gebhart/patrepeval huggingface dataset:
A randomised, placebo-controlled, double blind study of treatment of Huntington’s disease with unsaturated fatty acids (2002)

Huntington's Disease (HD) is a serious dominantly inherited neurodegenerative disorder for which there are no current treatments. Open label and animal studies have suggested that highly unsaturated fatty acids (HUFAs) may be beneficial. Seventeen patients with HD were entered into a randomised, placebo-controlled, double blind trial of HUFA therapy. Patients were assessed on the Rockland-Simpson Dyskinesia Rating Scale (RSDRS) and the Unified Huntington's Disease Rating Scale (UHDRS). On the RSDRS and the UHDRs motor scale patients on HUFA treatment improved while those on placebo deteriorated, with a significant difference between the two groups on the RSDRS. A similar trend was noted on the UHDRS functional performance scales. Little change was seen on the neuropsychology scales. There were no treatment-related adverse events. This is the first time that a significant improvement has been noted in a randomised trial in HD. The results are consistent with open label observations; a second placebo-controlled study in end-stage patients, and a study in a transgenic mouse model of HD.
TLR5 functions as an endocytic receptor to enhance flagellin‐specific adaptive immunity (2010)

Innate immune activation via TLR induces dendritic cell maturation and secretion of inflammatory mediators, generating favorable conditions for naïve T-cell activation. Here, we demonstrate a previously unknown function for TLR5, namely that it enhances MHC class-II presentation of flagellin epitopes to CD4(+) T cells and is required for induction of robust flagellin-specific adaptive immune responses. Flagellin-specific CD4(+) T cells expanded poorly in TLR5-deficient mice immunized with flagellin, a deficiency that persisted even when additional TLR agonists were provided. Flagellin-specific IgG responses were similarly depressed in the absence of TLR5. In marked contrast, TLR5-deficient mice developed robust flagellin-specific T-cell responses when immunized with processed flagellin peptide. Surprisingly, the adaptor molecule Myd88 was not required for robust CD4(+) T-cell responses to flagellin, indicating that TLR5 enhances flagellin-specific CD4(+) T-cell responses in the absence of conventional TLR signaling. A requirement for TLR5 in generating flagellin-specific CD4(+) T-cell activation was also observed when using an in vitro dendritic cell culture system. Together, these data uncover an Myd88-independent function for dendritic cell TLR5 in enhancing the presentation of peptides to flagellin-specific CD4(+) T cells.
Induced pluripotent stem cell–derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice (2010)

The ability to generate induced pluripotent stem (iPS) cells from a patient's somatic cells has provided a foundation for organ regeneration without the need for immune suppression. However, it has not been established that the differentiated progeny of iPS cells can effectively reverse failure of a vital organ. Here, we examined whether iPS cell-derived hepatocytes have both the functional and proliferative capabilities needed for liver regeneration in mice with fumarylacetoacetate hydrolase deficiency. To avoid biases resulting from random genomic integration, we used iPS cells generated without viruses. To exclude compensation by hepatocytes not derived from iPS cells, we generated chimeric mice in which all hepatocytes were iPS cell derived. In vivo analyses showed that iPS cells were intrinsically able to differentiate into fully mature hepatocytes that provided full liver function. The iPS cell-derived hepatocytes also replicated the unique proliferative capabilities of normal hepatocytes and were able to regenerate the liver after transplantation and two-thirds partial hepatectomy. Thus, our results establish the feasibility of using iPS cells generated in a clinically acceptable fashion for rapid and stable liver regeneration.
Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors (2004)

NR2E3, a photoreceptor-specific orphan nuclear receptor, is believed to play a pivotal role in the differentiation of photoreceptors. Mutations in the human NR2E3 gene and its mouse ortholog are associated with enhanced S-cones and retinal degeneration. In order to gain insights into the NR2E3 function, we performed temporal and spatial expression analysis, yeast two-hybrid screening, promoter activity assays and co-immunoprecipitation studies. The Nr2e3 expression was localized preferentially to the rod, and not to the cone, photoreceptor nuclei in rodent retina. The yeast two-hybrid screening of a retinal cDNA library, using NR2E3 as the bait, identified another orphan nuclear receptor NR1D1 (Rev-erbalpha). The interaction of NR2E3 with NR1D1 was confirmed by glutathione S-transferase pulldown and co-immunoprecipitation experiments. In transient transfection studies using HEK 293 cells, both NR2E3 and NR1D1 activated the promoters of rod phototransduction genes synergistically with neural retina leucine zipper (NRL) and cone-rod homeobox (CRX). All four proteins, NR2E3, NR1D1, NRL and CRX, could be co-immunoprecipitated from the bovine retinal nuclear extract, suggesting their existence in a multi-protein transcriptional regulatory complex in vivo. Our results demonstrate that NR2E3 is involved in regulating the expression of rod photoreceptor-specific genes and support its proposed role in transcriptional regulatory network(s) during rod differentiation.
Breath holding after breathing of oxygen (1959)

Following normal breathing of O 2 seven untrained subjects held their breath beginning with a maximal inspiration. Breath-holding times ranged from 3.1 to 8.5 minutes and ‘breaking-point’ alveolar CO2 tensions from 51 to 91 mm Hg. Under these conditions, the maximum breath-holding time in minutes ( x) can be related to the rise in alveolar CO 2 tension in mm Hg ( y), according to the equation x = 0.13 y + 1.4. After hyperventilation on O 2 , the breath-holding times were noticeably extended ranging from 6 to 14 minutes, but the breaking-point alveolar CO 2 tensions did not exceed those noted above. In all cases, the measured changes in lung volume can be explained by the uptake of oxygen alone since the amount of CO 2 is essentially unaltered during apnea. The decreases in lung volume observed are related to the total breath-holding time, about 13 minutes being required for a change in lung volume equal to the vital capacity. Three subjects were able to absorb their entire vital capacity volume during breath holding since no volume could be expired at the breaking point. Submitted on April 8, 1959
Group-oriented (t, n) threshold digital signature scheme and digital multisignature (1994)

The paper presents group-oriented (t,n) threshold digital signature schemes based on the difficulty of solving the discrete logarithm problem. By employing these schemes, any t out of n users in a group can represent this group to sign the group signature. The size of the group signature and the verification time of the group signature are equivalent to that of an individual digital signature. In other words, the (t, n) threshold signature scheme has the following five properties: (i) any group signature is mutually generated by at least t group members; (ii) the size of the group signature is equivalent to the size of an individual signature; (iii) the signature verification process is simplified because there is only one group public key required; (iv) the group signature can be verified by any outsider; and (v) the group holds the responsibility to the signed message. In addition to the above properties, two of the schemes proposed do not require the assistance of a mutually trusted party. Each member selects its own secret key and the group public key is determined by all group members. Each group member signs a message separately and sends the individual signature to a designated clerk. The clerk validates each individual signature and then combines all individual signatures into a group signature. The (n, n) threshold signature scheme can be easily extended to become a digital multisignature scheme.
Fine‐needle aspiration of leiomyosarcoma: A correlative cytohistopathological study of 96 tumors in 68 patients (2003)

To better define the cytological features of various leiomyosarcoma (LMS) variants, we reviewed the fine-needle aspiration material and the corresponding histologic sections of 96 tumors in 68 patients. Histological variants of LMS were as follows: 80 (83.3%) were of the classical/usual, seven (7.3%) were epithelioid, and nine (9.4%) were myxoid. Review of original cytology reports showed that 23 (24%) tumors were diagnosed as LMS and 69 (71.8%) as other types of malignancies. Two (2.1%) cases were reported as suspicious and two (2.1%) were unsatisfactory. The classical variants of LMS were characterized cytologically by various proportions of spindle-shaped, cohesive, small- or large-sized cells arranged in parallel alignment. Large spindle, round, binucleated, giant cells with intracytoplasmic granulations were frequently seen. Blunt-ended nuclei, intranuclear inclusions and mitotic figures were occasionally seen, as well as stromal fragments. The epithelioid tumors were composed of an admixture of small and large, spindle-shaped and round cells, also arranged in parallel alignment. Tumor cells with granular cytoplasm, blunt-ended nuclei, intranuclear inclusions, mitotic figures, fibrous or myxoid stroma were not observed. The myxoid tumors disclosed large amounts of background myxoid matrix containing large spindle-shaped and giant cells. Entities such as leiomyoma, malignant peripheral nerve sheath tumor, monophasic synovial sarcoma, and malignant fibrous histiocytoma should be considered in the differential diagnosis of LMS of the classical type. Epithelioid leiomyoma may share similar cytological features with epithelioid LMS. The cytological features of the myxoid variant of LMS can be easily confused with other types of benign and malignant mesenchymal tumors depicting degenerative myxoid changes and/or a myxoid matrix component.
Bcl-xL–inhibitory BH3 mimetics can induce a transient thrombocytopathy that undermines the hemostatic function of platelets (2011)

BH3 mimetics are a new class of proapo-ptotic anticancer agents that have shown considerable promise in preclinical animal models and early-stage human trials. These agents act by inhibiting the pro-survival function of one or more Bcl-2-related proteins. Agents that inhibit Bcl-x(L) induce rapid platelet death that leads to thrombocytopenia; however, their impact on the function of residual circulating platelets remains unclear. In this study, we demonstrate that the BH3 mimetics, ABT-737 or ABT-263, induce a time- and dose-dependent decrease in platelet adhesive function that correlates with ectodomain shedding of the major platelet adhesion receptors, glycoprotein Ibα and glycoprotein VI, and functional down-regulation of integrin α(IIb)β(3). Analysis of platelets from mice treated with higher doses of BH3 mimetics revealed the presence of a subpopulation of circulating platelets undergoing cell death that have impaired activation responses to soluble agonists. Functional analysis of platelets by intravital microscopy revealed a time-dependent defect in platelet aggregation at sites of vascular injury that correlated with an increase in tail bleeding time. Overall, these studies demonstrate that Bcl-x(L)-inhibitory BH3 mimetics not only induce thrombocytopenia but also a transient thrombocytopathy that can undermine the hemostatic function of platelets.
Long‐term efficacy and safety of a permeation‐enhanced testosterone transdermal system in hypogonadal men (1997)

The permeation-enhanced testosterone transdermal system produces physiological levels and circadian patterns of testosterone, and its metabolites, in hypogonadal men. Although transient erythema and itching is commonly reported, the TTD is generally well tolerated by most patients. This system offers a new treatment option for testosterone replacement therapy that results in physiological serum levels of sex hormones in hypogonadal men.
Immunologic potential of donor lymphocytes expressing a suicide gene for early immune reconstitution after hematopoietic T-cell–depleted stem cell transplantation (2003)

We have previously shown that the infusion of donor lymphocytes expressing the herpes simplex virus thymidine kinase (HSV-tk) gene is an efficient tool for controlling graft-versus-host disease (GVHD) while preserving the graft-versus-leukemia (GVL) effect. In addition to the GVL effect, the administration of donor HSV-tk(+) cells could have a clinical impact in promoting immune reconstitution after T-cell-depleted stem cell transplantation (SCT). To explore this hypothesis, we have investigated whether in vitro polyclonal activation, retroviral transduction, immunoselection, and expansion affect the immune competence of donor T cells. We have observed that, after appropriate in vitro manipulation, T cells specific for antigens relevant in the context of SCT are preserved in terms of frequency, expression of T-cell receptor, proliferation, cytokine secretion, and lytic activity. A reduction in the frequency of allospecific T-cell precursors is observed after prolonged T-cell culture, suggesting that cell manipulation protocols involving a short culture time and high transduction efficiency are needed. Finally, the long-term persistence of HSV-tk(+) cells was observed in a patient treated in the GVL clinical trial, and a reversion of the phenotype of HSV-tk(+) cells from CD45RO(+) to CD45RA(+) was documented more than 2 years after the infusion. Based on all this evidence, we propose a clinical study of preemptive infusions of donor HSV-tk(+) T cells after SCT from haploidentical donors to provide early immune reconstitution against infection and potential immune protection against disease recurrence.
Self‐Healing Supramolecular Gels Formed by Crown Ether Based Host–Guest Interactions (2012)

Automatische Reparatur: Ein Polymer mit Dibenzo[24]Krone-8-Einheiten (violett im Bild) als Seitenarmen wurde durch zwei Bisammoniumsalze (grün) unter Nutzung von Wirt-Gast-Wechselwirkungen zu supramolekularen Gelen verknüpft. Beide Gele sind Materialien, die auf externe Auslöser reagieren, hier auf Änderungen des pH-Wertes, und sind zudem selbstheilend, wie für das Auge sichtbar ist und mit Rheologie-Messungen gezeigt wurde.
A kinetic model for binding protein‐mediated arabinose transport (1992)

A kinetic model is presented based on the simplest plausible mechanism for bacterial binding protein-dependent transport. The transport phenotypes of the 18 variant arabinose-binding proteins analyzed by Kehres and Hogg (1992, Protein Sci. 1, 1652-1660) (wild type and 17 mutants) are interpreted to mean that in wild-type arabinose uptake the forward transport rate (k(for)) greatly exceeds the dissociation rate (kund) of a binding protein docked with the AraG:AraH membrane complex, and that k(for) dominance is preserved in all of the binding protein surface mutants. The assumptions and predictions of the model are consistent with existing data from other periplasmic transport systems.
A modified Watersheds Image Segmentation Algorithm for Blood Cell (2006)

In this paper, we present a new grayscale image segmentation algorithm, which combines edge- and region-based techniques through the morphological algorithm of watersheds. The method integrating top/bottom hat transformation with gray-level transformation and median filters is used as a preprocessing stage in order to reduce noise as well as augment the foreground. Then, an initial partitioning of the image into primitive regions is produced by applying the watershed transform. A region merging process based on the properties of watershed region is applied to control the oversegmentation. As additional contribution, we demonstrate a new method to establish the watershed regions based on the distance and elevation fall associated with pixels and minima and an approach to merge region to control oversegmentation according to the properties of initial watershed regions
Interactions of Plasminogen Activator Inhibitor-1 with Vitronectin Involve an Extensive Binding Surface and Induce Mutual Conformational Rearrangements (2009)

In order to explore early events during the association of plasminogen activator inhibitor-1 (PAI-1) with its cofactor vitronectin, we have applied a robust strategy that combines protein engineering, fluorescence spectroscopy, and rapid reaction kinetics. Fluorescence stopped-flow experiments designed to monitor the rapid association of PAI-1 with vitronectin indicate a fast, concentration-dependent, biphasic binding of PAI-1 to native vitronectin but only a monophasic association with the somatomedin B (SMB) domain, suggesting that multiple phases of the binding interaction occur only when full-length vitronectin is present. Nonetheless, in all cases, the initial fast interaction is followed by slower fluorescence changes attributed to a conformational change in PAI-1. Complementary experiments using an engineered, fluorescently silent PAI-1 with non-natural amino acids showed that concomitant structural changes occur as well in native vitronectin. Furthermore, we have measured the effect of vitronectin on the rate of insertion of the reactive center loop into beta-sheet A of PAI-1 during reaction with target proteases. With a variety of PAI-1 variants, we observe that both full-length vitronectin and the SMB domain have protease-specific effects on the rate of loop insertion but that the two exhibit clearly different effects. These results support a model for PAI-1 binding to vitronectin in which the interaction surface extends beyond the region of PAI-1 occupied by the SMB domain. In support of this model are recent results that define a PAI-1-binding site on vitronectin that lies outside the somatomedin B domain (Schar, C. R., Blouse, G. E., Minor, K. H., and Peterson, C. B. (2008) J. Biol. Chem. 283, 10297-10309) and the complementary site on PAI-1 (Schar, C. R., Jensen, J. K., Christensen, A., Blouse, G. E., Andreasen, P. A., and Peterson, C. B. (2008) J. Biol. Chem. 283, 28487-28496).
Las revistas científicas venezolanas: problemática actual y algunas posibles soluciones (2000)

Si consideramos que el proceso de investigacion comprende no solo la obtencion de resultados experimentales o teoricos, sino tambien la comunicacion de estos para ser sometidos al escrutinio social, y ser eventualmente aceptados, y que estas dos fases forman parte de un mismo proceso y por lo tanto son inseparables; entonces podemos ver claramente que el problema de la visibilidad de las publicaciones cientificas del Tercer Mundo o Mundo Subdesarrollado, es de capital importancia para el futuro de nuestros paises, no solo por la contribucion que pudiese hacerse a la ciencia de lo que ha sido llamado mainstream, sino a la importante contribucion que significaria para nuestros propios paises. 

La visibilidad de las publicaciones cientificas del tercer mundo en relacion con las publicaciones cientificas del mundo, es muy pobre. Los paises subdesarrollados tenemos el 24,1% de los cientificos mundiales y aportamos 5,3% del gasto mundial en investigacion.(1) Sin embargo el porcentaje de revistas del tercer mundo en el Science Citation Index (SCI) ha caido en 40% desde 1981 y la tendencia se mantiene.(2). Actualmente solo existen 28 revistas latinoamericanas o del area del caribe en este indice, 16 pertenecientes a las ciencias sociales y 12 en el campo de las ciencias naturales. La base de datos del SCI contiene 3300 revistas de un total de 70.000 en el campo de las ciencias naturales, lo cual da una idea del grado de selectividad de los criterios de inclusion
Activated and unactivated forms of human erythrocyte aldose reductase. (1985)

Aldose reductase (alditol:NADP+ 1-oxidoreductase, EC 1.1.1.21) has been partially purified from human erythrocytes by DEAE-cellulose (DE-52) column chromatography. This enzyme is activated severalfold upon incubation with 10 microM each glucose 6-phosphate, NADPH, and glucose. The activation of the enzyme was confirmed by following the oxidation of NADPH as well as the formation of sorbitol with glucose as substrate. The activated form of aldose reductase exhibited monophasic kinetics with both glyceraldehyde and glucose (Km of glucose = 0.68 mM and Km of glyceraldehyde = 0.096 mM), whereas the native (unactivated) enzyme exhibited biphasic kinetics (Km of glucose = 9.0 and 0.9 mM and Km of glyceraldehyde = 1.1 and 0.14 mM). The unactivated enzyme was strongly inhibited by aldose reductase inhibitors such as sorbinil, alrestatin, and quercetrin, and by phosphorylated intermediates such as ADP, glycerate 3-phosphate, glycerate 1,3-bisphosphate, and glycerate 2,3-trisphosphate. The activated form of the enzyme was less susceptible to inhibition by aldose reductase inhibitors and phosphorylated intermediates.
Cell Cycle-Regulated Expression of Mammalian CDC6 Is Dependent on E2F (1998)

The E2F transcription factors are essential regulators of cell growth in multicellular organisms, controlling the expression of a number of genes whose products are involved in DNA replication and cell proliferation. In Saccharomyces cerevisiae, the MBF and SBF transcription complexes have functions similar to those of E2F proteins in higher eukaryotes, by regulating the timed expression of genes implicated in cell cycle progression and DNA synthesis. The CDC6 gene is a target for MBF and SBF-regulated transcription. S. cerevisiae Cdc6p induces the formation of the prereplication complex and is essential for initiation of DNA replication. Interestingly, the Cdc6p homolog in Schizosaccharomyces pombe, Cdc18p, is regulated by DSC1, the S. pombe homolog of MBF. By cloning the promoter for the human homolog of Cdc6p and Cdc18p, we demonstrate here that the cell cycle-regulated transcription of this gene is dependent on E2F. In vivo footprinting data demonstrate that the identified E2F sites are occupied in resting cells and in exponentially growing cells, suggesting that E2F is responsible for downregulating the promoter in early phases of the cell cycle and the subsequent upregulation when cells enter S phase. Our data also demonstrate that the human CDC6 protein (hCDC6) is essential and limiting for DNA synthesis, since microinjection of an anti-CDC6 rabbit antiserum blocks DNA synthesis and CDC6 cooperates with cyclin E to induce entry into S phase in cotransfection experiments. Furthermore, E2F is sufficient to induce expression of the endogenous CDC6 gene even in the absence of de novo protein synthesis. In conclusion, our results provide a direct link between regulated progression through G1 controlled by the pRB pathway and the expression of proteins essential for the initiation of DNA replication.