gebhart/patrepeval huggingface dataset:
Improving the Affinity and the Fine Specificity of an Anti-Cortisol Antibody by Parsimonious Mutagenesis and Phage Display (1998)

Abstract Immunoassays are widely used to determine steroid concentrations. However, they are limited by the specificity of anti-steroid mAbs. We used the phage display system combined with molecular modeling and site-specific randomization to improve the affinity and the fine specificity of an anti-cortisol mAb. Using parsimonious mutagenesis, we have generated a library of mutant Ab fragments (scFv) derived from this Ab by randomizing five amino acids chosen by molecular modeling and Ab-hapten contact structural analysis. Anti-cortisol Ab fragments were selected from the library in the presence of steroid analogues to block cross-reacting binders. Specific elution with free cortisol allowed the recovery of clones with up to eightfold better affinity and fivefold less cross-reactivity than the wild-type scFv. This approach can be applied to any anti-hapten Ab and represents a useful approach for obtaining highly specific Abs for use in steroid immunoassays.
A Wearable Health Care System Based on Knitted Integrated Sensors (2005)

A comfortable health monitoring system named WEALTHY is presented. The system is based on a textile wearable interface implemented by integrating sensors, electrodes, and connections in fabric form, advanced signal processing techniques, and modern telecommunication systems. Sensors, electrodes and connections are realized with conductive and piezoresistive yarns. The sensorized knitted fabric is produced in a one step process. The purpose of this paper is to show the feasibility of a system based on fabric sensing elements. The capability of this system to acquire simultaneously several biomedical signals (i.e. electrocardiogram, respiration, activity) has been investigated and compared with a standard monitoring system. Furthermore, the paper presents two different methodologies for the acquisition of the respiratory signal with textile sensors. Results show that the information contained in the signals obtained by the integrated systems is comparable with that obtained by standard sensors. The proposed system is designed to monitor individuals affected by cardiovascular diseases, in particular during the rehabilitation phase. The system can also help professional workers who are subject to considerable physical and psychological stress and/or environmental and professional health risks.
The Surgical Anatomy of Lumbar Medial Branch Neurotomy (Facet Denervation) (2004)

If electrodes are placed parallel to the target nerve, the lesions made can be expected to encompass the target nerves. If electrodes are placed perpendicular to the nerve, the nerve may escape coagulation, or be only partially coagulated. Placing the electrode parallel to the nerve has a demonstrated anatomical basis, and has been vindicated clinically. Other techniques lack such a basis, and have not been vindicated clinically. Suboptimal techniques may underlie suboptimal outcomes from lumbar medial branch neurotomy.
Inhibition of telomerase activity in human cancer cells by RNA interference. (2003)

Telomerase is an attractive molecular target toward which to direct cancer therapeutic agents because telomerase activity is present in most malignant cells but undetectable in most normal somatic cells. Short duplex RNA (short-interfering RNA or siRNA) has recently been shown to be an effective method for inhibiting the expression of a given gene in human cells. Accordingly, we evaluated the ability of siRNA to inhibit telomerase activity in human cancer cells. Human cancer cell lines were transfected with 21 nt double-stranded RNA homologous to either the catalytic subunit of telomerase (human telomerase reverse transcriptase) or to its template RNA [human telomerase RNA(hTR)]. Both types of agents reduced telomerase activity in a variety of human cancer cell lines representing both carcinomas and sarcomas. Inhibition was dose-dependent, although modest in degree and, as expected, transient in duration. Transfection of HeLa cells using a plasmid containing the hTR gene in both forward and reverse orientations, intended to create a duplex of the hTR transcripts endogenously, resulted in decreased telomerase activity, decreased telomerase RNA content, and decreased telomeric DNA content but no decrease in the untargeted human telomerase reverse transcriptase mRNA. Telomerase inhibition by siRNA is notable because telomerase is regarded as restricted to the nucleus, whereas RNA interference is commonly regarded as restricted to the cytoplasm.
A Humanized Anti-CD70 Monoclonal Antibody Targets CD70-Expressing Multiple Myeloma. (2005)

Abstract The tumor necrosis factor family member CD70 (CD27L) is an integral membrane protein transiently expressed on antigen-activated T and B lymphocytes. CD70 regulates lymphocyte survival and differentiation of CD27 positive resting T cells and antigen-primed B cells. Aberrant CD70 expression has been detected on hematologic tumors including diffuse large cell, follicular, and mantle cell lymphomas, chronic lymphocytic leukemia and Reed-Sternberg cells in Hodgkin’s disease. Here we report for the first time the expression of CD70 on multiple myeloma (MM). Nine of thirteen MM cell lines examined expressed detectable surface CD70 with receptor copy numbers ranging from 9,000 to 145,000. Furthermore, seven of twelve primary MM isolates and six of six Waldenstrom’s macroglobulinemia (WM) isolates tested were positive for CD70. The presence of CD70 on MM and WM, combined with the antigen’s limited expression on normal non-hematopoietic tissues makes CD70 an attractive target for antibody-directed therapy of plasma cell disorders. We have engineered chimeric and humanized variants (human IgG1 isotype) of the murine anti-CD70 monoclonal antibody, 1F6. Both chimeric and humanized 1F6 variants retain the binding specificity of the murine parent monoclonal antibody (mAb) and acquired Fc-dependent effector functions including antibody-dependent cellular cytotoxicity (ADCC), complement dependent cytoxicity (CDC) and macrophage-mediated antibody-dependent cellular phagocytic (ADCP) activities against CD70+ tumor cells. Specific lysis (ADCC, CDC) or tumor cell uptake (ADCP) was observed when engineered anti-CD70 mAb were used at ≥10 ng/mL against a panel of CD70-expressing hematologic tumors. The significance of these in vitro observations was further established by the ability of anti-CD70 mAb to significantly improve the survival of mice bearing disseminated CD70-expressing tumors. The in vitro function and in vivo efficacy of anti-CD70 were dependent upon Fc-FcγR interactions, as activity and survival benefit was lost with anti-FcγR blockade or when the targeting antibody was engineered to eliminate FcγR binding. Our data suggest that humanized anti-CD70 mAb possesses potent antitumor activity and has potential utility for therapy of hematologic cancers including MM and WM.
Dependence of Transcriptional Repression on CpG Methylation Density (1994)

CpG methylation is known to suppress transcription. This repression is generally thought to be related to alterations of chromatin structure that are specified by the methylation. The nature of these chromatin alterations is unknown. Moreover, it has not been clear if the methylation repression occurs in an all-or-none fashion at some critical methylation density, or if intermediate densities of methylation can give intermediate levels of repression. Here I report a stable episomal system which recapitulates many dynamic features of methylation observed in the genome. I have determined the extent of transcriptional repression as a function of four densities of CpG methylation. I find that the repression is a graded but exponential function of the CpG methylation density such that low levels of methylation yield a 67 to 90% inhibition of gene expression. Higher levels of methylation extinguished gene expression completely. Transcription from methylated minichromosomes can be increased by butyrate treatment, suggesting that histone acetylation can reverse some of the repression specified by the methylated state. Sites of preferential demethylation occurred and may have resulted from transcription factor binding or DNA looping.
Genetic changes associated with immortalization. A review. (1997)

Human fibroblasts appear to have three terminal proliferative arrest (TPA) states that act as independent barriers to immortalization. The first of these TPA states is senescence, and several recent studies have shown that abrogation of p53 function permits temporary escape from senescence that ends in a poorly characterized form of arrest (referred to as p53-minus TPA) in which the pRB and p16INK4 genes appear to be involved. Abrogation of the function of both p53 and pRB (or p16INK4) results in continued proliferation until the cells enter crisis. Escape from crisis is always associated with the activation of a telomere maintenance mechanism. We also review evidence for the involvement of other genes in the immortalization process. Immortalization appears to be a complex process involving many genetic changes, not all of which are necessarily related to telomere maintenance.
The automated chemical synthesis of long oligoribuncleotides using 2'-O-silylated ribonucleoside 3'-O-phosphoramidites on a controlled-pore glass support: synthesis of a 43-nucleotide sequence similar to the 3'-half molecule of an Escherichia coli formylmethionine tRNA (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe automated chemical synthesis of long oligoribuncleotides using 2'-O-silylated ribonucleoside 3'-O-phosphoramidites on a controlled-pore glass support: synthesis of a 43-nucleotide sequence similar to the 3'-half molecule of an Escherichia coli formylmethionine tRNAN. Usman, K. K. Ogilvie, M. Y. Jiang, and R. J. CedergrenCite this: J. Am. Chem. Soc. 1987, 109, 25, 7845–7854Publication Date (Print):December 1, 1987Publication History Published online1 May 2002Published inissue 1 December 1987https://pubs.acs.org/doi/10.1021/ja00259a037https://doi.org/10.1021/ja00259a037research-articleACS PublicationsRequest reuse permissionsArticle Views1696Altmetric-Citations300LEARN 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
Biclustering Methods: Biological Relevance and Application in Gene Expression Analysis (2014)

DNA microarray technologies are used extensively to profile the expression levels of thousands of genes under various conditions, yielding extremely large data-matrices. Thus, analyzing this information and extracting biologically relevant knowledge becomes a considerable challenge. A classical approach for tackling this challenge is to use clustering (also known as one-way clustering) methods where genes (or respectively samples) are grouped together based on the similarity of their expression profiles across the set of all samples (or respectively genes). An alternative approach is to develop biclustering methods to identify local patterns in the data. These methods extract subgroups of genes that are co-expressed across only a subset of samples and may feature important biological or medical implications. In this study we evaluate 13 biclustering and 2 clustering (k-means and hierarchical) methods. We use several approaches to compare their performance on two real gene expression data sets. For this purpose we apply four evaluation measures in our analysis: (1) we examine how well the considered (bi)clustering methods differentiate various sample types; (2) we evaluate how well the groups of genes discovered by the (bi)clustering methods are annotated with similar Gene Ontology categories; (3) we evaluate the capability of the methods to differentiate genes that are known to be specific to the particular sample types we study and (4) we compare the running time of the algorithms. In the end, we conclude that as long as the samples are well defined and annotated, the contamination of the samples is limited, and the samples are well replicated, biclustering methods such as Plaid and SAMBA are useful for discovering relevant subsets of genes and samples.
Large Raman gain and nonlinear phase shifts in high-purity As_2Se_3 chalcogenide fibers (2004)

Third-order Kerr nonlinearities and Raman gain are studied experimentally in high-purity As2Se3 optical fibers for wavelengths near 1.55 μm. Kerr nonlinear coefficients are measured to be nearly 1000 times higher than those for silica fibers. In pulsed mode, nonlinear phase shifts near 1.2-π rad are measured in fibers only 85 cm long with peak pulse powers near 3 W. However, there are nonlinear losses near 20% for nonlinear phase shifts near π. By use of a cw optical pump, large Raman gains nearly 800 times that of silica were measured. In the cw case there were losses in the form of index gratings formed from standing waves at the exit face of the fiber. Discrete Raman amplifiers and optical regenerators are discussed as possible applications.
Re: Physician Use of Sacral Neuromodulation among Medicare Beneficiaries with Overactive Bladder and Urinary Retention (2015)

No AccessJournal of UrologyAdult Urology1 Mar 2016Re: Physician Use of Sacral Neuromodulation among Medicare Beneficiaries with Overactive Bladder and Urinary Retention David F. PensonMD, MPH David F. PensonDavid F. Penson More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.12.015AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Physician Use of Sacral Neuromodulation among Medicare Beneficiaries with Overactive Bladder and Urinary Retention." The Journal of Urology, 195(3), p. 689 © 2016 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 195Issue 3March 2016Page: 689 Advertisement Copyright & Permissions© 2016 by American Urological Association Education and Research, Inc.MetricsAuthor Information David F. Penson More articles by this author Expand All Advertisement PDF downloadLoading ...
An investigation of enumeration and DNA partitioning in Bacillus subtilis L‐form bacteria (1994)

Cell numbers of two morphogenic forms of Bacillus subtilis (the cell-walled parental and the derived stable cell wall-deficient L-form) have been compared by two methods: DNA hybridization (i.e. deduced genome numbers) and viable cell counts (i.e. number of colony-forming units (cfu)). The DNA hybridization method was shown to be a reliable and reproducible method for estimating genome numbers. Comparison of different L-form populations showed that the two methods of enumeration gave different values, with the deduced genome numbers much higher (by several orders of magnitude) than cell numbers deduced from viable cell counts. In contrast, when a culture of the cell-walled form was enumerated, the discrepancy between the two methods was low (by a factor of about 6) The combination of a high number of L-form genomes detected by DNA hybridization and a relatively low number of cfu was thought to be a consequence of a diminished co-ordination between the DNA replication and cell division processes in L-form bacteria. This suggestion was further substantiated by assessing the stability of plasmid pPL608 in a transformed B. subtilis L-form cell line, where even in the presence of continued kanamycin selection, 25% of the population lost kanamycin resistance. The results are discussed with particular reference to cell division in cell wall-deficient, stable L-form bacteria.
Analysis of SCARECROW expression using a rapid system for assessing transgene expression in Arabidopsis roots (1997)

Although the introduction of foreign genes into Arabidopsis has become routine, the production of transgenic Arabidopsis plants still requires several months. A transgene expression system (TES) has been developed that allows characterization of gene expression patterns and the effects of foreign genes in the Arabidopsis root in 2-4 weeks. The method is based on regeneration of stably transformed roots directly from callus tissue. TES has been used to study the expression of the SCARECROW gene, which is involved in establishing radial patterning in the root. The 2.5 kb region directly upstream of the SCARECROW coding region was found to be sufficient to confer cell-type specific expression. Furthermore, this promoter is active in the scr mutant background, indicating that factors essential for cell-type specific expression are present even in the absence of correct radial patterning. Finally, TES was used to demonstrate that the SCARECROW gene under control of this promoter complements the root organization defect of the scr mutant. These experiments demonstrate the utility of the TES system for studying gene expression in roots in wild-type and mutant backgrounds and for molecular complementation of root mutant phenotypes. It is possible that the method will also be applicable to other organs.
Note on Dipole Radiation Theory (1933)

By fitting certain general asymptotic series solutions of the wave equation to known expressions for wave function components at the surface of the ground and on the upper infinite hemisphere, recurrence relations between the successive terms of the asymptotic series for some of the dipole wave function components are obtained.
Multiple Forms of Immunoreactive Growth Hormone-Releasing Hormone in Human Plasma, Hypothalamus, and Tumor Tissues* (1989)

We examined the nature of GHRH in plasma of normal subjects and patients with acromegaly, hypothalamic tissue, pheochromocytoma, and GHRH-producing pancreatic tumor tissue using two RIAs of different specificity. One assay was a N-terminal assay that recognized GHRH-(1-44)-NH2, GHRH-(1-40)-OH, and GHRH-(1-37)-OH equally, and the other was a C-terminal assay that recognized only the COOH-terminal amidated sequence of GHRH-(1-44)-NH2. GHRH immunoreactivity was detectable in all samples in both assay systems, but the ratios of C- to N-terminal activity differed. The gel filtration profiles of plasma and tumor tissue revealed one peak in (or near) the position of synthetic GHRH-(1-44)-NH2. In contrast, two peaks were found in hypothalamic tissue; a major peak in the position of synthetic GHRH-(1-44)-NH2 and a higher mol wt peak. Ion exchange chromatography of the immunoreactive GHRH material from gel filtration of pooled plasma from normal subjects revealed three components of immunoreactive GHRH, one major peak in the position of GHRH-(1-40)-OH and two minor peaks in the positions of GHRH-(1-44)-NH2 and GHRH-(1-37)-OH. Two components of immunoreactive GHRH, a major peak in the position of GHRH-(1-44)-NH2 and a minor peak in the position of GHRH-(1-40)-OH, were found in hypothalamic tissue and pheochromocytomas. In the two ectopic GHRH-producing pancreatic tumors, three components of immunoreactive GHRH were detected: a major peak in the position of GHRH-(1-40)-OH, a smaller peak in the position of GHRH-(1-37)-OH, and a very small peak of GHRH-(1-44)-NH2. Synthetic GHRH-(1-44)-NH2 was not degraded by plasma during the extraction procedures. These results suggest that 1) the measured immunoreactive GHRH concentration differs when the same samples are measured by RIAs using antisera with different specificities; 2) such differences may be due to the presence of microheterogeneity of immunoreactive GHRH; 3) the microheterogeneity of immunoreactive GHRH in plasma is different from that in the hypothalamus; and 4) the posttranslational processing of GHRH in human hypothalamus is similar to that of pheochromocytomas but different from that of ectopic GHRH-producing pancreatic tumors.
Human NK cell lytic granules and regulation of their exocytosis (2012)

Natural killer (NK) cells form a subset of lymphocytes that play a key role in immuno-surveillance and host defense against cancer and viral infections. They recognize stressed cells through a variety of germline-encoded activating cell surface receptors and utilize their cytotoxic ability to eliminate abnormal cells. Killing of target cells is a complex, multi-stage process that concludes in the directed secretion of lytic granules, containing perforin and granzymes, at the immunological synapse. Upon delivery to a target cell, perforin mediates generation of pores in membranes of target cells, allowing granzymes to access target cell cytoplasm and induce apoptosis. Therefore, lytic granules of NK cells are indispensable for normal NK cell cytolytic function. Indeed, defects in lytic granule secretion lead or are related to serious and often fatal diseases, such as familial hemophagocytic lymphohistiocytosis (FHL) type 2-5 or Griscelli syndrome type 2. A number of reports highlight the role of several proteins involved in lytic granule release and NK cell-mediated killing of tumor cells. This review focuses on lytic granules of human NK cells and the advancements in understanding the mechanisms controlling their exocytosis.
Evolutionary Potential of an RNA Virus (2004)

RNA viruses are remarkably adaptable to changing environments. This is medically important because it enables pathogenic viruses to escape the immune response and chemotherapy and is of considerable theoretical interest since it allows the investigation of evolutionary processes within convenient time scales. A number of earlier studies have addressed the dynamics of adapting RNA virus populations. However, it has been difficult to monitor the trajectory of molecular changes in RNA genomes in response to selective pressures. To address the problem, we developed a novel in vitro evolution system based on a recombinant double-stranded RNA bacteriophage, phi 6, containing a beta-lactamase (bla) gene marker. Carrier-state bacterial cells are resistant to ampicillin, and after several passages, they become resistant to high concentrations of another beta-lactam antibiotic, cefotaxime, due to mutations in the virus-borne bla gene. We monitored the changes in bla cDNAs induced by cefotaxime selection and observed an initial explosion in sequence variants with multiple mutations throughout the gene. After four passages, a stable, homogeneous population of bla sequences containing three specific nonsynonymous mutations was established. Of these, two mutations (E104K and G238S) have been previously reported for beta-lactamases from cefotaxime-resistant bacterial isolates. These results extend our understanding of the molecular mechanisms of viral adaptation and also demonstrate the possibility of using an RNA virus as a vehicle for directed evolution of heterologous proteins.