gebhart/patrepeval huggingface dataset:
Histone deacetylase inhibitors in cancer treatment (2002)

Histone deacetylase (HDAC) inhibitors are emerging as an exciting new class of potential anticancer agents for the treatment of solid and hematological malignancies. In recent years, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in culture and in animal models. HDAC inhibition causes acetylated nuclear histones to accumulate in both tumor and normal tissues, providing a surrogate marker for the biological activity of HDAC inhibitors in vivo. The effects of HDAC inhibitors on gene expression are highly selective, leading to transcriptional activation of certain genes such as the cyclin-dependent kinase inhibitor p21WAF1/CIP1 but repression of others. HDAC inhibition not only results in acetylation of histones but also transcription factors such as p53, GATA-1 and estrogen receptor-alpha. The functional significance of acetylation of non-histone proteins and the precise mechanisms whereby HDAC inhibitors induce tumor cell growth arrest, differentiation and/or apoptosis are currently the focus of intensive research. Several HDAC inhibitors have shown impressive antitumor activity in vivo with remarkably little toxicity in preclinical studies and are currently in phase I clinical trial. The focus of this review is the development and clinical application of HDAC inhibitors for the treatment of cancer.
A Recombinant Hepatitis C Virus RNA-Dependent RNA Polymerase Capable of Copying the Full-Length Viral RNA (1999)

All of the previously reported recombinant RNA-dependent RNA polymerases (RdRp), the NS5B enzymes, of hepatitis C virus (HCV) could function only in a primer-dependent and template-nonspecific manner, which is different from the expected properties of the functional viral enzymes in the cells. We have now expressed a recombinant NS5B that is able to synthesize a full-length HCV genome in a template-dependent and primer-independent manner. The kinetics of RNA synthesis showed that this RdRp can initiate RNA synthesis de novo and yield a full-length RNA product of genomic size (9.5 kb), indicating that it did not use the copy-back RNA as a primer. This RdRp was also able to accept heterologous viral RNA templates, including poly(A)- and non-poly(A)-tailed RNA, in a primer-independent manner, but the products in these cases were heterogeneous. The RdRp used some homopolymeric RNA templates only in the presence of a primer. By using the 3'-end 98 nucleotides (nt) of HCV RNA, which is conserved in all genotypes of HCV, as a template, a distinct RNA product was generated. Truncation of 21 nt from the 5' end or 45 nt from the 3' end of the 98-nt RNA abolished almost completely its ability to serve as a template. Inclusion of the 3'-end variable sequence region and the U-rich tract upstream of the X region in the template significantly enhanced RNA synthesis. The 3' end of minus-strand RNA of HCV genome also served as a template, and it required a minimum of 239 nt from the 3' end. These data defined the cis-acting sequences for HCV RNA synthesis at the 3' end of HCV RNA in both the plus and minus senses. This is the first recombinant HCV RdRp capable of copying the full-length HCV RNA in the primer-independent manner expected of the functional HCV RNA polymerase.
Erythropoietin Induces Activation of Stat5 through Association with Specific Tyrosines on the Receptor That Are Not Required for a Mitogenic Response (1996)

The cytoplasmic domain of the erythropoietin receptor (EpoR) contains a membrane-distal region that is dispensable for mitogenesis but is required for the recruitment and tyrosine phosphorylation of a variety of signaling proteins. The membrane-proximal region of 96 amino acids is necessary and sufficient for mitogenesis as well as Jak2 activation, induction of c-fos, c-myc, cis, the T-cell receptor gamma locus (TCR-gamma), and c-pim-1. The studies presented here demonstrate that this region is also necessary and sufficient for the activation of Stat5A and Stat5B. The membrane-proximal domain contains a single tyrosine, Y-343, which when mutated eliminates the ability of the receptor to couple Epo binding to the activation of Stat5. Furthermore, peptide competitions demonstrate that this site, when phosphorylated, can disrupt Stat5 DNA binding activity, consistent with a role of Y-343 as a site of recruitment to the receptor. Cells expressing the truncated, Y343F mutant (a mutant with a Y-to-F alteration at position 343) proliferate in response to Epo in a manner comparable to that of the controls. However, in these cells, Epo stimulation does not induce the appearance of transcripts for cis, TCR-gamma, or c-fos, suggesting a role for Stat5 in their regulation.
Androgen and anti-androgen treatment modulates androgen receptor activity and DJ-1 stability (2006)

Stabilization of AR and its co-regulators in the absence of androgen may partially account for anti-androgen withdrawal syndrome and potentially contribute to the development of hormone refractory PCa.
ATF2 impairs glucocorticoid receptor–mediated transactivation in human CD8+ T cells (2007)

Chronic inflammatory diseases often have residual CD8(+) T-cell infiltration despite treatment with systemic corticosteroids, which suggests divergent steroid responses between CD4(+) and CD8(+) cells. To examine steroid sensitivity, dexamethasone (DEX)-induced histone H4 lysine 5 (K5) acetylation and glucocorticoid receptor alpha (GCR alpha) translocation were evaluated. DEX treatment for 6 hours significantly induced histone H4 K5 acetylation in normal CD4(+) cells (P = .001) but not in CD8(+) cells. DEX responses were functionally impaired in CD8(+) compared with CD4(+) cells when using mitogen-activated protein kinase phosphatase (1 hour; P = .02) and interleukin 10 mRNA (24 hours; P = .004) induction as a readout of steroid-induced transactivation. Normal DEX-induced GCR alpha nuclear translocation and no significant difference in GCR alpha and GCR beta mRNA expression were observed in both T-cell types. In addition, no significant difference in SRC-1, p300, or TIP60 expression was found. However, activating transcription factor-2 (ATF2) expression was significantly lower in CD8(+) compared with CD4(+) cells (P = .009). Importantly, inhibition of ATF2 expression by small interfering RNA in CD4(+) cells resulted in inhibition of DEX-induced transactivation in CD4(+) cells. The data indicate refractory steroid-induced transactivation but similar steroid-induced transrepression of CD8(+) cells compared with CD4(+) cells caused by decreased levels of the histone acetyltransferase ATF2.
CCCXVII.—The formation of 2-substituted benziminazoles (1928)

M. A. Phillips, J. Chem. Soc., 1928, 2393 DOI: 10.1039/JR9280002393
Binary Time Series (1980)

Abstract : This research dealt with higher order crossings, quantities which were defined and proved to be useful in discrimination in time series. In particular the Higher Order Crossings Theorem has been proved and a new goodness of fit and discrimination statistic has been suggested and applied in testing model adequacy in ARIMA processes, and in discrimination in EEG data. A connection with an application to particles arrangements in physics has been found and a quantity called an m'th order unit has been defined. This has been applied in finding the distribution of rare events in Binary Series.
Long Term Follow-Up of Transcatheter Embolization With Autologous Clot, Oxycel and Gelfoam in Domestic Swine (1977)

Transcatheter embolization of the distal gastrosplenic artery as well as the distal right renal artery or one of its bifurcational branches was performed in 9 domestic swine. The animals were embolized with fresh autologous clot, oxycel or gelfoam in groups of 3. The embolic material was opacified with tantalum in several animals. At 4 months, none of the initial occlusions was sustained and recanalization without residuals was found in the left gastroepipolic artery with only one minor exception. Organized thrombi as sole vascular residuals regardless of embolic substance were found in both the terminal splenic artery as well as in the right renal artery distribution in various degrees together with infarcts in both organs. No trace of either oxycel or gelfoam remained, nor tissue reaction against either material. All 3 agents are therefore regarded equivalent in their long term effects and are not suitable for permanent vascular occlusion.
Adenoviruses from Patients with AIDS: A Plethora of Serotypes and A Description of Five New Serotypes of Subgenus D (Types 43-47) (1988)

We analyzed 67 adenovirus isolates from 48 patients with AIDS. The isolates included 5 of subgenus A (all Ad31), 23 of subgenus B, 4 of subgenus C (all Ad5), and 35 of subgenus D. The subgenus A and C strains were from liver, lung, blood, urine, and stool and were unremarkable in their antigenic characteristics. The subgenus B strains were mostly from urine and were serotyped by neutralization (SN) and hemagglutination-inhibition (HAI) tests as Ad11 (12 isolates), Ad16 (1), Ad35 (3), and Ad21/H21 + 35 (1) plus new intermediate strains 34/H11 (3), 35/H11 (1), and 11 + 35/H11 (2). The subgenus D serotypes from 24 patients were mostly from stool specimens and consisted of 8 isolates of known serotypes, 16 of antigenically intermediate strains, and 11 of five new adenovirus types with distinct antigenic and restriction enzyme characteristics. The new serotypes were described as candidate types 43-47 in accordance with currently accepted taxonomic criteria. Ad45, 46, and 47 showed a major relation by HAI with Ad29, 24, and 20, respectively. Four intermediate types were related to the new serotypes. The plethora of serotypes from patients with AIDS suggests that no epidemiological significance can be attached to any one serotype.
Has repetitive transcranial magnetic stimulation (rTMS) treatment for depression improved? A systematic review and meta‐analysis comparing the recent vs. the earlier rTMS studies (2007)

Our findings suggest that recent rTMS clinical trials have shown larger antidepressant effects when compared with the earlier studies.
Intense longitudinal electric fields generated from transverse electromagnetic waves (2004)

We present a simple method for generating an intense longitudinal electric field from transverse electromagnetic waves (laser pulses) with radially symmetric polarization, to which a liquid crystal device converts linear polarization with energy efficiency of ∼99%. The laser-generated longitudinal electric field was observed in two dimensions and distinguished from the transverse component using the optical Kerr shutter method. The measured amplitude was 1.1 GV/m at the focus of a pulsed Nd:YAG laser beam of 0.25-MW peak-power.
Genomes of the Parapoxviruses Orf Virus and Bovine Papular Stomatitis Virus (2003)

Bovine papular stomatitis virus (BPSV) and orf virus (ORFV), members of the genus Parapoxvirus of the Poxviridae, are etiologic agents of worldwide diseases affecting cattle and small ruminants, respectively. Here we report the genomic sequences and comparative analysis of BPSV strain BV-AR02 and ORFV strains OV-SA00, isolated from a goat, and OV-IA82, isolated from a sheep. Parapoxvirus (PPV) BV-AR02, OV-SA00, and OV-IA82 genomes range in size from 134 to 139 kbp, with an average nucleotide composition of 64% G+C. BPSV and ORFV genomes contain 131 and 130 putative genes, respectively, and share colinearity over 127 genes, 88 of which are conserved in all characterized chordopoxviruses. BPSV and ORFV contain 15 and 16 open reading frames (ORFs), respectively, which lack similarity to other poxvirus or cellular proteins. All genes with putative roles in pathogenesis, including a vascular endothelial growth factor (VEGF)-like gene, are present in both viruses; however, BPSV contains two extra ankyrin repeat genes absent in ORFV. Interspecies sequence variability is observed in all functional classes of genes but is highest in putative virulence/host range genes, including genes unique to PPV. At the amino acid level, OV-SA00 is 94% identical to OV-IA82 and 71% identical to BV-AR02. Notably, ORFV 006/132, 103, 109, 110, and 116 genes (VEGF, homologues of vaccinia virus A26L, A33R, and A34R, and a novel PPV ORF) show an unusual degree of intraspecies variability. These genomic differences are consistent with the classification of BPSV and ORFV as two PPV species. Compared to other mammalian chordopoxviruses, PPV shares unique genomic features with molluscum contagiosum virus, including a G+C-rich nucleotide composition, three orthologous genes, and a paucity of nucleotide metabolism genes. Together, these data provide a comparative view of PPV genomics.
Long-term survival of Bordetella bronchiseptica in lakewater and in buffered saline without added nutrients (1993)

Bordetella bronchiseptica grew from small inocula, and retained viability for at least 24 weeks, in unsupplemented lakewater or phosphate-buffered saline. From washed inocula of around 103 colony-forming units/ml, there was growth at both 10°C and 37°C to give 106–107 colony-forming units/ml. At 10°C, these counts were maintained with little diminution up to week 24 when observations ceased. In the tests at 37°C, two of three strains tested showed similar retention of viability. These results suggest that B. bronchiseptica may exist as hitherto unsuspected reservoirs of infection in freshwater habitats.
Burned-out Testes Seminoma without Distant Metastasis (2014)

While complete regression of a primary testicular tumor with progressive growth of metastases is well recognized in cases of non-seminomatous germ cell tumors, this phenomenon is rarely reported with seminoma. We report a case of a spontaneously regressed testicular seminoma without accompanying metastatic lesions. A 33-year-old man had suffered from persistent scrotal induration and transient testicular pain of the left testicle for one month when he visited our hospital. He had undergone left orchiopexy for undescended testes in his early childhood. Serum levels of Alpha-fetoprotein, beta-human chorionic gonadotropin, and lactate dehydrogenase were all within normal limits. After 4 weeks of antibiotics treatment with cephalexin monohydrate, the left testicular mass remained unchanged. The patient was subjected to left radical orchiectomy. Histological examination revealed a fibrotic tumor with a small area of seminoma undergoing spontaneous regression. Postoperative imaging showed no concomitant metastatic lesions. Adjuvant radiation therapy was provided. The patient was free of disease at 2 years follow-up after surgery. We recommend that long term follow-up of patients with undescended testes, even if atrophic, is necessary for early detection of possible testicular tumors.
Improved h.264 intra coding based on bi-directional intra prediction, directional transform, and adaptive coefficient scanning (2008)

In this paper, a novel intra coding scheme is proposed. The proposed scheme improves H.264 intra coding from three aspects: 1) H.264 intra prediction is enhanced with additional bi-directional intra prediction modes; 2) H.264 integer transform is supplemented with directional transforms for some prediction modes; and 3) residual coefficient coding in CAVLC is improved. Compared to H.264, together the improvements can bring on average 7% and 10% coding gain for CABAC and for CAVLC, respectively, with average coding gain of 12% for HD sequences.
Detecting anomalous sensor events in smart home data for enhancing the living experience (2011)

The need to have a secure lifestyle at home is in demand more than ever. Today’s home is more than just four walls and a roof. Technology at home is on the rise and the place for smart home solutions is growing. One of the major concerns for smart home systems is the capability of adapting to the user. Personalizing the behavior of the home may provide improved comfort, control, and safety. One of the challenges of this goal is tackling anomalous events or actions. This work proposes using machine learning techniques to address this issue of detecting anomalous events or actions in smart environment datasets. The approaches are validated using real-world sensor data captured from a smart home testbed.
Antitumor Activity of BRAF Inhibitor and IFNα Combination in BRAF-Mutant Melanoma (2016)

The described results provide a strong rationale for the clinical trials implemented in BRAF(V600E) melanoma patients with BRAF-I and IFNα combination.
Proteins released from Mycobacterium tuberculosis during growth (1991)

Proteins secreted from Mycobacterium tuberculosis during growth are believed to be important for protective immunity against tuberculosis. We have investigated the growth of M. tuberculosis in an enriched liquid medium. The release of isocitrate dehydrogenase from the bacilli served as a marker of autolysis and was observed during the late logarithmic growth phase. The release of proteins during the culture period was investigated by enzyme-linked immunosorbent assay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Three major groups of proteins, which differed markedly with respect to profile of release and location in intact bacilli, were defined. A short-term filtrate devoid of autolytic products was defined and found to be composed of 33 major components. Five proteins were identified by monoclonal antibodies. Pronounced superoxide dismutase activity was detected in the filtrate. The enzyme was purified and identified as a dominating component of short-term filtrate.
Books with Voices : Paper Transcripts as a Tangible Interface to Oral Histories (2003)

Our contextual inquiry into the practices of oral historians unearthed a curious incongruity. While oral historians consider interview recordings a central historical artifact, these recordings sit unused after a written transcript is produced. We hypothesized that this is largely because books are more usable than recordings. Therefore, we created Books with Voices: bar-code augmented paper transcripts enabling fast, random access to digital video interviews on a PDA. We present quantitative results of an evaluation of this tangible interface with 13 participants. They found this lightweight, structured access to original recordings to offer substantial benefits with minimal overhead. Oral historians found a level of emotion in the video not available in the printed transcript. The video also helped readers clarify the text and observe nonverbal cues. Keywords tangible interface, interactive paper, video retrieval, reading, augmented reality, handheld, oral history
Complete Genome Sequence of Neisseria meningitidis Serogroup B Strain MC58 (2000)

The 2,272,351-base pair genome of Neisseria meningitidis strain MC58 (serogroup B), a causative agent of meningitis and septicemia, contains 2158 predicted coding regions, 1158 (53.7%) of which were assigned a biological role. Three major islands of horizontal DNA transfer were identified; two of these contain genes encoding proteins involved in pathogenicity, and the third island contains coding sequences only for hypothetical proteins. Insights into the commensal and virulence behavior of N. meningitidis can be gleaned from the genome, in which sequences for structural proteins of the pilus are clustered and several coding regions unique to serogroup B capsular polysaccharide synthesis can be identified. Finally, N. meningitidis contains more genes that undergo phase variation than any pathogen studied to date, a mechanism that controls their expression and contributes to the evasion of the host immune system.
Stimulation of CD40 on immunogenic human malignant melanomas augments their cytotoxic T lymphocyte-mediated lysis and induces apoptosis. (1999)

Here, we report the functional expression of CD40 on human malignant melanomas (MMs). Comparison of tumor specimen from MM precursor lesions, primary tumors, and metastases revealed that CD40 surface expression is down-regulated during tumor progression. CD40 expression was confirmed in 7 human MM cell lines established from immunogenic primary tumors or metastases, whereas 11 cell lines established from advanced stages were CD40 negative. CD40 expression could be enhanced in CD40-positive MM by stimulation with IFN-gamma and tumor necrosis factor-alpha but not by interleukin (IL)-1beta or CD40 triggering. CD40 ligation on MM by CD40L-transfected murine L-cells or by a soluble CD40L fusion protein up-regulated their expression of intercellular adhesion molecule-1 and MHC class I and class II molecules and their secretion of IL-6, IL-8, tumor necrosis factor-a, and granulocyte macrophage colony-stimulating factor and also induced a rapid activation of the transcription factor nuclear factor kappaB. Furthermore, CD40 ligation of a HLA-A2+, MelanA/MART1+ MM cell line enhanced its susceptibility to specific lysis by a HLA-A2-restricted, MelanA/MART-1-specific CTL clone. Finally, CD40 ligation induced growth inhibition and apoptosis in MM. These results indicate that CD40-CD40L interactions may play an important role in augmenting antitumor immunity and inducing apoptosis in some CD40-positive immunogenic human MMs.
Transcriptome changes in renal allograft protocol biopsies at 3 months precede the onset of interstitial fibrosis/tubular atrophy (IF/TA) at 6 months (2009)

Gene expression profiling of early protocol biopsies identified changes in the transcriptome of grafts, which may be important for the development of IF/TA. Such early detection of transcriptome changes can facilitate the identification of patients at risk shifting the intervention time point well before the histological diagnosis of irreversible IF/TA.
Transcriptional Regulation of the Human Acid α-Glucosidase Gene (2001)

Acid alpha-glucosidase, the product of a housekeeping gene, is a lysosomal enzyme that degrades glycogen. A deficiency of this enzyme is responsible for a recessively inherited myopathy and cardiomyopathy, glycogenesis type II. We have previously demonstrated that the human acid alpha-glucosidase gene expression is regulated by a silencer within intron 1, which is located in the 5'-untranslated region. In this study, we have used deletion analysis, electrophoretic mobility shift assay, and footprint analysis to further localize the silencer to a 25-base pair element. The repressive effect on the TK promoter was about 50% in both orientations in expression plasmid, and two transcriptional factors were identified with antibodies binding specifically to the element. Mutagenesis and functional analyses of the element demonstrated that the mammalian homologue 1 of Drosophila hairy and Enhancer of split (Hes-1) binding to an E box (CACGCG) and global transcription factor-YY1 binding to its core site function as a transcriptional repressor. Furthermore, the overexpression of Hes-1 significantly enhanced the repressive effect of the silencer element. The data should be helpful in understanding the expression and regulation of the human acid alpha-glucosidase gene as well as other lysosomal enzyme genes.