gebhart/patrepeval huggingface dataset:
Cloning and thermostability of TaqI endonuclease isoschizomers from Thermus species SM32 and Thermus filiformis Tok6A1 (1998)

Two TaqI endonuclease (hereafter referred to as TaqI) isoschizomer genes, tsp32IR from Thermus species SM32 of Azores and tfiTok6A1I from T. filiformis Tok6A1 of New Zealand, were cloned in Escherichia coli. The overexpressed enzymes were partly purified and their thermostability was determined. In the medium-salt buffer, Tsp32IR, TfiTok6A1I and one previously cloned TaqI isoschizomer (TthHB8I) were more thermostable than TaqI. Tsp32IR remained partly active up to 90 degreesC in the low-salt buffer. Six amino acid residues that are identical in the three high thermostability isoschizomers (Tsp32IR, TfiTok6A1I and TthHB8I) but differ in TaqI might provide added rigidity for thermostabilization. These include four proline residues located in or near loop regions, and one alanine and one arginine located at helix regions in the predicted TaqI endonuclease secondary structure. The possible role of these residues in thermostabilization was evaluated by mutagenizing the TaqI enzyme. Mutants generated at these six positions were less thermostable than wild-type TaqI. The results suggest that the surrounding sequence or structural context might be as important as the mutation itself.
The menkes protein (ATP7A; MNK) cycles via the plasma membrane both in basal and elevated extracellular copper using a C-terminal di-leucine endocytic signal (1999)

Menkes disease is an X-linked recessive copper deficiency disorder caused by mutations in the ATP7A ( MNK ) gene which encodes a copper transporting P-type ATPase (MNK). MNK is normally localized pre- dominantly in the trans -Golgi network (TGN); however, when cells are exposed to excessive copper it is rapidly relocalized to the plasma membrane where it functions in copper efflux. In this study, the c-myc epitope was introduced within the loop connecting the first and second transmembrane regions of MNK. This myc epitope allowed detection of the protein at the surface of living cells and provided the first experimental evidence supporting the common topological model. In cells stably expressing the tagged MNK protein (MNK-tag), extracellular antibodies were internalized to the perinuclear region, indicating that MNK-tag at the TGN constitutively cycles via the plasma membrane in basal copper conditions. Under elevated copper conditions, MNK-tag was recruited to the plasma membrane; however, internalization of MNK-tag was not inhibited and the protein continued to recycle through cyto- plasmic membrane compartments. These findings suggest that copper stimulates exocytic movement of MNK to the plasma membrane rather than reducing MNK retrieval and indicate that MNK may remove copper from the cytoplasm by transporting copper into the vesicles through which it cycles. Newly internalized MNK-tag and transferrin were found to co-localize, suggesting that MNK-tag follows a clathrin-coated pit/endosomal pathway into cells. Mutation of the di-leucine, L1487 L1488, prevented uptake of anti-myc antibodies in both basal and elevated copper conditions, thereby identifying this sequence as an endocytic signal for MNK. Analysis of the effects of the di-leucine mutation in elevated copper provided further support for copper-stimulated exocytic movement of MNK from the TGN to the plasma membrane.
Structure and topological symmetry of the glyphosate target 5-enolpyruvylshikimate-3-phosphate synthase: a distinctive protein fold. (1991)

5-enol-Pyruvylshikimate-3-phosphate synthase (EPSP synthase; phosphoenolpyruvate:3-phosphoshikimate 1-carboxyvinyltransferase, EC 2.5.1.19) is an enzyme on the pathway toward the synthesis of aromatic amino acids in plants, fungi, and bacteria and is the target of the broad-spectrum herbicide glyphosate. The three-dimensional structure of the enzyme from Escherichia coli has been determined by crystallographic techniques. The polypeptide backbone chain was traced by examination of an electron density map calculated at 3-A resolution. The two-domain structure has a distinctive fold and appears to be formed by 6-fold replication of a protein folding unit comprising two parallel helices and a four-stranded sheet. Each domain is formed from three of these units, which are related by an approximate threefold symmetry axis; in each domain three of the helices are completely buried by a surface formed from the three beta-sheets and solvent-accessible faces of the other three helices. The domains are related by an approximate dyad, but in the present crystals the molecule does not display pseudo-symmetry related to the symmetry of point group 32 because its approximate threefold axes are almost normal. A possible relation between the three-dimensional structure of the protein and the linear sequence of its gene will be described. The topological threefold symmetry and orientation of each of the two observed globular domains may direct the binding of substrates and inhibitors by a helix macrodipole effect and implies that the active site is located near the interdomain crossover segments. The structure also suggests a rationale for the glyphosate tolerance conferred by sequence alterations.
Efficient and scalable socware detection in online social networks (2012)

Online social networks (OSNs) have become the new vec-tor for cybercrime, and hackers are finding new ways to propagate spam and malware on these platforms, which we refer to as socware. As we show here, socware cannot be identified with existing security mechanisms (e.g., URL blacklists), because it exploits different weaknesses and of-ten has different intentions. In this paper, we present MyPageKeeper, a Facebook ap-plication that we have developed to protect Facebook users from socware. Here, we present results from the perspective of over 12K users who have installed MyPageKeeper and their roughly 2.4 million friends. Our work makes three main contributions. First, to enable protection of users at scale, we design an efficient socware detection method which takes advantage of the social context of posts. We find that our classifier is both accurate (97 % of posts flagged by it are indeed socware and it incorrectly flags only 0.005 % of benign posts) and efficient (it requires 46 ms on average to classify a post). Second, we show that socware significantly differs from traditional email spam or web-based malware. For example, website blacklists identify only 3 % of the posts flagged by MyPageKeeper, while 26 % of flagged posts point to malicious apps and pages hosted on Facebook (which no current antivirus or blacklist is designed to detect). Third, we quantify the prevalence of socware by analyzing roughly 40 million posts over four months; 49 % of our users were exposed to at least one socware post in this period. Finally, we identify a new type of parasitic behavior, which we refer to as “Like-as-a-Service”, whose goal is to artificially boost the number of “Likes ” of a Facebook page. 1
Inhibition of thymidine incorporation into the DNA of normal and neoplastic cells by a factor from bovine maternal placenta: interaction of the inhibitor with cell membranes (1982)

An inhibitor was isolated from the maternal part of bovine placentas which inhibits the incorporation of [3H]thymidine into the DNA of a variety of tumor cells to a significantly higher degree as compared to normal cells. This protein-type component was labeled by reaction with N-succinimidyl[2,3-3H]propionate, and interactions with receptors on cell membranes were investigated. Results indicated that receptors on tumor cell surfaces have higher binding capacities versus the inhibitor than those of normal cells. Moreover, an additional type of receptor was detected on tumor membranes. Obviously one of the reasons for the higher inhibitory capacity of the factor in tumor cells is the better internalization of this component.
KARYOTYPIC ABNORMALITIES IN ADENOCARCINOMAS OF THE LUNG (1994)

Cytogenetic analysis of 114 adenocarcinomas of the lung revealed clonal abnormalities in 67 tumors. The chromosome numbers ranged from near-diploid to hypertetraploid. Clonal abnormalities seen as the sole anomaly were loss of the Y chromosome (21 tumors), trisomy 7 (2 tumors), and trisomy 12 (1 tumor). A supernumerary ring chromosome was the only clonal change in 4 tumors. The bands most often affected were 17p11-13 (13 cases), 1q10-12 and 1p22 (10 cases each), 1p11-13 and 1q21 (9 cases each), and 11p11, 11p15 and 15p11-13 (6 cases each). The chromosomes most frequently involved in structural rearrangements were chromosomes 1 (30 cases), 11 (20 cases), 3 (17 cases), 17 and 7 (16 cases each). Repeated loss of material from chromosome arms 1p, 3p, 6q, 11p, and 17p and gains of 1q were found. Recurrent structural changes were del(1)(p22) and i(5)(p10) (5 cases each) i(1)(q10), i(13)(q10), i(14)(q10) and del(17)(p11) (3 cases each). We found no abnormalities that seemed to be specifically associated with pulmonary adenocarcinomas, but isochromosomes i(1)(q10), i(5)(p10) and i(13)(q10) and changes of 6q were present in our series at frequencies higher than those generally seen in the other main types of lung cancer.
Oxidative stress signalling in the apoptosis of Jurkat T‐lymphocytes (2001)

The pathways of transduction of oxidative stress signals have been studied using the Jurkat T cell model. The oxidative stress was induced by exposure of the cells to 100 microM H(2)O(2). DNA damage was detected within 15 min after commencement of treatment. DNA damage repair occurred within about 1 h in cells exposed to oxidative stress for 15 min. In continuous exposure to stress, DNA repair was slower and control levels of DNA integrity were not reached. DNA repair did not involve gene transcription. H(2)O(2) at 100 microM caused cell death by necrosis as well as by apoptosis. Both these processes were induced by 15 min exposure to the stress stimulus. However, some important differences were found between necrosis and apoptosis. Necrosis was more rapid, began within an hour of treatment and continued to increase during the full duration of the experiment. But apoptosis was seen after 4 h from treatment and was conspicuous between 6 and 20 h after the start of treatment. The necrotic phase preceded apoptosis, although these did show an overlap. In the necrotic phase, Bcl-2, Caspase 8 genes were down regulated. The 6-20 h phase characterised by a marked increase in apoptosis is accompanied by the up regulation of both Bcl-2 and Caspase genes. Expression of the Fas and p53 genes was not altered in either phase. We also analysed the levels of expression of the scavenging genes whose gene products are involved in detoxification. No modulation of the antioxidant enzymes, catalase, Cu/Zn superoxide dismutase and glutathione peroxidase was detectable.
Expression profiling in cancer using cDNA microarrays (1999)

Currently there are over 1,000,000 human expressed sequence tag (EST) sequences available on the public database, representing perhaps 50-90% of all human genes. The cDNA microarray technique is a recently developed tool that exploits this wealth of information for the analysis of gene expression. In this method, DNA probes representing cDNA clones are arrayed onto a glass slide and interrogated with fluorescently labeled cDNA targets. The power of the technology is the ability to perform a genome-wide expression profile of thousands of genes in one experiment. In our review we describe the principles of the microarray technology as applied to cancer research, summarize the literature on its use so far, and speculate on the future application of this powerful technique.
Effect of lyophilization on results of five enzymatic methods for cholesterol. (1989)

We studied the effect of lyophilization of serum pools on the determination of cholesterol with the enzymatic methods used in five automated analyzers: SMAC (Technicon), the RA-1000 (Technicon), the aca (Du Pont), the TDx (Abbott), and the Ektachem 700P (Kodak). We prepared two serum pools: pool A (2.2 g/L) and pool B (1.9 g/L). We separated each pool into three groups for treatment by lyophilizing or freezing at -20 and -70 degrees C. We determined cholesterol by the above methods at regular intervals during the next 270 days. For all methods, the measured concentration of cholesterol was less for the lyophilized serum than for frozen (P less than 0.007 by the paired-sample t-test). After adjusting for the dilutional effects of reconstitution, the decrease in original value was 0.7% for the SMAC, 1.7% for the RA-1000, 5.7% for the Ektachem, 9.4% for the TDx, and 14.3% for the aca. Lyophilization of cholesterol standards or serum samples may hamper the effective standardization of enzymatic methods and may be a source of apparent inaccuracy (bias) among enzymatic methods.
Cross linking of proteins in vitro by peroxidase (1977)

Abstract The enzyme peroxidase, a substrate (hydrogen donor), and hydrogen peroxide aggregated and polymerized soluble proteins included in the reaction mixture. Gel filtration and acrylamide disk gel electrophoresis revealed newly formed dimers, trimers, and higher protein polymers. Some of the protein polymers withstood the denaturing conditions of dodecyl sulfate disk gel electrophoresis; thus the formation of some covalent cross links was indicated. It is suggested that peroxidase catalyzes the oxidation of hydrogen donors to form free radicals or quinones, which subsequently interact with, cross link, and alter the soluble proteins.
Novel Targets in Non-Small Cell Lung Cancer: ROS1 and RET Fusions (2013)

The discovery of chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene in non-small cell lung cancer (NSCLC) has stimulated renewed interest in oncogenic fusions as potential therapeutic targets. Recently, genetic alterations in ROS1 and RET were identified in patients with NSCLC. Like ALK, genetic alterations in ROS1 and RET involve chromosomal rearrangements that result in the formation of chimeric fusion kinases capable of oncogenic transformation. Notably, ROS1 and RET rearrangements are rarely found with other genetic alterations, such as EGFR, KRAS, or ALK. This finding suggests that both ROS1 and RET are independent oncogenic drivers that may be viable therapeutic targets. In initial screening studies, ROS1 and RET rearrangements were identified at similar frequencies (approximately 1%-2%), using a variety of genotyping techniques. Importantly, patients with either ROS1 or RET rearrangements appear to have unique clinical and pathologic features that may facilitate identification and enrichment strategies. These features may in turn expedite enrollment in clinical trials evaluating genotype-directed therapies in these rare patient populations. In this review, we summarize the molecular biology, clinical features, detection, and targeting of ROS1 and RET rearrangements in NSCLC.
Evaluating a natural outbreak of porcine proliferative enteropathy and treatment with tylosin in the grow-finish phase (1998)

Objective: To determine approximate time and severity of a porcine proliferative enteropathy (PPE) outbreak in a herd with a history of PPE; to compare average daily gain (ADG), average daily feed intake (ADFI), feed efficiency (F:G), and clinical impression of disease in clinically affected nonmedicated controls versus pigs medicated with 110 ppm (100 g per ton) of tylosin for 21 days followed by 44 ppm (40 g per ton) tylosin for an additional 21 days; and to follow pigs to market to determine effects of the outbreak on clinical PPE lesions detected at slaughter.
Isolation and Transmission of Human Retrovirus (Human T-Cell Leukemia Virus) (1983)

Nine new isolates of human T-cell leukemia-lymphoma virus (HTLV) were obtained from cells of seven patients with malignancies of mature T cells and from two clinically normal relatives of a T-cell leukemia patient. These people were from the United States, Israel, the West Indies, and Japan. The virus was detected in the fresh T cells and was isolated from the established T-cell lines. Each isolate is closely related to the first HTLV isolate, and all the new HTLV isolates were transmitted into normal human T cells obtained from the umbilical cord blood of newborns.
Progress in studies on the antimutagenicity and anticarcinogenicity of green tea epicatechins. (1991)

An antioxidative fraction was extracted from green tea and the major compounds in the fraction identified as epicatechins. Experimental results showed that green tea epicatechin compounds (GTEC) inhibited the mutagenicity and/or chromosomal damage caused by different carcinogens in both bacterial and mammalian cells. In vitro, GTEC inhibited transformation of BALB/3T3 cells induced by BP, X-rays, or MCA/TPA. In vivo, green tea extract decreased the incidence of carcinoma in the forestomach and esophagus of mice induced by sarcosine and NaNO2. GTEC inhibited the development of gamma-glutamyl transpeptidase-positive foci in the livers of rats treated with diethyl nitrosamine (DEN) or DEN/phenobarbital. Our investigations indicate that the antimutagenic and anticarcinogenic mechanisms of GTBC are related to the following: increased glutathione-S-transferase activity; inhibition of edema, hyperplasia, and ODC activity induced by TPA; free radical scavenging; blocked tumor promoter-induced inhibition of intercellular communication; and enhanced cell-mediated immunity. GTEC might be useful in the prevention of some kinds of cancer and a variety of oxidation-related diseases.
Identification of a Negative Regulatory Surface within Estrogen Receptor α Provides Evidence in Support of a Role for Corepressors in Regulating Cellular Responses to Agonists and Antagonists (2002)

Several lines of evidence have indicated that the estrogen receptor (ER) can recruit the corepressors, nuclear receptor corepressor (NCoR) and silencing mediator of retinoid and thyroid receptors (SMRT), to target genes in the presence of tamoxifen, suggesting a possible role for NCoR/SMRT in regulating ER pharmacology. However, a tamoxifen-dependent, direct interaction between NCoR/SMRT and ER in vitro has not been demonstrated. To investigate the possible involvement of different corepressors in the actions of antiestrogen-bound ER, we have constructed a phage display library that expresses 23-amino acid peptides containing the canonical CoRNR box motif in an otherwise random background. Screening of the CoRNR box library with apo-ER or ER treated with tamoxifen or ICI 182,780 led to the isolation of peptides whose ability to interact with ER was influenced by the nature of the bound ligand. Using a series of ERalpha mutants, we found that helix 12 was not required for the binding of CoRNR box peptides, whereas disruption of helixes 3 and 5 had a marked effect on peptide binding. One mutant, ER-L372R, lost the ability to interact with CoRNR box-containing peptides without affecting its binding to LXXLL motif-containing peptides. The estradiol- and tamoxifen-mediated transcriptional activity of ER-L372R was dramatically increased by 11- and 3-fold, respectively, compared with that of wild-type ERalpha. The ICI 182,780-mediated repressional activity of this mutant was also reduced by 4-fold compared with that of wild-type ERalpha. These results suggest that leucine 372 may be an important part of the interaction surface on ER that is responsible for corepressor binding. In addition, our data suggest that corepressors, other than NCoR/SMRT, may be involved in ER signaling.
Chemical fixation of carbon dioxide to styrene carbonate under supercritical conditions with DMF in the absence of any additional catalysts (2000)

Chemical fixation of carbon dioxide to styrene carbonate proceeds effectively under supercritical conditions with DMF even in the absence of any additional catalysts, giving a maximum yield of 85% in the near-critical region.
Altered Histone Acetylation atGlutamate Receptor 2andBrain-Derived Neurotrophic FactorGenes Is an Early Event Triggered by Status Epilepticus (2002)

The mechanisms underlying seizure-induced changes in gene expression are unclear. Using a chromatin immunoprecipitation assay, we found that acetylation of histone H4 in rat hippocampal CA3 neurons was reduced at the glutamate receptor 2 (GluR2; GRIA2) glutamate receptor promoter but increased at brain-derived neurotrophic factor promoter P2 as soon as 3 hr after induction of status epilepticus by pilocarpine. This result indicates that status epilepticus rapidly activates different signal pathways to modulate histone acetylation in a promoter-specific manner. H4 deacetylation preceded seizure-induced GluR2 mRNA downregulation. The histone deacetylase inhibitor trichostatin A prevented and quickly reversed deacetylation of GluR2-associated histones. Trichostatin A also blunted seizure-induced downregulation of GluR2 mRNA in CA3. Thus, rapid gene-specific changes in histone acetylation patterns may be a key early step in the pathological processes triggered by status epilepticus.
A cellular wireless local area network with QoS guarantees for heterogeneous traffic (2002)

A wireless local area network (WLAN) or a cell with quality-of-service (QoS) guarantees for various types of traffic is considered. A centralized (i.e., star) network topology is adopted as the topology of a cell which consists of a base station and a number of mobile clients. Dynamic time division duplexed (TDD) transmission is used, and hence, the same frequency channel is time-shared for downlink and uplink transmissions under the dynamic control of the base station. We divide traffic into two classes: class I (real-time) and II (non-real-time). Whenever there is no eligible class-I traffic, class-II traffic is transmitted, while uplink transmissions are controlled with a reservation scheme. Class-I traffic is handled with the framing strategy combined with the admission test for adding new class-I connections. Finally, we present the performance (average delay and throughput) evaluation of the reservation scheme for class-II traffic using both analytical calculations and simulations.
T cell regulation of myelopoiesis: analysis at a clonal level. (1984)

Colony-stimulating factor (CSF) production by a series of cloned human T lymphocyte cell lines was examined by substituting cloned T cells for peripheral blood mononuclear cells in the feeder layer of a double-layer agar CFU-C assay system. Of 12 T cell lines tested, all produced CSF when stimulated by specific antigen, whereas CSF production in the absence of stimulation was generally negligible. In the case of soluble antigen-specific (ragweed or tetanus toxoid) clones, this required both nominal antigen and the appropriate MHC gene product on autologous antigen-presenting cells, whereas in the case of clones specific for EBV-transformed B cell lines (allogeneic or autologous), surface-bound EBV-related antigen and MHC was necessary. When tested in this manner, CSF production by different cloned T cells was heterogeneous in both amount and subclass. Thus, although most clones stimulated growth of granulocyte, monocyte, and eosinophil colonies, certain clones were identified which preferentially stimulated some colony types but not others. This heterogeneity was particularly evident with respect to eosinophil colony production. In addition, a soluble inhibitor of granulocyte colony growth was produced by one clone. These findings provide further support for the notion that antigen-specific T cells may, on activation, regulate myelopoiesis in a precise way, and provide a possible cellular basis for selective eosinophilia, monocytosis, or neutrophilia seen in certain disease states.