gebhart/patrepeval huggingface dataset:
Cross-resistance mechanism of respiratory syncytial virus against structurally diverse entry inhibitors (2014)

Respiratory syncytial virus (RSV) is a leading pediatric pathogen that is responsible for a majority of infant hospitalizations due to viral disease. Despite its clinical importance, no vaccine prophylaxis against RSV disease or effective antiviral therapeutic is available. In this study, we established a robust high-throughput drug screening protocol by using a recombinant RSV reporter virus to expand the pool of RSV inhibitor candidates. Mechanistic characterization revealed that a potent newly identified inhibitor class blocks viral entry through specific targeting of the RSV fusion (F) protein. Resistance against this class was induced and revealed overlapping hotspots with diverse, previously identified RSV entry blockers at different stages of preclinical and clinical development. A structural and biochemical assessment of the mechanism of unique, broad RSV cross-resistance against structurally distinct entry inhibitors demonstrated that individual escape hotspots are located in immediate physical proximity in the metastable conformation of RSV F and that the resistance mutations lower the barrier for prefusion F triggering, resulting in an accelerated RSV entry kinetics. One resistant RSV recombinant remained fully pathogenic in a mouse model of RSV infection. By identifying molecular determinants governing the RSV entry machinery, this study spotlights a molecular mechanism of broad RSV resistance against entry inhibition that may affect the impact of diverse viral entry inhibitors presently considered for clinical use and outlines a proactive design for future RSV drug discovery campaigns.
Sequence Variability of Simian Immunodeficiency Virus in a Persistently Infected Rhesus Monkey (1990)

A juvenile rhesus monkey that was inoculated intravenously with molecularly cloned SIVmac239 became persistently infected. A modified polymerase chain reaction (PCR) procedure was used to specifically amplify full-length envelope (env) gene sequences from DNA extracted from peripheral blood mononuclear cells (PBMC), lymph node tissue, and cells infected with recovered virus at 69 and 93 weeks post-infection. Extensive sequence variability accumulated in vivo in spite of infection with molecularly cloned virus. In the central portion of env. sequence variability was largely confined to three discrete regions.
Security information and event management in the cloud computing infrastructure (2014)

Security of information systems is a current topic. In the case of cloud environment it is even a critical factor. In large environments like the cloud computing systems, it can be difficult to maintain a comprehensive view of the safety of the individual elements. For this reason, the utilization of technology that would allow central monitoring and that would help to maintain this awareness. Such technology is precisely Security Information and Event Management (SIEM). The main objective of this paper is to analyze the possibilities and approaches of SIEM in terms of technical requirements, logic and legal framework of the Czech Republic. On the analytical basis, the framework, which is bounding the utilization of SIEM in a cloud computing environment is proposed.
Bias in Recent Papers on Diets and Drugs in Peer-Reviewed Medical Journals (2004)

Recent efforts by medical journal staffs to improve the quality of research papers have had mixed results. Examples are given to show that randomized, placebocontrolled trials are not free from bias and that the failure to include all-cause death rates can be extremely misleading, as can the use of relative risks in the absence of absolute risks. Other examples show how the conclusions in an abstract may not agree with the data in the body of the paper, or do not tell the whole truth. Still others use false surrogate endpoints or faulty trial protocols to favor a desired outcome. The whole picture may be seen as a breakdown of the peer-review system.
Salvage robotic prostatectomy for radio recurrent prostate cancer: technical challenges and outcome analysis (2016)

sRARP is increasingly acceptable as a treatment modality to be offered to men who fail initial radiation treatment but should be accompanied by appropriate counselling regarding the potential functional outcomes and complications. Series with longer follow up will be helpful to assess the durability of oncological outcomes while improvements in patient selection and adaption of meticulous surgical technique around the apex could improve continence rates. The concept of concomitant extended PLND remains an issue for debate and the experience with this approach at the time of sRARP and its benefit need further scrutiny.
Physiological evaluation of mungbean (Vigna radiata (l.) Wilczek) cultivars for heat tolerance (2015)

Mungbean is adapted to relatively warm, dry climatic conditions of summer when day temperatures rise above 40°C during reproductive period which often results in substantial yield reduction. Therefore breeding for heat tolerance with improved yield had been a long term goal for mungbean vaietal improvement programme. The effect of heat stress during reproductive stage was investigated based on yield attributing traits, stress indices and growing degree days (°Cd) in 20 high yielding mungbean cultivars released from different agro climatic zones of India. The cultivars were grown in Randomized Block Design with three replications in two environments, viz., non-stress environment (NSE) (15th July sowing) and heat-stress environment (HSE) (7th April sowing). It was seen that genotypic differences and genotype × environment interactions were significant for all the characters. Among the cultivars studied, three cultivars viz., Samrat, IPM 02-3 and IPM 2–14 were identified as the heat tolerant cultivars as indicated by their low heat susceptibility index. The thermal time (Growing degree days, °Cd) to reach mean cropgrowthdurationwas 1662°Cd under NSE while, itwas 1471°Cd under HSE.
The Pierre Auger Observatory: Contributions to the 33rd International Cosmic Ray Conference (ICRC 2013) (2013)

Abstract Not Provided
The protein folding challenge in psychrophiles: facts and current issues (2011)

Summary The protein folding process in psychrophiles is impaired by low temperature, which exerts several physicochemical constraints, such as a decrease in the folding rate, reduced molecular diffusion rates and increased solvent viscosity, which interfere with conformational sampling. Furthermore, folding assistance is required at various folding steps according to the protein size. Recent studies in the field have provided contrasting and sometimes contradictory results, although protein folding generally appears as a rate‐limiting step for the growth of psychrophiles. It is proposed here that these discrepancies reflect the diverse adaptive strategies adopted by psychrophiles in order to allow efficient protein folding at low temperature. Cold adaptations apparently superimpose on pre‐existing cellular organization, resulting in different adaptive strategies. In addition, microbial lifestyle further modulates the properties of the chaperone machinery, which possibly explains the occurrence of cold‐adapted and non‐cold‐adapted protein chaperones in psychrophiles.
On the volume of a hyperbolic octahedron with $$\bar 3$$ -symmetry (2015)

We consider hyperbolic octahedra with $$\bar 3$$ -symmetry. For these octahedra, we find existence conditions, establish relations between the edge lengths and dihedral angles, and obtain exact formulas for the volumes.
Impact of X Chromosome Genes in Explaining the Excess Risk of Cancer in Males (2009)

The authors examined cancer incidence sex ratios in Denmark for 1943-2003 by age group. At nongenital/nonbreast sites, incidences were consistently higher in males. While environmental factors dominate cancer risk, the authors hypothesized that the higher risk in males might be explained by unspecified X chromosome genes' protecting female cells from genotoxic damage. If so, cancer susceptibility would be passed from parent to offspring differently by sex. The authors compared relative risks in offspring of parents with and without cancer histories. For all comparisons, relative risks were similar in offspring of fathers with cancer (relative risk (RR) = 1.14, 95% confidence interval: 1.08, 1.20). Risks in offspring were higher for parents diagnosed before age 50 years and for cancers at the same site rather than different sites. Genital cancer risks were increased in same-sex offspring of parents with genital cancers. Breast cancer risks were high in both daughters (RR = 2.37) and sons (RR = 4.63) of mothers with breast cancer and in daughters (RR = 5.96) of fathers with breast cancer. Thus, X chromosome genetic factors were not responsible for the excess risk of cancer in males. Susceptibility to genital cancer was increased in same-sex offspring, and breast cancer risks were increased in both sons and daughters when either parent had had breast cancer.
Advanced Taste Sensors Based on Artificial Lipids with Global Selectivity to Basic Taste Qualities and High Correlation to Sensory Scores (2010)

Effective R&D and strict quality control of a broad range of foods, beverages, and pharmaceutical products require objective taste evaluation. Advanced taste sensors using artificial-lipid membranes have been developed based on concepts of global selectivity and high correlation with human sensory score. These sensors respond similarly to similar basic tastes, which they quantify with high correlations to sensory score. Using these unique properties, these sensors can quantify the basic tastes of saltiness, sourness, bitterness, umami, astringency and richness without multivariate analysis or artificial neural networks. This review describes all aspects of these taste sensors based on artificial lipid, ranging from the response principle and optimal design methods to applications in the food, beverage, and pharmaceutical markets.
The in vitro selection world (2016)

Through iterative cycles of selection, amplification, and mutagenesis, in vitro selection provides the ability to isolate molecules of desired properties and function from large pools (libraries) of random molecules with as many as 10(16) distinct species. This review, in recognition of a quarter of century of scientific discoveries made through in vitro selection, starts with a brief overview of the method and its history. It further covers recent developments in in vitro selection with a focus on tools that enhance the capabilities of in vitro selection and its expansion from being purely a nucleic acids selection to that of polypeptides and proteins. In addition, we cover how next generation sequencing and modern biological computational tools are being used to complement in vitro selection experiments. On the very least, sequencing and computational tools can translate the large volume of information associated with in vitro selection experiments to manageable, analyzable, and exploitable information. Finally, in vivo selection is briefly compared and contrasted to in vitro selection to highlight the unique capabilities of each method.
A DNA damage signal activates and derepresses exon inclusion in Drosophila TAF1 alternative splicing (2008)

Signal-dependent alternative splicing is important for regulating gene expression in eukaryotes, yet our understanding of how signals impact splicing mechanisms is limited. A model to address this issue is alternative splicing of Drosophila TAF1 pre-mRNA in response to camptothecin (CPT)-induced DNA damage signals. CPT treatment of Drosophila S2 cells causes increased inclusion of TAF1 alternative cassette exons 12a and 13a through an ATR signaling pathway. To evaluate the role of TAF1 pre-mRNA sequences in the alternative splicing mechanism, we developed a TAF1 minigene (miniTAF1) and an S2 cell splicing assay that recapitulated key aspects of CPT-induced alternative splicing of endogenous TAF1. Analysis of miniTAF1 indicated that splice site strength underlies independent and distinct mechanisms that control exon 12a and 13a inclusion. Mutation of the exon 13a weak 5' splice site or weak 3' splice site to a consensus sequence was sufficient for constitutive exon 13a inclusion. In contrast, mutation of the exon 12a strong 5' splice site or moderate 3' splice site to a consensus sequence was only sufficient for constitutive exon 12a inclusion in the presence of CPT-induced signals. Analogous studies of the exon 13 3' splice site suggest that exon 12a inclusion involves signal-dependent pairing between constitutive and alternative splice sites. Finally, intronic elements identified by evolutionary conservation were necessary for full repression of exon 12a inclusion or full activation of exon 13a inclusion and may be targets of CPT-induced signals. In summary, this work defines the role of sequence elements in the regulation of TAF1 alternative splicing in response to a DNA damage signal.
A Model‐Derived Global Climatology of UV Irradiation at the Earth's Surface (1999)

Abstract- We present calculations of the geographical distribution of the dose rate at the surface of UVB (280-320 nm), UVA (320-400 nm) and, using biological action spectra, the effective radiation for erythema, cataracts and keratitis. A multistream radiative transfer model is used in conjunction with a multiyear climatology of ozone, cloud, surface pressure, surface albedo, temperature and a rudimentary representation of aerosols to calculate the clear-sky and all-sky irradiances. Model outputs are evaluated using daily UV measurements and found to be accurate to about ±10% for clear skies and ±20% for all-sky conditions. The effects of UV-weighted surface albedo, surface altitude, sun-earth separation and the vertical distribution of ozone and temperature are included. The results show that the sun's position is the most important factor in determining the geographical pattern of global daily UV rather than column ozone, cloud, surface pressure, daylength or surface albedo. Over elevated regions, the effect of the differences in surface pressure on daily doses was found to be more significant than the effect of the differences in column ozone. Clouds reduce the clear-sky UV dose from a few percent over arid and semiarid regions to 45% in regions with frequent midlatitude depressions.
Synthesis of β‐Keto Esters Promoted by Yttria‐Zirconia Based Lewis Acid Catalyst. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
One‐step refolding and purification of recombinant human tumor necrosis factor‐α (rhTNF‐α) using ion‐exchange chromatography (2014)

Protein refolding is a key step for the production of recombinant proteins, especially at large scales, and usually their yields are very low. Chromatographic-based protein refolding techniques have proven to be superior to conventional dilution refolding methods. High refolding yield can be achieved using these methods compared with dilution refolding of proteins. In this work, recombinant human tumor necrosis factor-α (rhTNF-α) from inclusion bodies expressed in Escherichia coli was renatured with simultaneous purification by ion exchange chromatography with a DEAE Sepharose FF column. Several chromatographic parameters influencing the refolding yield of the denatured/reduced rhTNF-α, such as the urea concentration, pH value and concentration ratio of glutathione/oxidized glutathione in the mobile phase, were investigated in detail. Under optimal conditions, rhTNF-α can be renatured and purified simultaneously within 30 min by one step. Specific bioactivity of 2.18 × 10(8) IU/mg, purity of 95.2% and mass recovery of 76.8% of refolded rhTNF-α were achieved. Compared with the usual dilution method, the ion exchange chromatography method developed here is simple and more effective for rhTNF-α refolding in terms of specific bioactivity and mass recovery.
Assignment methods for spatial reuse TDMA (2000)

Spatial reuse TDMA is an access scheme for multi-hop radio networks. The idea is to increase capacity by letting several radio terminals use the same time slot when possible. A time slot can be shared when the radio units are geographically separated such that small interference is obtained. STDMA schedules can assign transmission rights to nodes or alternatively assign transmission rights to links, i.e. transmitter/receiver pairs. Here we compare these two methods and determine which one is preferable. We show that only the connectivity of the network and the input traffic load of the network is needed in order to determine whether node or link assignment is preferable.
A survey of pendant donor-functionalised (N,O) phosphine ligands for Cr-catalysed ethylene tri- and tetramerisation (2014)

Selected phosphine-based ligands plus chromium have been found to be promising candidates for MAO-free trimerisation and tetramerisation of ethylene.
New ethanol and propylene glycol free gel formulations containing a minoxidil-methyl-β-cyclodextrin complex as promising tools for alopecia treatment (2014)

New topical totally aqueous formulations that improve the low water solubility of minoxidil and realize an adequate permeability of drug in the skin are proposed. These formulations are lacking in propylene glycol and alcohol that are the principal irritant ingredients present in minoxidil commercial solutions. In order to enhance poor water solubility of minoxidil randomly methyl-β-cyclodextrin was used, and four hydrogels such as, calcium alginate, sodium alginate, carbopol 934 and hydroxyethylcellulose were utilized to ensure a prolonged time of contact with the scalp. The inclusion complex minoxidil/methyl-β-cyclodextrin with a molar ratio 1:1 was obtained by freeze drying and evaluated by NMR, FT-IR and DSC analysis. An apparent stability constant of formed inclusion complex was calculated by phase solubility diagram and its value was 400 M(-1). The solid inclusion complex was used to prepare gel formulations with similar dose to minoxidil commercial solution. The gels were evaluated for various technological parameters including rheological behavior, in vitro drug release and ex vivo permeation through pig skin. The best performance was observed for the calcium alginate formulation.
Amino Acids and Peptides. LII. Design and Synthesis of Opioid Mimetics Containing a Pyrazinone Ring and Examination of Their Opioid Receptor Binding Activity. (1998)

An amino group was introduced to the 3 or 6 position of a pyrazinone ring by cyclization of dipeptidyl chloromethyl ketones. Boc-Tyr-OH was coupled with the amino function, followed by removal of the Boc group to give pyrazinone ring-containing tyrosine derivatives. Of the various tyrosine derivatives prepared, 5-methyl-6-beta-phenethyl-3-tyrosylaminobutyl-2(1H)-pyrazinone exhibited strong binding to the mu-opioid receptor with a Ki value of 55.8 nM and to the delta-opioid receptor with a Ki value of 2165 nM and with a Ki mu/Ki delta value of 0.026.
Band-to-Band Tunneling Diode for Ultralow-Voltage Applications (2017)

This paper presents a band-to-band tunneling (BTBT) diode for use in ultralow-voltage (ULV) applications. The BTBT diode is shown to have nearly zero turn-on voltage, because it does not operate using diffusion current like a typical p-n junction diode. A simple analytical model was developed to better understand the BTBT diode and to help optimize the design. Simulations were designed and implemented in Silvaco ATLAS to accurately define the BTBT diode. The current-density versus voltage characteristics from the simulations were found to have large on/off current ratio, demonstrating that the BTBT diode has potential applications for circuits utilizing ULVs.
Regioselective monophosphorylation of glycols containing primary and secondary hydroxyl groups (2000)

A new approach to the synthesis of monophosphorylated glycols with the use of PIII-benzimidazolide has been suggested
Noninvasive Monitoring of Long-Term Lentiviral Vector-Mediated Gene Expression in Rodent Brain with Bioluminescence Imaging (2006)

Gene transfer into the central nervous system is an emerging therapeutic strategy for a range of neurological diseases, including neurodegeneration. This approach would benefit from imaging technologies that could determine the extent, magnitude, and duration of transgene expression. We have used bioluminescence imaging (BLI) to image lentiviral vector-mediated gene transfer into the mouse brain. We constructed human immunodeficiency virus type 1 lentiviral vectors that encode firefly luciferase and transduce cells in culture. After stereotactic injection of these vectors into the brain, we were able to detect luciferase expression in living mice and rats. We characterized the signal in mouse brain in terms of localization, kinetics, resolution, and reproducibility and demonstrated that it correlates with the level of firefly luciferase expression. Although the signal decreased gradually to about 20% of the initial value in the first month, the signal remained constant thereafter for more than 10 months. We demonstrated that the light signal can be used as a reporter by using a bicistronic vector. This is the first study to document noninvasive monitoring of long-term transgene expression in the adult mouse brain and provides the basis for applying BLI in the study of brain disease and gene therapeutic strategies.
Increased Procalcitonin Levels in End Stage Renal Disease and Chronic Kidney Disease as An Indicator of Inflammatory Activation (2008)

Abstract Increased levels of procalcitonin (PCT) and other calcitonin precursors are associated with systemic inflammatory responses in patients with burns, trauma or sepsis. Since end stage renal disease (ESRD) and chronic kidney disease (CKD) represent syndromes involving inflammatory responses, we hypothesized that PCT may also be elevated in patients with these pathologic conditions. Apparently sepsis-free blood plasma samples collected from normal donors (n=100) and patients with ESRD(n=67) and CKD (n=67) were retrospectively analyzed for circulating PCT levels using an immunocolorimetric assay (ILMA PCT,BRAHMS, Berlin Germany). This test utilizes two monoclonal antibodies that are directed to the calcitonin and katacalcin portions of PCT. The capturing antibody is immobilized on the surface of the coated tube and a labeled anti-calcitonin is used as a tracer. Diluted plasma samples incubated and both antibodies react with the PCT to form a sandwich complex. The excess tracer antibody is discarded after incubation. The amount of residual tracer is measured in a luminometer. The intensity of luminescence is proportional to the amount of PCT in the sample. PCT levels in normal individuals were 0.24±0.11 ng/ml, whereas higher levels were measured in CKD(0.81±0.35 ng/ml) and ESRD (0.93±0.36 ng/ml). Although wide ranges in the PCT values were observed, the levels were much higher than normal. These studies suggest that patients with ESRD and CKD may exhibit elevated levels of PCT which may not be due to sepsis. Measurement of PCT in these patients may be useful in the risk stratification and clinical management.