gebhart/patrepeval huggingface dataset:
Type VIII collagen from bovine Descemet's membrane: structural characterization of a triple-helical domain (1986)

Bovine corneal Descemet's membrane (DM) was subjected to limited pepsin digestion. Soluble native collagens were fractionated by differential salt precipitation, and a mixture of type V collagen and collagenous fragments with a chain Mr of 50,000 (50K) was obtained at a concentration of 1.5 M NaCl. Further purification of the 50K collagen by molecular sieve and high-performance liquid chromatography resulted in the isolation of two-non-disulfide-bonded polypeptides, 50K-A and 50K-B, which were susceptible to several neutral proteases, including bacterial collagenase. By the criteria of peptide mapping, amino acid composition, and N-terminal sequence analysis, 50K-A and 50K-B were structurally dissimilar, although both chains contained Gly-X-Y repeats. 50K-A and 50K-B were immunologically and structurally distinct from collagen type I, III, IV, V, and VI. Immunohistochemical studies of bovine ocular tissue showed preferential distribution of the collagen containing the 50K fragment in the DM, with a more disperse arrangement of apparently interconnecting fibrils in the corneal stroma. Type VIII collagen isolated from the culture medium of metabolically radiolabeled bovine corneal endothelial (BCE) cells and its pepsin-resistant Mr 50 000 domain(s) both cross-reacted with antisera to 50K polypeptides from the corneal DM. Additionally, the CNBr peptide maps of pepsin-resistant Mr 50 000 polypeptides of type VIII collagen isolated from BCE cells and bovine corneal DM were highly similar.(ABSTRACT TRUNCATED AT 250 WORDS)
Inflammatory Bowel Disease (1996)

In recent years there has been a series of advances in the treatment of inflammatory bowel disease (ulcerative colitis and Crohn's disease).16 Notwithstanding these advances, our understanding of inflammatory bowel disease7 has been hindered by the lack of representative animal models, an absence of pathognomonic features, and inadequate therapeutic end points. Sensitive or specific serologic or genetic markers of inflammatory bowel disease have yet to be identified.7 At present, the diagnosis of ulcerative colitis and Crohn's disease and the differentiation between them are based on nonspecific clinical and histologic patterns that are often obscured by intercurrent infectious or iatrogenic . . .
Incidence and survival patterns of cutaneous T-cell lymphomas in the United States (2012)

Using the United States Surveillance, Epidemiology and End Results (SEER) 17 dataset, we examined incidence and survival patterns for patients with cutaneous T-cell lymphomas (CTCLs) diagnosed following institution of the World Health Organization-European Organisation for Research and Treatment of Cancer (WHO-EORTC) classification. From 2005 to 2008, 2273 cases of CTCL were diagnosed. The age-adjusted incidence rate per 100,000 person-years for mycosis fungoides (MF) was 0.55 and for Sézary syndrome (SS) was 0.01. Incidence was higher among males (MF/SS male-to-female incidence rate ratio [IRR] 1.57) and black patients (MF black-to-white IRR 1.55). Black patients with CTCL were diagnosed at a younger age and black patients with MF/SS presented with advanced stage and had worse survival than white patients. In multiple-variable Cox-regression models, age > 60 (hazard ratio [HR] 4.78, 95% confidence interval [CI] 2.97-7.70), black race (HR 2.09, 95% CI 1.29-3.37) and advanced stage (HR 6.06, 95% CI 3.66-10.05) predicted worse survival for patients with MF/SS. Additional research identifying reasons for these differences are necessary to better understand these diseases and for new strategies in the treatment of CTCL.
On the Mechanism of the Acid-catalyzed Rearrangement of Siloxane Linkages in Organopolysiloxanes (1955)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOn the Mechanism of the Acid-catalyzed Rearrangement of Siloxane Linkages in OrganopolysiloxanesDallas T. HurdCite this: J. Am. Chem. Soc. 1955, 77, 11, 2998–3001Publication Date (Print):June 1, 1955Publication History Published online1 May 2002Published inissue 1 June 1955https://pubs.acs.org/doi/10.1021/ja01616a020https://doi.org/10.1021/ja01616a020research-articleACS PublicationsRequest reuse permissionsArticle Views425Altmetric-Citations42LEARN 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
Development and validation of a real-time quantification assay to detect and monitor BRAFV600E mutations in hairy cell leukemia (2012)

The BRAFV600E mutation was recently detected in hairy cell leukemia (HCL) by whole exome sequencing. To make use of this new marker for diagnosis and follow-up of HCL, we developed a BRAFV600Emut-specific quantitative real-time PCR assay and validated it in 117 HCL patients and 102 non-HCL/BRAFwt patients. The cut-off level to discriminate BRAFV600E-positive/-negative cases was set at 0.023% BRAFV600E/BRAFwt. A total of 115 of 117 HCL (98.3%) demonstrated percentage BRAFV600E/BRAFwt above the cut-off (mean, 29.6 ± 41.1). The remaining 2 of 117 HCL with lower percentage BRAFV600E/BRAFwt ratios were also BRAFwt by deep-sequencing technology. Sixteen HCL-variant patients showed percentage BRAFV600E/BRAFwt values corresponding to "non-HCL." Follow-up studies in 19 HCL cases demonstrated a decrease of percentage BRAFV600E/BRAFwt during therapy. The log-reductions as determined by RT-PCR and immunophenotyping correlated significantly (P < .001). In conclusion, we confirmed BRAFmut as a useful marker in HCL, its absence in HCL variant, and developed an RT-PCR-based assay to monitor minimal residual disease in HCL.
Signal transduction pathways implicated in neural recognition molecule L1 triggered neuroprotection and neuritogenesis (2005)

The signal transduction pathways involved in adhesion molecule L1-triggered neuritogenesis and neuroprotection were investigated using the extracellular domain of mouse or human L1 in fusion with the Fc portion of human immunoglobulin G or L1 purified from mouse brain by affinity chromatography. Substrate L1-triggered neuritogenesis and neuroprotection depended on distinct but also overlapping signal transduction pathways and on the expression of L1 at the neuronal cell surface. PI3 kinase inhibitors, Src family kinase inhibitors as well as mitogen-activated protein kinase kinase inhibitors reduced both L1-triggered neuritogenesis and neuroprotection. In contrast, fibroblast growth factor receptor inhibitors, a protein kinase A inhibitor, and an inhibitor of cAMP-mediated signal transduction pathways, blocked neuritogenesis, but did not affect L1-triggered neuroprotection. Proteolytic cleavage of L1 or its interaction partners is necessary for both L1-mediated neuritogensis and neuroprotection. Furthermore, L1-triggered neuroprotection was found to be associated with increased phosphorylation of extracellular signal-regulated kinases 1/2, Akt and Bad, and inhibition of caspases. These observations suggest possibilities of differentially targeting signal transduction pathways for L1-dependent neuritogenesis and neuroprotection.
Hemodynamic benefits and prolonged survival with long-term captopril therapy in rats with myocardial infarction and heart failure. (1987)

To determine whether the hemodynamic profile of chronic heart failure secondary to myocardial infarction could be altered, captopril was administered to female Wistar rats 3 weeks after coronary artery ligation and continued for 3 months. Captopril reduced left ventricular mass, prevented the increase in right ventricular mass observed with increasing infarct size, lessened the increase in left ventricular end-diastolic pressure, and reduced mean arterial pressure and total peripheral resistance, whereas cardiac output and heart rate were maintained. The end-diastolic volume of treated rats with moderate infarcts was significantly less than that of untreated rats, and therefore the ejection fraction index was significantly increased. In rats given captopril until death or for a period of up to 1 year, survival was significantly prolonged, particularly in those rats with moderate-sized infarcts.
Cell Differentiation,In vitroMammalian (2009)

Abstract There has been a significant increase in activity in the growth and manipulation of differentiating cell populations brought on by the interest in embryonic and adult stem cells. New methods of analysis have assisted in making important connections between in vivo biology and what one observes in a culture dish. Despite the many technical and interpretive challenges faced in the cultivation of differentiating mammalian cell populations, great strides have been made in understanding the constituents of differentiating cell populations and their behavior through the use of in vitro cultivation. This article reviews some of the important insights that have been gained in the last several years through work with a variety of culture systems and their comparison with what is observed in vivo . Continued comparison and benchmarking between organ systems and cell types should continue to improve our ability to effectively work with embryonic and adult cell populations with an appreciation for the need to distinguish between modulation and differentiation, growth and neogenesis, and fact from artifact.
Genes and enzymes of the acetyl cycle of arginine biosynthesis in Corynebacterium glutamicum: enzyme evolution in the early steps of the arginine pathway (1996)

A cluster of arginine biosynthetic genes of Corynebacterium glutamicum ATCC 13032, comprising argJ, argB and argD as well as part of argC and argF, has been cloned by heterologous complementation of an Escherichia coli argE mutant. The gene order has been established as argCJBDF by sequencing the entire 4.4 kb cloned DNA fragment. The C. glutamicum argB gene can be transcribed in E. coli cells from an internal promoter located in the coding part of the preceding argJ gene, whereas transcription of the argJ gene appears vector-dependent. Expression of the corynebacterial argB gene is repressed by arginine in the native host but not in recombinant E. coli cells. Feedback inhibition of the corresponding N-acetylglutamate kinase activity was observed both in cell extracts of C. glutamicum and in recombinant E. coli argB auxotrophic strains. Extracts of E. coli cells carrying cloned corynebacterial DNA display an ornithine acetyltransferase activity (encoded by argJ) which alleviates the acetylornithinase (encoded by argE) deficiency of the enterobacterial host. In contrast to Bacillus stearothermophilus ornithine acetyltransferase which also exhibits acetylglutamate synthase activity, C. glutamicum ornithine acetyltransferase appears monofunctional. ArgA and ArgB proteins from different sources share highly significant similarities. The evolutionary implications of these data are discussed.
Regulatory T‐lymphocytes mediate amyotrophic lateral sclerosis progression and survival (2012)

Abstract In amyotrophic lateral sclerosis (ALS) mice, regulatory T‐lymphocytes (Tregs) are neuroprotective, slowing disease progression. To address whether Tregs and FoxP3, a transcription factor required for Treg function, similarly influence progression rates of ALS patients, T‐lymphocytes from patients were assessed by flow cytometry. Both numbers of Tregs and their FoxP3 protein expressions were reduced in rapidly progressing ALS patients and inversely correlated with progression rates. The mRNA levels of FoxP3, TGF‐β, IL4 and Gata3, a Th2 transcription factor, were reduced in rapidly progressing patients and inversely correlated with progression rates. Both FoxP3 and Gata3 were accurate indicators of progression rates. No differences in IL10, Tbx21, a Th1 transcription factor or IFN‐γ expression were found between slow and rapidly progressing patients. A 3.5‐year prospective study with a second larger cohort revealed that early reduced FoxP3 levels were indicative of progression rates at collection and predictive of future rapid progression and attenuated survival. Collectively, these data suggest that Tregs and Th2 lymphocytes influence disease progression rates. Importantly, early reduced FoxP3 levels could be used to identify rapidly progressing patients.
B‐Cell Abnormalities in AIDS: Stable and Clonally‐Restricted Antibody Response in HIV‐1 Infection (1993)

Antibodies in sera of HIV-1 infected individuals against the HIV-1 core protein (p24), HIV-1 envelope glycoprotein (gp120) and reverse transcriptase (RT) are characterized by a skewed light chain isotype expression. The kappa/lambda ratios of antibodies to p24 and gp120 in infected individuals were found to be unique in each individual, but constant over several years independently from disease progression. The oligoclonal nature of the anti-HIV-1 antibodies suggested by skewed kappa/lambda expression was confirmed with isoelectric focusing of affinity purified antibodies to p24 and gp120. Analysis of the utilization of V gene families in purified anti-p24 and anti-gp120 antibodies revealed a restricted and biased VH gene family usage. In contrast, the utilization of VK gene families appeared to be random. The finding of stable and restricted antibody responses in infected individuals could be one of the causes for the failure to produce antibodies to HIV-1 that are effective against escape virus variants.
Human homologues of Delta-1 and Delta-4 function as mitogenic regulators of primitive human hematopoietic cells (2001)

Delta-mediated Notch signaling controls cell fate decisions during invertebrate and murine development. However, in the human, functional roles for Delta have yet to be described. This study reports the characterization of Delta-1 and Delta-4 in the human. Human Delta-4 was found to be expressed in a wide range of adult and fetal tissues, including sites of hematopoiesis. Subsets of immature hematopoietic cells, along with stromal and endothelial cells that support hematopoiesis, were shown to express Notch and both Delta-1 and Delta-4. Soluble forms of human Delta-1 (h Delta-1) and h Delta-4 proteins were able to augment the proliferation of primitive human hematopoietic progenitors in vitro. Intravenous transplantation of treated cultures into immune-deficient mice revealed that h Delta-1 is capable of expanding pluripotent human hematopoietic repopulating cells detected in vivo. This study provides the first evidence for a role of Delta ligands as a mitogenic regulator of primitive hematopoietic cells in the human. (Blood. 2001;97:1960-1967)
Photonic-Lantern-Based Mode Multiplexers for Few-Mode-Fiber Transmission (2014)

We report transmission experiments in few-mode fibers supporting 6 spatial-and polarization modes, where low-loss photonic lanterns are used as mode multiplexers. We measured a transmission distance of 900 km for 32 WDM channels with a 100 GHz channel spacing and a distance of 1500 km for a single wavelength channel experiment.
Network anomaly confirmation, diagnosis and remediation (2009)

Identifying and diagnosing network traffic anomalies, and rectifying their effects are standard, daily activities of network operators. While there is a large and growing literature on techniques for detecting network anomalies, there has been little or no treatment of what to do after a candidate anomaly has been identified. In this paper, we present a first step toward formalizing and automating the time-consuming and challenging tasks associated with network anomaly confirmation, diagnosis and remedy. Our work assumes that potential anomalies are identified either through visual analysis of key traffic measurements or from a Network Anomaly Detection System (NADS). We describe a flexible framework for network anomaly confirmation, diagnosis and remedy that is based on workflow concepts. The key features of this framework include data types/sources, analyses and decision points. We present an instantiation of our framework that includes a taxonomy of network traffic anomalies and detailed steps for confirmation of anomalies associated with malicious attacks. We demonstrate our framework by applying it to traffic in our university network. We propose that our framework is a starting point for streamlining operational tasks associated with traffic anomalies, and for the generation of annotated data sets that can be used in future NADS development.
In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry (2007)

Quantitation of circulating tumor cells (CTCs) constitutes an emerging tool for the diagnosis and staging of cancer, assessment of response to therapy, and evaluation of residual disease after surgery. Unfortunately, no existing technology has the sensitivity to measure the low numbers of tumor cells (<1 CTC per ml of whole blood) that characterize minimal levels of disease. We present a method, intravital flow cytometry, that noninvasively counts rare CTCs in vivo as they flow through the peripheral vasculature. The method involves i.v. injection of a tumor-specific fluorescent ligand followed by multiphoton fluorescence imaging of superficial blood vessels to quantitate the flowing CTCs. Studies in mice with metastatic tumors demonstrate that CTCs can be quantitated weeks before metastatic disease is detected by other means. Analysis of whole blood samples from cancer patients further establishes that human CTCs can be selectively labeled and quantitated when present at approximately 2 CTCs per ml, opening opportunities for earlier assessment of metastatic disease.
Excipients for Protein Drugs (2006)

With the advent of recombinant DNA technology, protein-based drugs have become continually and increasingly commonplace in the repertoire of medicines available to medical practitioners for the treatment of a wide range of diseases from cancer to rheumatoid arthritis. Along with the scientiﬁc and technical advances in the production of recombinant proteins, the principal reason for the success of protein drugs is their high speciﬁcity towards targets and superior safety proﬁles when compared to their small molecule counterparts.
Retrovirus silencer blocking by the cHS4 insulator is CTCF independent (2003)

Silencing of retrovirus vectors poses a significant obstacle to genetic manipulation of stem cells and their use in gene therapy. We describe a mammalian silencer blocking assay using insulator elements positioned between retrovirus silencer elements and an LCRbeta-globin reporter transgene. In transgenic mice, we show that retrovirus silencers are blocked by the cHS4 insulator. Silencer blocking is independent of the CTCF binding site and is most effective when flanking the internal reporter transgene. These data distinguish silencer blocking activity by cHS4 from its enhancer blocking activity. Retrovirus vectors can be created at high titer with one but not two internal dimer cHS4 cores. cHS4 in the LTRs has no effect on expression in transduced F9 cells, suggesting that position effect blocking is not sufficient to escape silencing. The Drosophila insulators gypsy and Scs fail to block silencing in transgenic mice, but gypsy stimulates vector expression 2-fold when located in the LTRs of an infectious retrovirus. The silencer blocking assay complements existing insulator assays in mammalian cells, provides new insight into mechanisms of insulation and is a valuable tool to identify additional silencer blocking insulators that cooperate with cHS4 to improve stem cell retrovirus vector design.
Anti-Cocaine Catalytic Antibodies:  A Synthetic Approach to Improved Antibody Diversity (1996)

Catalytic antibodies are potential therapeutic agents for drug overdose and addiction, and we previously reported the first such artificial enzymes to degrade cocaine. However, as described herein, these catalytic monoclonal antibodies (Mab's) were found to have nearly identical complementarity-determining regions (CDR's). Such limited diversity among catalytic antibodies of similar specificity has been reported previously and poses a problem since the capacity of any single group of homologous catalytic antibodies to yield one of high activity, whether through repetitive screening of hybridomas or through antibody mutagenesis, is unpredictable. One strategy to increase the diversity of the immune response to an analog would be to vary the tether site of the immunogenic conjugate thereby exposing unique epitopes for immunorecognition. We now report the syntheses of three immunogenic conjugates of a transition-state analog (TSA) of cocaine benzoyl ester hydrolysis which have identical phosphonate monoester core structures but varying tether sites for attachment to carrier protein: TSA 1 at the methyl ester, TSA 2 at the 4‘-phenyl position, and TSA 3 at the tropane nitrogen. Mixed phosphonate diester precursors were obtained from phosphonic dichlorides and ecgonine alkyl esters through our 1H-tetrazole catalysis method. We found that all three analogs provided catalytic antibodies that hydrolyze cocaine at the benzoyl ester; the most active catalytic antibody, Mab 15A10, displayed a rate acceleration (kcat/kuncat = 2.3 × 104) sufficient to commence preclinical studies. On competitive ELISA, all nine catalytic antibodies, regardless of the eliciting antigen, bound TSA 1 with high affinity but four bound TSA 3 poorly and five failed to bind TSA 2 despite the inhibition of all antibodies by free TSA (TSA 4). A comparison of heavy and of light chain CDR's showed four discrete groups with TSA 1 and 3 each yielding two non-overlapping families of catalytic antibodies; TSA 2 yielded one antibody with CDR's nearly identical to those of the largest group of catalytic antibodies elicited by TSA 1. The failure of TSA 2 and TSA 3 to bind to catalytic antibodies derived from alternative immunogenic conjugates demonstrates that the tether site does limit the catalytic antibodies produced and supports the general strategy of varying the attachment to carrier protein.
Comparison of Live Attenuated Cold-Adapted and Avian-Human Influenza A/Bethesda/85 (H3N2) Reassortant Virus Vaccines in Infants and Children (1990)

Randomized, placebo-controlled studies with 10(3)-10(7) 50% tissue-culture infectious dose (TCID50) of avian-human (ah) and cold-adapted (ca) influenza A/Bethesda/85 (H3N2) reassortant viruses were completed in 106 seronegative young children 6-48 months of age. Although the reassortants differed in six of eight RNA segments, they exhibited similar properties in level of attenuation, infectivity, immunogenicity, and efficacy. The 50% human infectious dose was 10(4.6) TCID50 for ah and 10(4.4) for ca vaccines. Both reassortants were satisfactorily attenuated with restricted replication and were no more reactogenic than placebo. The mean peak titer of virus shed was 10(1.5) (ah) to 10(2.0) (ca) TCID50/ml, and each of 37 isolates tested retained their characteristic vaccine phenotypes. Infection with ah or ca virus conferred immunity to experimental challenge with homologous virus. These findings indicate that both ah and ca influenza A/Bethesda/85 (H3N2) reassortants should be suitable vaccine candidates for use in healthy infants and young children.