gebhart/patrepeval huggingface dataset:
Role of dihydrotestosterone in androgen action (1996)

Androgen action differs from that of most hormones in the testosterone, the major androgen secreted from the testes and the most abundant androgen in the circulation of men, is not the principal androgen within target cells. Indeed, abundant evidence indicates that most androgen actions are mediated by the 5alpha-reduced metabolite dihydrotestosterone that is formed in target tissues. The conversion of testosterone to dihydrotestosterone is mediated by two isoenzymes; mutations in the steroid 5alpha-reductase 2 gene cause a rare autosomal-recessive form of male pseudohermaphroditism, and inhibition of this enzyme causes regression of the prostate gland. Dihydrotestosterone binds more tightly to the androgen receptor that does testosterone, but it is not clear whether this property is the sole explanation for its essential role in androgen action. Nor is it clear whether some androgenic effects may be mediated by circulating dihydrotestosterone acting as a hormone.
<title>Polymer microfluidics: the technology chain</title> (2000)

In addition to existing microfabrication technologies for the manufacturing of glass or silicon-based microfluidic devices, the increasing demand for polymer based systems requires the establishment of equivalent technologies for the microstructuring of polymers. These technologies can be divided into two fields, the structuring of the polymer itself and the subsequent back-end processes. This article describes a complete technology chain covering these two technology fields.
The subcutaneous lipolytic response to regional neural stimulation is reduced in obese women. (2000)

Disturbed fat tissue metabolism with a reduction of the lipolytic rate could be an important pathogenetic factor in obesity. Lipolysis of the subcutaneous tissue of the thigh is partly under neural control and can be increased by intraneural stimulation of the lateral cutaneous femoral nerve in lean women. In the present study, we tested whether the lipolytic response to intraneural stimulation is altered in vivo in obese subjects. Seven obese women were examined and the results were compared with those of seven age-matched lean women. After an overnight fast, the lateral cutaneous femoral nerve was intraneurally stimulated for 10 min, and the local subcutaneous lipolytic response to this procedure was evaluated with microdialytic measurements of interstitial glycerol concentrations in the receptive field of the stimulated nerve fascicle. To exclude unspecific effects of stimulation, lipolysis was also controlled in a corresponding area of the contralateral leg. Intraneural stimulation produced no significant change in subcutaneous lipolysis in obese women (25.7 +/- 9.7%, NS). This finding is in sharp contrast with the marked regional lipolytic response in lean women in which the same stimulation procedure enhanced the regional interstitial glycerol levels by 72 +/- 17% (P < 0.05) compared with the unstimulated corresponding area of the contralateral leg. These in vivo results suggest that human obesity is characterized by a profound unresponsiveness of the subcutaneous adipose tissue to neurally stimulated lipolysis. This could be an important factor in the development and treatment of obesity.
Human beta 2-microglobulin specifically enhances cell-surface expression of HLA class I molecules in transfected murine cells. (1988)

Sequential transfections of P815 murine mastocytoma cells with class I gene encoding either HLA-Cw3, HLA-A3, or HLA-B7 H chain and subsequently with a human beta 2-microglobulin gene were performed to evaluate the relative efficiency of human and murine beta 2-microglobulins in promoting the cell-surface expression of HLA-class I molecules. A 6-, 11-, and 40-fold specific enhancement of the cell-surface expression of HLA-Cw3, HLA-A3, and HLA-B7 molecules, respectively, was observed in cells co-transfected with human beta 2-microglobulin gene. This effect was attributed to a more efficient association of HLA H chains with human than with murine beta 2-microglobulin, which apparently allowed a more rapid transport of the HLA molecules from the endoplasmic reticulum to the Golgi apparatus.
Immunogenicity and Protective Efficacy of Oligomeric Human Immunodeficiency Virus Type 1 gp140 (2001)

The biologically active form of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein is oligomeric. We previously described a soluble HIV-1 IIIB Env protein, gp140, with a stable oligomeric structure composed of uncleaved gp120 linked to the ectodomain of gp41 (P. L. Earl, C. C. Broder, D. Long, S. A. Lee, J. Peterson, S. Chakrabarti, R. W. Doms, and B. Moss, J. Virol. 68:3015-3026, 1994). Here we compared the antibody responses of rabbits to gp120 and gp140 that had been produced and purified in an identical manner. The gp140 antisera exhibited enhanced cross-reactivity with heterologous Env proteins as well as greater neutralization of HIV-1 compared to the gp120 antisera. To examine both immunogenicity and protective efficacy, we immunized rhesus macaques with oligomeric gp140. Strong neutralizing antibodies against a homologous virus and modest neutralization of heterologous laboratory-adapted isolates were elicited. No neutralization of primary isolates was observed. However, a substantial fraction of the neutralizing activity could not be blocked by a V3 loop peptide. After intravenous challenge with simian-HIV virus SHIV-HXB2, three of the four vaccinated macaques exhibited no evidence of virus replication.
Biochemically differentiated clonal human glial cells in tissue culture (1969)

Abstract A clonal line of astrocytes (designated CHB) derived from a brain tumor of human origin has been established in tissue culture. This cell line is capable of synthesizing an acid protein unique to the nervous system (S100‐protein). The S100‐protein synthesized by CHB cells is immunologically indistinguishable (by micro‐complement fixation) from S100‐protein present in human brain.
Depth Profiling in Diffusely Scattering Media Using Raman Spectroscopy and Picosecond Kerr Gating (2005)

We demonstrate how pulsed laser Raman excitation (approximately 1 ps) followed by fast optical Kerr gating (approximately 4 ps) can be used to effectively separate Raman signals originating from different depths in heterogeneous diffusely scattering media. The diffuse scattering slows down photon propagation through turbid samples enabling higher depth resolution than would be obtained for a given instrumental time resolution in an optically transparent medium. Two types of experiments on two-layer systems demonstrate the ability to differentiate between surface and sub-surface Raman signals. A Raman spectrum was obtained of stilbene powder buried beneath a 1 mm over-layer of PMMA (poly(methyl methacrylate)) powder. The signal contrasts of the lower stilbene layer and upper PMMA layer were improved by factors >or=5 and >or=180, respectively, by rejecting the Raman component of the counterpart layer. The ability to select the Raman signal of a thin top surface layer in preference to those from an underlying diffusely scattering substrate was demonstrated using a 100 mum thick optically transparent film of PET (poly(ethylene terephthalate)) on top of stilbene powder. The gating resulted in the suppression of the underlying stilbene Raman signal by a factor of 1200. The experiments were performed in back-scattering geometry using 400 nm excitation wavelength. The experimental technique should be well suited to biomedical applications such as disease diagnosis.
Mouse models of acute promyelocytic leukemia (2001)

Translocations involving a variety of fusion partners, such as promyelocytic leukemia gene, promyelocytic leukemia zinc finger, nucleophosmin, nuclear matrix protein, and signal transducer and activator of transcription protein 5B, with the retinoic acid receptor alpha gene are commonly associated with development of acute promyelocytic leukemia. Through the development of transgenic mouse models, some retinoic acid receptor alpha translocation fusion proteins have been shown to be capable of initiating acute promyelocytic leukemia development, and dictate the leukemias' responsiveness to retinoic acid. Transgenic mouse models also have identified the influence of reciprocal translocation fusion proteins on acute promyelocytic leukemia development, and have demonstrated that additional mutations can contribute to the development of acute promyelocytic leukemia. In this review, the authors summarize current mouse models of acute promyelocytic leukemia and describe current knowledge about additional genetic alterations that occur during development of acute promyelocytic leukemia in the mouse.
Recent advances in engineering proteins for biocatalysis (2014)

Protein engineers are increasingly able to rely on structure-function insights, computational methods, and deeper understanding of natural biosynthesis processes, to streamline the design and applications of enzymes. This review highlights recent successes in applying new or improved protein engineering strategies toward the design of improved enzymes and enzymes with new activities. We focus on three approaches: structure-guided protein design, computational design, and the use of novel scaffolding and compartmentalization techniques to improve performance of multienzyme systems. Examples described address problems relating to enzyme specificity, stability, and/or activity, or aim to balance sequential reactions and route intermediates by co-localizing multiple enzymes. Specific applications include improving production of biofuels using enzymes with altered cofactor specificity, production of high-value chiral compounds by enzymes with tailored substrate specificities, and accelerated cellulose degradation via multi-enzyme scaffold assemblies. Collectively, these studies demonstrate a growing variety of computational and molecular biology tools. Continued advances on these fronts coupled with better mindfulness of how to apply proteins in unique ways offer exciting prospects for future protein engineering and biocatalysis research.
Fibers of aligned single-walled carbon nanotubes: Polarized Raman spectroscopy (2000)

To probe the one-dimensional nature of single-wall carbon nanotubes (SWNTs) in bulk samples, we have devised a simple method for generating fibers of aligned SWNTs. We measured polarization-dependent Raman spectra on the oriented fibers. Contrary to what is expected from their theoretically assigned vibration-mode symmetries, all the Raman line intensities are observed to decrease in nearly equal amounts for the 647.1 nm laser excitation polarized perpendicular to the fiber axis versus that polarized parallel to the fiber axis. The effect is explained as a loss of resonance Raman scattering for the perpendicular polarization case.
A factorial HMM aproach to robust isolated digit recognition in background music (2004)

This paper presents a novel solution to the problem of isolated digit recognition in background music. A Factorial Hidden Markov Model (FHMM) architecture is proposed to accurately model the simultaneous occurrence of two independent processes, such as an utterance of a digit and an excerpt of music. The FHMM is implemented with its equivalent HMM by extending Nadas’ MIXMAX algorithm to a mixture of Gaussians PDF. At around 0 dB SNR, the proposed system shows an average relative reduction in word error rate of 57% in the recognition of isolated digits in background music.
Dendritic cells (1998)

Dendritic cells are potent stimulators of immune responses against foreign antigens. Recent advances in this area include the delineation of distinct developmental pathways for different dendritic cell subsets; the emerging concept that one dendritic cell subset has regulatory functions that may contribute to induction of tolerance to self antigens; increased understanding of the interaction of dendritic cells with microbial products and viruses, such as HIV; and the application of dendritic cells for immunotherapy in certain cancers and possibly for the induction of transplantation tolerance.
The Dbl family of oncogenes (1996)

Genetic screening and biochemical studies during the past few years have led to the discovery of a family of cell growth regulatory proteins and oncogene products for which the Dbl oncoprotein is a prototype. These putative guanine nucleotide exchange factors for Rho family small GTP-binding proteins (G proteins) all contain a Dbl homology domain in tandem with a pleckstrin homology domain, and seem to activate specific members of the Rho family of proteins to elicit various biological functions in cells. The Dbl homology domain is directly responsible for binding and activating the small G proteins to mediate downstream signaling events, whereas the pleckstrin homology domain may serve to target these positive regulators of G proteins to specific cellular locations to carry out the signaling task. Despite the increasing interest in the Dbl family of proteins, there is still a good deal to learn regarding the biochemical mechanisms that underlie their diverse biological functions.
Interferon-β and serum 25-hydroxyvitamin D interact to modulate relapse risk in MS (2012)

This study provided Class III evidence that IFN-β is associated with reduced risk of relapse, and this effect may be modified by a positive effect of IFN-β on serum 25(OH)D levels.
Double diastereocontrol in the synthesis of enantiomerically pure polyoxamic acid (1998)

Polyoxamic acid 4 is prepared by a short and efficient process involving diastereochemically matched cycloaddition of 5-(S)-phenylmorpholin-2-one 1 with (S)-glyceraldehyde acetonide 2, followed by sequential hydrolysis and hydrogenolysis of the adduct.
Down-regulation of alphav/beta3 integrin via misrouting to lysosomes by overexpression of a beta3Lamp1 fusion protein (2003)

We present a general strategy for the dominant negative reduction in the levels of type-1 membrane-bound heterodimeric proteins within the secretory pathway through fusion of the soluble ectodomain of one of the partners to the transmembrane-cytosolic tail of the lysosomal protein Lamp1. Thus, in human embryonic kidney (HEK)-293 cells, overexpression of an integrin beta 3Lamp1 chimera resulted in a drastic reduction of its endogenous partner, the integrin alpha v subunit. The mechanism involves the formation in the endoplasmic reticulum of a alpha v/beta 3Lamp1 complex that is subsequently sorted towards a lysosomal/endosomal degradation pathway. The specificity of this approach is afforded by the invariance in the levels of the endogenous integrins alpha 5 and beta1 as compared with control cells. Conversely overexpression of integrin beta 3 in HEK-293 cells led to an increased level of alpha v beta 3 at the cell surface. Functionally beta 3Lamp1 and beta 3 overexpressors exhibit decreased and increased adhesion to vitronectin, respectively, as well as diminished cellular aggregation. The application of this technology should enable the analysis of the functional importance of homodimers or heterodimers in the cell types of choice and the identification of novel partner proteins by proteomic approaches.
Evaluation of Toxorhynchites Splendens (Diptera: Culicidae) as a Bioassay Host for Dengue Viruses1 (1982)

Toxorhynchites splendens, a nonhematophagous mosquito, was evaluated as a bioassay host for the detection and propagation of dengue viruses. All dengue virus serotypes and strains attained titers in Tx. splendens comparable to those observed for 2 strains of Aedes aegypti. Peak virus titers occurred in Tx. splendens approximately 6 days postinoculation; however, specific fluorescence for all viruses was not observed in 100% of mosquito heads until 12 days postinoculation. A 100% correlation was noted between specific fluorescence in Tx. splendens heads and the recovery of virus from corresponding thoraxabdomens. The volume of inoculum tolerated by Tx. splendens was approximately 5 times greater than that injected into Ae. aegypti. Thus, for a given volume of inoculum, the number of Tx. splendens required for virus assays was appreciably less than that needed for Ae. aegypti. The overall survival rate for Tx. splendens following intrathoracic inoculation with dengue viruses was 92%, compared to 41 and 42% for 2 strains of male Ae. aegypti. These findings imply that Tx. splendens would be more efficient than Ae. aegypti as a laboratory assay host for detecting dengue viruses in blood of infected patients and for use in experimental investigations.
Eating habits of children with autism. (2002)

Autism is a developmental disorder characterized by severe deficits in social interaction and communication, as well as by stereotyped and repetitive behaviors. Children with autism frequently have significant eating difficulties with highly restricted range of food choices. Eating habits and patterns are often unusual and have an impact on family life. The purpose of this article was to review pertinent information regarding this complex developmental disorder and describe a recent study based on a parent survey of feeding patterns in children with autism to give a new perspective for both parents and professionals.
Influence of Pollination Treatments on Fruit Set and Development in Parthenocarpic Tomato (1984)

Abstract Flowers of 3 parthenocarpic tomato ( Lycopersicon esculentum Mill.) genotypes, ‘Severianin’ ( pat -2), PSET-1 ( pat -2) and RP 75/79, and one nonparthenocarpic genotype, ‘Tiny Tim’ ( pat -2 + ), were given various pollination treatments in a greenhouse study: a) natural pollination, b) pollination with a hand vibrator, c) emasculation followed by pollination with mentor (heat-killed) pollen, d) emasculation only, e) removal of stigmas, and f) removal of the distil half of the anthers and styles. RP 75/59 had greater total fruit set than did the pat-2 genotypes. Treatments preventing pollination inhibited seed formation of all genotypes and inhibited fruit set of ‘Tiny Tim’. Mentor pollen did not increase parthenocarpic fruit set for any genotype. Vibration of the flowers completely inhibited parthenocarpic fruit set for all genotypes except PSET-1, which had 15.7% parthenocarpic fruit. No difference in fruit size or days to ripening for seeded vs. seedless fruit were evident for the pat -2 genotypes. Seeded fruit of RP 75/59 were larger than seedless fruit (34.2 g vs. 20.3 g), and also took longer to ripen (2.9 days).
Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: Do cytokines trigger off exacerbations? (1988)

We have carried out a longitudinal study of interferon (IFN) and tumor necrosis factor (TNF) using a whole-blood mitogen stimulation assay in 20 multiple sclerosis (MS) patients and in a healthy control group. We set up individual profiles and the results were quite constant for each individual, both in healthy donors and in the patients in remission. Before exacerbations, however, we found an increase of IFN-gamma and TNF production preceding clinical symptoms by a maximum of 2 weeks. In benign cases, the increase disappeared rapidly, even before the appearance of symptoms, whereas we found sequelae whenever the increase persisted during weeks. In chronic progressive patients, we frequently found intervening increases. It may be that IFN-gamma and TNF trigger off exacerbations at a very early stage and that these cytokines may also play a role in maintaining disease in chronic progressive and invalidating forms.
The role and properties of the iron-sulfur cluster in Escherichia coli dihydroxy-acid dehydratase (1993)

Dihydroxy-acid dehydratase has been purified from Escherichia coli and characterized as a homodimer with a subunit molecular weight of 66,000. The combination of UV visible absorption, EPR, magnetic circular dichroism, and resonance Raman spectroscopies indicates that the native enzyme contains a [4Fe-4S]2+,+ cluster, in contrast to spinach dihydroxy-acid dehydratase which contains a [2Fe-2S]2+,+ cluster (Flint, D. H., and Emptage, M. H. (1988) J. Biol. Chem. 263, 3558-3564). In frozen solution, the reduced [4Fe-4S]+ cluster has a S = 3/2 ground state with minor contributions from forms with S = 1/2 and possibly S = 5/2 ground states. Resonance Raman studies of the [4Fe-4S]2+ cluster in E. coli dihydroxy-acid dehydratase indicate non-cysteinyl coordination of a specific iron, which suggests that it is likely to be directly involved in catalysis as is the case with aconitase (Emptage, M. H., Kent, T. A., Kennedy, M. C., Beinert, H., and Münck, E. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 4674-4678). Dihydroxy-acid dehydratase from E. coli is inactivated by O2 in vitro and in vivo as a result of oxidative degradation of the [4Fe-4S]cluster. Compared to aconitase, the oxidized cluster of E. coli dihydroxy-acid dehydratase appears to be less stable as either a cubic or linear [3Fe-4S] cluster or a [2Fe-2S] cluster. Oxidative degradation appears to lead to a complete breakdown of the Fe-S cluster, and the resulting protein cannot be reactivated with Fe2+ and thiol reducing agents.
The Effects of an Antacid or Cimetidine on the Serum Concentrations of Azithromycin (1991)

The effects of an antacid and of cimetidine on the serum concentrations of azithromycin were examined in volunteers. Ten subjects were given 500 mg azithromycin alone and immediately after being given 30 mL Maalox (Rorer, Fort Washington, PA) in a crossover design. There were no statistically significant differences in Tmax or AUC0-48 after administration of azithromycin alone or with antacid, but mean values of Cmax were reduced by 24% (P = .015). Thus, although Cmax was decreased, the extent of absorption of azithromycin was not affected by coadministration with an antacid. Two groups of six volunteers were given 500 mg azithromycin on day 1. On day 8, one group was given 800 mg cimetidine 2 hours before a dose of azithromycin; the remaining group received placebo before azithromycin. There were no differences in the pharmacokinetic parameters produced by administration with cimetidine or placebo, relative to those on day 1. Thus, cimetidine administered 2 hours before a dose of azithromycin had no apparent effect on the serum concentrations of azithromycin.
Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis (2001)

Neonatal necrotizing enterocolitis (NEC) is a major cause of morbidity in preterm infants. We hypothesize that the intestinal injury in this disease is a consequence of synergy among three of the major risk factors for NEC: prematurity, enteral feeding, and bacterial colonization. Together these factors result in an exaggerated inflammatory response, leading to ischemic bowel necrosis. Human milk may decrease the incidence of NEC by decreasing pathogenic bacterial colonization, promoting growth of nonpathogenic flora, promoting maturation of the intestinal barrier, and ameliorating the proinflammatory response.
Charge Transfer from Adsorbed Proteins (2004)

We have used transistor devices with carbon nanotubes as the conducting channel to explore the interaction between the nanotube surface and streptavidin, both in dry and in buffer environments. We find charge transfer between the protein and the nanotubes in both cases. Comparison with simpler molecules allows the estimation of the transferred charge. We argue that this effect can be understood as being due to the interaction between the −NH2 groups of the protein and the aromatic surface.