gebhart/patrepeval huggingface dataset:
Cross-linking of a B25 azidophenylalanine insulin derivative to the carboxyl-terminal region of the alpha-subunit of the insulin receptor. Identification of a new insulin-binding domain in the insulin receptor. (1994)

To identify a site within the insulin receptor ectodomain which forms a binding pocket for B25 Phe and is responsible for initiating conformational changes required for high affinity binding of insulin we have used a novel photoreactive insulin, despentapeptide-(B26-B30) [B25 p-azidophenylalanine-alpha-carboxamide] insulin (APC insulin). This derivative has a highly photoreactive azido group incorporated into the aromatic ring of the B25 phenylalanine amide. APC insulin bound to human insulin receptors overexpressed on a transfected Chinese hamster ovary cell line (P3-A) with an apparent potency of 9-fold relative to that of native insulin and stimulated lipogenesis in rat adipocytes with an average potency equal to porcine insulin. Addition of biotin to the B1 Phe amino group to form despentapeptide-(B26-B30) [B1 (6-biotinylamidocaproyl)phenylalanine B25 p-azidophenylalanine-alpha-carboxamide] insulin derivative (Bio-APC insulin) did not adversely affect receptor-binding affinity and provided a convenient ligand for purification of cross-linked complexes. The efficiency of receptor cross-linking with these reagents was high (70%). To identify the site(s) of cross-linking, the insulin receptor in P3-A cells was first metabolically labeled with various individual 3H-labeled amino acids and then photoaffinity labeled with 125I-Bio-APC insulin, isolated, and digested with Lys-C endoproteinase. The resulting cross-linked peptide fragments were separated by streptavidin-affinity chromatography and sequenced. The smallest identified fragment comprised residues 704-718 of the COOH terminus of the alpha-subunit of the insulin receptor. This B25 Phe cross-linked region of the alpha-subunit lies just upstream of the Exon 11-encoded 12-amino acid COOH-terminal region. Aromatic residues in this predicted alpha-helical region may form a binding pocket for B25 Phe to initiate conformational changes required for stabilizing the high affinity binding state.
Effect of Channel Estimation Error on Bit Error Probability in OFDM Systems over Rayleigh and Ricean Fading Channels (2008)

A characteristic function-based method is used to derive closed-form bit error probability (BEP) expressions for orthogonal frequency-division multiplexing (OFDM) systems in the presence of channel estimation error over frequency-selective Rayleigh fading channels and frequency-selective Ricean fading channels. Both single channel reception and diversity reception with maximal ratio combining (MRC) are examined. The BEP expressions are shown to be sums of several conditional probability functions which can be calculated by using proper complex Gaussian random variable theory and a characteristic function method. The closed-form BEP expressions can be used to accurately investigate the bit error rate performance degradation caused by channel estimation error under different wireless channel environment models. The performances of two interpolation methods, a sine interpolator with Hamming windowing and a Wiener interpolator, are compared.
Continuous separation of cells by balanced dielectrophoretic forces at multiple frequencies (2007)

We present a particle-sorting device based on the opposition of dielectrophoretic forces. The forces are generated by an array of electrode chambers located in both sidewalls of a main flow channel. Particles with different dielectric response perceive different force magnitudes and are therefore continuously focused to different streamlines in the flow channel. We relate the particles' dielectric response to their output position in the downstream channel. We demonstrate the performance of the device by separating a mixed yeast cell population into pure fractions of viable and nonviable cells. Finally, we use the device to enrich red blood cells infected with Babesia bovis, a major pathogen in cattle and simultaneously confirm the hypothesis that infection with B. bovis causes significant changes in the dielectric response of red blood cells.
The Influence of Protein Binding upon Tissue Fluid Levels of Six -Lactam Antibiotics (1980)

The effect of protein binding upon the penetration of six-beta-lactam (three penicillins and three cephalosporins) antibiotics into tissue fluid was studied in humans. A cantharides blister technique was used. It was found that there was a linear relationship between the percentage of protein binding and the penetration into the blister fluid of the antibiotic as measured by the area under the curve of the protein-free fraction. This finding is further evidence that protein binding may have important influence upon the likely efficacy of an antimicrobial agent.
A multimedia-enhanced x86 processor (2002)

This x86 compatible CPU with multimedia functionality includes DRAM controller, accelerated graphics controller, and PCI bus interface. The integer pipeline and L1 cache of the CPU are enhanced to accelerate graphics and multimedia applications, and take advantage of the on-chip peripherals. Modules integrated onto the die are chosen because they are high-value functions with compelling performance or reduced complexity when integrated with the CPU. Graphics and video functions benefit from a tight integration with the CPU since partitioning of functions between hardware and software can differ from a traditional architecture without hurting performance.
A growth-stimulating activity derived from the proximal small intestine is associated with an adaptive response (1990)

Luminal nutrition is important for the maintenance of small intestinal structure and function. The equilibrium between crypt cell production and villous cell loss in the mucosal epithelium of the small intestine is altered under certain conditions such as after a small bowel resection. Immediately after resection, there is a marked increase in crypt cell proliferation giving rise to an adaptive hyperplasia in the remnant intestine and for this response luminal nutrition is a critical factor. We have previously demonstrated the presence of a growth-stimulating (GS) activity in a heat-stable acidic extract of the rat proximal intestine 24, 48, and 96 h after resection, which is coincidental with an increase in crypt cell proliferation as measured by thymidine kinase activity. Eight days after resection when the GS activity is no longer detectable, the thymidine kinase activity returns to control values. The molecular weights of the peptides associated with this GS activity are 4500 and 1500, as determined by Sephadex gel filtration. Of note is that the oral intake of food is necessary for the appearance of the GS activity postoperatively. The presence of the GS activity has also been demonstrated upon refeeding after a fast, as well as at weaning in the rat, two physiological situations known to be associated with increased proliferation in the small intestine. This GS activity in the proximal intestine first detected in the resection model may represent a general mechanism by which food controls the cell renewal pattern of the small intestine.
Retention of Fluorine in Silica Gels and Glass* (1989)

F − ions enter silica gels as Si‐F bonds and free and hydrogen‐bonded HF. During drying, heating, and sintering, all HF is removed, and a significant portion of the structural fluoride (Si‐F) is also eliminated through reaction with Si—OH, which results in formation of siloxane bonds. Substitution of Si‐Cl bonds for Si—OH bonds assists in retention of fluoride, and up to ∼1 wt% F can be preserved in gels heated to 1000 °C. Introduction of SiF 4 into the sintering atmosphere can increase the amount of retained fluoride in the silica glass up to ∼1.8%.
Controversies Concerning Vitamin K and the Newborn (1993)

Vitamin K deficiency may cause unexpected bleeding (0.25% to 1.7% incidence) during the first week of life in previously healthy-appearing neonates (classic hemorrhagic disease of the newborn [HDN]). The efficacy of neonatal vitamin K prophylaxis (either oral or parenteral) in the prevention of classic HDN is firmly established. It has been the standard of care since the recommendation by the Committee on Nutrition was adopted as policy by the American Academy of Pediatrics in 19611 Late HDN, a syndrome defined as unexpected bleeding due to severe vitamin K deficiency in infants aged 2 to 12 weeks, occurs primarily in exclusively breast-fed infants who have received no or inadequate neonatal vitamin K prophylaxis. In addition, infants who have intestinal malabsorption defects (cholestatic jaundice, cystic fibrosis, etc) may also present with late HDN. The rate of late HDN (often manifested by sudden central nervous system hemorrhage) ranges from 4.4 to 7.2 per 100 000 births based on reports from Europe and Asia. When a single dose of oral vitamin K has been used as neonatal prophylaxis, the rate has decreased to 1.4 to 6.4 per 100 000 births. Parenteral neonatal vitamin K prophylaxis prevents the development of late HDN, with the rare exception of infants with severe malabsorption syndromes. Oral regimens that have a similar efficacy as parenteral vitamin K in prevention of late HDN include the repeated administration of oral vitamin K1 (Germany) or K2 (Japan) at birth, 1 week, and 2 to 4 weeks. In 1990 Golding et al2 reported a study of a 1970 birth cohort in Britain in which they noted an unexpected association between childhood cancer and pethidine given in labor and the neonatal administration of vitamin K. Subsequently, Golding and others3 conducted a case-control study designed to examine the risk of cancer associated with intramuscular vitamin K administration among infants born in two hospitals in Avon between 1965 and 1987 and diagnosed with cancer between 1971 and 1989.
Guanine nucleotide-binding proteins that enhance choleragen ADP-ribosyltransferase activity: nucleotide and deduced amino acid sequence of an ADP-ribosylation factor cDNA. (1988)

Three (two soluble and one membrane) guanine nucleotide-binding proteins (G proteins) that enhance ADP-ribosylation of the Gs alpha stimulatory subunit of the adenylyl cyclase (EC 4.6.1.1) complex by choleragen have recently been purified from bovine brain. To further define the structure and function of these ADP-ribosylation factors (ARFs), we isolated a cDNA clone (lambda ARF2B) from a bovine retinal library by screening with a mixed heptadecanucleotide probe whose sequence was based on the partial amino acid sequence of one of the soluble ARFs from bovine brain. Comparison of the deduced amino acid sequence of lambda ARF2B with sequences of peptides from the ARF protein (total of 60 amino acids) revealed only two differences. Whether these are cloning artifacts or reflect the existence of more than one ARF protein remains to be determined. Deduced amino acid sequences of ARF, Go alpha (the alpha subunit of a G protein that may be involved in regulation of ion fluxes), and c-Ha-ras gene product p21 show similarities in regions believed to be involved in guanine nucleotide binding and GTP hydrolysis. ARF apparently lacks a site analogous to that ADP-ribosylated by choleragen in G-protein alpha subunits. Although both the ARF proteins and the alpha subunits bind guanine nucleotides and serve as choleragen substrates, they must interact with the toxin A1 peptide in different ways. In addition to serving as an ADP-ribose acceptor, ARF interacts with the toxin in a manner that modifies its catalytic properties.
Fetal hemoglobin levels and morbidity in untransfused patients with β-thalassemia intermedia (2011)

To evaluate the association between fetal hemoglobin (HbF) levels and morbidity in β-thalassemia intermedia (TI), we analyzed data from 63 untransfused patients who had also never received HbF induction therapy. Patient records were reviewed for any history of 10 predefined morbidities. Laboratory measurements for markers of ineffective erythropoiesis were also obtained. The mean age of patients was 32.1 years, 47.6% were males, and the median HbF level was 37.2%. HbF levels correlated positively with total hemoglobin, yet negatively with growth differentiation factor-15 and non-transferrin-bound iron levels. Median HbF levels were significantly lower in patients with the majority of evaluated morbidities than in those without. There was a strong negative adjusted linear correlation between the HbF level and the total number of morbidities (R(2) = 0.825, P < .001). The HbF threshold of 63.7% had 95.5% sensitivity and 100% specificity for ensuring absence of morbidity. There exists a strong association between HbF levels and morbidity in the subset of untransfused patients with TI.
Thermodynamics of the Melting of PNA2/DNA Triple Helices (2001)

Equilibrium melting curves were obtained for triplexes, formed by single stranded DNA containing an A10 target with bis-PNA consisting of two T10 decamers. Thermodynamic parameters of melting were determined for Na(+) concentrations 50, 200 and 600mM by two methods. The melting enthalpy Delta H degrees was evaluated from the width of the differential melting curves and from the concentration dependence of the melting temperature. The latter method allowed also evaluating the melting entropy Delta S degrees. The following results were obtained: Delta H degrees = - 137 kcal/M, Delta S degrees = - 368 cal/M.K, Delta G degrees (298)= - 27 kcal/M. No dependence of Delta H degrees, Delta S degrees and Delta G degrees (298) was observed upon ionic strength within the accuracy of the experiment (+/- 10%). The absolute values of Delta H degrees, Delta S degrees and Delta G degrees(298) are 2 to 3 times higher than the published values of corresponding melting parameters for decameric PNA/DNA duplexes of various nucleic base sequences. The origin of the extremely high stability of the triplexes is discussed.
Penetration of Tenofovir and Emtricitabine in Mucosal Tissues: Implications for Prevention of HIV-1 Transmission (2011)

A mainstay of strategies to prevent HIV-1 transmission is to use antiretroviral therapy (ART) for pre-exposure prophylaxis (PrEP). Critical to the design and interpretation of PrEP prevention trials is the ability to make accurate pharmacological measurements of ART drugs in human genital and colorectal mucosal tissues, the principal route of HIV transmission. Here, we evaluated two drugs that are preferentially used for PrEP: tenofovir (TFV) disoproxil fumarate (TDF) and emtricitabine (FTC). A single oral dose of TDF/FTC (Truvada) was administered to 15 healthy individuals. Over the next 14 days, TFV and FTC were measured in blood plasma and genital secretions using a sensitive assay (lower level of quantification, 0.1 ng/ml). The active intracellular phosphorylated metabolites of these drugs [TFV diphospate (TFV-DP) and FTC triphosphate (FTC-TP)] were measured in homogenates prepared from rectal, vaginal, and cervical tissues. TFV and FTC were detected in blood plasma 14 days after administration of a single dose. The area under the concentration-time curve from 24 hours to 14 days (AUC(1-14d)) for FTC in genital secretions was 27-fold greater than in blood plasma, whereas the AUC(1-14d) for TFV was only 2.5-fold greater in genital secretions than in blood plasma. In rectal tissue, TFV and TFV-DP concentrations were detectable for 14 days and were 100-fold higher than the concentrations in vaginal and cervical tissues. Vaginal and cervical tissue concentrations of FTC were 10- to 15-fold higher than in rectal tissue. Despite high concentrations of FTC in vaginal and cervical tissue, FTC-TP concentrations in all tissue types were detected for only 2 days after dose. The exposure to TFV, TFV-DP, FTC, and FTC-TP was wide ranging depending on the type of mucosal tissue. These results demonstrate the need for detailed pharmacological studies to improve the application of ART for PrEP to prevent transmission of HIV.
Pharmacological Chaperones as Therapeutics for Lysosomal Storage Diseases (2013)

Lysosomal enzymes are responsible for the degradation of a wide variety of glycolipids, oligosaccharides, proteins, and glycoproteins. Inherited mutations in the genes that encode these proteins can lead to reduced stability of newly synthesized lysosomal enzymes. While often catalytically competent, the mutated enzymes are unable to efficiently pass the quality control mechanisms of the endoplasmic reticulum, resulting in reduced lysosomal trafficking, substrate accumulation, and cellular dysfunction. Pharmacological chaperones (PCs) are small molecules that bind and stabilize mutant lysosomal enzymes, thereby allowing proper cellular translocation. Such compounds have been shown to increase enzyme activity and reduce substrate burden in a number of preclinical models and clinical studies. In this Perspective, we review several of the lysosomal diseases for which PCs have been studied and the SAR of the various classes of molecules.
A Self-Directed Growth Process for Creating Covalently Bonded Molecular Assemblies on the H−Si(100)-3×1 Surface (2004)

A chain reaction initiated at a dangling bond on a H-terminated Si(100)-3×1 surface leads to the creation of contiguous, linear multimolecular assemblies. In contrast to a similar growth process observed on the H−Si(100)-2×1 surface, the linear structures grow in the cross-row direction, rather than parallel to dimer rows. This process is enabled by both an uncommonly high rate of H atom diffusion, specifically in the cross-row direction, and a low barrier to H atom abstraction from dihydride sites. These results demonstrate that anisotropy inherent to the substrate can be imposed upon molecular assemblies formed via this “self-directed” growth process.
A Comparison of Lithium and T 3 Augmentation Following Two Failed Medication Treatments for Depression: A STAR*D Report (2006)

Remission rates with lithium and T(3) augmentation for participants who experienced unsatisfactory results with two prior medication treatments were modest and did not differ significantly. The lower side effect burden and ease of use of T(3) augmentation suggest that it has slight advantages over lithium augmentation for depressed patients who have experienced several failed medication trials.
Autocrine production of pre-B-cell stimulating activity by a variety of transformed murine pre-B-cell lines. (1988)

Current evidence suggests that the proliferation and differentiation of normal pre-B-cells may be regulated by interactions with mesenchymally derived stromal cells. The nature of these cell-cell interactions has not yet been fully elucidated, but the involvement of pre-B-cell stimulating factors produced by various mesenchymal cell lines has recently been demonstrated in the murine system. In this model, transformed pre-B-cells differ from their normal counterparts in their acquisition of autonomous growth potential, as seen by an ability to be maintained in vitro in the absence of mesenchymal cell feeders. To test the hypothesis that autonomy might be associated with autocrine growth factor production, we tested the ability of a spontaneous pre-B-cell transformant (H9 cells) and two independently derived Abelson murine leukemia virus transformed pre-B-cell lines to produce pre-B-cell stimulating factors. All three lines released activities that stimulated the proliferation of themselves or H9 cells when cultured at low cell densities. One of the three transformed pre-B-cell lines could also substitute for mesenchymal feeders to stimulate normal pre-B-cells. Time course studies of an evolving Abelson murine leukemia virus transformant showed that the production of an autocrine pre-B-cell growth factor increased concomitantly with the acquisition of autonomous growth potential suggesting a relationship between these two phenotypic changes. Preliminary characterization of the growth factor responsiveness of H9 cells and the nature of the autostimulatory activity produced by this line suggested its nonidentity with any known hemopoietic growth factor. Activation of autocrine growth factor production appears to be a common event in the evolution of malignant pre-B-cells arising through different oncogenic mechanisms and may therefore be relevant to the pathogenesis of human acute lymphoid leukemia.
Induced Cholesteric Mesophases: Origin and Application (1985)

Abstract The relationship between the twisting power (β) and the molecular structure of the dopant and neraatic solvent are discussed. High values of β are observed whenever two (or more) planar or quasi-planar moieties, chirally distorted one with respect to the other, are present in the dopant. For high twisting powers, the mechanism of induction seems to be connected to the transfer of chirality from the solute to the solvent via chiral conformations of the latter. Sterochemical and analytical applications are briefly discussed.
Defining the directionality and quality of influenza virus–specific CD8+ T cell cross-reactivity in individuals infected with hepatitis C virus (2008)

Cross-reactivity of murine and recently human CD8(+) T cells between different viral peptides, i.e., heterologous immunity, has been well characterized. However, the directionality and quality of these cross-reactions is critical in determining their biological importance. Herein we analyzed the response of human CD8(+) T cells that recognize both a hepatitis C virus peptide (HCV-NS3) and a peptide derived from the influenza neuraminidase protein (Flu-NA). To detect the cross-reactive CD8(+) T cells, we used peptide-MHC class I complexes (pMHCs) containing a new mutant form of MHC class I able to bind CD8 more strongly than normal MHC class I complexes. T cell responses against HCV-NS3 and Flu-NA peptide were undetectable in normal donors. In contrast, some responses against the Flu-NA peptide were identified in HCV(+) donors who showed strong HCV-NS3-specific reactivity. The Flu-NA peptide was a weak agonist for CD8(+) T cells in HCV(+) individuals on the basis of novel pMHCs and functional assays. These data support the idea of cross-reactivity between the 2 peptides, but indicate that reactivity toward the Flu-NA peptide is highly CD8-dependent and occurs predominantly after priming during HCV infection. Our findings indicate the utility of the novel pMHCs in dissecting cross-reactivity and suggest that cross-reactivity between HCV and influenza is relatively weak. Further studies are needed to relate affinity and functionality of cross-reactive T cells.
Banked bone grafting for bone defect repair--clinical evaluation of bone union and graft incorporation. (1988)

One hundred and twenty-four banked bone grafts performed during the past 15 years were studied in respect to union and graft incorporation processes using X-ray, bone scintigraphy and histology. Radiological study of the chip graft showed an absence of cavity contours, and homogenization of the grafted area, followed by development of the trabecular structure. In the block graft, initial union was shown at the junctional area followed by the appearance of mottled shadows throughout the entire graft and finally differentiation of bone marrow and cortex. Bone scintigraphy showed an initial increase in RI uptake at the junction and then a gradual increase in the entire graft. Histological study showed that bone apposition on the trabeculae of the graft starts in the junction and later extends to other areas. The replacement of cancellous bone is more rapid than that of cortical bone. The porous surface seems to promote bone union and incorporation when large block grafts of cortical bone are used.