gebhart/patrepeval huggingface dataset:
Design, engineering and production of functional single-chain T cell receptor ligands (1999)

Major histocompatibility complex (MHC) class II molecules are membrane-anchored heterodimers on the surface of antigen presenting cells (APCs) that bind the T cell receptor, initiating a cascade of interactions that results in antigen-specific activation of clonal populations of T cells. The peptide binding/T cell recognition domains of rat MHC class II (alpha-1 and beta-1 domains) were expressed as a single exon for structural and functional characterization. These recombinant single-chain T cell receptor ligands (termed 'beta1alpha1' molecules) of approximately 200 amino acid residues were designed using the structural backbone of MHC class II molecules as template, and have been produced in Escherichia coli with and without N-terminal extensions containing antigenic peptides. Structural characterization using circular dichroism predicted that these molecules retained the antiparallel beta-sheet platform and antiparallel alpha-helices observed in the native MHC class II heterodimer. The proteins exhibited a cooperative two-state thermal folding-unfolding transition. Beta1alpha1 molecules with a covalently linked MBP-72-89 peptide showed increased stability to thermal unfolding relative to the empty beta1alpha1 molecules. This new class of small soluble polypeptide provides a template for designing and refining human homologues useful in detecting and regulating pathogenic T cells.
B lymphocyte development and activation independent of MHC class II expression (1993)

A murine model of MHC class II deficiency created by targeted gene disruption was used to investigate whether class II expression influences B cell maturation and function. There appeared to be fewer total B cell precursors, a higher proportion of which were in a very early stage of maturation, in class II-deficient vs control bone marrow; however, the differences did not reach statistical significance. Mature B cells were unaffected; IgM, IgD, B220, and CD5 surface expression were similar in class II-deficient and control animals. Serum Ig determinations revealed that the class II-deficient animals had elevated IgM but decreased IgG1 (and, variably, IgE) compared to control. The antibody response against thymic-independent Ag was intact in class II-animals, as was the in vitro response of small resting B cells from class II deficient animals to stimulation with polyclonal B cell activators. Preactivated T cells were able to induce differentiation and proliferation of class II-deficient, small resting B cells. Together, these data indicate that B cell development, T cell-independent, and T cell-dependent B-cell activation, can occur independently of class II MHC expression.
Power converter analysis and design using Matlab: a transfer function approach (2002)

The design and steady-state analysis of static power converters has usually been realized in the time domain. This approach however is subject to numerical convergence problems and long simulation times, which worsen as the converter's switching frequency increases. This paper proposes a novel design and steady-state analysis method to overcome these problems using Matlab. The method is based on the Fourier transform (FT) and a generalized converter transfer function. Thus obtains steady-state results without requiring the transient power-up, neither the circuit components' initial conditions. The FT and converter transfer function are used to model and solve the converter in the frequency domain. Desired variables are then obtained in the time domain using the inverse FT. The method eliminates numerical problems and reduces simulation times significantly. For example, the simulation of a PWM voltage source inverter operating at 5 kHz takes 320 times longer in PSpice than in the proposed method. It also presents a minor processing time dependency from the converter's switching frequency. The paper includes a detailed presentation of the proposed method, a complete analysis example using Matlab 4.02, together with an evaluation comparing it to conventional simulating techniques. Finally, experimental results with a 10 kVA AC motor drive are presented to validate the proposed analysis and design method.
Cofactor Engineering: a Novel Approach to Metabolic Engineering in Lactococcus lactis by Controlled Expression of NADH Oxidase (1998)

NADH oxidase-overproducing Lactococcus lactis strains were constructed by cloning the Streptococcus mutans nox-2 gene, which encodes the H2O-forming NADH oxidase, on the plasmid vector pNZ8020 under the control of the L. lactis nisA promoter. This engineered system allowed a nisin-controlled 150-fold overproduction of NADH oxidase at pH 7.0, resulting in decreased NADH/NAD ratios under aerobic conditions. Deliberate variations on NADH oxidase activity provoked a shift from homolactic to mixed-acid fermentation during aerobic glucose catabolism. The magnitude of this shift was directly dependent on the level of NADH oxidase overproduced. At an initial growth pH of 6.0, smaller amounts of nisin were required to optimize NADH oxidase overproduction, but maximum NADH oxidase activity was twofold lower than that found at pH 7.0. Nonetheless at the highest induction levels, levels of pyruvate flux redistribution were almost identical at both initial pH values. Pyruvate was mostly converted to acetoin or diacetyl via alpha-acetolactate synthase instead of lactate and was not converted to acetate due to flux limitation through pyruvate dehydrogenase. The activity of the overproduced NADH oxidase could be increased with exogenously added flavin adenine dinucleotide. Under these conditions, lactate production was completely absent. Lactate dehydrogenase remained active under all conditions, indicating that the observed metabolic effects were only due to removal of the reduced cofactor. These results indicate that the observed shift from homolactic to mixed-acid fermentation under aerobic conditions is mainly modulated by the level of NADH oxidation resulting in low NADH/NAD+ ratios in the cells.
Phylogenetic Signal in the Eukaryotic Tree of Life (2008)

Molecular sequence data have been sampled from 10% of all species known to science. Although it is not yet feasible to assemble these data into a single phylogenetic tree of life, it is possible to quantify how much phylogenetic signal is present. Analysis of 14,289 phylogenies built from 2.6 million sequences in GenBank suggests that signal is strong in vertebrates and specific groups of nonvertebrate model organisms. Across eukaryotes, however, although phylogenetic evidence is very broadly distributed, for the average species in the database it is equivalent to less than one well-supported gene tree. This analysis shows that a stronger sampling effort aimed at genomic depth, in addition to taxonomic breadth, will be required to build high-resolution phylogenetic trees at this scale.
An annotation framework for the semantic web (2001)

Creating metadata by annotating documents is one of the major techniques for putting machine understandable data on the Web. Though there exist many tools for annotating web pages, few of them fully support the creation of semantically interlinked metadata, such as necessary for a truely Semantic Web. In this paper, we present an ontology-based annotation environment, OntoAnnotate, which offers comprehensive support for the creation of semantically interlinked metadata by human annotators.
Recovery of sparse 1-D signals from the magnitudes of their Fourier transform (2012)

The problem of signal recovery from the autocorrelation, or equivalently, the magnitudes of the Fourier transform, is of paramount importance in various fields of engineering. In this work, for one-dimensional signals, we give conditions, which when satisfied, allow unique recovery from the autocorrelation with very high probability. In particular, for sparse signals, we develop two non-iterative recovery algorithms. One of them is based on combinatorial analysis, which we prove can recover signals up to sparsity o(n <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/3</sup> ) with very high probability, and the other is developed using a convex optimization based framework, which numerical simulations suggest can recover signals upto sparsity o(n <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sup> ) with very high probability.
Current evolution of the GSM systems (1995)

The central topic of the article is the past, present and future evolution of the technical aspects of the GSM system and its derivatives such as DCS 1800 and DCS 1900, as viewed from the European standardization bodies. An important part of the article outlines the current evolution, trying to identify the major trends that are likely to show where the future lies. While the past can be reported rather objectively, this is not the case for the present or the future. In a number of places, working assumptions are presented which are not fully stabilized; they may or may not represent the solution finally adopted by the engineers. The article reflects the state of the work as of summer 1995. Similarly, the stress on this evolving trend reflects the authors choice, as independent consultants.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
TRPA1 Agonists Evoke Coughing in Guinea Pig and Human Volunteers (2009)

This study identifies the TRPA1 receptor as a promiscuous receptor, activated by a wide range of stimuli, making it a perfect target for triggering cough and as such one of the most promising targets currently identified for the development of antitussive drugs.
Cytokine changes in tears and relationship to contact lens discomfort. (2015)

Ocular comfort during the day is magnified by contact lens wear. However, the increase in the change in comfort during lens wear was not associated with changes in 15 cytokines in the tear film.
NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesis (2001)

Immunofluorescence mapping demonstrates that the NG2 proteoglycan is invariably expressed by the mural cell component of mouse neovascular structures. This pattern is independent of the developmental mechanism responsible for formation of the vasculature (vasculogenesis or angiogenesis). Thus, NG2 is expressed in the embryonic heart by cardiomyocytes, in developing macrovasculature by smooth muscle cells, and in nascent microvessels by vascular pericytes. Due to the scarcity of proven markers for developing pericytes, NG2 is especially useful for identification of this cell type. The utility of NG2 as a pericyte marker is illustrated by two observations. First, pericytes are associated with endothelial tubes at an early point in microvessel development. This early interaction between pericytes and endothelial cells has important implications for the role of pericytes in the development and stabilization of microvascular tubes. Second, the pericyte to endothelial cell ratio in developing capillaries varies from tissue to tissue. Because the extent of pericyte investment is likely to affect the physical properties of the vessel in question, it is important to understand the mechanisms that control this process. Additional insight into these and other aspects of vascular morphogenesis should be possible through use of NG2 as a mural cell marker.
Emergence of clonal cytogenetic abnormalities in Ph−cells in some CML patients in cytogenetic remission to imatinib but restoration of polyclonal hematopoiesis in the majority (2003)

Chronic myelogenous leukemia (CML) is characterized by the presence of a Bcr-Abl fusion protein with deregulated tyrosine kinase activity that is required for maintaining the malignant phenotype. Imatinib, a selective inhibitor of Bcr-Abl, induces major cytogenetic remission (MCR) or complete cytogenetic remission (CCR) in the majority of patients with CML in first chronic phase. However, thorough re-evaluation of cytogenetics in a cohort of patients in MCR or CCR demonstrated clonal karyotypic abnormalities in more than 10% of cases, some of which were clinically associated with a myelodysplastic syndrome (MDS). Further analysis identified previous exposure to cytarabine and idarubicin as significant risk factors for the subsequent occurrence of abnormalities in Philadelphia chromosome-negative (Ph-) cells. To investigate if cytogenetically normal but clonal hematopoiesis might be present in other patients in cytogenetic remission, we studied X-chromosome inactivation as a marker of clonality by polymerase chain reaction analysis of the human androgen receptor (HUMARA). We find that imatinib restores a polyclonal pattern in most patients in CCR and MCR. Nonetheless, our results are consistent with the notion that targeted therapy of CML with imatinib favors the manifestation of Ph- clonal disorders in some patients. They indicate that patients on imatinib should be followed with conventional cytogenetics, even after induction of CCR.
On the induction of fetal hemoglobin by butyrates: in vivo and in vitro studies with sodium butyrate and comparison of combination treatments with 5-AzaC and AraC (1989)

To obtain information on the cellular mechanism of induction of fetal hemoglobin (HbF) by sodium butyrate (NaB), we treated adult baboons with NaB and assessed its effects on HbF expression. Infusion of NaB increased F reticulocytes and F-positive CFUe and e-cluster colonies without induction of reticulocytosis or increase in progenitor cell numbers. Addition of NaB in bone marrow cultures increased the frequency of F-positive CFUe and e-clusters without increasing progenitor cell numbers. NaB induced HbF in human adult BFUe cultures and increased the gamma/gamma + beta globin chain and mRNA ratios in short-term incubations of culture-derived erythroblasts. There was a synergistic induction of HbF by NaB and 5-azacytidine (5-azaC), but not when the animal was treated with NaB and cytarabine (AraC). Our results suggest that the activation of gamma-globin expression by NaB reflects an action of this compound on globin genes or globin chromatin.
Utilisation de la culture in vitro d'embryons immatures pour les croisements interspécifiques entre Lactuca sativa L. et L. saligha L. ou L. virosa L. ; étude des hybrides obtenus (1987)

Des hybridations entre espèces de la sous-section Lactuca du genre Lactuca ont été réussies par culture in vitro d'embryons mis en culture 7 à 10 jours après la pollinisation sur milieu gélosé avec 20 g/1 de saccharose.Ainsi des hybrides FI (L.sativa x L. saligna) et des plantes RC1 (L.sativa x L. virosa) x L. sativa ont été obte- nus.Les taux de réussite variaient selon l'origine des parents : 17 et 83 plantes hybrides pour 100 capitules pollinisés de chacune des 2 L. saligna étudiées, 0, 5, 8 et 11 plantes RC1 pour 100 capitules pollinisés de chacun des 4 hybrides (L.sativa x L. virosa).Dans des conditions de culture sous serre favorables à la croissance des plantes, quelques descendances F2 ou RC avec L. saliva ont été obtenues.
A novel 248-nm wet-developable BARC for trench applications (2007)

A novel polyamic acid-based, 248-nm wet-developable BARC has been prepared to improve structure clear-out and lessen post-development residue. This material showed an excellent process window and controllable development rates that can be achieved by simply changing the formulation. It is a highly absorbing BARC with <i>n</i> and <i>k</i> values equal to 1.73 and 0.49, respectively. Lithography with this material has shown 180-nm dense profiles with P338 and M230Y. These profiles exhibited minimal undercutting with good clearing between the lines. Clear-out has been demonstrated for 120-nm trenches. Post-development residue of the material was tested at various temperatures and was determined to be 6 Å or less. In addition, sublimation was evaluated.
3D Printed Reversible Shape Changing Components with Stimuli Responsive Materials (2016)

The creation of reversibly-actuating components that alter their shapes in a controllable manner in response to environmental stimuli is a grand challenge in active materials, structures, and robotics. Here we demonstrate a new reversible shape-changing component design concept enabled by 3D printing two stimuli responsive polymers-shape memory polymers and hydrogels-in prescribed 3D architectures. This approach uses the swelling of a hydrogel as the driving force for the shape change, and the temperature-dependent modulus of a shape memory polymer to regulate the time of such shape change. Controlling the temperature and aqueous environment allows switching between two stable configurations - the structures are relatively stiff and can carry load in each - without any mechanical loading and unloading. Specific shape changing scenarios, e.g., based on bending, or twisting in prescribed directions, are enabled via the controlled interplay between the active materials and the 3D printed architectures. The physical phenomena are complex and nonintuitive, and so to help understand the interplay of geometric, material, and environmental stimuli parameters we develop 3D nonlinear finite element models. Finally, we create several 2D and 3D shape changing components that demonstrate the role of key parameters and illustrate the broad application potential of the proposed approach.
Creating adaptive Web sites through usage-based clustering of URLs (2003)

We describe an approach to usage based Web personalization taking into account both the offline tasks related to the mining of usage data, and the online process of automatic Web page customization based on the mined knowledge. Specifically, we propose an effective technique for capturing common user profiles based on association rule discovery and usage based clustering. We also propose techniques for combining this knowledge with the current status of an ongoing Web activity to perform real time personalization. Finally, we provide an experimental evaluation of the proposed techniques using real Web usage data.
CCR6 expression defines regulatory effector/memory-like cells within the CD25+CD4+ T-cell subset (2004)

Regulatory CD25(+)CD4+ T cells (Treg cells) are a central element of peripheral tolerance. Little is known, however, about phenotypic and functional characteristics of these cells with regard to memory. In this study we show that the chemokine receptor CCR6 is expressed on a distinct subset of mouse Treg cells. Similar to their CD25- counterparts, CCR6+ Treg cells exhibit markers of activation, memory, and expansion that are indicative for an effector-memory function. They are memory-like cells, generated in vivo from CCR6(-)CD25+ T cells after the encounter of antigen. As conventional CD25- effector-memory T cells, they have a high turnover rate and, in contrast to CCR6- Treg cells, they respond rapidly to restimulation in vitro with up-regulation of interleukin 10. CCR6+ Treg cells are enriched in the peripheral blood and accumulate in the central nervous system after induction of experimental autoimmune encephalomyelitis (EAE). This subset therefore seems to represent a population of regulatory effector-memory T cells (T(REM)), destined to control potentially destructive immune responses directly in inflamed tissues. Importantly, these cells are also present in humans. Here the expression of CCR6 fully cosegregates with CD45RO, an established marker of human memory T cells.
Double-stranded RNA binding proteins and their substrates. (1995)

Double-stranded RNA (dsRNA) binding proteins (dsRBPs) pose unique questions in regard to how proteins interact with RNA. This article presents a general overview of these questions and also introduces specific dsRBPs that are studied by my laboratory.
Pathogenesis of osteoporosis: concepts, conflicts, and prospects (2005)

Osteoporosis is a disorder in which loss of bone strength leads to fragility fractures. This review examines the fundamental pathogenetic mechanisms underlying this disorder, which include: (a) failure to achieve a skeleton of optimal strength during growth and development; (b) excessive bone resorption resulting in loss of bone mass and disruption of architecture; and (c) failure to replace lost bone due to defects in bone formation. Estrogen deficiency is known to play a critical role in the development of osteoporosis, while calcium and vitamin D deficiencies and secondary hyperparathyroidism also contribute. There are multiple mechanisms underlying the regulation of bone remodeling, and these involve not only the osteoblastic and osteoclastic cell lineages but also other marrow cells, in addition to the interaction of systemic hormones, local cytokines, growth factors, and transcription factors. Polymorphisms of a large number of genes have been associated with differences in bone mass and fragility. It is now possible to diagnose osteoporosis, assess fracture risk, and reduce that risk with antiresorptive or other available therapies. However, new and more effective approaches are likely to emerge from a better understanding of the regulators of bone cell function.
A Non-radioactive DNA Sequencing Method Using Biotinylated Dideoxynucleoside Triphosphates and Tth DNA Polymerase (1995)

We synthesized a set of four biotinylated dideoxynucleoside triphosphates (biotin-9-ddNTPs) and optimized the reaction conditions for non-radioactive cycle sequencing using modified Tth DNA polymerase (delta Tth) and a chemiluminescent detection system. The resulting sequencing ladders showed lower background compared to those with the conventional non-radioactive sequencing method which uses 5'-biotinylated primers, especially when PCR products were analysed. With our method, DNA sequences can be determined at any primer positions without preparing 5'-biotinylated primers for dideoxy chain-termination.
Juvenile hormone: The status of its “status quo” action (1996)

Juvenile hormone (JH) allows larval molting in response to ecdysteroids but prevents the switching of gene expression necessary for metamorphosis. I first review our efforts to isolate the nuclear receptor for JH in the larval epidermis of Manduca sexta using photoaffinity analogs and our recent findings that the molecule isolated does not bind JH I with high affinity. The reported apparent high affinity binding of JH I by the recombinant 29 kDa protein (rJP29) was artifactual due to the presence of contaminating esterases. Purified rJP29 bound little detectable JH I, but its binding of the photoaffinity analog was prevented by JH I as well as other isoprenoids, indicating a low affinity for these compounds. Our recent studies focus on the effects of JH on the early molecular events induced by 20-hydroxyecdysone (20E). Culture of day 2 5th larval epidermis with 10(-6)M 20E for 24 h caused first pupal commitment, then the onset of the predifferentiative events necessary for pupation. Biphasic increases in the mRNAs of the two isoforms of the ecdysone receptor (EcR-A and EcR-B1) and of E75A, an ecdysteroid-induced transcription factor, coincided with these two phases. The mRNAs for Ultraspiracle (USP) and the metamorphosis-specific Broad-Complex (BR-C) increased only during the second phase. The presence of JH had no effect on the initial increases in EcR mRNAs but caused an increased accumulation of E75A mRNA. This JH also prevented the later changes in EcR, USP, and BR-C mRNAs. Thus, JH influences only certain of the early actions of 20E which then result in its preservation of the "status quo."