gebhart/patrepeval huggingface dataset:
Length-dependent structure formation in Friedreich ataxia (GAA)n{middle dot}(TTC)n repeats at neutral pH (2004)

More than 15 human genetic diseases have been associated with the expansion of trinucleotide DNA repeats, which may involve the formation of non-duplex DNA structures. The slipped-strand nucleation of duplex DNA within GC-rich trinucleotide repeats may result in the changes of repeat length; however, such a mechanism seems less likely for the AT-rich (GAA)n*(TTC)n repeats. Using two-dimensional agarose gels, chemical probing and atomic force microscopy, we characterized the formation of non-B-DNA structures in the Friedreich ataxia-associated (GAA)n*(TTC)n repeats from the FRDA gene that were cloned with flanking genomic sequences into plasmids. For the normal genomic repeat length (n = 9) our data are consistent with the formation of a very stable protonated intramolecular triplex (H-DNA). Its stability at pH 7.4 is likely due to the high proportion of the T.A.T triads which form within the repeats as well as in the immediately adjacent AT-rich sequences with a homopurine. homopyrimidine bias. At the long normal repeat length (n = 23), a family of H-DNAs of slightly different sizes has been detected. At the premutation repeat length (n = 42) and higher negative supercoiling, the formation of a single H-DNA structure becomes less favorable and the data are consistent with the formation of a bi-triplex structure.
Optimal subchannel structuring and basis selection for discrete multicarrier modulation (1995)

We propose an intelligent subchannel structuring and orthogonal basis selection algorithm for the discrete multicarrier modulation. This algorithm examines the unevenness and power levels of the given channel spectrum. The orthogonal modulation basis is well tailored to the properties of the channel in the proposed scheme. It is shown that the proposed approach leads to a smaller number of unequal bandwidth discrete carriers than the current technology. This provides a reduced complexity in digital transceivers with a near optimum performance.
Regulation of Colony-Stimulating Factor 1 Receptor Signaling by the SH2 Domain-Containing Tyrosine Phosphatase SHPTP1 (1996)

SHPTP1 (PTP1C, HCP, SHP) is an SH2 domain-containing tyrosine phosphatase expressed predominantly in hematopoietic cells. A frameshift mutation in the SHPTP1 gene causes the motheaten (me/me) mouse. These mice are essentially SHPTP1 null and display multiple hematopoietic abnormalities, most prominently hyperproliferation and inappropriate activation of granulocytes and macrophages. The me/me phenotype suggests that SHPTP1 negatively regulates macrophage proliferative pathways. Using primary bone marrow-derived macrophages from me/me mice and normal littermates, we examined the role of SHPTP1 in regulating signaling by the major macrophage mitogen colony-stimulating factor 1 (CSF-1) (also known as macrophage colony-stimulating factor). Macrophages from me/me mice hyperproliferate in response to CSF-1. In the absence of SHPTP1, the CSF-1 receptor (CSF-1R) is hyperphosphorylated upon CSF-1 stimulation, suggesting that SHPTP1 dephosphorylates the CSF-1R. At least some CSF-1R-associated proteins also are hyperactivated. SHPTP1 is associated constitutively, via its SH2 domains, with an unidentified 130-kDa phosphotyrosyl protein (P130). P130 and SHPTP1 are further tyrosyl phosphorylated upon CSF-1 stimulation. Tyrosyl-phosphorylated SHPTP1 binds to Grb2 via the Grb2 SH2 domain. Moreover, in me/me macrophages, Grb2 is associated, via its SH3 domains, with several tyrosyl phosphoproteins. These proteins are hyperphosphorylated on tyrosyl residues in me/me macrophages, suggesting that Grb2 may recruit substrates for SHPTP1. Our results indicate that SHPTP1 is a critical negative regulator of CSF-1 signaling in vivo and suggest a potential new function for Grb2.
Dietary Influences on Alpha-Methylacyl-CoA Racemase (AMACR) Expression in the Prostate (2007)

Abstract : Alpha Methyl Acyl CoA Racemase (AMACR), a peroxisomal and mitochondrial enzyme, is up regulated in majority of prostate cancers (PCa). This enzyme is involved in the breakdown of phytanic & pristanic acids, which are derived primarily through the ingestion of dairy and red meat products. There are no studies done so far that have examined the relationship of this enzyme with red meat and dairy intake and therefore PCa risk. The current research focuses on examining the relationships between AMACR expression in the prostate and phytanic/pristanic acid levels in the blood and prostate. So far, ten patients with Pca have been recruited in the study. Research staff has been trained to obtain dietary information as well as process tissue and blood samples from participants. Protocols for processing biological samples have been established. Preliminary optimization of laboratory assays relevant to the study is being performed. The long term goal of this project is to better understand relationships between diet and AMACR expression and its implication in PCa risk. prostate cancer risk.
CMC‐544 (inotuzumab ozogamicin) shows less effect on multidrug resistant cells: analyses in cell lines and cells from patients with B‐cell chronic lymphocytic leukaemia and lymphoma (2009)

The effect of CMC-544, a calicheamicin-conjugated anti-CD22 monoclonal antibody, was analysed in relation to CD22 and P-glycoprotein (P-gp) in B-cell chronic lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma (NHL) in vitro. The cell lines used were CD22-positive parental Daudi and Raji, and their P-gp positive sublines, Daudi/MDR and Raji/MDR. Cells obtained from 19 patients with B-cell CLL or NHL were also used. The effect of CMC-544 was analysed by viable cell count, morphology, annexin-V staining, and cell cycle distribution. A dose-dependent, selective cytotoxic effect of CMC-544 was observed in cell lines that expressed CD22. CMC-544 was not effective on Daudi/MDR and Raji/MDR cells compared with their parental cells. The MDR modifiers, PSC833 and MS209, restored the cytotoxic effect of CMC-544 in P-gp-expressing sublines. In clinical samples, the cytotoxic effect of CMC-544 was inversely related to the amount of P-gp (P = 0.003), and to intracellular rhodamine-123 accumulation (P < 0.001). On the other hand, the effect positively correlated with the amount of CD22 (P = 0.010). The effect of CMC-544 depends on the levels of CD22 and P-gp. Our findings will help to predict the clinical effectiveness of this drug on these B-cell malignancies, suggesting a beneficial effect with combined use of CMC-544 and MDR modifiers.
Brain and mind (2012)

Abstract Descartes's ontological dualism of mind and body made it difficult for him to describe the phenomenology of embodiment, the way we experience our own body. Contemporary theories of the mind–brain relation are predominantly physicalist, rather than dualist, in their ontology. But the duality of objective and subjective conceptions still presents a challenge for the sciences of the mind. Persons understood as such, partly from the first-person perspective—persons conceived as subjects and agents, with their experiences, thoughts, plans and actions—will not be visible in a purely objective, scientific story of the physical world.
Fityk : a general-purpose peak fitting program (2010)

Fityk is portable, open-source software for nonlinear curve fitting and data analysis. It specializes in fitting a sum of bell-shaped functions to experimental data. In particular, it enables Pawley refinement of powder diffraction data and size–strain analysis.
Functional Sites in the Laminin Alpha Chains (2005)

Laminins, heterotrimers composed of alpha, beta, and gamma chains, are multifunctional glycoproteins present in basement membranes. Laminins, the most important component of basement membranes during basement membrane assembly in early development, are involved in various biological activities such as cell adhesion, migration, growth, differentiation, tumor metastasis, and angiogenesis. Fully 15 laminin isoforms have been identified and are tissue- and/or developmental stage-specifically expressed. Integrins, dystroglycan, syndecans, and the other several cell surface molecules are cellular receptors for laminins. The globular domains located in the N- and C-terminus of the laminin alpha chains are critical for interactions with the cellular receptors. There are highly conserved functional sites and chain-specific functional sites among the laminin alpha chains. Additionally, laminins are processed by specific endogenous proteases and the processing regulates laminin functions. Binding of the functional sequences in laminins to the cellular receptors triggers intracellular signaling, followed by inducing various cell activities including cell spreading and migration. Laminins possess multifunctional sequences and are key molecules that determine cell fate.
Fertilization and Subsequent Development in Vitro of Pig Oocytes Inseminated in a Modified Tris-buffered Medium with Frozen-Thawed Ejaculated Spermatozoa1 (1997)

The present study examined the penetrability of pig oocytes by frozen-thawed ejaculated boar spermatozoa, prepared by the pellet method, coincubated in a modified Tris-buffered medium. Subsequent embryonic development of fertilized oocytes was also determined. Porcine oocyte-cumulus complexes were cultured in BSA-free North Carolina State University (NCSU) 23 medium containing porcine follicular fluid (10%), cysteine (0.1 mg/ml), and hormonal supplements (eCG and hCG: 10 IU/ml each) for 20-22 h. They were then cultured in the same medium but without hormonal supplements for an additional 20-22 h. After culture, cumulus cells were removed and oocytes were coincubated for 12 h with three different (1 x 10(5), 5 x 10(5) and 1 x 10(6)/ml) sperm concentrations (experiment 1). In experiment 2, oocytes were coincubated with sperm (5 x 10(5)/ml) for 3, 6, 9, and 12 h. In experiment 3, at 6 h after coincubation with sperm at 5 x 10(5)/ml concentration, oocytes were transferred into NCSU 23 + 0.4% BSA medium. At 48 and 144 h, cleavage and blastocyst formation rates, respectively, were evaluated. Insemination with 1 x 10(5)/ml resulted in a 40% sperm penetration rate of oocytes with 16% polyspermy. Mean number of sperm (MNS) per oocyte was 1.2 +/- 0.1. At 5 x 10(5) and 1 x 10(6)/ml, penetration rate (84-87%) and polyspermy (57-64%) increased (p < 0.001), with no difference between the two concentrations. However, MNS per oocyte increased (p < 0.05) with increasing sperm concentration. Penetration rate was 31% at 3 h and increased (p < 0.001) at 6-12 h (80-88%), with no difference between these time points. Polyspermy increased (p < 0.05) in a time-dependent manner up to 9 h, with no difference between 9 and 12 h. Compared to 3 h, MNS per oocyte increased (p < 0.05) at 9 and 12 h, with no mean difference at 6 h. At 48 after culture, the cleavage rate was 40%, and at 144 h, the blastocyst rate was 19%. This study describes the cryopreservation of ejaculated boar semen by the pellet method and the successful in vitro fertilization of pig oocytes by frozen-thawed spermatozoa with subsequent development to the blastocyst stage.
Downregulation of liver X receptor-α in mouse kidney and HK-2 proximal tubular cells by LPS and cytokines (2005)

The acute-phase response (APR) suppresses type II nuclear hormone receptors and alters the expression of their target genes involved in lipid metabolism in the liver and heart. Therefore, we examined the expression of liver X receptor/retinoid X receptor (LXR/RXR) and their target genes in kidney from mice treated with lipopolysaccharide (LPS) and in human proximal tubular HK-2 cells treated with interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). We found that LXRalpha and RXRalpha expression was suppressed by LPS in kidney and by IL-1beta or TNF-alpha in HK-2 cells. The decrease in LXRalpha/RXRalpha expression was associated with a decrease in the expression of several LXRalpha target genes [apolipoprotein E (apoE), ABCA1, ABCG1, and sterol-regulatory element binding protein-1c (SREBP-1c)] and a decrease in ligand-induced apoE expression. Moreover, IL-1beta and TNF-alpha significantly reduced liver X receptor response element (LXRE)-driven transcription as measured by LXRE-linked luciferase activity. However, overexpression of LXRalpha/RXRalpha only partially restored the cytokine-mediated reduction in LXRE-linked luciferase activity. Additionally, expression of the LXR coactivators peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha) and steroid receptor coactivator-2 (SRC-2) was decreased by IL-1beta or TNF-alpha. We conclude that the APR suppresses the expression of both nuclear receptors LXRalpha/RXRalpha and several LXRalpha coactivators in kidney, which could be a mechanism for coordinately regulating the expression of multiple LXR target genes that play important roles in lipid metabolism in kidney during the APR.
Stabilization of Si Photoanodes in Aqueous Electrolytes through Surface Alkylation (1998)

A two-step chlorination/alkylation method was used to introduce −CnH2n+1 (n = 1−6) functionality onto single-crystal, (111)-oriented, n-type Si surfaces. H-terminated Si photoanodes were unstable under illumination in contact with an aqueous 0.35 M K4Fe(CN)6−0.05 M K3Fe(CN)6 electrolyte. Such electrodes displayed low open-circuit voltages and exhibited a pronounced time-dependent deterioration in their current density vs potential characteristics due to anodic oxidation. In contrast, Si surfaces functionalized with −CH3 and −C2H5 groups displayed significant improvements in stability while displaying excellent electrochemical properties when used as photoelectrodes in the aqueous Fe(CN)63-/4- electrolyte.
Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection (2007)

Because proinflammatory cytokines are markedly elevated during H5N1 influenza virus infection, the "cytokine storm" is hypothesized to be the main cause of mortality. Here, we demonstrate that mice deficient in the hallmark inflammatory cytokines TNF-alpha, IL-6, or CC chemokine ligand 2 succumb to infection with A/Vietnam/1203/04 (H5N1) virus, as do wild-type mice treated with glucocorticoids for suppression of cytokines. Because cytokine inhibition does not protect against death, therapies that target the virus rather than cytokines may be preferable.
Two high-affinity interleukin 1 receptors represent separate gene products. (1989)

Interleukin 1 (IL-1) is a polypeptide hormone that mediates a broad range of biological activities and interacts with surface receptors on numerous cell types. Equilibrium binding studies have identified a class of IL-1 receptors on T cells, fibroblasts, and epithelial cells that have 2- to 5-fold higher affinity than the receptors on bone marrow cells, pre-B cells, and macrophage cell lines. Affinity cross-linking with human 125I-labeled IL-1 alpha (125I-IL-1 alpha) labels an approximately 100-kDa protein on T cells and fibroblasts and an approximately 80-kDa protein on pre-B cells and macrophage cell lines. Monoclonal and polyclonal antibodies specific for the IL-1 receptor on T cells and fibroblasts block human 125I-IL-1 alpha binding to T cells, fibroblasts, and epithelial cells but cannot block IL-1 binding to bone marrow cells, pre-B cells, and macrophages. These antibodies immunoprecipitate the IL-1 receptor-human 125I-IL-1 alpha complex from T cells and fibroblasts but not from pre-B cells and macrophage cell lines. An S1 nuclease protection assay demonstrated that T cells and fibroblasts contain identical IL-1 receptor mRNA but that pre-B cells and macrophages do not contain this receptor mRNA. Taken together, the data demonstrate that mouse T cells, fibroblasts, and epithelial cells express an identical IL-1 receptor, whereas the IL-1 receptor on pre-B cells, macrophages, and bone marrow cells represents a different gene product.
Optimized In Vivo Transfer of Small Interfering RNA Targeting Dermal Tissue Using In Vivo Surface Electroporation (2012)

Electroporation (EP) of mammalian tissue is a technique that has been used successfully in the clinic for the delivery of genetic-based vaccines in the form of DNA plasmids. There is great interest in platforms which efficiently deliver RNA molecules such as messenger RNA and small interfering RNA (siRNA) to mammalian tissue. However, the in vivo delivery of RNA enhanced by EP has not been extensively characterized. This paper details the optimization of electrical parameters for a novel low-voltage EP method to deliver oligonucleotides (both DNA and RNA) to dermal tissue in vivo. Initially, the electrical parameters were optimized for dermal delivery of plasmid DNA encoding green fluorescent protein (GFP) using this novel surface dermal EP device. While all investigated parameters resulted in visible transfection, voltage parameters in the 10 V range elicited the most robust signal. The parameters optimized for DNA, were then assessed for translation of successful electrotransfer of siRNA into dermal tissue. Robust tagged-siRNA transfection in skin was detected. We then assessed whether these parameters translated to successful transfer of siRNA resulting in gene knockdown in vivo. Using a reporter gene construct encoding GFP and tagged siRNA targeting the GFP message, we show simultaneous transfection of the siRNA to the skin via EP and the concomitant knockdown of the reporter gene signal. The siRNA delivery was accomplished with no evidence of injection site inflammation or local tissue damage. The minimally invasive low-voltage EP method is thus capable of efficiently delivering both DNA and RNA molecules to dermal tissue in a tolerable manner.
Activity of a novel nonpeptidyl growth hormone secretagogue, L-700,653, in swine (1995)

L-700,653 is a potent nonpeptidyl GH secretagogue consisting of a benzolactam structure: (4'-[[3(R)-[[3-[(2(S),3-dihydroxypropyl) amino]3-methyl-1-oxobutyl]amino]2,3,4,5-tetrahydro-2-oxo-1H-1-benzaze pin- 1-yl]methyl][1,1'-biphenyl]2-carboxamide hydrochloride). When administered sc by a Medi-Jector device at 0, 0.003, 0.01, 0.03, and 0.1 mg/kg BW to male castrated swine (approximately 50 kg BW), L-700,653 stimulated dose-related increases in peak plasma GH concentrations by 20% (P = NS), 150% (P = NS), 250% (P < 0.05), and 340% (P < 0.05), respectively, over the saline vehicle control value (11.3 +/- 6.5 ng/ml) and stimulated increases in GH areas under the curve (AUCs) by 10% (P = NS), 30% (P = NS), 90% (P < 0.05), and 100% (P < 0.01), respectively, over the saline vehicle control value (799 +/- 145 ng/min.ml). After sc administration of L-700, 653, there were no significant changes in plasma LH levels. Subcutaneous dose of 0.03 or 0.1 mg/kg increased plasma cortisol AUCs by 60% (P = NS) and 150% (P < 0.03) over the control value (2461 +/- 935 ng/min.ml) and increased cortisol peaks by 80% (P = NS) and 200% (P < 0.01), respectively, over the control value (38.3 +/- 12.3 ng/ml). Repeated sc administration of L-700,653 (0.03 or 0.1 mg/kg) at 0800, 1400, and 2000 h daily over 3 days consistently increased mean GH peak and GH AUC at each treatment period, with minimal and maximal increases of 40% and 190% in GH peak level at the 0.03 mg/kg dose and 100% and 400% increases in GH peak level at the 0.01 mg/kg dose, respectively. Continuous i.v. infusion of L-700,653, at either 0.01 or 0.1 mg/kg BW.h over a 180-min period, increased GH AUCs by 60% (P = NS) or 470% (P < 0.01) and GH peaks by 190% (P = NS) or 1520% (P < 0.01), respectively, over the control value (589 +/- 313 ng/min.ml; 7.0 +/- 11.1 ng/ml). After a 180- to 300-min saline infusion, an iv bolus dose of 0.1 mg/kg L-700,653 resulted in GH responses inversely proportional to the previous infusion dose, i.e. 0, 0.01, or 0.1 mg/kg.
Current status of sexing mammalian spermatozoa (2002)

Thousands of offspring have now been produced via artificial insemination with spermatozoa sexed by flow cytometry and cell sorting. We are unaware of any other practical approach to sexing spermatozoa that maintains fertility. Accuracy of sexing usually is 85-95% in most species, but somewhat lower with human spermatozoa. Spermatozoa are sexed in series, one at a time, at routine rates of about 3000 live spermatozoa of each sex per second for most species, and nearly twice that rate under optimal conditions for some species. Owing to various constraints and statistical considerations, there appears to be an upper theoretical limit to sexing spermatozoa of about 10,000 live spermatozoa of each sex per second with current methodology. About a quarter of the spermatozoa processed are sexed; the rest are discarded in the process or lost due to logistical constraints. Spermatozoa undergo some damage during sorting, although much less in terms of viability than with routine cryopreservation; fertility is lower with sexed than control spermatozoa. Offspring from sexed spermatozoa appear to have no more abnormalities than do controls, and both groups grow and thrive similarly. Despite high costs and complex procedures, sexing spermatozoa, usually followed by cryopreservation, is being used commercially for cattle and horse production in several countries, and is used to produce girls to avoid X-chromosome-linked genetic diseases.
Control of black Sigatoka disease: Challenges and prospects (2011)

Accepted 12 January, 2011 Plantains and bananas are staple food for about 70 million people throughout the humid and subhumid tropic of Africa. They provide an important source of revenue for small holders who cultivate them. Production, however, has always been threatened by a variety of constraints; the most overriding constraint being black Sigatoka disease caused by a wind-borne fungus, Mycosphaerella fijiensis Morelet. As much as 27% of the total cost of production is apportioned to curb the menace the disease. Hence in this write up, the various methods applied so far to control black sigatoka disease in plantains and bananas are reviewed with emphasis on their apparent challenges and prospects. Findings showed that the consumption of plantains and bananas has risen tremendously in recent years, and black Sigatoka disease can be controlled in various ways ‐ culturally, chemically, quarantine, and breeding for disease resistance. A proper management of organic matter using different crop residues as mulch builds up the soil fertility level, and substantially reduced the effect of the disease. The use of forecasting methods could be part of an integrated disease management strategy, as this would reduce the number of fungicide treatment, disease production cost, and partially eliminate pollution challenges. The production and cultivation of disease resistant cultivars in combination with good cultural practices is generally considered to be the most appropriate intervention strategies that would control black sigatoka disease of plantains and bananas.
Increased endothelin in experimental heart failure. (1990)

Recent studies demonstrate that endothelin, a potent endogenous vasoconstrictor peptide, circulates in plasma of normal animals and humans. However, the role of this peptide in pathophysiological states remains unclear. The present study was designed to test the hypothesis that circulating endothelin concentrations are increased in experimental congestive heart failure (CHF), a pathophysiological state characterized by activation of vasoconstrictor mechanisms. In anesthetized dogs with CHF produced by 8 days of rapid ventricular pacing (n = 28), circulating plasma endothelin was increased compared with values for normal controls (n = 28; 20.4 +/- 1.4 versus 9.7 +/- 0.9 pg/ml, respectively; p less than 0.0001). A plasma endothelin level of more than 14.0 was a sensitive and specific indicator of significant CHF. Moreover, within the group with experimental CHF, right atrial pressure and pulmonary capillary wedge pressure correlated independently with circulating endothelin levels. Based on recent studies demonstrating the physiological actions of twofold increases in circulating endothelin, as observed in the present study, a possible role for endothelin in the pathophysiology of CHF is advanced.