gebhart/patrepeval huggingface dataset:
Peroxisome proliferator-activated receptor gamma and retinoid X receptor ligands are potent inducers of differentiation and apoptosis in leukemias. (2004)

The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a member of the nuclear receptor family that forms heterodimers with retinoid X receptor. These heterodimers bind to DNA and activate the transcription of target genes. Here, we report that the PPAR gamma receptor protein is expressed in primary myeloid and lymphoid leukemias and in lymphoma and myeloma cell lines. In this study, we compared the activity of several PPAR gamma ligands including BRL49653 (rosiglitazone), 15-deoxy-Delta 12,14-prostaglandin J(2), and the novel triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid on leukemia cells. Exposure to these PPAR gamma ligands induced apoptosis in myeloid (U937 and HL-60) and lymphoid (Su-DHL, Sup-M2, Ramos, Raji, Hodgkin's cell lines, and primary chronic lymphocytic leukemia) cells. A similar exposure to these PPAR gamma ligands induced the differentiation of myeloid leukemic cells. A combination of PPAR gamma ligands with a retinoid X receptor agonist (i.e., LG100268) or a retinoic acid receptor agonist (i.e., all trans-retinoic acid) enhanced differentiating and growth-inhibitory effects. 2-Cyano-3,12-dioxooleana-1,9-dien-28-oic acid induced differentiation and apoptosis with much greater potency than the other PPAR gamma ligands in established cell lines and primary chronic lymphocytic leukemia samples. Exposure to 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induced mitochondrial depolarization and caspase activation, which was associated with apoptosis induction. In Bcl-2-overexpressing chronic lymphocytic leukemia cells, the small-molecule Bcl-2 inhibitor HA14-1 sensitized these cells to 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid-induced apoptosis. These results suggest that PPAR gamma ligation alone and in combination with retinoids holds promise as novel therapy for leukemias by activating the transcriptional activity of target genes that control apoptosis and differentiation in leukemias.
In vivo microRNA-155 expression influences antigen-specific T cell-mediated immune responses generated by DNA vaccination (2011)

These results suggest that miR-155 may repress the expression of key molecules involved in lymph node migration, antigen presentation, or T cell activation in DCs, and thus forms part of a negative regulatory pathway that dampens the generation of T cell-mediated immune responses. Modulation of miR-155 expression in epidermis therefore represents a potentially promising form of gene therapy for the control of diseases ranging from autoimmunity to cancer and viral infection.
Dendritic cells are potent antigen-presenting cells for microbial superantigens. (1992)

Dendritic cells are a small subset of human blood mononuclear cells that are potent stimulators of several T cell functions. Here we show they are 10-50-fold more potent than monocytes or B cells in inducing T cell responses to a panel of superantigens. Furthermore, dendritic cells can present femtomolar concentrations of superantigen to T cells even at numbers where other antigen-presenting cells (APCs) are inactive. Although dendritic cells express very high levels of the major histocompatibility complex products that are required to present superantigens, it is only necessary to pulse these APCs for 1 hour with picomolar levels of one superantigen, staphylococcal enterotoxin B, to maximally activate T cells. Our results suggest that very small amounts of superantigen will be immunogenic in vivo if presented on dendritic cells.
Cathelicidin Peptides Inhibit Multiply Antibiotic-Resistant Pathogens from Patients with Cystic Fibrosis (2001)

Endogenous peptide antibiotics are under investigation as inhaled therapeutic agents for cystic fibrosis (CF) lung disease. The bactericidal activities of five cathelicidin peptides (LL37 [human], CAP18 [rabbit], mCRAMP [mouse], rCRAMP [rat], and SMAP29 [sheep]), three novel alpha-helical peptides derived from SMAP29 and termed ovispirins (OV-1, OV-2, and OV-3), and two derivatives of CAP18 were tested by broth microdilution assays. Their MICs were determined for multiply antibiotic-resistant Pseudomonas aeruginosa (n = 24), Burkholderia cepacia (n = 5), Achromobacter xylosoxidans (n = 5), and Stenotrophomonas maltophilia (n = 5) strains isolated from CF patients. SMAP29 was most active and inhibited mucoid and nonmucoid P. aeruginosa strains (MIC, 0.06 to 8 microg/ml). OV-1, OV-2, and OV-3 were nearly as active (MIC, 0.03 to 16 microg/ml), but CAP18 (MIC, 1.0 to 32 microg/ml), CAP18-18 (MIC, 1.0 to >32 microg/ml), and CAP18-22 (MIC, 0.5 to 32 microg/ml) had variable activities. LL37, mCRAMP, and rCRAMP were least active against the clinical isolates studied (MIC, 1.0 to >32 microg/ml). Peptides had modest activities against S. maltophilia and A. xylosoxidans (MIC range, 1.0 to > 32 microg/ml), but none inhibited B. cepacia. However, CF sputum inhibited the activity of SMAP29 substantially. The effects of peptides on bacterial cell membranes and eukaryotic cells were examined by scanning electron microscopy and by measuring transepithelial cell resistance, respectively. SMAP29 caused the appearance of bacterial membrane blebs within 1 min, killed P. aeruginosa within 1 h, and caused a dose-dependent, reversible decrease in transepithelial resistance within 5 h. The tested cathelicidin-derived peptides represent a novel class of antimicrobial agents and warrant further development as prophylactic or therapeutic agents for CF lung disease.
The Extent of Histone Acetylation Correlates with the Differential Rearrangement Frequency of Individual VH Genes in Pro-B Cells (2005)

During B lymphocyte development, Ig heavy and L chain genes are assembled by V(D)J recombination. Individual V, D, and J genes rearrange at very different frequencies in vivo, and the natural variation in recombination signal sequence does not account for all of these differences. Because a permissive chromatin structure is necessary for the accessibility of VH genes for VH to DJH recombination, we hypothesized that gene rearrangement frequency might be influenced by the extent of histone modifications. Indeed, we found in freshly isolated pro-B cells from muMT mice a positive correlation between the level of enrichment of VHS107 genes in the acetylated histone fractions as assayed by chromatin immunoprecipitation, and their relative rearrangement frequency in vivo. In the VH7183 family, the very frequently rearranging VH81X gene showed the highest association with acetylated histones, especially in the newborn. Together, our data show that the extent of histone modifications in pro-B cells should be considered as a mechanism by which accessibility and the rearrangement level of individual VH genes is regulated.
Improved side‐chain torsion potentials for the Amber ff99SB protein force field (2010)

Recent advances in hardware and software have enabled increasingly long molecular dynamics (MD) simulations of biomolecules, exposing certain limitations in the accuracy of the force fields used for such simulations and spurring efforts to refine these force fields. Recent modifications to the Amber and CHARMM protein force fields, for example, have improved the backbone torsion potentials, remedying deficiencies in earlier versions. Here, we further advance simulation accuracy by improving the amino acid side-chain torsion potentials of the Amber ff99SB force field. First, we used simulations of model alpha-helical systems to identify the four residue types whose rotamer distribution differed the most from expectations based on Protein Data Bank statistics. Second, we optimized the side-chain torsion potentials of these residues to match new, high-level quantum-mechanical calculations. Finally, we used microsecond-timescale MD simulations in explicit solvent to validate the resulting force field against a large set of experimental NMR measurements that directly probe side-chain conformations. The new force field, which we have termed Amber ff99SB-ILDN, exhibits considerably better agreement with the NMR data.
New enzymatic assay for calcium in serum. (1996)

We established a simple and rapid kinetic assay for measurement of calcium in serum by using urea amidolyase (EC 3.5.1.45) from yeast species. The method is based on inhibition of the enzyme by calcium. In the assay, we eliminated endogenous ammonium ion by use of glutamate dehydrogenase (GLDH; EC 1.4.1.4); then in the presence of urea amidolyase, urea, ATP, bicarbonate, magnesium, and potassium ions, ammonium ion production was inversely proportional to calcium ion concentration in serum. The concentration of ammonium ion formed was determined by adding GLDH to produce NADP+ in the presence of 2-oxoglutarate and NADPH; we then monitored the change of absorbance at 340 nm. The within-run CVs of this method were 1.7-3.2% (n = 10) at 1.53-3.08 mmol/L, respectively. Day-to-day (total) CVs were 2.8-4.1%. Analytical recovery was 92-112%. The presence of other ions, ascorbic acid, reduced glutathione, bilirubin, hemoglobin, citrate, lipemic material, or human serum albumin did not affect this assay system. The correlation between values obtained with our method (y) and o-cresolphthalein complexone method (CPC) (x) was: y = 1.001x + 0.077 mmol/L (r = 0.949, Sy[symbol: see text]x = 0.079, n = 100); with the other enzymatic method (x) it was: y = 0.952x + 0.021 mmol/L (r = 0.955, Sy[symbol: see text]x = 0.074, n = 100). The SEs for each method were: 0.025 mmol/L, our method; 0.023 mmol/L, CPC method; and 0.025 mmol/L, the other enzymatic method.
Activities of Tizoxanide and Nitazoxanide Compared to Those of Five Other Thiazolides and Three Other Agents against Anaerobic Species (2006)

ABSTRACT Agar dilution was used, and MICs of metronidazole, tizoxanide, nitazoxanide, denitrotizoxanide, RM 4803, RM 4807, RM 4809, RM 4819, amoxicillin-clavulanate, and clindamycin were measured against 412 anaerobes. Nitazoxanide, tizoxanide, RM 4807, and RM 4809 were active against all groups, except for gram-positive non-spore-forming rods with 50% minimum inhibitory concentrations (when the latter were excluded) of 1 to 2 μg/ml and 90% minimum inhibitory concentrations of 4 to 8 μg/ml, respectively. Metronidazole MICs were usually lower against all groups except clostridia.
Recurrent angina after coronary revascularization: a clinical challenge (2007)

Coronary revascularization procedures by means of percutaneous coronary interventions or coronary artery bypass graft surgeries are performed worldwide daily for the symptomatic treatment of patients with myocardial ischaemia. Nevertheless, angina remains a significant clinical problem. Management of angina recurring or persisting after coronary revascularization is particularly challenging. This review attempts to summarize the most common causes of recurrent chest pain after coronary revascularization, to analyse the possible diagnostic approaches, and to discuss the potential treatment modalities.
Tetronothiodin, a novel cholecystokinin type-B recepter antagonist produced by Streptomyces sp. NR0489. I. Taxonomy, yield improvement and fermentation. (1993)

Streptomyces sp. NR0489 produces tetronothiodin, a novel brain-type cholecystokinin receptor antagonist. This species was differentiated from its related species S. gelaticus, S. griseolus and S. hydrogenans on the basis of their cultural characteristics, such as the utilization of carbohydrates and the presence or absence of various enzymatic activities. We applied the DNA-DNA hybridization method using photobiotin, which proved the genetic difference between the four species mentioned above. The yield improvement effort including single colony isolation, mutation, and protoplast regeneration together with medium optimization resulted in more than an 81-fold increase of the productivity of tetronothiodin as compared to that of the wild type strain.
3D Lithography, Etching, and Deposition Simulation (Sample-3D) (1991)

Here we report on the new 3D topography simulator SAMPLE-3D for lithoggraphy, etching and deposition, that uses both surface and cell based topology representations, for high accuracy and efficiency.
The dynameomics rotamer library: Amino acid side chain conformations and dynamics from comprehensive molecular dynamics simulations in water (2010)

We have recently completed systematic molecular dynamics simulations of 807 different proteins representing 95% of the known autonomous protein folds in an effort we refer to as Dynameomics. Here we focus on the analysis of side chain conformations and dynamics to create a dynamic rotamer library. Overall this library is derived from 31,000 occurrences of each of 86,217 different residues, or 2.7 × 10(9) rotamers. This dynamic library has 74% overlap of rotamer distributions with rotamer libraries derived from static high-resolution crystal structures. Seventy-five percent of the residues had an assignable primary conformation, and 68% of the residues had at least one significant alternate conformation. The average correlation time for switching between rotamers ranged from 22 ps for Met to over 8 ns for Cys; this time decreased 20-fold on the surface of the protein and modestly for dihedral angles further from the main chain. Side chain S(2) axis order parameters were calculated and they correlated well with those derived from NMR relaxation experiments (R = 0.9). Relationships relating the S(2) axis order parameters to rotamer occupancy were derived. Overall the Dynameomics rotamer library offers a comprehensive depiction of side chain rotamer preferences and dynamics in solution, and more realistic distributions for dynamic proteins in solution at ambient temperature than libraries derived from crystal structures, in particular charged surface residues are better represented. Details of the rotamer library are presented here and the library itself can be downloaded at http://www.dynameomics.org.
Video Data Shuffling for the 4:2:2 DVTR (1986)

Shuffling, as a means of concealing errors on videotape, is discussed in general terms, as it might apply to any DVTR. The requirements and nature of shuffling as they specifically apply to the 4:2:2 DVTR are covered, with emphasis on the relationship between shuffling and other system-level considerations, especially error-correction coding. The particular shuffling algorithm adopted by the SMPTE in the 4:2:2 DVTR standard, including its superior error-concealment properties, picture-in-shuttle quality, and ease and simplicity of implementation, are also described.
Arsenic Trioxide Stabilizes Accumulations of Adeno-Associated Virus Virions at the Perinuclear Region, Increasing Transduction In Vitro and In Vivo (2013)

Interactions with cellular stress pathways are central to the life cycle of many latent viruses. Here, we utilize adeno-associated virus (AAV) as a model to study these interactions, as previous studies have demonstrated that cellular stressors frequently increase transduction of recombinant AAV (rAAV) vectors and may even substitute for helper virus functions. Since several chemotherapeutic drugs are known to increase rAAV transduction, we investigated the effect of arsenic trioxide (As(2)O(3)), an FDA-approved chemotherapeutic agent with known effects on several other virus life cycles, on the transduction of rAAV. In vitro, As(2)O(3) caused a dose-dependent increase in rAAV2 transduction over a broad range of cell lines from various cell types and species (e.g., HEK-293, HeLa, HFF hTERT, C-12, and Cos-1). Mechanistically, As(2)O(3) treatment acted to prevent loss of virions from the perinuclear region, which correlated with increased cellular vector genome retention, and was distinguishable from proteasome inhibition. To extend our investigation of the cellular mechanism, we inhibited reactive oxygen species formation and determined that the As(2)O(3)-mediated increase in rAAV2 transduction was dependent upon production of reactive oxygen species. To further validate our in vitro data, we tested the effect of As(2)O(3) on rAAV transduction in vivo and determined that treatment initiated transgene expression as early as 2 days posttransduction and increased reporter expression by up to 10-fold. Moreover, the transduction of several other serotypes of rAAV was also enhanced in vivo, suggesting that As(2)O(3) affects a pathway used by several AAV serotypes. In summary, our data support a model wherein As(2)O(3) increases rAAV transduction both in vitro and in vivo and maintains perinuclear accumulations of capsids, facilitating productive nuclear trafficking.
Variable major proteins of Borrellia hermsii. (1982)

Borrelia hermsii, a relapsing fever agent, manifests antigenic variation in vivo and in vitro. We studied three mouse-passaged serotypes of strain HS1 (7, 14, and 21) and a HS1 derivative obtained after multiple in vitro passages (C serotype). All four serotypes had two major proteins in whole cell lysates fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. One major protein species (pII) had the same apparent subunit molecular weight (or approximately 3.9 X 10(4) in all the serotypes. In contrast, the other abundant protein in lysates, pI, had a different apparent molecular weight in each serotype. In one gel the molecular weights of pIc, pI7, pI14, and pI21 were 1.9, 4.2, 4.1, and 4.0 X 10(4), respectively. Serotype-specific mouse antisera bound to both hemologous and heterologous pIIs, to homologous pI, but not to heterologous pI in Western blots. Hybridomas were raised from spleens of mice infected with B. hermsii. Monoclonal antibodies were identified by immunofluorescence assays using whole organisms. Monoclonal antibodies specific for serotype 7 (H1826) or for serotype 21 (H3326) bound only to pI7 or pI21, respectively, in Western blots. The surface location of the pI was suggested not only by the immunofluorescence studies but also by the labeling of pI7 and pI21 when whole cells of serotypes 7 and 21 were incubated with 125I in the presence of Iodogen. Under the same circumstances, pII was relatively poorly labeled. These studies have identified the variable pI proteins of B. hermsii as serotype-specific antigens. A change from one pI to another may be the basis of antigenic variation of Borrelia species during relapsing fever.
Distortion analysis of periodically switched nonlinear circuits using time-varying Volterra series (2001)

This paper presents a new frequency-domain method for distortion analysis of general periodically switched nonlinear circuits. It generalizes Zadeh's time-varying network functions and bifrequency transfer functions from linear time-varying systems to nonlinear time-varying systems. The periodicity of time-varying network functions of linear and nonlinear periodically time-varying systems is investigated using time-varying Volterra series. We show that a periodically switched nonlinear circuit can be characterized by a set of coupled periodically switched linear circuits. Distortion of the periodically switched nonlinear circuit is obtained by solving these linear circuits. This result is a generalization of the multi-linear theory known for nonlinear time-invariant circuits. We also show that the aliasing effect encountered in noise analysis of switched analog circuits exists in distortion analysis of periodically switched nonlinear circuits. Computation associated with the folding effect can be minimized by using the adjoint network of periodically switched linear circuits, in particular, the frequency reversal theorem. The method presented in this paper has been implemented in a computer program. Distortion of practical switched circuits is analyzed and the results are compared with SPICE simulation.
A new neural network architecture for efficient close proximity match of large databases (2002)

A new paradigm of multiple neural networks organized in a hierarchical structure is used to perform close proximity matches in large databases. The basic unit of this hierarchical structure is a modified Hopfield neural network with a new off-line training scheme. This scheme is adopted as it provides a quick learning property with no spurious states. The neural networks are not trained by the actual data, rather signatures which are obtained by superimposed coding on partitions of the input data. This allows the networks to be smaller sizes and the hierarchical structure allows a small sample of input data for training the networks. The paradigm is tested on two extremely opposite databases, viz., library retrieval systems and protein databases. The experimental results are reported to corroborate that high level of precision can be obtained for efficient recall of inexact queries using the proposed neural network.
Mechanisms of drug loading and release kinetics. (1999)

In an effort to overcome the limitations of local drug delivery associated with the use of catheters, drug-loaded stents have been developed. Loading of such stents is achieved through either drug absorption (incorporation into a matrix) or drug adsorption (surface layering). The type of drug binding determines the elution profile/release kinetics of the drug, while the therapeutic target determines both the choice of drug used and the manner in which it is bound, i.e. eluting or non-eluting. While non-eluting stents have clinically reduced thrombotic complications following stent implantation, current experimental work concentrates on the use of eluting stents to combat restenosis.
责任会计会干扰公司目标的达到 责任会计:警告审计员 (1988)

大多数公司面临的问题不是建立责任会计制度与否,而是实施这样一项计划该是多么的复杂。责任会计——也称为利润中心会计,获利能力会计,或者作业会计——是处于分散经营下一种重要的、通常必不可少的控制工具。然而,审慎地使用这一工具要求管理部门,特别是审计人员了解责任会计制度可能引起企业功能紊乱的后果。进一步说,内部审计人员必须设计包括检查功能紊乱行为过程在内的审计项目。
Adeno-associated virus mediated interferon-gamma inhibits the progression of hepatic fibrosis in vitro andin vivo (2005)

All these results indicated that rAAV-INF-gamma has potential effects for gene therapy of hepatic fibrosis, which could inhibit the progression of hepatic fibrosis.
One-Step Cloning and Chromosomal Integration of DNA (2013)

We describe "clonetegration", a method for integrating DNA into prokaryotic chromosomes that approaches the simplicity of cloning DNA within extrachromosomal vectors. Compared to existing techniques, clonetegration drastically decreases the time and effort needed for integration of single or multiple DNA fragments. Additionally, clonetegration facilitates cloning and expression of genetic elements that are impossible to propagate within typical multicopy plasmids.
Facile preparation of porous NiTiO3 nanorods with enhanced visible-light-driven photocatalytic performance (2012)

Porous NiTiO3 nanorods have been successfully synthesized by an ethylene glycol-mediated route at room temperature followed by calcination at 600 °C in air. Characterisation results reveal that the obtained NiTiO3 nanorods are 3 μm in length and 400 nm in diameter. They possess rough surfaces and accumulation holes, which are beneficial for adsorption and thereby superior for photocatalysis. The porous NiTiO3 nanorods possess a noticeable optical absorbance in the visible range, indicating they have visible light photoresponse. The photocatalytic activity is evaluated in the degradation of nitrobenzene, which is a highly toxic organic pollutant in wastewaters. The porous NiTiO3 nanorods exhibit better photocatalytic activity under visible light irradiation than that of NiTiO3 nanoparticles and commercial TiO2 (Degussa P25). The enhancement is attributed to the porous texture, which offers more active sites and facilitates mass transport, and the special 1D structure that favors the separation of photogenerated electron–hole pairs, which is confirmed by surface photovoltage spectra.