gebhart/patrepeval huggingface dataset:
Mutational pattern of hepatitis B virus on sequential therapy with famciclovir and lamivudine in patients with hepatitis B virus reinfection occurring under hbig immunoglobulin after liver transplantation (1999)

Famciclovir (FCV) and lamivudine (LAM) reduce viral replication in patients with recurrent hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). Eighteen of 20 patients with insufficient response to FCV were treated with 100 mg LAM daily after OLT. These patients had shown nonresponse (n = 5), partial response (n = 7), or breakthrough (n = 6) during FCV therapy. Despite passive immunoprophylaxis with hepatitis B immunoglobulin after liver transplantation, HBV reinfection had occurred in 14 of 15 transplanted patients. HBV-DNA levels and the regions A to E of the HBV-DNA polymerase gene were analyzed before and after treatment failure to either therapy. Within 4 weeks on LAM, all but 1 patient showed a 95% average reduction of the HBV-DNA level. As with FCV, we did not observe any severe side-effects attributable to LAM. However, 7 patients developed a breakthrough within 12, 29 (n = 2), 32, 37, 54, and 145 weeks under treatment with LAM associated with the methionine-to-valine signature mutation (M552V) in the YMDD motif in all. With FCV, no unique, but a dominant, resistance pattern with the L528M mutation was identified for patients with breakthrough under FCV. In contrast, nonresponders or patients with partial response to FCV did not exhibit such mutations. Our results indicate that the L528M mutation is a risk factor for LAM breakthrough, because breakthrough during LAM occurred earlier in patients with this mutation (50 +/- 10 weeks vs. 120 +/- 21 weeks). Because breakthrough on either treatment is frequent for this specific group of patients, the use of combination therapy should be explored.
Which effective property of amino acids is best preserved by the genetic code? (1998)

Simple procedures are proposed to quantify how much an effective property embodied in a given ranking of the twenty amino acids can be affected by random point mutations at nucleotide bases. As expected, of the various orderings tested, rankings based on most hydrophobicity scales exhibit low scores, thus offering better immunity towards such single-base mutations. This, however, occurs to different extents and the method allows sharp discriminations between the scales. Hydrophobicity scales based on global properties such as spatial environment data of proteins residues, or mutation matrices of amino acid replacements, generally behave better than those based on pure physicochemical properties of isolated residues. An averaged scale built from the available hydrophobicity scales exhibits one of the most favorable scores. A systematic search for the best amino acid order has been carried out across all possible scales. Optimized scales are characterized by the existence of a clustering scheme into three zones, within which permutations are more or less tolerated, depending on the zone and on the summation procedure used in the score calculation. The first cluster corresponds to the hydrophobic side, and includes the ten amino acids WMCFILVGRS. Next follows the ATP triad. The third cluster coincides with the hydrophilic side and includes, in the last seven positions, the amino acids EDKNQHY. Interpretation of these optimized scales in terms of codon positions in the genetic code further suggests a clustering scheme composed of four groups, WMCFILV-GRS-ATP-EDKNQHY, emphasizing the role of the second base as the main driving parameter. As a consequence, the conserved character of the genetic code is better reflected when it is displayed in UGCA ordering rather than in the commonly used UCAG ordering. The present a priori classification of the amino acids could find potential use in protein sequence homology and structure prediction.
Selective Synthesis of Secondary and Tertiary Amines by Cp*Iridium-Catalyzed Multialkylation of Ammonium Salts with Alcohols (2007)

The efficient selective synthesis of secondary and tertiary amines has been achieved by means of Cp*Ir-catalyzed multialkylation of ammonium salts with alcohols without solvent: the reactions of ammonium acetate with alcohols gave tertiary amines exclusively, while those of ammonium tetrafluoroborate afforded secondary amines selectively. Using this method, secondary 5- and 6-membered cyclic amines were synthesized from ammonium tetrafluoroborate and diols in one pot.
Characterization of lymphocyte responses to peanuts in normal children, peanut-allergic children, and allergic children who acquired tolerance to peanuts (2003)

Comparing lymphocyte responses to allergenic and nonallergenic foods could reveal the differences between pathogenic and normal immune responses to foods. Defining the cytokine-producing phenotypes of peanut-specific lymphocytes from peanut-allergic children, children who outgrew peanut allergy, and children who have always tolerated peanuts may be useful for understanding the mechanisms of food tolerance. Investigating immune responses against foods is hindered, however, by the fact that circulating food antigen-specific lymphocytes are very rare. In a novel approach we used carboxyfluorescein succinimidyl ester to detect peanut-specific lymphocytes by flow cytometry. We confirmed that these cells are indeed peanut specific by cloning. Peanut-allergic donors show Th2 polarization of cytokine production by peanut-specific cells (IFN-gamma (low), TNF-alpha (low), IL-4 (high), IL-5 (high), IL-13 (high)). Conversely, nonallergic children and children who have outgrown their allergy show Th1 skewing to peanut antigens (IFN-gamma (high), TNF-alpha (high), IL-4 (low), IL-5 (low), IL-13 (low)), similarly to nonallergenic food antigens (beta-lactoglobulin, OVA). This finding suggests that peanut antigens do not intrinsically induce Th2 skewing, but that the type of response depends upon the donor's allergic status. In conclusion, food allergic status is characterized by a Th2 response whereas Th1-skewed responses underlie oral tolerance
Chemokine-Guided CD4+ T Cell Help Enhances Generation of IL-6RαhighIL-7Rαhigh Prememory CD8+ T Cells (2007)

CD4(+) T cells promote effective CD8(+) T cell-mediated immunity, but the timing and mechanistic details of such help remain controversial. Furthermore, the extent to which innate stimuli act independently of help in enhancing CD8(+) T cell responses is also unresolved. Using a noninfectious vaccine model in immunocompetent mice, we show that even in the presence of innate stimuli, CD4(+) T cell help early after priming is required for generating an optimal pool of functional memory CD8(+) T cells. CD4(+) T cell help increased the size of a previously unreported population of IL-6Ralpha(high)IL-7Ralpha(high) prememory CD8(+) T cells shortly after priming that showed a survival advantage in vivo and contributed to the majority of functional memory CD8(+) T cells after the contraction phase. In accord with our recent demonstration of chemokine-guided recruitment of naive CD8(+) T cells to sites of CD4(+) T cell-dendritic cell interactions, the generation of IL-6Ralpha(high)IL-7Ralpha(high) prememory as well as functional memory CD8(+) T cells depended on the early postvaccination action of the inflammatory chemokines CCL3 and CCL4. Together, these findings support a model of CD8(+) T cell memory cell differentiation involving the delivery of key signals early in the priming process based on chemokine-guided attraction of naive CD8(+) T cells to sites of Ag-driven interactions between TLR-activated dendritic cells and CD4(+) T cells. They also reveal that elevated IL-6Ralpha expression by a subset of CD8(+) T cells represents an early imprint of CD4(+) T cell helper function that actively contributes to the survival of activated CD8(+) T cells.
Modeling tasks with mechanisms (1993)

Building a problem solver and acquiring the knowledge needed to operate it are the two central goals of knowledge engineering. to achieve these goals, knowledge engineers construct models of the domain and of the task of interest. the various approaches used for modeling, however, have so far failed to define methods and techniques that can be applied across domains and tasks, and to produce models that can be reused in future applications. In this article, we propose that both of these objectives can be achieved by the use of building blocks called mechanisms. We examine the composition of mechanisms and also show how these mechanisms can be manipulated to construct problemsolving methods. We present PROTÉGÉ-II, a knowledge-acquisition shell that uses problem-solving methods to drive the modeling of tasks, the automatic generation of knowledge-acquisition tools, and the control flow of the problem solver. the modeling of tasks, within the context of PROTÉGÉ-II, is illustrated with two examples: one from the game domain and another from the medical-therapy domain. In addition, we introduce the conceptual basis for a library of mechanisms that serves as a repository of reusable knowledge components. © 1993 John Wiley & Sons, Inc.
Oxygen tension influences the differentiation, maturation and apoptosis of human megakaryocytes (2000)

Megakaryocytes (Mks) mature adjacent to bone marrow (BM) sinus walls and subsequently release platelets within the sinusoidal space or in lung capillaries. As the sites for platelet release have higher levels of oxygen tension (pO(2)) than the core of the BM where stem and progenitor cells reside, we investigated whether pO(2) influences Mk maturation. Mks were generated from CD34(+) cells (from mobilized peripheral blood from cancer patients) under 5% and 20% O(2). At day 15, CD41(+) Mk expansion in 20% and 5% O(2) cultures was 85-fold and 31-fold respectively. Twenty percent O(2) cultures also had higher levels of high ploidy (> or = 8N, eightfold higher) and proplatelet-forming (fivefold higher) Mks. At day 21, 20% O(2) cultures had a fivefold higher number of apoptotic Mks. In contrast, 5% O(2) promoted Mk colony-forming unit (CFU-Mk) generation and maintenance. Similar results were observed in cultures initiated with CD41(+) Mks, indicating that pO(2) directly affects Mks. The change from 20% to 5% O(2) on day 5 and day 7 delayed both maturation and apoptosis, suggesting that these two processes are closely linked. These results were confirmed in CD34(+) cultures from normal BM samples. These data may provide insights into in vivo Mk maturation, such as an explanation for hypoxia-induced thrombocytopenia in animals.
Elevated B cell activating factor (BAFF) in patient plasma after allogeneic stem cell transplantation is a potential biomarker for chronic graft versus host disease (2006)

Previous studies have identified a highly significant correlation between specific antibody responses directed against recipient H-Y minor histocompatibility antigens and the development of chronic graft versus host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). These findings suggest that donor B cells play a role in the development of cGVHD and clinical trials utilizing anti-CD20 monoclonal antibody, rituximab, have demonstrated clinical improvement in some patients with active resistant cGVHD. B cell activating factor, BAFF, is a member of the TNF cytokine family that binds to one of three cell surface receptors on B cells. Activation of these B cell receptors by antigen and BAFF results in rapid induction of proliferation and differentiation of germinal center B cells into either Ig-secreting cells or memory B cells. The finding that elevated BAFF levels in patients with autoimmune diseases are associated with disease severity and autoantibody production has led to clinical trials using anti-BAFF monoclonal antibody in these diseases. To test whether BAFF contributes to the activation of B cells in patients with cGVHD, we employed a sandwich ELISA to measure soluble BAFF in plasma from 27 patients after allogeneic HSCT. Mean BAFF levels for extensive (n = 8), limited (n = 8), resolved (n = 6) or no (n = 5) cGVHD groups were: 7.3 ng/ml, 5.37 ng/ml, 3.92 ng/ml and 2.02 ng/ml, respectively. The differences between the extensive or limited groups versus the no cGVHD group were statistically significant (each P = .03) suggesting that BAFF levels corresponded with cGVHD activity. B cell subsets in peripheral blood were also examined by flow cytometry to identify circulating memory B cells. Of four cGVHD patients analyzed thus far, individuals with active disease and high BAFF levels also had high numbers of CD27+ memory B cells in peripheral blood compared to patients with resolved cGVHD and low BAFF levels. Ongoing prospective, serial assessment of BAFF levels and B cell phenotype in larger numbers of patients will extend these results. We propose that BAFF may serve as a new biomarker for cGVHD, specifically identifying patients with active disease. If further studies identify a pathologic role for increased BAFF in cGVHD, anti-BAFF monoclonal antibodies may provide a new therapeutic approach for this serious complication of allogeneic HSCT.
Developmental‐ and tissue‐specific expression of an inhibitor of apoptosis protein 1 homologue from Aedes triseriatus mosquitoes (2002)

We have identified a homologue of the Drosophila inhibitor of apoptosis protein 1 in Aedes triseriatus mosquitoes (designated AtIAP1). The AtIAP1 gene maps to a single locus on chromosome 2. The translation product is a 403 amino acid protein that contains two baculovirus IAP repeat (BIR) domains and a RING finger motif. AtIAP1 mRNA was detectable by RT-PCR amplification in all the mosquito developmental stages (embryos, first-fourth instar larvae, early and late pupae, adults) and adult tissues (midguts, ovaries) examined. In contrast, immunoblots with AtIAP1-specific antibodies revealed that the protein was detectable only in certain developmental stages (first instar larvae, early pupae, adults) and tissues (ovaries). AtIAP1-specific serum also recognized proteins in Ae. aegypti, Ae. albopictus and Culex tritaeniorhynchus. Immunoblot analysis revealed that similar amounts of IAP1 were expressed in LaCrosse virus infected and uninfected Ae. albopictus cell cultures.
An affordable solution to real-time video compression (2002)

In today's multimedia market, there are several hardware and software solutions to the transmission of video over a low bit-rate channel. The decoding part is relatively simple and inexpensive to implement. However, the encoding of full-size, high-quality video in real-time remains a complex and costly matter for the compression algorithms currently in use. A real-time digital video compression system (DVCS) has been developed to provide a solution to this problem, and make real-time video applications such as videoconferencing, digital video editing and several others affordable. Three-dimensional subband coding is used in the compression process because this algorithm is most compatible with the human visual system. The DVCS described in this paper is based on a simple subband coding algorithm which can be implemented in ASIC form with less than 50,000 gates. Hence, a much simpler and less expensive encoder/decoder chip can be implemented. The DVCS supports full screen, full-motion images at 30 frames/sec. A number of other standard resolution formats such as CCIR 601, CIF and QCIF are also supported. The intrinsic scalability of subband coding makes the compression system expandable to high-definition television by simply adding an additional image detail band.
Granulocyte-macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptidesin vivo (1996)

Peptide epitopes derived from differentiation antigens of the melanocyte lineage were recently identified in human melanomas as targets for MHC-restricted cytotoxic T lymphocytes (CTL). The characterization of multiple CTL-defined antigenic determinants has opened possibilities of development of antigen-targeted vaccines. In the present study, we determined CTL reactivity against melanoma-associated peptides derived from Melan A/MART-1, tyrosinase, and gp100/Pmel17 in 3 HLA-A2+ melanoma patients. Then, we assessed the immune responses to synthetic melanoma-associated peptides injected intradermally. After 3 cycles of immunization with peptide alone, we used systemic GM-CSF as an adjuvant during the fourth cycle of immunization. Enhanced DTH reactions and CD8+ CTL responses were observed after treatment with systemic GM-CSF. Immunohistochemical characterization of DTH-constituting elements revealed infiltrates of CD4+ and CD8+ T lymphocytes and strong expression of IL-2 and gammaIFN, suggesting the activation of CD4+ ThI and CD8+ CTL by peptides presented by MHC-class-I molecules of dermal APC. Objective tumor regression was documented in all patients. We conclude that systemic GM-CSF enhances immune responses to melanoma-associated peptides and supports CTL-mediated tumor rejection in vivo.
Tissue‐specific patterns of a maize Myb transcription factor are epigenetically regulated (2001)

The maize p1 gene encodes a Myb-homologous regulator of red pigment biosynthesis. To investigate the tissue-specific regulation of the p1 gene, maize plants were transformed with constructs combining promoter and cDNA sequences of two alleles which differ in pigmentation patterns: P1-wr (white pericarp/red cob) and P1-rr (red pericarp/red cob). Surprisingly, all promoter/cDNA combinations produced transgenic plants with red pericarp and red cob (RR pattern), indicating that the P1-wr promoter and encoded protein can function in pericarp. Some of the RR patterned transgenic plants produced progeny plants with white pericarp and red cob (WR pattern), and this switch in tissue-specificity correlated with increased transgene methylation. A similar inverse correlation between pericarp pigmentation and DNA methylation was observed for certain natural p1 alleles, which have a gene structure characteristic of standard P1-wr alleles, but which confer red pericarp pigmentation and are consistently less methylated than standard P1-wr alleles. Although we cannot rule out the possible existence of tissue-specific regulatory elements within the p1 non-coding sequences or flanking regions, the data from transgenic and natural alleles suggest that the tissue-specific pigmentation pattern characteristic of the P1-wr phenotype is epigenetically controlled.
Gaining electricity from in situ oxidation of hydrogen produced by fermentative cellulose degradation (2005)

For the first time, it is shown that an insoluble complex carbohydrate like cellulose can be used for electricity generation in a microbial fuel cell. The concept represents a first step to the utilization of macromolecular biomass components for microbial electricity generation.
Progress in drug therapy of advanced non-small cell lung cancer (2011)

Incidence of lung cancer has an increasing trend year by year,the most common malignancy in clinical practice.Chemotherapy for the advanced non-small cell lung cancer is the main treatment.The efficacy of conventional chemotherapy is limited,and 5-year survival rate is still less than 15%.Currently,the target therapy and multidisciplinary treatment represent the new treatment;enrich means of medical treatment for advanced lung cancer.This paper reviews the latest progress of the current drug treatment of lung cancer and future development trends.
IL-15 Superagonist–Mediated Immunotoxicity: Role of NK Cells and IFN-γ (2015)

IL-15 is currently undergoing clinical trials to assess its efficacy for treatment of advanced cancers. The combination of IL-15 with soluble IL-15Rα generates a complex termed IL-15 superagonist (IL-15 SA) that possesses greater biological activity than IL-15 alone. IL-15 SA is considered an attractive antitumor and antiviral agent because of its ability to selectively expand NK and memory CD8(+) T (mCD8(+) T) lymphocytes. However, the adverse consequences of IL-15 SA treatment have not been defined. In this study, the effect of IL-15 SA on physiologic and immunologic functions of mice was evaluated. IL-15 SA caused dose- and time-dependent hypothermia, weight loss, liver injury, and mortality. NK (especially the proinflammatory NK subset), NKT, and mCD8(+) T cells were preferentially expanded in spleen and liver upon IL-15 SA treatment. IL-15 SA caused NK cell activation as indicated by increased CD69 expression and IFN-γ, perforin, and granzyme B production, whereas NKT and mCD8(+) T cells showed minimal, if any, activation. Cell depletion and adoptive transfer studies showed that the systemic toxicity of IL-15 SA was mediated by hyperproliferation of activated NK cells. Production of the proinflammatory cytokine IFN-γ, but not TNF-α or perforin, was essential to IL-15 SA-induced immunotoxicity. The toxicity and immunological alterations shown in this study are comparable to those reported in recent clinical trials of IL-15 in patients with refractory cancers and advance current knowledge by providing mechanistic insights into IL-15 SA-mediated immunotoxicity.
InP digital optical switch: key element for guided-wave photonic switching (1993)

The InP digital optical switch presented is compared with other types of switch. In addition to reverse- and forward-bias operation, its push-pull mode of operation is demonstrated for the first time, as well as its high-speed behaviour. The high potential of the digital optical switch and switching matrix fabrication are described. The results show that the InP-based digital optical switch has to be considered as a key element for guided-wave photonic switching.
The Nucleation with SnCl[sub 2]-PdCl[sub 2] Solutions of Glass Before Electroless Plating (1973)

It has been generally accepted that metallic palladium nuclei are formed by the nucleation procedure of nonconducting substrates with stannous chloride and palladium chloride solutions. However, results of experiments on glass using radioactive tracers and ellipsometry have shown that no metallic palladium is present after the nucleation procedure. The results indicate that presumably a tin‐palladium complex, containing one palladium atom per two tin atoms is formed and that this initiates the nickel‐phosphorus deposition from a suitable electroless plating solution.
Pharmacokinetic and Pharmacodynamic Analysis of Circulating Biomarkers of Anti-NRP1, a Novel Antiangiogenesis Agent, in Two Phase I Trials in Patients with Advanced Solid Tumors (2012)

These data show that MNRP1685A inhibits the VEGF pathway in humans as assessed by an increase in plasma PlGF. MNRP1685A seems to enhance bevacizumab-mediated VEGF pathway blockade, as showed by an increase in the magnitude of PlGF elevation when combined with bevacizumab. PK/PD analysis of biomarkers in the phase I population allowed identification of doses at which apparent maximal pathway modulation was observed.