gebhart/patrepeval huggingface dataset:
Test of Association Between Haplotypes and Phenotypes in Case–Control Studies: Examination of Validity of the Application of an Algorithm for Samples From Cohort or Clinical Trials to Case–Control Samples Using Simulated and Real Data (2006)

The use of haplotype information in case-control studies is an area of focus for the research on the association between phenotypes and genetic polymorphisms. We examined the validity of the application of the likelihood-based algorithm, which was originally developed to analyze the data from cohort studies or clinical trials, to the data from case-control studies. This algorithm was implemented in a computer program called PENHAPLO. In this program, haplotype frequencies and penetrances are estimated using the expectation-maximization algorithm, and the haplotype-phenotype association is tested using the generalized likelihood ratio. We show that this algorithm was useful not only for cohort studies but also for case-control studies. Simulations under the null hypothesis (no association between haplotypes and phenotypes) have shown that the type I error rates were accurately estimated. The simulations under alternative hypotheses showed that PENHAPLO is a robust method for the analysis of the data from case-control studies even when the haplotypes were not in HWE, although real penetrances cannot be estimated. The power of PENHAPLO was higher than that of other methods using the likelihood-ratio test for the comparison of haplotype frequencies. Results of the analysis of real data indicated that a significant association between haplotypes in the SAA1 gene and AA-amyloidosis phenotype was observed in patients with rheumatoid arthritis, thereby suggesting the validity of the application of PENHAPLO for case-control data.
Immobilisation of P450 BM‐3 and an NADP+ Cofactor Recycling System: Towards a Technical Application of Heme‐Containing Monooxygenases in Fine Chemical Synthesis (2003)

Abstract Abstract: Cytochrome P450 monooxygenases are potentially a very useful class of hydroxylation catalysts; they are able to introduce oxygen at activated and non‐activated carbon‐hydrogen bonds and thus lead to regio‐ and/or stereochemically pure compounds. However, this potential is lowered by their intrinsic low activity and inherent instability. P450‐catalysed biotransformations require a constant supply of NAD(P)H, making the process an expensive one. To render these catalysts more suitable for industrial biocatalysis, the immobilisation of P450 BM‐3 (CYP 102A1) from Bacillus megaterium in a sol‐gel matrix was combined with a cofactor recycling system based on NADP + ‐dependent formate dehydrogenase (EC 1.2.1.2) from Pseudomonas sp. 101 and tested for practical applicability. This approach was used for the conversion of β‐ionone, octane and naphthalene to the respective hydroxy compounds with DMSO as cosolvent using sol‐gel immobilised P450 BM‐3 mutants.
VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor (1999)

The potential role of the very low density lipoprotein (VLDL) receptor in mediating VLDL-induced plasminogen activator inhibitor-1 (PAI-1) expression was studied in vitro. Cultured endothelial cells incubated with VLDL showed an increased secretion of PAI-1. This response to VLDL could be completely prevented by the receptor-associated protein (RAP) and partially blocked by rabbit polyclonal anti-VLDL receptor IgG. Furthermore, Chinese hamster ovary (CHO) control cells and cells overexpressing the VLDL receptor were transiently transfected with a PAI-1 promoter-reporter construct and incubated with VLDL. The PAI-1 promoter activity in response to VLDL was significantly higher in the VLDL receptor overexpressing cells compared to the control cells. Addition of RAP completely blocked the VLDL-activated PAI-1 transcription. Electromobility shift assay was performed to investigate whether the enhanced PAI-1 promoter activity seen in the VLDL receptor overexpressing cells in response to VLDL involved induction of the previously described VLDL-inducible factor(s) binding to the -675 to -653 region of the PAI-1 promoter. We found that the binding of the VLDL-inducible factor in VLDL receptor overexpressing cells was markedly enhanced by addition of VLDL as compared to control cells where no increased binding could be seen in response to VLDL. In summary, these results indicate that the VLDL receptor is a strong candidate for mediating VLDL effects on PAI-1 synthesis and secretion in cells expressing this receptor.
Nanostructured silicon for studying fundamental aspects of nanomechanics (2002)

Nanomechanics features three-dimensional nanostructuring, which allows full exploitation of the mechanical degree of freedom on the nanometre scale. In this work a number of exemplifying experiments on nano-electromechanical systems realized in silicon materials will be presented. First an introduction to the underlying mechanics will be given and finite element methods required for simulations will be discussed. Further topics presented include measurement methods for probing the mechanical properties of free standing nanowires, sensor applications and nonlinear properties of nanomechanical resonators. Other applications such as parametric frequency tuning are demonstrated and the major sources of dissipation are discussed. Finally, an outlook over the fundamental limits of nanoresonators is given.
Transformation of Tooth Type Induced by Inhibition of BMP Signaling (1998)

Mammalian dentitions are highly patterned, with different types of teeth positioned in different regions of the jaws. BMP4 is an early oral epithelial protein signal that directs odontogenic gene expression in mesenchyme cells of the developing mandibular arch. BMP4 was shown to inhibit expression of the homeobox gene Barx-1 and to restrict expression to the proximal, presumptive molar mesenchyme of mouse embryos at embryonic day 10. The inhibition of BMP signaling early in mandible development by the action of exogenous Noggin protein resulted in ectopic Barx-1 expression in the distal, presumptive incisor mesenchyme and a transformation of tooth identity from incisor to molar.
Inhibition of Neointima Formation After Experimental Coronary Artery Stenting (2000)

The results from this study demonstrate beneficial effects of a polymeric stent coating with polylactic acid releasing r-PEG-hirudin and iloprost on the development of restenosis after coronary stent placement at 4 weeks, independent of the extent of vascular injury. Future studies are proposed to investigate the integration of other substances to further enhance the potential of the stent coating on reducing neointimal formation.
Annexin A2 Is a Novel RNA-binding Protein (2004)

Annexin A2 (ANXA2) is a Ca(2+)-binding protein that is up-regulated in virally transformed cell lines and in human tumors. Here, we show that ANXA2 binds directly to both ribonucleotide homopolymers and human c-myc RNA. ANXA2 was shown to bind specifically to poly(G) with high affinity (K(d) = 60 nM) and not to poly(A), poly(C), or poly(U). The binding of ANXA2 to poly(G) required Ca(2+) (A(50%) = 10 microM). The presence of RNA in the immunoprecipitates of ANXA2 isolated from HeLa cells established that ANXA2 formed a ribonucleoprotein complex in vivo. Sucrose gradient analysis showed that ANXA2 associates with ribonucleoprotein complexes and not with polyribosomes. Reverse transcriptase-PCR identified c-myc mRNA as a component of the ribonucleoprotein complex formed by ANXA2 in vivo, and binding studies confirmed a direct interaction between ANXA2 and c-myc mRNA. Transfection of LNCaP cells with the ANXA2 gene resulted in the up-regulation of c-Myc protein. These findings identify ANXA2 as a Ca(2+)-dependent RNA-binding protein that interacts with the mRNA of the nuclear oncogene, c-myc.
Fas-Independent Apoptosis of Activated T Cells Induced by Antibodies to the HLA Class I α1 Domain (1997)

In addition to their major function in antigen presentation and natural killer cell activity regulation, HLA class I molecules may modulate T-cell activation and proliferation. Monoclonal antibodies (MoAbs) that recognize distinct epitopes of HLA class I molecules were reported to interfere with T-cell proliferation. We show here that two MoAbs (mouse MoAb90 and rat YTH862) that bind to an epitope of the alpha1 domain of HLA class I heavy chain induce apoptotic cell death of activated, but not resting, peripheral T lymphocytes. Other reference anti-HLA class I antibodies specific for distinct epitopes of the alpha1 (B9.12.1), alpha2 (W6/32), or alpha3 (TP25.99) domains of the heavy chain decreased T-cell proliferation but had little or no apoptotic effect. Apoptosis shown by DNA fragmentation, phosphatidylserine externalization, and decrease of mitochondrial transmembrane potential was observed whatever the type of T-cell activator. Apoptosis did not result from Fas/Fas-L interaction and distinct though partly overlapping populations of activated T cells were susceptible to Fas- and HLA class I-mediated apoptosis, respectively. Induction of apoptosis did not require HLA class I cross-linking inasmuch as it could be observed with monovalent Fab' fragments. The data indicate that MoAb90 and YTH862 directed against the alpha1 domain of HLA class I trigger apoptosis of activated T lymphocytes by a pathway which does not involve Fas-ligand.
Electric tweezers: negative dielectrophoretic multiple particle positioning (2012)

Electric tweezers are a touchless positioning apparatus that employs dielectrophoresis and electroorientation to arbitrarily position cell-sized particles. In this paper, we develop an algorithm which enables electric tweezers to operate on multiple particles. Furthermore, we probe the limits of this technique in simulation, examining the range of electric field magnitudes and forces that can be applied. We then demonstrate this new functionality on two particles. The device can apply forces on any particle of non-zero polarizability and here this is highlighted by manipulating negatively polarized glass beads. Additionally, we demonstrate that negligibly polarized particles can also be manipulated through mechanical forces applied by other particles.
Mouse monoclonal antibodies against outer membrane proteins of a vaccine strain of Neisseria meningitidis B: 4:P1.15 (1998)

Background. Neisseria meningitidis (Nm) is a Gram negative diplococcus causing bacterial meningitis and fulminant septicemia. In order to allow efficient characterization of infecting strains, antibody reagents for use as analytical tools have proven to be invaluable tools. Similarly, antibodies against relevant bacterial antigens may guide in the selection of components to be included in developing vaccine strategies. Methods. We have thus developed mouse monoclonal antibodies specific for class 1, 3 and 5 antigens expressed by the B:4:P1.15 isolate CU385/83, also being used in a recently developed protective vaccine. In particular, two antibodies CB-Nm.1 and CB- Nm.2 recognize epitopes partly overlapping the subserotype (class 1 antigens) and serotype (class 3 antigen) specificities detected by the previously defined antibodies C6 and 15-1-P4 respectively, were evaluated. Results. As judged by strain recognition, the absolute requirement for binding differs between both the class 1-specific and class 3 specific antibodies suggesting the importance of using multiple antibodies when evaluating subserotype/serotype characteristics of clinical isolates of Nm by serological methods. Conclusion. Furthermore, the development of antibodies crossreactive with subserotype/serotype antigens may partly explain the ability of outer membrane protein vaccine to induce protective activity against strains considered as carrying different class 1 and 3 antigens as determined by available (sub)serotyping reagents.
4D-QSAR Models of HOE/BAY-793 Analogues as HIV-1 Protease Inhibitors (2004)

HIV-1 protease is a homodimer composed of monomer subunits, each containing 99 amino acids with a single catalytic Asp residue. Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis was applied to a series of 32 C2-symmetric diol inhibitors of HIV-1 protease. The 4D-QSAR approach can be applied to both receptor-dependent (RD) and receptor-independent (RI) problems. In the first scheme, the geometry of the receptor (molecular target, usually an enzyme) is available. By contrast, in the second scheme, the geometry of the receptor is not available or is not included in the data necessary to the analysis. Twenty-eight compounds belong to the training set, and four to the test set, which was used for external validation. These compounds are analogues of inhibitor HOE/BAY-793, important for its outstanding potency in vitro and, especially, in HIV-1 infected cell culture. Five thousand conformations of each analogue were sampled by molecular dynamic simulation for 50 ps at a constant temperature of 300 K. For each of the three trial alignments, each conformation was placed in a 2 Å grid cell lattice. Optimized 4D-QSAR models were constructed by genetic algorithm (GA) optimization and partial least squares (PLS) fitting, and evaluated by the leave-one-out cross-validation method. The models developed in this analysis suggest that alignment 3 yields the best results, both statistically and qualitatively. The 4D-QSAR models developed in this study suggest novel molecular regions to be explored in the search for better anti-HIV agents to inhibit HIV-1 protease.
Extrahepatic transcription of human C-reactive protein. (1991)

We synthesized and cloned cDNA from human peripheral blood mononuclear cell (PBMC) transcripts that were hybrid selected by pCRP5, a liver C-reactive protein (CRP)-specific cDNA (Woo, P.,J.R. Korenberg, and A.S. Whitehead. 1985. J.Biol. Chem. 260:13384). Three hybrid-selected cDNA clones, HScDNA1, HScDNA3, and HScDNA8, were isolated and characterized. Nucleotide sequence analysis of the 5' end of the smaller clones, HScDNA1 and HScDNA8, demonstrated that these two PBMC clones are homologous to the 3' and 5' ends, respectively, of pCRP5. Our largest clone, HScDNA3, is larger than pCRP5, extending beyond both the 5' and 3' limits of pCRP5. Therefore, HScDNA3 was coded by human PBMC and not by the hybrid selection vehicle, pCRP5. HScDNA3 lacks the intervening sequence verifying that this clone is DNA made from a PBMC mRNA and not genomic DNA. The complete nucleotide sequence revealed that HScDNA3 is greater than 99% homologous to the CRP gene. These results demonstrate that PBMC express the CRP gene. Based on our previous report, which shows that peripheral blood cells synthesize a peptide recognized by anti-CRP (Kuta, A.E., and L.L. Baum. 1986. J. Exp. Med. 164:321), in conjunction with the data presented here, we conclude that human PBMC can synthesize CRP.
Current State of the Art of New Tubulin Inhibitors in the Clinic (2006)

For years the microtubule stabilizing agents docetaxel and paclitaxel belong to the most successful clinical chemotherapeutic agents. Several attempts have been made over the years to equal and better these drugs. Both taxanes are associated with the notorious side effect neurotoxicity and are often accompanied with increased drug resistance and cross resistance with other chemotherapeutic agents. In addition their high lipophilicity demands use of co-solvents, which are associated with less favorable side effects such as hypersensitivity. To prevent these disadvantages and improve the clinical application of the taxanes several new agents have entered clinical testing. The agents that are discussed are the drug class of the discodermolides; XAA296A and the epothilones; BMS-247550, BMS-310705, epo906, kos-862 and the agents ABT-751 and D-24851. Here we present an overview of recently performed clinical studies to determine the current state of the art of the tubulin inhibitors which are intended to enlarge and improve the clinical use of the taxanes docetaxel and paclitaxel.
Mitochondrial Targeting with Antioxidant Peptide SS-31 Prevents Mitochondrial Depolarization, Reduces Islet Cell Apoptosis, Increases Islet Cell Yield, and Improves Posttransplantation Function (2006)

Apoptotic cell death is a defined pathway for islet cell demise, and mitochondrial dysfunction contributes to islet cell apoptosis. The hypothesis that the novel peptide D-Arg-2', 6'-dimethyltyrosine-Lys-Phe-NH2 (SS-31), previously shown to target inner mitochondrial membrane and prevent oxidative damage of neuronal cells and other cell types, optimizes pancreatic islet isolation and improves posttransplantation function in recipients with diabetes was investigated. Herein is demonstrated that SS-31 readily penetrates intact mouse islets, preserves mitochondrial polarization, reduces islet cell apoptosis, and increases islet cell yield. Optimization of islet isolation is demonstrable after SS-31 pretreatment of islet (pancreas) donor mice and with the addition of SS-31 to reagents that are used in the isolation of mouse islets. The supplementation of in vitro culture medium with SS-31 reduced islet cell apoptosis and increased the viability of human islets, as ascertained by dual-parameter flow cytometry analysis. In a stringent marginal islet cell mass transplantation model (200 mouse islets transplanted under the renal capsule of syngeneic diabetic mice) and using islets that were derived from old mice (>24 wk), SS-31 treatment was associated with prompt and sustained normoglycemia, whereas the untreated islet graft recipients remained diabetic. Our data suggest a novel strategy to optimize islet isolation and reduce the need for multiple pancreata to achieve insulin independence in the recipient with type 1 diabetes. Because SS-31 was effective with "extended" islet donors, it is hypothesized that the antioxidant SS-31 may serve to increase the pool of eligible organ donors.
Synthesis and characterization of highly efficient and thermally stable diphenylamino‐substituted thiophene stilbene chromophores for nonlinear optical applications (1997)

Highly nonlinear chromophores with good thermal stabilities (&gt; 250 °C) are required if organic polymeric materials are to be developed for electro‐optical (EO) applications. The synthesis and characterization of highly efficient and thermally stable diphenylamino‐substituted thiophene stilbenes (e.g., see Figure) are reported, one of which was used to form a high‐EO‐coefficient composite with a polyquinoline. magnified image
Expression of bicistronic measles virus P/C mRNA by using hybrid adenoviruses: levels of C protein synthesized in vivo are unaffected by the presence or absence of the upstream P initiator codon (1988)

The measles virus (MV) P/C mRNA is functionally bicistronic. Translation is presumed to initiate at both the first and second 5'-proximal AUG codons, leading, respectively, to synthesis of the P and C polypeptides from different overlapping reading frames. To study the function and differential expression of these polypeptides, we have constructed hybrid human adenoviruses capable of expressing high levels of P and C together or of C alone. Cloned cDNA corresponding to the MV P/C gene was coupled to the adenovirus type 2 (Ad2) major late promoter, most of the Ad2 tripartite leader sequence, and the simian virus 40 3'-end processing signal and then used to replace most of the E1a-E1b region of the Ad5 genome in two hybrid adenoviruses: one (Ad5MV/PC13) which contained both 5'-proximal AUG codons of the P/C mRNA and another (Ad5MV/C3) which retained only the second. The sequence context for the P protein initiator AUG codon in Ad5MV/PC13 was made more favorable (GAGAUGG) than the relatively unfavorable context (CCGAUGG) seen in the native MV P/C mRNA. After infection of 293 cells (which provide complementary E1a-E1b functions), both viruses directed equal amounts of P/C-specific mRNA transcription. Ad5MV/PC13 directed the synthesis of both P and C proteins, while Ad5MV/C3 directed the synthesis of C protein alone. Ad5-expressed P protein was phosphorylated, while C was not. C protein had a similar diffuse cytoplasmic localization in both MV and Ad5-infected cells. Ad5MV/C3 and Ad5MV/PC13 directed equal amounts of C protein expression in 293 cells at a level approximately 15 times greater than that seen in MV-infected cells. Thus the level of C protein expression was unaffected by the presence or absence of an out-of-frame upstream AUG codon in a favorable sequence context. This observation cannot be explained by the scanning model for ribosomal initiation and suggests that ribosomes may be binding directly at an internal mRNA site at or near the initiator AUG codon for the C protein.
Expression of the Granule-Bound Starch Synthase I (Waxy) Gene from Snapdragon Is Developmentally and Circadian Clock Regulated1 (1999)

The granule-bound starch synthase I (GBSSI or waxy) enzyme catalyzes one of the enzymatic steps of starch synthesis. This enzyme is responsible for the synthesis of amylose and is also involved in building the final structure of amylopectin. Little is known about expression of GBSSI genes in tissues other than storage organs, such as seeds, endosperm, and tuber. We have isolated a gene encoding the GBSSI from snapdragon (Antirrhinum majus). This gene is present as a single copy in the snapdragon genome. There is a precise spatial and developmental regulation of its expression in flowers. GBSSI expression was observed in all floral whorls at early developmental stages, but it was restricted to carpel before anthesis. These results give new insights into the role of starch in later reproductive events such as seed filling. In leaves the mRNA level of GBSSI is regulated by an endogenous circadian clock, indicating that the transition from day to night may be accompanied by abolition of expression of starch synthesis genes. This mechanism does not operate in sink tissues such as roots when grown in the dark.
Crystallization of Escherichia coli ribosomes (1982)

U)-directed synthesis Polyphenylalanine
Characterization of MSM1, the structural gene for yeast mitochondrial methionyl‐tRNA synthetase (1989)

Respiratory-deficient mutants of Saccharomyces cerevisiae assigned to pet complementation group G72 are impaired in mitochondrial protein synthesis. The loss of this activity has been correlated with the inability of the mutants to acylate the two methionyl-tRNAs of yeast mitochondria. A nuclear gene (MSM1) capable of complementing the respiratory deficiency has been cloned by transformation of the G72 mutant C122/U3 with a yeast genomic library. In situ disruption of the MSM1 gene in a wild-type haploid strain of yeast induces a respiratory-deficient phenotype but does not affect the ability of the mutant to grow on fermentable substrates indicating that the product of MSM1 functions only in mitochondrial protein synthesis. Mitochondrial extracts prepared from the mutant with the disrupted copy of MSM1 were found to be defective in acylation of the two mitochondrial methionyl-tRNAs thereby confirming the identity of MSM1 as the structural gene for the mitochondrial methionyl-tRNA synthetase. The sequence of the protein encoded by MSM1 is similar to the Escherichia coli and yeast cytoplasmic methionyl-tRNA synthetases. Based on the primary-sequence similarities of the three proteins, the mitochondrial enzyme appears to be more related to the bacterial than to the yeast cytoplasmic methionyl-tRNA synthetase.