worldwide and is also associated with chronic hepatitis, especially in immunocompromised patients. Although often an acute and self-limiting infection in the general population, HEV can cause severe morbidity and mortality in certain patients, a problem compounded by the lack of FDA-approved anti-HEV medication available. In this study, we have investigated the role of the nucleotide synthesis pathway in HEV infection and its potential for antiviral drug development. We show that targeting the later but not the early steps of the purine synthesis pathway exerts strong anti-HEV activity. In particular, IMP dehydrogenase (IMPDH) is the most important anti-HEV target of this cascade. Importantly, the clinically used IMPDH inhibitors, including mycophenolic acid and ribavirin, have potent anti-HEV activity. Furthermore, targeting the pyrimidine synthesis pathway also exerts potent antiviral activity against HEV. Interestingly, antiviral effects of nucleotide synthesis pathway inhibitors appear to depend on the medication-induced transcription of antiviral interferon-stimulated genes. Thus, this study reveals an unconventional novel mechanism as to how nucleotide synthesis pathway inhibitors can counteract HEV replication.
Effects of the antimitotic natural product dolastatin 10, and related peptides, on the human malarial parasite Plasmodium falciparum (2003)

Microtubule inhibitors from several chemical classes can block the growth and development of malarial parasites, reflecting the importance of microtubules in various essential parasite functions. With the spread of antimalarial drug resistance, there is an urgent need for new approaches to the chemotherapy of this devastating disease. We investigated the effects of two naturally occurring marine peptides, dolastatin 10 and dolastatin 15, and 10 synthetic dolastatin 10-based compounds (auristatins), on cultured malarial parasites of the species most lethal to humans, Plasmodium falciparum. Dolastatin 10 was a more potent inhibitor of P. falciparum than any other previously described microtubule inhibitor, with a median inhibitory concentration (IC50) of 10-10 M. Dolastatin 15 was less active, and compounds of the auristatin series had various potencies. Comparison of the concentrations required to inhibit P. falciparum and mammalian cell proliferation showed that the orders of potency were not the same. Dolastatin 10 and auristatin PE caused arrested nuclear division and apparent disassembly of mitotic microtubular structures in the parasite. The effects of these agents were, superficially at least, similar to those of vinblastine but different from those of paclitaxel. These studies indicate that compounds binding in the 'Vinca domain' of tubulin can be highly potent antimalarial agents.
Syntheses of 3-Nitro-2-pyridinesulfenates (1981)

In the presence of tertiary mine under anhydrous conditions 3-nitro-2pyridinesulfenyl (Npys) chloride reacts smoothly with hydroxy compounds, including various alcohols and hydroxy acids, to give the corresponding sulfenates.+ 0 6 .
Digitally programmable wavelength-switching technology (2002)

As the information flow in the fiber rapidly increased, dense wavelength-division-multiplexing (DWDM) technology becomes the ultimate solution in meeting the challenge of huge bandwidth demand. In this paper, we introduce a novel wavelength slicing concept that results a digitally programmable wavelength switch for the DWDM networks. The wavelength switch demonstrated not only achieves wavelength filtering and signal routing operations in one single compact device, but also provides superior performance based on its innovative architecture. Moreover, this concept provides a scale factor of log/sub 2/ N for the controlling management, as the number of optical channel N is increased. This unique logarithm scaling relation will greatly simplify the hardware complexity to implement large-size WDM interconnection networks.
Peptide hormones and lipopeptides: from self‐assembly to therapeutic applications (2017)

This review describes the properties and activities of lipopeptides and peptide hormones and how the lipidation of peptide hormones could potentially produce therapeutic agents combating some of the most prevalent diseases and conditions. The self-assembly of these types of molecules is outlined, and how this can impact on bioactivity. Peptide hormones specific to the uptake of food and produced in the gastrointestinal tract are discussed in detail. The advantages of lipidated peptide hormones over natural peptide hormones are summarised, in terms of stability and renal clearance, with potential application as therapeutic agents. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.
In Situ‐Gelling, Erodible N‐Isopropylacrylamide Copolymers (2005)

Copolymers of N-isopropylacrylamide, 2-hydroxyethyl methacryl lactate [(HEMA)-lactate] and acrylic acid (AAc) were prepared with varying mole ratios of monomers to develop copolymers with gelation properties above a certain concentration for a bioerodible, in-situ gelling material. The copolymers formed gels in situ under physiological condition. The gelation temperature of the copolymers decreased as the HEMA-lactate content of the copolymers increased due to the hydrophobicity of HEMA-lactate, and increased as the AAc content increased due to the hydrophilicity of AAc. The gels redissolve at 37 degrees C as their LCSTs increase above 37 degrees C due to the hydrolysis of the HEMA-lactate pendant groups.
RESPONSE OF BROILER CHICKEN TO DIETARY SUPPLEMENTATION OF ORGANIC ACIDS (2011)

The aim of the study was to determine the effect of dietary supplementation of organic acids on the performance, gut health and carcass characteristics of broiler chicken. Results indicated that the birds fed diets supplemented with organic acids showed significantly (p<0.05) higher body weight gains and feed conversion ratio. Maximum improvement was achieved in the group fed 3% fumaric acid in the diet. Differences in the cumulative feed consumption were non-significant (p>0.05) among all the treatment groups. Addition of organic acids in broiler diets increased the villus height in all the segments of small intestines but the differences were non-significant (p>0.05) in case of ileum. No effect (p>0.05) on carcass characteristics was observed among all treatments except for length and weight of small intestines which were significantly (p<0.05) increased in the groups fed supplemental organic acids.
A Simple Model of Bipedal Walking Predicts the Preferred Speed–Step Length Relationship (2001)

We used a simple model of passive dynamic walking, with the addition of active powering on level ground, to study the preferred relationship between speed and step length in humans. We tested several hypothetical metabolic costs, with one component proportional to the mechanical work associated with pushing off with the stance leg at toe-off, and another component associated with several possible costs of forcing oscillations of the swing leg. For this second component, a cost based on the amount of force needed to oscillate the leg divided by the time duration of that force predicts the preferred speed-step length relationship much better than other costs, such as the amount of mechanical work done in swinging the leg. The cost of force/time models the need to recruit fast muscle fibers for large forces at short durations. The actual mechanical work performed by muscles on the swing leg appears to be of relatively less importance, although it appears to be minimized by the use of short bursts of muscle activity in near-isometric conditions. The combined minimization of toe-off mechanical work and force divided by time predicts the preferred speed-step length relationship.
Dialogue Act Modeling for Automatic Tagging and Recognition of Conversational Speech (2000)

We describe a statistical approach for modeling dialogue acts in conversational speech, i.e., speech-act-like units such as Statement, Question, Backchannel, Agreement, Disagreement, and Apology. Our model detects and predicts dialogue acts based on lexical, collocational, and prosodic cues, as well as on the discourse coherence of the dialogue act sequence. The dialogue model is based on treating the discourse structure of a conversation as a hidden Markov model and the individual dialogue acts as observations emanating from the model states. Constraints on the likely sequence of dialogue acts are modeled via a dialogue act n-gram. The statistical dialogue grammar is combined with word n-grams, decision trees, and neural networks modeling the idiosyncratic lexical and prosodic manifestations of each dialogue act. We develop a probabilistic integration of speech recognition with dialogue modeling, to improve both speech recognition and dialogue act classification accuracy. Models are trained and evaluated using a large hand-labeled database of 1,155 conversations from the Switchboard corpus of spontaneous human-to-human telephone speech. We achieved good dialogue act labeling accuracy (65% based on errorful, automatically recognized words and prosody, and 71% based on word transcripts, compared to a chance baseline accuracy of 35% and human accuracy of 84%) and a small reduction in word recognition error.
Treatment Options for Rheumatoid Arthritis: Celecoxib, Leflunomide, Etanercept, and Infliximab (2000)

Celecoxib, leflunomide, etanercept, and infliximab are the newest agents approved for RA. Clinical trials have shown that these agents are beneficial in the treatment of RA; however, long-term safety and efficacy data are lacking.
Combined use of root conditioning, fibrin-fibronectin system and a collagen membrane to treat a localized gingival recession: a 10-case report. (1997)

The purpose of this research was to evaluate the effectiveness of combined root surface conditioning with tetracycline HCI, fibrin sealing system, guided tissue regeneration procedure and coronal sliding flap application in the treatment of localized gingival recessions. The present study was conducted on 10 patients with localized facial recessions of at least 3mm. A trapezium-shaped flap was elevated apically to the margin of the bone dehiscence and the root surface was thoroughly scaled by hand instruments and burs. Tetracycline HCI (pH 1.9) solution was then topically applied for 5 minutes and the root surface thoroughly rinsed with sterile saline. A collagen membrane was trimmed and shaped to cover the entire root surface and later removed and a fibrin sealing system injected onto the root surface. Immediately membrane was placed again on the root surface without applying any pressure. The flap was sutured in the coronal position to completely cover the root surface and membrane. Control group patients were treated with only coronal sliding flap operation. Sutures were removed 10 days after surgery. Patients were clinically reevaluated 6 months postoperatively. The mean amount of root surface coverage obtained was similar in the test and control groups (test = 71.7%; control = 68.55%) but the clinical attachment gain (test = 4.21mm; control = 2.86mm) and pocket depth variations (test = 1.14mm reduction; control = 0.07mm reduction) differed significantly (P < 0.001). This study found promising healing of localized gingival recessions to result from a combined use of tetracycline HCI root demineralization, fibrin sealing system application, guided tissue regeneration procedure and coronal sliding flap operation.
Intraventricular Brain-Derived Neurotrophic Factor Reduces Infarct Size after Focal Cerebral Ischemia in Rats (1997)

Brain-derived neurotrophic factor (BDNF), acting through the high-affinity receptor tyrosine kinase (TrkB), is widely distributed throughout the central nervous system and displays in vitro trophic effects on a wide range of neuronal cells, including hippocampal, cerebellar, and cortical neurons. In vivo, BDNF rescues motorneurons, hippocampal, and substantia nigral dopaminergic cells from traumatic and toxic brain injury. After transient middle cerebral artery occlusion (MCAO), upregulation of BDNF-mRNA in cortical neurons suggests that BDNF potentially plays a neuroprotective role in focal cerebral ischemia. In the current study, BDNF (2.1 micrograms/d) in vehicle or vehicle alone (controls) was delivered intraventricularly for 8 days, beginning 24 hours before permanent middle cerebral artery occlusion by intraluminal suture in Wistar rats (n = 13 per group). There were no differences in physiological variables recorded during surgery for the two groups. Neurological deficit (0 to 4 scale), which was assessed on a daily basis, improved in BDNF-treated animals compared with controls (P < 0.05; analysis of variance and Scheffe's test). There were no significant differences in weight in BDNF-treated animals and controls during the experiment. After elective killing on day 7 after MCAO, brains underwent 2,3,5-triphenyltetrazolium chloride staining for calculation of the infarct volume and for histology (hematoxylin and eosin and glial fibrillary acid protein). The mean total infarct volume was 83.1 +/- 27.1 mm3 in BDNF-treated animals and 139.2 +/- 56.4 mm3 in controls (mean +/- SD; P < 0.01, unpaired, two-tailed t-test). The cortical infarct volume was 10.8 +/- 7.1 mm3 in BDNF-treated animals and 37.9 +/- 19.8 mm3 in controls (mean +/- SD; P < 0.05; unpaired, two-tailed t-test), whereas ischemic lesion volume in caudoputaminal infarction was not significantly different. These results show that pretreatment with intraventricular BDNF reduces infarct size after focal cerebral ischemia in rats and support the hypothesis of a neuroprotective role for BDNF in stoke.
Emerging drugs for overactive bladder (2015)

Newer antimuscarinics have better tolerability. Long-term data for mirabegron has shown that it is more effective in severe OAB. Combination drugs may prove to be more effective with less adverse effects. Emerging treatments with TSI, lipotoxin and gene therapy appear promising.
Subunit Composition Determines E2F DNA-Binding Site Specificity (1997)

The product of the retinoblastoma (Rb) susceptibility gene, Rb-1, regulates the activity of a wide variety of transcription factors, such as E2F, in a cell cycle-dependent fashion. E2F is a heterodimeric transcription factor composed of two subunits each encoded by one of two related gene families, denoted E2F and DP. Five E2F genes, E2F-1 through E2F-5, and two DP genes, DP-1 and DP-2, have been isolated from mammals, and heterodimeric complexes of these proteins are expressed in most, if not all, vertebrate cells. It is not yet clear whether E2F/DP complexes regulate overlapping and/or specific cellular genes. Moreover, little is known about whether Rb regulates all or a subset of E2F-dependent genes. Using recombinant E2F, DP, and Rb proteins prepared in baculovirus-infected cells and a repetitive immunoprecipitation-PCR procedure (CASTing), we have identified consensus DNA-binding sites for E2F-1/DP-1, E2F-1/DP-2, E2F-4/DP-1, and E2F-4/DP-2 complexes as well as an Rb/E2F-1/DP-1 trimeric complex. Our data indicate that (i) E2F, DP, and Rb proteins each influence the selection of E2F-binding sites; (ii) E2F sites differ with respect to their intrinsic DNA-bending properties; (iii) E2F/DP complexes induce distinct degrees of DNA bending; and (iv) complex-specific E2F sites selected in vitro function distinctly as regulators of cell cycle-dependent transcription in vivo. These data indicate that the specific sequence of an E2F site may determine its role in transcriptional regulation and suggest that Rb/E2F complexes may regulate subsets of E2F-dependent cellular genes.
Biochemical Characterization of the DNA Helicase Activity of the Escherichia coli RecQ Helicase (2001)

We demonstrate that RecQ helicase from Escherichia coli is a catalytic helicase whose activity depends on the concentration of ATP, free magnesium ion, and single-stranded DNA-binding (SSB) protein. Helicase activity is cooperative in ATP concentration, with an apparent S(0.5) value for ATP of 200 microm and a Hill coefficient of 3.3 +/- 0.3. Therefore, RecQ helicase utilizes multiple, interacting ATP-binding sites to mediate double-stranded DNA (dsDNA) unwinding, implicating a multimer of at least three subunits as the active unwinding species. Unwinding activity is independent of dsDNA ends, indicating that RecQ helicase can unwind from both internal regions and ends of dsDNA. The K(M) for dsDNA is 0.5-0.9 microm base pairs; the k(cat) for DNA unwinding is 2.3-2.7 base pairs/s/monomer of RecQ helicase; and unexpectedly, helicase activity is optimal at a free magnesium ion concentration of 0.05 mm. Omitting Escherichia coli SSB protein lowers the rate and extent of dsDNA unwinding, suggesting that RecQ helicase associates with the single-stranded DNA (ssDNA) product. In agreement, the ssDNA-dependent ATPase activity is reduced in proportion to the SSB protein concentration; in its absence, ATPase activity saturates at six nucleotides/RecQ helicase monomer and yields a k(cat) of 24 s(-1). Thus, we conclude that SSB protein stimulates RecQ helicase-mediated unwinding by both trapping the separated ssDNA strands after unwinding and preventing the formation of non-productive enzyme-ssDNA complexes.
Latent Heat Storage Materials and Systems: A Review (2005)

The use of a latent heat storage system using Phase Change Materials (PCM) is an effective way of storing thermal energy (solar energy, off-peak electricity, industrial waste heat) and has the advantages of high storage density and the isothermal nature of the storage process. It has been demonstrated that, for the development of a latent heat storage system, choice of the PCM plays an important role in addition to heat transfer mechanism. The information on the latent heat storage materials and systems is enormous and published widely in the literatures. In this paper, we make an effort to gather the information from the previous works on PCMs and latent heat storage systems. This review will help to find a suitable PCM for various purposes a suitable heat exchanger with ways to enhance the heat transfer, and it will also help to provide a variety of designs to store the heat using PCMs for different applications, i.e. space heating & cooling, solar cooking, greenhouses, solar water heating and waste heat recovery systems. Measurement techniques of thermophysical properties, studies on thermal cycles for long term stability, corrosion of the PCMs and enhancement of heat transfer in PCM are discussed. New PCM innovations are also included for the awareness of new applications. This paper contains a list of about 250 PCMs and more than 250 references.
Marketing at the Frontier (2003)

Abstract This paper examines the role of informal marketers and the sale, promotion and distribution of branded consumer goods in African countries and in other less developed countries. The emphasis of this paper is on the motivations of small-scale informal market vendors, the pressures they face in developing their selling strategies and the implications of each for multinationals seeking access to these markets. This research posits that three major “drivers” inform the behavior of small-scale vendors and that these drivers are themselves closely related to the level of economic uncertainty that exists at a macro level and micro level in LDCs. Implications for multinational companies with branded products are discussed as well as areas in which marketing mix adaptations may allow for more control over the distribution of branded goods. The Makola market in Accra, Ghana provides the field context for exploring these issues.
Signatures of β-Peptide Unfolding in Two-Dimensional Vibrational Echo Spectroscopy:  A Simulation Study (2001)

An ensemble of exciton Hamiltonians for the amide-I band of the folded and unfolded states of a helical beta-heptapeptide is generated using a molecular dynamics (MD) simulation. The correlated fluctuations of its parameters and their signatures in two-dimensional (2D) vibrational echo spectroscopy are computed. This technique uses infrared pulse sequences to provide ultrafast snapshots of molecular structural fluctuations, in analogy with multidimensional NMR. The present study demonstrates that, by combining a method of calculating the vibrational Hamiltonian from MD snapshots and the nonlinear exciton equations (NEE), it may be possible to simulate realistic multidimensional IR spectra of chemically and biologically interesting systems.
Activation of the antioxidant response element in primary cortical neuronal cultures derived from transgenic reporter mice (2002)

Many phase II protective genes contain a cis -acting enhancer region known as the antioxidant response element (ARE). Increased expression of these genes contributes to the protection of cells from oxidative stress. Transgenic reporter mice were created that carry in their genome the core ARE coupled to the human placental alkaline phosphatase (hPAP) reporter gene. Primary cortical cultures derived from these mice were treated with tBHQ resulting in a dose-dependent increase in hPAP activity. Histochemical staining for hPAP activity was observed in both glia and neurons from tBHQ-treated cultures. The tBHQ-mediated increase in hPAP was not affected by the antioxidant glutathione monoethyl ester (GSHEE), whereas the increase in hPAP following DEM treatment was completely blocked by GSHEE. Pre-treatment of cultures with the PI3-kinase inhibitor LY 294002 demonstrated a dose-dependent decrease in tBHQ-induced hPAP activity. In addition, the tBHQ-mediated expression of ARE-driven genes in primary cortical cultures was blocked by LY 294002. Interestingly, basal expression of Nrf2 was also inhibited by LY 294002. We theorize that increased levels of genes controlled by the ARE are important for cellular protection against oxidative stress. These ARE-hPAP transgenic mice will be an important in vivo model for testing our hypothesis.