gebhart/patrepeval huggingface dataset:
Nucleotide modification at the -phosphate leads to the improved fidelity of HIV-1 reverse transcriptase (2005)

The mechanism by which HIV-1 reverse transcriptase (HIV-RT) discriminates between the correct and incorrect nucleotide is not clearly understood. Chemically modified nucleotides containing 1-aminonaphthalene-5-sulfonate (ANS) attached to their g-phosphate were synthesized and used to probe nucleotide selection by this error prone polymerase. Primer extension reactions provide direct evidence that the polymerase is able to incorporate the gamma-modified nucleotides. Forward mutation assays reveal a 6-fold reduction in the mutational frequency with the modified nucleotides, and specific base substitutions are dramatically reduced or eliminated. Molecular modeling illustrates potential interactions between critical residues within the polymerase active site and the modified nucleotides. Our data demonstrate that the fidelity of reverse transcriptase is improved using modified nucleotides, and we suggest that specific modifications to the g-phosphate may be useful in designing new antiviral therapeutics or, more generally, as a tool for defining the structural role that the polymerase active site has on nucleotide selectivity.
Contemporary imaging of mild TBI: the journey toward diffusion tensor imaging to assess neuronal damage (2013)

Modern imaging techniques, when applied in the appropriate clinical setting, may serve as a valuable tool for diagnosis and management of patients with mTBI. An understanding of modern neuroanatomical imaging will enhance our ability to analyse injury and recognize the manifestations of mTBI.
Differential effect of transforming growth factor β on the synthesis of Th1‐ and Th2‐like lymphokines by human T lymphocytes (1992)

(TGF)-beta is a pluripotent cytokine exerting differential effects on distinct components of the immune response. The present report, based on lymphokine determination in culture supernatants and Northern blot analysis of lymphokine mRNA, demonstrates that TGF-beta 2 markedly inhibits interleukin (IL)-4 and IL-5 synthesis by polyclonally activated human T cells in the absence of any significant effect on (IFN)-gamma, lymphotoxin or IL-2, suggesting a modulatory effect of TGF-beta 2 on the interferon Th1/Th2) balance of immune responses. The inhibitory effect of TGF-beta on IFN-gamma production by unfractionated peripheral blood mononuclear cells is likely to reflect the blunting of natural killer cell activation by TGF-beta.
Design of a Synthetic Leptin Agonist: Effects on Energy Balance, Glucose Homeostasis, and Thermoregulation* (2000)

We have previously reported that a synthetic peptide amide corresponding to amino acid residues 116-130 of mouse leptin, LEP-(116-130), reduces body weight gain, food intake, and blood glucose levels in ob/ob and db/db mice. In the present study we show that the activity of LEP-(116-130) resides in a restricted sequence between amino acid residues 116-122. A synthetic peptide corresponding to this sequence (Ser-Cys-Ser-Leu-Pro-Gln-Thr) has been named OB3. Single point D-amino acid substitution was used to study the structure-function relationship of each residue in OB3. D-Amino acid analogs of OB3 were synthesized by the solid phase method, purified to 98+%, and administered (1 mg/day, ip) for 7 days to female C57BL/6J ob/ob mice. The effects of the peptides on body weight gain, food and water intake, glucose homeostasis, and thermoregulation were assessed. In most cases, the efficacy of OB3 on all parameters tested was reduced by substitution of an L-amino acid with its corresponding D-isoform. A statistically significant increase (2.6-fold) in the weight-reducing effect of OB3, however, was observed by inversion of the configuration of the leucine residue at position 4 (Leu-4) of OB3 by substitution with its D-amino acid isoform [D-Leu-4]. Compared with OB3, mice treated with [D-Leu-4]-OB3 consumed 7.9% less food and 16.5% less water. Blood glucose was normalized to levels comparable to those in wild-type control mice within 2 days after initiation of [D-Leu-4]-OB3 treatment. Unlike native leptin, however, neither OB3 nor any of its D-amino acid-substituted analogs had any apparent effect on thermogenesis. Our results indicate that synthetic peptide strategies may be useful in the development of potent and stabile pharmacophores with potential therapeutic significance in the treatment of human obesity and its related metabolic dysfunctions.
Efficient RNase H-Directed Cleavage of RNA Promoted by Antisense DNA or 2‘F-ANA Constructs Containing Acyclic Nucleotide Inserts (2002)

The ability of modified antisense oligonucleotides (AONs) containing acyclic interresidue units to support RNase H-promoted cleavage of complementary RNA is described. Manipulation of the backbone and sugar geometries in these conformationally labile monomers shows great benefits in the enzymatic recognition of the nucleic acid hybrids, while highlighting the importance of local strand conformation on the hydrolytic efficiency of the enzyme more conclusively. Our results demonstrate that the duplexes support remarkably high levels of enzymatic degradation when treated with human RNase HII, making them efficient mimics of the native substrates. Furthermore, interesting linker-dependent modulation of enzymatic activity is observed during in vitro assays, suggesting a potential role for this AON class in an RNase H-dependent pathway of controlling RNA expression. Additionally, the butyl-modified 2'F-ANA AONs described in this work constitute the first examples of a nucleic acid species capable of eliciting high RNase H activity while possessing a highly flexible molecular architecture at predetermined sites along the AON.
Technique for expanding the donor liver pool: Heat shock preconditioning in a rat fatty liver model (2004)

Fatty liver is a common predisposing risk factor for postoperative liver failure and accounts for most discarded livers during triage of donors. We investigated the effect of heat shock preconditioning (HPc) on recipient survival in a rat fatty liver transplantation model. Fatty liver donor rats were exposed to brief whole-body hyperthermia (10 minutes at 42.5 degrees C) and allowed to recover. HPc induced heat shock proteins (HSPs) (HSP72, HSP90, and heme oxygenase [HO]-1) in donor livers, with levels peaking 12 to 48 hours after HPc. Subsequently, donor livers were harvested 24 hours after HPc, placed in cold storage for 10 hours, and transplanted into normal rats. At 3 hours posttransplantation, HPc reduced serum liver enzymes in the recipients and almost completely suppressed the release of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10. Histologic evaluation 3 and 24 hours after transplantation showed that HPc significantly reduced hepatic inflammation and hepatocellular necrosis without affecting the steatotic appearance of hepatocytes. One week after transplantation, control non-heat-shocked and heat-shocked fatty liver recipients exhibited survival rates of less than 10% and more than 80%, respectively. The evaluation of the survival of recipients receiving fatty livers at different times after HPc showed that the protective effect of HPc was significant when donor livers were transplanted 3 to 48 hours after HPc, with the maximum effect seen 6 to 48 hours after HPc. In conclusion, HPc is a promising avenue to salvage rejected donor fatty livers and enhance the survival rate of fatty liver recipients. We estimate that this technique could increase the annual donor pool by 600 livers.
Antibodies against nickel‐albumin in rabbits and man (1979)

Five albino rabbits were immunized every 2 weeks by intradermal injections of a nickel rabbit-albumin complex and during alternate weeks by occluded cutaneous applications of 5% nickel sulphate in petrolatum. After 6 weeks of immunization, passive immunodiffusion disclosed precipitating antibodies against the nickel-albumin complex in the serum of the rabbits. The specificity of these antibodies was substantiated by the precipitation of anti-albumin antibodies with rabbit albumin prior to immunodiffusion. Passive immunodiffusion was used to examine serum from 14 nickel-sensitive patients for precipitating antibodies against nickel human-albumin complex. Five of the patients had widespread erythematous, non-eczematous reactions following oral challenge with 2.5 mg nickel as nickel sulphate, while five others suffered an aggravation of their nickel dermatitis. Precipitating antibodies were found in three patients, all of whom had experienced rapid-onset erythema after oral challenge. A weak precipitate was seen in one of nine controls. The specificity of the precipitates was substantiated by reproducibility and by negative immunodiffusion after precipitation in the positive sera with the antigen.
Danazol treatment of advanced prostate cancer: Clinical and hormonal effects (1986)

Danazol was administered to 19 patients with advanced prostate cancer. These patients were treated for periods ranging from 3 days to 18 weeks. There were no objective remissions, but three patients (15.8%) had objectively stable disease (N.P.C.P. criteria) with complete pain control for periods ranging 15-18 weeks. Seven patients experienced tumor flare reactions, one requiring withdrawal of treatment and one resulting in rapid clinical deterioration and death. Four other patients died within 3 weeks and, although they were already in the terminal phase of disease when treatment commenced, it is possible that the deaths were treatment related. This study indicates that danazol has only limited activity in the treatment of advanced prostate cancer and is associated with a high incidence of tumor flare reactions with the risk of rapid clinical deterioration.
Genetic Control by Metabolite‐Binding Riboswitches (2003)

Metabolite-sensing mRNAs: Riboswitches are highly structured RNA domains that typically reside in the 5′-untranslated regions of certain bacterial mRNAs. These RNA domains serve as ligand-dependent genetic switches that provide a means by which RNA can control gene expression without the need for protein factors. Distinct classes of riboswitches are responsive to seven different metabolites and guide the maintenance of fundamental biochemical processes. One example is the regulation of the E. coli thiM mRNA by thiamine pyrophosphate (TPP; see representation).
A monoclonal antibody-defined antigen associated with gastrointestinal cancer is a ganglioside containing sialylated lacto-N-fucopentaose II. (1982)

Two monoclonal antibodies produced by hybridomas obtained from a mouse immunized with a colorectal carcinoma cell line bind specifically to human gastrointestinal cancer cells. The antigen of this antibody in the carcinoma cell line, a monosialoganglioside, has been isolated. Its carbohydrate structure is probably (formula: see text). This oligosaccharide is a sialyl derivative of lacto-N-fucopentaose II, a hapten of the human Lea blood group antigen. About 30 micrograms of ganglioside is obtained from 1 g of cells, wet weight. The ganglioside was detected by autoradiography in lipid extracts of some carcinomas and of meconium, but not in lipid extracts of normal adult tissues. Antigen was detected by solid phase radioimmunoassay in lipid extracts from 12 out of 21 adenocarcinomas of the colon, from 4 out of 5 gastric adenocarcinomas, and from 4 out of 7 pancreatic carcinomas. Antigen was not detected in lipid extracts from 5 esophageal carcinomas or from normal colon and gastric mucosa, pancreas, kidney, liver, and bone marrow.
Cladding-pumped passively mode-locked femtosecond fiber lasers (1996)

Summary form only given. We demonstrate for the first time that high-power and high-repetition-rate femtosecond fiber lasers can be constructed that require only simple broad-area diode-array pump lasers. To allow pumping with diode arrays, the standard single-mode erbium fiber of conventional oscillator designs is replaced with double-clad erbium/ytterbium fiber. Reliable femtosecond pulse operation is ensured by exploiting nonlinear polarization evolution for steady-state pulse shaping in environmentally stable cavity. Furthermore the use of chirped Bragg gratings allows the extension of the operation range of these types of laser into the picosecond regime.
Stepwise Analysis of Differential Item Functioning Based on Multiple‐Group Partial Credit Model (1999)

Bock, Muraki, and Pfeiffenberger (1988) proposed a dichotomous item response theory (IRT) model for the detection of differential item functioning (DIF), and they estimated the IRT parameters and the means and standard deviations of the multiple latent trait distributions. This IRT DIF detection method is extended to the partial credit model (Masters, 1982; Muraki, 1993) and presented as one of the multiple‐group IRT models. Uniform and non‐uniform DIF items and heterogeneous latent trait distributions were used to generate polytomous responses of multiple groups. The DIF method was applied to this simulated data using a stepwise procedure. The standardized DIF measures for slope and item location parameters successfully detected the non‐uniform and uniform DIF items as well as recovered the means and standard deviations of the latent trait distributions.This stepwise DIF analysis based on the multiple‐group partial credit model was then applied to the National Assessment of Educational Progress (NAEP) writing trend data.
Design and Implementation of Common Drain Class-B RF Power Amplifier in 90 nm CMOS Technology (2011)

Power Amplifer (PA), is a key component in a wireless communication system. It is challanging to design a PA having sucient gain, linearity and eciency all at the same time. Linearity is important to avoid interference among the channels while high effciency corresponds to longer battery life. Gain is important to reduce multiple stages. All the RF power ampli ers are made in common source configuration which offers high power gain but significant nonlinearity. To improve linearity, the amplifer is operated in backoff or advanced techniques like digital predistortion are used. On the other hand, common drain amplifer has inherent potential to provide both linearity and efficiency. Operating the common drain in class B mode can provide high efficiency as well as additional linearity due to suppression of nonlinear gate-source capacitance. The scope of this thesis is to design a stable single-ended as well as dierential common drain class-B RF power ampli er, while maintaining adequate transducer gain so that the power added efficiency (PAE) is not compromised by low gain and thus resulting in better overall performance. The technology to be employed for the implementation of the amplifer is the 90 nm CMOS process and the operating frequency is 2.55 GHz, the 3GPP Long Term Evolution (LTE) standard. For additional performance evaluation, the results are to be compared with that of a single-ended common source amplifer.
The Glucagon-Like Peptide-1 Analogue Liraglutide Inhibits Oxidative Stress and Inflammatory Response in the Liver of Rats with Diet-Induced Non-alcoholic Fatty Liver Disease (2015)

Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, has been demonstrated to reduce hepatic steatosis. However, the mechanism of the lipid-lowering effect of liraglutide in the liver remains unclear. The aim of the present study was to investigate the beneficial effect of liraglutide on diet-induced non-alcoholic fatty liver disease (NAFLD) and the underlying mechanism in rats. NAFLD was induced in Sprague-Dawley rats by feeding a high fat and high cholesterol (HFHC) diet. Liraglutide (0.6 mg/kg body weight/d) was injected intraperitoneally to the rats subjected to HFHC diet four weeks before sacrificing the animals. Body and liver weight, fasting blood glucose (FBG), fasting insulin, serum aminotransferase (ALT) and lipid accumulation in the liver were determined. Markers of oxidative stress, such as malondialdehyde (MDA), free fatty acid (FFAs), superoxide dismutase (SOD), and pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) were detected by colorimetric detection or enzyme-linked immunosorbent assay (ELISA). Serum and hepatic adiponectin were measured by ELISA. The expression of c-Jun N-terminal kinase-1 (JNK-1) and phosphorylated JNK-1 were examined by Western blotting. Liraglutide improved insulin resistance, decreased hepatic steatosis and reversed liver dysfunction. The hepatic levels of MDA, FFAs, and TNF-α were significantly decreased versus controls. Meanwhile, administration of liraglutide significantly increased SOD and adiponectin levels in the liver and inhibited the expression of JNK-1 and phosphorylated JNK-1 versus control rats. Liraglutide exerted anti-oxidative and anti-inflammatory effects in the liver and consequently reversed hepatic steatosis and insulin resistance. Such effects might be mediated by the elevation of adiponectin levels and the inactivation of JNK-1.
Wide-band frequency-modulation system using optical techniques (1979)

A modified (frequency-shifted) Michelson interferometer uses a laser, an acoustooptic cell, and a movable mirror to produce a wide-band FM signal having a center frequency of 80 MHz. The basic concepts are reviewed, and a report of an operating system is given. The angle modulation scheme may be used to produce very wide-band FM or PM. Systems configurations are explored that allow several communication channels in a frequency-division multiplexing arrangement.
Genetic transmission of Alzheimer's disease among families in a Dutch population based study. (1993)

We evaluated age at onset and transmission patterns of Alzheimer's disease (AD) in families of 198 patients who had onset of symptoms before the age of 65 years and were diagnosed before the age of 70 years. Patients were ascertained in a population based study in The Netherlands. The results suggest that the risk of AD by the age of 90 in first degree relatives is 39% (95% confidence interval 27 to 51). By the age of 90, this risk is 2.8 (95% confidence interval 1.5-5.2) times greater than the corresponding risk of 14% among relatives of age and sex matched control subjects. Segregation analysis indicated that patterns of familial clustering are best explained by transmission of a major autosomal dominant gene with reduced penetrance and a multifactorial component. However, the single major locus model could be rejected in favour of the mixed model only when a cohort effect for heritability was allowed for. The frequency of the AD susceptibility allele was estimated to be 0.48% in the single major locus model and 0.31% in the mixed model. Although our study confirms that a dominant major gene is implicated in early onset AD, the results suggest that other genetic or perhaps non-genetic factors may account for the disease in a considerable number of patients.
Neural transplantation : a practical approach (1992)

Staging and dissection of rat embryos, S.B. Dunnett grafting genetically modified cells within the rat CNS, M.D. Kawaja et al neural transplantation in adult rats, A. Bjorklund and S.B. Dunnett intracerebral transplantation to immature hosts, R.D. Lund and K.T. Yee the use of peripheral nerve grafts to study CNS regeneration, M. Vidal-Sanz et al transplantation of glial cells into areas of demyelination in the adult rat spinal cord, W.F. Blakemore and A.J. Crang neural transplantation in primates, L.E. Annett and R.M. Ridley dissection, preparation and implantation of human embryonic brain tissue, P. Brundin immonological considerations in neural transplantation, R.D. Lund and R. Bannerjee identifying grafted cells, J, Cadusseau and M. Peschanski.
Speed of progression to AIDS and degree of antibody response to accessory gene products of HIV‐1 (1990)

Antibodies to E. coli-produced HIV-1 nef, rev, tat, vpu, and vpr proteins were measured by enzyme immunoassay in serial sets of sera from 72 men seroconverting for antibodies to HIV-1 structural proteins, and from 190 initially symptom-free men who were seropositive for these antibodies at entry into the study. In the men seroconverting for antibodies to structural proteins the levels of nef-, rev-, and tat-specific antibodies, but not of vpu-, and vpr-specific antibodies, within 3 months of seroconversion, appeared to be lower in the five men progressing to AIDS, compared with the men remaining symptom-free during follow-up. Analysis of the prevalence of previously described antibody profiles to these accessory gene products was carried out. In all HIV-1 antibody seroconverters and in those HIV-1 antibody seropositive men with 15 or more months of follow-up who progressed to AIDS, there was a shift from predominantly nef- and vpu-specific antibody negative profiles in the men developing AIDS in the early years of the study to predominantly nef- and vpu-specific antibody positive profiles in men who developed AIDS later. Rev- and tat-specific antibody negative profiles were dominant in men progressing to AIDS throughout follow-up. No vpr-specific antibody profile occurred preferentially in the men progressing to AIDS throughout follow-up. Low antibody reactivity to accessory gene products nef, rev, and tat appears, like low anti-core antibody reactivity, to be associated with progression to AIDS relatively rapidly after infection with HIV-1.
Structural Requirements for a Lipoamino Acid in Modulating the Anticonvulsant Activities of Systemically Active Galanin Analogues (2009)

Introduction of lipoamino acid (LAA), Lys-palmitoyl, and cationization into a series of galanin analogues yielded systemically active anticonvulsant compounds. To study the relationship between the LAA structure and anticonvulsant activity, orthogonally protected LAAs were synthesized in which the Lys side chain was coupled to fatty acids varying in length from C(8) to C(18) or was coupled to a monodispersed polyethylene glycol, PEG(4). Galanin receptor affinity, serum stability, lipophilicity (log D), and activity in the 6 Hz mouse model of epilepsy of each of the newly synthesized analogues were determined following systemic administration. The presence of various LAAs or Lys(MPEG(4)) did not affect the receptor binding properties of the modified peptides, but their anticonvulsant activities varied substantially and were generally correlated with their lipophilicity. Our results suggest that varying the length or polarity of the LAA residue adjacent to positively charged amino acid residues may effectively modulate the antiepileptic activity of the galanin analogues.
Molecular Nanocapsules Based on Amphiphilic Hyperbranched Polyglycerols (1999)

Polar dyes can be solubilized in apolar media-molecular nanocapsules with hydrophilic interiors have been prepared (see schematic representation) using polyglycerols with narrow polydispersity and simple esterification with fatty acids. These unimolecular micelles offer attractive potential for a variety of applications ranging from controlled drug release to the design of microreactors and catalysts.
Second-generation radiation sensitive 193-nm developable bottom antireflective coatings (DBARC): recent results (2008)

We will discuss our recent results using a second generation radiation sensitive developable 193 Bottom Antireflective coatings (DBARCs). These DBARC materials are made solvent resistant the application of a resist coating on top of them through a crosslinking mechanism that is reversible by acid catalyzed reaction upon exposure of the DBARC/resist stack. Typically this is done by crosslinking a copolymer containing a hydroxyl moiety with a polyfunctional vinylether during post applied bake. This DBARC approach, after exposure, allows for development of the stack in exposed areas down to the substrate eschewing the plasma etch breakthrough needed for conventional bottom antireflective coatings which are irreversibly crosslinked. We will give an update on the performance our latest 193 nm DBARC materials used with different Implant 193 nm resists when using a phase shift mask with off axis illumination.