gebhart/patrepeval huggingface dataset:
Cinnamate 4‐hydroxylase from Catharanthus roseus and a strategy for the functional expression of plant cytochrome P450 proteins as translational fusions with P450 reductase in Escherichia coli (1995)

A PCR-based approach was used to isolate cDNAs for cinnamate 4-hydroxylase (C4H) from Catharanthus roseus cell cultures. The protein shared 75.9% identity with C4H from other plants, and the transcription was induced under various stress conditions. The cloned protein was used to investigate the functional expression of plant P450/P450-reductase fusions in E. coli. Fusions containing a modified N-terminal membrane anchor were located in the membrane and possessed C4H activity without solubilization or addition of other factors. The results indicate that the fusion protein strategy provides a useful tool to analyze the activities encoded in the rapidly increasing number of plant P450 sequences of uncertain or unknown function. We also discuss critical elements of the strategy: the choice of the E. coli host strain, the N-terminal membrane anchor, and the conditions for protein expression.
The chaperone/usher pathways of Pseudomonas aeruginosa : Identification of fimbrial gene clusters ( cup ) and their involvement in biofilm formation (2001)

Pseudomonas aeruginosa, an important opportunistic human pathogen, persists in certain tissues in the form of specialized bacterial communities, referred to as biofilm. The biofilm is formed through series of interactions between cells and adherence to surfaces, resulting in an organized structure. By screening a library of Tn5 insertions in a nonpiliated P. aeruginosa strain, we identified genes involved in early stages of biofilm formation. One class of mutations identified in this study mapped in a cluster of genes specifying the components of a chaperone/usher pathway that is involved in assembly of fimbrial subunits in other microorganisms. These genes, not previously described in P. aeruginosa, were named cupA1-A5. Additional chaperone/usher systems (CupB and CupC) have been also identified in the genome of P. aeruginosa PAO1; however, they do not appear to play a role in adhesion under the conditions where the CupA system is expressed and functions in surface adherence. The identification of these putative adhesins on the cell surface of P. aeruginosa suggests that this organism possess a wide range of factors that function in biofilm formation. These structures appear to be differentially regulated and may function at distinct stages of biofilm formation, or in specific environments colonized by this organism.
Pharmacokinetics of valaciclovir (2004)

While active against Herpesviridae, oral aciclovir is limited by low and inconsistent bioavailability. Modification of aciclovir by valine esterification, producing valaciclovir, results in significant increases in systemic aciclovir plasma levels. The exact mechanism of increased absorption with valaciclovir is not fully determined but probably involves intestinal dipeptide transporters, followed by rapid ester hydrolysis in the small intestine and liver. The enhanced pharmacokinetics of valaciclovir have translated into improvements in clinical efficacy and patient convenience.
A 7nm CMOS technology platform for mobile and high performance compute application (2017)

We present a fully integrated 7nm CMOS platform featuring a 3 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">rd</sup> generation finFET architecture, SAQP for fin formation, and SADP for BEOL metallization. This technology reflects an improvement of 2.8X routed logic density and >40% performance over the 14nm reference technology described in [1-3]. A full range of Vts is enabled on-chip through a unique multi-workfunction process. This enables both excellent low voltage SRAM response and highly scaled memory area simultaneously. The HD 6-T bitcell size is 0.0269um <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . This 7nm technology is fully enabled by immersion lithography and advanced optical patterning techniques (like SAQP and SADP). However, the technology platform is also designed to leverage EUV insertion for specific multi-patterned (MP) levels for cycle time benefit and manufacturing efficiency. A complete set of foundation and complex IP is available in this advanced CMOS platform to enable both High Performance Compute (HPC) and mobile applications.
Oligonucleotide Synthesis (2004)

Nucleic acids chemistry has progressed rapidly in the last 10 years with the introduction of many new techniques and the development of many novel therapeutic entities. In Oligonucleotide Synthesis: Methods and Applications, laboratory experts describe in step-by-step detail the powerful new techniques they have developed for oligonucleotide synthesis and for the use of modified oligonucleotides in biotechnology. Among the protocol highlights are the synthesis of phosphorothioates via new sulfur transfer agents, the synthesis of LNA, peptide conjugation methods to improve cellular delivery and cell-specific targeting, triple helix formation, and a novel two-step process that yields a high purity DNA that is less costly. Novel applications include the use of molecular beacons to monitor the PCR amplification process, nuclease footprinting to study the sequence-selective binding of small molecules to DNA, nucleic acid libraries, optimization of RNA synthesis for siRNA applications, and the use of small interference RNA (siRNA) as an inhibitor of gene expression. The protocols follow the successful Methods in Molecular Biology™ series format, each one offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and highly practical, Oligonucleotide Synthesis: Methods and Applications offers today's investigators not only insight into important new biotechnologies, but also a full range of the detailed protocols needed to work successfully in DNA synthesis and its applications today
Learning task constraints for robot grasping using graphical models (2010)

This paper studies the learning of task constraints that allow grasp generation in a goal-directed manner. We show how an object representation and a grasp generated on it can be integrated with the task requirements. The scientific problems tackled are (i) identification and modeling of such task constraints, and (ii) integration between a semantically expressed goal of a task and quantitative constraint functions defined in the continuous object-action domains. We first define constraint functions given a set of object and action attributes, and then model the relationships between object, action, constraint features and the task using Bayesian networks. The probabilistic framework deals with uncertainty, combines a-priori knowledge with observed data, and allows inference on target attributes given only partial observations. We present a system designed to structure data generation and constraint learning processes that is applicable to new tasks, embodiments and sensory data. The application of the task constraint model is demonstrated in a goal-directed imitation experiment.
Blank beam fabrication of regenerated type IA gratings (2004)

We demonstrate an idealized method for the fabrication of regenerated type IA fibre Bragg gratings using commonly available apparatus. We use this technique to show that gratings written in the same fibre with the same period may have central wavelengths which are 14.4 nm apart and have an + 11.5% and - 1.2% difference in temperature and strain coefficients, respectively. We use these results to show that temperature compensated dual grating sensor heads, of an arbitrary length, may be quickly and consistently manufactured.
From molecules to opto-chips: organic electro-optic materials (1999)

Recent advances in polymeric electro-optic materials and device fabrication techniques have significantly increased the potential for incorporation of these materials and devices into modern high bandwidth (fiber and wireless) telecommunication, information processing, and radar systems. Charge transfer π-electron chromophores characterized by molecular first hyperpolarizability (second order optical non-linearity) values approaching 3000×10 –30 esu have been synthesized. Elucidation of the role of intermolecular electrostatic interactions in inhibiting the efficient translation of molecular optical non-linearity to macroscopic electro-optic activity has permitted systematic modification of materials to achieve electro-optic coefficients approaching 100 pm V –1 . Improvements in the optical loss of polymeric materials at wavelengths of 1.3 and 1.55 µm have been effected. Mode matching of passive transmission and active electro-optic waveguides has been addressed, permitting a dramatic reduction in insertion loss. The putative ability of polymeric electro-optic materials to be efficiently integrated with very large scale integration semiconductor electronic circuitry and with passive optical circuitry has been demonstrated. Several devices of varying degrees of complexity have been fabricated and evaluated to operational frequencies as high as 150 GHz. The operational stability of polymeric devices is very competitive with devices fabricated from lithium niobate and gallium arsenide.
Natural anti-Gal and Salmonella-specific antibodies in bile and plasma of hens differing in diet efficiency (2006)

Specific anti-Salmonella enteritidis (SE) and natural anti-alpha-gal epitope (Galalpha1-3Galbeta-1-4GlcNAc-R; anti-Gal) antibodies were measured in plasma sample pools and individual bile specimens obtained from hens differing in diet efficiency. More SE somatic (O) and flagellar (H) antibodies were found in plasma pools from efficient hens (R-) compared with nonefficient hens (R+) after oral challenge with live SE. Mean titers of somatic agglutinins in bile were 2.3 in R- hens and 1.9 in R+ hens (P = 0.06) following live challenge. Salmonella enteritidis antibodies were also found in bile of nonchallenged hens of both types but their levels were not significantly different. Flagellar (H) agglutinin scores were higher in SE-challenged hens compared with nonchallenged hens (3.1 vs. 2.1; P < or = 0.004) but efficiency types did not differ. Bile also contained high titers of the anti-Gal antibody indicated by the agglutination of glutaraldehyde-stabilized rabbit erythrocytes. The average titer of all SE-nonexposed hens was 9.0 corresponding to 1:5,120 when corrected for the initial dilution and expressed in conventional terms. Salmonella enteritidis exposure was associated with higher anti-Gal titers. The average anti-Gal titer for all SE-exposed hens was 10.0, corresponding to 1:10,240 in conventional terms; this difference was significant (P < or = 0.016). Diet efficiency type-associated differences in anti-Gal titers were not significant. Collectively, our data indicate that diet efficiency status is not associated with compromised Salmonella-specific immune responses. Rather it appears that the immune responses of diet efficient hens (R-) are also more efficient. This is because R- hens produced higher levels of O- and H-type antibody only as the result of direct exposure to living SE. On the contrary, R+ hens produced H-type antibody because of challenge with heat-killed SE, a circumstance that will not result in disease. Moreover, the hen type difference does not seem to occur at the expense of innate immunity as measured by anti-Gal antibody levels.
Identification of an N-terminal Transactivation Domain of Runx1 That Separates Molecular Function from Global Differentiation Function (2006)

RUNX1, or AML1, is a transcription factor that is the most frequent target for chromosomal gene translocations in acute leukemias. RUNX1 is essential for definitive hematopoiesis in embryos and profoundly influences adult steady-state hematopoiesis both positively and negatively. To investigate this wide range of normal activities and the pathological role of RUNX1, it is important to define the functions of different domains of the protein. RUNX1, RUNX2, and RUNX3 are highly conserved in their DNA binding runt homology domain and contain divergent sequences of unknown function N-terminal to this domain. Here we analyzed the role of the N-terminal sequence and the alpha-helix of the runt homology domain of Runx1 in DNA binding, transactivation, and megakaryocytopoiesis. Both the N terminus and the alpha-helix were found to reduce DNA binding of Runx1 and be essential for transactivation of the granulocyte-macrophage colony-stimulating factor and Ialpha1 promoters by Runx1. The N terminus of Runx1, including the alpha-helix, was also required for transactivation of a Gal4 reporter when expressed as fusion proteins with a Gal4 DNA binding domain, and the N terminus alone was capable of stimulating transcription when fused to the Gal4 DNA binding domain. The N terminus and the alpha-helix, however, were not required for megakaryocyte development from embryonic stem cells differentiated in vitro. Thus, our findings define a second transactivation domain of Runx1 that is differentially required for activation of transcription of some Runx1-dependent promoters and megakaryocytopoiesis.
Laban head-motions convey robot state: A call for robot body language (2016)

Functional robots are an increasing presence in shared human-machine environments. Humans efficiently parse motion expressions, gaining an immediate impression of an agent's current action and state. Past work has shown that motion can effectively reveal a robot's current task objective to bystanders and collaborators, however, the layering of expression on pre-existing robot task motions has yet to be explored. Rather than showing us what the robot is doing, these layered motion characteristics leverage the how of the task motions to convey additional robot attitudes, e.g., confidence, adherence to deadline or flexibility of attention. To lay the foundations for this objective, we adapt the Laban Efforts, a system from dance and acting training in use for over 50 years. We operationalize features representing the four Laban Efforts (Time, Space, Weight, and Flow) to the movements of a 2-DOF Nao head and a 4-DOF Keepon robot during simple dance and look-for-someone behaviors. Using online survey, we collect 1028 motion ratings for 72 robot motion videos depicting contrasting Effort motion examples. We achieve statistically significant legibility results for all four Effort implementations. Even without human degrees of freedom, we find that robot motion patterns can convey complex expressions to people.
Facilitating the commercialization and use of organ platforms generated by the microphysiological systems (Tissue Chip) program through public–private partnerships (2016)

Microphysiological systems (organs-on-chips, tissue chips) are devices designed to recapitulate human physiology that could be used to better understand drug responses not easily addressed using other in vivo systems or in vitro animal models. Although still in development, initial results seem promising as tissue chips exhibit in vivo systems-like functional responses. The National Center for Advancing Translation Science (NCATS) identifies this technology as a potential tool that could improve the process of getting safer, more effective treatments to patients, and has led to the Tissue Chip Program, which aims to develop, integrate and validate major organ systems for testing. In addition to organ chip development, NCATS emphasizes disseminating the technology to researchers. Commercialization has become an important issue, reflecting the difficulty of translation from discovery to adoption and wide availability. Therefore, NCATS issued a Request for Information (RFI) targeted to existing partnerships for commercializing tissue chips. The goal was to identify successes, failures and the best practices that could provide useful guidance for future partnerships aiming to make tissue chip technology widely available.
Tyrosine kinase inhibitors: Multi-targeted or single-targeted? (2010)

Since in most tumors multiple signaling pathways are involved, many of the inhibitors in clinical development are designed to affect a wide range of targeted kinases. The most important tyrosine kinase families in the development of tyrosine kinase inhibitors are the ABL, SCR, platelet derived growth factor, vascular endothelial growth factor receptor and epidermal growth factor receptor families. Both multi-kinase inhibitors and single-kinase inhibitors have advantages and disadvantages, which are related to potential resistance mechanisms, pharmacokinetics, selectivity and tumor environment. In different malignancies various tyrosine kinases are mutated or overexpressed and several resistance mechanisms exist. Pharmacokinetics is influenced by interindividual differences and differs for two single targeted inhibitors or between patients treated by the same tyrosine kinase inhibitor. Different tyrosine kinase inhibitors have various mechanisms to achieve selectivity, while differences in gene expression exist between tumor and stromal cells. Considering these aspects, one type of inhibitor can generally not be preferred above the other, but will depend on the specific genetic constitution of the patient and the tumor, allowing personalized therapy. The most effective way of cancer treatment by using tyrosine kinase inhibitors is to consider each patient/tumor individually and to determine the strategy that specifically targets the consequences of altered (epi)genetics of the tumor. This strategy might result in treatment by a single multi kinase inhibitor for one patient, but in treatment by a couple of single kinase inhibitors for other patients.
CEL1: a novel cellulose binding protein secreted by Agaricus bisporus during growth on crystalline cellulose (1994)

The cell gene of Agaricus bisporus encodes a protein (CEL1) that has an architecture resembling the multi-domain fungal cellulases, although the sequence of its putative catalytic core is not matched by any other in the protein and nucleic acid data bases. The N-terminal half of the putative catalytic domain of CEL1 was expressed in Escherichia coli as a fusion protein with glutathione-S-transferase. The fusion protein was used to raise a CEL1-specific antibody. CEL1 was detected as an extracellular 49.8 kDa protein in A. bisporus cellulose-grown cultures, where it bound strongly to cellulose. CEL1 was neither an endoglucanase, a cellobiohydrolase able to hydrolyze fluorogenic cellobiosides, a β-glucosidase, a xylanase, nor a cellobiose: quinone oxidoreductase. CEL1 was present in some fractions of culture fluid separated by electrophoresis which released soluble sugars from crystalline cellulose.
Prognostic Value of Cytokine Concentrations (Tumor Necrosis Factor–α, Interleukin‐6, and Interleukin‐10) and Clinical Parameters in Severe Melioidosis (2000)

Raised serum concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, or IL-10 are associated with mortality in patients with sepsis, but it is not known whether elevated cytokine levels are independently predictive of mortality. Cytokine assays (TNF-alpha, IL-6, and IL-10) were performed on admission plasma samples from 172 adult Thai patients with severe melioidosis. Mortality was 31.4%. APACHE II score; septicemia; plasma lactate; TNF-alpha, IL-6, and IL-10 concentrations; and IL-10/TNF-alpha and IL-6/IL-10 ratios were each associated with outcome (P</=.001 for all variables). Only the APACHE II score and either IL-6 or IL-10 concentration were independent predictors of mortality, as determined by use of multiple logistic regression (with cytokine concentrations and ratios entered separately). In a multivariate analysis, including both IL-6 and IL-10, the IL-10 concentration was no longer predictive. Therefore, APACHE II scores and either IL-6 or IL-10 concentration may be the most reliable parameters for stratification of patients in future studies of severe gram-negative sepsis.
Down-regulation of the expression and function of the transporter associated with antigen processing in murine tumor cell lines expressing IL-10 (1997)

The MHC class I molecules present antigenic peptides to CTL. The peptides are delivered to the secretory pathway by TAP, which is formed by the association of MHC-encoded TAP1 and TAP2 gene products. Tumor cells incubated or transfected with IL-10 had decreased but peptide-inducible expression of MHC class I, decreased sensitivity to MHC class I-restricted CTL, and increased NK sensitivity. We here demonstrate that IL-10 expression in the murine lymphoma RMA inhibits the TAP-dependent translocation of peptides to the endoplasmic reticulum, resulting in accumulation of immature MHC class I molecules in the endoplasmic reticulum and subsequently low expression of cell surface MHC class I molecules. This finding is explained by a down-regulation of expression of TAP1 and TAP2, observed in IL-10-transfected RMA cells as well as in IL-10-transfected P815 mastocytoma cells. In the J558L plasmacytoma cell line, constitutively expressing high levels of IL-10, increased TAP-dependent translocation of peptides and expression of cell surface MHC class I could be induced by IL-10 antisense expression. IL-10 is the first example to demonstrate that a cytokine can decrease the expression and function of the TAP1/2 molecular complex and, in more general terms, the first example of a cytokine with an inhibitory effect on MHC class I-mediated Ag presentation.
Dermal infection with vaccinia virus reveals roles for virus proteins not seen using other inoculation routes (2002)

Previously, we developed a model for testing the virulence and immunogenicity of vaccinia virus (VV) mutants based on the intradermal injection of BALB/c mouse ear pinnae. The model is characterized by a local infection in the inoculated skin without signs of systemic illness, mimicking dermal vaccination with VV. Here a further characterization of this model is presented, including the responses of mice to infectious virus doses as low as 10 p.f.u., a quantification of the infiltrate at the site of infection and use of different virus and mouse strains. The model was then used to compare the pathogenesis of six mutants of VV strain Western Reserve (WR) lacking genes A36R, A40R, A44L, B12R, B13R or B15R with that of appropriate control viruses. All of these genes except B12R and B15R influence the outcome of dermal infection with WR and for A40R and B13R this is the first role that has been reported after infection of mammals. A comparison of new and published results from intradermal and intranasal models is presented, showing that out of 16 gene deletion or insertion mutants of VV, half have phenotypes distinct from controls in only one of these models. Thus, the intranasal and intradermal models are complementary tools for dissecting the genetic basis of VV virulence.