gebhart/patrepeval huggingface dataset:
Characterization of the Response to Zinc Deficiency in the Cyanobacterium Anabaena sp. Strain PCC 7120 (2012)

Zur regulators control zinc homeostasis by repressing target genes under zinc-sufficient conditions in a wide variety of bacteria. This paper describes how part of a survey of duplicated genes led to the identification of the open reading frame all2473 as the gene encoding the Zur regulator of the cyanobacterium Anabaena sp. strain PCC 7120. All2473 binds to DNA in a zinc-dependent manner, and its DNA-binding sequence was characterized, which allowed us to determine the relative contribution of particular nucleotides to Zur binding. A zur mutant was found to be impaired in the regulation of zinc homeostasis, showing sensitivity to elevated concentrations of zinc but not other metals. In an effort to characterize the Zur regulon in Anabaena, 23 genes containing upstream putative Zur-binding sequences were identified and found to be regulated by Zur. These genes are organized in six single transcriptional units and six operons, some of them containing multiple Zur-regulated promoters. The identities of genes of the Zur regulon indicate that Anabaena adapts to conditions of zinc deficiency by replacing zinc metalloproteins with paralogues that fulfill the same function but presumably with a lower zinc demand, and with inducing putative metallochaperones and membrane transport systems likely being involved in the scavenging of extracellular zinc, including plasma membrane ABC transport systems and outer membrane TonB-dependent receptors. Among the Zur-regulated genes, the ones showing the highest induction level encode proteins of the outer membrane, suggesting a primary role for components of this cell compartment in the capture of zinc cations from the extracellular medium.
File synchronization and sharing: User practices and challenges (2014)

ABSTRACT In this paper, we present results of qualitative analysis of interviews with 16 university faculty regarding their use of file synchronization and sharing technologies in their work and personal lives. We identify key problems and considerations that influence file synchronization and sharing practices, and describe commonly used strategies. Our findings show that while behaviors have evolved as technology changes, users continue to make extensive use of familiar patterns of access, including automated and manual methods. We identified several factors that influence users’ choice of methods for synchronization, including privacy and security concerns, data size, institutional policies, and knowledge of systems. We present insights about how boundaries and data separation affect synchronization practices, and about specific synchronization issues users faced when collaborating. Our findings extend research on personal and group information management practices and provide insight for the design of synchronization and sharing systems.
Paracrine Hedgehog Signaling in Cancer (2009)

Ligand-dependent and ligand-independent activation of the Hedgehog (Hh) signaling pathway is involved in tumorigenesis. The importance of mutations in Hh pathway components leading to constitutive signaling has been well established in basal cell carcinoma and medulloblastoma. However, the role of ligand-driven Hh pathway activation in cancer remains to be established. Three recent articles support a model in which, in the absence of mutations in the Hh pathway, Hh ligands expressed by a subset of epithelial cancers, including colon, pancreatic, and ovarian cancer, promote tumor growth indirectly by activating Hh signaling in the surrounding stroma, which, in turn, provides a more favorable environment for tumor growth. These data have important implications for the use of Hh pathway inhibitors currently in development and for selection of tumors likely to respond to such inhibitors.
Isolation and characterization of human hematopoietic progenitor cells: an effective method for positive selection of CD34+ cells. (1992)

Immunomagnetic beads are well suited for positive selection of CD34+ cells. However, both unspecific binding of beads to cells as well as the effectiveness of detachment of beads from cells may represent significant problems. We used an anti-Fab antiserum (DETACHaBEAD, Dynal) for rapid and effective detachment of immunomagnetic beads from the positively selected cells. By this detachment technique, the cells remained phenotypically unaltered. To reduce unspecific binding, we have coated various anti-CD34 monoclonal antibodies directly to paramagnetic beads M450 (Dynal). Use of beads coated with BI-3C5 was found to be optimal with regard to yield and purity of the isolated cells. The yield was on average 1.5% (range 0.5-2.5%) of bone marrow mononuclear cells and the purity was usually greater than 95% CD34+ cells of the isolated cells. Subpopulations of the cells expressed myeloid markers (CD13, CD33, and to a lesser extent CD15 and CD14) or early B-lineage markers (CD19 and CD10). Most of the cells expressed CD38, and a majority of the cells also expressed CD41. In general, most of the CD34+ cells with low forward scatter expressed B-lineage markers, as was also the case for the few contaminating CD34- cells which were found to be predominantly CD37+ mature B cells. Reactivity with antibodies against T-lineage markers (CD2, CD3, CD4, CD7, and CD8) was generally detected only on 1-2% of the cells or less. Isolated cells responded to interleukin 3, granulocyte-macrophage colony-stimulating factor, mast cell growth factor, and/or granulocyte colony-stimulating factor alone or in combinations in short-term liquid cultures. The cells were also markedly enriched for granulocyte-macrophage colony-forming units as well as for early progenitor cells capable of forming blast colonies on preformed stromal feeder layers. Moreover, the CD34- population was depleted of 70-80% of CFU-GM and cells capable of blast colony formation. Thus, we conclude that the isolated cells are phenotypically unaltered after isolation, and show a normal response in various in vitro assays.
Determination of Cole parameters in multiple frequency bioelectrical impedance analysis using only the measurement of impedances (2006)

Conventional bioimpedance spectrometers measure resistance and reactance over a range of frequencies and, by application of a mathematical model for an equivalent circuit (the Cole model), estimate resistance at zero and infinite frequencies. Fitting of the experimental data to the model is accomplished by iterative, nonlinear curve fitting. An alternative fitting method is described that uses only the magnitude of the measured impedances at four selected frequencies. The two methods showed excellent agreement when compared using data obtained both from measurements of equivalent circuits and of humans. These results suggest that operational equivalence to a technically complex, frequency-scanning, phase-sensitive BIS analyser could be achieved from a simple four-frequency, impedance-only analyser.
4-Hydroxynonenal, a product of lipid peroxidation, inhibits dephosphorylation of the microtubule-associated protein tau (1997)

In Alzheimer's disease (AD) the microtubule-associated protein tau is excessively phosphorylated in degenerating neurons, but the mechanisms underlying the increased phosphorylation are unknown. Recent findings suggest that oxidative stress, and membrane lipid peroxidation in particular, contributes to the neurodegenerative process in AD. We now report that following exposure of cultured rat hippocampal neurons to 4-hydroxynonenal (HNE), an aldehydic product of membrane lipid peroxidation, tau is resistant to dephosphorylation. Immunocytochemical and Western blot analyses using phosphorylation-sensitive tau antibodies showed that HNE treatment causes a moderate increase in basal levels of tau phosphorylation, and prevents tau dephosphorylation by alkaline phosphatase in neurons pretreated with the phosphatase inhibitor okadaic acid. Studies with anti-HNE antibodies showed that HNE binds directly to tau, and that HNE immunoreactivity localizes to cell bodies and axons, cell compartments that contain tau. These data suggest a role for HNE in altered tau phosphorylation and neurofibrillary degeneration in AD.
Budding yeast Saccharomyces cerevisiae as a model to study oxidative modification of proteins in eukaryotes. (2006)

The budding yeast Saccharomyces cerevisiae is a well studied unicellular eukaryotic organism the genome of which has been sequenced. The use of yeast in many commercial systems makes its investigation important not only from basic, but also from practical point of view. Yeast may be grown under both aerobic and anaerobic conditions. The investigation of the response of eukaryotes to different kinds of stresses was pioneered owing to yeast and here we focus mainly on the so-called oxidative stress. It is a result of an imbalance between the formation and decomposition of reactive oxygen species increasing their steady-state concentration. Reactive oxygen species may attack any cellular component. In the present review oxidation of proteins in S. cerevisiae is analyzed. There are two connected approaches to study oxidative protein modification - characterization of the overall process and identification of individual oxidized proteins. Because all aerobic organisms possess special systems which defend them against reactive oxygen species, the involvement of so-called antioxidant enzymes, particularly superoxide dismutase and catalase, in the protection of proteins is also analyzed.
Custom-Designed Molecular Scissors for Site-Specific Manipulation of the Plant and Mammalian Genomes (2009)

Zinc finger nucleases (ZFNs) are custom-designed molecular scissors, engineered to cut at specific DNA sequences. ZFNs combine the zinc finger proteins (ZFPs) with the nonspecific cleavage domain of the FokI restriction enzyme. The DNA-binding specificity of ZFNs can be easily altered experimentally. This easy manipulation of the ZFN recognition specificity enables one to deliver a targeted double-strand break (DSB) to a genome. The targeted DSB stimulates local gene targeting by several orders of magnitude at that specific cut site via homologous recombination (HR). Thus, ZFNs have become an important experimental tool to make site-specific and permanent alterations to genomes of not only plants and mammals but also of many other organisms. Engineering of custom ZFNs involves many steps. The first step is to identify a ZFN site at or near the chosen chromosomal target within the genome to which ZFNs will bind and cut. The second step is to design and/or select various ZFP combinations that will bind to the chosen target site with high specificity and affinity. The DNA coding sequence for the designed ZFPs are then assembled by polymerase chain reaction (PCR) using oligonucleotides. The third step is to fuse the ZFP constructs to the FokI cleavage domain. The ZFNs are then expressed as proteins by using the rabbit reticulocyte in vitro transcription/translation system and the protein products assayed for their DNA cleavage specificity.
A New Zirconium Inorganic Building Brick Forming Metal Organic Frameworks with Exceptional Stability (2008)

Porous crystals are strategic materials with industrial applications within petrochemistry, catalysis, gas storage, and selective separation. Their unique properties are based on the molecular-scale porous character. However, a principal limitation of zeolites and similar oxide-based materials is the relatively small size of the pores, typically in the range of medium-sized molecules, limiting their use in pharmaceutical and fine chemical applications. Metal organic frameworks (MOFs) provided a breakthrough in this respect. New MOFs appear at a high and an increasing pace, but the appearances of new, stable inorganic building bricks are rare. Here we present a new zirconium-based inorganic building brick that allows the synthesis of very high surface area MOFs with unprecedented stability. The high stability is based on the combination of strong Zr-O bonds and the ability of the inner Zr6-cluster to rearrange reversibly upon removal or addition of mu3-OH groups, without any changes in the connecting carboxylates. The weak thermal, chemical, and mechanical stability of most MOFs is probably the most important property that limits their use in large scale industrial applications. The Zr-MOFs presented in this work have the toughness needed for industrial applications; decomposition temperature above 500 degrees C and resistance to most chemicals, and they remain crystalline even after exposure to 10 tons/cm2 of external pressure.
Expression of an exogenous peptide epitope genetically engineered in the variable domain of an immunoglobulin: implications for antibody and peptide folding (1990)

Immunoglobulins bind antigens and express individual antigenic specificities mainly through residues located in hypervariable loops of their N-terminal domains. Hypervariable loops are kept in place by a molecular scaffold organized in a sandwich-like structure with two beta-sheets stabilized by a disulfide bridge (the immunoglobulin fold). This structural feature, together with the possibility of obtaining high level expression, extracellular secretion, easy purification and stability of the protein product, render immunoglobulin an ideal 'molecular vehicle' for the expression of exogenous peptides. Here we report on the engineering of an immunoglobulin expressing an exogenous epitope, the repetitive tetrapeptide Asn-Ala-Asn-Pro (NANP)3. By recombinant DNA techniques, we inserted three copies of the tetrapeptide (NANP)3 in the third hypervariable loop (D region) of an immunoglobulin heavy chain variable domain. We show that the engineered antibody was properly assembled and secreted. A panel of polyclonal and monoclonal antibodies, including anti-synthetic peptides and anti-(NANP)n antibodies, were used to study the molecular configuration of the engineered domain's surface. The results indicate that (i) the exogenous sequence did not appreciably alter the overall fold of the variable domain; and (ii) the inserted epitope folded with a configuration immunologically similar to the one assumed in the native protein, suggesting that short- and medium- rather than long-range interactions stabilized the structure of the (NANP)3 peptide in the folded protein. We propose this system for the expression of peptidic sequences, and their structural and functional analysis.
Construction and identification of bacterial plasmids containing nucleotide sequence for human leukocyte interferon. (1980)

Bacterial plasmids containing human leukocyte interferon sequences were constructed and identified. Identification was confirmed by correspondence of the nucleotide sequence with out amino acid sequence of human leukocyte interferon. The finding of bacterial recombinants containing distinct leukocyte interferon sequences is consistent with our purification of different leukocyte interferon species. We conclude that what has been designated human leukocyte interferon is, indeed, a class of homologous proteins. Preliminary indications suggest that their diversity appears to be represented by individual genomic equivalents. Each of the individual species exhibits characteristic activities. The structural modulation of these biological activities has immense significance for understanding the natural role of the interferons and for refining and developing their ultimate therapeutic potential.
Real-world study of treatment patterns and outcomes among patients with metastatic pancreatic ductal adenocarcinoma (PDAC) in Europe. (2021)

391 Background: Few data are available regarding real-world treatment patterns and outcomes for metastatic PDAC (mPDAC) in Europe. Methods: This retrospective, observational, chart-review study involved medical oncologists and gastroenterologists from France, Germany, Italy, Spain, and the UK. Physicians completed online patient (pt) reports for 20 consecutive pts diagnosed with PDAC between 01 and 10/2016. Here, the analysis is focused on treated pts diagnosed with mPDAC. Reports provided information on general disease and pt characteristics, diagnosis, and treatment of metastatic disease. Outcomes included median PFS and OS according to each line of metastatic therapy. In addition, how baseline performance status (PS) and treatment sequence affected OS and PFS were assessed. Results: 304 physicians (France [n=62], Germany [n=60], Italy [n=63], Spain [n=66], UK [n=53]) participated and enrolled 6,000 pts with PAC, of whom 3827 had mPDAC. Of the 3827, 3432 were treated for their metastatic disease. The most common first-line therapies were modified FOLFIRINOX (28.4%), gemcitabine + nab-paclitaxel (28.0%), and gemcitabine monotherapy (23.0%), while the most common second-line therapies were gemcitabine monotherapy (25.0%), 5-FU + oxaliplatin (21.8%), and gemcitabine + nab-paclitaxel (16.7%). The longest median PFS and OS were obtained when using mFOLFIRINOX as first-line therapy, with gemcitabine-based combinations as second-line therapy. However, pt characteristics were more favorable with FOLFIRINOX compared with the other regimens used in first line. The most common treatment in first line for patients with a worse baseline PS (PS &gt;1) was gemcitabine monotherapy (571 patients [46%]); in addition, having a worse baseline PS was predictive of shorter survival in second line. The most common reason for discontinuation of either line was disease progression. The study showed that the choice of first- and second-line treatment among European physicians is in accordance with current ESMO guidelines; in contrast, the choice of subsequent line was more heterogeneous, according to local practices. Additional data concerning first and second line OS and PFS per treatment regimen will be presented at the meeting. Conclusions: This large real-life study highlights a clear picture of treatment patterns in European real-world clinical practice and outcomes for metastatic PDAC, which may help in more effectively managing such patients in the future. Further univariate and multivariate analysis will complete this first description.
Electronic Effects on Reductive Elimination To Form Carbon−Carbon and Carbon−Heteroatom Bonds from Palladium(II) Complexes (2007)

The electronic properties of reactive and ancillary ligands have a large impact on the rate and scope of reductive elimination reactions. The purpose of this review is to compare and discuss published data on the effect of ligand electronic properties on the rates and scope of reductive eliminations from palladium(II). An understanding of these effects is important because reductive elimination from palladium(II) is the product-forming step of a variety of catalytic processes. The scope of this review will encompass the effect of the electron-donating abilities of alkyl, aryl, amido, alkoxo, thiolato, and phosphido groups on the rate of reductive elimination, the relative importance of inductive and resonance effects on the rate of reductive elimination, the relative sensitivity of the different classes of reductive eliminations to electronic perturbations, and the effect of the differences in electronic properties between the two aryl groups of biaryl complexes undergoing reductive elimination. In addition, this review will include the effects of electronic properties of the ancillary ligands on the rate of reductive eliminations from palladium(II). The effect of the overall electron-donating ability of ancillary ligands and the effect of the relative orientation of ancillary ligands to the two reactive ligands on the rate of reductive elimination will be discussed. Where appropriate, electronic effects on reductive elimination from complexes of other metals are described.
Cross-linking methods of electrospun fibrinogen scaffolds for tissue engineering applications (2008)

The purpose of this study was to enhance the mechanical properties and slow the degradation of an electrospun fibrinogen scaffold, while maintaining the scaffold's high level of bioactivity. Three different cross-linkers were used to achieve this goal: glutaraldehyde vapour, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) in ethanol and genipin in ethanol. Scaffolds with a fibrinogen concentration of 120 mg ml(-1) were electrospun and cross-linked with one of the aforementioned cross-linkers. Mechanical properties were determined through uniaxial tensile testing performed on scaffolds incubated under standard culture conditions for 1 day, 7 days and 14 days. Cross-linked scaffolds were seeded with human foreskin fibroblasts (BJ-GFP-hTERT) and cultured for 7, 14 and 21 days, with histology and scanning electron microscopy performed upon completion of the time course. Mechanical testing revealed significantly increased peak stress and modulus values for the EDC and genipin cross-linked scaffolds, with significantly slowed degradation. However, cross-linking with EDC and genipin was shown to have some negative effect on the bioactivity of the scaffolds as cell migration throughout the thickness of the scaffold was slowed.
Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants (2004)

The Notch signaling pathway is essential for embryonic vascular development in vertebrates. Here we show that mouse embryos heterozygous for a targeted mutation in the gene encoding the DLL4 ligand exhibit haploinsufficient lethality because of defects in vascular remodeling. We also describe vascular defects in embryos homozygous for a mutation in the Rbpsuh gene, which encodes the primary transcriptional mediator of Notch signaling. Conditional inactivation of Rpbsuh function demonstrates that Notch activation is essential in the endothelial cell lineage. Notch pathway mutant embryos exhibit defects in arterial specification of nascent blood vessels and develop arteriovenous malformations. These results demonstrate that vascular remodeling in the mouse embryo is sensitive to Dll4 gene dosage and that Notch activation in endothelial cells is essential for embryonic vascular remodeling.
Does Radiotherapy for the Primary Tumor Benefit Prostate Cancer Patients with Distant Metastasis at Initial Diagnosis? (2016)

Our data suggest that radiotherapy to the primary tumor was associated with improved OS and BCFFS in metastatic prostate cancer. The results of this study warrant prospective controlled clinical trials of this approach in stage IV prostate cancer patients with limited extent of bone metastasis and good performance status.
Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination (2015)

The efficiency of central nervous system remyelination declines with age. This is in part due to an age-associated decline in the phagocytic removal of myelin debris, which contains inhibitors of oligodendrocyte progenitor cell differentiation. In this study, we show that expression of genes involved in the retinoid X receptor pathway are decreased with ageing in both myelin-phagocytosing human monocytes and mouse macrophages using a combination of in vivo and in vitro approaches. Disruption of retinoid X receptor function in young macrophages, using the antagonist HX531, mimics ageing by reducing myelin debris uptake. Macrophage-specific RXRα (Rxra) knockout mice revealed that loss of function in young mice caused delayed myelin debris uptake and slowed remyelination after experimentally-induced demyelination. Alternatively, retinoid X receptor agonists partially restored myelin debris phagocytosis in aged macrophages. The agonist bexarotene, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profile in multiple sclerosis patient monocytes to a more youthful profile and enhanced myelin debris phagocytosis by patient cells. These results reveal the retinoid X receptor pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics.