gebhart/patrepeval huggingface dataset:
Vaccination with a Mixed Vaccine of Autogenous and Allogeneic Breast Cancer Cells and Tumor Associated Antigens CA15-3, CEA and CA125 - Results in Immune and Clinical Responses in Breast Cancer Patients (2000)

In breast cancer there is often overexpression of the breast cancer antigen CA15-3, the carcinoembryonic antigen (CEA) and the ovarian cancer antigen CA125, which makes them potential target antigens for immunotherapy. In this study, we used a multi-antigen vaccine, which included the following antigens: autologous breast cancer cells (AUTOC), allogeneic breast cancer MCF-7 cells (ALLOC), and the tumor associated antigens CA15-3, CEA and CA125, plus low doses of granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin 2 (IL-2). Forty-two breast cancer patients received weekly subcutaneous vaccination at the 1st, 2nd, 3rd, 7th, 11th and 15th weeks. Their lymphocyte proliferative responses to AUTOC, ALLOC, CA15-3, CEA and CA125 were tested in lymphocyte blastogenesis assays (LBA) before and after vaccination. The disease stage and serum CA15-3, CEA and CA125 concentrations were also determined pre- and post-vaccination. We found that the vaccine was safe, and the only major side effects were swelling at the site of injection, muscle pain, and weakness or fatigue. The vaccine induced a significant increase in post-vaccination lymphocyte proliferative responses to AUTOC, CA15-3, CEA and CA125 but not ALLOC, compared to pre-vaccination (p < 0.05, p < 0.01, p < 0.05, p < 0.01 and p > 0.05, respectively, a paired t Test). Computed tomography (CT), ultrasound or bone scan showed evidence of disease improvement in 2 (12%) patients after vaccination. Hepatic metastases were reduced in size and number and some actually disappeared one patient. Metastatic disease in the L5 vertebra and the skull decreased in size and some osteolytic sites completely healed in a second patient. In addition, 7 patients (44%) had stable disease and 7 patients (44%) had disease progression. We did not find vaccination significantly reduced serum tumor markers CA15-3, CEA and CA125 of these breast cancer patients. These results suggest that the vaccine mixture of autologous and allogeneic breast cancer cells and tumor associated antigens plus GM-CSF and IL-2 can be administered safely to breast cancer patients and there is evidence for improved immunity and clinical efficacy.
Photogeneration of Amines from α-Keto Carbamates:  Photochemical Studies (1996)

We investigate the design of new photoprecursors of organic bases and the steric and electronic factors that control their photocleavage to give free amines. The design strategy involves the protection of an amine with novel [(benzoinyl)oxy]carbonyl groups and substituted analogs. The resulting masked amines owe their photosensitivity to the rich photochemistry of the benzoinyl chromophore. The photochemistry of this chromophore allows for the clean photogeneration of free amine upon irradiation with UV light below 400 nm in both the solid state and in solution. The structure of the benzoinyl chromophore was varied to determine the optimal chromophore design. By varying the chromophore design, the influence of various steric and electronic effects on the photoliberation of free amines from α-keto carbamates could be gauged. Structural modification of the aryl rings was intended to probe the electronic factors of the photocyclization. Substitution at the 2 position was varied to investigate the steric factors involved in photocyclization. The practical potential of these photoactive carbamates as organic sources of photogenerated base was demonstrated spectroscopically (UV, IR, and NMR). GC-MS product studies also proved diagnostic in identifying photogenerated base. The thermal properties of this class of base photogenerators were also determined. α-Keto carbamates derived from 3‘,5‘-dimethoxybenzoin and its substituted analogs appear particularly attractive. These carbamates undergo near quantitative photocleavage to give free amine along with the corresponding substituted benzo[b]furan photocyclization product. Preliminary evaluation of the solid state quantum yield for cyclohexylamine photogeneration from 3,3‘,5,5‘-tetramethoxybenzoin cyclohexyl carbamate ranged from 0.03 to 0.08 depending on the exposure wavelength. The variation in photoefficiency correlates with the UV absorbance of the keto chromophore indicating direct excitation of the carbonyl group is the preferred pathway for photocleavage.
NEW INSIGHTS INTO THE DIVERSITY AND FUNCTION OF NEURONAL IMMUNOGLOBULIN SUPERFAMILY MOLECULES (2003)

Immunoglobulin superfamily (IgSF) proteins are implicated in diverse steps of brain development, including neuronal migration, axon pathfinding, target recognition and synapse formation, as well as in the maintenance and function of neuronal networks in the adult. We provide here a review of recent findings on the diversity and the role of transmembrane and secreted members of IgSF proteins in the nervous system. We illustrate that the complexity of IgSF protein function results from various different levels of regulation including regulation of gene expression, protein localization, and protein interactions.
Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics (2003)

Identifying the genes responsible for human diseases requires combining information about gene position with clues about biological function. The recent availability of whole-genome data sets of RNA and protein expression provides powerful new sources of functional insight. Here we illustrate how such data sets can expedite disease-gene discovery, by using them to identify the gene causing Leigh syndrome, French-Canadian type (LSFC, Online Mendelian Inheritance in Man no. 220111), a human cytochrome c oxidase deficiency that maps to chromosome 2p16-21. Using four public RNA expression data sets, we assigned to all human genes a "score" reflecting their similarity in RNA-expression profiles to known mitochondrial genes. Using a large survey of organellar proteomics, we similarly classified human genes according to the likelihood of their protein product being associated with the mitochondrion. By intersecting this information with the relevant genomic region, we identified a single clear candidate gene, LRPPRC. Resequencing identified two mutations on two independent haplotypes, providing definitive genetic proof that LRPPRC indeed causes LSFC. LRPPRC encodes an mRNA-binding protein likely involved with mtDNA transcript processing, suggesting an additional mechanism of mitochondrial pathophysiology. Similar strategies to integrate diverse genomic information can be applied likewise to other disease pathways and will become increasingly powerful with the growing wealth of diverse, functional genomics data.
Mycotic Acid Patterns of Four Vaccine Strains of Mycobacterium bovis BCG (1983)

Thin-layer chromatography of methanolysates of four widely used vaccine strains of Mycobacterium bovis BCG showed that only one organism had the expected pattern of mycolic acid methyl esters characteristic of Mycobacterium bovis and Mycobacterium tuberculosis. The remaining three BCG strains lacked methoxy mycolic acid.
Steerable filter based multiscale registration method for JERS-1 SAR and ASTER images (2007)

It is a challenging problem to automatically register the SAR and optical satellite images in remote sensing applications. In this paper, a novel intensity based multiscale registration method using steerable Simoncelli filters is proposed to register JERS-1 SAR and ASTER images. The mutual information is used as the similarity measure, and a hybrid search technique is used to do the parameter optimization. The experimental results showed that the proposed registration scheme is competent for JERS-1 SAR and ASTER images, though the robustness of this scheme should be verified further more.
The interdisciplinary study of coordination (1994)

This survey characterizes an emerging research area, sometimes called coordination theory , that focuses on the interdisciplinary study of coordination. Research in this area uses and extends ideas about coordination from disciplines such as computer science, organization theory, operations research, economics, linguistics, and psychology. A key insight of the framework presented here is that coordination can be seen as the process of managing dependencies among activities. Further progress, therefore, should be possible by characterizing different kinds of dependencies and identifying the coordination processes that can be used to manage them. A variety of processes are analyzed from this perspective, and commonalities across disciplines are identified. Processes analyzed include those for managing shared resources, producer/consumer relationships, simultaneity constraints , and task/subtask dependencies . Section 3 summarizes ways of applying a coordination perspective in three different domains:(1) understanding the effects of information technology on human organizations and markets, (2) designing cooperative work tools, and (3) designing distributed and parallel computer systems. In the final section, elements of a research agenda in this new area are briefly outlined.
[The modifying cytogenetic effects of gossypol and its derivatives]. (1995)

The method of micronuclei account allowed to demonstrate protective effect of gossypol and its derivatives megacin and batriden of chromosomes of rat male germ cells from mutagenic effect of nitrosomethylurea (NMU) and, conversely, enhancement of clastogenic effect of another alkylating agent, fotrin. Strong antimutagenic effect of gossypol from NMU was also observed in external granular layer of young rat cerebellum. Possible mechanisms of antimutagenic action of this unique polyphenol of cotton plant are discussed.
Free zinc ions outside a narrow concentration range are toxic to a variety of cells in vitro (2010)

The zinc(II) ion has recently been implicated in a number of novel functions and pathologies in loci as diverse as the brain, retina, small intestine, prostate, heart, pancreas, and immune system. Zinc ions are a required nutrient but elevated concentrations are known to kill cells in vitro. Paradoxical observations regarding zinc's effects have appeared frequently in the literature, and often their physiological relevance is unclear. We found that for PC-12, HeLa and HT-29 cell lines as well as primary cultures of cardiac myocytes and neurons in vitro in differing media, approximately 5 nmol/L free zinc (pZn = 8.3, where pZn is defined as--log(10) [free Zn(2+)]) produced apparently healthy cells, but 20-fold higher or (in one case) lower concentrations were usually harmful as judged by multiple criteria. These results indicate that (1) the free zinc ion levels of media should be controlled with a metal ion buffer; (2) adding zinc or strong zinc ligands to an insufficiently buffered medium may lead to unpredictably low or high free zinc levels that are often harmful to cells; and (3) it is generally desirable to measure free zinc ion levels due to the presence of contaminating zinc in many biochemicals and unknown buffering capacity of many media.
Foundations of chaotic mixing (2004)

The simplest mixing problem corresponds to the mixing of a fluid with itself; this case provides a foundation on which the subject rests. The objective here is to study mixing independently of the mechanisms used to create the motion and review elements of theory focusing mostly on mathematical foundations and minimal models. The flows under consideration will be of two types: two-dimensional (2D) 'blinking flows', or three-dimensional (3D) duct flows. Given that mixing in continuous 3D duct flows depends critically on cross-sectional mixing, and that many microfluidic applications involve continuous flows, we focus on the essential aspects of mixing in 2D flows, as they provide a foundation from which to base our understanding of more complex cases. The baker's transformation is taken as the centrepiece for describing the dynamical systems framework. In particular, a hierarchy of characterizations of mixing exist, Bernoulli --> mixing --> ergodic, ordered according to the quality of mixing (the strongest first). Most importantly for the design process, we show how the so-called linked twist maps function as a minimal picture of mixing, provide a mathematical structure for understanding the type of 2D flows that arise in many micromixers already built, and give conditions guaranteeing the best quality mixing. Extensions of these concepts lead to first-principle-based designs without resorting to lengthy computations.
PKC-θ knockout mice are protected from fat-induced insulin resistance (2004)

Insulin resistance plays a primary role in the development of type 2 diabetes and may be related to alterations in fat metabolism. Recent studies have suggested that local accumulation of fat metabolites inside skeletal muscle may activate a serine kinase cascade involving protein kinase C�벿� (PKC-罐), leading to defects in insulin signaling and glucose transport in skeletal muscle. To test this hypothesis, we examined whether mice with inactivation of PKC-罐 are protected from fat-induced insulin resistance in skeletal muscle. Skeletal muscle and hepatic insulin action as assessed during hyperinsulinemic-euglycemic clamps did not differ between WT and PKC-罐 KO mice following saline infusion. A 5-hour lipid infusion decreased insulin-stimulated skeletal muscle glucose uptake in the WT mice that was associated with 40��50% decreases in insulin-stimulated tyrosine phosphorylation of insulin receptor substrate��1 (IRS-1) and IRS-1�밶ssociated PI3K activity. In contrast, PKC-罐 inactivation prevented fat-induced defects in insulin signaling and glucose transport in skeletal muscle. In conclusion, our findings demonstrate that PKC-罐 is a crucial component mediating fat-induced insulin resistance in skeletal muscle and suggest that PKC-罐 is a potential therapeutic target for the treatment of type 2 diabetes.
Association of Elevated E6 Oncoprotein With Grade of Cervical Neoplasia Using PDZ Interaction-Mediated Precipitation of E6 (2011)

There is a significant association between elevated expression of E6 oncoprotein and grade of CIN. This finding seems consistent with the role played by E6 oncoprotein in carcinogenesis.
Macromolecular crowding increases binding of DNA polymerase to DNA: an adaptive effect. (1987)

Macromolecular crowding extends the range of ionic conditions supporting high DNA polymerase reaction rates. Reactions tested were nick-translation and gap-filling by DNA polymerase I of Escherichia coli, nuclease and polymerase activities of the large fragment of that polymerase, and polymerization by the T4 DNA polymerase. For all of these reactions, high concentrations of nonspecific polymers increased enzymatic activity under otherwise inhibitory conditions resulting from relatively high ionic strength. The primary mechanism of the polymer effect seems to be to increase the binding of polymerase to DNA. We suggest that this effect on protein-DNA complexes is only one example of a general "metabolic buffering" action of crowded solutions on a variety of macromolecular interactions.
RNA splicing specificity determined by the coordinated action of RNA recognition motifs in SR proteins (1997)

Pre-mRNA splicing requires a large number of RNA-binding proteins that have one or more RNA-recognition motifs (RRMs). Among these is the SR protein family, whose members are essential for splicing and are able to commit pre-mRNAs to the splicing pathway with overlapping but distinct substrate specificity. Some SR proteins, such as SC35, contain an N-terminal RRM and a C-terminal arginine/serine-rich (RS) domain, whereas others, such as SF2/ASF, also contain a second, atypical RRM. Although both the RRMs and the RS domain of SR proteins are required for constitutive splicing, it is unclear which domain(s) defines their substrate specificity, and whether two RRMs in a given SR protein function independently or act coordinately. Using domain swaps between SC35 and SF2/ASF and a functional commitment assay, we demonstrate that individual domains are functional modules, RS domains are interchangeable, and substrate specificity is defined by the RRMs. The atypical RRM of SF2/ASF does not appear to function alone in splicing, but can either activate or suppress the splicing specificity of an N-terminal RRM. Therefore, multiple RRMs in SR proteins act coordinately to achieve a unique spectrum of pre-mRNA substrate specificity.
The family of bacterial ADP-ribosylating exotoxins (1995)

Pathogenic bacteria utilize a variety of virulence factors that contribute to the clinical manifestation of their pathogenesis. Bacterial ADP-ribosylating exotoxins (bAREs) represent one family of virulence factors that exert their toxic effects by transferring the ADP-ribose moiety of NAD onto specific eucaryotic target proteins. The observations that some bAREs ADP-ribosylate eucaryotic proteins that regulate signal transduction, like the heterotrimeric GTP-binding proteins and the low-molecular-weight GTP-binding proteins, has extended interest in bAREs beyond the bacteriology laboratory. Molecular studies have shown that bAREs possess little primary amino acid homology and have diverse quaternary structure-function organization. Underlying this apparent diversity, biochemical and crystallographic studies have shown that several bAREs have conserved active-site structures and possess a conserved glutamic acid within their active sites.
Phenylketonuria in adulthood: A collaborative study (2002)

During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty-five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status. Fourteen of the original clinics (1967-1983) participated in the Follow-up Study effort. Each clinic director was provided with a list of PKU subjects who had completed the original study (1967-1983), and was asked to evaluate as many as possible using a uniform protocol and data collection forms. In a subset of cases, magnetic resonance imaging and spectroscopy (MRI/MRS) were performed to study brain Phe concentrations. The medical evaluations revealed that the subjects who maintained a phenylalanine-restricted diet reported fewer problems than the diet discontinuers, who had an increased rate of eczema, asthma, mental disorders, headache, hyperactivity and hypoactivity. Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations. Abnormal MRI results were associated with higher brain Phe concentrations. Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability, but also in achievement test scores and increased rates of medical and behavioural problems.
Crystal Structure of an Initiation Factor Bound to the 30 S Ribosomal Subunit (2001)

Initiation of translation at the correct position on messenger RNA is essential for accurate protein synthesis. In prokaryotes, this process requires three initiation factors: IF1, IF2, and IF3. Here we report the crystal structure of a complex of IF1 and the 30S ribosomal subunit. Binding of IF1 occludes the ribosomal A site and flips out the functionally important bases A1492 and A1493 from helix 44 of 16S RNA, burying them in pockets in IF1. The binding of IF1 causes long-range changes in the conformation of H44 and leads to movement of the domains of 30S with respect to each other. The structure explains how localized changes at the ribosomal A site lead to global alterations in the conformation of the 30S subunit.
Thrombin Receptor Antagonists (1996)

Thrombin's proteolytically activated "tethered-ligand" receptor is widely expressed and mediates many of thrombin's actions on cells. Its central role in thrombin-stimulated human platelet activation and vascular smooth muscle proliferation as well as location in atherosclerotic plaques suggests receptor involvement in arterial thrombosis and atherosclerosis. Thrombin receptor antagonists, should they be effective, could be more selective than thrombin active site inhibitors in antithrombotic therapy as well as other indications. Blocking antibodies to peptides derived from the thrombin receptor have been used as prototypical thrombin receptor antagonists in vitro and have been useful in implicating this receptor in thrombin's actions on a variety of cell types. These antibodies have also shown the involvement of the receptor in arterial thrombosis models in nonhuman primates. Amino acid substitution studies have shown the structural requirements for receptor activation of peptides homologous to the new NH2-terminus. Peptide-based partial agonists and antagonists have been synthesized by NH2-terminal replacements of the serine in the receptor activating peptides. Current thrombin receptor antagonists lack potency and some are partial agonists; however, it is expected that more potent compounds will result from further investigation. The potency limitations are important to overcome before serious evaluation of their efficacy can be determined.
bcl-xl antisense treatment induces apoptosis in breast carcinoma cells (2000)

Upregulated expression of bcl-xL is involved in the initiation and progression of breast cancer by inhibiting tumor cell apoptosis. Here we describe the use of the 2;-O-methoxy-ethoxy antisense oligonucleotide 4259 targeting nucleotides 687-706 of the bcl-xL mRNA, a sequence that does not occur in the pro-apoptotic bcl-xS transcript, to restore apoptosis in estrogen-dependent and independent breast carcinoma cells. The antisense effect of oligonucleotide 4259 was examined on the mRNA and protein level using real-time PCR and Western blot analysis, respectively, and the induction of cell death was investigated in viability and apoptosis assays. Treatment of MCF7 cells with oligonucleotide 4259 at a concentration of 600 nM for 20 hr decreased bcl-xL mRNA and protein levels by more than 80% and 50%, respectively. This resulted in the induction of apoptosis characterized by mitochondrial cytochrome c release, decrease of mitochondrial transmembrane potential, and the appearance of condensed nuclei in approximately 40% of cells. Moreover, oligonucleotide 4259 efficiently downregulated bcl-xL expression and decreased cell growth in the breast carcinoma cell lines T-47D, ZR-75-1, and MDA-MB-231. Our data emphasize the importance of bcl-xL as a survival factor for breast carcinoma cells and suggest that oligonucleotide 4259 deserves further investigations for use in breast cancer therapy.