gebhart/patrepeval huggingface dataset:
The Wilms' tumor suppressor gene WT1 is negatively autoregulated. (1994)

The Wilms' tumor suppressor gene WT1 encodes a zinc-finger DNA-binding protein that functions as a transcriptional repressor. WT1 is expressed in a dramatic spatial and temporal pattern during kidney development and is thought to be critical during mesenchymal-epithelial conversion. The WT1 protein bound multiple sites in the WT1 promoter and functioned as a powerful transcriptional repressor of its gene in vivo (> 50-fold). The WT1 protein carrying an NH2-terminal 17-amino acid insertion and a 3-amino acid insertion (KTS) between zinc fingers 3 and 4, arising from the most abundant of four alternatively spliced transcripts, was the most powerful repressor. Of importance, a subset of WT1-binding sites differs from the Egr-1 consensus sequence, which has been shown to bind one splice variant of the WT1 protein (WT1(-KTS)). We characterized two of these sites and show that they bind both -KTS and +KTS forms of the WT1 zinc-finger protein and can confer repression on a heterologous promoter construct. Our data demonstrate that WT1, in addition to its known effects on insulin-like growth factor II, platelet-derived growth factor A, and Pax-2 transcription, is a powerful repressor of its own gene. These observations emphasize its critical role as a transcriptional regulatory protein during normal kidney development.
TSGene 2.0: an updated literature-based knowledgebase for tumor suppressor genes (2015)

Tumor suppressor genes (TSGs) are a major type of gatekeeper genes in the cell growth. A knowledgebase with the systematic collection and curation of TSGs in multiple cancer types is critically important for further studying their biological functions as well as for developing therapeutic strategies. Since its development in 2012, the Tumor Suppressor Gene database (TSGene), has become a popular resource in the cancer research community. Here, we reported the TSGene version 2.0, which has substantial updates of contents (e.g. up-to-date literature and pan-cancer genomic data collection and curation), data types (noncoding RNAs and protein-coding genes) and content accessibility. Specifically, the current TSGene 2.0 contains 1217 human TSGs (1018 protein-coding and 199 non-coding genes) curated from over 9000 articles. Additionally, TSGene 2.0 provides thousands of expression and mutation patterns derived from pan-cancer data of The Cancer Genome Atlas. A new web interface is available at http://bioinfo.mc.vanderbilt.edu/TSGene/. Systematic analyses of 199 non-coding TSGs provide numerous cancer-specific non-coding mutational events for further screening and clinical use. Intriguingly, we identified 49 protein-coding TSGs that were consistently down-regulated in 11 cancer types. In summary, TSGene 2.0, which is the only available database for TSGs, provides the most updated TSGs and their features in pan-cancer.
Stage- and tissue-specific expression of the neu oncogene in rat development. (1987)

The neu oncogene (also referred to as c-erbB-2 and HER2) encodes a 185-kDa transmembrane glycoprotein with tyrosine kinase activity termed p185. The p185 glycoprotein is structurally related to the epidermal growth factor receptor. It is thought that p185 is the receptor for an as yet unidentified growth factor. In the present study, RNA blot analyses and immunohistochemical studies were performed on rat tissues obtained from a variety of prenatal and postnatal stages to examine the expression of the neu oncogene and its product, p185, during normal development. Expression of the neu gene was detected in mid-gestation embryos in a variety of tissues including nervous system, connective tissue, and secretory epithelium, but not in lymphoid tissue. In adult animals, secretory epithelial tissues and basal cells of the skin expressed neu. These studies demonstrate that the neu gene is expressed in a tissue- and developmental stage-specific manner. We suggest that the p185 molecule plays an important role in the growth and development of a variety of tissues, and, in particular, in epithelial tissue.
Enhancement of osteoblastic differentiation of mesenchymal stromal cells cultured by selective combination of bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2) (2007)

It is well known that bone marrow contains mesenchymal stromal cells (MSCs), which can show osteoblastic differentiation when cultured in osteogenic medium containing ascorbic acid, beta-glycerophosphate and dexamethasone. The differentiation results in the appearance of osteoblasts, together with the formation of bone matrix; thus, in vitro cultured bone (osteoblasts/bone matrix) could be fabricated by MSC culture. This type of cultured bone has already been used in clinical cases involving orthopaedic problems. To improve the therapeutic effect of the cultured bone, we investigated the culture conditions that contributed to extensive osteoblastic differentiation. Rat bone marrow was primarily cultured to expand the number of MSCs and further cultured in osteogenic medium for 12 days. The culture was also conducted in a medium supplemented with either bone morphogenetic protein-2 (BMP-2) or fibroblast growth factor (FGF-2), or with sequential combinations of both supplements. Among them, the sequential supplementation of FGF-2 followed by BMP-2 showed high alkaline phosphatase activity, sufficient bone-specific osteocalcein expression and abundant bone matrix formation of the MSC culture. These data implied that the number of responding cells or immature osteoblasts was increased by the supplementation of FGF-2 in the early phase of the culture and that these cells can show osteoblastic differentiation, of which capability was augmented by BMP-2 in the late phase. The sequential supplementation of these cytokines into MSC culture might be suitable for the fabrication of ideal cultured bone for use in bone tissue engineering.
Vaccine against group B Neisseria meningitidis: protection trial and mass vaccination results in Cuba. (1991)

The Cuban vaccine, first in the world with proven efficacy against group B-caused disease, is based on outer membrane proteins from B meningococci capable of inducing long-lasting and high-titered bactericidal antibodies in humans. This bactericidal activity has a wide spectrum against all pathogenic group B Neisseria meningitidis tested. A randomized, double-blind controlled trial of the vaccine efficacy was performed during 1987-1989 with 106,000 10-14 years old students from 197 boarding schools in seven provinces. The efficacy obtained was 83% (chi 2, p less than 0.002; Fischer exact, p less than 0.001). In a second field trial including 133,600 persons from 5 months to 24 years of age in Ciego de Avila province (30 cases/10(5) inhabitants, the highest incidence rate in Cuba) by comparing vaccinated and non-vaccinated population after 2.5 years of observation and careful follow-up, the efficacy and safety was confirmed. Because of these results and because of the very low reactogenicity of the vaccine, the Ministry of Public Health took the advice of the Scientific Council to vaccinate all children between 3 months and 6 years of age in the most affected provinces. No severe or long lasting reactions to the vaccine were observed after the millions of doses administered. The efficacy of vaccination varied in the provinces between 83% and 94%, among age groups ranging from 3 months and 20 years. After 3 years of massive application no severe reactions occurred and one of the most severe epidemics has been practically eradicated.
Implantable polycrystalline diamond neural probe for in vivo and in vitro physiological recording (2009)

A second generation (Gen-2) diamond neural probe equipped with both electrical and electrochemical recording abilities is reported for the first time. Fabrication problems related to the high temperature and power requirements associated with diamond growth and the integration of diamond into neural probe technology have been addressed. In this design, polycrystalline diamond (poly-C) is used as the material for the probe's shank and working electrode. Ag/AgCl and gold are used for reference and counter electrodes, respectively. The probe's efficacy for in vivo electrical recording and in vitro electrochemical detection of Norepinephrine ( ~10 muM) is demonstrated.
THE EFFECT OF HEMOGLOBIN ON RENAL FUNCTION IN THE HUMAN (1951)

12-15 gm. of hemoglobin administered over a period of 15 minutes.
Second gene for gonadotropin-releasing hormone in humans (1998)

Gonadotropin-releasing hormone (GnRH) is a decapeptide widely known for its role in regulating reproduction by serving as a signal from the hypothalamus to pituitary gonadotropes. In addition to hypothalamic GnRH (GnRH-I), a second GnRH form (pGln-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly; GnRH-II) with unknown function has been localized to the midbrain of many vertebrates. We show here that a gene encoding GnRH-II is expressed in humans and is located on chromosome 20p13, distinct from the GnRH-I gene that is on 8p21-p11.2. The GnRH-II genomic and mRNA structures parallel those of GnRH-I. However, in contrast to GnRH-I, GnRH-II is expressed at significantly higher levels outside the brain (up to 30x), particularly in the kidney, bone marrow, and prostate. The widespread expression of GnRH-II suggests it may have multiple functions. Molecular phylogenetic analysis shows that this second gene is likely the result of a duplication before the appearance of vertebrates, and predicts the existence of a third GnRH form in humans and other vertebrates.
Macrophages in gene therapy: cellular delivery vehicles and in vivo targets (2002)

The appearance and activation of macrophages are thought to be rapid events in the development of many pathological lesions, including malignant tumors, atherosclerotic plaques, and arthritic joints. This has prompted recent attempts to use macrophages as novel cellular vehicles for gene therapy, in which macrophages are genetically modified ex vivo and then reintroduced into the body with the hope that a proportion will then home to the diseased site. Here, we critically review the efficacy of various gene transfer methods (viral, bacterial, protozoan, and various chemical and physical methods) in transfecting macrophages in vitro, and the results obtained when transfected macrophages are used as gene delivery vehicles. Finally, we discuss the use of various viral and nonviral methods to transfer genes to macrophages in vivo. As will be seen, definitive evidence for the use of macrophages as gene transfer vehicles has yet to be provided and awaits detailed trafficking studies in vivo. Moreover, although methods for transfecting macrophages have improved considerably in efficiency in recent years, targeting of gene transfer specifically to macrophages in vivo remains a problem. However, possible solutions to this include placing transgenes under the control of macrophage-specific promoters to limit expression to macrophages or stably transfecting CD34(+) precursors of monocytes/macrophages and then differentiating these cells into monocytes/macrophages ex vivo. The latter approach could conceivably lead to the bone marrow precursor cells of patients with inherited genetic disorders being permanently fortified or even replaced with genetically modified cells.
Dialogue Act Modeling for Automatic Tagging and Recognition of Conversational Speech (2000)

We describe a statistical approach for modeling dialogue acts in conversational speech, i.e., speech-act-like units such as STATEMENT, Question, BACKCHANNEL, Agreement, Disagreement, and Apology. Our model detects and predicts dialogue acts based on lexical, collocational, and prosodic cues, as well as on the discourse coherence of the dialogue act sequence. The dialogue model is based on treating the discourse structure of a conversation as a hidden Markov model and the individual dialogue acts as observations emanating from the model states. Constraints on the likely sequence of dialogue acts are modeled via a dialogue act n-gram. The statistical dialogue grammar is combined with word n-grams, decision trees, and neural networks modeling the idiosyncratic lexical and prosodic manifestations of each dialogue act. We develop a probabilistic integration of speech recognition with dialogue modeling, to improve both speech recognition and dialogue act classification accuracy. Models are trained and evaluated using a large hand-labeled database of 1,155 conversations from the Switchboard corpus of spontaneous human-to-human telephone speech. We achieved good dialogue act labeling accuracy (65% based on errorful, automatically recognized words and prosody, and 71% based on word transcripts, compared to a chance baseline accuracy of 35% and human accuracy of 84%) and a small reduction in word recognition error.
In Vitro Activities of Quinupristin-Dalfopristin and the Streptogramin RPR 106972 against Mycoplasma pneumoniae (1998)

The in vitro activities of quinupristin-dalfopristin and streptogramin RPR 106972 were determined with 44 strains of Mycoplasma pneumoniae and compared to those of macrolides, minocycline, and quinolones. All isolates tested were highly susceptible to macrolides and to quinupristin-dalfopristin (MIC at which 90% of the isolates are inhibited [MIC90], 0.0625 microg/ml), followed by RPR 106972 (MIC90, 0.5 microg/ml), quinolones, and minocycline.
Downstream control of upstream open reading frames: Figure 1. (2006)

Department of Environmental and Biomolecular Systems, Oregon Health and Science University, Beaverton, Oregon 97006, USA; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon 97201, USA; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA; Department of Microbiology and Department of Medicine, University of Washington, Seattle, Washington 98115, USA
Modeling of transcellular Ca transport in rat duodenum points to coexistence of two mechanisms of apical entry (2001)

Employing realistic parameters, we have demonstrated that a relatively simple mathematical model can reproduce key features of steady-state Ca2+ transport with the assumption of two mechanisms of Ca2+ entry: a channel-like flux and a carrier-mediated transport. At low luminal [Ca2+] (1-5 mM), facilitated entry dominates and saturates with Km = 0.4 mM. At luminal [Ca2+] of tens of millimolar, apical permeability is dominated by the channel flux that in turn is regulated by cytosolic Ca2+. The model reproduces the linear relationship between maximum Ca2+ transport rate and intestinal calbindin D9K (CaBP) content. At luminal [Ca2+] > 50 mM, local sensitivity analysis shows transcellular transport to be most sensitive to variations in CaBP. At low luminal [Ca2+], transport becomes sensitive to apical entry regulation. The simulations have been run within the Virtual Cell modeling environment, yielding the time course of external Ca2+ and spatiotemporal distributions of both intracellular Ca2+ and CaBP. Coexistence of two apical entry mechanisms accords with the properties of the duodenal Ca2+ transport protein CaT1 and the epithelial Ca2+ channel ECaC.
Reconstructing Native Language Typology from Foreign Language Usage (2014)

Linguists and psychologists have long been studying cross-linguistic transfer, the influence of native language properties on linguistic performance in a foreign language. In this work we provide empirical evidence for this process in the form of a strong correlation between language similarities derived from structural features in English as Second Language (ESL) texts and equivalent similarities obtained from the typological features of the native languages. We leverage this finding to recover native language typological similarity structure directly from ESL text, and perform prediction of typological features in an unsupervised fashion with respect to the target languages. Our method achieves 72.2% accuracy on the typology prediction task, a result that is highly competitive with equivalent methods that rely on typological resources.
Peroxisome proliferator-activated receptor modulators as potential chemopreventive agents. (2002)

Peroxisome proliferator-activated receptors (PPARs), members of the superfamily of nuclear steroid hormone receptors, have traditionally been studied for their role in lipid, glucose, and energy homeostasis. Recent evidence suggests that pharmacological activation of PPARgamma and PPARalpha, and inhibition of PPARdelta, may prevent cancer. PPARgamma agonists induce differentiation, inhibit the growth of established tumor cells in vitro and in vivo, and have chemopreventive effects in animal models. PPARalpha has anti-inflammatory and differentiating activity and protects against the oxidative damage associated with aging. In contrast, PPARdelta expression may be a factor in colorectal carcinogenesis. PPARdelta is normally repressed by the adenomatous polyposis coli tumor suppressor gene, and impaired adenomatous polyposis coli is strongly associated with human colorectal cancer risk. This review presents a rationale for using PPAR modulators as cancer chemopreventive drugs.
Fundus changes in mesangiocapillary glomerulonephritis type II: clinical and fluorescein angiographic findings. (1989)

Previously we have demonstrated a deposit in Bruch's membrane in a single case of mesangiocapillary glomerulonephritis type II. We studied a group of patients with this disease and described extensive clinical and fluorescein angiographic abnormalities, which were in marked contrast to the findings in a group of patients with other forms of glomerulonephritis. This finding contributes to our understanding of the pathophysiology of the complex of the retinal pigment epithelium, Bruch's membrane, and choriocapillaris.
Recombinant retroviral systems for the analysis of drug resistant HIV (1993)

Two recombinant retroviral systems are described that can be used to analyze antiretroviral drug activity and HIV breakthrough (replication in the presence of the drug). The first system utilizes a recombinant HIV encoding beta-galactosidase as a reporter gene (HIV-LacZ). The defective HIV-LacZ virus is produced in COS cells after co-transfection of a plasmid encoding the HIV-LacZ genome with a plasmid encoding HIV proteins necessary for packaging and infectivity. Subsequent infection of CD4+ target cells, followed by assay for LacZ expression, permits the rapid identification of individual virus-infected cells. This system can be used to quantitate the inhibition of early events in the HIV replicative cycle and is suitable for the screening of compounds for anti-HIV activity. However, this system cannot be used to analyze HIV drug resistance because of the limited genetic heterogeneity of the virus that is produced in COS cells. To circumvent this problem, a second system has been developed in which heterogenous recombinant HIV is produced by rescue with replication-competent 'helper' HIV. This system required the production of CD4+ cell lines containing defective proviruses encoding either LacZ or guanosine phosphoribosyl transferase (gpt). The defective proviruses are rescued by infection of the cell lines with 'helper' HIV and used to infect target cells in the presence of antiretroviral agents. Subsequent reporter gene assay is used to identify virus-infected cells. This system has been used to detect rare HIV breakthrough infection of cells in the presence of the non-nucleoside reverse transcriptase inhibitor TIBO R82150. Similar analyses with other antiretroviral agents, alone and in combination, may help identify therapeutic strategies that minimize breakthrough replication of HIV.
Conformational changes in p53 analysed using new antibodies to the core DNA binding domain of the protein. (1995)

The p53 protein contains a protease resistant core section that binds to DNA in a sequence specific manner and whose crystal structure has been determined. This core is flanked at the N-terminus by the transcriptional transactivation domain and at the C-terminus by sequences involved in the oligomerisation of the protein. Extensive immunochemical analysis of p53 has shown that dominant antigenic sites lie within these N- and C-terminal domains while few antibodies to the central core have been identified. One of these, PAb240, has been extensively characterised as its epitope is cryptic in the native DNA binding core structure but is exposed by denaturation. This epitope is also exposed on many p53 proteins that contain point mutations in the core domain suggesting that these mutations may have a common affect on the structure of the core. To investigate this further we have generated several new antibodies to novel sites on p53 and mapped their epitopes using synthetic peptides. We find that antibodies to two other discrete sites in the core can also, like PAb240, recognize cryptic epitopes and distinguish mutant from wild-type conformations implying that the point mutations found in p53 in human tumours have widespread effects on the folding pattern of the DNA binding domain.
Screening for Prostatic Carcinoma with Prostate Specific Antigen (1992)

Prostate specific antigen (PSA), neutral serine protease secreted exclusively by prostatic epithelial cells, has a number of applications in the management of men with prostatic carcinoma. While it is widely recognized that elevated PSA correlates with the presence of carcinoma, little data exist regarding the use of PSA as the initial test in the early detection of prostatic cancer. We measured serum PSA levels in men older than 50 years and performed digital rectal examination and ultrasound guided prostate biopsy of those who had a PSA level of greater than 4.0 ng./ml. A total of 1,249 men entered the protocol, of whom 187 (15.0%) had PSA levels above 4.0 ng./ml. Digital rectal examination and ultrasound guided biopsy were performed at our facility in 105 patients (56.2%). A total of 32 carcinomas (30.5%) was detected, including 23 in men with PSA between 4.1 and 10.0 ng./ml. and 9 in men with a PSA of greater than 10.0 ng./ml. Of the 32 carcinomas 12 (37.5%) occurred in men with normal prostates or glands demonstrating only asymmetry on digital rectal examination, and 3 men had carcinoma despite normal digital rectal examination and no hypoechoic peripheral zone lesion detected on ultrasound. Of the 32 patients 30 had clinically localized carcinoma but 7 of the 16 undergoing radical prostatectomy had pathological upstaging. We conclude that PSA represents an important adjunct to digital rectal examination for the early detection of prostatic carcinoma. The efficacy of this or any other early detection test to decrease prostate cancer mortality necessitates the results of prospectively randomized clinical trials.
Engineering Microbial Fuels Cells: Recent Patents and New Directions (2008)

Fundamental research into how microbes generate electricity within microbial fuel cells (MFCs) has far outweighed the practical application and large scale development of microbial energy harvesting devices. MFCs are considered alternatives to standard commercial polymer electrolyte membrane (PEM) fuel cell technology because the fuel supply does not need to be purified, ambient operating temperatures are maintained with biologically compatible materials, and the biological catalyst is self-regenerating. The generation of electricity during wastewater treatment using MFCs may profoundly affect the approach to anaerobic treatment technologies used in wastewater treatment as a result of developing this energy harvesting technology. However, the materials and engineering designs for MFCs were identical to commercial fuel cells until 2003. Compared to commercial fuel cells, MFCs will remain underdeveloped as long as low power densities are generated from the best systems. The variety of designs for MFCs has expanded rapidly in the last five years in the literature, but the patent protection has lagged behind. This review will cover recent and important patents relating to MFC designs and progress.