gebhart/patrepeval huggingface dataset:
New Strategies for Organic Catalysis:  The First Enantioselective Organocatalytic 1,3-Dipolar Cycloaddition (2000)

Our laboratory has been engaged in the design of broadly useful new strategies for enantioselective catalysis that utilize organic chemicals as reaction catalysts. In our recent study, we reported that the LUMO-lowering activation of α,β-unsaturated aldehydes using the reversible formation of iminium ions with chiral imidazolidinones 1 (eq 1) is a valuable platform for the development of enantioselective organocatalytic Diels−Alder reactions (eq 2). In this work, we reveal that this catalytic strategy is also amenable to [3 + 2] cycloadditions between nitrones and α,β-unsaturated aldehydes to provide isoxazolidines (eq 3), useful synthons for the construction of biologically important amino acids, β-lactams, amino carbohydrates, and alkaloids. To our knowledge, this is the first example of an organocatalytic 1,3-dipolar cycloaddition. Moreover, this study further documents that chiral amines can be employed as asymmetric catalysts for a range of transformations that traditionally utilize metal salts.
Identification of Genetic Variants in Base Excision Repair Pathway and Their Associations with Risk of Esophageal Squamous Cell Carcinoma (2004)

The etiology of esophageal squamous cell carcinoma (ESCC) has been shown to be associated with genetic and certain environmental factors that produce DNA damage. Base excision repair (BER) genes are responsible for repair of DNA damage caused by reactive oxygen species and other electrophiles and therefore are good candidate susceptibility genes for ESCC. We first screened eight BER genes for new and potential functional polymorphisms by resequencing 27 DNA samples. We then identified and genotyped for important tagging single nucleotide polymorphisms (SNPs) in a case-control study of 419 patients with newly diagnosed esophageal cancer and 480 healthy controls by frequency matching on age and sex. The association between genotypes and ESCC risk was estimated by unconditional multivariate logistic regression analysis, and stepwise regression procedure was used for constructing the final logistic regression model. We identified 129 SNPs in the eight BER genes, including 18 SNPs that cause amino acid changes. In the final model, 4 SNPs, including 2 in the coding regions (ADPRT Val762Ala and MBD4 Glu346Lys) and others in noncoding regions (LIG3 A3704G and XRCC1 T-77C), remained as significant predictors for the risk of ESCC. The adjusted odd ratios were 1.25 [95% confidence interval (CI) 1.02-1.53] for the ADPRT 762Ala allele, 1.25 (95% CI 1.02-1.53) for the MBD4 346 Lys allele, 0.78 (95% CI 0.63-0.97) for the LIG3 3704G allele, and 1.38 (95% CI 1.01-1.89) for the XRCC1-77C allele. In addition, we observed a significant gene-gene interaction between XRCC1 Gln399Arg and ADPRT Val762Ala. The results suggest that the polymorphisms in five BER genes may be associated with the susceptibility to ESCC in a Chinese population.
Preparation and Properties of Magnetite and Polymer Magnetite Nanoparticles (1999)

A novel approach to prepare magnetic polymeric nanoparticles by synthesis of the magnetite core and polymeric shell in a single inverse microemulsion is reported. Stable magnetic nanoparticles colloid dispersion with narrow size distribution can thus be produced. The microemulsion seed copolymerization of methacrylic acid, hydroxyethyl methacrylate, and cross-linker results in a stable hydrophilic polymeric shell of the nanoparticles. The preparation of the nanoparticles was carried out also by the two-stage microemulsion process and the seed precipitation polymerization. The particle size was varied in the range 80−320 nm by changing of the monomer concentration and water/surfactant ratio. The magnetic properties and the size distribution of the nanoparticles synthesized by these three methods were compared. The polymeric nanoparticles synthesized in single microemulsion have superparamagnetic properties and the narrowest size distribution.
Predicting and Monitoring Stress and Deformation Behaviour of Backfill in Deep-level Mining Excavations (1988)

Backfill is being placed in deep South African gold mines in an attempt to control mining induced displacements in the rock mass and hence reduce the incidence of rockbursts and rockfalls. To assist with the design and selection of backfill systems for this purpose it is necessary to predict the stress and deformation in the backfill as well as in the rock mass. Laboratory testing, numerical modelling and in situ measurements are being carried out to assist with the predictions. The choice of laboratory test methods to reasonably determine the stress-strain behaviour of hydraulically placed backfill in deep-level, tabular mining operations is briefly discussed. Using parameters calculated from triaxial laboratory tests, the response of a classified tailings backfill material in a typical stope environment is simulated numerically. The validity of the model to predict the backfill behaviour at high stresses is discussed. The computer simulations are then compared with measurements of stress and strain in backfill taken underground using specially developed stress meters and closure meters. The agreement between observed and predicted results is discussed in terms of how, and to what extent, the models can be used to predict the in situ behaviour of backfill.
Insulin-like growth factor II mediates epidermal growth factor-induced mitogenesis in cervical cancer cells. (1995)

There is increasing evidence that activation of the insulin-like growth factor I (IGF-I) receptor plays a major role in the control of cellular proliferation of many cell types. We studied the mitogenic effects of IGF-I, IGF-II, and epidermal growth factor (EGF) on growth-arrested HT-3 cells, a human cervical cancer cell line. All three growth factors promoted dose-dependent increases in cell proliferation. In untransformed cells, EGF usually requires stimulation by a "progression" factor such as IGF-I, IGF-II, or insulin (in supraphysiologic concentrations) in order to exert a mitogenic effect. Accordingly, we investigated whether an autocrine pathway involving IGF-I or IGF-II participated in the EGF-induced mitogenesis of HT-3 cells. With the RNase protection assay, IGF-I mRNA was not detected. However, IGF-II mRNA increased in a time-dependent manner following EGF stimulation. The EGF-induced mitogenesis was abrogated in a dose-dependent manner by IGF-binding protein 5 (IGFBP-5), which binds to IGF-II and neutralizes it. An antisense oligonucleotide to IGF-II also inhibited the proliferative response to EGF. In addition, prolonged, but not short-term, stimulation with EGF resulted in autophosphorylation of the IGF-I receptor, and coincubations with both EGF and IGFBP-5 attenuated this effect. These data demonstrate that autocrine secretion of IGF-II in HT-3 cervical cancer cells can participate in EGF-induced mitogenesis and suggest that autocrine signals involving the IGF-I receptor occur "downstream" of competence growth factor receptors such as the EGF receptor.
Bacterial growth inhibition by overproduction of protein (1996)

Multicopy plasmids that have been engineered to produce large quantities of a single gratuitous (non-functional, non-toxic) protein are often problematic. When fully induced, these engineered constructions produce very sick bacteria. The reasons for this may be found in the physiology of wild-type laboratory strains that have been selected to grow at maximum rates with optimal quantities of their proteins. Such bacteria apparently experience the accumulation of gratuitous proteins as an internal shift down and they respond to this with a starvation response. Unlike the shift down associated with a change of growth media, the production of large quantities of gratuitous protein is not associated with a new pre-programmed steady-state of balanced growth. Consequently, the starvation response continues until the bacteria commit suicide by, among other things, destroying their ribosomes.
Serum Steroids in Relation to Benign Prostatic Hyperplasia (1997)

In order to investigate the endocrine etiology of benign prostatic hyperplasia (BPH), we conducted a case-control study in Athens, Greece using 52 patients with histologically confirmed BPH and 52 healthy controls matched according to age and town of residence. Blood samples were collected from all participants and analyzed blindly in Boston, Mass. regarding testosterone (T), dihydrotestosterone, estradiol (E2), sex hormone-binding globulin, and dehydroepiandrosterone sulfate (DHEAS). Results from logistic regression models, adjusting for age, height, body mass index, years of schooling, and mutually among the measured hormones, indicate that DHEAS is significantly positively associated with the risk of BPH [odds ratio = 3.10 per standard deviation (60 micrograms/dl), 95% confidence interval (1.28,7.50)]. T and E2 were not significantly related to the risk of BPH.
Pharmacological characterization of the chemokine receptor, hCCR1 in a stable transfectant and differentiated HL‐60 cells: antagonism of hCCR1 activation by MIP‐1β (2002)

C-C chemokine receptor-1 (CCR1) has been implicated in mediating a variety of inflammatory conditions including multiple sclerosis and organ rejection. Although originally referred to as the MIP-1alpha/RANTES receptor, CCR1 is quite promiscuous and can be activated by numerous chemokines. We used radioligand binding and [35S]-GTPgammaS exchange assays in membranes from a cell line transfected to express CCR1 (Ba/F3-hCCR1) to characterize a panel of chemokines (HCC-1, MIP-1alpha, MIP-1beta, MIP-1delta, MPIF-1, MCP-2, MCP-3, and RANTES) as CCR1 ligands. In this recombinant model, these chemokines displaced 125I-MIP-1alpha with a wide range of potencies and, with the exception of MCP-2, acted as full agonists in stimulating [35S]-GTPgammaS exchange. We then assessed the utility of HL-60 cells cultured with known differentiating agents (PMA, DMSO, dibutyryl-cAMP or retinoic acid) for investigating CCR1 pharmacology. In [35S]-GTPgammaS exchange assays, membranes from cells cultured with retinoic acid (4-6 days) were the most responsive to activation by MIP-1alpha and MPIF-1. FACS analysis and comparative pharmacology confirmed that these activities were mediated by CCR1. Using [35S]-GTPgammaS exchange assays, intracellular calcium flux and/or whole cell chemotaxis assays in HL-60(Rx) cells, we validated that MIP-1alpha was the most potent CCR1 ligand (MIP-1alpha>MPIF-1>RANTES>or=MIP-1beta) although the ligands differed in their efficacy as agonists. MPIF-1 was the more efficacious (MPIF-1>RANTES=MIP-1alpha>>MIP-1beta). 125I-MIP-1beta binding in Ba/F3-hCCR1 and HL-60(Rx) membranes was competitively displaced by MIP-1alpha, MPIF-1 and MIP-1beta. The binding K(i) for these chemokines with 125I-MIP-1beta were essentially identical in the two membrane systems. Lastly, MIP-1beta antagonized [35S]-GTPgammaS exchange, Ca2+ flux and chemotaxis in HL-60(Rx) cells in response to robust agonists such as MIP-1alpha, RANTES and MPIF-1. Based on our results, we propose that MIP-1beta could function as an endogenous inhibitor of CCR1 function.
Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus (2005)

Systemic autoimmune disease in humans and mice is characterized by loss of immunologic tolerance to a restricted set of self-nuclear antigens. Autoantigens, such as double-stranded (ds) DNA and the RNA-containing Smith antigen (Sm), may be selectively targeted in systemic lupus erythematosus because of their ability to activate a putative common receptor. Toll-like receptor 9 (TLR9), a receptor for CpG DNA, has been implicated in the activation of autoreactive B cells in vitro, but its role in promoting autoantibody production and disease in vivo has not been determined. We show that in TLR9-deficient lupus-prone mice, the generation of anti-dsDNA and antichromatin autoantibodies is specifically inhibited. Other autoantibodies, such as anti-Sm, are maintained and even increased in TLR9-deficient mice. In contrast, ablation of TLR3, a receptor for dsRNA, did not inhibit the formation of autoantibodies to either RNA- or DNA-containing antigens. Surprisingly, we found that despite the lack of anti-dsDNA autoantibodies in TLR9-deficient mice, there was no effect on the development of clinical autoimmune disease or nephritis. These results demonstrate a specific requirement for TLR9 in autoantibody formation in vivo and indicate a critical role for innate immune activation in autoimmunity.
High-Titer, Wild-Type Free Recombinant Adeno-Associated Virus Vector Production Using Intron-Containing Helper Plasmids (2000)

Recombinant adeno-associated virus (rAAV) is capable of directing long-term, high-level transgene expression without destructive cell-mediated immune responses. However, traditional packaging methods for rAAV vectors are generally inefficient and contaminated with replication-competent AAV (rcAAV) particles. Although wild-type AAV is not associated with any known human diseases, contaminating rcAAV particles may affect rAAV gene expression and are an uncontrolled variable in many AAV gene transfer studies. In the current study, a novel strategy was designed to both optimize AAV rep gene expression and increase vector yield, as well as simultaneously to diminish the potential of generating rcAAV particles from the helper plasmid. The strategy is based on the insertion of an additional intron in the AAV genome. In the AAV infectious clone, the intron insertion had no effects on the properties of Rep proteins expressed. Normal levels of both Rep and Cap proteins were expressed, and the replication of the AAV genome was not impaired. However, the generation of infectious rcAAV particles using intronized AAV helper was greatly diminished, which was due to the oversized AAV genome caused by the insertion of the artificial introns. Moreover, the rAAV packaging was significantly improved with the appropriate choice of intron and insertion position. The intron is another element that can regulate the rep and cap gene expression from the helper plasmid. This study provides for a novel AAV packaging system which is highly versatile and efficient. It can not only be combined with other AAV packaging systems, including rep-containing cell lines and herpes simplex virus hybrid packaging methods, but also be used in other vector systems as well.
Vaccination with the major secretory protein of Legionella induces humoral and cell-mediated immune responses and protective immunity across different serogroups of Legionella pneumophila and different species of Legionella (1991)

In a previous study, we demonstrated that immunization of guinea pigs with the major secretory protein (MSP) of Legionella pneumophila, serogroup 1 induced humoral and cell-mediated immune responses to MSP and protective immunity against lethal aerosol challenge with this serogroup of L. pneumophila. Although serogroup 1 L. pneumophila cause most cases of Legionnaires' disease, other serogroups of L. pneumophila and species of Legionella cause many cases. In this study, we have examined if immunization with MSP induces humoral and cell-mediated immune responses and protective immunity across different serogroups of L. pneumophila and species of Legionella. By immunoblot analysis, MSP from L. pneumophila serogroup 1 (Lp1 MSP), L. pneumophila serogroup 6 (Lp6 MSP), and Legionella bozemanii (Lb MSP) shared common epitopes recognized by guinea pig anti-Lp1 MSP antiserum. These MSP molecules, however, were not identical as they had different apparent m.w. Immunization of guinea pigs with MSP induced strong cell-mediated immune responses across the different serogroups and species, as indicated by splenic lymphocyte proliferation and cutaneous delayed-type hypersensitivity in response to both homologous and heterologous MSP. Immunization with MSP induced strong protective immunity across two serogroups of L. pneumophila; overall, 9 survived aerosol challenge with L. pneumophila serogroup 1 compared to 0 of 12 (0%) sham-immunized control animals (p = 3 x 10(-4), Cochran-Mantel-Haenzel chi 2 statistic for pooled data). Immunization with MSP also induced protective immunity across species of Legionella but protection was species-specific. Whereas immunization with Lb MSP induced protective immunity against L. pneumophila, neither immunization with Lp1 MSP nor immunization with Lb MSP induced protective immunity against L. bozemanii, which produces MSP. Not surprisingly, immunization with MSP did not induce protective immunity against MSP-negative Legionella micdadei. In the case of both L. bozemanii and L. micdadei, immunization with a sublethal dose did confer protective immunity to aerosol challenge indicating that these species do contain immunoprotective components. This study demonstrates that immunization with MSP induces humoral and cell-mediated immune responses across different serogroups of L. pneumophila and species of Legionella, but that the capacity of MSP immunization to induce protective immunity is species-specific. Nevertheless, an MSP vaccine has the potential to induce protective immunity against the great majority of cases of Legionnaires' disease.
An automated computer vision and roboticsbased technique for 3-D flexible biomolecular docking and matching (1995)

The generation of binding modes between two molecules, also known as molecular docking, is a key problem in rational drug design and biomolecular recognition. Docking a ligand, e.g., a drug molecule or a protein molecule, to a protein receptor, involves recognition of molecular surfaces as molecules interact at their surface. Recent studies report that the activity of many molecules induces conformational transitions by 'hinge-bending', which involves movements of relatively rigid parts with respect to each other. In ligand-receptor binding, relative rotational movements of molecular substructures about their common hinges have been observed. For automatically predicting flexible molecular interactions, we adapt a new technique developed in Computer Vision and Robotics for the efficient recognition of partially occluded articulated objects. These type of objects consist of rigid parts which are connected by rotary joints (hinges). Our approach is based on an extension and generalization of the Geometric Hashing and Generalized Hough Transform paradigm for rigid object recognition. Unlike other techniques which match each part individually, our approach exploits forcefully and efficiently enough the fact that the different rigid parts do belong to the same flexible molecule. We show experimental results obtained by an implementation of the algorithm for rigid and flexible docking. While the 'correct', crystal-bound complex is obtained with a small RMSD, additional, predictive 'high scoring' binding modes are generated as well. The diverse applications and implications of this general, powerful tool are discussed.
Long‐Chain Branches in Syndiotactic Polypropene Induced by Vinyl Chloride (2010)

Abstract Syndiotactic polypropene was synthesized using a metallocene catalyst system and traces of VC. The use of VC was found to decrease the molar mass $\overline M _{\rm w} $ of the samples distinctly and linearly, while retaining the molar mass distribution, the crystallinity, and the syndiotacticity. The VC, however, initiates the formation of long‐chain branches, which were detected by GPC‐MALLS and rheology. Besides their effect on the viscosity and modulus functions, a thermorheologic complexity can be observed. Also the flow activation energy E a was found to be increased. The modified samples did not obey the $\eta _0 /\overline M _{\rm w} $ relation for linear sPP, indicating the presence of LCBs. magnified image
Monoclonal Antibodies Detect Occult Breast Carcinoma Metastases in the Bone Marrow of Patients with Early Stage Disease (1988)

Thirty-five to 40% of patients with operable breast carcinoma develop metastases after primary therapy. There is a need for more specific prognostic parameters to identify patients who are most likely to benefit from adjuvant therapy. The success of such treatment stems from its ability to eradicate preclinical microscopic metastases. The bone marrow is an accessible and frequent site of breast carcinoma metastases. Following studies of Redding et al. (16), we used monoclonal antibodies that recognize membrane and cytoskeletal antigens expressed by epithelial cells (C26, T16, AE-1) in an immunohistochemical assay to find cancer cells in bone marrow aspirates. The assay can detect one cancer cell among 50,000-100,000 hematopoietic cells. None of the 44 control bone marrows (from normal individuals and patients with leukemias and lymphomas) contained antigen-positive (extrinsic) cells. We found extrinsic cells in the bone marrow of 35% (18 of 51) of patients with operable breast carcinoma; no extrinsic cells were identified by routine bone marrow cytology in these patients. Twenty-seven percent (six of 22) of patients with negative lymph nodes had antigen-positive cells, while 41% (12 of 29) of patients with lymph node metastases had such cells. Similarly, 23% (three of 13) of patients with TNM stage I disease, 38% (13 of 34) of patients with stage II disease, and 50% (two of four) of patients with stage III disease had extrinsic cells. In those cases where extrinsic cells were identified, stage II patients with negative lymph nodes and patients with stage I disease were found to have fewer such cells in their marrow than patients with lymph node metastases and patients with stage II disease. These trends did not reach the level of statistical significance in this small number of patients. The presence of extrinsic cells did not correlate with tumor size of lymphatic invasion around the tumor. We conclude that the epithelial cells detected in the bone marrow of the patients with breast carcinoma were carcinoma cells based on the following criteria: (a) they expressed both membrane and cytoplasmic epithelia-specific antigens, (b) they possessed the cytologic characteristics of malignant epithelial cells, and (c) these cells were not detected in the bone marrow from normal individuals or patients with nonepithelial neoplasms involving the bone marrow. We have shown that the technique described here can detect occult metastases in bone marrow and that the presence of extrinsic cells correlates with some established predictors of prognosis. Long-term clinical correlative follow-up studies are now underway.