gebhart/patrepeval huggingface dataset:
Tuning the Affinity for Lanthanides of Calcium Binding Proteins (2003)

The possibility of selectively substituting one or more lanthanides into the four canonical calcium binding sites of calcium-loaded vertebrate calmodulin (CaM) was investigated by monitoring changes in the (1)H-(15)N HSQC NMR spectra of the (15)N-enriched protein upon titration with Yb(3+). The affinity of lanthanides for both N-terminal sites I and II is only moderately higher than that of calcium, and comparable with that of calcium for the two C-terminal sites. This situation induces binding of lanthanides to other noncanonical sites located at the interdomain linker, the N- and C-terminal ends, and at the inter-EF-hand linkers. Therefore, mutants were designed to alter the metal binding properties of calcium sites I (D22N, D24E), II (D58N, N60D, D58N-N60D), III (N97D), II-III (N60D-N97D), and IV (D129N), as well as of the inter-EF-hand linker of the N-terminal domain (N42K, T44K). The most striking effects were obtained for the N60D mutant at site II, as selective lanthanide binding is achieved even in the presence of excess calcium, and little or no population of the noncanonical sites occurs. Similar although less pronounced effects were observed for the N97D mutant. These findings allow us to better define some of the determinants of the relative affinities of calcium and lanthanides in CaM and, by extension, in other calcium binding proteins. Finally, by using CaM samples containing only three of the four calcium ions, it was possible to prepare well-defined Ca(3)Ln-CaM derivatives (Ln = Tb, Dy, Tm, and Yb), with interesting properties as NMR probes.
Activity of Taxol in Patients With Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus (1994)

These data indicate that paclitaxel is an active agent against adenocarcinoma and squamous cell carcinoma of the esophagus.
Efficacy of orally administered superfine dispersed lentinan (beta-1,3-glucan) for the treatment of advanced colorectal cancer. (2009)

SDL was safe and effective for suppressing the adverse effects of chemotherapy as well as improving QOL. The binding ability of PBM to LNT appears to be a promising predictor of QOL improvement after SDL administration.
Comments on the report of ‘association’ of omeprazole with DNA by Phillips et al (1992)

Journal Article Comments on the report of ‘association’ of omeprazole with DNA by Phillips et al Get access Stephen P. Adams, Stephen P. Adams Genetic and Cellular Toxicology, Merck Research LaboratoriesWest Point, PA 19486, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard D. Storer, Richard D. Storer Genetic and Cellular Toxicology, Merck Research LaboratoriesWest Point, PA 19486, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar John G. Deluca, John G. Deluca Genetic and Cellular Toxicology, Merck Research LaboratoriesWest Point, PA 19486, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Sheila M. Galloway, Sheila M. Galloway Genetic and Cellular Toxicology, Merck Research LaboratoriesWest Point, PA 19486, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Warren W. Nichols Warren W. Nichols Genetic and Cellular Toxicology, Merck Research LaboratoriesWest Point, PA 19486, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Mutagenesis, Volume 7, Issue 5, September 1992, Pages 395–396, https://doi.org/10.1093/mutage/7.5.395 Published: 01 September 1992
Current techniques in protein glycosylation analysis. A guide to their application. (1999)

The importance of glycosylation in biological events and the role it plays in glycoprotein function and structure is an area in which there is growing interest. In order to understand how glycosylation affects the shape or function of a protein it is however important to have suitable techniques available to obtain structural information on the oligosaccharides attached to the protein. For many years the complexity of the structures required sophisticated analytical techniques only available to a few specialist laboratories. In many cases these techniques were not available or required a large amount of material and therefore the number of glycoproteins which were fully characterised were relatively few. In recent years there have been substantial developments in the analysis of glycosylation which has significantly changed the capability to fully characterise molecules of biological interest. A number of different techniques are available which differ in terms of their complexity, the amount of information which is available from them, the skill needed to perform them and their cost. It is now possible for many laboratories who do not specialise in glycosylation analysis to obtain some information although this may be incomplete. These developments do, however, also make complete characterisation of a glycoprotein a much less daunting task and in many cases this can be performed more easily and with less starting material than was previously required. In this review a summary will be given of current techniques and their suitability for different types of analysis will be considered.
Comprehensive in vivo micro-vascular imaging of the human eye by dual-beam-scan Doppler optical coherence angiography (2011)

Comprehensive angiography provides insight into the diagnosis of vascular-related diseases. However, complex microvascular networks of unstable in vivo organs such as the eye require micron-scale resolution in three dimensions and a high sampling rate to access a wide area as maintaining the high resolution. Here, we introduce dual-beam-scan Doppler optical coherence angiography (OCA) as a label-free comprehensive ophthalmic angiography that satisfies theses requirements. In addition to high resolution and high imaging speed, high sensitivity to motion for detecting tiny blood flow of microvessels is achieved by detecting two time-delayed signals with scanning of two probing beams separated on a sample. We present in vivo three-dimensional imaging of the microvasculature of the posterior part of the human eye. The demonstrated results show that this technique may be used for comprehensive ophthalmic angiography to evaluate the vasculature of the posterior human eye and to diagnose variety of vascular diseases.
PIM Kinase Inhibitors Downregulate STAT3Tyr705 Phosphorylation (2010)

Using a cell-based high-throughput screen designed to detect small chemical compounds that inhibit cell growth and survival, we identified three structurally related compounds, 21A8, 21H7, and 65D4, with differential activity on cancer versus normal cells. Introduction of structural modifications yielded compound M-110, which inhibits the proliferation of prostate cancer cell lines with IC(50)s of 0.6 to 0.9 μmol/L, with no activity on normal human peripheral blood mononuclear cells up to 40 μmol/L. Screening of 261 recombinant kinases and subsequent analysis revealed that M-110 is a selective inhibitor of the PIM kinase family, with preference for PIM-3. The prostate cancer cell line DU-145 and the pancreatic cancer cell line MiaPaCa2 constitutively express activated STAT3 (pSTAT3(Tyr705)). Treatment of DU-145 cells with M-110 or with a structurally unrelated PIM inhibitor, SGI-1776, significantly reduces pSTAT3(Tyr705) expression without affecting the expression of STAT3. Furthermore, treatment of DU-145 cells with M-110 attenuates the interleukin-6-induced increase in pSTAT3(Tyr705). To determine which of the three PIM kinases is most likely to inhibit expression of pSTAT3(Tyr705), we used PIM-1-, PIM-2-, or PIM-3-specific siRNA and showed that knockdown of PIM-3, but not of PIM-1 or PIM-2, in DU-145 cells results in a significant downregulation of pSTAT3(Tyr705). The phosphorylation of STAT5 on Tyr694 in 22Rv1 cells is not affected by M-110 or SGI-1776, suggesting specificity for pSTAT3(Tyr705). These results identify a novel role for PIM-3 kinase as a positive regulator of STAT3 signaling and suggest that PIM-3 inhibitors cause growth inhibition of cancer cells by downregulating the expression of pSTAT3(Tyr705).
Herbicide-Resistant Tobacco Plants Expressing the Fused Enzyme between Rat Cytochrome P4501A1 (CYP1A1) and Yeast NADPH-Cytochrome P450 Oxidoreductase (1994)

Transgenic tobacco (Nicotiana tabacum cv Xanthi) plants expressing a genetically engineered fused enzyme between rat cytochrome P4501A1 (CYP1A1) and yeast NADPH-cytochrome P450 oxidoreductase were produced. The expression plasmid pGFC2 for the fused enzyme was constructed by insertion of the corresponding cDNA into the expression vector pNG01 under the control of the cauliflower mosaic virus 35S promoter and nopaline synthase gene terminator. The fused enzyme cDNA was integrated into tobacco genomes by Agrobacterium infection techniques. In transgenic tobacco plants, the fused enzyme protein was localized primarily in the microsomal fraction. The microsomal monooxygenase activities were approximately 10 times higher toward both 7-ethoxycoumarin and benzo[a]pyrene than in the control plant. The transgenic plants also showed resistance to the herbicide chlortoluron.
An Incremental Redundancy Hybrid ARQ Scheme via Puncturing and Extending of Polar Codes (2015)

We construct polar codes for the specific purpose of incremental redundancy hybrid automatic repeat request (IR-HARQ) schemes. The rate compatibility of our scheme is ensured by both puncturing and extending of the code. A new puncturing algorithm for polar codes is proposed, and we develop an algorithm for finding good extending sequences for polar codes from any arbitrary punctured rate, with the goal of improving the throughput as much as possible. Simulation results for different types of puncturing and extending algorithms are presented. We show how the proposed extending algorithm, when properly operated with a good puncturing algorithm and a well-chosen puncturing rate, yields IR-HARQ coding schemes which can operate within 1 dB of Shannon capacity over a very wide range of signal-to-noise ratios.
Susceptibility of mouse primary cortical neuronal cells to coxsackievirus B (2004)

Coxsackievirus B (CVB) is often associated with aseptic meningitis and encephalitis, but the six serotypes of CVB vary in their relative disease severity. To elucidate the detailed mechanisms of CVB-induced cytopathological effects, the morphological and biochemical characteristics caused by the CVB serotypes in mouse primary cortical neuronal cells were investigated. By 24 h post-infection, all CVB serotypes except CVB2 induced severe cytotoxic alterations, including a loss of neurites. Both fluorescence and transmission electron microscopy revealed CVB-induced morphological changes indicative of apoptosis, including heavily condensed nuclei, subsequent chromatin condensation into the periphery of the nuclei and oligonucleosomal DNA fragmentation. It was also found that infection with all six CVB serotypes led to productive virus replication, which was completed prior to an apoptotic signal. The caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone significantly inhibited nuclear changes associated with virus-induced apoptosis, but had less effect on virus-associated cytopathic effects and no effect on virus production. In contrast, the transcription inhibitor actinomycin D profoundly inhibited all three virus-induced events. Taken together, these findings demonstrate that all six CVB serotypes can efficiently replicate in mouse cortical neuronal cells and that productive replication of these CVBs, except for CVB2, induces multiple cytopathological effects, including apoptotic alterations.
Retention of CXCR4 in the endoplasmic reticulum blocks dissemination of a T cell hybridoma (2001)

The dissemination of T cell hybridomas to multiple nonhematopoietic tissues is blocked by pertussis toxin, suggesting the involvement of a chemokine. To study whether this chemokine is SDF-1, we employed a strategy proposed previously for gene therapy of AIDS, whereby the SDF-1 receptor CXCR4 (also a coreceptor for HIV) is retained in the endoplasmic reticulum (ER) and fails to reach the cell surface. We transfected SDF-1, carrying an ER retention sequence, into a T cell hybridoma. This altered chemokine is retained in the ER, where it binds CXCR4 and prevents the latter protein from reaching the surface. These cells failed to migrate toward SDF-1 or to invade fibroblast monolayers, although they could still migrate toward thymus and activation-regulated chemokine (TARC) and invade TARC-treated monolayers. Furthermore, the ability of the transfected cells to disseminate to multiple organs upon intravenous injection into mice was abolished. This dissemination reflects the in vivo migration patterns of activated and memory T cells into nonhematopoietic tissues, which is thus likely to depend on CXCR4. Attempts to block CXCR4 function as a therapy for AIDS may affect this migration with consequences for T cell function. Our results also suggest a decisive role for CXCR4 in the dissemination of hematopoietic malignancies expressing this receptor.
Affinity maturation of human botulinum neurotoxin antibodies by light chain shuffling via yeast mating (2010)

Botulism is caused by the botulinum neurotoxins (BoNTs), the most poisonous substance known. Because of the high potency of BoNT, development of diagnostic and therapeutic antibodies for botulism requires antibodies of very high affinity. Here we report the use of yeast mating to affinity mature BoNT antibodies by light chain shuffling. A library of immunoglobulin light chains was generated in a yeast vector where the light chain is secreted. The heavy chain variable region and the first domain of the constant region (V(H)-C(H)1) from a monoclonal antibody was cloned into a different yeast vector for surface display as a fusion to the Aga2 protein. Through yeast mating of the two haploid yeasts, a library of light chain-shuffled Fab was created. Using this approach, the affinities of one BoNT/A and two BoNT/B scFv antibody fragments were increased from 9- to more than 77-fold. Subcloning the V-genes from the affinity-matured Fab yielded fully human IgG1 with equilibrium binding constants for BoNT/A and BoNT/B of 2.51 x 10(-11) M or lower for all three monoclonal antibodies. This technique provides a rapid route to antibody affinity maturation.
Reopening the Emmett Till Case: Lessons and Challenges for Critical Race Practice (2005)

As part of the symposium panel on "Re- Trying Racial Injustices," I devote this Essay to an expansion of themes addressed in my earlier work on the reopening of civil rights era prosecutions. I draw upon this work, as well as upon the insights of my co-panelists Anthony Alfieri and Sherrilyn Ifill, to examine the reopening of the Emmett Till case and its critical race practice possibilities. In this Essay, I consider other aspects of these "cleansing moments." Are they illusory? Do they provide a misleading sense of closure at the expense of the ongoing hard work of racial justice that leads up to -and must proceed from-those moments? What lessons or "teaching moments" might these cases create for critical race lawyers in their ongoing social justice work? In notable respects, the impetus to reopen long-dormant cases shares with critical legal theory a justified skepticism of the construct of finality and an idealistic vision of the possibilities for ultimate justice. Procedural and substantive bulwarks of finality may be necessary in a legalistic sense, but they do not signify closure or justice, particularly when structural inequality persists. Reopening, with its promise of restorative justice through racial healing and reconciliation, has the potential to provide the closure that mere finality lacks, but only if that restorative justice is authentic and far-reaching. This Essay proceeds to address the above concerns as follows. In Part I, I discuss the Emmett Till case in greater detail, with brief contextual reference to two historical eras that frame it chronologically and thematically: lynching in the late nineteenth to mid-twentieth centuries, and the civil rights movement of the mid-to late1950s. In Part II, I focus on the significance of the 2004 Till case reopening and lessons that it may offer for critical race practice. These lessons dovetail with recurrent questions in the literature of critical race theory and offer suggestions for fostering the integration of theory and practice (race praxis). Finally, I conclude that the Till case and other similar reopenings will yield transcendent meaning and "closure" only if a self-reflective approach propels them past the transitory "cleansing moments" toward a deeper commitment to restorative justice.
Patterning Poly(organophosphazenes) for Selective Cell Adhesion Applications (2005)

Five polyphosphazenes with different hydrophilicites were synthesized and screened in vitro. The purpose was to identify unique types of polymeric substrates that distinctly favored or markedly prevented cellular adhesion. The SK-N-BE(2c) human neuroblastoma cell line, utilized for its electrogenic responses, was used to test this differential adhesion. In particular, the objective was to specifically culture this cell line in a highly selective pattern. Each candidate polymer was cast into films and plated with neuroblastoma cells for 3 days. The polyphosphazene materials which showed negative cellular adhesive properties (-CAPs) were poly[bis(trifluoroethoxy)phosphazene] (TFE) and poly[bis(methoxyethoxyethoxy)phosphazene] (MEEP). The polyphosphazenes which showed positive cellular adhesive properties (+CAPs) were poly[(methoxyethoxyethoxy)(1.0)(carboxylatophenoxy)(1.0)phosphazene] (PMCPP), poly[(methoxyethoxyethoxy)(1.0)(cinnamyloxy)(1.0)phosphazene] (PMCP), and poly[(methoxyethoxyethoxy)(1.0)(p-methylphenoxy)(1.0)phosphazene] (PMMP). To test cellular selectivity, films of -CAP and +CAP were copatterned onto glass substrates. The micropatterned films were plated with SK-N-BE(2c) neuroblastoma cells for one week. The results showed that neuroblastoma cells adhere selectively (over 60%) to the +CAP microfeatures. We also showed that multiple properties can be achieved with a single material and that we can use TFE as both a -CAP and an insulation layer and PMCP as a conductive +CAP layer.
Reliability analysis of clustered computing systems (2002)

Clustered computing systems, using commercially available computers networked in a loosely-coupled fashion, can provide high levels of reliability if appropriate levels of error detection and recovery software are implemented in the middleware and application layers. In this paper, we present a modeling approach for analyzing the hardware and software reliability of clustered computing systems. The clustered system is modeled as an irreducible Markov chain with working and failed states, and intermediate recovery states. The failure and recovery behavior is characterized in terms of the frequency and duration of fault recoveries and outages for a single processor in the cluster and for the entire clustered system. We apply the model to a telecommunication switching system application that uses the Lucent Technologies Reliable Clustered Computing product. The model results are presented for a range of values of the processor failure rate and the fault recovery coverage factor.
Bronchodilation using combined urodilatin - albuterol administration in asthma: a randomized, double-blind, placebo-controlled trial. (1999)

Urodilatin, the renal form of natriuretic peptide type A, induces bronchodilation, increasing intracellular cyclic guanosine monophosphate (cGMP), whereas the bronchorelaxant effect by b2-agonists is triggered by cyclic adenosine monophosphate (cAMP). The objective of this investigation is to demonstrate the efficacy of urodilatin in inducing bronchodilation, and to show this activity alone or in combination with albuterol. Therefore, a randomized, double-blind, placebo-controlled, dose-finding study with cross-over design was carried out including 12 stable, mild to severe (step 2 to 4, definition by NIH/NHLBI guideline 1997) asthmatics. 96 treatments were thus performed. The intervention was comprised of an intravenous infusion of urodilatin (0, 10, 30, or 60 ng/kg/min) combined with inhaled albuterol (0 or 200 microg). As primary objective, the increase in forced expiratory volume in one second (FEV subset1) was measured. - The trial shows that urodilatin at all applied doses or 200 microg albuterol significantly increases FEV subset1 (p < 0.05). Combination of urodilatin and albuterol treament significantly improves FEV subset1 (p < 0.05) compared to either monotherapy and results in maximum bronchodilation. - From the results, the following conclusions can be drawn. In stable asthmatics, the combined activation of cGMP- and cAMP-mediated pathways results in a significantly improved, maximal bronchodilation in comparison to either type of monotherapy. This shows that urodilatin combined with albuterol improves lung function and ameliorates the therapy in asthmatics.
Evidence for a new hepatitis C virus antigen encoded in an overlapping reading frame (2001)

Many viruses have overlapping genes and/or regions in which a nucleic acid signal is embedded in a coding sequence. To search for dual-use regions in the hepatitis C virus (HCV), we developed a facile computer-based sequence analysis method to map dual-use regions in coding sequences. Eight diverse full-length HCV RNA and polyprotein sequences were aligned and analyzed. A cluster of unusually conserved synonymous codons was found in the core-encoding region, indicating a potential overlapping open reading frame (ORF). Four peptides (A1, A2, A3, and A4) representing this alternate reading frame protein (ARFP), two others from the HCV core protein, and one from bovine serum albumin (BSA) were conjugated to BSA and used in western blots to test sera for specific antibodies from 100 chronic HCV patients, 44 healthy controls, and 60 patients with non-HCV liver disease. At a 1:20,000 dilution, specific IgGs to three of the four ARFP peptides were detected in chronic HCV sera. Reactivity to either the A1 or A3 peptides (both ARFP derived) was significantly associated with chronic HCV infection, when compared to non-HCV liver disease serum samples (10/100 versus 1/60; p < 0.025). Antibodies to A4 were not detected in any serum sample. Our western blot assays confirmed the presence of specific antibodies to a new HCV antigen encoded, at least in part, in an alternate reading frame (ARF) overlapping the core-encoding region. Because this novel HCV protein stimulates specific immune responses, it has potential value in diagnostic tests and as a component of vaccines. This protein is predicted to be highly basic and may play a role in HCV replication, pathogenesis, and carcinogenesis.