gebhart/patrepeval huggingface dataset:
Biologically Active Compounds in Seaweed Extracts - the Prospects for the Application (2012)

The paper covers the latest developments in research on the utilitarian properties of algal extracts. Their appli- cation as the components of pharmaceuticals, feeds for animals and fertilizers was discussed. The classes of various bio- logically active compounds were characterized in terms of their role and the mechanism of action in an organism of hu- man, animal and plant. Recently, many papers have been published which discuss the methods of manufacture and the composition of algal ex- tracts. The general conclusion is that the composition of extracts strongly depends on the raw material (geographical loca- tion of harvested algae and algal species) as well as on the extraction method. The biologically active compounds which are transferred from the biomass of algae to the liquid phase include polysaccharides, proteins, polyunsaturated fatty ac- ids, pigments, polyphenols, minerals, plant growth hormones and other. They have well documented beneficial effect on humans, animals and plants, mainly by protection of an organism from biotic and abiotic stress (antibacterial activity, scavenging of free radicals, host defense activity etc.) and can be valuable components of pharmaceuticals, feed additives and fertilizers.
A Foundation for Multi-dimensional Databases (1997)

We present a multi-dimensional database model, which we believe can serve as a conceptual model for On-Line Analytical Processing (OLAP)-based applications. Apart from providing the functionalities necessary for OLAP-based applications, the main feature of the model we propose is a clear separation between structural aspects and the contents. This separation of concerns allows us to define data manipulation languages in a reasonably simple, transparent way. In particular, we show that the data cube operator can be expressed easily. Concretely, we define an algebra and a calculus and show them to be equivalent. We conclude by comparing our approach to related work. The conceptual multi-dimensional database model developed here is orthogonal to its implementation, which is not a subject of the present paper. 1 Introduction Currently, there is significant interest in multidimensional database systems for developing business analysis and decision support applications. Codd proposed the c...
Salt-inducible Kinase Represses cAMP-dependent Protein Kinase-mediated Activation of Human Cholesterol Side Chain Cleavage Cytochrome P450 Promoter through the CREB Basic Leucine Zipper Domain (2002)

Salt-inducible kinase (SIK), one of the serine/threonine protein kinases, was transiently expressed in Y1 cells during the early phase of the ACTH/cAMP-dependent protein kinase (PKA)-mediated signal transduction. The overexpression of SIK(N), the SIK's N-terminal kinase domain, repressed the expression of the side chain cleavage cytochrome P450 (CYP11A) gene. To elucidate the mechanism of the repression by SIK, several CYP11A promoter constructs were tested for the promoter activities in the presence of PKA and/or SIK(N). A cAMP-response element (CRE)-like sequence present in the promoter was shown to be responsible not only for the PKA-mediated promoter activation but also for the SIK(N)-mediated repression. When the Gal4 DNA binding domain-linked full-length CRE-binding protein (CREB) construct was cotransfected with Gal4 reporter gene, SIK(N) repressed the PKA-induced reporter gene expression. However, SIK(N) could not repress the PKA-induced reporter activity conferred by Gal4 DNA binding domain-linked basic leucine zipper (bZIP)-less CREB or bZIP-disrupted CREB. On the other hand, SIK(N) could repress the kinase-inducible domain-disrupted CREB-dependent reporter gene expression in the presence of PKA. The in vitro kinase reaction studies showed that SIK(N) could not phosphorylate CREB, and PKA failed to phosphorylate SIK(N). Taken together, these results suggest that SIK(N), cooperating with PKA, may act on the CREB's bZIP domain and repress the CREB-mediated transcriptional activation of the CYP11A gene.
Genetic alterations in untreated metastases and androgen-independent prostate cancer detected by comparative genomic hybridization and allelotyping. (1996)

A newly developed method of comparative genomic hybridization (CGH) employing quantitative statistical comparisons was applied to DNA from two different types of advanced prostate cancer tissue. Multiple CGH analyses were obtained for each chromosome in each tumor, and the results of point-by-point comparison of the mean tumor:normal color ratio to a control normal:normal color ratio in each of 1247 evenly distributed data channels constituting the entire human genome were interpreted as loss, gain, or no change in copy number in the tumor genome. Group I tissue was obtained from prostate cancer metastases from 20 patients, 19 of whom had received no prior prostate cancer treatment. This DNA also was analyzed by Southern and microsatellite allelotyping at 53 different loci on 20 different chromosome arms. CGH results agreed with allelotyping results at 92% of the informative loci studied. These samples, which contained highly enriched tumor DNA, showed the highest rates of alteration yet reported in several chromosomal regions known to be altered frequently in prostate cancer: 8q gain (85%), 8p loss (80%), 13q loss (75%), 16q loss (55%), 17p loss (50%), and 10q loss (50%). Group II tissue was obtained predominately from primary or recurrent tumor from 11 patients who had been treated with long-term androgen-deprivation therapy and developed androgen-independent metastatic disease. Quantitative CGH analysis on DNA from these tissues showed chromosomal alterations that were very similar to those found in group I, suggesting that untreated metastatic tumors contain the bulk of chromosomal alterations necessary for recurrence to occur during androgen deprivation. In the entire data set, a number of previously undetected regions of frequent loss or gain were identified, including losses of chromosomes 2q (42%), 5q (39%), 6q (39%), and 15q (39%) and gains of chromosomes 11p (52%), 1q (52%), 3q (52%), and 2p (45%). Chi-squared analysis showed a significantly higher frequency of gain of the 4q25-q28 region in tumors from African-American patients, indicating a possible oncogene whose activation may play a role in the higher rate of progression seen in this ethnic group. Additional study of these frequently altered regions may provide insight into the mechanism of prostate cancer progression and lead to important tools for tumor-specific prognosis and therapy.
Bioaffinity magnetic reactor for peptide digestion followed by analysis using bottom‐up shotgun proteomics strategy (2008)

Abstract We report an efficient and streamlined way to improve the analysis and identification of peptides and proteins in complex mixtures of soluble proteins, cell lysates, etc . By using the shotgun proteomics methodology combined with bioaffinity purification we can remove or minimize the interference contamination of a complex tryptic digest and so avoid the time‐consuming separation steps before the final MS analysis. We have proved that by means of enzymatic fragmentation (endoproteinases with Arg‐C or/and Lys‐C specificity) connected with the isolation of specific peptides we can obtain a simplified peptide mixture for easier identification of the entire protein. A new bioaffinity sorbent was developed for this purpose. Anhydrotrypsin (AHT), an inactive form of trypsin with an affinity for peptides with arginine (Arg) or lysine (Lys) at the C‐terminus, was immobilized onto micro/nanoparticles with superparamagnetic properties (silica magnetite particles (SiMAG)–Carboxyl, Chemicell, Germany). This AHT carrier with a determined binding capacity (26.8 nmol/mg of carrier) was tested with a model peptide, human neurotensin, and the resulting MS spectra confirmed the validity of this approach.
Antihistamines (2000)

To prescribe antihistamines rationally it is important to be familiar with the role of histamine in the production of allergic disease. Histamine is widely distributed through the body with the highest concentrations in the lung, skin and gastrointestinal tract. Mast cells and basophils contain the majority of histamine, but it is also found in gastric mucosa, epidermal cells, rapidly growing tissue, enterochromaffin cells and the central nervous system.KeywordsAtopic DermatitisAllergic RhinitisPeak Serum ConcentrationFederal Aviation AdministrationGeneration AntihistamineThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Raising the Bar: The Curative Potential of Human Cancer Immunotherapy (2012)

Immunotherapy with interleukin-2 can cure 5 to 10% of patients with metastatic melanoma and renal cancer. Recent adoptive cell transfer (ACT) immunotherapies have improved cure rates in metastatic melanoma to 20 to 40%. Genetic engineering of T cells to express conventional alpha/beta T cell receptors or antibody-based chimeric antigen receptors provides an opportunity to extend ACT to patients with common epithelial cancers.
Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence (2003)

Despite their high degree of genomic similarity, reminiscent of their relatively recent separation from each other ( approximately 6 million years ago), the molecular basis of traits unique to humans vs. their closest relative, the chimpanzee, is largely unknown. This report describes a large-scale single-contig comparison between human and chimpanzee genomes via the sequence analysis of almost one-half of the immunologically critical MHC. This 1,750,601-bp stretch of DNA, which encompasses the entire class I along with the telomeric part of the MHC class III regions, corresponds to an orthologous 1,870,955 bp of the human HLA region. Sequence analysis confirms the existence of a high degree of sequence similarity between the two species. However, and importantly, this 98.6% sequence identity drops to only 86.7% taking into account the multiple insertions/deletions (indels) dispersed throughout the region. This is functionally exemplified by a large deletion of 95 kb between the virtual locations of human MICA and MICB genes, which results in a single hybrid chimpanzee MIC gene, in a segment of the MHC genetically linked to species-specific handling of several viral infections (HIV/SIV, hepatitis B and C) as well as susceptibility to various autoimmune diseases. Finally, if generalized, these data suggest that evolution may have used the mechanistically more drastic indels instead of the more subtle single-nucleotide substitutions for shaping the recently emerged primate species.
Instillation of Taurolidine/Heparin after Laparotomy Reduces Intraperitoneal Tumour Growth in a Colon Cancer Rat Model (2007)

Taurolidine/heparin effectively reduces intraperitoneal tumour growth when used as an intraoperative lavage. These results represent a good rationale for intraoperative adjuvant irrigation with taurolidine/heparin during resection of colon cancer.
A systematic review of the economic burden of chronic angina. (2004)

Chronic angina carries substantial healthcare costs caused by frequent medical visits, medications, and expensive revascularization procedures. Workplace productivity loss because of angina is also substantial, but lasting long-term improvement in work status has been difficult to achieve.
An Extensible Markup Language (XML) Based Format for Watcher Information (2004)

Watchers are defined as entities that request (i.e., subscribe to)
information about a resource. There is fairly complex state associated
with these subscriptions. The union of the state for all subscriptions
to a particular resource is called the watcher information for that
resource. This state is dynamic, changing as subscribers come and go.
As a result, it is possible, and indeed useful, to subscribe to the
watcher information for a particular resource. In order to enable
this, a format is needed to describe the state of watchers on a
resource. This specification describes an Extensible Markup Language
(XML) document format for such state. [STANDARDS-TRACK]
A frequent ala 4 to val superoxide dismutase-1 mutation is associated with a rapidly progressive familial amyotrophic lateral sclerosis (1994)

Familial amyotrophic lateral sclerosis (FALS), a degenerative disorder of motor neurons, is associated with mutations in the Cu/Zn superoxide dismutase gene SOD1 in some affected families. We confirm a recently reported ala4-->val mutation in exon 1 of the SOD1 gene and report that this mutation is both the most commonly detected of all SOD1 mutations and among the most clinically severe. By comparison with our other FALS families, the exon 1 mutation is associated with reduced survival time after onset: 1.2 years, as compared to 2.5 years for all other FALS patients. We also demonstrate that SOD1 is prominently expressed in normal motor neurons and that neural expression of SOD1 is not prevented by this exon 1 mutation. Assays of SOD1 enzymatic activity in extracts from red blood cells, lymphoblastoid cells, and brain tissues revealed an approximately 50% reduction in activity of cytosolic SOD1 in patients with this mutation compared to normal individuals. By contrast, patients with sporadic ALS had normal levels of SOD1 enzymatic activity. Why this SOD1 mutation causes motor neuron death in FALS remains to be established. While it may be that FALS is a consequence of loss of SOD1 function, it is also possible that motor neuron death in this dominantly inherited disease occurs because the mutations confer an additional, cytotoxic function on the SOD1 protein.
The Pannexin 1 Channel Activates the Inflammasome in Neurons and Astrocytes (2009)

The inflammasome is a multiprotein complex involved in innate immunity. Activation of the inflammasome causes the processing and release of the cytokines interleukins 1beta and 18. In primary macrophages, potassium ion flux and the membrane channel pannexin 1 have been suggested to play roles in inflammasome activation. However, the molecular mechanism(s) governing inflammasome signaling remains poorly defined, and it is undetermined whether these mechanisms apply to the central nervous system. Here we show that high extracellular potassium opens pannexin channels leading to caspase-1 activation in primary neurons and astrocytes. The effect of K(+) on pannexin 1 channels was independent of membrane potential, suggesting that stimulation of inflammasome signaling was mediated by an allosteric effect. The activation of the inflammasome by K(+) was inhibited by the pannexin 1 channel blocker probenecid, supporting a role of pannexin 1 in inflammasome activation. Co-immunoprecipitation of neuronal lysates indicates that pannexin 1 associates with components of the multiprotein inflammasome complex, including the P2X7 receptor and caspase-1. Moreover antibody neutralization of the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD) blocked ATP-induced cell death in oocytes co-expressing P2X7 receptor and pannexin 1. Thus, in contrast to macrophages and monocytes in which low intracellular K(+) has been suggested to trigger inflammasome activation, in neural cells, high extracellular K(+) activates caspase-1 probably through pannexin 1.
Molecular cloning of the Ecotin gene in Escherichia coli (1991)

The nucleotide sequence of a 876 bp region in E. coli chromosome that encodes Ecotin was determined. The proposed coding sequence for Ecotin is 486 nucleotides long, which would encode a protein consisting of 162 amino acids with a calculated molecular weight of 18,192 Da. The deduced primary sequence of Ecotin includes a 20-residue signal sequence, cleavage of which would give rise to a mature protein with a molecular weight of 16,099 Da. Ecotin does not contain any consensus reactive site sequences of known serine protease inhibitor families, suggesting that Ecotin is a novel inhibitor.
Interaction between human CD2 and CD58 involves the major beta sheet surface of each of their respective adhesion domains. (1994)

The CD58 binding site on human CD2 was recently shown by nuclear magnetic resonance structural data in conjunction with site-directed mutagenesis to be a highly charged surface area covering approximately 770A2 on the major AGFCC'C" face of the CD2 immunoglobulin-like (Ig-like) NH2-terminal domain. Here we have identified the other binding surface of the CD2-CD58 adhesion pair by mutating charged residues shared among CD2 ligands (human CD58, sheep CD58, and human CD48) that are predicted to be solvent exposed on a molecular model of the Ig-like adhesion domain of human CD58. This site includes beta strand residues along the C strand (E25, K29, and K30), in the middle of the C' strand (E37) and in the G strand (K87). In addition, several residues on the CC' loop (K32, D33, and K34) form this site. Thus, the interaction between CD2 and CD58 involves the major beta sheet surface of each adhesion domain. Possible docking orientations for the CD2-CD58 molecular complex are offered. Strict conservation of human and sheep CD58 residues within the involved C and C' strands and CC' loop suggests that this region is particularly important for stable formation of the CD2-CD58 complex. The analysis of this complex offers molecular insight into the nature of a receptor-ligand pair involving two Ig family members.
Matrix-Induced Autologous Chondrocyte Implantation (MACI ® ): Biological and Histological Assessment (2007)

Matrix-induced autologous chondrocyte implantation (MACI) has been a treatment of cartilage injury since 2000, but little is known of the histological paradigm of tissue regeneration after implantation. MACI is a stable cell-based delivery system that enables the regeneration of hyaline-like cartilage. From a cohort of 56 MACI patients, we examined the phenotype of chondrocytes seeded on type I/III collagen scaffold, and conducted progressive histologic assessment over a period of 6 months. Chondrocyte-seeded collagen scaffolds from patient implants were analyzed by electron microscopy, immunohistochemistry (type II collagen and S-100), and reverse transcription polymerase chain reaction (RT-PCR) (aggrecan and type II collagen). Coincidental cartilage biopsies were obtained at 48 hours, 21 days, 6 months, 8 months, 12 months, 18 months, and 24 months. Our data showed that chondrocytes on the collagen scaffold appeared spherical, well integrated into the matrix, and maintained the chondrocyte phenotype as evidenced by aggrecan, type II collagen, and S-100 expression. Progressive histologic evaluation of the biopsies showed the formation of cartilage-like tissue as early as 21 days, and 75% hyaline-like cartilage regeneration after 6 months. This preliminary study has suggested that MACI may offer an improved alternative to traditional treatments for cartilage injury by regenerating hyaline-like cartilage as early as 6 months after surgery.
Ras history (2010)

Although the roots of Ras sprouted from the rich history of retrovirus research, it was the discovery of mutationally activated RAS genes in human cancer in 1982 that stimulated an intensive research effort to understand Ras protein structure, biochemistry and biology. While the ultimate goal has been developing anti-Ras drugs for cancer treatment, discoveries from Ras have laid the foundation for three broad areas of science. First, they focused studies on the origins of cancer to the molecular level, with the subsequent discovery of genes mutated in cancer that now number in the thousands. Second, elucidation of the biochemical mechanisms by which Ras facilitates signal transduction established many of our fundamental concepts of how a normal cell orchestrates responses to extracellular cues. Third, Ras proteins are also founding members of a large superfamily of small GTPases that regulate all key cellular processes and established the versatile role of small GTP-binding proteins in biology. We highlight some of the key findings of the last 28 years.
Discovery of 4-Amino-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamides As Selective, Orally Active Inhibitors of Protein Kinase B (Akt) (2010)

Protein kinase B (PKB or Akt) is an important component of intracellular signaling pathways regulating growth and survival. Signaling through PKB is frequently deregulated in cancer, and inhibitors of PKB therefore have potential as antitumor agents. The optimization of lipophilic substitution within a series of 4-benzyl-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-amines provided ATP-competitive, nanomolar inhibitors with up to 150-fold selectivity for inhibition of PKB over the closely related kinase PKA. Although active in cellular assays, compounds containing 4-amino-4-benzylpiperidines underwent metabolism in vivo, leading to rapid clearance and low oral bioavailability. Variation of the linker group between the piperidine and the lipophilic substituent identified 4-amino-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamides as potent and orally bioavailable inhibitors of PKB. Representative compounds modulated biomarkers of signaling through PKB in vivo and strongly inhibited the growth of human tumor xenografts in nude mice at well-tolerated doses.
The mechanism for hydrothermal growth of zinc oxide (2011)

The mechanism for hydrothermal growth of ZnO was studied in ammonium hydroxide solution at pH near 11 (0.3 M NH4OH). The products formed at 20–90 °C and ambient pressure were characterised using Fourier Transform Infrared Spectroscopy (FTIR), X-ray Photon Spectroscopy (XPS), X-ray Diffraction (XRD) and Secondary Ion Mass Spectroscopy (SIMS). Under these conditions, the growth of ZnO occurs via the initial precipitation of ε-Zn(OH)2 (Wülfingite), which subsequently dehydrates, to form Würtzite ZnO. Isotope tracking experiments show that most of the oxygen atoms do not mix with water during the conversion from Wülfingite to ZnO, and thus that the reaction proceeds primarily in the solid phase rather than through dissolution then reprecipitation. XPS results show that the surface of hydrothermal ZnO consists primarily of zinc hydroxide at lower temperatures, and there is a significant fraction of zinc hydroxide persisting at higher temperatures. Together these results show that much of the solid-solution interface is mainly comprised of zinc hydroxide not ZnO. These findings may have implications for understanding how small organic molecules can be used to control the morphology of zinc oxide crystals grown under hydrothermal conditions.
Demonstration of a quantum error detection code using a square lattice of four superconducting qubits (2015)

The ability to detect and deal with errors when manipulating quantum systems is a fundamental requirement for fault-tolerant quantum computing. Unlike classical bits that are subject to only digital bit-flip errors, quantum bits are susceptible to a much larger spectrum of errors, for which any complete quantum error-correcting code must account. Whilst classical bit-flip detection can be realized via a linear array of qubits, a general fault-tolerant quantum error-correcting code requires extending into a higher-dimensional lattice. Here we present a quantum error detection protocol on a two-by-two planar lattice of superconducting qubits. The protocol detects an arbitrary quantum error on an encoded two-qubit entangled state via quantum non-demolition parity measurements on another pair of error syndrome qubits. This result represents a building block towards larger lattices amenable to fault-tolerant quantum error correction architectures such as the surface code.