gebhart/patrepeval huggingface dataset:
Evolutionary Trace Residues in Noroviruses: Importance in Receptor Binding, Antigenicity, Virion Assembly, and Strain Diversity (2004)

Noroviruses cause major epidemic gastroenteritis in humans. A large number of strains of these single-stranded RNA viruses have been reported. Due to the absence of infectious clones of noroviruses and the high sequence variability in their capsids, it has not been possible to identify functionally important residues in these capsids. Consequently, norovirus strain diversity is not understood on the basis of capsid functions, and the development of therapeutic compounds has been hampered. To determine functionally important residues in noroviruses, we have analyzed a number of norovirus capsid sequences in the context of the Norwalk virus capsid crystal structure by using the evolutionary trace method. This analysis has identified capsid protein residues that uniquely characterize different norovirus strains and provide new insights into capsid assembly and disassembly pathways and the strain diversity of these viruses. Such residues form specific three-dimensional clusters that may be of functional importance in noroviruses. One of these clusters includes residues known to participate in the proteolytic cleavage of these viruses at high pH. Other clusters are formed in capsid regions known to be important in the binding of antibodies to noroviruses, thereby indicating residues that may be important in the antigenicity of these viruses. The highly variable region of the capsid shows a distinct cluster whose residues may participate in norovirus-receptor interactions.
Dose-related effects of oral acetaminophen on cold-induced pain: A double-blind, randomized, placebo-controlled trial* (1998)

The cold-pressor test is a widely used pain-induction model in humans. This method has been shown to be a sensitive measure for detecting opioid analgesia. However, nonsteroidal anti-inflammatory drugs have not produced consistent analgesic effects with use of this model. The analgesic effect of acetaminophen (INN, paracetamol) on cold pressor-induced pain has not been reported by other investigators. In this study, a double-blind, randomized, placebo-controlled design was used to evaluate the dose-related effects of oral acetaminophen on cold pressor-induced pain in 18 normal healthy human subjects. We observed dose-related analgesic activity of oral acetaminophen using the cold pressor-induced pain model in these subjects. There were statistically significant main effects of both dose and time (pain and bothersomeness ratings decreased with increasing drug dose and increased over time). In pairwise comparisons only the contrast between the highest dose of acetaminophen (1000 mg) and placebo reached statistical significance. Results from our study suggest that the cold-pressor method may have clinical value in evaluating nonopioid analgesic agents.
Cognitive Function and Endogenous Sex Hormones in Older Women (1999)

In these older women, higher endogenous estrogen levels were not associated with significantly better performance on any cognitive function test. In contrast, higher levels of testosterone predicted better categorical performance on the MMSE and the World component of the MMSE. These novel findings warrant further research.
Guinea pig maximization test: effect of type of Freund's complete adjuvant emulsion and of challenge site location. (1985)

Guinea pig maximization tests (GPMT) with chlorocresol were performed to ascertain whether the sensitization rate was affected by minor changes in the Freund's complete adjuvant (FCA) emulsion used. Three types of emulsion were evaluated: the oil phase was mixed with propylene glycol, saline with 30% (v/v) ethanol or saline, respectively. Relative viscosity was used as one measure of physical properties of the emulsion. Higher degrees of sensitization (but not rates) were obtained at the 48 h challenge reading with the oil/propylene glycol and oil/saline + ethanol emulsions compared to the saline/oil emulsion. Placing of the challenge patches affected the response, as simultaneous chlorocresol challenge on the flank located 2 cm closer to the abdomen than the usual challenge site gave decreased reactions.
Characteristics and Precipitation of Glucose Oligomers in the Fresh Liquid Products Obtained from the Hydrolysis of Cellulose in Hot-Compressed Water (2009)

Using a high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD), this study shows the presence of a wide range of glucose oligomers with the degrees of polymerization (DPs) up to 30 and their derivatives in the fresh liquid products produced from cellulose hydrolysis in hot-compressed water (HCW) using a semicontinuous reactor system at 280 °C and 20 MPa. None of those oligomers can be detected by a high-performance liquid chromatography with evaporative light scattering detector (HPLC-ELSD) that however can detect glucose oligomers with DPs up to 6 after the liquid solutions are concentrated by 25 times via vacuum evaporation at 40 °C, during which a large amount of precipitate is formed. While quantitative analysis of the glucose oligomers with DPs > 5 cannot be done due to the lack of standards, that of the glucose oligomers from glucose (DP = 1) to cellopentaose (DP = 5) using both HPAEC-PAD and HPLC-ELSD are in good agreement, suggesting that these low-DP glucose oligomers do not contribute to the precipitate formation. Results from a set of purposely designed precipitation experiments indicate that the precipitation starts as the fresh liquid sample is collected and is fast during the initial 8 h, levels off as the precipitation time increases further, and completes after 120 h (5 days). On the basis of a new approach developed for the quantification of glucose oligomer retention during the precipitation process, it is found that the contribution of glucose oligomers to precipitate formation increases with DP. The higher the DP is, the lower the solubility of the glucose oligomer is. The glucose oligomers from glucose to cellopentaose and their derivatives (DPs = 1−5) contribute little to the precipitate formation, which explains why HPLC-ELSD can correctly analyze these glucose oligomers in the concentrated solutions prepared by vacuum evaporation. The glucose oligomers and their derivatives with DP > 5, which are soluble in HCW but become supersaturated in the solutions under ambient conditions, are responsible for precipitate formation. Most (but not all) of the glucose oligomers and their derivatives with DPs > 16 contribute to the precipitate formation as tiny peaks of these glucose oligomers are still shown in the chromatograms, suggesting that these glucose oligomers have very low (but nonzero) solubilities in ambient water. The retentions of glucose oligomers and their derivatives increase substantially with the DP decreasing from 16 to 6, indicating that less of these lower-DP oligomers contribute to the precipitate formation. To avoid the effect of precipitation on oligomer analysis, the fresh liquid products must be analyzed immediately after sample collection.
Neurocognitive functioning in Lesch-Nyhan disease and partial hypoxanthine-guanine phosphoribosyltransferase deficiency (2001)

Lesch-Nyhan disease (LND) is a rare, X-linked genetic disorder that involves the nearly complete absence of an enzyme (hypoxanthine-guanine phosphoribosyltransferase, or HPRT) that is essential for purine salvage. In addition to hyperuricemia, all patients with classic LND suffer from movement disorder and compulsive self-injury, and most have mental retardation. Patients with partial HPRT deficiency (variants) always have hyperuricemia and often have neurologic abnormalities, but do not self-injure and usually are described as having normal intelligence. Here we compare 15 patients with LND to 9 variants and 13 normal adolescents and adults. Testing revealed unambiguous and qualitatively similar cognitive deficits in both patient groups. The variants produced scores that were intermediate between those of patients with LND and normal participants on nearly every cognitive measure. We discuss these findings in terms of what is known about the neuropathology of LND.
Encapsulation Study of 6-Methylprednisolone in Lipid Microspheres (1997)

AbstractThe search for new pharmaceutical forms that provide greater security and efficiency is one of the main research activities of pharmaceutical technology. This paper concerns a detailed study of the encapsulation of a glucoconicoid with anti-inflammatory action (6-methylprednisolone) in lipid microspheres, one of the systems used for the transport and delivery of lipid-soluble-type drugs. The method used, in common with previous experiments, was that of the solubilization of the constituents of the oil phase (refined soybean oil, soybean lecithin, cholesterol, and the active agent) and, separately, of the aqueous phase of the emulsion (Tween 80, glycerol, and distilled water). The two phases were then mixed by mechanical shaking, and the micelles were homogenized and filtered through membranes of 1.20-μm pore diameter. To determine the percentage encapsulated of the active agent, the first step was the separation of the encapsulated fraction from the free fraction in the medium by molecular exclusion chromatography or filtration in gel. A dextrose (Sephadex G-50 fine) gel was used for the absorbent or stationary phase, and distilled water was used for the eland, or mobile phase. me determination of the free glucocorticoid in the hydroethanol solution by ultraviolet spectrophotometry at 243 nm permits us to calculate the percentage taken by the microspheres. The formula composed of soybean oil and lecithin in the ratio 1:1.1 (w/w), cholesterol (0.50 g/100 ml), Tween 80 (0.25 g/100 ml), and glycerol (0.63 g/100 ml) produced the greatest quantity of encapsulated active agent: 84.91 ± 4.45%.Key Words:: Drug transport and delivery systemsFat emulsionsGlucocorticoidsLipid microspheres6-Methylprednisolone
Development of improved cell lysis, solubilization and imaging approaches for proteomic analyses (2002)

Analysis of complex biochemical processes at the level of the proteome requires methods that quantitatively solubilize cytosolic and membrane bound proteins yet are compatible with isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In addition, it is often necessary to employ several highly sensitive detection methods to identify key proteins that are modified or exhibit a change in expression levels in response to a given experimental stimulus or condition. Methods were developed that efficiently extract tissues or lyse cultured cells and quantitatively solubilize proteins in a single step without the need to shear nucleic acids. These approaches utilize urea, thiourea, a mixture of detergents, low levels of an ampholyte blend, reductant and a combination of alcohols. To aid in the detection of low abundance proteins and the accurate identification of specific proteins of interest in these samples, two approaches were pursued. In one, proteins are transferred from two-dimensional (2-D) gels to blot membranes. Proteins are then detected by staining with SYPRO Ruby and the resulting 2-D protein pattern is captured using a charge-coupled device (CCD) camera. The blots are then probed with antibodies directed against the protein(s) or functionalities of interest. The resulting chemiluminescent blot image is also generated with the CCD camera and the fluorescent SYPRO Ruby image is recaptured again without moving the membrane. It is thereby possible to generate a direct image overlay of the blot pattern on that of the stained protein pattern. This approach significantly aids in the accurate identification of the dye-stained protein that is detected by the specific antibody. In addition to detecting protein post-gel transfer, a second approach utilizes protein samples labeled with fluorescent dyes prior to 2-D electrophoresis in an effort to increase the sensitivity of protein detection and to facilitate protein quantitation. It is also possible to stain the blots with different dyes and overlay these images as well. Using these approaches, it is possible to perform more rapid and accurate comparative analyses and proteomic, post-gel characterization of proteins of interest than using comparative image analysis of multiple gels.
Logic Synthesis Through Local Transformations (1981)

A logic designer today faces a growing number of design requirements and technology restrictions, brought about by increases in circuit density and processor complexity. At the same time, the cost of engineering changes has made the correctness of chip implementations more important, and minimization of circuit count less so. These factors underscore the need for increased automation of logic design. This paper describes an experimental system for synthesizing synchronous combinational logic. It allows a designer to start with a naive implementation produced automatically from a functional specification, evaluate it with respect to these many factors, and incrementally improve this implementation by applying local transformations until it is acceptable for manufacture. The use of simple local transformations in this system ensures correct implementations, isolates technology-specific data, and will allow the total process to be applied to larger, VLSI designs. The system has been used to synthesize masterslice chip implementations from functional specifications, and to remap implemented masterslice chips from one technology to another while preserving their functional behavior.
Developmental Fate of Skeletal Muscle Satellite Cells (1979)

Radioisotopically labeled satellite cells from clonal cultures were implanted into normal muscle of the original donor. Implanted cells invariably retained their myogenic potential by participating in the regeneration of damaged myofibers or in the development of existing fibers.
Osmolalities of Propylene Glycol-Containing Drug Formulations for Parenteral Use. Should Propylene Glycol Be Used as a Solvent? (1992)

Propylene glycol (PG) is a widely used vehicle for water-insoluble drugs. Injection of drugs formulated with this solvent often results in pain, thrombosis, or thrombophlebitis that can be reduced by premedication with local anesthetics or opioids. Because osmolality and pH that are unphysiologic may cause these adverse effects, we assessed the contribution of PG to the osmolality of parenteral drug formulations. Osmolality of PG measured in distilled water showed that PG content and osmolality were directly related: 2% wt/vol PG, 264 mOsm/L; 100% PG, 15, 200 mOsm/L. The osmolalities of commercially available preparations of drugs dissolved in PG ranged from 365 mOsm/L (2% PG content) to 12,800 mOsm/L (83.46% PG), with most above 1000 mOsm/L. Replacement of PG by a solvent with lower osmolality in Germany has effectively reduced the incidence of side effects for one drug. Until PG can be replaced in drugs, we recommend diluting drugs in a large volume of saline solution; this may help to minimize the undesirable effects of this solvent.
Distinct Roles of CONSTANS Target Genes in Reproductive Development of Arabidopsis (2000)

In plants, flowering is triggered by endogenous and environmental signals. CONSTANS (CO) promotes flowering of Arabidopsis in response to day length. Four early target genes of CO were identified using a steroid-inducible version of the protein. Two of these genes, SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1) and FLOWERING LOCUS T (FT), are required for CO to promote flowering; the others are involved in proline or ethylene biosynthesis. The SOC1 and FT genes are also regulated by a second flowering-time pathway that acts independently of CO. Thus, early target genes of CO define common components of distinct flowering-time pathways.
Nanocomposites—a new material design concept (2004)

Ceramic-based nanocomposites were reviewed, emphasizing the newly developed concept of material design for ceramics. First, characteristics of the nanocomposites observed by previous researchers were summarized as, significant or moderate improvement in strength, drastic change of the fracture mode from intergranular fracture of monolithic ceramics to transgranular fracture of nanocomposites, moderate enhancement of fracture toughness, improvement of other mechanical properties, and observations of dislocations. Second, several mechanisms proposed previously to explain these characteristics were reviewed. Third, our strengthening and toughening mechanisms of nanocomposites on the basis of dislocation activities were explained. In nanocomposites, the highly localized residual stresses in the matrix grains are generated by the mismatch of thermal expansion coefficients between the matrix and the dispersed particles, and the dislocations are yielded during the cooling process after sintering. These dislocations then release the tensile residual stresses intrinsically existing in the matrix grains of sintered ceramics and improve the strength of the materials. In addition, as these dislocations cannot move at room temperature the sessile dislocations in the matrix operate as nano-crack nuclei in a frontal process zone (FPZ) ahead of the crack tip when the tip of a propagating crack approaches this area. Therefore, the size of the FPZ is expanded and as a result the fracture toughness is improved. Finally, estimation of the critical FPZ size was explained in order to clarify its toughening mechanism in nanocomposites.
Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4. (1994)

Bone morphogenetic proteins (BMPs) are multifunctional proteins, structurally related to transforming growth factor-beta (TGF-beta) and activin. TGF-beta and activin exert their effects by forming heteromeric complexes of type I and type II serine/threonine kinase receptors. We have previously identified a series of type I serine/threonine kinase receptors, termed activin receptor-like kinase (ALK)-1 to -6. ALK-5 is a TGF-beta type I receptor, whereas ALK-2 and ALK-4 are activin type I receptors. Here we investigated the binding of proteins in the BMP family to ALKs. In transfected COS cells, the binding of osteogenic protein (OP)-1 and BMP-4 to certain ALKs was observed in the absence of type II receptors, and their binding was increased after co-transfection of a BMP type II receptor from Caenorhabditis elegans, DAF-4. OP-1 bound to ALK-2 and ALK-6 efficiently, and to ALK-3 less efficiently, whereas BMP-4 bound to ALK-3 and ALK-6 efficiently. Similarly, OP-1 bound to ALK-2, ALK-3, and/or ALK-6 in various nontransfected cell lines, although the binding profiles were different between different cell types. BMP-4 bound to ALK-3 in MC3T3-E1 osteoblasts and human foreskin fibroblasts. These results suggest that ALK-3 and ALK-6 are type I receptors for OP-1 and BMP-4; in addition, ALK-2 is a type I receptor shared by activin and OP-1, but not by BMP-4.
Feasibility study of current mode differential amplifier design (2003)

A new class of current mode amplifiers, designed to operate in a true current-mode environment, is introduced. They utilize the FCS (floating current source), a novel current-mode building block, in various configurations. Two current-mode differential amplifiers of this type are described. The first one employs two translinear gain stages. The CM (common mode) response is reduced by a negative feedback loop responding to the CM only. The translinear gain can be adjusted by varying the value of two current source pairs in unison. The second is a differential feedback amplifier, employing two independent feedback loops which apply parallel feedback to the input virtual ground, one for the differential and another for the common mode. Its input admittance and output impedance are both increased significantly by the feedback applied.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Design, Synthesis, and Structure−Activity Relationships of Acetylene-Based Histamine H3 Receptor Antagonists (1999)

New, potent, and selective histamine H3 receptor antagonists have been synthesized by employing the use of (1) an appropriately positioned nonpolar acetylene spacer group, (2) either a two-carbon straight chain linker or a conformationally restricting trans-cyclopropane ring between the C-4 position of an imidazole headgroup and the acetylene spacer, and (3) a Topliss operational scheme for side-chain substitution for optimizing the hydrophobic domain. Compounds 9-18 are examples synthesized with the two-carbon straight chain linker, whereas 26-31 are analogues prepared by incorporation of the trans-(+/-)-cyclopropane at the C-4 position of an imidazole headgroup. Synthesis of both the (1R,2R)- and (1S, 2S)-cyclopropyl enantiomers of the most potent racemic compound 31 (Ki = 0.33 +/- 0.13 nM) demonstrated a stereopreference in H3 receptor binding affinity for the (1R,2R) enantiomer 32 (Ki = 0.18 +/- 0.04 nM) versus the (1S,2S) enantiomer 33 (Ki = 5.3 +/- 0.5 nM). (1R,2R)-4-(2-(5,5-Dimethylhex-1-ynyl)cyclopropyl)imidazole (32) is one of the most potent histamine H3 receptor antagonists reported to date.
Reduced corpus callosum, fornix and hippocampus in PDAPP transgenic mouse model of Alzheimer's disease (2001)

Persons with Alzheimer's disease (AD) have progressive reductions in the relative sizes of the corpus callosum and hippocampus. Homozygotic PDAPP transgenic mice over-expressing a mutant form of the human amyloid precursor protein have more pronounced reductions in these regions, which are apparent prior to the deposition of amyloid plaques and do not progress with advancing age. The length of the corpus callosum was reduced by two-thirds, the fornix commissure was negligible, and the hippocampal volume was reduced by one-third, suggesting a massive disconnection between the cerebral hemispheres and the hippocampi in PDAPP mice. These findings, which might account for the early, nonprogressive behavioral abnormalities observed in these animals, have implications for the study of AD.
Management of small cell lung cancer (2001)

Small cell lung cancer is a tumor that has a very poor prognosis without treatment. It is however, highly responsive to chemotherapy and radiotherapy. Pretreatment clinical and laboratory parameters--in addition to staging--can prognosticate outcome and help define the aim of treatment. Different schedules of chemotherapy have been developed and varied strategies, such as chemotherapy dose intensification have been tried to improve outcomes. New agents, such as irinotecan, gemcitabine and topotecan have also been tested. Clinical trials have helped to define strategies of integrating thoracic radiotherapy and prophylactic cranial radiotherapy into management of those patients with limited disease to improve survival further. Despite good initial responses to treatment, most patients eventually relapse. Maintenance strategies with ongoing chemotherapy or novel agents, such as interferon, matrix metalloproteinase inhibitors, thalidomide and vaccines are discussed.
The Role of IL-8 in Patients With Fibromyalgia (2008)

Our results suggest that IL-8 level contributes in patients with FM whose pain intensity and back function can be improved under influence of multidisciplinary pain therapy without need of an anti-IL-8 therapy.
Passive range estimation using over sea multipath (1988)

This thesis suggests an unconventional, unique method for passive range and height estimation of a cruising missile, or other microwave transmitter. Based on multipath propagation, the method uses 5 receiving antennas in a ladder configuration. Ratios of received signal powers are compared with values from lookup tables to determine the correct location of the transmitter. Computer simulation results are presented, to verify the suggested method.