gebhart/patrepeval huggingface dataset:
Correlation of serum CNTO 328-Anti IL-6 monoclonal antibody (MAb) concentrations and biomarker expression in renal cell carcinoma (RCC) patients (2004)

2560 Background: RCC is the most common malignant tumor of the kidney and is associated with high expression of interleukin-6 (IL-6). IL-6 modulates the transcription of several liver-specific genes including C-reactive protein (CRP) and serum amyloid protein (SAA), both of which are prognostic markers in RCC. The goal of the present study was to assess the serum concentrations of an intravenously administered chimeric anti-IL-6 MAb (CNTO 328) in RCC patients and evaluate if the anti -L-6 MAb could inhibit the serum expression of IL-6, CRP, and SAA in these patients. Methods: Anti IL-6 MAb (1, 3, & 6 mg/kg) was administered by i.v. infusion to metastatic RCC patients on days 1, 29, 43, and 57. Blood samples were collected at various time points following treatment. MAb and biomarker concentrations in these samples were analyzed using validated ELISA methods. Results: Preliminary results following a single intravenous infusion of the anti-IL-6 MAb indicated that all patients exhibited significant serum exposure to the antibody. The serum concentrations of the anti-IL-6 MAb were proportional to the dose of the antibody administered. The half-life of the antibody ranged from 14.69 –17.54 days. Serum CRP and SAA levels, which have a strong correlation and mechanistic association with IL-6 activity, were both significantly inhibited in these patients. The degree of inhibition of the serum biomarkers was dependent on the dose of anti IL-6 MAb administered, serum anti-IL-6 concentrations and the baseline levels of these biomarkers. Conclusions: Collectively, these results indicate that the anti-IL-6 MAb used in this study is showing early promising changes in potentially predictive biomarkers of RCC and may have therapeutic impact in this disease. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Centocor, Inc. Centocor Centocor
Sources of Law (1990)

In this chapter we shall be concerned with the way in which rules of law are created and altered.
Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations (2020)

Homodimeric class I cytokine receptors are assumed to exist as preformed dimers that are activated by ligand-induced conformational changes. We quantified the dimerization of three prototypic class I cytokine receptors in the plasma membrane of living cells by single-molecule fluorescence microscopy. Spatial and spatiotemporal correlation of individual receptor subunits showed ligand-induced dimerization and revealed that the associated Janus kinase 2 (JAK2) dimerizes through its pseudokinase domain. Oncogenic receptor and hyperactive JAK2 mutants promoted ligand-independent dimerization, highlighting the formation of receptor dimers as the switch responsible for signal activation. Atomistic modeling and molecular dynamics simulations based on a detailed energetic analysis of the interactions involved in dimerization yielded a mechanistic blueprint for homodimeric class I cytokine receptor activation and its dysregulation by individual mutations.
Retroviral integrase domains: DNA binding and the recognition of LTR sequences (1991)

Integration of retroviral DNA into the host chromosome requires a virus-encoded integrase (IN). IN recognizes, cuts and then joins specific viral DNA sequences (LTR ends) to essentially random sites in host DNA. We have used computer-assisted protein alignments and mutagenesis in an attempt to localize these functions within the avian retroviral IN protein. A comparison of the deduced amino acid sequences for 80 retroviral/retrotransposon IN proteins reveals strong conservation of an HHCC N-terminal 'Zn finger'-like domain, and a central D(35)E region which exhibits striking similarities with sequences deduced for bacterial IS elements. We demonstrate that the HHCC region is not required for DNA binding, but contributes to specific recognition of viral LTRs in the cutting and joining reactions. Deletions which extend into the D(35)E region destroy the ability of IN to bind DNA. Thus, we propose that the D(35)E region may specify a DNA-binding/cutting domain that is conserved throughout evolution in enzymes with similar functions.
Prevalence of the NKG2D Thr72Ala Polymorphism in Patients with Cervical Carcinoma (2012)

Our studies may suggest that the women with cervical cancer bearing the NKG2D 72Thr gene variant might be protected against progression to advanced stages of this cancer.
Thermal [2+2] Intramolecular Cycloadditions of Fuller‐1,6‐enynes (2006)

More fused rings for fullerenes: Fuller-1,6-enynes are a peculiar class of 1,6-enynes that involve a highly strained double-bond component as well as a curved molecular surface. They undergo an unprecedented thermal [2+2] cycloaddition to afford products with three neighboring fused rings on one six-membered ring of the C60 core as shown in the scheme.
Effects of scatter modeling on time-activity curves estimated directly from dynamic SPECT projections (2004)

Quantitative analysis of uptake and washout of cardiac single photon emission computed tomography (SPECT) radiopharmaceuticals has the potential to provide better contrast between healthy and diseased tissue, compared to conventional reconstruction of static images. Previously, we used B-splines to model time-activity curves (TACs) for segmented volumes of interest and developed fast least-squares algorithms to estimate spline TAC coefficients and their statistical uncertainties directly from dynamic SPECT projection data. This previous work incorporated physical effects of attenuation and depth-dependent collimator response. In the present work, we incorporate scatter and use a computer simulation to study how scatter modeling affects directly estimated TACs and subsequent estimates of compartmental model parameters. An idealized single-slice emission phantom was used to simulate a 15 min dynamic /sup 99m/Tc-teboroxime cardiac patient study in which 500,000 events containing scatter were detected from the slice. When scatter was modeled, unweighted least-squares estimates of TACs had root mean square (RMS) error that was less than 0.6% for normal left ventricular myocardium, blood pool, liver, and background tissue volumes and averaged 3% for two small myocardial defects. When scatter was not modeled, RMS error increased to average values of 16% for the four larger volumes and 35% for the small defects. Noise-to-signal ratios (NSRs) for TACs ranged between 1-18% for the larger volumes and averaged 110% for the small defects when scatter was modeled. When scatter was not modeled, NSR improved by average factors of 1.04 for the larger volumes and 1.25 for the small defects, as a result of the better-posed (though more biased) inverse problem. Weighted least-squares estimates of TACs had slightly better NSR and worse RMS error, compared to unweighted least-squares estimates. Compartmental model uptake and washout parameter estimates obtained from the TACs were less sensitive to whether or not scatter was modeled, compared to the TACs themselves.
Immobilization of poly(ethylene glycol) onto a poly(vinyl alcohol) hydrogel. 1. Synthesis and characterization (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTImmobilization of poly(ethylene glycol) onto a poly(vinyl alcohol) hydrogel. 1. Synthesis and characterizationGerard R. Llanos and Michael V. SeftonCite this: Macromolecules 1991, 24, 23, 6065–6072Publication Date (Print):November 1, 1991Publication History Published online1 May 2002Published inissue 1 November 1991https://pubs.acs.org/doi/10.1021/ma00023a003https://doi.org/10.1021/ma00023a003research-articleACS PublicationsRequest reuse permissionsArticle Views985Altmetric-Citations40LEARN 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-Alertsclose Get e-Alerts
The HIV wasting syndrome: a review. (1994)

The HIV wasting syndrome and other HIV-associated weight loss is a major problem in HIV-infected patients. The available data strongly suggest that wasting is associated with decreased survival. It may also further impair immune function. A variety of etiologies probably contribute to this wasting, including hypermetabolism, alterations in metabolism, lessened oral intake, malabsorption, cytokine effects, and endocrine dysfunction. The relative contributions of each of these etiologies to wasting probably varies considerably from patient to patient. Successful treatment calls for identification of possible etiologies of wasting in the individual patient with AIDS. Further treatment may include treating underlying conditions and controlling such symptoms as diarrhea, nausea, or fever. Nutritional support, including both parenteral and enteral nutrition, has shown some promise of efficacy, and a variety of drugs appears to be helpful. Future treatment to reverse wasting may include the use of several of these agents in combination. Currently, there is much that clinicians can do to evaluate and treat the HIV wasting syndrome, with significant potential benefits to their patients.
Treatment of carcinoid syndrome (2000)

Lanreotide and octreotide are equally efficacious in terms of symptom control and reduction in tumor cell markers for patients with carcinoid syndrome. Due to its simplified mode of administration, most patients prefer treatment with lanreotide.
Idelalisib: First-in-Class PI3K Delta Inhibitor for the Treatment of Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, and Follicular Lymphoma (2015)

Idelalisib [Zydelig (Gilead Sciences, Inc.), also known as CAL-101 and GS-1101] was approved in 2014 in the United States and European Union for the treatment of three indolent B-cell neoplasms: relapsed/refractory chronic lymphocytic leukemia (CLL, in combination with rituximab), relapsed follicular lymphoma, and relapsed small lymphocytic lymphoma (as monotherapy). Furthermore, it was approved in the European Union as first-line therapy for poor-prognosis CLL with 17p deletions or TP53 mutations and in patients unsuitable for chemoimmunotherapy. Idelalisib is an orally bioavailable ATP-competitive kinase inhibitor that targets the PI3K p110 isoform δ (PI3Kδ) with high potency and selectivity. PI3Kδ is hyperactivated in B-cell malignancies and plays a pivotal role in the B-cell receptor pathway, a key oncogenic driver in B-cell malignancies. The near exclusive expression of the PI3Kδ isoform in hematopoietic cells and the selectivity of idelalisib for the PI3Kδ isoform are essential for its efficacy and tolerability, even in elderly patients unfit for chemotherapy. Idelalisib is the first PI3K inhibitor approved by the regulatory agencies; this approval will change the treatment landscape of indolent B-cell malignancies.
SILVA: a comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB (2007)

Sequencing ribosomal RNA (rRNA) genes is currently the method of choice for phylogenetic reconstruction, nucleic acid based detection and quantification of microbial diversity. The ARB software suite with its corresponding rRNA datasets has been accepted by researchers worldwide as a standard tool for large scale rRNA analysis. However, the rapid increase of publicly available rRNA sequence data has recently hampered the maintenance of comprehensive and curated rRNA knowledge databases. A new system, SILVA (from Latin silva, forest), was implemented to provide a central comprehensive web resource for up to date, quality controlled databases of aligned rRNA sequences from the Bacteria, Archaea and Eukarya domains. All sequences are checked for anomalies, carry a rich set of sequence associated contextual information, have multiple taxonomic classifications, and the latest validly described nomenclature. Furthermore, two precompiled sequence datasets compatible with ARB are offered for download on the SILVA website: (i) the reference (Ref) datasets, comprising only high quality, nearly full length sequences suitable for in-depth phylogenetic analysis and probe design and (ii) the comprehensive Parc datasets with all publicly available rRNA sequences longer than 300 nucleotides suitable for biodiversity analyses. The latest publicly available database release 91 (August 2007) hosts 547 521 sequences split into 461 823 small subunit and 85 689 large subunit rRNAs.
Conditional Glycosylation in Eukaryotic Cells Using a Biocompatible Chemical Inducer of Dimerization (2008)

Chemical inducers of dimerization (CIDs) are cell-permeable small molecules capable of dimerizing two protein targets. The most widely used CID, the natural product rapamycin and its relatives, is immunosuppressive due to interactions with endogenous targets and thus has limited utility in vivo. Here we report a new biocompatible CID, Tmp-SLF, which dimerizes E. coli DHFR and FKBP and has no endogenous mammalian targets that would lead to unwanted in vivo side effects. We employed Tmp-SLF to modulate gene expression in a yeast three-hybrid assay. Finally, we engineered the Golgi-resident glycosyltransferase FucT7 for tunable control by Tmp-SLF in mammalian cells.
Drosophila MyD88 is an adapter in the Toll signaling pathway (2001)

Toll-like receptors comprise a family of cell surface receptors that play a crucial role in the innate immune recognition of both Drosophila and mammals. Previous studies have shown that Drosophila Toll-1 mediates the induction of antifungal peptides during fungal infection of adult flies. Through genetic studies, Tube, Pelle, Cactus, and Dif have been identified as downstream components of the Toll-1 signaling pathway. Here we report characterization of a Drosophila homologue of human MyD88, dMyD88. We show that dMyD88 is an adapter in the Toll signaling pathway that associates with both the Toll receptor and the downstream kinase Pelle. Expression of dMyD88 in S2 cells strongly induced activity of a Drosomycin reporter gene, whereas a dominant-negative version of dMyD88 potently inhibited Toll-mediated signaling. We also show that dMyD88 associates with the death domain-containing adapter Drosophila Fas-associated death domain-containing protein (dFADD), which in turn interacts with the apical caspase Dredd. This pathway links a cell surface receptor to an apical caspase in invertebrate cells and therefore suggests that the Toll-mediated pathway of caspase activation may be the evolutionary ancestor of the death receptor-mediated pathway for apoptosis induction in mammals.
Impact of Iron Assessment by MRI (2011)

The use of magnetic resonance imaging (MRI) to estimate tissue iron was conceived in the 1980s, but has only become a practical reality in the last decade. The technique is most often used to estimate hepatic and cardiac iron in patients with transfusional siderosis and has largely replaced liver biopsy for liver iron quantification. However, the ability of MRI to quantify extrahepatic iron has had a greater impact on patient care and on our understanding of iron overload pathophysiology. Iron cardiomyopathy used to be the leading cause of death in thalassemia major, but is now relatively rare in centers with regular MRI screening of cardiac iron, through earlier recognition of cardiac iron loading. Longitudinal MRI studies have demonstrated differential kinetics of uptake and clearance among the difference organs of the body. Although elevated serum ferritin and liver iron concentration (LIC) increase the risk of cardiac and endocrine toxicities, some patients unequivocally develop extrahepatic iron deposition and toxicity despite having low total body iron stores. These observations, coupled with the advent of increasing options for iron chelation therapy, are allowing clinicians to more appropriately tailor chelation therapy to individual patient needs, producing greater efficacy with fewer toxicities. Future frontiers in MRI monitoring include improved prevention of endocrine toxicities, particularly hypogonadotropic hypogonadism and diabetes.
Structural Changes and Coordinatively Unsaturated Metal Atoms on Dehydration of Honeycomb Analogous Microporous Metal–Organic Frameworks (2008)

Porous metal-organic framework compounds with coordinatively unsaturated metal sites on the inner surface of the pores promise to be valuable adsorbents and catalyst systems, either in industrial applications or as model systems to study interactions with guest molecules. The dehydration process of two isostructural microporous coordination polymers, [M2(dhtp)(H2O)2].8 H2O, termed CPO-27-M (M=Co, Zn; H(4)dhtp=2,5-dihydroxyterephthalic acid) was investigated by in situ variable temperature X-ray diffraction. Both compounds contain accessible coordination sites at the metal after complete removal of the solvent. However, despite the analogy of their crystal structures, they behave differently during dehydration. For CPO-27-Co, water desorption is a smooth topotactic process of second order with no concomitant space group change and no increase in microstrain, which is beneficial for the applicability of the material. Removal of the water propagates from the center of the channels outwards. The coordinating water molecule at the metal desorbs only when almost all the bulk water in the pores has disappeared. In contrast, discontinuities in the powder pattern of CPO-27-Zn indicate the occurrence of first-order transitions. The crystal structures of four of the five individual phases could be determined. The structure of the intermediate phase occurring just before the framework is completely evacuated was elusive in respect to full structure solution and refinement, but it is most probably related to the removal of the axis of threefold symmetry. The zinc-based material experiences a significant amount of strain.
Dependence of deposition rate on base materials in TEOS/O/sub 3/ AP CVD (2002)

The dependence of deposition rate and film quality on base materials in TEOS/O/sub 3/ atmospheric pressure chemical vapor deposition has been studied. Films deposited on thermal oxide at high ozone concentration had lower deposition rate and film quality. The dependence on base materials is caused by surface rate-limited reaction of the CVD, which leads to excellent conformality and low particle generation, although it should be improved for device fabrication. In deposition at low ozone concentration, films had the same deposition rate and film quality as those on silicon. When deposited on silicon, films of higher quality were obtained at high ozone concentration. By a double-layer deposition method (depositing thin film on thermal oxide at low ozone concentration and then depositing at high ozone concentration), films of high quality were deposited. This makes TEOS/O/sub 3/ APCVD more versatile in VLSI fabrication.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Fish and Shellfish Consumption in Relation to Death from Myocardial Infarction among Men in Shanghai, China (2001)

Between 1986 and 1989, 18,244 men aged 45-64 years in Shanghai, China, participated in a prospective study of diet and cancer. All participants completed an in-person, structured interview and provided blood and urine samples. As of September 1, 1998, 113 deaths from acute myocardial infarction were identified. After analyses were adjusted for age, total energy intake, and known cardiovascular disease risk factors, men who consumed >or=200 g of fish/shellfish per week had a relative risk of 0.41 (95% confidence interval: 0.22, 0.78) for fatal acute myocardial infarction compared with men consuming <50 g per week. Similarly, dietary intake of n-3 fatty acids derived from seafood also was significantly associated with reduced mortality from myocardial infarction. Neither dietary seafood nor n-3 fatty acid intake was associated with a reduced risk of death from stroke or ischemic heart disease other than acute myocardial infarction. However, approximately a 20% reduction in total mortality associated with weekly fish/shellfish intake was observed in the study population (relative risk = 0.79, 95% confidence interval: 0.69, 0.91). These prospective data suggest that eating fish and shellfish weekly reduces the risk of fatal myocardial infarction in middle-aged and older men in Shanghai, China.
The influence of added aluminum nanoparticles on the sensitivity of pentaerythritol tetranitrate to laser irradiation (2011)

The dependences of the probability of the explosion of pentaerythritol tetranitrate with various contents of aluminum nanoparticles on the energy density of initiating laser pulses were obtained. The optimum concentration of nanoparticles, 0.1 wt %, at which sensitivity to laser radiation was maximum was determined.
Targeted transcriptional repression using a chimeric TALE-SRDX repressor protein (2011)

Transcriptional activator-like effectors (TALEs) are proteins secreted by Xanthomonas bacteria when they infect plants. TALEs contain a modular DNA binding domain that can be easily engineered to bind any sequence of interest, and have been used to provide user-selected DNA-binding modules to generate chimeric nucleases and transcriptional activators in mammalian cells and plants. Here we report the use of TALEs to generate chimeric sequence-specific transcriptional repressors. The dHax3 TALE was used as a scaffold to provide a DNA-binding module fused to the EAR-repression domain (SRDX) to generate a chimeric repressor that targets the RD29A promoter. The dHax3.SRDX protein efficiently repressed the transcription of the RD29A::LUC transgene and endogenous RD29A gene in Arabidopsis. Genome wide expression profiling showed that the chimeric repressor also inhibited the expression of several other genes that contain the designer TALE-target sequence in their promoters. Our data suggest that TALEs can be used to generate chimeric repressors to specifically repress the transcription of genes of interest in plants. This sequence-specific transcriptional repression by direct on promoter effector technology is a powerful tool for functional genomics studies and biotechnological applications.