gebhart/patrepeval huggingface dataset:
Capacitive Biosensors (2001)

Work on a new type of biosensor, in which changes in the dielectric properties of an electrode surface are detected, started during the late 80s. The binding of an analyte to an immobilized affinity element can be detected directly without the need for a label or an indicating reaction. The changes can be determined by measuring the electrical capacitance or impedance either by using interdigitated electrodes or more commonly by potentiostatic methods. Capacitive biosensors have been used for detection of antigens, antibodies, proteins, DNA fragments and heavy metal ions. Extremely low detection limits, down below 10−15 M, have been reached with plugged, self-assembled recognition layers.
Ustekinumab improves nail disease in patients with moderate‐to‐severe psoriasis: results from PHOENIX 1 (2013)

Ustekinumab significantly improves nail psoriasis, and improvements continue over time until up to 1 year of treatment in those receiving maintenance treatment.
Orchestration of Neutrophil Movement by Intestinal Epithelial Cells in Response toSalmonella typhimuriumCan Be Uncoupled from Bacterial Internalization (1999)

Intestinal epithelial cells respond to Salmonella typhimurium by internalizing this pathogen and secreting, in a polarized manner, an array of chemokines which direct polymorphonuclear leukocyte (PMN) movement. Notably, interleukin-8 (IL-8) is secreted basolaterally and directs PMN through the lamina propria, whereas pathogen-elicited epithelial chemoattractant (PEEC) is secreted apically and directs PMN migration across the epithelial monolayer to the intestinal lumen. While most studies of S. typhimurium pathogenicity have focused on the mechanism by which this bacterium invades its host, the enteritis characteristically associated with salmonellosis appears to be more directly attributable to the PMN movement that occurs in response to this pathogen. Therefore, we sought to better understand the relationship between S. typhimurium invasion and epithelial promotion of PMN movement. First, we investigated whether S. typhimurium becoming intracellular was necessary or sufficient to induce epithelial promotion of PMN movement. Blocking S. typhimurium invasion by preventing, with cytochalasin D, the epithelial cytoskeletal rearrangements which mediate internalization did not reduce the epithelial promotion of PMN movement. Conversely, bacterial attainment of an intracellular position was not sufficient to induce model epithelia to direct PMN transmigration, since neither basolateral invasion by S. typhimurium nor apical internalization of an invasion-deficient mutant (achieved by inducing membrane ruffling with epidermal growth factor) induced this epithelial cell response. These results indicate that specific interactions between the apical surface of epithelial cells and S. typhimurium, rather than simply bacterial invasion, mediate the epithelial direction of PMN transmigration. To further investigate the means by which S. typhimurium induces epithelia to direct PMN movement, we investigated whether the same signaling pathways regulate secretion of IL-8 and PEEC. IL-8 secretion, but not PEEC secretion, was activated by phorbol myristate acetate and blocked by an inhibitor (mg-132) of the proteosome which mediates NF-kappabeta activation. Further, secretion of IL-8, but not PEEC, was activated by an entry-deficient (HilDelta) S. typhimurium mutant or by basolateral invasion of a wild-type strain. Together, these results indicate that distinct signaling pathways mediate S. typhimurium invasion, induction of IL-8 secretion, and induction of PEEC secretion in model intestinal epithelia.
Expanding the Genetic Code of Escherichia coli with Phosphoserine (2011)

O-Phosphoserine (Sep), the most abundant phosphoamino acid in the eukaryotic phosphoproteome, is not encoded in the genetic code, but synthesized posttranslationally. Here, we present an engineered system for specific cotranslational Sep incorporation (directed by UAG) into any desired position in a protein by an Escherichia coli strain that harbors a Sep-accepting transfer RNA (tRNA(Sep)), its cognate Sep-tRNA synthetase (SepRS), and an engineered EF-Tu (EF-Sep). Expanding the genetic code rested on reengineering EF-Tu to relax its quality-control function and permit Sep-tRNA(Sep) binding. To test our system, we synthesized the activated form of human mitogen-activated ERK activating kinase 1 (MEK1) with either one or two Sep residues cotranslationally inserted in their canonical positions (Sep(218), Sep(222)). This system has general utility in protein engineering, molecular biology, and disease research.
Plasma Biomarkers of Oxidant Stress and Development of Organ Failure in Severe Sepsis (2011)

We hypothesized that circulating levels of lipid peroxidation products in patients with severe sepsis are associated with the development of pulmonary, renal, hepatic, circulatory, and coagulation failure. Plasma levels of F2-isoprostanes and isofurans were measured by mass spectroscopy on intensive care unit day 2 in 50 critically ill patients with severe sepsis. Plasma F2-isoprostane levels were higher in patients who developed renal failure compared with those who did not (65 pg/mL [interquartile range {IQR} 44-112] vs. 44 pg/mL [IQR 29-54], P = 0.009) as were isofuran levels (1,223 pg/mL [IQR 348-2,531] vs. 329 pg/mL [IQR 156-1,127], P = 0.009). Plasma F2-isoprostane levels were higher in patients who developed hepatic failure compared with those who did not (72 pg/mL [IQR 44-112] vs. 44 pg/mL [IQR 30-65], P = 0.023), and there was also a trend for higher isofuran levels (1,411 pg/mL [IQR 298-1,965] vs. 525 pg/mL [IQR 160-1,223], P = 0.14). Coagulation failure (thrombocytopenia) was associated with higher isofuran levels. Circulatory failure and acute lung injury were not associated with elevated levels of isoprostanes or isofurans. Patients with isoprostane levels above the 25th percentile had higher mortality (42%) compared with patients with levels below the 25th percentile (8%, P = 0.03). Plasma levels of F2-isoprostanes and isofurans are associated with renal, hepatic, and coagulation failure, but not with circulatory or pulmonary failure in severe sepsis, suggesting that lipid peroxidation is a prominent feature of septic multisystem organ failure. Plasma isoprostanes and isofurans may be useful for monitoring oxidative stress in treatment trials of antioxidant therapies in severe sepsis.
Transposition of Gram-Positive Transposon Tn 916 in Acholeplasma laidlawii and Mycoplasma pulmonis (1987)

Mycoplasma genetics has been limited by a lack of genetic tools such as selectable markers, methods to transfer DNA, and suitable vectors for cloning. Studies were undertaken to examine the potential of using the streptococcal transposon Tn916 as a mycoplasma genetic tool. The Escherichia coli plasmid pAM120, which contains Tn916, was transformed into Acholeplasma laidlawii and Mycoplasma pulmonis. Transposition of Tn916 into the mycoplasma chromosome apparently occurred by an excision-insertion mechanism. This example shows that newly introduced DNA from other bacteria can be successfully expressed in mycoplasma and that Tn916 should serve as a powerful genetic tool for the study of mycoplasmas.
SAMStat: monitoring biases in next generation sequencing data (2010)

timolassmann@gmail.com.
Classification using cultural co-evolution and genetic programming (1996)

Genetic programming has been used to evolve decision trees for classification [Koza, 1992] but its role as an inductive learner remains elusive. This paper examines a possible role of genetic programming as a learner in a cultural co-evolution model of learners developed by Hunter. We demonstrate that this cooperation allows classification to evolve much faster than their individual components and report encouraging results on a class of problems.
Preinduction Cervical Assessment (2000)

Systems of quantifying and scoring cervical factors have been sought for years to predict the duration of labor and to determine which patients may successfully and safely undergo induction of labor. Early methods of cervical assessment generally attempted to classify patients as having favorable or unfavorable cervices based on dichotomous variables. Since then, obstetricians have begun to appreciate the usefulness of having a single score derived from the degree of ripeness of several cervical characteristics. The scoring system that has become most prevalent is the Bishop score. This system and its modifications take into account the dilation, effacement, consistency, and position of the cervix in addition to the station of the presenting part. Many have evaluated and confirmed the validity of the Bishop score. Among the factors considered in assigning the score, the strongest association with successful labor seems to be with cervical dilation. The Bishop score has been criticized for not attributing more significance to cervical dilation. However, despite this criticism, none of the modifications to the original scoring system have been shown to improve predictability. More recently, the use of ultrasound assessment of the cervix has been suggested to improve prediction of the success of labor induction. However, convincing evidence that this technique provides significant additional information when compared to digital examination is lacking. The Bishop score would seem to be the best and most cost-effective method currently available to assess the cervix and predict the likelihood of success of labor induction and the duration of such an induction.
Creutzfeldt-Jakob disease probably acquired from a cadaveric dura mater graft (1988)

✓ A case of Creutzfeldt-Jakob disease (CJD) is reported in a 28-year-old woman who had received a cadaveric dural graft 19 months earlier after resection of a cholesteatoma. The circumstances of the case point to the graft as the most likely source of the disease. Cadaveric dura should be added to the list of materials that may transmit CJD, and it must be very carefully screened if it is used at all for grafting. Autologous tissue should be considered whenever possible.
A Novel Small-Molecule Inhibitor Targeting the IL-6 Receptor β Subunit, Glycoprotein 130 (2015)

IL-6 is a major causative factor of inflammatory disease. Although IL-6 and its signaling pathways are promising targets, orally available small-molecule drugs specific for IL-6 have not been developed. To discover IL-6 antagonists, we screened our in-house chemical library and identified LMT-28, a novel synthetic compound, as a candidate IL-6 blocker. The activity, mechanism of action, and direct molecular target of LMT-28 were investigated. A reporter gene assay showed that LMT-28 suppressed activation of STAT3 induced by IL-6, but not activation induced by leukemia inhibitory factor. In addition, LMT-28 downregulated IL-6-stimulated phosphorylation of STAT3, gp130, and JAK2 protein and substantially inhibited IL-6-dependent TF-1 cell proliferation. LMT-28 antagonized IL-6-induced TNF-α production in vivo. In pathologic models, oral administration of LMT-28 alleviated collagen-induced arthritis and acute pancreatitis in mice. Based on the observation of upstream IL-6 signal inhibition by LMT-28, we hypothesized IL-6, IL-6Rα, or gp130 to be putative molecular targets. We subsequently demonstrated direct interaction of LMT-28 with gp130 and specific reduction of IL-6/IL-6Rα complex binding to gp130 in the presence of LMT-28, which was measured by surface plasmon resonance analysis. Taken together, our data suggest that LMT-28 is a novel synthetic IL-6 inhibitor that functions through direct binding to gp130.
Lack of BIC and microRNA miR‐155 expression in primary cases of Burkitt lymphoma (2005)

We previously demonstrated high expression of primary-microRNA BIC (pri-miR-155) in Hodgkin lymphoma (HL) and lack of expression in most non-Hodgkin lymphoma subtypes including some Burkitt lymphoma (BL) cases. Recently, high expression of BIC was reported in BL in comparison to pediatric leukemia and normal peripheral-blood samples. In this study, we extended our series of BL cases and cell lines to examine expression of BIC using RNA in situ hybridization (ISH) and quantitative RT-PCR (qRT-PCR) and of miR-155 using Northern blotting. Both BIC RNA ISH and qRT-PCR revealed no or low levels of BIC in 25 BL tissue samples [including 7 Epstein-Barr virus (EBV)-positive cases] compared to HL and normal controls. In agreement with these findings, no miR-155 was observed in BL tissues. EBV-negative and EBV latency type I BL cell lines also showed very low BIC and miR-155 expression levels as compared to HL cell lines. Higher levels of BIC and miR-155 were detected in in vitro transformed lymphoblastoid EBV latency type III BL cell lines. An association of latency type III infection and induction of BIC was supported by consistent expression of BIC in 11 and miR-155 in 2 posttransplantation lymphoproliferative disorder (PTLD) cases. In summary, we demonstrated that expression of BIC and miR-155 is not a common finding in BL. Expression of BIC and miR-155 in 3 latency type III EBV-positive BL cell lines and in all primary PTLD cases suggests a possible role for EBV latency type III specific proteins in the induction of BIC expression.
The human programmed cell death-2 (PDCD2) gene is a target of BCL6 repression: Implications for a role of BCL6 in the down-regulation of apoptosis (2002)

BCL6, a gene on chromosome 3 band q27, encodes a Kruppel-type zinc finger transcriptional repressor. Rearrangements of this gene are frequent in various kinds of lymphomas, particularly of the large-cell B-cell type. The BCL6 nuclear phosphoprotein is expressed in a variety of tissues and is up-regulated particularly in lymph node germinal centers. The zinc fingers of BCL6 bind DNA in a sequence-specific manner. To identify targets of the BCL6 repressive effects, we used a VP16-BCL6 fusion protein containing the zinc fingers but devoid of the repressor domains to compete with the binding of endogenous BCL6 in a transiently transfected B-cell line and then performed subtractive hybridization by using a method to selectively amplify sequences that are differentially expressed. We found that the programmed cell death-2 (PDCD2) gene is a target of BCL6 repression. This gene is the human homolog of Rp8, a rat gene associated with programmed cell death in thymocytes. Immunohistochemistry reveals the anticipated inverse relationship between BCL6 and PDCD2 expression in human tonsil. PDCD2 is detectable in cells of the germinal center in areas where there is less BCL6 expression as well as in the mantle zone, where there is little or no BCL6 expression. These results raise the possibility that BCL6 may regulate apoptosis by means of its repressive effects on PDCD2. BCL6 deregulation may lead to persistent down-regulation of PDCD2, reduced apoptosis, and, as a consequence, accumulation of BCL6-containing lymphoma cells.
Development of multiplex rt-PCR assays for rapid detection and subtyping of influenza type A viruses from clinical specimens. (2008)

We developed multiplex RT-PCR assays that can detect and identify 12 hemagglutinin (H1-H12) and 9 neuraminidase (N1-N9) subtypes that are commonly isolated from avian, swine, and human influenza A viruses. RT-PCR products with unique sizes characteristic of each subtype were amplified by multiplex RT-PCRs, and sequence analysis of each amplicon was demonstrated to be specific for each subtype with 24 reference viruses. The specificity was demonstrated further with DNA or cDNA templates from 7 viruses, 5 bacteria, and 50 influenza A virus negative specimens. Furthermore, the assays could detect and subtype up to 105 dilution of each of the reference viruses that had an original infectivity titer of 106 EID50/ml. Of 188 virus isolates, the multiplex RT-PCR results agreed completely with individual RT-PCR subtyping results and with results obtained from virus isolations. Furthermore, the multiplex RT-PCR methods efficiently detected mixed infections with at least two different subtypes of influenza viruses in one host. Therefore, these methods could facilitate rapid and accurate subtyping of influenza A viruses directly from field specimens.
Chromosome 17 Deletions and p53 Gene Mutations in Colorectal Carcinomas (1989)

Previous studies have demonstrated that allelic deletions of the short arm of chromosome 17 occur in over 75% of colorectal carcinomas. Twenty chromosome 17p markers were used to localize the common region of deletion in these tumors to a region contained within bands 17p12 to 17p13.3. This region contains the gene for the transformation-associated protein p53. Southern and Northern blot hybridization experiments provided no evidence for gross alterations of the p53 gene or surrounding sequences. As a more rigorous test of the possibility that p53 was a target of the deletions, the p53 coding regions from two tumors were analyzed; these two tumors, like most colorectal carcinomas, had allelic deletions of chromosome 17p and expressed considerable amounts of p53 messenger RNA from the remaining allele. The remaining p53 allele was mutated in both tumors, with an alanine substituted for valine at codon 143 of one tumor and a histidine substituted for arginine at codon 175 of the second tumor. Both mutations occurred in a highly conserved region of the p53 gene that was previously found to be mutated in murine p53 oncogenes. The data suggest that p53 gene mutations may be involved in colorectal neoplasia, perhaps through inactivation of a tumor suppressor function of the wild-type p53 gene.
A Diametric Role for OX40 in the Response of Effector/Memory CD4+ T Cells and Regulatory T Cells to Alloantigen (2013)

OX40 is a member of the TNFR superfamily that has potent costimulatory properties. Although the impact of blockade of the OX40-OX40 ligand (OX40L) pathway has been well documented in models of autoimmune disease, its effect on the rejection of allografts is less well defined. In this article, we show that the alloantigen-mediated activation of naive and memory CD4(+) T cells results in the induction of OX40 expression and that blockade of OX40-OX40L interactions prevents skin allograft rejection mediated by either subset of T cells. Moreover, a blocking anti-OX40 had no effect on the activation and proliferation of T cells; rather, effector T cells failed to accumulate in peripheral lymph nodes and subsequently migrate to skin allografts. This was found to be the result of an enhanced degree of cell death among proliferating effector cells. In clear contrast, blockade of OX40-OX40L interactions at the time of exposure to alloantigen enhanced the ability of regulatory T cells to suppress T cell responses to alloantigen by supporting, rather than diminishing, regulatory T cell survival. These data show that OX40-OX40L signaling contributes to the evolution of the adaptive immune response to an allograft via the differential control of alloreactive effector and regulatory T cell survival. Moreover, these data serve to further highlight OX40 and OX40L as therapeutic targets to assist the induction of tolerance to allografts and self-Ags.
Class of algorithms for decoding block codes with channel measurement information (1972)

A class of decoding algorithms that utilizes channel measurement information, in addition to the conventional use of the algebraic properties of the code, is presented. The maximum number of errors that can, with high probability, be corrected is equal to one less than <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">d</tex> , the minimum Hamming distance of the code. This two-fold increase over the error-correcting capability of a conventional binary decoder is achieved by using channel measurement (soft-decision) information to provide a measure of the relative reliability of each of the received binary digits. An upper bound on these decoding algorithms is derived, which is proportional to the probability of an error for <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">d</tex> th order diversity, an expression that has been evaluated for a wide range of communication channels and modulation techniques. With the aid of a lower bound on these algorithms, which is also a lower bound on a correlation (maximum-likelihood) decoder, we show for both the Gaussian and Rayleigh fading channels, that as the signal-to-noise ratio (SNR) increases, the asymptotic behavior of these decoding algorithms cannot be improved. Computer simulations indicate that even for !ow SNR the performance of a correlation decoder can be approached by relatively simple decoding procedures. In addition, we study the effect on the performance of these decoding algorithms when a threshold is used to simplify the decoding process.
Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients (2011)

Thirteen patients with acute myeloid leukemia, 5 with active disease, 2 in molecular relapse, and 6 in morphologic complete remission (CR; median age, 62 years; range, 53-73 years) received highly purified CD56(+)CD3(-) natural killer (NK) cells from haploidentical killer immunoglobulin-like receptor-ligand mismatched donors after fludarabine/cyclophosphamide immunosuppressive chemotherapy, followed by IL-2. The median number of infused NK cells was 2.74 × 10(6)/Kg. T cells were < 10(5)/Kg. No NK cell-related toxicity, including GVHD, was observed. One of the 5 patients with active disease achieved transient CR, whereas 4 of 5 patients had no clinical benefit. Both patients in molecular relapse achieved CR that lasted for 9 and 4 months, respectively. Three of 6 patients in CR are disease free after 34, 32, and 18 months. After infusion, donor NK cells were found in the peripheral blood of all evaluable patients (peak value on day 10). They were also detected in BM in some cases. Donor-versus-recipient alloreactive NK cells were shown in vivo by the detection of donor-derived NK clones that killed recipient's targets. Adoptively transferred NK cells were alloreactive against recipient's cells, including leukemia. In conclusion, infusion of purified NK cells is feasible in elderly patients with high-risk acute myeloid leukemia. This trial was registered at www.clinicaltrial.gov as NCT00799799.
Induction of DNA topoisomerase II-mediated DNA cleavage by beta-lapachone and related naphthoquinones. (1997)

Recent studies have suggested that 3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5,6-dione (beta-lapachone) inhibits DNA topoisomerase I by a mechanism distinct from that of camptothecin. To study the mechanism of action of beta-lapachone, a series of beta-lapachone and related naphthoquinones were synthesized, and their activity against drug-sensitive and -resistant cell lines and purified human DNA topoisomerases as evaluated. Consistent with the previous report, beta-lapachone does not induce topoisomerase I-mediated DNA breaks. However, beta-lapachone and related naphthoquinones, like menadione, induce protein-linked DNA breaks in the presence of purified human DNA topoisomerase IIalpha. Poisoning of topoisomerase IIalpha by beta-lapachone and related naphthoquinones is independent of ATP and involves the formation of reversible cleavable complexes. The structural similarity between menadione, a para-quinone, and beta-lapachone, an ortho-quinone, together with their similar activity in poisoning topoisomerase IIalpha, suggests a common mechanism of action involving chemical reactivity of these quinones. Indeed, both quinones form adducts with mercaptoethanol, and beta-lapachone is 10-fold more reactive. There is an apparent correlation between the rates of the adduct formation with thiols and of the topoisomerase II-poisoning activity of the aforementioned quinones. In preliminary studies, beta-lapachone and related naphthoquinones are found to be cytotoxic against a panel of drug-sensitive and drug-resistant tumor cell lines, including MDR1-overexpressing cell lines, camptothecin-resistant cell lines, and the atypical multidrug-resistant CEM/V-1 cell line.