gebhart/patrepeval huggingface dataset:
General and Modular Synthesis of Isomeric 5-Substituted Pyridin-2-yl and 6-Substituted Pyridin-3-yl C-Ribonucleosides Bearing Diverse Alkyl, Aryl, Hetaryl, Amino, Carbamoyl, and Hydroxy Groups (2011)

A general modular and practical methodology for preparation of diverse 5-substituted pyridin-2-yl and 6-substituted pyridin-3-yl C-ribonucleosides was developed. Regioselective lithiation of 2,5-dibromopyridine proceeded at position 5 or 2 depending on the solvent, and the resulting bromopyridyl lithium species underwent additions to TBS-protected ribonolactone and follow-up transformations to corresponding acetylated hemiketal intermediates 7 and 10 that were diastereoselectively reduced to give either 5-bromopyridin-2-yl or 6-bromopyridin-3-yl silyl-protected C-ribonucleosides 8 or 11 in 68% and 77% overall yields as pure β-anomers. These bromopyridyl C-nucleoside intermediates were then subjected to a series of palladium-catalyzed cross-coupling reactions, aminations, aminocarbonylations, and hydroxylations to give a series of protected 1β-(5-alkyl-, 5-aryl-, 5-amino-, 5-carbamoyl-, and 5-hydroxypyridin-2-yl)-C-ribonucleosides 13a-i and β-(6-alkyl-, 6-aryl-, 6-amino-, 6-carbamoyl-, and 6-hydroxypyridin-3-yl)-C-ribonucleosides 15a-i. Deprotection of silylated nucleosides by Et(3)N·3HF, TBAF, or TFA gave a series of free C-nucleosides 14a-i and 16a-i.
Inhaled nitric oxide and congenital cardiac disease (2001)

An abstract is not available for this content so a preview has been provided. Please use the Get access link above for information on how to access this content.
Suppressing the out-of-band power radiation in multi-carrier systems: A comparative study (2012)

As of today, orthogonal frequency-division multiplexing (OFDM) has been the dominant technique in broadband transmission systems. However, for the application in cognitive radios, the sidelobes of rectangularly pulsed OFDM signals must be well suppressed to satisfy the rigorous spectral masks. In this context, filter-bank based multi-carrier (FBMC) transmission, which allows designing prototype filters for signal pulse shaping, is considered to be more effective. In this article, different sidelobe suppression schemes for OFDM and pulse-shaped FBMC are comparatively investigated with respect to their out-of-band power radiation and their demand in computational complexity. Our results reveal that FBMC, thanks to the excellent time-frequency localization of the pulse shape, allows for a superior isolation of the transmit signal in frequency, enabling to achieve the minimal out-of-band power leakage for the operation in both contiguous and non-contiguous spectrum. Moreover, the additional complexity required for FBMC compared to the other schemes is very moderate.
Asynchronous verifiable secret sharing and proactive cryptosystems (2002)

Verifiable secret sharing is an important primitive in distributed cryptography. With the growing interest in the deployment of threshold cryptosystems in practice, the traditional assumption of a synchronous network has to be reconsidered and generalized to an asynchronous model. This paper proposes the first practical verifiable secret sharing protocol for asynchronous networks. The protocol creates a discrete logarithm-based sharing and uses only a quadratic number of messages in the number of participating servers. It yields the first asynchronous Byzantine agreement protocol in the standard model whose efficiency makes it suitable for use in practice. Proactive cryptosystems are another important application of verifiable secret sharing. The second part of this paper introduces proactive cryptosystems in asynchronous networks and presents an efficient protocol for refreshing the shares of a secret key for discrete logarithm-based sharings.
A study of two ODM-201 formulations with a safety and tolerability extension phase in patients with metastatic chemotherapy-naive castration-resistant prostate cancer (CRPC). (2014)

115^ Background: This open phase I trial assessed the bioavailability, and the effect of food on the bioavailability of ODM-201 600mg tablets compared to a 600mg capsule formulation. Efficacy, safety, and tolerability of ODM-201 were studied in the extension period. Methods: The study had two parts: a pharmacokinetic (PK), and a safety and tolerability part. Dosing was 600mg bid with or without food. In the PK part, three single doses of ODM-201 were given over 3 weeks. In the extension part patients could continue treatment until disease progression or until an intolerable adverse event or condition that prevented further dosing of ODM-201. Results: Thirty men with metastatic chemotherapy-naïve castration-resistant prostate cancer (CRPC) were enrolled, the median age was 68. The median prostate-specific antigen (PSA) was 18.2 ng/mL and testosterone 23.1 ng/dL at baseline. Food interaction was observed when ODM-201 formulations were administered after a high fat content breakfast compared to administration at fast. AUC and C max values were about 50% lower after fast. Twenty nine patients have completed the 4-week visit. The PSA response rate (50% or more PSA decline) was 86%, with a median PSA decrease of -66% (-96, 5) at week 4 (N=18/21). Most commonly reported adverse events so far are fatigue, abdominal pain, diarrhea, hematuria, and nausea. Conclusions: ODM-201 600mg bid as tablets has comparable PK to capsules used in the phase II ARADES trial. It is well tolerated and has good PSA response in chemotherapy-naïve patients with CRPC . Clinical trial information: NCT01784757.
Animal Health Research Reviews – the past 10 years (2012)

An abstract is not available for this content. As you have access to this content, full HTML content is provided on this page. A PDF of this content is also available in through the ‘Save PDF’ action button.
Expression of the embryonal neural cell adhesion molecule N‐CAM in lung carcinoma. Diagnostic usefulness of monoclonal antibody 735 for the distinction between small cell lung cancer and non‐small cell lung cancer (1989)

Paraffin sections of 19 surgically resected small cell lung carcinomas (SCLC), 33 non-small cell lung carcinomas (NSCLC) of various types, and four bronchial carcinoids were immunostained with monoclonal antibodies (MoAbs) 735 and anti-Leu 7, both recognizing some sugar epitopes present on the neural cell adhesion molecule N-CAM. With MoAb 735, all SCLC were stained focally or diffusely, and one carcinoid was stained focally. Only three of the 33 NSCLC were faintly and focally positive with MoAb 735; these three tumours showed relatively small tumour cells and small, oval nuclei. Anti-Leu 7 stained all the carcinoids, only eight SCLC, sometimes focally, and eight NSCLC. MoAb 735 was thus superior to anti-Leu 7 in distinguishing between SCLC and NSCLE. Since MoAb 735 stained all SCLC strongly and is applicable on paraffin sections, it provides a well-needed addition to the immunomarkers used in the diagnostic distinction of SCLC and NSCLC.
The Network Architecture of the Saccharomyces cerevisiae Genome (2013)

We propose a network-based approach for surmising the spatial organization of genomes from high-throughput interaction data. Our strategy is based on methods for inferring architectural features of networks. Specifically, we employ a community detection algorithm to partition networks of genomic interactions. These community partitions represent an intuitive interpretation of genomic organization from interaction data. Furthermore, they are able to recapitulate known aspects of the spatial organization of the Saccharomyces cerevisiae genome, such as the rosette conformation of the genome, the clustering of centromeres, as well as tRNAs, and telomeres. We also demonstrate that simple architectural features of genomic interaction networks, such as cliques, can give meaningful insight into the functional role of the spatial organization of the genome. We show that there is a correlation between inter-chromosomal clique size and replication timing, as well as cohesin enrichment. Together, our network-based approach represents an effective and intuitive framework for interpreting high-throughput genomic interaction data. Importantly, there is a great potential for this strategy, given the rich literature and extensive set of existing tools in the field of network analysis.
Aspect ratio dependence on surface enhanced Raman scattering using silver and gold nanorod substrates (2005)

Silver and gold nanorods with aspect ratios from 1 to 16 have been used as substrates for surface enhanced Raman spectroscopy (SERS) in colloidal solution. The nanorod aspect ratio is varied to give different degrees of overlap between the nanorod longitudinal plasmon band and excitation source in order to determine its effect on overall surface enhancement. Results suggest that enhancement factors are a factor of 10-10(2) greater for substrates that have plasmon band overlap with the excitation source than for substrates whose plasmon bands do not.
LOAD CHARACTERISTICS UNDER OPTIMAL TRAJECTORY CONTROL OF SERIES RESONANT DC/DC CONVERTERS OPERATING ABOVE RESONANT FREQUENCY (2005)

In the paper resonant DC/DC converters optimal trajectory control method is examined. This control method allows the resonant tank energy is fully controlled with the tank energy, current and voltage, all staying well within bounds under all circumstance, including a short circuit across the converter output. The emphasis in this paper is on the obtained of steady- state equations, described DC/DC resonant converter operation above resonant frequency as a function of the diode trajectory radius, using as control parameter. Solving equations can be drawn an inverter family of load characteristics. Experimental results from the investigation of the DC/DC resonant converter are shown.
Comparative Study of the Optical and Heat Generation Properties of IR820 and Indocyanine Green (2012)

AbstractNear-infrared (NIR) fluorophores are the focus of extensive research for combined molecular imaging and hyperthermia. In this study, we showed that the cyanine dye IR820 has optical and thermal generation properties similar to those of indocyanine green (ICG) but with improved in vitro and in vivo stability. The fluorescent emission of IR820 has a lower quantum yield than ICG but less dependence of the emission peak location on concentration. IR820 demonstrated degradation half-times approximately double those of ICG under all temperature and light conditions in aqueous solution. In hyperthermia applications, IR820 generated lower peak temperatures than ICG (4-9%) after 3-minute laser exposure. However, there was no significant difference in hyperthermia cytotoxicity, with both dyes causing significant cell growth inhibition at concentrations ≥ 5 μM. Fluorescent images of cells with 10 μM IR820 were similar to ICG images. In rats, IR820 resulted in a significantly more intense fluorescence signal and significantly higher organ dye content than for ICG 24 hours after intravenous dye administration (p < .05). Our study shows that IR820 is a feasible agent in experimental models of imaging and hyperthermia and could be an alternative to ICG when greater stability, longer image collection times, or more predictable peak locations are desirable.
Glycosylation of the Collagen Adhesin EmaA ofAggregatibacter actinomycetemcomitansIs Dependent upon the Lipopolysaccharide Biosynthetic Pathway (2010)

The human oropharyngeal pathogen Aggregatibacter actinomycetemcomitans synthesizes multiple adhesins, including the nonfimbrial extracellular matrix protein adhesin A (EmaA). EmaA monomers trimerize to form antennae-like structures on the surface of the bacterium, which are required for collagen binding. Two forms of the protein have been identified, which are suggested to be linked with the type of O-polysaccharide (O-PS) of the lipopolysaccharide (LPS) synthesized (G. Tang et al., Microbiology 153:2447-2457, 2007). This association was investigated by generating individual mutants for a rhamnose sugar biosynthetic enzyme (rmlC; TDP-4-keto-6-deoxy-d-glucose 3,5-epimerase), the ATP binding cassette (ABC) sugar transport protein (wzt), and the O-antigen ligase (waaL). All three mutants produced reduced amounts of O-PS, and the EmaA monomers in these mutants displayed a change in their electrophoretic mobility and aggregation state, as observed in sodium dodecyl sulfate (SDS)-polyacrylamide gels. The modification of EmaA with O-PS sugars was suggested by lectin blots, using the fucose-specific Lens culinaris agglutinin (LCA). Fucose is one of the glycan components of serotype b O-PS. The rmlC mutant strain expressing the modified EmaA protein demonstrated reduced collagen adhesion using an in vitro rabbit heart valve model, suggesting a role for the glycoconjugant in collagen binding. These data provide experimental evidence for the glycosylation of an oligomeric, coiled-coil adhesin and for the dependence of the posttranslational modification of EmaA on the LPS biosynthetic machinery in A. actinomycetemcomitans.
Mutations in the lysyl oxidase gene are not associated with amyotrophic lateral sclerosis (2001)

Mutations in the LOX gene are unlikely to be directly causative of ALS.
A Randomized Trial of Immediate versus Delayed Elective Angioplasty after Intravenous Tissue Plasminogen Activator in Acute Myocardial Infarction (1987)

We compared the efficacy of immediate coronary angioplasty after acute myocardial infarction with that of elective angioplasty at 7 to 10 days in patients treated initially with intravenous tissue plasminogen activator. The plasminogen activator (150 mg) was administered 2.95 +/- 1.1 hours after the onset of symptoms, to 386 patients with acute myocardial infarction. Ninety minutes later, patency of the coronary artery serving the area of the infarct was demonstrated by coronary angiography in 288 patients (75 percent). Bleeding problems were frequently encountered, as evidenced by an average drop in hematocrit of 11.7 +/- 6.5 points from base line to nadir and by a need for transfusion not related to bypass surgery in 70 patients (18 percent). After successful thrombolysis, 197 patients with a patent but severely stenotic vessel suitable for angioplasty were randomly assigned to immediate angioplasty (n = 99) or, if indicated 7 to 10 days after infarction, to deferred (elective) angioplasty (n = 98). The incidence of reocclusion was similar in the two groups: 11 percent in the group assigned to immediate angioplasty and 13 percent in the group assigned to elective angioplasty. Neither group had a significant improvement in global left ventricular function, and regional wall motion in the infarct zone improved to a similar extent in the two groups. In the elective-angioplasty group, the rate of crossover to emergency angioplasty for recurrent ischemia was 16 percent (whereas 5 percent of the immediate-angioplasty group required emergency repeated angioplasty; P = 0.01). In 14 percent of the patients in the elective group, the stenosis was substantially reduced by the time of the seven-day follow-up angiography, obviating the need for angioplasty. We conclude that in patients with initially successful thrombolysis and suitable coronary-artery anatomy, immediate angioplasty offers no clear advantage over delayed elective angioplasty.
Antisense oligonucleotide reduction of DGAT2 expression improves hepatic steatosis and hyperlipidemia in obese mice† (2005)

In this study, we investigated the role of acyl-coenzyme A:diacylglycerol acyltransferase 2 (DGAT2) in glucose and lipid metabolism in obese mice by reducing its expression in liver and fat with an optimized antisense oligonucleotide (ASO). High-fat diet-induced obese (DIO) C57BL/6J mice and ob/ob mice were treated with DGAT2 ASO, control ASO, or saline. DGAT2 ASO treatment reduced DGAT2 messenger RNA (mRNA) levels by more than 75% in both liver and fat but did not change DGAT1 mRNA levels in either of these tissues, which resulted in decreased DGAT activity in liver but not in fat. DGAT2 ASO treatment did not cause significant changes in body weight, adiposity, metabolic rate, insulin sensitivity, or skin microstructure. However, DGAT2 ASO treatment caused a marked reduction in hepatic triglyceride content and improved hepatic steatosis in both models, which was consistent with a dramatic decrease in triglyceride synthesis and an increase in fatty acid oxidation observed in primary mouse hepatocytes treated with DGAT2 ASO. In addition, the treatment lowered hepatic triglyceride secretion rate and plasma triglyceride levels, and improved plasma lipoprotein profile in DIO mice. The positive effects of the DGAT2 ASO were accompanied by a reduction in the mRNA levels of several hepatic lipogenic genes, including SCD1, FAS, ACC1, ACC2, ATP-citrate lyase, glycerol kinase, and HMG-CoA reductase. In conclusion, reduction of DGAT2 expression in obese animals can reduce hepatic lipogenesis and hepatic steatosis as well as attenuate hyperlipidemia, thereby leading to an improvement in metabolic syndrome.
EXTH-59. THE IDH1 MUTANT INHIBITOR AG-120 SHOWS STRONG INHIBITION OF 2-HG PRODUCTION IN AN ORTHOTOPIC IDH1 MUTANT GLIOMA MODEL IN VIVO (2017)

Mutations in isocitrate dehydrogenase (IDH) 1 and 2 result in accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), which drives multiple oncogenic processes, including increased histone and DNA methylation, leading to a block in cellular differentiation. IDH1/2 mutations occur in >70% of diffuse low-grade gliomas (LGG). Standard of care treatment for patients with diffuse LGG involves combined modality approaches including surgery, radiation, and chemotherapy. Here we present preclinical data from studies using AG-120, a potent, orally available inhibitor of the mIDH1 protein currently in clinical trials. In an orthotopic mouse xenograft model of a human mIDH1-R132H glioma, strong inhibition of 2-HG production in brain tumor samples (>77% inhibition) was observed when AG-120 was dosed orally at 150 mg/kg twice daily. Pharmacokinetic analysis revealed that AG-120 was detectable in the brain and brain-tumor tissues of the mice, although at much lower exposures than in the plasma, indicating that AG-120 is highly potent against the mIDH1-R132H protein in vivo. Results from ongoing preclinical studies testing the potential activity of AG-120 combined with radiation therapy in an orthotopic human mIDH1-R132H glioma model will also be shared.
Biodegradation of aromatic compounds under mixed oxygen/denitrifying conditions: a review (1997)

Bioremediation of aromatic hydrocarbons in groundwater and sediments is often limited by dissolved oxygen. Many aromatic hydrocarbons degrade very slowly or not at all under anaerobic conditions. Nitrate is a good alternative electron acceptor to oxygen, and denitrifying bacteria are commonly found in the subsurface and in association with contaminated aquifer materials. Providing both nitrate and microaerophilic levels of oxygen may result in oxidation of the stable benzene rings in aromatic contaminants and allow for the intermediates of this oxidation to degrade via denitrification. The effects of using mixed electron acceptors on biodegradation of subsurface contaminants is unclear. Below some critical oxygen threshold, aerobic biodegradation is inhibited, however high levels of oxygen inhibit denitrification. The mechanisms which regulate electron transfer to oxygen and nitrate are complex. This review: 1) describes the factors which may affect the utilization of oxygen and nitrate as dual electron acceptors during biodegradation; 2) summarizes the incidence of dual use of nitrate and oxygen (aerobic denitrification); and 3) presents evidence of the effectiveness of bioremediation under mixed oxygen/nitrate conditions.
Serotype-Specific Detection of Dengue Viruses in a Fourplex Real-Time Reverse Transcriptase PCR Assay (2005)

The dengue (DEN) viruses are positive-strand RNA viruses in the genus Flavivirus. Dengue fever and dengue hemorrhagic fever/dengue shock syndrome are important human arboviral diseases caused by infection with one of four closely related but serologically distinct DEN viruses, designated DEN-1, DEN-2, DEN-3, and DEN-4 viruses. All four DEN serotypes are currently co-circulating throughout the subtropics and tropics, and genotypic variation occurs among isolates within a serotype. A real-time quantitative nucleic acid amplification assay has been developed to detect viral RNA of a single DEN virus serotype. Each primer-probe set is DEN serotype specific, yet detects all genotypes in a panel of 7 to 10 representative isolates of a serotype. In single reactions and in fourplex reactions (containing four primer-probe sets in a single reaction mixture), standard dilutions of virus equivalent to 0.002 PFU of DEN-2, DEN-3, and DEN-4 viruses were detected; the limit of detection of DEN-1 virus was 0.5 equivalent PFU. Singleplex and fourplex reactions were evaluated in a panel of 40 viremic serum specimens with 10 specimens per serotype, containing 0.002 to 6,000 equivalent PFU/reaction (0.4 to 1.2 x 10(6) PFU/ml). Viral RNA was detected in all viremic serum specimens in singleplex and fourplex reactions. Thus, this serotype-specific, fourplex real-time reverse transcriptase PCR nucleic acid detection assay can be used as a method for differential diagnosis of a specific DEN serotype in viremic dengue patients and as a tool for rapid identification and serotyping of DEN virus isolates.
<title>Laser speckle microstrain measurement in vascular tissue</title> (1999)

Changes in the ultrastructure of vascular tissue due to pathologies such as atherosclerosis may be manifested as subtle changes in the mechanical properties of the arterial wall. The ability to detect these changes is considered to be important in the early diagnosis of atherosclerosis. In order to evaluate the subtle viscoelastic properties of the arterial wall, a highly sensitive means of evaluating mechanical strain in the tissue is required. Herein we will present a novel laser speckle strain gauge for evaluating mechanical microstrains in perfused and superfused vessel segments. The strain gauge relies upon 2D frequency transforms of stacked speckle histories, which are time sequences of one dimensional views of the backscattered light stacked into a 2D array such that time is along the vertical axis and space is along the horizontal axis. The gauge can be made sensitive only to in-plane strains. Sensitivity of the gauge is on the order of single microstrain. By mechanically straining the vessel segments in a custom microtensile testing machine fitted with a high sensitivity load cell, mechanical constants of the vessel wall can be derived and changes in the mechanical behavior due to disease can be evaluated.
Large-Scale Production and Purification of a Vaccinia Recombinant-Derived HIV-1 gp160 and Analysis of Its Immunogenicity (1989)

The human immunodeficiency virus (HIV-1) envelope gene was expressed in large-scale microcarrier cultures of Vero cells using a system involving coinfection with two recombinant vaccinia viruses. One recombinant contained the bacteriophage T7 RNA polymerase gene under control of a vaccinia virus promoter. The second contained the HIV-1 gp160 gene flanked by T7 promoter and termination sequences. The protein was expressed on the surface of infected cells, and it was shown to have a molecular weight of 160 kD and to react with gp41 and gp120 specific monoclonal antibodies. After purification by successive affinity and ion-exchange chromatography, the protein was demonstrated to be present in a particulate form with a diameter in the range of 15-30 nm. When injected into goats a high-titer gp160 specific antibody response was elicited and group-specific neutralizing activity could be demonstrated in vitro. The immunogenicity of the protein was also studied in conjunction with a number of adjuvant formulations, and the highest potency in mice was obtained using a preparation with 0.2% Al(OH)3 and 0.25% deoxycholate.