gebhart/patrepeval huggingface dataset:
High rate of morphological reversion in tumor cell line H-19 associated with permanent transcriptional suppression of the LTR, v-src, LTR provirus. (1994)

The highly malignant line of morphologically transformed H-19 hamster tumor cells that harbor a single LTR, v-src, LTR provirus segregates morphologically flat revertants at the rate of 1.4 to 2.4 x 10(-3)/cell/cycle. Revertants behave like almost nonmalignant cells; they keep the provirus within an unaltered junction DNA fragment. However, the provirus is methylated, permanently transcriptionally silent, and not rescuable. Using the polymerase chain reaction, we have synthesized the whole proviral structure from two revertants and established that the left-hand long terminal repeats assuring transcription remained structurally intact. Moreover, the cloned proviral DNAs from three revertants were shown to produce tumors in chickens. The unusually high reversion rate together with the finding of structural integrity of proviral transcriptional signals in revertants indicate strongly that the reversion has been mediated by cell-regulatory mechanisms.
Antilymphocyte globulin and adrenal steroids in the treatment of multiple sclerosis: short report based on seven cases. (1979)

A therapeutic trial of antilymphocyte globulin (ALG) combined with dexamethasone was carried out in 7 patients with chronic, relapsing multiple sclerosis. ALG was given intravenously in daily doses of 0.25-0.5 g on the weekdays over 1 to 2 months. Total doses of ALG ranged from 12.5 to 17.7 g. Follow-up made after 1 year showed that 2 had no deterioration and 2 became worse in "tolerant" group, and 2 showed no deterioration and 1 revealed fatal progression in "non-tolerant" group. The treatment proved to be toxic in 3 patients. This pilot study suggests that ALG enhances anti-inflammatory activity of adrenal steroids in some patients, but does not seem to change natural course of the disease.
BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma. (2003)

BRAF oncogenic mutations have been identified in significant numbers of melanocytic lesions. To correlate BRAF mutation and melanoma progression, we screened BRAF mutations in 65 melanocytic lesions, including nevi, radial growth phase (RGP), vertical growth phase (VGP) melanomas, and melanoma metastases, as well as 25 melanoma cell lines. PCR and direct sequencing were used to analyze DNA samples extracted from laser capture microdissected tissues. A similar high frequency (62-72%) of BRAF oncogenic mutations was identified in melanocytic nevi, VGP, metastatic melanomas, and melanoma cell lines [H. Davies et al., Nature (Lond.), 417: 949-954, 2002; P. M. Pollock et al., Nat. Genet., 33: 19-20, 2002; and M. S. Brose et al., Cancer Res., 62: 6997-7000, 2002]. In striking contrast, we found BRAF lesions in only 10% of the earliest stage or RGP melanomas. These findings imply that BRAF mutations cannot be involved in the initiation of the great majority of melanomas but instead reflect a progression event with important prognostic implications in the transition from the great majority of RGP melanomas to VGP and/or metastatic melanoma.
Multi-objective evolutionary biclustering of gene expression data (2006)

Biclustering or simultaneous clustering of both genes and conditions have generated considerable interest over the past few decades, particularly related to the analysis of high-dimensional gene expression data in information retrieval, knowledge discovery, and data mining. The objective is to find sub-matrices, i.e., maximal subgroups of genes and subgroups of conditions where the genes exhibit highly correlated activities over a range of conditions. Since these two objectives are mutually conflicting, they become suitable candidates for multi-objective modeling. In this study, a novel multi-objective evolutionary biclustering framework is introduced by incorporating local search strategies. A new quantitative measure to evaluate the goodness of the biclusters is developed. The experimental results on benchmark datasets demonstrate better performance as compared to existing algorithms available in literature.
UPDATING RELATIONAL DATABASES THROUGH XML VIEWS (2001)

This paper presents an overview of a process for updating relational databases through XML views. The process is based on a query language called R2X and on a concept of normalization for XML views. The R2X language constructs XML views from relational databases, while normalization removes the ambiguity in an XML view, thus solving the update problem. In order to normalize an XML view, we benefit from the relation between XML and non-first normal form relations (NF ).
Lower Respiratory Illnesses Promote FEV1 Decline in Current Smokers But Not Ex-Smokers with Mild Chronic Obstructive Pulmonary Disease (2001)

We analyzed Lung Health Study (LHS) data to assess the effect of self-reported lower respiratory illnesses resulting in physician visits (LRI) on lung function. Participants were 5,887 smokers aged 35-60 yr, FEV(1)/FVC < 0.70 and FEV(1) of 55-90% predicted. Two-thirds were randomized into an intensive smoking cessation program (SI); one-third were advised only to stop smoking (UC). For 5 yr participants had annual spirometry and questioning regarding LRI. SI had greater rates of smoking cessation than usual care (UC) with fewer LRI (p = 0.0008). Sustained quitters had fewer LRI than continuing smokers (p = 0.0003). In the year LRI occurred, FEV(1) did not change in sustained quitters, but decreased significantly in smokers (p = 0.0001) with some recovery the following year if no LRI occurred. Over 5 yr, LRI had a significant effect on rate of decline of FEV(1) only in smokers. In smokers averaging one LRI/yr over 5 yr there were additional declines in FEV(1) of 7 ml /yr (p = 0.001). Smokers with more than one LRI/yr had greater declines. Chronic bronchitis was associated with increased frequencies of LRI, but did not affect their influence on lung function. Smoking and LRI had an interactive effect on FEV(1) in people with mild COPD, and in smokers frequent LRI may influence the long-term course of the disease.
DNA methylation status of a distinctively different subset of genes is associated with each histologic Lauren classification subtype in early gastric carcinogenesis (2014)

DNA methylation change is known to play a crucial role in early gastric carcinogenesis. The present study aimed to identify and validate the correlation between differentially methylated regions (DMRs) and the subtypes of early gastric cancers (EGCs). Illumina Infinium methylation assay (IIMA; 450K BeadChip kit) was performed on fresh tumor and non‑tumor tissues of 12 EGCs to screen the methylation status of 450,000 CpG sites. To evaluate the significance of DNA methylation in each histologic subtype, pyrosequencing assay (PA) was performed on 38 EGCs (18 intestinal-, 12 mixed- and 8 diffuse-type) using 12 genes selected from the screening. Between tumors of the intestinal-type (n=6), and diffuse- (n=4) plus mixed-types (n=2), 169 regions showed significant differences (intensity>3,000, Δβ>0.2) in IIMA. Hierarchical clustering using the 169 DMRs revealed distinct separation between the two groups. In PA using 12 selected genes from the IIMA results, the aberrant methylation statuses of DVL2 (p=0.0186) and ETS1 (p=0.0222) were significantly related to diffuse- and mixed-types rather than the intestinal-type, while C19orf35 (p=0.019) and CNRIP1 (p=0.0473) were related to the diffuse‑type rather than intestinal‑type, and GAL3ST2 (p=0.0158) and ITGA3 (p=0.0273) were related to the mixed-type rather than the other two types. The methylation of other genes, CLIP4, XKR6, CCDC57, MAML3 and SDC2, was related with age, tumor location, or Helicobacter infection rather than the histologic subtype. Aberrant DNA methylation of certain genes may be independently involved in each histologic subtype of EGC. Furthermore, mixed-type EGCs may be a distinctive histologic subtype based on the different subset of DMRs compared to those of other subtypes.
Isolated Hexanuclear Hydroxo Lanthanide Secondary Building Units in a Rare-Earth Polymeric Framework Based on p-Sulfonatocalix[4]arene (2009)

RPF9 is a new family of catalytically active metal−organic frameworks (MOFs) prepared with rare-earth elements and p-sulfonatocalix[4]arene, hexanuclear hydroxo lanthanide clusters forming the secondary building units in an open-framework with two-dimensional channels. The synthesis, characterization, and evaluation of sorption properties and catalytic activity of this new rare-earth polymeric framework type are here described.
The Design, Synthesis, and Evaluation of Coumarin Ring Derivatives of the Novobiocin Scaffold that Exhibit Antiproliferative Activity (2008)

Novobiocin, a known DNA gyrase inhibitor, binds to a nucleotide-binding site located on the Hsp90 C-terminus and induces degradation of Hsp90-dependent client proteins at approximately 700 microM in breast cancer cells (SKBr3). Although many analogues of novobiocin have been synthesized, it was only recently demonstrated that monomeric species exhibit antiproliferative activity against various cancer cell lines. To further refine the essential elements of the coumarin core, a series of modified coumarin derivatives was synthesized and evaluated to elucidate structure-activity relationships for novobiocin as an anticancer agent. Results obtained from these studies have produced novobiocin analogues that manifest low micromolar activity against several cancer cell lines.
3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 2. Structural modification of 7-(substituted aryl)-3,5-dihydroxy-6-heptenoic acids and their lactone derivatives (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 2. Structural modification of 7-(substituted aryl)-3,5-dihydroxy-6-heptenoic acids and their lactone derivativesWilliam F. Hoffman, A. W. Alberts, E. J. Cragoe Jr., A. A. Deana, B. E. Evans, J. L. Gilfillan, N. P. Gould, J. W. Huff, F. C. Novello, and Cite this: J. Med. Chem. 1986, 29, 2, 159–169Publication Date (Print):February 1, 1986Publication History Published online1 May 2002Published inissue 1 February 1986https://pubs.acs.org/doi/10.1021/jm00152a001https://doi.org/10.1021/jm00152a001research-articleACS PublicationsRequest reuse permissionsArticle Views399Altmetric-Citations36LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Electrical stimulation of the prefrontal cortex increases dopamine release in the nucleus accumbens of the rat: modulation by metabotropic glutamate receptors (1995)

In vivo microdialysis was used to assess the effects of electrical stimulation of the prefrontal cortex (PFC) on dopamine (DA) release in the nucleus accumbens (NAC) of awake, unrestrained rats. The PFC was stimulated bilaterally for 20 min at parameters previously shown to support intracranial self-stimulation in this structure. Stimulation at 50 microA evoked a 38% increase in DA release while 100 microA produced a 69% increase. Thus, phasic activation of the PFC increases DA release in the NAC. Additional experiments were performed to establish whether glutamate receptors in the NAC mediated these effects. The noncompetitive NMDA antagonist dizocilpine maleate (MK-801) and the broad spectrum competitive antagonist kynurenic acid were each applied locally to the NAC via reverse dialysis alone or in combination with electrical stimulation of the PFC (100 microA). Both MK-801 (10 microM) and kynurenic acid (5 mM) increased DA release when administered alone. When a "subthreshold" concentration (i.e., the highest concentration employed that did not itself increase DA release) of either compound was administered together with PFC stimulation, neither kynurenic acid (1 mM) nor MK-801 (1 microM) attenuated the effect of stimulation on DA release, thereby indicating that this effect is not mediated by ionotropic glutamate receptors located within the NAC. To examine the possible role of metabotropic glutamate receptors in regulating DA release, the metabotropic glutamate agonist trans(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) was employed. When applied locally to the NAC, ACPD had a dose-dependent effect on DA release with a high concentration (1 mM) causing an increase and a lower concentration (100 microM) causing a small decrease.(ABSTRACT TRUNCATED AT 250 WORDS)
Preferential Susceptibility of Brain Tumors to the Antiangiogenic Effects of an αv Integrin Antagonist (2001)

The cyclic pentapeptide EMD 121974 may become a treatment option specific to brain tumors. Because of its antiangiogenic effect, its use may be especially indicated after tumors are removed surgically.
Volumetric and Multi-view CNNs for Object Classification on 3D Data (2016)

3D shape models are becoming widely available and easier to capture, making available 3D information crucial for progress in object classification. Current state-of-theart methods rely on CNNs to address this problem. Recently, we witness two types of CNNs being developed: CNNs based upon volumetric representations versus CNNs based upon multi-view representations. Empirical results from these two types of CNNs exhibit a large gap, indicating that existing volumetric CNN architectures and approaches are unable to fully exploit the power of 3D representations. In this paper, we aim to improve both volumetric CNNs and multi-view CNNs according to extensive analysis of existing approaches. To this end, we introduce two distinct network architectures of volumetric CNNs. In addition, we examine multi-view CNNs, where we introduce multiresolution filtering in 3D. Overall, we are able to outperform current state-of-the-art methods for both volumetric CNNs and multi-view CNNs. We provide extensive experiments designed to evaluate underlying design choices, thus providing a better understanding of the space of methods available for object classification on 3D data.
A phase 1b study of the anti-cancer stem cell agent demcizumab (DEM), pemetrexed (PEM) & carboplatin (CARBO) in patients (pts)with 1st line non-squamous NSCLC. (2016)

9023 Background: DEM is a humanized IgG2 anti-DLL4 antibody that inhibits tumor growth, decreases CSC frequency & produces an antiangiogenic effect in human tumor xenograft models by inhibiting the Notch ligand Delta like ligand 4 (DLL4). In addition, inhibition of DLL4 may produce an immunomodulatory effect by reducing the myeloid derived suppressor cells within the tumor. This was a phase 1b study of DEM, PEM & CARBO in pts with 1st line non-squamous NSCLC. Methods: Pts received DEM (2.5 or 5 mg/kg), PEM 500 mg/m2 & CARBO (AUC = 6) induction every 3 wks X 6 cycles followed by maintenance DEM (cohorts 1-4) or truncated DEM (5 or 7.5 mg/kg), PEM 500 mg/m2 & CARBO (AUC = 6) induction every 3 wks X 4 cycles followed by maintenance PEM (cohorts 5 & 6). The objectives were to determine the MTD, safety, efficacy, immunogenicity, pharmacokinetics & biomarkers. Results: Forty-six pts were enrolled; 6 received continuous 2.5 mg/kg, 17 received continuous 5 mg/kg, 6 received 7.5 mg/kg of truncated DEM & 17 received 5 mg/kg of truncated DEM. Related AEs in > 25% of pts were: fatigue (48%), nausea (46%), hypertension (44%) and vomiting (28%). Increased BNP values are an early indicator of the cardiac effects of DEM & mildly elevated values were used to start treatment with a cardioprotective ACE inhibitor or carvedilol. Two pts receiving continuous DEM dosing 5 mg/kg developed reversible related Grade 3 pulmonary hypertension & heart failure on days 167 & 183, respectively. As a result, DEM treatment was limited to 63 days in cohorts 5, 6 & 7. The overall response and disease control rates were 50% and 88%, respectively. The Kaplan Meier estimated median PFS and survival for the truncated demcizumab pts were 5.8 months & 11.6 months, respectively. Eight of 23 (35%) of the truncated demcizumab pts are alive between 12 & 34 months. Conclusions: The truncated DEM regimen was generally well tolerated with fatigue, nausea & hypertension being the most common drug related toxicities. Encouraging activity has been observed. The optimal DEM dose was determined to be a truncated course of 5 mg/kg once every 3 weeks. This regimen is being used in an ongoing randomized Phase 2 study. Final data will be presented. Clinical trial information: NCT01189968.
Role of atrial fibrillation threshold evaluation on guiding treatment. (2003)

Atrial fibrillation could be induced reproducibly by 50 Hz rapid stimulation which was given through systolic and early diastolic phase of atrial excitation. Duration of atrial fibrillation induced in this way was roughly dependent on the current amplitude of the stimulation. The minimum current that could induce long-lasting atrial fibrillation (30 sec in the clinical setting, 2 sec in the rabbit or rat model) was defined as atrial fibrillation threshold (AFT). AFT was larger in patients who had history of atrial fibrillation than those who did not. Anti-arrhythmic drugs raised AFT by various degrees both in experimental and clinical cases. Long-term efficacy of a drug could be predicted in a patient, measuring how much the drug increased AFT (cut-off point = 5 mA increase). AFT is a useful marker to evaluate atrial vulnerability and to guide pharmacological treatment of atrial fibrillation.
Biochemical and molecular mechanisms of drug resistance in parasites (2001)

Drug resistance is complicating the treatment of parasitic diseases. We review here the basic mechanisms of parasite resistance in malaria, sleeping sickness, leishmaniasis and common helminthiases. Parasites resort to multiple biochemical means to achieve resistance and we have begun to isolate and characterize the genes/proteins implicated in resistance. Understanding drug resistance is essential for the control of parasitic diseases.
A New Device for Nonoperative Repair of Internal Cardiac Pacemakers (1966)

EACH YEAR in the United States 25,000 to 30,000 cases of heart block associated with Stokes-Adams seizures and chronic congestive heart failure are recorded. The development of implantable cardiac stimulators for the treatment of this problem began over 15 years ago and the first successful clinical application was reported in 1960.<sup>1</sup>Several units are now commercially available and are being improved. However, a marked discrepancy still exists between industrial data on component durability and clinical experience. In a recent representative series, a total of 53 pacemakers and 22 reparative operations were required by 37 patients. Failures occurred from four months to 2½ years after implantation.<sup>2</sup>The need for improvement is evident and a technique for the nonoperative repair of internal cardiac pacemakers will therefore be presented. <h3>Instruments and Use</h3> Figure 1 illustrates the design of the reed switch used in the repair procedures. The nitrogen gas filled glass
Repression of Glucocorticoid Receptor Transactivation and DNA Binding of a Glucocorticoid Response Element within the Serum/Glucocorticoid-Inducible Protein Kinase (sgk) Gene Promoter by the p53 Tumor Suppressor Protein (1997)

sgk is a novel member of the serine/threonine protein kinase family that is transcriptionally regulated by serum and glucocorticoids in Rat2 fibroblasts and in mammary epithelial cells. 5'-Deletion analysis of the sgk promoter, using a series of sgk-CAT. (chloramphenicol acetyltransferase) chimeric reporter gene plasmids, defined a glucocorticoid-responsive region that contains a glucocorticoid response element (sgkGRE) between -1000 and -975 bp. The sgkGRE is specifically bound by glucocorticoid receptors and is sufficient to confer glucocorticoid responsiveness to a heterologous promoter in several cell lines. Strikingly, cotransfection of either the murine or human wild type p53, but not a mutant p53, repressed the dexamethasone-stimulated transactivation of reporter plasmids containing either the sgkGRE or a consensus GRE. Gel shift analysis revealed that in vitro synthesized p53 prevented binding of the glucocorticoid receptor both to the sgkGRE as well as to a consensus GRE. The p53-mediated repression of dexamethasone-induced sgkGRE activity required both the DNA binding and transactivation functions of the p53 protein. Activation of endogenous p53, by exposure to UV light, repressed the glucocorticoid receptor transactivation of a consensus GRE-CAT reporter plasmid in transfected cells. Conversely, activated glucocorticoid receptors suppressed the transactivation function of p53, while transrepression by p53 was largely unaffected. The presented data demonstrate that sgk is a primary glucocorticoid-responsive protein kinase gene that implicates a new pathway of cross-talk between steroid receptor signaling and cellular phosphorylation cascades. In addition, our study provides the first evidence of mutual interference of transactivation functions of p53 and the glucocorticoid receptor, possibly through their direct interaction.
Case-control study of the risk factors for age related macular degeneration (2008)

Objective To explore the possible risk factors of age related macular degeneration(AMD).Method A group comparing case-control study was carried out.The cases were eighty-five AMD.The controls were one hundred subjects without AMD.All the participants underwent stardard questionnaire survey and correlative eye examination.Uniform questionnaires were administered to obtain demographic information and exposure information of related factors.Statistical analysis of x2 test and multi-factors non-conditional Logistic regression were performed to screen the risk factors.Results:Statistical analysis of Logistic regression displayed that ultimate factors,such as smoking(X1),taking antioxidant(X2)and hypertension(X3)entered the model.The established regression equation was ln[P/(1-P)]=-0.485+0.778 X1-0.897 X,+0.694 X1.The multi-factors Logistic regression show that smoking(OR=2.177,95%CI=1.167～4.062)and hypertension(OR=2.001,95%CI=1.063～3.766)are risk factors for AMD,while taking antioxidant regularly(OR=0.408,95%CI=0.200～0.832)is a protective factor.The dose-response were observed between smoking and odds ratio of AMD by fiend test.Conclusions AMD is caused by many kinds of factors.Smoking and hypertension can increase the risk of AMD,while taking antioxidant regularly can reduce the risk of AMD.

Key words: 
Age related macular degeneration; Risk factors; Case-control study