gebhart/patrepeval huggingface dataset:
The BUGS project: Evolution, critique and future directions (2009)

BUGS is a software package for Bayesian inference using Gibbs sampling. The software has been instrumental in raising awareness of Bayesian modelling among both academic and commercial communities internationally, and has enjoyed considerable success over its 20-year life span. Despite this, the software has a number of shortcomings and a principal aim of this paper is to provide a balanced critical appraisal, in particular highlighting how various ideas have led to unprecedented flexibility while at the same time producing negative side effects. We also present a historical overview of the BUGS project and some future perspectives.
Cytokeratin 8 functions as a major plasminogen receptor in select epithelial and carcinoma cells (2001)

Cytokeratin 8 (K8) is a member of the intermediate filament (IF) gene family expressed by simple epithelial cells and by some carcinoma cells. The majority of the cellular K8 is assembled with its partner, K18, into highly insoluble 10 nm filaments that extend from the nucleus to the internal leaflet of the plasma membrane. At desmosomes and hemidesmosomes, K8, K18, and other IF proteins are bridged to proteins with transmembrane domains by a family of proteins called plakins. K8 does not have a signal peptide or a well-defined transmembrane domain; however, there is substantial evidence that this protein is available to bind plasminogen and K8-specific antibodies on the surfaces of certain epithelial cells in culture, including hepatocytes, hepatocellular carcinoma cells, and various breast cancer cell lines. This may reflect a novel mechanism of protein penetration through the plasma membrane or binding of secreted K8 to other cell-surface molecules. Cancer cells are known to secrete K8-containing protein complexes in vitro and in vivo. These complexes bind plasminogen as well. The plasminogen-binding activity of K8 is unique amongst IF proteins, probably because its sequence includes a carboxyl-terminal Lys residue. However, a K8 mutant that lacks the C-terminal Lys still binds plasminogen, albeit with decreased affinity. K18 does not bind plasminogen; however, K8 and K18 bind tissue-type plasminogen activator (tPA) equivalently. tPA-binding to K18 may be important in the mechanism whereby K8-K18 complexes promote plasminogen activation by tPA. Numerous studies have demonstrated correlations between high levels of K8 expression and increased migration and invasion of certain cancer cells. These correlations are most easily explained by the function of IF proteins in determining the rigidity of the cytoskeleton; however, the function of cell-surface K8 as a plasminogen receptor merits consideration. We have demonstrated that certain aggressive breast cancer cell lines, which have highly activated endogenous urokinase type-plasminogen activator (uPA)-uPA receptor (uPAR) systems, do not express high levels of cell-surface K8. The membrane macromolecule that is responsible for plasminogen-binding and for supporting activation of plasminogen by uPA on the surfaces of these cell types remains to be determined. This review focuses on the function of K8 as a plasminogen receptor and its potential role in cancer.
Mechanistic Studies of a Calcium-Dependent MRI Contrast Agent (2002)

Intracellular Ca(2+) plays an important role in signal transduction, and we are developing new MRI techniques to study its regulation in living animals. We have reported on an MRI contrast agent (DOPTA-Gd) where the relaxivity of the complex is controlled by the presence or absence of the divalent ion Ca(2+). By structurally modulating inner-sphere access of water to a chelated Gd(3+) ion, we observe a substantial and reversible change in T(1) upon the addition of Ca(2+) and not other divalent ions. Luminescence lifetime and NMRD measurements of the complex have been acquired, and several parameters contribute to the Ca(2+) dependent relaxivity change of DOPTA-Gd. The number of inner-sphere water molecules is more than doubled after the Ca(2+) concentration is increased. This finding strongly supports the proposed conformational change of DOPTA-Gd when Ca(2+) is bound. Relaxometric measurements confirm these results and provide an indication that second-sphere water molecules are probably responsible for paramagnetic relaxation enhancement in the absence of Ca(2+). After Ca(2+) is bound to DOPTA-Gd, the molecule undergoes a substantial conformational change that opens up the hydrophilic face of the tetraazacyclododecane macrocycle. This change dramatically increases the accessibility of chelated Gd(3+) ion to bulk solvent. The design of this class of calcium-activated MR contrast agent was based primarily on the assumption that the number of coordinated inner-sphere water molecules would be the dominating factor in observed relaxivity measurements. This result has been confirmed; however, careful mechanistic studies reveal that additional factors are involved in this process.
Tyrosine phosphorylation of membrane proteins mediates cellular invasion by transformed cells. (1992)

Tyrosine phosphorylation of membrane-associated proteins is involved at two distinct sites of contact between cells and the extracellular matrix: adhesion plaques (cell adhesion and de-adhesion) and invadopodia (invasion into the extracellular matrix). Adhesion plaques from chicken embryonic fibroblasts or from cells transformed by Rous sarcoma virus contain low levels of tyrosine-phosphorylated proteins (YPPs) which were below the level of detection in 0.5-microns thin, frozen sections. In contrast, intense localization of YPPs was observed at invadopodia of transformed cells at sites of degradation and invasion into the fibronectin-coated gelatin substratum, but not in membrane extensions free of contact with the extracellular matrix. Local extracellular matrix degradation and formation of invadopodia were blocked by genistein, an inhibitor of tyrosine-specific kinases, but cells remained attached to the substratum and retained their free-membrane extensions. Invadopodia reduced or lost YPP labeling after treatment of the cells with genistein, but adhesion plaques retained YPP labeling. The plasma membrane contact fractions of normal and transformed cells have been isolated form cells grown on gelatin cross-linked substratum using a novel fractionation scheme, and analyzed by immunoblotting. Four major YPPs (150, 130, 81, and 77 kD) characterize invadopodial membranes in contact with the matrix, and are probably responsible for the intense YPP labeling associated with invadopodia extending into sites of matrix degradation. YPP150 may be an invadopodal-specific YPP since it is approximately 3.6-fold enriched in the invasive contact fraction relative to the cell body fraction and is not observed in normal contacts. YPP130 is enriched in transformed cell contacts but may also be present in normal contacts. The two major YPPs of normal contacts (130 and 71 kD) are much lower in abundance than the major tyrosine-phosphorylated bands associated with invadopodial membranes, and likely represent major adhesion plaque YPPs. YPP150, paxillin, and tensin appear to be enriched in the cell contact fractions containing adhesion plaques and invadopodia relative to the cell body fraction, but are also present in the soluble supernate fraction. However, vinculin, talin, and alpha-actinin that are localized at invadopodia, are equally concentrated in cell bodies and cell contacts as is the membrane-adhesion receptor beta 1 integrin. Thus, tyrosine phosphorylation of the membrane-bound proteins may contribute to the cytoskeletal and plasma membrane events leading to the formation and function of invadopodia that contact and proteolytically degrade the extracellular matrix; we have identified several candidate YPPs that may participate in the regulation of these processes.
Integrated Synthesis of Zeolites Using Coal Fly Ash: Element Distribution in the Products, Washing Waters and Effluent (2016)

Coal fly ash has been proposed as an alternative raw material for zeolite synthesis, however, the mobilization of toxic elements of this material into zeolite products, washing water and effluent is rarely addressed. In this study, Brazilian coal fly ash was used in the integrated synthesis (two steps) of zeolites Na-P1 and 4A and the distribution of approximately 40 major, minor and trace elements was investigated in all the input and output flows involved in the process. The mobilization of several elements was observed in the zeolite products, a number of which are highly toxic, such as As, Cd, Cr, Ni and Pb. With regard to the amount present in the ash, both zeolites were enriched in several elements, such as Ni in zeolite Na-P1 and As in zeolite 4A. The latter exhibited high purity, with most of the elements investigated having concentrations close to those measured in commercial zeolite 4A. Important information was gathered regarding zeolite synthesis using fly ash, which will ensure safer application of these materials and, if necessary, propose a contaminant-free synthesis route.
[Significance of SAMD9 expression in esophageal squamous cell carcinoma]. (2014)

Over-expression of SAMD9 is correlated with the metastasis of ESCC, indicating that it might play an important role in the metastasis of ESCC.
Requirement for Macrophage Elastase for Cigarette Smoke-Induced Emphysema in Mice (1997)

To determine which proteinases are responsible for the lung destruction characteristic of pulmonary emphysema, macrophage elastase-deficient (MME-/-) mice were subjected to cigarette smoke. In contrast to wild-type mice, MME-/- mice did not have increased numbers of macrophages in their lungs and did not develop emphysema in response to long-term exposure to cigarette smoke. Smoke-exposed MME-/- mice that received monthly intratracheal instillations of monocyte chemoattractant protein-1 showed accumulation of alveolar macrophages but did not develop air space enlargement. Thus, macrophage elastase is probably sufficient for the development of emphysema that results from chronic inhalation of cigarette smoke.
Reaction-Driven Restructuring of Rh-Pd and Pt-Pd Core-Shell Nanoparticles (2009)

The structure and composition of core-shell Rh{sub 0.5}Pd{sub 0.5} and Pt{sub 0.5}Pd{sub 0.5} nanoparticle catalysts were studied in situ, during oxidizing, reducing, and catalytic reactions involving NO, O{sub 2}, CO, and H{sub 2} using X-ray photoelectron spectroscopy in the Torr pressure range. The Rh{sub 0.5}Pd{sub 0.5} nanoparticles undergo dramatic and reversible changes in composition and chemical state in response to oxidizing or reducing conditions. Under oxidizing conditions the Rh atoms segregate to the shell region while in reducing atmospheres the Pd atoms diffuse to the shell region. In contrast no significant segregation of Pd or Pt atoms was found in Pt{sub 0.5}Pd{sub 0.5} nanoparticles. The distinct behavior in restructuring and chemical response of Rh{sub 0.5}Pd{sub 0.5} and Pt{sub 0.5}Pd{sub 0.5} nanoparticle catalysts under the same reaction conditions illustrates the flexibility and tunability of the structure of bimetallic nanoparticle catalysts during catalytic reactions.
CRISPR/Cas, the Immune System of Bacteria and Archaea (2010)

Microbes rely on diverse defense mechanisms that allow them to withstand viral predation and exposure to invading nucleic acid. In many Bacteria and most Archaea, clustered regularly interspaced short palindromic repeats (CRISPR) form peculiar genetic loci, which provide acquired immunity against viruses and plasmids by targeting nucleic acid in a sequence-specific manner. These hypervariable loci take up genetic material from invasive elements and build up inheritable DNA-encoded immunity over time. Conversely, viruses have devised mutational escape strategies that allow them to circumvent the CRISPR/Cas system, albeit at a cost. CRISPR features may be exploited for typing purposes, epidemiological studies, host-virus ecological surveys, building specific immunity against undesirable genetic elements, and enhancing viral resistance in domesticated microbes.
Immunogenicity and Safety of a Combination of Two Serogroup B Meningococcal Outer Membrane Vesicle Vaccines (2007)

MenBvac and MeNZB are safe and efficacious vaccines against serogroup B meningococcal disease. MenBvac is prepared from a B:15:P1.7,16 meningococcal strain (strain 44/76), and MeNZB is prepared from a B:4:P1.7-2,4 strain (strain NZ98/254). At 6-week intervals, healthy adults received three doses of MenBvac (25 microg), MeNZB (25 microg), or the MenBvac and MeNZB (doses of 12.5 microg of each vaccine) vaccines combined, followed by a booster 1 year later. Two-thirds of the subjects who received a monovalent vaccine in the primary schedule received the other monovalent vaccine as a booster dose. The immune responses to the combined vaccine were of the same magnitude as the homologous responses to each individual vaccine observed. At 6 weeks after the third dose, 77% and 87% of the subjects in the combined vaccine group achieved serum bactericidal titers of > or = 4 against strains 44/76 and NZ98/254, respectively, and 97% and 93% of the subjects achieved a fourfold or greater increase in opsonophagocytic activity against strains 44/76 and NZ98/254, respectively. For both strains, a trend of higher responses after the booster dose was observed in all groups receiving at least one dose of the respective strain-specific vaccine. Local and systemic reactions were common in all vaccine groups. Most reactions were mild or moderate in intensity, and there were no vaccine-related serious adverse events. The safety profile of the combined vaccine was not different from those of the separate monovalent vaccines. In conclusion, use of either of the single vaccines or the combination of MenBvac and MeNZB may have a considerable impact on the serogroup B meningococcal disease situation in many countries.
Rapamycin Reverses Cellular Phenotypes and Enhances Mutant Protein Clearance in Hutchinson-Gilford Progeria Syndrome Cells (2011)

Hutchinson-Gilford progeria syndrome (HGPS) is a lethal genetic disorder characterized by premature aging. HGPS is most commonly caused by a de novo single-nucleotide substitution in the lamin A/C gene (LMNA) that partially activates a cryptic splice donor site in exon 11, producing an abnormal lamin A protein termed progerin. Accumulation of progerin in dividing cells adversely affects the integrity of the nuclear scaffold and leads to nuclear blebbing in cultured cells. Progerin is also produced in normal cells, increasing in abundance as senescence approaches. Here, we report the effect of rapamycin, a macrolide antibiotic that has been implicated in slowing cellular and organismal aging, on the cellular phenotypes of HGPS fibroblasts. Treatment with rapamycin abolished nuclear blebbing, delayed the onset of cellular senescence, and enhanced the degradation of progerin in HGPS cells. Rapamycin also decreased the formation of insoluble progerin aggregates and induced clearance through autophagic mechanisms in normal fibroblasts. Our findings suggest an additional mechanism for the beneficial effects of rapamycin on longevity and encourage the hypothesis that rapamycin treatment could provide clinical benefit for children with HGPS.
rse, a novel receptor-type tyrosine kinase with homology to Axl/Ufo, is expressed at high levels in the brain. (1994)

We have isolated cDNA clones that encode the human and murine forms of a novel receptor-type tyrosine kinase termed Rse. Sequence analysis indicates that human Rse contains 890 amino acids, with an extracellular region composed of two immunoglobulin-like domains followed by two fibronectin type III domains. Murine Rse contains 880 amino acids and shares 90% amino acid identity with its human counterpart. Rse is structurally similar to the receptor-type tyrosine kinase Axl/Ufo, and the two proteins have 35 and 63% sequence identity in their extracellular and intracellular domains, respectively. To study the synthesis and activation of this putative receptor-type tyrosine kinase, we constructed a version of Rse (termed gD-Rse, where gD represents glycoprotein D) that contains an NH2-terminal epitope tag. NIH3T3 cells were engineered to express gD-Rse, which could be detected at the cell surface by fluorescence-activated cell sorting. Moreover, gD-Rse was rapidly phosphorylated on tyrosine residues upon incubation of the cells with an antibody directed against the epitope tag, suggesting that rse encodes an active tyrosine kinase. In the human tissues we examined, the highest level of expression of rse mRNA was observed in the brain; rse mRNA was also detected in the premegakaryocytopoietic cell lines CMK11-5 and Dami. The gene for rse was localized to human chromosome 15.
Role of N-Terminal Amino Acids in the Potency of Anthrax Lethal Factor (2008)

Anthrax lethal factor (LF) is a Zn(+2)-dependent metalloprotease that cleaves several MAPK kinases and is responsible for the lethality of anthrax lethal toxin (LT). We observed that a recombinant LF (LF-HMA) which differs from wild type LF (LF-A) by the addition of two residues (His-Met) to the native Ala (A) terminus as a result of cloning manipulations has 3-fold lower potency toward cultured cells and experimental animals. We hypothesized that the "N-end rule", which relates the half-life of proteins in cells to the identity of their N-terminal residue, might be operative in the case of LF, so that the N-terminal residue of LF would determine the cytosolic stability and thereby the potency of LF. Mutational studies that replaced the native N-terminal residue of LF with known N-end rule stabilizing or destabilizing residues confirmed that the N-terminal residue plays a significant role in determining the potency of LT for cultured cells and experimental animals. The fact that a commercially-available LF preparation (LF-HMA) that is widely used in basic research studies and for evaluation of vaccines and therapeutics is 3-fold less potent than native LF (LF-A) should be considered when comparing published studies and in the design of future experiments.
Power efficient architecture for (3,6)-regular low-density parity-check code decoder (2004)

Most of the current LDPC decoder VLSI architecture research focuses on increasing system throughput or reducing hardware implementation complexity, but neglects power consumption. In this paper, we analyze the power consumption of the (3,k)-regular LDPC decoder architecture. Our analysis shows that 95% of the power consumption is consumed in accessing the memory. A new architecture is proposed which reduces memory access, hence power consumption, without sacrificing the performance. Experimental results show reduction in the power consumption by 14% and lower hardware complexity without sacrificing the Bit-Error-Ratio performance compared to previous work.
Efficacy of Pimobendan in the Prevention of Congestive Heart Failure or Sudden Death in Doberman Pinschers with Preclinical Dilated Cardiomyopathy (The PROTECT Study) (2012)

The administration of pimobendan to Dobermans with preclinical DCM prolongs the time to the onset of clinical signs and extends survival. Treatment of dogs in the preclinical phase of this common cardiovascular disorder with pimobendan can lead to improved outcome.
Mass‐Transfer Studies in a Plating Cell with a Reciprocating Paddle (1987)

Deposition of Cu2+ ions under mass‐transfer limited conditions was used to study mass transfer in an electrochemical cell with a reciprocating paddle. The reciprocating paddle induced a nearly periodic mass‐transfer limited current. Fourier analysis of the current revealed that the frequency of maximum power dissipation was not necessarily at the paddle frequency but depended upon the test cathode position in the cell. The time‐averaged Sherwood number for the Cu2+ ions was found to depend on the paddle Reynolds number. The results suggest that the wake trailing the paddle interacts with the diffusion layer at the cathode and induces periodic plating that is modulated by the mass‐transfer rate of the Cu2+ ions.
Borrelia burgdorferi Binds to, Invades, and Colonizes Native Type I Collagen Lattices (2004)

Borrelia burgdorferi binds strongly to the extracellular matrix and cells of the connective tissue, a binding apparently mediated by specific proteins and proteoglycans. We investigated the interactions between B. burgdorferi cells and intact type I collagen using hydrated lattices that reproduce features of in vivo collagen matrices. B. burgdorferi cells of several strains adhered avidly to these acellular matrices by a mechanism that was not mediated by decorin or other proteoglycans. Moreover, following adhesion to these matrices, B. burgdorferi grew and formed microcolonies. The collagen used in these studies was confirmed to lack decorin by immunoblot analysis; B. burgdorferi cells lacking the decorin adhesin bound readily to intact collagen matrices. B. burgdorferi also bound to collagen lattices that incorporated enzymes that degraded glycosaminoglycan chains in any residual proteoglycans. Binding of the bacteria to intact collagen was nonetheless specific, as bacteria did not bind agar and showed only minimal binding to bovine serum albumin, gelatin, pepsinized type I collagen, and intact collagen that had been misassembled under nonphysiological pH and ionic-strength conditions. Proteinase K treatment of B. burgdorferi cells decreased the binding, as did a lack of flagella, suggesting that surface-exposed proteins and motility may be involved in the ability of B. burgdorferi to interact with intact collagen matrices. The high efficiency of binding of B. burgdorferi strains to intact collagen matrices permits replacement of the commonly used isotopic binding assay with visual fluorescent microscopic assays and will facilitate future studies of these interactions.
Designing for the Digital Age: How to Create Human-Centered Products and Services (2009)

Whether youre designing consumer electronics, medical devices, enterprise Web apps, or new ways to check out at the supermarket, todays digitally-enabled products and services provide both great opportunities to deliver compelling user experiences and great risks of driving your customers crazy with complicated, confusing technology. Designing successful products and services in the digital age requires a multi-disciplinary team with expertise in interaction design, visual design, industrial design, and other disciplines. It also takes the ability to come up with the big ideas that make a desirable product or service, as well as the skill and perseverance to execute on the thousand small ideas that get your design into the hands of users. It requires expertise in project management, user research, and consensus-building. This comprehensive, full-color volume addresses all of these and more with detailed how-to information, real-life examples, and exercises. Topics include assembling a design team, planning and conducting user research, analyzing your data and turning it into personas, using scenarios to drive requirements definition and design, collaborating in design meetings, evaluating and iterating your design, and documenting finished design in a way that works for engineers and stakeholders alike.