gebhart/patrepeval huggingface dataset:
Neurofilament-M Interacts with the D1Dopamine Receptor to Regulate Cell Surface Expression and Desensitization (2002)

We used the yeast two-hybrid assay to identify novel proteins that interact with the D(1) dopamine receptor. The third cytoplasmic loop (residues 217-273) of the rat D(1) receptor was used as bait to identify clones encoding interacting proteins from a rat brain cDNA library. This identified two clones encoding the C terminus of rat neurofilament-M (NF-M) (residues 782-846). The NF-M clone did not interact with the third cytoplasmic loops of the rat D(2), D(3), or D(4) receptors, but showed weak interaction with that of the D(5) receptor. Coexpression of full-length NF-M with the D(1) receptor in HEK-293 cells resulted in >50% reduction of receptor binding accompanied by a reduction in D(1) receptor-mediated cAMP accumulation. NF-M had no effect on the expression of other dopamine receptor subtypes. Using a D(1) receptor-green fluorescent protein chimera and confocal fluorescence microscopy, we found that NF-M reduced D(1) receptor expression at the cell surface and promoted accumulation of the receptor in the cytosol. Interestingly, the D(1) receptors that were expressed at the cell surface in the presence of NF-M were resistant to agonist-induced desensitization. Cellular colocalization of NF-M and the D(1) receptor in the rat brain was examined by epifluorescence microscopy. These experiments showed that approximately 50% of medium-sized striatal neurons expressed both proteins. Colocalization was also observed in pyramidal cells and interneurons within the frontal cortex. Similar immunohistochemical analyses using NF-M-deficient mice showed decrements in D(1) receptor expression compared with control mice. These results suggest that NF-M interacts with the D(1) receptor in vivo and may modify its expression and regulation.
Magnesium depletion and pathogenesis of Alzheimer's disease. (1990)

Mg depletion, particularly in the hippocampus, appears to represent an important pathogenic factor in Alzheimer's disease. It is associated with high aluminium incorporation into brain neurones. This type of Mg deficit cannot respond to mere Mg supplementation, but requires correction of the dysregulation inducing this Mg depletion. Further research should seek to control the alterations of albumin, which may induce this brain Mg depletion.
Attentive Tasks: Process-Driven Document Analysis for Multichannel Documents (2012)

The increasing amount of email data has led many companies to new challenges with their employees now having to deal with information overload while managing multiple communication channels at the same time, e.g., email, mail, and phone. Moreover, emails can contain attachments, i.e., files with additional information. Most existing approaches for reducing email processing time require significant domain specific customization efforts to achieve good performance and lack attachment handling. We aim at providing a more domain independent approach by integrating the process context and using the information expectations of a process to guide the document analysis (DA) schedule for emails and their attachments. We rely on the concepts of Attentive Tasks (ATs) and Specialist Board (SB). ATs are templates that describe all relevant and expected information about a process currently waiting for input. The SB provides a machine readable description of DA methods, so-called specialists, that extract all relevant information for further processes. We present our approach and demonstrate the benefits for a domain specific application, i.e., a financial institution.
Receptor dimerization is not a factor in the signalling activity of a transforming variant epidermal growth factor receptor (EGFRvIII) (1997)

The type-III deletion variant of the epidermal growth factor receptor (EGFRvIII) is frequently found in glioblastomas and other malignant human tumours. Although EGFRvIII confers ligand-independent oncogenic transformation of cell lines, the mechanism by which it promotes aberrant cellular proliferation is unknown. Using cell lines expressing comparable numbers of either wild-type receptor (EGFRwt) or EGFRvIII, we compared several parameters of receptor activation: dimerization, tyrosine phosphorylation and activation of intracellular signalling proteins. Like activated EGFRwt, EGFRvIII was phosphorylated and bound constitutively to the Shc adapter protein. Indeed, EGFRvIII-associated Shc had a higher phosphotyrosine content than Shc associated with stimulated EGFRwt. EGFRwt dimerized in response to either EGF or transforming growth factor alpha. Higher cross-linker concentrations and incubation at higher temperatures (37 degrees C) allowed detection of EGFRwt dimers even in the absence of exogenous ligand. In contrast, EGFRvIII failed to dimerize under any conditions studied. Moreover, neither mitogen-activated protein kinase nor phospholipase Cgamma were phosphorylated in EGFRvIII-expressing cells. We conclude that the deletion of 267 amino acids from the 621-amino-acid N-terminal domain of EGFR does not result simply in a constitutively activated receptor, but alters the spectrum of signalling cascades utilized. Furthermore the ligand-independent transforming activity of EGFRvIII is independent of receptor dimerization.
Canonical/ -Catenin Wnt Pathway Activation Improves Retinal Pigmented Epithelium Derivation From Human Embryonic Stem Cells (2015)

Our findings demonstrated the importance of canonical/β-catenin Wnt signaling in RPE differentiation and showed that manipulating the pathway significantly improves RPE derivation from hESC.
A Folksonomy-Based Model of Web Services for Discovery and Automatic Composition (2008)

In this paper, we propose a novel way of modeling web services using folksonomies. The key advantage of our model is that it allows a large number of users to participate, easily, in annotating services with tags. This is in contrast to more expressive, logic based models of services, such as Semantic Web Service models, which require significant expertise for annotation and maintenance. Our folksonomy-based model allows associating semantic constraints on the input and output messages of web service operations using tags obtained from a folksonomy. We show how the model can be used for discovery and composition of services. We also describe a planner that uses this model to compose services and create workflows, automatically. We present performance results for the planner and our experiences in using this model in a sample real-world domain.
The immunotherapy of lung cancer (2015)

Lung cancer is characterized by high malignancy and the majority of patients are diagnosed at the advanced or late stage. Chemoradiotherapy has insufficient effect on this malignant tumor. At present the immune therapy has become a new choice for lung cancer treatment. Ipilimumab, antibody to programmed death-1, immune cells, cytokines, melanoma-associated antigen A3 vaccine, liposomal BLP25, belagenpumatucel-L and polypeptide vaccine have been proved effective for lung cancer through various clinical trials. Futhermore, most of them have been moved forward to phase Ⅲ clinical trials in order to get more strong evidence to support the immunotherapy incorporated into the multidisciplinary treatment of lung cancer.


Key words: 
Lung neoplasms; Immunity, passive; Antibody, monoclonal
Single Delivery of High-Diversity Fecal Microbiota Preparation by Colonoscopy Is Safe and Effective in Increasing Microbial Diversity in Active Ulcerative Colitis (2017)

High-diversity, 2-donor FMP delivery by colonoscopy seems safe and effective in increasing fecal microbial diversity in patients with active ulcerative colitis. Donor composition correlated with clinical response and further characterization of immunological parameters may provide insight into factors influencing clinical outcome.
Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression (2018)

Under steady-state conditions, bone marrow-derived immature myeloid cells (IMC) differentiate into granulocytes, macrophages and dendritic cells (DCs). This differentiation is impaired under chronic inflammatory conditions, which are typical for tumour progression, leading to the accumulation of IMCs. These cells are capable of inducing strong immunosuppressive effects through the expression of various cytokines and immune regulatory molecules, inhibition of lymphocyte homing, stimulation of other immunosuppressive cells, depletion of metabolites critical for T cell functions, expression of ectoenzymes regulating adenosine metabolism, and the production of reactive species. IMCs are therefore designated as myeloid-derived suppressor cells (MDSCs), and have been shown to accumulate in tumour-bearing mice and cancer patients. MDSCs are considered to be a strong contributor to the immunosuppressive tumour microenvironment and thus an obstacle for many cancer immunotherapies. Consequently, numerous studies are focused on the characterisation of MDSC origin and their relationship to other myeloid cell populations, their immunosuppressive capacity, and possible ways to inhibit MDSC function with different approaches being evaluated in clinical trials. This review analyses the current state of knowledge on the origin and function of MDSCs in cancer, with a special emphasis on the immunosuppressive pathways pursued by MDSCs to inhibit T cell functions, resulting in tumour progression. In addition, we describe therapeutic strategies and clinical benefits of MDSC targeting in cancer.
Bicyclams, Selective Antagonists of the Human Chemokine Receptor CXCR4, Potently Inhibit Feline Immunodeficiency Virus Replication (1999)

Bicyclams are low-molecular-weight anti-human immunodeficiency virus (HIV) agents that have been shown to act as potent and selective CXC chemokine receptor 4 (CXCR4) antagonists. Here, we demonstrate that bicyclams are potent inhibitors of feline immunodeficiency virus (FIV) replication when evaluated in Crandell feline kidney (CRFK) cells. With a series of bicyclam derivatives, 50% inhibitory concentrations (IC50s) against FIV were obtained in this cell system that were comparable to those obtained for HIV-1 IIIB replication in the human CD4(+) MT-4 T-cell line. The bicyclams were also able to block FIV replication in feline thymocytes, albeit at higher concentrations than in the CRFK cells. The prototype bicyclam AMD3100, 1-1'-[1,4-phenylene-bis(methylene)]-bis(1,4,8, 11-tetraazacyclotetradecane), was only fourfold less active in feline thymocytes (IC50, 62 ng/ml) than in CRFK cells (IC50, 14 ng/ml). AMD2763, 1,1'-propylene-bis(1,4,8, 11-tetraazacyclotetradecane), which is a less potent CXCR4 antagonist, was virtually inactive against FIV in feline thymocytes (IC50, >66.5 microgram/ml), while it was clearly active in CRFK cells (IC50, 0.9 microgram/ml). The CXC chemokine stromal-cell-derived factor 1alpha had anti-FIV activity in CRFK cells (IC50, 200 ng/ml) but not in feline thymocytes (IC50, >2.5 microgram/ml). When primary FIV isolates were evaluated for their drug susceptibility in feline thymocytes, the bicyclams AMD3100 and its Zn2+ complex, AMD3479, inhibited all six primary isolates at equal potency. The marked susceptibility of FIV to the bicyclams suggests that FIV predominantly uses feline CXCR4 for entering its target cells.
DRAMATIC IMPROVEMENTS IN VIRAL INACTIVATION WITH BROMINATED PSORALENS, NAPHTHALENES AND ANTHRACENES (1993)

Amino or polyamino derivatives of naphthalene (N-H), anthracene (A-H) and 8-alkoxypsoralen (PSR-H) were prepared along with their monobrominated analogs (N-Br, A-Br and PSR-Br). The ammonium salts of these compounds are all water soluble and bind strongly to calf thymus DNA and to lambda phage, a double-helical DNA, protein-coated virus. Binding of the sensitizer to DNA occurs, presumably by a mixture of hydrophobic, intercalative and electrostatic interactions. Relative binding constants to calf thymus DNA and to lambda phage were measured by the ethidium bromide fluorescence quenching assay. In general the brominated analogs bind more tightly to calf thymus DNA and to the virus than to the nonhalogenated analogs. It is demonstrated that the brominated aromatics are much more effective at inactivating lambda phage upon photoactivation (lambda approximately 310 or 350 nm) than are their nonbrominated analogs. At identical sensitizer concentrations (by weight) and light flux N-Br, A-Br, and PSR-Br produce 5-6 more logs of viral inactivation than their nonbrominated counterparts (N-H, A-H and PSR-H, respectively). The bromine effect may originate from light-induced electron transfer and subsequent cleavage of the C-Br bond of the sensitizer radical anion bonds to form aryl radicals. Singlet oxygen cannot be responsible for the viral inactivation because the brominated sensitizers are equally effective in the presence and absence of oxygen. Dithiothreitol does not protect lambda phage from light-induced inactivation by the brominated sensitizer thereby demonstrating that the photogenerated reactive intermediates responsible for the effect are complexed to the virus and are not generated free in solution.
The DNA sequence coding for the 5' untranslated region of herpes simplex virus type 1 ICP22 mRNA mediates a high level of gene expression (1994)

The sequence coding for the 5' untranslated region (UTR) of ICP22 mRNA of herpes simplex virus type 1 has been tested for its ability to regulate gene expression. This sequence was placed in frame with the chloramphenicol acetyltransferase (CAT) coding sequence and under the control of the simian virus 40 early promoter-enhancer. Under these conditions, the sequence coding for the 5'UTR led to an increase of about 13-fold in CAT activity, measured during transient expression. The use of mutants with progressive deletions within the sequence coding for the 5'UTR allowed localization of the sequence responsible for the enhancement of gene expression to the first exon of the ICP22 gene. Precise quantification of hybrid ICP22-CAT mRNA showed that the sequence coding for the 5'UTR induced an increase in the amounts of transcripts, which resulted in a parallel increase in CAT activity. This increase in the level of hybrid ICP22-CAT mRNA is not the result of an increase in mRNA stability, nor is it due to more efficient nucleo-cytoplasmic transport of the transcripts. Moreover, the distribution of hybrid mRNA in the different ribosomal populations indicates that the 5'UTR of ICP22 mRNA does not induce a preferential recruitment of the transcripts by the translational apparatus. Taken together, these results indicate that a cis-acting element located in the sequence coding for the 5'UTR of ICP22 mRNA can mediate a high level of gene expression independently of the viral promoter and of viral trans-acting factors.
Phase-shifting masks for microlithography: automated design and mask requirements (1994)

The problem of automated design of phase-shifting masks for enhanced-resolution optical lithography is examined. We propose a computationally viable algorithm for the rapid design of phase-shifting masks for arbitrary two-dimensional patterns. Our approach is based on the use of a class of optimal coherent approximations to partially coherent imaging systems described by the Hopkins model. These approximations lead to substantial computational and analytical benefits, and, in addition, the resultant approximation error can be quite small for imaging systems with coherence factor σ ≤ 0.5. These approximate models allow us to reduce the mask-design problem to the classical phase-retrieval problem in optics. A fast iterative algorithm, closely related to the Gerchberg–Saxton algorithm, is then applied to generate (suboptimal) phase-shifting masks. Analytical results related to practical requirements for phase-shifting masks are also presented. These results address questions related to the number of discrete phase levels required for arbitrary patterns and provide some insight into alternative strategies for the use of phase-shifting masks. A number of simulated phase-shifting mask-design examples are provided to illustrate the methods and ideas presented.
Development of a LightCycler PCR Assay for Detection and Quantification ofAspergillus fumigatusDNA in Clinical Samples from Neutropenic Patients (2003)

The increasing incidence of invasive aspergillosis, a life-threatening infection in immunocompromised patients, emphasizes the need to improve the diagnostic tools for this disease. We established a LightCycler-based real-time PCR assay to detect and quantify rapidly, specifically, and sensitively Aspergillus fumigatus DNA in both bronchoalveolar lavage (BAL) and blood samples from high-risk patients. The primers and hybridization probes were derived from an A. fumigatus-specific sequence of the mitochondrial cytochrome b gene. The assay is linear in the range between 13.2 fg and 1.3 ng of A. fumigatus DNA, corresponding to 3 to 300,000 CFU per ml of BAL fluid or blood. No cross-amplification was observed with human DNA or with the DNA of fungal or bacterial pathogens. For clinical evaluation we investigated 10 BAL samples from nine neutropenic patients with malignant hematological diseases and 12 blood samples from seven neutropenic patients with malignant hematological diseases. Additionally, we tested one blood sample and one BAL sample from each of two neutropenic patients. In order to characterize the validity of the novel PCR assay, only samples that had shown positive results by a previously described sensitive and specific nested PCR assay were tested. Twelve of 12 BAL samples and 6 of 14 blood samples gave positive results by the LightCycler PCR assay. Eight of 14 blood samples gave negative results by the novel method. The LightCycler PCR-mediated quantification of the fungal burden showed 15 to 269,018 CFU per ml of BAL sample and 298 to 104,114 CFU per ml of blood sample. Twenty of 20 BAL samples and 50 of 50 blood samples from subjects without evidence of invasive pulmonary aspergillosis (IPA) were PCR negative. Compared to a previously described nested PCR assay, these preliminary data for the novel real-time PCR assay indicate a less sensitive rate of detection of IPA in high-risk patients, but the assay may be valuable for quantification of the fungal burden in individual clinical samples.
Analysis of 99 microdissected prostate carcinomas reveals a high frequency of allelic loss on chromosome 8p12-21. (1996)

To investigate the possible involvement of a tumor suppressor gene(s) on chromosome 8 in prostatic neoplasms, we performed a comprehensive loss of heterozygosity (LOH) study on 99 tumors from 97 prostate cancer patients. One of the carcinomas was a lymph node metastasis; the other 98 were primary carcinomas. Pure populations of carcinoma cells and normal epithelia were procured by tissue microdissection. Two separate tumor foci were obtained from each of two patients. Microsatellite markers from 25 loci on the short arm and one locus on the long arm of chromosome 8 were used for PCR-based LOH analysis on matched normal and tumor DNA samples. The overall LOH on 8p in this study was 85.9% (85 of 99) of carcinomas. The loss was highest at markers D8S133, D8S136, NEFL, and D8S137 (62,72, 64, and 75%, respectively), which are located at 8p12-21. Seventy-nine of 99 tumors exhibited loss in at least one of these four loci. In contrast, LOH at 8p22 was much lower: 17,18,18, and 19% at D8S549, D8S602, D8S254, and D8S261, respectively, with 25 of 99 tumors showing deletion in one or more of the four loci. All but 5 tumors with deletions in this more distal region had at least one retained locus between the 8p22 deletion and a more proximal region of loss at 8p12-21; 1 tumor had loss at 8p22 but not 8p12-21. This suggests there may be two distinct regions of loss and, therefore, two tumor suppressor genes on this chromosomal arm. The loss on 8p12-21 showed little or no correlation with grade or stage of disease.
Molecular cloning and protein structure of a human blood group Rh polypeptide. (1990)

cDNA clones encoding a human blood group Rh polypeptide were isolated from a human bone marrow cDNA library by using a polymerase chain reaction-amplified DNA fragment encoding the known common N-terminal region of the Rh proteins. The entire primary structure of the Rh polypeptide has been deduced from the nucleotide sequence of a 1384-base-pair-long cDNA clone. Translation of the open reading frame indicates that the Rh protein is composed of 417 amino acids, including the initiator methionine, which is removed in the mature protein, lacks a cleavable N-terminal sequence, and has no consensus site for potential N-glycosylation. The predicted molecular mass of the protein is 45,500, while that estimated for the Rh protein analyzed in NaDodSO4/polyacrylamide gels is in the range of 30,000-32,000. These findings suggest either that the hydrophobic Rh protein behaves abnormally on NaDodSO4 gels or that the Rh mRNA may encode a precursor protein, which is further matured by a proteolytic cleavage of the C-terminal region of the polypeptide. Hydropathy analysis and secondary structure predictions suggest the presence of 13 membrane-spanning domains, indicating that the Rh polypeptide is highly hydrophobic and deeply buried within the phospholipid bilayer. In RNA blot-hybridization (Northern) analysis, the Rh cDNA probe detects a major 1.7-kilobase and a minor 3.5-kilobase mRNA species in adult erythroblasts, fetal liver, and erythroid (K562, HEL) and megakaryocytic (MEG01) leukemic cell lines, but not in adult liver and kidney tissues or lymphoid (Jurkat) and promyelocytic (HL60) cell lines. These results suggest that the expression of the Rh gene(s) might be restricted to tissues or cell lines expressing erythroid characters.
Pituitary adenylate cyclase-activating polypeptide is an autocrine inhibitor of mitosis in cultured cortical precursor cells (1997)

During brain development, an intricate array of signals is likely to control the transition from proliferation to differentiation, particularly in the complex cerebral cortex. Although factors regulating proliferation and differentiation have been identified, little is known about mechanisms governing the exit of precursors from the cell cycle. We now report that pituitary adenylate cyclase-activating polypeptide (PACAP), a new member of the vasoactive intestinal peptide family expressed in embryonic brain, promotes this transition. In virtually pure cultures of embryonic day 13.5 (E13.5) rat cortical precursors, PACAP inhibited [3H]thymidine incorporation by 43%, decreasing the proportion of mitotic cells. Moreover, the peptide promoted morphological and biochemical differentiation; PACAP elicited a 2-fold increase in cells bearing neurites and a 30% increase in neurotrophin trkB receptor expression, indicating that PACAP induced cell cycle withdrawal and promoted neuronal differentiation. The expression of PACAP ligand and receptor in precursors raised the possibility of autocrine function. Indeed, 85% of cells exhibited PACAP immunoreactivity while 64% expressed type I receptor, which, in turn, mediated cAMP activation and phosphorylated cAMP response element binding protein nuclear signaling. Furthermore, treatment with the PACAP antagonist or neutralizing antibody increased DNA synthesis and proliferation, which is consistent with interruption of ongoing mitotic inhibition mediated by endogenous PACAP. Our observations suggest that cortical precursors produce PACAP as an autocrine signal to elicit cell cycle withdrawal, inducing the transition from proliferation to neuronal differentiation.