gebhart/patrepeval huggingface dataset:
Induction of phosphorylation on BRCA1 during the cell cycle and after DNA damage. (1997)

BRCA1, the familial breast cancer susceptibility gene product, is a 220-kDA phosphorylated protein. BRCA1 immunoprecipitated from MCF7 cells blocked in G1-S phase or progressing through S-phase of the cell cycle migrated more slowly through SDS polyacrylamide gels than BRCA1 from cells maintained in serum-supplemented media, serum-free media for 24 h, or delayed in G2-M phase by treatment with colchicine. Restoration of BRCA1 to the faster-migrating form, which occurred on release of cells from the G1-S-phase block, was prevented by the phosphatase inhibitor okadaic acid. Phosphatase treatment of immunoprecipitated BRCA1 resulted in the conversion of the slower-migrating form to the faster-migrating form. Although these results suggested that BRCA1 was preferentially hyperphosphorylated near the G1-S-phase boundary of the cell cycle, exposure of cells to DNA-damaging agents including UV light or treatment with hydrogen peroxide (H2O2) also promoted BRCA1 hyperphosphorylation. These same stimuli also eliminated the punctate nuclear staining pattern normally observed for BRCA1 in control cells. These results indicate that BRCA1 undergoes cyclic hyperphosphorylation during the cell cycle; however, this modification, as well as changes in BRCA1 nuclear staining, also occurs in response to DNA damage.
Core requirements for glmS ribozyme self-cleavage reveal a putative pseudoknot structure (2006)

The glmS ribozyme is a self-cleaving RNA catalyst that resides in the 5'-untranslated region of glmS mRNA in certain bacteria. The ribozyme is specifically activated by glucosamine-6-phosphate (GlcN6P), the metabolic product of the GlmS protein, and is thus proposed to provide a feedback mechanism of riboswitch regulation. Both phylogenetic and biochemical analyses of the glmS ribozyme have established a highly conserved core sequence and secondary structure required for GlcN6P-dependent self-cleavage. However, the high degree of nucleotide conservation offers few clues regarding the higher-order structural organization of the catalytic core. To further investigate core ribozyme structure, minimal 'consensus-type' glmS ribozymes that retain GlcN6P-dependent activity were produced. Mutational analyses of consensus-type glmS ribozymes support a model for core ribozyme folding through a pseudoknot structure formed by the interaction of two highly conserved sequence segments. Moreover, GlcN6P-dependent function is demonstrated for bimolecular constructs in which substrate interaction with the ribozyme is minimally comprised of sequence representing that involved in putative pseudoknot formation. These studies suggest that the glmS ribozyme adopts an intricate multi-strand catalytic core through the formation of a pseudoknot structure, and provide a refined model for further considering GlcN6P interaction and GlcN6P-dependent ribozyme function.
G-actin as a risk factor and modulatable endpoint for cancer chemoprevention trials (1996)

Because tumorigenesis is an ongoing process, biomarkers can be used to identify individuals at risk for bladder cancer, and treatment of those at risk to prevent or slow further progression could be an effective means of cancer control given accurate individual risk assessment. Tumorigenesis proceeds through a series of defined phenotypic changes, including those in genetically altered cells destined to become cancer as well as in surrounding normal cells responding to the altered cytokine environment. A panel of biomarkers for the changes can provide a useful system for individual risk assessment in cancer patients and in individuals exposed to carcinogens. The use of such markers can increase the specificity of chemoprevention trials by targeting therapy to patients likely to respond, and thereby markedly reduce the costs of the trials. Previous studies in our laboratories showed the cytoskeletal proteins G- and F-actin reflect differentiation-related changes in cells undergoing tumorigenesis and in adjacent "field" cells, and a pattern of low F-actin and high G-actin is indicative of increased risk. Actin changes may be a common feature in genetic and epigenetic carcinogenic mechanisms. In a group of over 1600 workers exposed to benzidine, G-actin correlated with exposure, establishing it as an early marker of effect. In another study, a profile of biomarkers was monitored in patients who underwent transurethral resection of bladder tumor (TURBT) and received Bacillus Calmette Guerin (BCG) and/or DMSO. The primary objective was to determine how the defined biomarkers expressed in the tumor and the field correlate with clinical response and recurrence. DMSO, known to modulate G-actin in vitro, was used as an agent. Results strongly support the hypothesis that cytosolic G-actin levels measured by quantitative fluorescence image analysis (QFIA) can be an important intermediate endpoint marker for chemoprevention and that the p300 (M344) and DNA ploidy markers identify a high-risk group that requires more aggressive therapy and recurrence monitoring. Further research with other markers has shown that DD23 and nuclear actin, both of which identify late, specific changes, may increase the battery of useful markers. Taken together these studies show how biomarkers are employed to study individuals at risk, aid in the selection of chemopreventive compounds and assist in the understanding of the pathogenesis of malignancy.
Characterisation of particle-particle interactions using the atomic force microscope (2002)

An investigation has been conducted into factors affecting the interparticulate cohesion profile of three micronised drugs, as a function of humidity. An atomic force microscope (AFM) colloid probe technique was correlated with physico-chemical properties and in-vitro performance. Briefly, micronised drug particles of salbutamol sulphate, triamcinolone acetonide (TAA) and disodium cromoglycate (DSCG) were mounted onto Vshaped tipless cantilevers using a developed micromanipulation technique. Interactions between the AFM ‘drug probes’ and a series of model drug surfaces were conducted at a 15,30, 45, 60 and 75% relative humidity using a custom built perfusion apparatus connected to the AFM. As expected, separation energy distributions for drug probe interactions were dependent on the surface rugosity of the drug model surfaces. Separation energy measurements conducted between drug probes and individual micronised drug particles (mounted in polymer resin) suggested large variations in separation energy. Further analysis of such data suggested a lognormal separation energy distribution, however, limitations in individual particle measurements (finite particle measurements per experiment) allowed restricted statistical analysis.
The Bis(tricyclohexylstannyl) Sulfide Thionation of 3H-1,2,4- Triazol-3-ones (1987)

5-Aryl-2,4-dialkyl-2,4-dihydro-3H-1,2,4-triazol-3-ones may be converted in 55-74% yield to the corresponding 3H-1,2,4-triazole-3-thiones by using the combination bis(tricyclohexylstannyl) sulfide/boron trichloride.
A2AAdenosine Receptor Activation Improves Survival in Mouse Models of Endotoxemia and Sepsis (2004)

AR agonists increase mouse survival in endotoxemia and sepsis via A(2A) AR-mediated mechanisms and reduce the number of live bacteria in blood.
A new approach to the synthesis of the 5′-deoxy-5′-methylphosphonate linked thymidine oligonucleotide analogues (1995)

A new synthetic method for the preparation of the 5'-deoxy-5'-methylphosphonate linked thymidine oligonucleotides (5'-methylenephosphonate analogues) was developed. The method is based on the use of a phosphonate protecting group, 4-methoxy-1-oxido-2-picolyl, enabling intramolecular nucleophilic catalysis which together with the condensing agent, 2,4,6-triisopropylbenzenesulfonyl chloride, secures fast and efficient formation of the 5'-methylenephosphonate internucleosidic bonds. The produced protected oligomers were treated with thiophenol and triethylamine to remove the phosphonate protecting groups, cleaved from the solid support using concentrated aqueous ammonia, and purified by HPLC. Several thymidine oligonucleotide analogues with the chain length of up to 20 nucleotidic units, in which all internal 5'-oxygen atoms have been replaced by methylene groups directly bound to phosphorus, were synthesised using this methodology.
Alterations in NF-κB and RBP-Jκ by Arenavirus Infection of Macrophages In Vitro and In Vivo (2002)

Pichinde virus is an arenavirus that infects guinea pigs and serves as an animal model for human Lassa fever. An attenuated Pichinde virus variant (P2) and a virulent variant (P18) are being used to delineate pathogenic mechanisms that culminate in shock. In guinea pigs, the infection has been shown to begin in peritoneal macrophages following intraperitoneal inoculation and then spreads to the spleen and other reticuloendothelial organs. We show here that infection of the murine monocytic cell line P388D1 with either Pichinde virus variant resulted in the induction of inflammatory cytokines and effectors, including interleukin-6 and tumor necrosis factor alpha. Since these genes are regulated in part by the cellular transcription factors NF-kappaB and RBP-Jkappa, we compared the activities of NF-kappaB and RBP-Jkappa in P388D1 cells following infection with Pichinde virus. The attenuated P2 virus inhibited NF-kappaB activation and caused a shift in the size of the RBP-Jkappa complex. The virulent P18 virus showed less inhibition of NF-kappaB and failed to alter the size of the RBP-Jkappa complex. Peritoneal cells from P2-infected guinea pigs showed induction of NF-kappaB RelA/p50 heterodimer and p50/p50 homodimer and manifested an increase in the size of RBP-Jkappa. By contrast, P18 induced large amounts of the NF-kappaB p50/p50 dimer but failed to induce RelA/p50 or to cause an increase in the RBP-Jkappa size. Taken together, these changes suggest that the attenuated viral strain induces an "activation" of macrophages, while the virulent form of the virus does not.
A workload characterization study of the 1998 World Cup Web site (2000)

This article presents a detailed workload characterization study of the 1998 World Cup Web site. Measurements from this site were collected over a three-month period. During this time the site received 1.35 billion requests, making this the largest Web workload analyzed to date. By examining this extremely busy site and through comparison with existing characterization studies, we are able to determine how Web server workloads are evolving. We find that improvements in the caching architecture of the World Wide Web are changing the workloads of Web servers, but major improvements to that architecture are still necessary. In particular, we uncover evidence that a better consistency mechanism is required for World Wide Web caches.
Atherosclerosis and arterial influx of lipoproteins (1994)

Accumulation of atherogenic lipoproteins in the arterial intima is a key event in the development of atherosclerosis. The likelihood of increased lipoprotein accumulation in the intima increases with increasing influx: arterial influx of lipoproteins is increased by increased arterial wall permeability, increased lipoprotein concentration in plasma, and by high blood pressure. On entrance into the arterial intima, lipoproteins can either efflux as intact particles, be retained in the intima, or be degraded by intimal cells. Increased degradation as well as increased retention of lipoproteins in the intima have both been associated with increased development of atherosclerosis. Therefore, low rates of efflux of intact particles, as appears to be the case for large particles like VLDL, IDL, and possibly lipoprotein (a) could potentially promote atherosclerosis.
Upscaled Lattice Boltzmann Method for Simulations of Flows in Heterogeneous Porous Media (2017)

An upscaled Lattice Boltzmann Method (LBM) for flow simulations in heterogeneous porous media at the Darcy scale is proposed in this paper. In the Darcy-scale simulations, the Shan-Chen force model is used to simplify the algorithm. The proposed upscaled LBM uses coarser grids to represent the average effects of the fine-grid simulations. In the upscaled LBM, each coarse grid represents a subdomain of the fine-grid discretization and the effective permeability with the reduced-order models is proposed as we coarsen the grid. The effective permeability is computed using solutions of local problems (e.g., by performing local LBM simulations on the fine grids using the original permeability distribution) and used on the coarse grids in the upscaled simulations. The upscaled LBM that can reduce the computational cost of existing LBM and transfer the information between different scales is implemented. The results of coarse-grid, reduced-order, simulations agree very well with averaged results obtained using a fine grid.
Theory of the kinetics of reactions catalyzed by enzymes attached to the interior surfaces of tubes (1974)

Abstract A theoretical treatment is given of the kinetics of reactions catalyzed by enzymes attached to the inner surface of a tube, through which the substrate solution passes. A utilization factor, the ratio of the actual reaction rate to that in the absence of diffusional effects, is defined. A numerical procedure is proposed and numerical and approximate solutions for the utilization factor are given for five kinetic conditions: (a) Michaelis‐Menten behavior, (b) substrate inhibition, (c) product inhibition (competitive), (d) product, inhibition (non‐competitive), and (e) product inhibition (anticompetitive). When the enzyme chemically attached to a tube obeys a Michaelis‐Menten relationship, criteria for insignificant and significant diffusional effects are proposed.
Crystallization Maps for SiCO Amorphous Ceramics (2007)

Amorphous silicon–oxycarbide (SiCO) can retain large mole fractions of carbon when it is made from controlled pyrolysis of silicon‐based polymers. The crystallization resistance of these ceramics, which is quite remarkable, varies with the carbon content. In high‐carbon materials, crystallization is usually accompanied by weight loss (resulting from the carbothermal reduction of silica), whereas phase separation can lead to crystallization without significant weight loss in the low‐carbon materials. A simple graphical method is developed to estimate the composition of the crystallized material, and the concomitant weight loss. The results are presented as maps for a quick estimate of crystallization and weight loss for any composition. Experiments with a medium–high carbon SiCO are used to quantify the degree of crystallization and the associated weight loss at 1300°C and at 1350°C; these results show that, in the case of medium high carbon content, crystallization begins with phase separation but becomes quickly dominated by weight loss.
c-erbB-2 expression in breast cancer detected by immunoblotting and immunohistochemistry. (1990)

Evidence that the c-erbB-2 proto-oncogene is important in prognosis and oncogenesis in a number of human malignancies is increasing. DNA (Southern) hybridization and immunoblotting (Western) techniques are most commonly utilized to determine the amplification and protein expression of this proto-oncogene, respectively. These extraction techniques are often time consuming, costly, and subject to variability depending on the histological characteristics of the tumor. Immunohistochemistry (IHC), on the other hand, is more often time and cost effective. In addition, IHC may offer enhanced sensitivity over extraction techniques because of the in situ nature of analysis. In data presented here, 71 cases of human mammary carcinoma were concomitantly assessed for c-erbB-2 gene copy number and oncoprotein expression by dilution DNA hybridization and IHC, respectively. In 65 (92%) of 71 cases, high-level expression was associated with gene amplification, whereas moderate or low-level expression was associated with a normal diploid gene copy number. In five of the six discrepant cases, IHC predicted amplification which was not corroborated by Southern analysis. In these cases, tumor mass was limited by the intraductal component of the lesion or by an abundance of stromal elements within the specimen. In 39 of the 71 total cases, Western immunoblotting was compared with IHC in the assessment of oncoprotein expression. Concordance was found in 33 (85%) of 39 cases. In four of the six discrepant cases, high levels of c-erbB-2 expression were demonstrated by IHC but not by immunoblotting. In these cases, intraductal disease and stroma-rich tumors again led to a relative paucity of neoplastic tissue within the specimens. We conclude that IHC offers a favorable alternative to either Southern analysis or Western immunoblotting in the assessment of c-erbB-2 gene copy number and expression levels of oncoprotein in human mammary carcinoma. Furthermore, IHC may prove advantageous to either extraction technique in specimens with limited tumor mass, such as biopsy materials, stroma-rich tumors, or early stage lesions such as intraductal carcinoma.
The ada Verb of being in Bahasa Malaysia (1974)

This paper examines the various syntactic and semantic functions of the ada verb of 'being' in Malay. The claim is made that there is an abstract uppermost ada in the underlying structure of Malay sentences, which asserts or denies the truth of the surface main clause. A further claim is made that the ada of the uppermost sentence is identical to the ada of location and possession, the difference in meaning arising from the distinction in sentence structures in which the ada verb appears. Informants for the study were Miss Noraini Aziz of Kuala Selangor (Selangor State) and Miss Latifah Abdol Latif, of Alor Gajah (Malacca State).
Purification and characterization of hydrolytic haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 (1985)

A new enzyme, haloalkane dehalogenase, was isolated from the 1,2-dichloroethane-utilizing bacterium Xanthobacter autotrophicus GJ10. The purified enzyme catalyzed the hydrolytic dehalogenation of n-halogenated C1 to C4 alkanes, including chlorinated, brominated, and iodinated compounds. The highest activity was found with 1,2-dichloroethane, 1,3-dichloropropane, and 1,2-dibromoethane. The enzyme followed Michaelis-Menten kinetics, and the Km for 1,2-dichloroethane was 1.1 mM. Maximum activity was found at pH 8.2 and 37 degrees C. Thiol reagents such as p-chloromercuribenzoate and iodoacetamide rapidly inhibited the enzyme. The protein consists of a single polypeptide chain of a molecular weight of 36,000, and its amino acid composition and N-terminal sequence are given.
Recommendations for the management of cough in adults (2006)

N Cough is a forced expulsive manoeuvre, usually against a closed glottis and which is associated with a characteristic sound.
Phylogenetic Inference Based on Information Theory‐Based PCR Amplification (1998)

Abstract As a method for the determination of the taxonomic affinities of plant pathogens and other organisms, a set of ‘universal’ polymerase chain reaction (PCR) primers which amplify a taxonomically diverse sequence domain of 28S ribosomal DNA (rDNA) were designed. The PCR primers chosen by information‐theory analysis generated PCR products using DNA templates from a wide diversity of organisms. Sequences of PCR products were then obtained which allowed phylogenetic dendrograms to be constructed. Based on the above analysis, the Oomycete pathogen Phytophthora infestans clustered with the protist Prorocentrum micans rather than with representatives of the true fungi, consistent with its designation as a ‘pseudofungus’, Magnaporthe grisea. another important plant pathogen, clustered with the true fungi as expected. The approach described can be used with other plant pathogens to clarify phytogeny of new or ambiguously designated species.
Abstract 5477: Engineered toxin body demonstrating CD20-specific binding and cell kill in B-cell non-Hodgkin's lymphoma cells. (2013)

Abstract Non-Hodgkin's lymphoma (NHL) offers an attractive area for therapeutic biologics. The most successful example of this targeted approach is rituximab, which is approved for front and second line therapy of NHL. Rituximab targets the CD20 antigen expressed on 90% of B-cell NHL cells. However, rituximab has limited direct cell-kill effects, acting instead primarily through indirect immune responses induced by antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC). Direct-cell kill approaches to CD20 have been limited to radioimmunotherapy because CD20 does not efficiently internalize. Despite improved clinical efficacy seen over Rituximab with both 131 tositumomab and ibritumomab tiuxetan, challenges around the administration of radioimmunotherapies have severely curtailed therapeutic use. We have developed an engineered toxin body (ETB) comprising a CD20 scFv and a modified Shiga-like Toxin A (3F7) capable of specifically recognizing and killing CD20 expressing cells. Utilizing a flow cytometry based binding affinity assay, 3F7 demonstrated selective binding to CD20 positive Raji cells whereas no significant binding was observed in CD20 negative BC-1 cells. Further, direct competition of 3F7 binding to Raji cells was observed in the presence of rituximab or the parent monoclonal antibody. 3F7 demonstrated CD20-specific direct cell kill of Raji, Daudi and Ramos cells with minimal cell kill of CD20 negative BC-1 or Jurkat cells. Initial dose finding studies in mice found that a therapeutic dosing schedule was well tolerated. Raji xenograft studies in mice are ongoing. 3F7 is a novel therapeutic approach with direct cell-kill activity against CD20-expressing cells which could expand treatment options for B-cell lymphoma. Citation Format: Rachel Wirth, Sangeetha Rajagopalan, Erin Willert, William Null, Jennifer Erdman, Jen-Sing Liu, Jack P. Higgins. Engineered toxin body demonstrating CD20-specific binding and cell kill in B-cell non-Hodgkin's lymphoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5477. doi:10.1158/1538-7445.AM2013-5477
Intermediate biomarkers of precancer and their application in chemoprevention (1992)

The Chemoprevention Branch of the National Cancer Institute has established a program for the development of safe and effective cancer chemopreventive agents. This program includes identification of new agents, testing for efficacy in vitro and in animals, studies in animals to model clinical use, and preclinical toxicity and metabolism evaluation. Ultimately, the most promising agents progress to clinical trials. The long period required for cancer onset presents a significant challenge to the design of clinical trials for chemoprevention. Phase III trials in which cancer reduction is the endpoint require large subject groups (tens of thousands) and follow-up duration of more than five years. Because of these requirements, the cost of such trials are high. The Chemoprevention Branch is addressing this challenge by expansion of the preclinical and Phase II clinical efficacy efforts to include intermediate biomarkers of carcinogenesis as study endpoints. The Chemoprevention Branch's studies focus on the development of biomarkers with high reliability and predictive value for cancer. Both single markers and batteries of complementary and parallel markers are evaluated. Among the criteria for biomarkers for chemoprevention studies are the following: (1) differential expression in normal and high risk tissue, (2) appearance early in carcinogenesis (the earlier a reliable biomarker appears, the greater is the chance for successful intervention with a chemopreventive agent), (3) high sensitivity, specificity, and accuracy relative to cancer, (4) ease of measurement (use of non-invasive techniques and small tissue samples is preferable), (5) demonstration of modulation by chemopreventive agents, and (6) correlation of modulation with decreased cancer incidence.