gebhart/patrepeval huggingface dataset:
Reactivity of Silica-Supported Hafnium Tris-neopentyl with Dihydrogen:  Formation and Characterization of Silica Surface Hafnium Hydrides and Alkyl Hydride (2007)

Surface organometallic chemistry represents an approach to the preparation of well-defined single sites for catalysis, the possibility of observing some elementary reaction steps, and the development of a fundamental basis for the synthesis of tailor-made catalysts. Silica-supported metal hydrides are an important class of new catalysts for alkane metathesis, methanolysis of alkanes, Ziegler−Natta depolymerization, alkane hydrogenolysis, etc. Understanding their mechanism of formation and aging is crucial. In the work presented here, the reaction of the well-defined silica surface organometallic complex [(⋮SiO)Hf(CH2tBu)3], 1, ((⋮SiO) = silica surface ligand) with dihydrogen has been performed at different temperatures (θ). At θ ≤ 100 °C, there is formation of a stable hafnium neopentyl dihydride, [(⋮SiO)Hf(CH2tBu)(H)2], 2. For 100 ≤ θ ≤ 200 °C, 2 affords, via a succession of β-methyl transfer and subsequent hydrogenolysis of the resulting Hf−alkyl bonds, the formation of [(⋮SiO)2Hf(H)2], 3, and [(⋮SiO)3SiH] with evolution of methane (C1) and ethane (C2). For 150 ≤ θ ≤ 300 °C, 3 is totally converted into [(⋮SiO)3Hf(H)], 4, and [(⋮SiO)2Si(H)2]. For θ ≥ 300 °C, [(⋮SiO)3Hf(H)], 4, is transformed into [(⋮SiO)4Hf], 5, and [(⋮SiO)2Si(H)2] into [(⋮SiO)3SiH]. At this temperature, [(⋮SiO)3SiH] is the only hydride remaining on the surface. All these species have been characterized with a multitude of techniques such as elemental analysis and infrared, 1H solid-state NMR, 1H DQ solid-state NMR, and EXAFS spectroscopies. The results elucidate a complete mechanism of surface organometallic chemistry by which one observes the stepwise transformation of a hafnium tris-neopentyl to hafnium neopentyl hydrides, hafnium mono- and bis-hydrides, silicon bis-hydride with the ultimate formation of tetrasiloxy surface species [(⋮SiO)4Hf)], and silicon mono-hydride, the only hydride stable at very high temperature. It is suggested that the formation of these surface silicon hydrides is responsible for the aging of such catalysts in any reaction involving dihydrogen.
Mitosis-specific phosphorylation of nucleolin by p34cdc2 protein kinase. (1990)

Nucleolin is a ubiquitous multifunctional protein involved in preribosome assembly and associated with both nucleolar chromatin in interphase and nucleolar organizer regions on metaphasic chromosomes in mitosis. Extensive nucleolin phosphorylation by a casein kinase (CKII) occurs on serine in growing cells. Here we report that while CKII phosphorylation is achieved in interphase, threonine phosphorylation occurs during mitosis. We provide evidence that this type of in vivo phosphorylation involves a mammalian homolog of the cell cycle control Cdc2 kinase. In vitro M-phase H1 kinase from starfish oocytes phosphorylated threonines in a TPXK motif present nine times in the amino-terminal part of the protein. The same sites which matched the p34cdc2 consensus phosphorylation sequence were used in vivo during mitosis. We propose that successive Cdc2 and CKII phosphorylation could modulate nucleolin function in controlling cell cycle-dependent nucleolar function and organization. Our results, along with previous studies, suggest that while serine phosphorylation is related to nucleolin function in the control of rDNA transcription, threonine phosphorylation is linked to mitotic reorganization of nucleolar chromatin.
Analysis of the photocurrent action spectra of MEH-PPV polymer photodiodes (1997)

We have measured the photocurrent action spectra of the conjugated polymers poly[2-methoxy, 5 ethyl (2\ensuremath{'} hexyloxy) paraphenylenevinylene] (MEH-PPV) and poly(phenylenevinylene) (PPV) in sandwich cells between indium tin oxide (ITO) and aluminum electrodes. Under forward bias and illumination through ITO, the photocurrent spectrum is broad and has a maximum at high energy, where the absorption coefficient is greatest (the symbatic response). Under reverse bias and illumination through ITO, the photocurrent spectrum consists of a very narrow peak (the full width at half maximum is 0.1 eV), located in the low-energy tail of the absorption profile (the antibatic response). Several established models attempt to explain this behavior and to relate the photocurrent action spectrum to the absorption coefficient, considering penetration depth of the light and diffusion of excitons or directly photogenerated charges. At a qualitative level many of these seem to provide an adequate description. In this paper, we undertake a quantitative examination of these models and we find that none of them can reproduce the very narrow antibatic response that we observe in both MEH-PPV and PPV. Upon exposure to air, we observe an enhancement of the photocurrent by a much greater factor than the dark current, from which we conclude that charge generation is mediated by exciton dissociation. As the temperature decreases we observe a progressive redshift of the absorption edge, although the photocurrent onset undergoes a much smaller redshift. We therefore conclude that the narrow antibatic peak is due to a specific enhancement of dissociation upon excitation at low energy. We propose that the particularly sharp onset of photocurrent at low energy may be due to enhanced intermolecular charge separation within crystallite grains between those neighboring conjugated segments that are more extended and more planar.
Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells (2000)

We have reported that fusions of murine dendritic cells (DCs) and murine carcinoma cells reverse unresponsiveness to tumor-associated antigens and induce the rejection of established metastases. In the present study, fusions were generated with primary human breast carcinoma cells and autologous DCs. Fusion cells coexpressed tumor-associated antigens and DC-derived costimulatory molecules. The fusion cells also retained the functional potency of DCs and stimulated autologous T cell proliferation. Significantly, the results show that autologous T cells are primed by the fusion cells to induce MHC class I-dependent lysis of autologous breast tumor cells. These findings demonstrate that fusions of human breast cancer cells and DCs activate T cell responses against autologous tumors.
PNU-142731A Pharmacia. (2000)

Pharmacia is developing PNU-142731A, a potential lead compound as a treatment for asthma [294718]. It is in phase I clinical trials. PNU-142731A is a potent inhibitor of eosinophilic lung inflammation in rodents, and shows a good bioavailability profile in animals; the mechanism of action is being investigated. Unlike the original compound PNU-104067F, PNU-142731A does not give rise to gall bladder toxicity [295987], [298023].
Single cell transcriptome analysis of human, marmoset and mouse embryos reveals common and divergent features of preimplantation development (2018)

The mouse embryo is the canonical model for mammalian preimplantation development. Recent advances in single cell profiling allow detailed analysis of embryogenesis in other eutherian species, including human, to distinguish conserved from divergent regulatory programs and signalling pathways in the rodent paradigm. Here, we identify and compare transcriptional features of human, marmoset and mouse embryos by single cell RNA-seq. Zygotic genome activation correlates with the presence of polycomb repressive complexes in all three species, while ribosome biogenesis emerges as a predominant attribute in primate embryos, supporting prolonged translation of maternally deposited RNAs. We find that transposable element expression signatures are species, stage and lineage specific. The pluripotency network in the primate epiblast lacks certain regulators that are operative in mouse, but encompasses WNT components and genes associated with trophoblast specification. Sequential activation of GATA6, SOX17 and GATA4 markers of primitive endoderm identity is conserved in primates. Unexpectedly, OTX2 is also associated with primitive endoderm specification in human and non-human primate blastocysts. Our cross-species analysis demarcates both conserved and primate-specific features of preimplantation development, and underscores the molecular adaptability of early mammalian embryogenesis.
An Evaluation of a New Two-Electrode Myocardial Electrical Impedance Monitor for Detecting Myocardial Ischemia (2001)

The objective of this study was to determine the efficacy of a two-electrode myocardial electrical impedance (MEI) monitor in reproducibly detecting induced myocardial ischemia by comparing MEI changes with hemodynamic changes, including sonomicrometric changes. With institutional approval, 80 dogs were anesthetized with sodium thiamylal, intubated, ventilated, and had venous, arterial, and pulmonary artery catheters placed. Medial sternotomy was performed to facilitate myocardial exposure and allow the left anterior descending coronary artery (LAD) to be isolated. Two pacing electrodes were attached to the myocardium to measure MEI with a monitor. Seventy dogs were randomly assigned to the 15, 30, 45, 60, or 120 min LAD occlusion group. Sonomicrometric transducers were attached to the myocardium of the ten remaining dogs and their LAD was occluded for 36 min. MEI increased immediately after LAD occlusion to a level significantly more (P < 0.05) than baseline and returned to the baseline level upon reperfusion. Twenty dogs developed ventricular fibrillation with no attempts at resuscitation. MEI changes paralleled the sonomicrometric changes expected with ischemia. No significant cardiovascular hemodynamic changes were found with less than 45 min of LAD occlusion. Sixty and 120 min LAD occlusion resulted in significant decreases in cardiac output. The results of these experiments demonstrate that the two-electrode MEI monitor reproducibly changes in response to myocardial ischemia.
Comparative sensitivity of Histoplasma capsulatum conidiospores and blastospores to oxidative antifungal systems (1981)

The comparative sensitivity of blastospores and conidiospores of Histoplasma capsulatum to hydrogen peroxide, to hydrogen peroxide and halides, and to a combination of hydrogen peroxide and halide with the enzyme myeloperoxidase was studied. Blastospores of different strains of H. capsulatum varied in their sensitivity to hydrogen peroxide. This variation correlated with the amount of catalase in cell-free extracts from the strains. Blastospores and conidiospores of a single isolate were about equally susceptible to hydrogen peroxide, but this sensitivity could obviously vary with the catalase content of the two types of spores. Halides augmented the antifungal activity of hydrogen peroxide for both types of spores. Iodide was far more efficient in this regard than was chloride. A crude granule lysate from guinea pig polymorphonuclear leukocytes was quite inhibitory to blastospore but not to conidiospore germination. A study of the myeloperoxidase activity of such preparations against blastospores was thus precluded. A sample of a very highly purified human myeloperoxidase functioned in the presence of hydrogen peroxide and either iodide or chloride to prevent germination of both blastospores and conidiospores. The preparation had no toxicity for spores apart from its interaction with hydrogen peroxide and halides.
An Evaluation of the Significance of Amino Acid Sequence Homologies in Human Histocompatibility Antigens (HLA‐A and HLA‐B) with Immunoglobulins and Other Proteins, Using Relatively Short Sequences (1980)

A computer search was carried out for homologies between HLA-A and HLA-B antigen sequences and the sequences of constant and variable regions of immunoglobulins and of all other sequenced proteins. Searches were made both with relatively short peptide sequences from the HLA antigens and with those longer peptide sequences which were available in 1978. Significant homology of HLA antigen sequences to immunoglobulin constant region sequences was found in two cases: (1) a short decapeptide sequence which includes the fourth cysteine residue of HLA-B7 and (2) an 89-amino-acid residue (Ac-2) C-terminal fragment of the papainsolubilized HLA-B7 molecule. The difficulty of establishing statistically significant sequence homology with relatively short peptide sequences is emphasized by computer-based comparisons of the decapeptide sequence with randomly generated peptide sequences. It is concluded that statistically significant homology with short sequences can be assured only when extraordinarily high degrees of homology are present and additional constraints are included in the matches, for example, matches at relatively rare amino acid residues such as Cys, His and Trp. The homology of the 89-amino-acid residue sequence to constant region sequences of immunoglobulins is as great as or greater than that of beta 2-microglobulin. These findings and the unique domain structure involving a disulphide loop of comparable size strongly favour a common evolutionary origin for this region of HLA-A and -B, beta 2-microglobulin and immunoglobulin constant regions.
Molecular genetics of malignant insulinoma. (1996)

Malignant insulinoma is an rare form of cancer with poor prognosis and a reported 5-year survival of 35%. Relatively little is known about the etiology of this disease or of the oncogenes and tumor suppressor genes that participate in its genesis and progression. To address this issue, several protooncogenes, including K-ras, N-ras, erbB-2, erbB-3,c-myc, c-fos, c-jun were examined. Also analyzed was the expression of the growth factors TGF-alpha, EGF, and insulin as well as the EGF receptor (EGF-R), p53 and the putative anti-metastasis gene nm23-H1. These were examined in malignant insulinomas, benign insulinomas, pancreatic B cell hyperplasias and in normal endocrine pancreas. Normal endocrine pancreas showed moderate immunoreaction for c-myc and a strong reaction for insulin. All other parameters were negative. Benign pancreatic B cell hyperplasias were slightly or moderately positive for N-ras and TGF-alpha, and were weakly positive for EGF-R. They were strongly positive for c-myc and insulin. In malignant insulinomas there was strong immunoreaction for c-myc, TGF-alpha, N-ras, K-ras and p53. Insulin reaction was moderate or strong. Molecular genetic studies have been performed for the presence of activating point mutations in codon 12 of the c-K-ras oncogene. Mutations were detected using primer-mediated, mutant-enriched, polymerase chain reaction-restriction fragment length polymorphism analysis and were further characterized by allele-specific oligonucleotide hybridization. Four out of six patients with malignant insulinoma and two out of eight patients with benign insulinoma harbored K-ras point mutations at codon 12. All patients with mutated K-ras oncogene also had elevated levels of p53 protein as well as c-myc and TGF-alpha. In one extremely malignant case we found concomitant mutation at codon 12 of K-ras and codon 61 of the N-ras gene. Our data are consistent with the idea that malignant progression is accompanied by the progressive accumulation of multiple genetic lesions and suggest that activation of myc, TGF-alpha and ras genes may be early events in the development of insulinoma.
A Novel Triple-Mutant AAV6 Capsid Induces Rapid and Potent Transgene Expression in the Muscle and Respiratory Tract of Mice (2018)

Gene therapy for the treatment of genetic disorders has demonstrated considerable therapeutic success in clinical trials. Among the most effective and commonly used gene delivery vectors are those based on adeno-associated virus (AAV). Despite these advances in clinical gene therapy, further improvements in AAV vector properties such as rapid intracellular processing and transgene expression, targeted transduction of therapeutically relevant cell types, and longevity of transgene expression, will render extension of such successes to many other human diseases. Engineering of AAV capsids continues to evolve the specificity and efficiency of AAV-mediated gene transfer. Here, we describe a triple AAV6 mutant, termed AAV6.2FF, containing F129L, Y445F, and Y731F mutations. AAV6.2FF yielded 10-fold greater transgene expression in lung than AAV6 after 21 days. Additionally, this novel capsid demonstrated 101-fold and 49-fold increased transgene expression in the muscle and lungs, respectively, 24 hr post vector delivery when compared with the parental AAV6. Furthermore, AAV6.2FF retains heparin sulfate binding capacity and displays a 10-fold increase in resistance to pooled immunoglobulin neutralization <i>in vitro</i>. The rapid and potent expression mediated by AAV6.2FF is ideally suited to applications such as vectored immunoprophylaxis, in which rapid transgene expression is vital for use during an outbreak response scenario.
Preparation of Metallic Films on Elastomeric Stamps and Their Application for Contact Processing and Contact Printing (2003)

Abstract The formation of permanent or reversible metallic patterns on a substrate has applications in microfabrication and analytical techniques. Here, we investigate how to metallize an elastomeric stamp, either for processing of a substrate mediated by the proximity between the metal on the stamp and an active layer on the substrate, or for contact printing of the metal from a stamp to a substrate. The stamps were made from poly(dimethylsiloxane) (PDMS) and were modified before metallizing them with Au by adding to or removing from their bulk mobile silicone residues, by oxidizing their surface with an O 2 ‐plasma, by surface‐fluorination via silanization, or by priming them with a Ti layer. The interplay between the adhesion of the different layers defines two categories of application: contact processing and contact printing. Contact processing corresponds to keeping the metal on the stamp after contacting a substrate; it is reversible and nondestructive, and useful to define transient electrical contacts or quench fluorescence on a surface, for example. Contact printing occurs when the metal on the stamp adheres to the printed surface. Contact printing can transfer a metal, layers of metals, or an oxide onto a substrate with submicrometer lateral resolution. The transfer can be total or localized to the regions of contact, depending on the morphology of the metal on the stamp and/or the surface chemistry of the substrate.
Topology of outer membrane pore protein PhoE of Escherichia coli. Identification of cell surface-exposed amino acids with the aid of monoclonal antibodies. (1986)

Monoclonal antibodies which recognize the cell surface-exposed part of outer membrane protein PhoE of Escherichia coli were used to select for antigenic mutants producing an altered PhoE protein. The selection procedure was based on the antibody-dependent bactericidal action of the complement system. Using two distinct PhoE-specific monoclonal antibodies, seven independent mutants with an altered PhoE protein were isolated. Among these seven mutants, five distinct binding patterns were observed with a panel of 10 monoclonal antibodies. DNA sequence analysis revealed the following substitutions in the 330-residue-long PhoE protein: Arg-201----His (three isolates), Arg-201----Cys, Gly-238----Ser, Gly-275----Ser and Gly-275----Asp. It is argued that amino acid residues 201, 238, and 275 are most likely directly involved in antibody binding and, therefore, exposed at the cell surface. Together with Arg-158, which was previously shown to be cell surface exposed as it is changed in phage TC45-resistant phoE mutants, these four positions show a remarkably regular spacing, being approximately 40 residues apart. A model is suggested in which the PhoE polypeptide repeatedly traverses the outer membrane in an antiparallel beta-pleated sheet structure, exposing eight areas to the outside which are all separated by approximately 40 residues.
A Straightforward Approach to Markov Chain Monte Carlo Methods for Item Response Models (1999)

This paper demonstrates Markov chain Monte Carlo (MCMC) techniques that are particularly well-suited to complex models with item response theory (IRT) assumptions. MCMC may be thought of as a successor to the standard practice of first calibrating the items using E-M methods and then taking the item parameters to be known and fixed at their calibrated values when proceeding with inference regarding the latent trait, in contrast to this two-stage E-M approach, MCMC methods treat item and subject parameters at the same time; this allows us to incorporate standard errors of item estimates into trait inferences, and vice versa. We develop a MCMC methodology, based on Metropolis-Hastings sampling, that can be routinely implemented to fit novel IRT models, and we compare the algorithmic features of the Metropolis- Hastings approach to other approaches based on Gibbs sampling. For concreteness we illustrate the methodology using the familiar two-parameter logistic (2PL) IRT model; more complex models are treated in a subsequent paper (Patz &amp; Junker, in press).
Factors influencing T-cell turnover in HIV-1–seropositive patients (2000)

HIV-1 disease is associated with pathological effects on T-cell production, destruction, and distribution. Using the deuterated (2H) glucose method for endogenous labeling, we have analyzed host factors that influence T-cell turnover in HIV-1-uninfected and -infected humans. In untreated HIV-1 disease, the average half life of circulating T cells was diminished without compensatory increases in cell production. Within 12 weeks of the initiation of highly active antiretroviral therapy (HAART), the absolute production rates of circulating T cells increased, and normal half-lives and production rates were restored by 12-36 months. Interpatient heterogeneity in the absolute degree of turnover correlated with the relative proportion of naive- and memory/effector-phenotype T cells in each of the CD4+ and CD8+ populations. The half-lives of naive-phenotype T cells ranged from 116-365 days (fractional replacement rates of 0.19-0.60% per day), whereas memory/effector-phenotype T cells persisted with half-lives from 22-79 days (fractional replacement rates of 0.87-3.14% per day). Naive-phenotype T cells were more abundant, and the half-life of total T cells was prolonged in individuals with abundant thymic tissue, as assessed by computed tomography. Such interpatient variation in T-cell kinetics may be reflective of differences in functional immune reconstitution after treatment for HIV-1 disease.