gebhart/patrepeval huggingface dataset:
Genome-wide analysis of survival in early stage non-small cell lung cancer (2008)

1694 INTRODUCTION: Lung cancer, of which 85% is non-small cell, is the leading cause of cancer-related death in the United States. Most of the genome-wide association studies were done with SNPs in germline DNA which did not take into account loss of heterozygosity and copy number variation in tumor DNA. No study has been published using genome-wide tumor SNP discovery analysis in cancer survival. Our goal in this study is to identify candidate SNPs that predict survival in NSCLC using genome-wide SNP data from resected tumors.  METHODS: A series of 100 early stage NSCLC patients were studied from cases diagnosed between 1992 and 2001 at the Massachusetts General Hospital (MGH), Boston, MA. Another series of 89 NSCLC patients diagnosed between 1988 and 1998 collected by National Institute of Occupational Health in Norway was used for validating the finding in MGH cohort. DNA was extracted from flash frozen lung tissues collected during surgery. SNPs were evaluated in genomic DNA extracted from micro-dissected tumor tissue with at least 70% tumor cellularity. Genome-wide genotyping was done using Affymetrix® 250K Nsp GeneChip®. Univariate Cox proportional hazard model in additive mode was used to screen significant SNPs with false discovery rate (FDR) adjustment for multiple testing. Hazard ratios (HR) were derived by multivariate Cox model adjusting for the demographic and clinical information, and copy number variation inferred by dCHIP.  RESULTS: Median survival time was 6.3 and 3.7 years, and there were 43 and 55 deaths in MGH and Norway cases, respectively. There were more male patients and squamous cell carcinoma but lower smoking pack-years in Norway cases than MGH cases. After excluding those with genotype call rate less than 95%, with variant homozygous plus heterozygous alleles less than 10% and with variant homozygous less than 3%, 74,666 SNPs were used for analysis in MGH discovery set. There were 19 SNPs significantly associated with patients’ survival with FDR
Structure–Property Relations of Methylamine Vapor Treated Hybrid Perovskite CH<sub>3</sub>NH<sub>3</sub>PbI<sub>3</sub> Films and Solar Cells (2017)

The power conversion efficiency of halide perovskite solar cells is heavily dependent on the perovskite layer being sufficiently smooth and pinhole-free. It has been shown that these features can be obtained even when starting out from rough and discontinuous perovskite film by briefly exposing the film to methylamine (MA) vapor. The exact underlying physical mechanisms of this phenomenon are, however, still unclear. By investigating smooth, MA treated films based on very rough and discontinuous reference films of methylammonium triiode (MAPbI<sub>3</sub>) and considering their morphology, crystalline features, local conductive properties, and charge carrier lifetime, we unraveled the relation between their characteristic physical qualities and their performance in corresponding solar cells. We discovered that the extensive improvement in photovoltaic performance upon MA treatment is a consequence of the induced morphological enhancement of the perovskite layer together with improved electron injection into TiO<sub>2</sub>, which in fact compensates for an otherwise compromised bulk electronic quality simultaneously caused by the MA treatment.
Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. (2003)

The purpose of the following study was to investigate the safety and efficacy of the novel multitargeted indolinone receptor tyrosine kinase (RTK) inhibitor, SU11654, using a canine model of spontaneous tumors. This p.o. bioavailable compound exhibits potent inhibitory activity against members of the split kinase family of RTKs, including vascular endothelial growth factor receptor, platelet-derived growth factor receptor, Kit, and Flt-3, resulting in both direct antitumor and antiangiogenic activity.This was a Phase I trial in which successive cohorts of dogs with spontaneous tumors that had failed standard treatment regimens received escalating doses of SU11654 as oral therapy. Pharmacokinetics, toxicity, and tumor response were assessed.Fifty-seven dogs with a variety of cancers were enrolled; of these, 10 experienced progressive disease within the first 3 weeks. Measurable objective responses were observed in 16 dogs (including 6 complete responses), primarily in mast cell tumors (n = 11), mixed mammary carcinomas (n = 2), soft tissue sarcomas (n = 2), and multiple myeloma (n = 1), for an overall response rate of 28% (16 of 57). Stable disease of sufficient duration to be considered clinically meaningful (>10 weeks) was seen in an additional 15 dogs, for a resultant overall biological activity of 54% (31 of 57).This study provides the first evidence that p.o. administered kinase inhibitors can exhibit activity against a variety of spontaneous malignancies. Given the similarities of canine and human cancers with regard to tumor biology and the presence of analogous RTK dysregulation, it is likely that such agents will demonstrate comparable antineoplastic activity in people.
Exercise-induced skeletal muscle damage and adaptation following repeated bouts of eccentric muscle contractions (1997)

Repeated bouts of eccentric muscle contractions were used to examine indirect indices of exercise-induced muscle damage and adaptation in human skeletal muscle. Twenty-four subjects (18 females, 6 males) aged 20.0 +/- 1.4 years (mean +/- S.D.) performed an initial bout of either 10 (n = 7), 30 (n = 9) or 50 (n = 8) maximum voluntary eccentric contractions of the knee extensors, followed by a second bout of 50 contractions 3 weeks later using the same leg. Muscle soreness was elevated after all bouts (P < 0.05, Wilcoxon test), although the initial bout reduced the soreness associated with the second bout. Force loss and a decline in the 20:100 Hz percutaneous electrical myostimulation force ratio were observed after all exercise bouts (P < 0.01). Serum creatine kinase activity was elevated following the initial bouts of 30 and 50 repetitions (P < 0.01), but there was no increase following 10 repetitions. No increase in serum creatine kinase activity was observed in any group following the second bout of contractions (P > 0.05). We conclude that skeletal muscle adaptation can be brought about by a single bout of relatively few eccentric muscle contractions. Increasing the number of eccentric muscle repetitions did not result in an increased prophylactic effect on skeletal muscle.
Development of Two Stable Oral Suspensions of Levodopa-Carbidopa for Children With Amblyopia (2000)

Levodopa-carbidopa in extemporaneous suspensions prepared in Ora Plus and Ora Sweet were stable for 28 days when stored at 25 degrees C and for 42 days at 4 degrees C. Our data suggest our liquid formulation may be used safely in children with amblyopia.
Low temperature growth of ultrananocrystalline diamond (2004)

Ultrananocrystalline diamond (UNCD) films were prepared by microwave plasma chemical vapor deposition using argon-rich Ar∕CH4 plasmas at substrate temperatures from ∼400 to 800°C. Different seeding processes were employed to enhance the initial nucleation density for UNCD growth to about 1011sites∕cm2. High-resolution transmission electron microscopy, near-edge x-ray absorption fine structure, visible and ultraviolet Raman spectroscopy, and scanning electron microscopy were used to study the bonding structure as a function of growth temperature. The results showed that the growth of UNCD films is much less dependent on substrate temperature than for hydrogen-based CH4∕H2 plasmas. UNCD with nearly the same nanoscale structure as those characteristic of high-temperature deposition can be grown at temperatures as low as 400°C with growth rates of about 0.2μm∕hr. The average grain size increased to about 8nm from 3 to 5nm that is characteristic of high-temperature growth, but the relative amounts of sp3 and sp2 bonding remained unchanged. These results suggest that the activation energy for UNCD growth is about 2–3Kcal∕mole compared with ∼28kcal∕mole for traditional growth chemistries, and that hydrogen plays an important role in the growth of UNCD films using hydrogen-poor plasmas.
Automatic Bifurcation Detection in Coronary IVUS Sequences (2012)

In this paper, we present a fully automatic method which identifies every bifurcation in an intravascular ultrasound (IVUS) sequence, the corresponding frames, the angular orientation with respect to the IVUS acquisition, and the extension. This goal is reached using a two-level classification scheme: first, a classifier is applied to a set of textural features extracted from each image of a sequence. A comparison among three state-of-the-art discriminative classifiers (AdaBoost, random forest, and support vector machine) is performed to identify the most suitable method for the branching detection task. Second, the results are improved by exploiting contextual information using a multiscale stacked sequential learning scheme. The results are then successively refined using a-priori information about branching dimensions and geometry. The proposed approach provides a robust tool for the quick review of pullback sequences, facilitating the evaluation of the lesion at bifurcation sites. The proposed method reaches an F-Measure score of 86.35%, while the F-Measure scores for inter- and intraobserver variability are 71.63% and 76.18%, respectively. The obtained results are positive. Especially, considering the branching detection task is very challenging, due to high variability in bifurcation dimensions and appearance.
Discovery of SHR1653, a Highly Potent and Selective OTR Antagonist with Improved Blood–Brain Barrier Penetration (2019)

The oxytocin receptor (OTR) plays a major role in the control of male sexual responses. Antagonists of the OTR have been reported to inhibit ejaculation in animal models and serve as a potential treatment for premature ejaculation (PE). Herein, we describe a novel scaffold featuring an aryl substituted 3-azabicyclo [3.1.0] hexane structure. The lead compound, SHR1653, was shown to be a highly potent OTR antagonist, which exhibited excellent selectivity over V<sub>1A</sub>R, V<sub>1B</sub>R, and V<sub>2</sub>R. This novel molecule was shown to have a favorable pharmacokinetic profile across species, as well as robust <i>in vivo</i> efficacy in a rat uterine contraction model. Interestingly, SHR1653 exhibited excellent blood-brain barrier penetration, which might be beneficial for the treatment of CNS-related PE.
Networks and groups within the genus Neisseria: analysis of argF, recA, rho, and 16S rRNA sequences from human Neisseria species (1999)

To understand the pattern of nucleotide sequence variation among bacteria that frequently exchange chromosomal genes, we analyzed sequences of the recA, argF, and rho genes, as well as part of the small-subunit (16S) rRNA gene, from about 50 isolates of human commensal Neisseria species and the pathogenic N. meningitidis and N. gonorrhoeae. Almost all isolates of these species could be assigned to five phylogenetic groups that are found for all genes examined and generally are supported by high bootstrap values. In contrast, the phylogenetic relationships among groups varied according to the gene analyzed with notable incongruences involving N. cinerea and N. lactamica. Further analysis using split decomposition showed that for each gene, including 16S rRNA, the patterns of sequence divergence within N. meningitidis and closely related species were inconsistent with a bifurcating treelike phylogeny and better represented by an interconnected network. These data indicate that the human commensal Neisseria species can be separated into discrete groups of related species but that the relationships both within and among these groups, including those reconstructed using 16S rRNA, have been distorted by interspecies recombination events.
Radiobiologically guided optimisation of the prescription dose and fractionation scheme in radiotherapy using BioSuite (2012)

Individualising the prescription dose and number of fractions with the help of BioSuite results in improved therapeutic ratios as evaluated by radiobiological models.
Solid-Phase Synthesis of Peptide Mimetics with (<i>E</i>)-Alkene Amide Bond Replacements Derived from Alkenylaziridines (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSolid-Phase Synthesis of Peptide Mimetics with (E)-Alkene Amide Bond Replacements Derived from AlkenylaziridinesPeter Wipf and Todd C. HenningerView Author Information Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260 Cite this: J. Org. Chem. 1997, 62, 6, 1586–1587Publication Date (Web):March 21, 1997Publication History Received22 January 1997Published online21 March 1997Published inissue 1 March 1997https://pubs.acs.org/doi/10.1021/jo9701039https://doi.org/10.1021/jo9701039rapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views637Altmetric-Citations81LEARN 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 SUBJECTS:Amides,Crystal cleavage,Organic polymers,Peptides and proteins,Reagents Get e-Alerts
Treatment of the Internal Mammary Lymph Nodes by Implantation of Radioisotopes into the Internal Mammary Artery (1958)

A technic for the treatment of the lymph nodes along the internal mammary vessels in breast cancer has been developed in which radioactive sources are inserted into the internal mammary vessels. Usually the internal mammary artery is chosen. At the conclusion of the radical mastectomy but before closure of the skin flaps, a small transverse incision is made in the first intercostal space on the side of the operation. The internal mammary vessels are exposed without entering the pleural cavity, and the internal mammary artery is ligated as close as possible to the first rib. With a knife, a small slit is made in the artery just below the ligature. A small nylon tube, whose leading end has previously been closed by heat, is introduced through the slit into the artery. The tube can usually be threaded down for approximately 15 to 25 cm., to a point below the level of the xiphoid process. A ligature is then tied around the artery directly below the slit to prevent back bleeding. The end of the nylon tube outside of the artery is brought out through the skin in the supraclavicular fossa by threading it through a large-bore hypodermic needle. The radical mastectomy is then completed in the routine manner. The whole implantation procedure can be carried out in five minutes. In a few instances, the technic has been modified by implanting both the internal mammary artery and the vein or both internal mammary arteries at the same time. Ligation of the internal mammary vessels is simple and carries no risk. After the patient has returned to her room, radioactive sources are introduced into the whole length of the inserted nylon tube. Ir192 sources have been used in most of our applications, but other radioisotopes such as Co60 or Ta182 are also suitable. These radioactive sources are left in place until the desired dose is reached, usually five to ten days. Doses up to 9,000 r, calculated at a point 0.5 cm. from the middle of the radioactive sources, have been delivered in patients, and up to 25,000 r in dogs, without untoward reactions. It is felt that in many patients cancerocidal doses can be delivered to the nodes along the internal mammary vessels, because in most cases which are suitable for a radical mastectomy, the internal mammary nodes are small and lie close to the vessels. The procedure has been used clinically since January 1957 in 19 patients, and no complications have developed.
Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21<sup>WAF1/CIP1</sup> and C/EBPβ expressions and suppressing NF‐κB activation (2002)

The incorporation of CCM into cytotoxic therapies may be a promising strategy for the treatment of AIPC.
Photopolymerization of styrene,p-chlorostyrene, methyl methacrylate, and butyl methacrylate with polymethylphenylsilane as photoinitiator (1996)

The rates of photochemical polymerization of styrene (St), p-chlorostyrene (Cl-St), methyl methacrylate (MMA), and butyl methacrylate (BMA) with polymethylphenylsilane (PMPS) as an initiator were measured. Polymethylphenylsilane is photodegrated to form silyl radicals that may initiate polymerization of vinyl monomers. Rate constants kp and kt have been determined for these systems. A good correlation (log P = α + βμ) of the resonance stabilization (P) of the chain radicals and the dipole moment (μ) of the monomers is observed for these polymerization systems. This equation may be used to estimate the resonance stabilization (P) of a monomer and the polymerization rate constant (kp). © 1996 John Wiley & Sons, Inc.
Supertasting and PROP Bitterness Depends on More Than the TAS2R38 Gene (2008)

Polymorphisms in the TAS2R38 gene provide insight to phenotypes long associated 6-n-propylthiouracil (PROP) and phenylthiocarbamide bitterness. We tested relationships between TAS2R38 genotype, taste phenotype, and fungiform papillae (FP) number in 139 females and 59 males (age range 21-60 years), primarily of European ancestry. DNA was analyzed for 3 polymorphic sites, identifying common (alanine-valine-isoleucine [AVI/AVI], heterozygotes, proline-alanine-valine [PAV/PAV]) and rare (proline-valine-isoleucine, alanine-alanine-valine, AAI) forms. Individuals with PROP threshold >0.15 mM were almost exclusively AVI/AVI; those with threshold <0.1 mM could have any genotype. PAV/PAVs were more difficult to identify with PROP taste measures, although perceived bitterness of moderate PROP concentrations (0.32, 1 mM) had better correspondence with genotype than did threshold. For AVI/AVIs, increases in bitterness from 1 to 3.2 mM PROP nearly paralleled those of TAS2R38 heterozygotes and PAV/PAVs. Some bitterness gains were related to FP number sampled from a standard area on the tongue tip, yet the PROP bitterness-FP relationship differed across genotype. Among homozygotes, FP was a significant determinant of PROP bitterness; heterozygotes showed a flat relationship. Those tasting concentrated PROP as more bitter also tasted concentrated sucrose, citric acid, sodium chloride, and quinine as more intense, even after statistically controlling for TAS2R38 genotype, FP, and intensity of tones (nonoral standard). To summarize, although PROP threshold generally exhibited single-gene complete dominance, PROP bitterness may involve additional bitter receptors as evidenced by misclassification of some nontaster homozygotes and the bitterness functions for concentrated PROP. Variability in receptor expression may explain attenuated bitterness-FP relationships. PROP bitterness does associate with heightened taste sensations (i.e., supertasting), but this is not due to TAS2R38 polymorphisms.
Engineered Histidine-Enriched Facial Lipopeptides for Enhanced Intracellular Delivery of Functional siRNA to Triple Negative Breast Cancer Cells (2019)

Cytosolic delivery of functional siRNA remains the major challenge to develop siRNA-based therapeutics. Designing clinically safe and effective siRNA transporter to deliver functional siRNA across the plasma and endosomal membrane remains a key hurdle. With the aim of improving endosomal release, we have designed cyclic and linear peptide-based transporters having an Arg-<sup>D</sup>His-Arg template. Computational studies show that the Arg-<sup>D</sup>His-Arg template is also stabilized by the Arg-His side-chain hydrogen bonding interaction at physiological pH, which dissociates at lower pH. The overall atomistic interactions were examined by molecular dynamics simulations, which indicate that the extent of peptide_siRNA assembly formation depends greatly on physicochemical properties of the peptides. Our designed peptides having the Arg-<sup>D</sup>His-Arg template and two lipidic moieties facilitate high yield of intracellular delivery of siRNA. Additionally, unsaturated lipid, linoleic acid moieties were introduced to promote fusogenicity and facilitate endosomal release and cytosolic delivery. Interestingly, such protease-resistant peptides provide serum stability to siRNA and exhibit high efficacy of erk1 and erk2 gene silencing in the triple negative breast cancer (TNBC) cell line. The peptide having two linoleyl moieties demonstrated comparable efficacy with commercial transfection reagent HiPerFect, as evidenced by the erk1 and erk2 gene knockdown experiment. Additionally, our study shows that ERK1/2 silencing siRNA and doxorubicin-loaded gramicidin-mediated combination therapy is more effective than siRNA-mediated gene silencing-based monotherapy for TNBC treatment.
Creating flexible data quality validationprocesses using Business Rules (2009)

Over the past few years, the quality of data has become increasingly important to organisations. This is caused by the fact that these organisations rely more and more on the
data they collect to make decisions and to react to an ever faster changing environment. Changes in this environment mean changes in the internal processes of an organisation,
which in turn puts more emphasis on the need for high quality data. Organisations such as those in the Dutch Health Care system have learned that using high quality data is of major importance. Yet the change in demands on this data is not being met by flexibility of the processes within these organisations. Topicus is currently developing an application to automate the handling of electronic
claim messages. The demand on the quality of these claims changes often, and must be met by a flexible validation process. However, this is currently not the case: the
validation methods that are available have been implemented hard-code, which makes the process very inflexible to changes. This problem was the justification for this thesis:
the application of the Business Rules approach to a data validation process to increase its flexibility and thereby its ability to react to changing demands from the environment. The concept of data quality is explored in detail to ensure a good understanding of what causes data quality to be poor and with which methods and tools the quality of data can be assessed and influenced. The Business Rules approach is also extensively explored to be able to effectively apply this approach to the data validation process. The result is a combined approach to the validation of the quality of data using checks stated
in Business Rules and evaluated using a Business Rule Engine from ILOG. The results of the prototype are positive: the rule engine performed well and even
uncovered some quality defects that were not expected initially. Subsequently, this thesis concludes with the recommendation to start using Business Rules in future projects where a more flexible data quality validation process is needed. However, more research has to be conducted to fully grasp the change in performance and to assess what exactly theimpact of the use of Business Rules will be in Topicus’ applications.