gebhart/patrepeval huggingface dataset:
Glycosidase inhibitors: inhibitors of N‐linked oligosaccharide processing (1991)

The biosynthesis of the various types of N-linked oligosaccharide structures involves two series of reactions: 1) the formation of the lipid-linked saccharide precursor, Glc3Man9(GlcNAc)2-pyrophosphoryl-dolichol, by the stepwise addition of GlcNAc, mannose and glucose to dolichyl-P, and 2) the removal of glucose and mannose by membrane-bound glycosidases and the addition of GlcNAc, galactose, sialic acid, and fucose by Golgi-localized glycosyltransferases to produce different complex oligosaccharide structures. For most glycoproteins, the precise role of the carbohydrate is still not known, but specific N-linked oligosaccharide structures are key players in targeting of lysosomal hydrolases to the lysosomes, in the clearance of asialoglycoproteins from the serum, and in some cases of cell:cell adhesion. Furthermore, many glycoproteins have more than one N-linked oligosaccharide, and these oligosaccharides on the same protein frequently have different structures. Thus, one oligosaccharide may be of the high-mannose type whereas another may be a complex chain. One approach to determining the role of specific structures in glycoprotein function is to use inhibitors that block the modification reactions at different steps, causing the cell to produce glycoproteins with altered carbohydrate structures. The function of these glycoproteins can then be assessed. A number of alkaloid-like compounds have been identified that are specific inhibitors of the glucosidases and mannosidases involved in glycoprotein processing. These compounds cause the formation of glycoproteins with glucose-containing high mannose structures, or various high-mannose or hybrid chains, depending on the site of inhibition. These inhibitors have also been useful for studying the processing pathway and for comparing processing enzymes from different organisms.
Plasma Concentrations of Cystatin C in Patients with Coronary Heart Disease and Risk for Secondary Cardiovascular Events: More than Simply a Marker of Glomerular Filtration Rate (2004)

These data support the possibly important prognostic value of cystatin C among patients with known CHD and suggest that it may be a useful clinical marker providing complementary information to established risk determinants.
Phase I study with an autologous tumor cell vaccine for locally advanced or metastatic prostate cancer. (2007)

To attempt the isolation and primary culture of prostate tumor cells, to use the cultured cells for active immunotherapy, and to evaluate the safety and efficacy in a Phase I clinical trial.Tumor fragments were collected from 50 patients with prostate-specific antigen (PSA) > or = 10 ng/mL, < or = cT2 PCa who underwent radical retropubic prostatectomy (RRP) and 6 patients with metastatic PCa who underwent transurethral resection of the prostate (TURP). Cultured tumor cells were incubated with IFN-fi, irradiated, and cryopreserved. Seven vaccine inoculations were performed into > or = pT3 and/or N+ patients, and M+ patients, with the first two doses admixed with Bacille Calmette-Guerin (BCG). Follow-up was performed with measurement of delayed-type hypersensitivity (DTH) reactions, PSA and hemato-chemical tests, and bone scans.No cell culture was obtained in the TURP group. Cell culture and vaccine production were obtained in 37 cases (74%) in the RRP group. Eleven > or = pT3 and/or N+ patients were vaccinated. Toxicity was generally limited to the inoculation sites. DTH reactions > or = 10 mm were observed in 2 patients and > or = 5 mm in 6 patients. Two patients had a decrease in PSA levels after vaccine administration.The autologous cell vaccine is safe and seems to induce a positive immune cellular response. Primary cell culture and vaccine production can be obtained for most RRP patients, but not for TURP patients using our method. There seems to be some influence of the vaccine in PSA evolution after RRP.
Production of erythrocytes from directly isolated or Delta1 Notch ligand expanded CD34+ hematopoietic progenitor cells: process characterization, monitoring and implications for manufacture (2013)

Erythroid differentiation chronology is partly determined by the heterogeneous CD34(+) progenitor compartment with implications for input control; Delta1 ligand-mediated progenitor culture can alter differentiation profile with control benefits for engineering production strategy. Differentiation correlated changes in cytokine response, markers and metabolic state will enable scientifically designed monitoring and timing of manufacturing process steps.
Identification of an Estrogen Response Element Activated by Metabolites of 17β-Estradiol and Raloxifene (1996)

17beta-Estradiol modulates gene transcription through the estrogen receptor and the estrogen response element in DNA. The human transforming growth factor-beta3 gene was shown to be activated by the estrogen receptor in the presence of estrogen metabolites or estrogen antagonists. Activation was mediated by a polypurine sequence, termed the raloxifene response element, and did not require the DNA binding domain of the estrogen receptor. Interaction of the estrogen receptor with the raloxifene response element appears to require a cellular adapter protein. The observation that individual estrogens modulate multiple DNA response elements may explain the tissue-selective estrogen agonist or antagonist activity of compounds such as raloxifene.
International Meeting on Cancer Vaccines (2004)

The major aims of the International Meeting on Cancer Vaccines were to review the state-of-the-art research on cancer vaccines, to compare different experimental approaches of therapeutic vaccination and to discuss critical issues and perspectives. The results from recent clinical trials in patients treated with different types of cancer vaccines were presented. Reasons for the limited response and possible modalities for enhancing efficacy of therapeutic vaccines were subjects of major discussion. A consensus was achieved on the need of combining cancer vaccines with other anticancer treatments. Of note, evidence stemming from studies in animal models pointed out new rationales for a selective combination of cancer vaccines with chemotherapy. In addition, some main presentations focused on new adjuvants (CpG oligonucleotides) and on the role of cytokines (i.e., type I IFN, interleukin 12, and interleukin 15) in promoting an antitumor immune response to vaccines. A considerable attention was given to regulatory T cells and to strategies for suppressing their function, thus enhancing vaccine efficacy. An entire session was devoted to the use of dendritic cells for the development of cancer vaccines. The results of clinical studies and the advantages of using new modalities for preparing dendritic cell-based vaccines were discussed.
A Short Introduction to Boosting (1999)

Boosting is a general method for improving the accuracy of any given learning algorithm. This short overview paper introduces the boosting algorithm AdaBoost, and explains the underlying theory of boosting, including an explanation of why boosting often does not suffer from overfitting as well as boosting&amp;apos;s relationship to support-vector machines. Some examples of recent applications of boosting are also described.
Multibank memory optimization for parallel data access in multiple data arrays (2016)

To realize high throughput out of a relatively low bandwidth, memory partitioning algorithms have been proposed to separate data arrays into multiple memory banks, from which multiple data can be accessed in parallel. However, previous partitioning schemes only considered the case of single-pattern and single-array. In this paper, we propose an efficient two-step memory partitioning strategy for multi-pattern access in multiple multidimensional arrays. First, a fast, low complexity and low difference-based data splitting algorithm provides a multi-bank solution for multiple patterns access. Then an area-efficiency bank merging algorithm reduce the area overhead caused by partitioning. Experimental results show that our memory splitting algorithm saves up to 83.0% in searching time finding a multi-bank solution, compared to the state-of-the-art approach and the storage overhead can be reduced by 34.5%. Meanwhile the area overheads are saved up to 18.86% and the whole partition time are saved up to 45.6% through our entire algorithm.
A Three-component Dicamba O-Demethylase from Pseudomonas maltophilia, Strain DI-6 (2005)

Dicamba O-demethylase is a multicomponent enzyme from Pseudomonas maltophilia, strain DI-6, that catalyzes the conversion of the widely used herbicide dicamba (2-methoxy-3,6-dichlorobenzoic acid) to DCSA (3,6-dichlorosalicylic acid). We recently described the biochemical characteristics of the three components of this enzyme (i.e. reductase(DIC), ferredoxin(DIC), and oxygenase(DIC)) and classified the oxygenase component of dicamba O-demethylase as a member of the Rieske non-heme iron family of oxygenases. In the current study, we used N-terminal and internal amino acid sequence information from the purified proteins to clone the genes that encode dicamba O-demethylase. Two reductase genes (ddmA1 and ddmA2) with predicted amino acid sequences of 408 and 409 residues were identified. The open reading frames encode 43.7- and 43.9-kDa proteins that are 99.3% identical to each other and homologous to members of the FAD-dependent pyridine nucleotide reductase family. The ferredoxin coding sequence (ddmB) specifies an 11.4-kDa protein composed of 105 residues with similarity to the adrenodoxin family of [2Fe-2S] bacterial ferredoxins. The oxygenase gene (ddmC) encodes a 37.3-kDa protein composed of 339 amino acids that is homologous to members of the Phthalate family of Rieske non-heme iron oxygenases that function as monooxygenases. Southern analysis localized the oxygenase gene to a megaplasmid in cells of P. maltophilia. Mixtures of the three highly purified recombinant dicamba O-demethylase components overexpressed in Escherichia coli converted dicamba to DCSA with an efficiency similar to that of the native enzyme, suggesting that all of the components required for optimal enzymatic activity have been identified. Computer modeling suggests that oxygenase(DIC) has strong similarities with the core alphasubunits of naphthalene 1,2-dioxygenase. Nonetheless, the present studies point to dicamba O-demethylase as an enzyme system with its own unique combination of characteristics.
The human gene encoding acetylcholinesterase is located on the long arm of chromosome 7. (1992)

Acetylcholinesterase (AChE) is a secreted enzyme essential for regulating cholinergic neurotransmission at neuronal and neuromuscular synapses. In view of the altered expression of AChE in some central neurological and neuromuscular disorders with a probable genetic basis, we have identified the chromosomal location of the gene encoding AChE. Chromosomal in situ suppression hybridization analysis revealed a single gene to be at 7q22, a result which was confirmed by PCR analysis of genomic DNA from a human/hamster somatic cell hybrid containing a single human chromosome 7. The AChE gene thus maps to the same region in which frequent nonrandom chromosome 7 deletions occur in leukemias of myeloid cell precursors known to express the enzyme during normal differentiation.
Downregulation and aberrant promoter methylation of p16INK4A: A possible novel heritable susceptibility marker to retinoblastoma (2009)

RB loss has long been recognized as the causative genetic alteration underlying retinoblastoma but it is increasingly evident that other alterations are required for the tumor to develop. Therefore, we set out to identify additional inheritable susceptibility markers and new potential preventive and therapeutic targets for retinoblastoma. We focused on the p16INK4A tumor suppressor gene because of its possible role in retinoblastoma pathogenesis and its involvement in predisposition to familial cancer. p16INK4A expression was analyzed in tumor samples from retinoblastoma patients by immunohistochemistry and in peripheral blood cells from both patients and their parents by real-time quantitative reverse transcription-PCR (qRT-PCR). Since promoter methylation is a common mechanism regulating p16INK4A expression, the methylation status of its promoter was also analyzed in blood samples from patients and their parents by methylation-specific PCR. A downregulation of p16INK4A was observed in 55% of retinoblastoma patients. Interestingly, in 56% of the cases showing p16INK4A downregulation at least one of the patients' parents bore the same alteration in blood cells. Analysis of p16INK4A promoter methylation showed hypermethylation in most patients with p16INK4A downregulation and in the parents with the same alteration in p16INK4A expression. The finding that p16INK4A was downregulated both in patients and their parents suggests that this alteration could be a novel inheritable susceptibility marker to retinoblastoma. The observation that p16INK4A downregulation seems to be due to its promoter hypermethylation opens the way for the development of new preventive and therapeutic strategies using demethylating agents.
Combination chemoimmunotherapy in a pancreatic cancer model. (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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With a 5-year survival rate of only 4%, pancreatic cancer is one of the most aggressive malignancies known. Despite intensive research efforts, the current front-line therapy for pancreatic cancer remains limited to gemcitabine and 5-fluorouracil. The minimal response rate of pancreatic patients to chemotherapeutic agents has underscored the need to develop alternative approaches for intervention of this disease. Preclinical and clinical studies have indicated that interferons have the ability to upregulate tumor associated antigens, major histocompatibility complex (MHC) surface molecules, and other molecules that may make tumor cells more susceptible to vaccine mediated T cell attack. The present study was designed to assess the role that recombinant interferon-alpha (IFN-α) may play in suppressing growth and/or altering cell surface antigen expression in an experimental murine pancreatic tumor model. The murine pancreatic tumor cell line, Panc02.CEA, shares many characteristics with human pancreatic tumors: 1) low cell surface expression ( 95%) of the human tumor-associated antigen, carcinoembryonic antigen (CEA). Despite the inability of IFN-α to effectively inhibit Panc02 cell growth in-vitro, titrating doses of IFN-α (0-500 IU/mL, 48 hrs.) upregulated MHC (H-2b) expression on the Panc02 cell surface in a dose-dependent manner. In a 2 × 2 factorial designed study, CEA transgenic mice with established subcutaneous Panc02.CEA tumors were treated as follows: 1) untreated (controls), 2) IFN-α (50K IU/mouse/injection, s.q., 3X/week), 3) gemcitabine (150 mg/kg/mouse, i.p., 2X/week), or 4) the combination of IFN-α and gemcitabine. Relative to the control mice in group 1, tumor growth was inhibited in groups 2, 3, and 4 by 46%, 41%, and 61%, respectively, following two weeks of treatment. A higher percentage of CD3+ and, specifically CD3+CD8+, tumor infiltrating lymphocytes was observed in tumor-bearing mice treated with IFN-α but not the combination of IFN-α and gemcitabine. Additionally, a greater number of CD3+ T cells were found in the draining lymph nodes (inguinal, sacral, and popliteal) of tumor-bearing mice treated with IFN-α. The tumor growth inhibition observed with IFN-α, in-vivo, cannot be explained by its direct effect on tumor growth in-vitro, suggesting that host immune anti-tumor responses could be induced by virtue of the upregulation of MHC class I expression on the Panc02 cell surface of IFN-α treated mice. We hypothesize that upregulation of MHC class I expression enhances the sensitivity of tumor cells to immune-based interventions and we will test this hypothesis in future studies in which IFN-α will be combined with antigen-specific cancer vaccines. These results may provide the framework for future preclinical studies of an immune-based approach to pancreatic cancer treatment.
SR 121787, a New Orally Active Fibrinogen Receptor Antagonist (1998)

The aim of this study was to describe the pharmacological properties of SR 121787, a new antiaggregating drug which is metabolized in vivo into SR 121566, a potent non-peptide antagonist of Gp IIb/IIIa. In vitro, SR 121566 antagonized the binding of [125I]-fibrinogen (IC50 = 19.8+/-6.3 nM) and of [125I]-L-692,884, an RGD-containing peptide (IC50 = 291+/-96 nM) to activated human platelets. SR 121566 inhibited the aggregation of human platelets induced by ADP, collagen, thrombin, arachidonic acid and PAF at concentrations lower than 0.1 microM. Adhesion of human platelets to adhesive proteins was inhibited by SR 121566 (IC50 = 40.3+/-2.5 nM) only when Gp IIb/IIIa and fibrinogen were involved. No effect was found with regard to other adhesive proteins and/or other integrins. SR 121787 demonstrated a potent and sustained antiaggregating effect when administered intravenously to baboons at a dose 50 microg/kg, and eight hours after the administration of 100 microg/kg, ADP-induced aggregation was still strongly inhibited (more than 80%). A single oral administration of 2 mg/kg of SR 121787 produced a nearly complete inhibition of platelet aggregation for up to 8 h (ED50 at 8 h = 193+/-20 microg/kg), a significant residual antiaggregating activity being still observed 24h after the administration. When administered orally to rabbits, SR 121787 exhibited a potent antiaggregating (ED50 = 2.3+/-0.3 mg/kg) and antithrombotic activity in an arterio-venous shunt thrombosis model (ED50 = 10.4+/-0.8 mg/kg). After oral and IV administration, SR 121787 was well tolerated suggesting that SR 121787, the most potent and long lasting orally active Gp IIb/IIIa antagonist described to date, is a promising antithrombotic compound.
Binding-incompetent adenovirus facilitates molecular conjugate-mediated gene transfer by the receptor-mediated endocytosis pathway. (1993)

Molecular conjugate vectors may be constructed that accomplish high efficiency gene transfer by the receptor-mediated endocytosis pathway. In order to mediate escape from lysosomal degradation, we have incorporated adenoviruses into the functional design of the conjugate. In doing so, however, we have introduced an additional ligand, which can bind to receptors on the cell surface, undermining the potential for cell specific targeting. To overcome this, we have treated the adenovirus with a monoclonal anti-fiber antibody, which renders the virus incapable of binding to its receptor. The result is a multi-functional molecular conjugate vector, which has preserved its binding specificity while at the same time being capable of preventing lysosomal degradation of endosome-internalized conjugate-DNA complexes. This finding indicates that adenoviral binding is not a prerequisite for adenoviral-mediated endosome disruption.
Blood-based biomarkers for the diagnosis and monitoring of gliomas (2018)

Monitoring patient response to treatment is challenging for most cancers, but it is particularly difficult in glioblastoma multiform, the most common and aggressive form of malignant brain tumor. These tumors exhibit a high degree of heterogeneity which may not be reflected in a biopsy. To determine if the current standard of care is effective, glioma patients are monitored using MRI or CT scans, an effective but sometimes misleading approach due to the phenomenon of pseudoprogression. As such, there is incredible need for a minimally invasive "liquid biopsy" to assist in molecularly characterizing the tumors while also aiding in the identification of true progression in glioblastoma. This review details the status and potential impact for circulating tumor cells, extracellular vesicles, ctDNA, and ctRNA, putative circulating biomarkers found in the blood in glioblastoma patients. As mutation-based therapy becomes more prevalent in gliomas, blood-based analyses may offer a non-invasive method of identifying mutations. The ability to obtain serial "liquid biopsies" will provide unique opportunities to study the evolution of tumors and mechanisms of treatment resistance and monitor for mutational changes in response to therapy.
Building a statistical machine translation system for French using the Europarl corpus (2007)

This paper describes the development of a statistical machine translation system based on the Moses decoder for the 2007 WMT shared tasks. Several different translation strategies were explored. We also use a statistical language model that is based on a continuous representation of the words in the vocabulary. By these means we expect to take better advantage of the limited amount of training data. Finally, we have investigated the usefulness of a second reference translation of the development data.
SIRT1 and AMPK in regulating mammalian senescence: A critical review and a working model (2010)

Ageing in mammals remains an unsolved mystery. Anti-ageing is a recurring topic in the history of scientific research. Lifespan extension evoked by Sir2 protein in lower organisms has attracted a large amount of interests in the last decade. This review summarizes recent evidence supporting the role of a Sir2 mammalian homologue, SIRT1 (Silent information regulator T1), in regulating ageing and cellular senescence. The various signaling networks responsible for the anti-ageing and anti-senescence activity of SIRT1 have been discussed. In particular, a counter-balancing model involving the cross-talks between SIRT1 and AMP-activated protein kinase (AMPK), another stress and energy sensor, is suggested for controlling the senescence program in mammalian cells.
A Robust CRISPR/Cas9 System for Convenient, High-Efficiency Multiplex Genome Editing in Monocot and Dicot Plants (2015)

由同时的指向的 Arabidopsis 植物多重(多达八) 一个基因家庭，在一条 biosynthetic 小径的多重基因，或在单个基因的多重地点的成员。这个系统为为基本研究和基因改进在植物学习多重基因和基因家庭的功能提供了一个万用的工具箱。
The Influences of Hinge Length and Composition on the Susceptibility of Human IgA to Cleavage by Diverse Bacterial IgA1 Proteases (2005)

The influences of IgA hinge length and composition on its susceptibility to cleavage by bacterial IgA1 proteases were examined using a panel of IgA hinge mutants. The IgA1 proteases of Streptococcus pneumoniae, Streptococcus sanguis strains SK4 and SK49, Neisseria meningitidis, Neisseria gonorrhoeae, and Haemophilus influenzae cleaved IgA2-IgA1 half hinge, an Ab featuring half of the IgA1 hinge incorporated into the equivalent site in IgA1 protease-resistant IgA2, whereas those of Streptococcus mitis, Streptococcus oralis, and S. sanguis strain SK1 did not. Hinge length reduction by removal of two of the four C-terminal proline residues rendered IgA2-IgA1 half hinge resistant to all streptococcal IgA1 metalloproteinases but it remained sensitive to cleavage by the serine-type IgA1 proteases of Neisseria and Haemophilus spp. The four C-terminal proline residues could be substituted by alanine residues or transferred to the N-terminal extremity of the hinge without affect on the susceptibility of the Ab to cleavage by serine-type IgA1 proteases. However, their removal rendered the Ab resistant to cleavage by all the IgA1 proteases. We conclude that the serine-type IgA1 proteases of Neisseria and Haemophilus require the Fab and Fc regions to be separated by at least ten (or in the case of N. gonorrhoeae type I protease, nine) amino acids between Val(222) and Cys(241) (IgA1 numbering) for efficient access and cleavage. By contrast, the streptococcal IgA1 metalloproteinases require 12 or more appropriate amino acids between the Fab and Fc to maintain a minimum critical distance between the scissile bond and the start of the Fc.
Distributed shared memory: concepts and systems (1996)

In surveying current approaches to distributed shared memory computing, the authors find that the reduced cost of parallel software development will help make the DSM paradigm a viable solution to large scale, high performance computing.