gebhart/patrepeval huggingface dataset:
Progress of olefin polymerization by metallocene catalysts (2000)

New C1-symmetric metallocenes such as [Me2C(PhCp)(Flu)ZrCl2, [Me3Pen(Flu)]ZrCl2, [PhMe3Pen(Flu)]ZrCl2 were synthesized and used for the polymerization of propene by higher polymerization temperatures. Different polypropylene micro structures were obtained. Important for industrial processes are the high molecular weights of the polymers produced by the pentalenelike catalysts, which are very stable by higher temperatures. For synthesis of syndiotactic polystyrene and new substituted half-sandwich titanocenes are used such as 1,3-Me2-CpTiCl3, Me4CpTiCl3, PhCpTiCl3, cyclohexyl-CpTiCl3. If they are fluorinated, the activity for the production of syndiotactic polystyrene can be increased 10 times. The synthesized polymer shows a high melting point of 275°C.
High efficiency electroporation of Pseudomonas aeruginosa using frozen cell suspensions (1990)

High efficiency transformation of Pseudomonas aeruginosa was achieved using frozen cell suspensions and high voltage electroporation. We have obtained frequencies as high as 5.8 x 10(8) transformants/micrograms of plasmid DNA using PA01 strain OT684 and a buffer of 15% glycerol-1 mM MOPS. The method allows for easy and reproducible production of frozen cell suspensions for rapid transformation of P. aeruginosa.
Trastuzumab, a humanized anti-HER2 monoclonal antibody, for the treatment of breast cancer. (1999)

The HER2/neu gene encodes a 185 kDa transmembrane receptor (HER2) that belongs to the epidermal growth factor receptor family and has intrinsic tyrosine kinase activity. HER2 is overexpressed in 25-30% of breast cancers and is suggested to have a direct role in the pathogenesis and clinical aggressiveness of HER2 overexpressing tumors. A murine monoclonal antibody, 4D5, directed against the extracellular domain of HER2, is a potent inhibitor of growth of human breast cancer cells overexpressing HER2 in vitro and in xenograft models. To facilitate clinical investigation, 4D5 was humanized by inserting the complementary determining regions of 4D5 into the framework of a consensus human IgG1. The resulting recombinant humanized anti-HER2 MAb, trastuzumab, was found to inhibit the growth of human cancer cells and tumor xenografts overexpressing HER2. Data from phase II trials in women with breast cancer whose tumors overexpress HER2 have shown that trastuzumab has a favorable toxicity profile, is active as a single agent and induces long-lasting objective tumor responses. In combination studies, there was no evidence that trastuzumab enhanced the toxicity of cisplatin and the pharmacokinetic parameters of trastuzumab were unaltered by coadministration of cisplatin. Furthermore, clinical response rates were higher than those reported with either agent alone in a similar patient population. Results of a multicenter, phase III clinical trial of chemotherapy (doxorubicin- or paclitaxel-based) plus trastuzumab as compared to chemotherapy alone in patients with advanced breast cancers overexpressing HER2 showed a significant enhancement in the effects of chemotherapy on time to disease progression, response rates and survival with coadministration of trastuzumab, without increases in overall severe adverse events. Myocardial dysfunction syndrome, similar to that observed with anthracyclines, was reported more commonly with chemotherapy plus trastuzumab. Positive results from clinical studies led to the approval of trastuzumab in the U.S in October 1998 for the treatment of metastatic breast cancer in patients with tumors overexpressing HER2. Since then, the MAb has also been marketed in Switzerland and Canada.
Characterization of the gene for the membrane and secretory form of the IgM heavy‐chain constant region gene (Cμ) of the cow (Bos taurus) (1998)

Our present understanding of the evolution of immunoglobulins is derived from a few vertebrate species. In order to obtain additional information on the development of the humoral immune system, we cloned and determined the nucleotide sequence of the bovine cDNA and genomic IgM heavy-chain constant region gene (C mu). The gene contains four constant region domain-encoding exons (CH1 to CH4) and two exons encoding the transmembrane domain (TM1, TM2), expressed in the membrane-bound receptor form of the IgM. The sequence of a cDNA clone encoding the 3' portion of the membrane form of the mu-chain revealed that the TM1 exon is spliced to the CH4 exon, as occurs in other mammals. Comparison of deduced amino acid sequence data from different vertebrates revealed a high similarity to sheep C mu (88%) and a lower degree of similarity to pig (62%), rat (62%), rabbit (58%) human (56%), hamster (55%), mouse (54%), chicken (28%) and horned shark (22%) C mu.
The nephrotoxicity of FK506 as compared with cyclosporine (1993)

FK506, a new macrolide immunosuppressant agent, is approximately 100 times more potent than cyclosporine. Early clinical trials demonstrated FK506 to be effective in reversing refractory rejection in liver, kidney, and heart transplantation. Like cyclosporine, FK506 has significant nephrotoxicity. The clinical presentation and morphology of FK506 nephrotoxicity are identical to those of cyclosporine. Many animal and in vitro studies suggest that FK506 may be less nephrotoxic than cyclosporine. Studies in humans after transplantation have not confirmed this advantage. FK506 has pursued the same pattern in drug development as cyclosporine, with progressive dose reductions over the years. Studies from this early developmental period suggest that the nephrotoxicity of FK506 and cyclosporine in clinical use are approximately equivalent. Further refinement in the clinical use of FK506 will likely reduce its toxicity further. Appropriate studies conducted at that stage will determine which drug possesses less nephrotoxicity.
Combination of ACY1215, a Selective Histone Deacetylase 6 (HDAC6) Inhibitor with the Bruton Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, Represents a Novel Therapeutic Strategy in Mantle Cell Lymphoma (MCL) (2012)

Abstract Abstract 1660 Recently, we have found that HDAC6 is overexpressed in MCL cell lines and in primary human MCL cells. Knocking-down HDAC6 in MCL cells with a shRNA lentiviral system resulted in cell cycle arrest and apoptosis induction. Interestingly, MCL cells lacking HDAC6 displayed a significantly decreased STAT3 phosphorylation and abrogation of IL-10 gene transcriptional activity. ACY1215 is a novel, selective, orally bioavailable HDAC6 inhibitor. Treatment of MCL cell lines with this agent resulted in decreased cell viability and proliferation. In addition, ACY1215 inhibits IL-10 production in a dose dependent manner. Bruton tyrosine kinase (BTK) is a member of Tec family of kinases with a very distinct role in B-cell antigen receptor (BCR) signaling. The selective BTK-inhibitor PCI-32765 has shown promising pre-clinical and clinical activity in MCL. In addition to their direct anti-lymphoma effects, disruption of BTK also induces positive immunological changes such as inhibition of the immunosuppressive STAT3/IL-10 signaling pathway1. The above observations led us to determine whether the direct antitumor effects and the immunological properties of ACY1215 and PCI-32765 could be potentiated when these agents are used in combination. First, the viability of MCL cells was decreased when they were treated in vitro with either PCI-32765 or ACY1215. However, combination of these two agents resulted in a 3-fold increase in apoptosis induction, pointing to a synergistic effect of BTK and HDAC6 inhibition in MCL. The additional findings that this approach can increase the immunogenicity of MCL cells and anti-MCL immune responses has provided the proper framework for combining the selective HDAC6 inhibitor ACY1215 with BTK inhibition as a novel therapeutic strategy in MCL. Disclosures: Chen-Kiang: Bristol Myers Squibb: Consultancy; Pfizer: Research Funding. Jones:Acetylon Pharmaceuticals, Inc: Employment.
1,8-Diazabicyclo[5.4.0]undec-7-ene as a Mild Deprotective Agent for Acetyl Groups (1989)

A simple acetyl cleavage is described. The method showed selective acetyl deprotection of polyfunctionalized molecules.
Comparative in vitro activities of six new fluoroquinolones and other oral antimicrobial agents against Campylobacter pylori (1989)

The in vitro susceptibilities of 56 clinical isolates of Campylobacter pylori to six new fluoroquinolones and other oral antimicrobial agents were determined by an agar dilution technique. Ciprofloxacin was the most active of the fluoroquinolones (MIC for 90% of strains tested [MIC90], 0.05 microgram/ml). Other fluoroquinolones had variable activities, although most isolates were moderately susceptible to fleroxacin (MIC90, 4 micrograms/ml) and lomefloxacin (MIC90, 4 micrograms/ml).
Rubella Immunity:Defining the Level of Protective Antibody (1996)

The Rubella Subcommittee of the National Committee for Clinical Laboratory Standards has proposed lowering the breakpoint to define rubella immunity from 15 to 10 IU/mL. This recommendation stems from epidemiologic studies on vaccinated persons with low levels of antibody and anecdotal reports. Additional support comes from Centers for Disease Control and Prevention studies and reports. The effectiveness of rubella vaccination is well documented and the 10 IU/mL antibody level is protective in the vast majority of persons. Sporadic reports of viremia and/or reinfection among previously immunized persons with low antibody levels have been reported but proven cases of reinfection have also occurred in persons with titers greater than or equal to the 15 IU/mL cut-off. Despite the occasional occurrence of rubella reinfection in persons with low titers, the theoretical risks are small especially as compared with significantly greater risk in persons who have not been vaccinated. Immunity in a given patient is a clinical decision and the results of antibody tests for rubella, like other laboratory tests, must be evaluated in the context of the clinical setting.
Purified RNA polymerase II recognizes specific termination sites during transcription in vitro. (1987)

We have studied the ability of certain well-defined prokaryotic DNA sequences to act as specific termination signals for highly purified calf thymus RNA polymerase II. We used duplex DNA fragments modified to direct efficient and specific transcription of defined DNA templates to follow transcription with RNA polymerase alone in the absence of additional protein factors. Elongation of RNA chains by RNA polymerase II is processive through most DNA sequences. However, certain DNA sequences serve as effective "intrinsic" terminators for RNA polymerase II; in this they resemble the "rho-independent" terminators for the bacterial RNA polymerase. Several rho-independent bacterial terminators are also able to act as termination signals for RNA polymerase II. However, there is no apparent correlation between the efficiency of termination for the bacterial enzyme and that found for the calf thymus enzyme. One very efficient bacterial terminator (phage T7 early terminator) gives no termination with RNA polymerase II, and we have identified at least two sites that cause the eukaryotic enzyme to terminate but have no effect on transcription by the bacterial enzyme. Hence, the signals recognized as intrinsic termination sites for the two enzymes are substantially different. All of the sites that act as intrinsic terminators for RNA polymerase II contain a series of consecutive thymidine residues in the nontranscribed DNA strand (T-run), and the 3' end of the completed RNA normally lies within this sequence. It is plausible that the T-run is part of the signal for an RNA polymerase II termination site; however, there is no apparent correlation between the number of T residues and the efficiency of the terminator, suggesting that other sequence elements are required for, or modulate, termination. Several lines of evidence suggest that the formation of RNA secondary structures in the nascent transcript is not an essential element of the intrinsic RNA polymerase II termination signal.
Kinetics of Surface-Initiated Photoiniferter-Mediated Photopolymerization (2005)

Surface-tethered poly(methyl methacrylate) films were synthesized by surface-initiated photoiniferter-mediated photopolymerization (SI-PMP), and the kinetics of film growth were followed by measuring layer thickness as a function of reaction time, monomer concentration, and light intensity using variable angle ellipsometry. The initial rate of photopolymerization had approximate first-order dependence on monomer concentration. However, the rate of photopolymerization decreased with reaction time, indicating the presence of termination reactions. To determine which termination reactions are prevalent, kinetic models accounting for bimolecular termination as well as chain transfer to monomer were developed for the photoiniferter-mediated photopolymerization reactions and used to analyze the experimental data. Comparisons of model predictions to experimental data as functions of reaction time and light intensity suggest that bimolecular termination is the dominant termination mechanism in these systems for the range of reaction conditions investigated.
On The Adjoint of a Nonlinear Diffusion-Convection Equation to Describe Flow in Porous Media (2005)

Abstract In this study Optimal Control Theory (OCT) was used to formulate the adjoint equation of a one-dimensional horizontal two-phase flow reservoir described by linear and nonlinear Diffusion-Convection Equations (DCEs). The use of tuning parameters allowed for a gradual transition between the linear and the nonlinear equations to determine the effect of nonlinearities on the solution of the adjoint equation. A numerical adjoint formulation was obtained from explicit and implicit finite difference discretizations of the linear and the nonlinear DCEs. A semi-analytical solution was obtained for the continuous adjoint of the linear DCE which served as a reference for analysis of some of the numerical results. Based on a simple example we found that for the linear model numerical dispersion did not affect the stability of the adjoint equation and that the resulting gradients remained stable. Explicit numerical implementation of the nonlinearities in the capillary pressure and fractional flow functions resulted in non-smooth (mildly oscillating) gradients of the objective function with respect to the controls for a number of time steps. A matrix stability analysis revealed the occasional occurrence of eigenvalues with magnitude one, indicating marginal stability, but no true instabilities were encountered. The observed oscillations in the gradients are not desirable for optimization purposes, since the resulting injection rates are fluctuating and the convergence of the optimization algorithm becomes difficult. However, the gradients became smoother for smaller time step sizes which suggests the need to use a smaller time step size for solving the adjoint equation than for solving the forward model.
Performance analysis of a reconfigurable antenna system for MIMO communications (2011)

In this paper an adaptive antenna system that allows for dynamic changes in the array radiation pattern while providing full elevation and azimuth coverage is presented. The antenna system is used at the transmitter of a 2×2 MIMO system to demonstrate the gain achievable with respect to 3×2 and 4×2 MIMO systems that do not employ reconfigurable antennas. Results show an improvement in throughput of up to 5 times with respect to standard 3×2 MIMO systems that employ spatial multiplexing and antenna selection and up to 50% with respect to a 4×2 MIMO system that employ spatial multiplexing and digital beamforming.
Nerve growth factor stimulates clonal growth of human lung cancer cell lines and a human glioblastoma cell line expressing high-affinity nerve growth factor binding sites involving tyrosine kinase signaling. (1995)

The growth of a panel of 22 different human tumor, leukemia, and lymphoma cell lines was examined in a human tumor cloning assay in agar or methylcellulose and a tritiated thymidine uptake assay. The cultures were performed in the absence or presence of increasing concentrations (0.5-500 ng/ml) of nerve growth factor (NGF). The growth of 17 of the 22 cell lines was not significantly and reproducibly affected by NGF. There was minor (1.2-fold) but reproducible stimulation of clonal growth in one glioblastoma cell line (86-HG-39) by NGF, but in this cell line NGF induced no growth modulation in a tritiated thymidine uptake assay. However, clonal growth of another glioblastoma cell line (87-HG-31) and all three lung cancer cell lines tested (HTB 119, HTB 120, CCL 185) could be stimulated up to 3-fold by NGF with a dose-response relationship for the growth factor. Growth stimulation by NGF could be completely reversed by neutralizing anti-NGF antibody and by the tyrosine kinase inhibitor genistein. Evaluation of secondary plating efficiency revealed the stimulation of colony formation as representing self-renewal and not terminal differentiation. Reverse transcriptase-PCR experiments in the five responding cell lines showed expression of both low-affinity NGF receptor (glycoprotein 75) and c-trk transcripts on the mRNA level. Of the five responding cell lines, only 86-HG-39, the cell line with the lowest responsiveness, revealed low-affinity NGF receptor on the protein level; the other four cell lines with high responsiveness, including the three lung cancer cell lines, expressed no low-affinity NGF receptor as shown by fluorescence-activated cell sorter analysis and immunoprecipitation using the ME 20.4 antibody. Immunoprecipitation using anti-trk antibodies was negative in all five responding cell lines. However, binding studies with iodinated NGF showed only low-affinity binding on the 86-HG-39 cell line and only high-affinity binding on the high-responder cell lines CCL 185 and 87-HG-31. In summary, our data suggest that NGF can be operative in stimulation of clonal growth of malignant tumor cells. High-affinity but not low-affinity binding sites mediate signal transduction for clonal growth and signaling involves tyrosine kinase activity.
Interleukin-6 Regulation of Matrix Metalloproteinase (MMP-2 and MMP-9) and Tissue Inhibitor of Metalloproteinase (TIMP-1) Expression in Malignant Non-Hodgkin’s Lymphomas (1999)

We showed previously that human malignant non-Hodgkin's lymphomas (NHL) degrade extracellular matrix (ECM) components through the action of metalloproteinases and that elevated expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) correlated with a poor clinical outcome in patients with NHL. In the present study we sought to investigate whether there is any correlation between the expression of gelatinases (MMP-2 and MMP-9), TIMP-1, and the expression of cytokines and growth factors such as interleukin-1beta (IL-1beta), IL-6, IL-10, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGFbeta), and basic fibroblast growth factor (bFGF) in human NHL. In lymphoma tissues obtained from 32 patients, elevated expression of IL-6 correlated significantly with elevated messenger RNA (mRNA) levels of MMP-9, MMP-2, and TIMP-1. Moreover, in human lymphoid cell lines of B- and T-cell origin (Raji, Jurkat, and NC-37), IL-6 stimulated production of MMP-9 and MMP-2 but not TIMP-1. In the Matrigel invasion assay IL-6 significantly upregulated transmigration of Raji and Jurkat cells, which in turn was inhibited by recombinant human TIMP-1 and anti-MMP-9 and MMP-2 antibodies. We postulate that IL-6 may play a role in the clinical aggressiveness of human NHL by stimulating MMP production.
The main biological determinants of tumor line taxonomy elucidated by a principal component analysis of microarray data (2001)

By using principal components analysis (PCA) we demonstrate here that the information relevant to tumor line classification linked to the activity of 1375 genes expressed in 60 tumor cell lines can be reproduced by only five independent components. These components can be interpreted as cell motility and migration, cellular trafficking and endo/exocytosis, and epithelial character. PCA, at odds with cluster analysis methods routinely used in microarray analysis, allows for the participation of individual genes to multiple biochemical pathways, while assigning to each cell line a quantitative score reflecting fundamental biological functions.
Synthesis and fate of immunological surface receptors on cultured burkitt lymphoma cells (1969)

Abstract The distribution and rate of appearance of newly synthesized receptors on the surface of Burkitt lymphoma cells were determined by membrane immunofluorescence tests on trypsinized cell lines growing as continuous cultures in a medium containing gamma globulins with specificity for the receptors. An attempt was made to determine the fate of the „surface receptor‐serum globulin”︁ complex by examining serial samples of cultures of stained positive cells for membrane immunofluorescence. There is partial evidence to suggest that observed fluctuations in the numbers of receptor‐producing cells are partly due to active shedding of receptors from the cell surfaces.
The Structure and Specificity of Escherichia coli Maltose Acetyltransferase Give New Insight into the LacA Family of Acyltransferases, (2003)

The crystallographic three-dimensional structure of the Escherichia coli maa gene product, previously identified as a maltose O-acetyltransferase (MAT) [Brand, B., and Boos, W. (1991) J. Biol. Chem. 266, 14113-14118] has been determined to 2.15 A resolution by the single anomalous dispersion method using data from a crystal cocrystallized with trimethyllead acetate. It is shown here that MAT acetylates glucose exclusively at the C6 position and maltose at the C6 position of the nonreducing end glucosyl moiety. Furthermore, MAT shows higher affinity toward artificial substrates containing an alkyl or hydrophobic chain as well as a glucosyl unit. The presence of a long hydrophobic patch near the acceptor site provides the structural explanation for this preference. The three-dimensional structure reveals the expected trimeric left-handed parallel beta-helix structure found in all other known hexapeptide repeat enzymes. In particular, the structure shows similarities both overall and at the putative active site to the recently determined structure of galactoside acetyltransferase (GAT), the lacA gene product [Wang, X.-G., Olsen, L. R., and Roderick, S. L. (2002) Structure 10, 581-588]. The structure, together with the new biochemical data, suggests that GAT and MAT are more closely related than previously thought and might have similar cellular functions. However, while GAT is specific for acetylation of galactosyl units, MAT is specific for glucosyl units and is able to acetylate maltooligosaccharides, an important property for biotechnological applications. Structural differences at the acceptor site reflect the differences in substrate specificity.