gebhart/patrepeval huggingface dataset:
OX40 controls effector CD4<sup>+</sup> T‐cell expansion, not follicular T helper cell generation in acute <i>Listeria</i> infection (2014)

To investigate the importance of OX40 signals for physiological CD4(+) T-cell responses, an endogenous antigen-specific population of CD4(+) T cells that recognise the 2W1S peptide was assessed and temporal control of OX40 signals was achieved using blocking or agonistic antibodies (Abs) in vivo. Following infection with Listeria monocytogenes expressing 2W1S peptide, OX40 was briefly expressed by the responding 2W1S-specific CD4(+) T cells, but only on a subset that co-expressed effector cell markers. This population was specifically expanded by Ab-ligation of OX40 during priming, which also caused skewing of the memory response towards effector memory cells. Strikingly, this greatly enhanced effector response was accompanied by the loss of T follicular helper (TFH) cells and germinal centres. Mice deficient in OX40 and CD30 showed normal generation of TFH cells but impaired numbers of 2W1S-specific effector cells. OX40 was not expressed by 2W1S-specific memory cells, although it was rapidly up-regulated upon challenge whereupon Ab-ligation of OX40 specifically affected the effector subset. In summary, these data indicate that for CD4(+) T cells, OX40 signals are important for generation of effector T cells rather than TFH cells in this response to acute bacterial infection.
Manufacturing systems engineering (1993)

Providing a description of some of the phenomena in material flow in manufacturing systems, this text details some of the potentially disruptive events that affect the production process, the control action that managers can take in anticipation or response, and the consequences of disruptions and the managers's actions. It focuses on two major areas: the effects of unreliability, variability, and finite storage space on system performance; and control-theoretic methods for operating advanced manufacturing systems to obtain high performance.
Sorptive dilation of polysulfone and poly(ethylene terephthalate) films by high‐pressure carbon dioxide (1988)

Abstract Dilation of polysulfone (PSUL) and crystalline poly(ethylene terephthalate) (PET) films accompanying sorption of carbon dioxide is measured by a cathetometer under high pressure up to 50 atm over the temperature range of 35–65°C. Sorptive dilation isotherms of PSUL are concave and convex to the pressure and concentration axes, respectively, and both isotherms exhibit hysteresis. Each dilation isotherm plotted versus pressure and concentration for the CO 2 ‐PET system shows an inflection point, i.e., a glass transition point, at which the isotherm changes from a nonlinear curve to a straight line. Dilation isotherms of PET below the glass transition point are similar to those of the CO 2 ‐PSUL system, whereas the isotherms above the glass transition point are linear and exhibit no hysteresis. Partial molar volumes of CO 2 in these polymers are determined from data of sorptive dilation. On the basis of the extended dual‐mode sorption model and the current data, primitive equations for gas‐sorptive dilation of glassy polymers are proposed.
Evolving Applications, Technological Challenges and Future Opportunities in Neuromodulation: Proceedings of the Fifth Annual Deep Brain Stimulation Think Tank (2018)

The annual Deep Brain Stimulation (DBS) Think Tank provides a focal opportunity for a multidisciplinary ensemble of experts in the field of neuromodulation to discuss advancements and forthcoming opportunities and challenges in the field. The proceedings of the fifth Think Tank summarize progress in neuromodulation neurotechnology and techniques for the treatment of a range of neuropsychiatric conditions including Parkinson's disease, dystonia, essential tremor, Tourette syndrome, obsessive compulsive disorder, epilepsy and cognitive, and motor disorders. Each section of this overview of the meeting provides insight to the critical elements of discussion, current challenges, and identified future directions of scientific and technological development and application. The report addresses key issues in developing, and emphasizes major innovations that have occurred during the past year. Specifically, this year's meeting focused on technical developments in DBS, design considerations for DBS electrodes, improved sensors, neuronal signal processing, advancements in development and uses of responsive DBS (closed-loop systems), updates on National Institutes of Health and DARPA DBS programs of the BRAIN initiative, and neuroethical and policy issues arising in and from DBS research and applications in practice.
Improving Tumor‐to‐Background Contrast through Hydrophilic Tetrazines: The Construction of <sup>18</sup>F‐Labeled PET Agents Targeting Nonsmall Cell Lung Carcinoma (2020)

Bioorthogonal reactions have been widely used in the biomedical field. <sup>18</sup> F-TCO/Tetrazine ligation is the most reactive radiolabelled inverse electron demand Diels-Alder reaction, but its application had been limited due to modest contrast ratios of the resulting conjugates. Herein, we describe the use of hydrophilic tetrazines to improve tumor-to-background contrast of neurotensin receptor targeted PET agents. PET agents were constructed using a rapid Diels-Alder reaction of the radiolabeled trans-cyclooctene (<sup>18</sup> F-sTCO) with neurotensin (NT) conjugates of a 3,6-diaryltetrazine, 3-methyl-6-aryltetrazine, and a derivative of 3,6-di(2-hydroxyethyl)tetrazine. Although cell binding assays demonstrated all agents have comparable binding affinity, the conjugate derived from 3,6-di(2-hydroxyethyl)tetrazine demonstrated the highest tumor to muscle contrast, followed by conjugates of the 3-methyl-6-aryltetrazine and 3,6-diaryltetrazine.
The Crystal Structure of Shiga Toxin Type 2 with Bound Disaccharide Guides the Design of a Heterobifunctional Toxin Inhibitor (2013)

Shiga toxin type 2 (Stx2a) is clinically most closely associated with enterohemorrhagic E. coli O157:H7-mediated hemorrhagic colitis that sometimes progresses to hemolytic-uremic syndrome. The ability to express the toxin has been acquired by other Escherichia coli strains, and outbreaks of food poisoning have caused significant mortality rates as, for example, in the 2011 outbreak in northern Germany. Stx2a, an AB5 toxin, gains entry into human cells via the glycosphingolipid receptor Gb3. We have determined the first crystal structure of a disaccharide analog of Gb3 bound to the B5 pentamer of Stx2a holotoxin. In this Gb3 analog,-GalNAc replaces the terminal-Gal residue. This co-crystal structure confirms previous inferences that two of the primary binding sites identified in theB5 pentamer of Stx1 are also functional in Stx2a. This knowledge provides a rationale for the synthesis and evaluation of heterobifunctional antagonists for E. coli toxins that target Stx2a. Incorporation of GalNAc Gb3 trisaccharide in a heterobifunctional ligand with an attached pyruvate acetal, a ligand for human amyloid P component, and conjugation to poly[acrylamide-co-(3-azidopropylmethacrylamide)] produced a polymer that neutralized Stx2a in a mouse model of Shigatoxemia.
Bmk-1 regulates lifespan in<i>Caenorhabditis elegans</i>by activating hsp-16 (2015)

The genetics of aging is typically concerned with lifespan determination that is associated with alterations in expression levels or mutations of particular genes. Previous reports in C. elegans have shown that the bmk-1 gene has important functions in chromosome segregation, and this has been confirmed with its mammalian homolog, KIF11. However, this gene has never been implicated in aging or lifespan regulation. Here we show that the bmk-1 gene is an important lifespan regulator in worms. We show that reducing bmk-1 expression using RNAi shortens worm lifespan by 32%, while over-expression of bmk-1 extends worm lifespan by 25%, and enhances heat-shock stress resistance. Moreover, bmk-1 over-expression increases the level of hsp-16 and decreases ced-3 in C. elegans. Genetic epistasis analysis reveals that hsp-16 is essential for the lifespan extension by bmk-1. These findings suggest that bmk-1 may act through enhanced hsp-16 function to protect cells from stress and inhibit the apoptosis pathway, thereby conferring worm longevity. Though it remains unclear whether this is a distinct function from chromosomal segregation, bmk-1 is a potential new target for extension of lifespan and enhancement of healthspan.
Novel Therapeutic Targets for Axonal Degeneration in Multiple Sclerosis (2010)

Multiple sclerosis (MS) is a devastating neurological condition that mainly affects young adults and is associated with long-standing morbidity. The pathophysiology of MS is believed to involve immune-mediated multifocal lesions in the CNS that are characterized by inflammation, demyelination, and axonal injury. Most research efforts to date have concentrated on the mechanisms of immune-mediated demyelination, whereas mechanisms of axonal injury, the major determinant of neurological deficits in MS patients, have been elusive beyond observational analyses. This review discusses current understanding of the pathology and novel clinical investigations of axonal injury in MS and the commonly used MS animal model, experimental autoimmune encephalomyelitis. The review focuses on the etiology and the induction of axonal degeneration through molecular signaling cascades downstream of myelin-associated inhibitory factors. Defining and eventually elucidating the signaling pathways elicited during the onset and progression of MS may provide novel therapeutic strategies to limit axonal degeneration in the acute phase of the disease. Furthermore, blocking or potentiating specific signaling pathways, particularly those that mediate axon retraction and promote disassembly of the tubulin network, may promote regrowth of damaged axons in CNS regions affected by many acute and chronic disease processes.
Physiological Dysfunction of Dorsolateral Prefrontal Cortex in Schizophrenia (1988)

• In previous studies we found that patients with chronic schizophrenia had lower regional cerebral blood flow (rCBF) in dorsolateral prefrontal cortex (DLPFC) than did normal subjects during performance of the Wisconsin Card Sort Test, an abstract reasoning task linked to DLPFC function. This was not the case during less complex tasks. To examine further whether this finding represented regionally circumscribed pathophysiology or a more general correlate of abstract cognition, 24 medication-free patients and 25 age- and sexmatched normal control subjects underwent rCBF measurements with the xenon 133 technique while they performed two tasks: Raven's Progressive Matrices (RPM) and an active baseline control task. While performing RPM, normal subjects activated posterior cortical areas over baseline, but did not activate DLPFC, as had been seen during the Wisconsin Card Sort Test. Like normal subjects, patients showed maximal rCBF elevations posteriorly and, moreover, they had no significant DLPFC or other cortical deficit while performing RPM. These results suggest that DLPFC dysfunction in schizophrenia is linked to pathophysiology of a regionally specific neural system rather than to global cortical dysfunction, and that this pathophysiology is most apparent under prefrontally specific cognitive demand.
High-Speed Photodiodes (2014)

To meet the challenge of broad bandwidth and high-responsivity numerous photodetector approaches have been investigated. Normal-incidence photodiodes have the advantages of relatively simple structures, high responsivity, and relaxed packaging constraints for bandwidths of a few gigahertz. Achieving acceptable responsivity at higher speed necessitates the use of waveguide structures. The emergence of Si photonics has also relied on developing suitable waveguide photodiodes. This paper reviews the technologies employed for high-speed photodiodes and state-of-the-art performance.
A self-aligned gate III-V heterostructure FET process for ultrahigh-speed digital and mixed analog/digital LSI/VLSI circuits (1989)

A planar ion-implanted self-aligned gate process for the fabrication of high-speed digital and mixed analog/digital LSI/VLSI integrated circuits is reported. A 4-b analog-to-digital converter, a 2500-gate 8*8 multiplier/accumulator, and a 4500-gate 16*16 complex multiplier have been demonstrated using enhancement-mode n/sup +/-(Al,Ga)As/MODFETs, superlattice MODFETs, and doped channel heterostructure field-effect transistors (FETs) whose epitaxial layers were grown by molecular-beam epitaxy. With nominal 1- mu m gate-length devices, direct-coupled FET logic ring oscillators with realistic circuit structures have propagation delays of 30 ps/stage at a power dissipation of 1.2 mW/stage. In LSI circuit operation, these gates have delays of 89 ps/gate at a power dissipation of 1.38 mW/gate when loaded with an average fan-out of 2.5 gates and about 1000 mu m of high-density interconnects. High-performance voltage comparator circuits operated at sampling rates greater than 2.5 GHz at Nyquist analog input rates and with static hysteresis of less than 1 mV at room temperature. Fully functional 4-b analog-to-digital circuits operating at frequencies up to 2 GHz were obtained.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Nanoscale Deformation Analysis With High-Resolution Transmission Electron Microscopy and Digital Image Correlation (2015)

We present an application of the digital image correlation (DIC) method to high-resolution transmission electron microscopy (HRTEM) images for nanoscale deformation analysis. The combination of DIC and HRTEM offers both the ultrahigh spatial resolution and high displacement detection sensitivity that are not possible with other microscope-based DIC techniques. We demonstrate the accuracy and utility of the HRTEM-DIC technique through displacement and strain analysis on amorphous silicon. Two types of error sources resulting from the transmission electron microscopy (TEM) image noise and electromagnetic-lens distortions are quantitatively investigated via rigid-body translation experiments. The local and global DIC approaches are applied for the analysis of diffusion- and reaction-induced deformation fields in electrochemically lithiated amorphous silicon. The DIC technique coupled with HRTEM provides a new avenue for the deformation analysis of materials at the nanometer length scales.
Error Sign Feedback as an Alternative to Pilots for the Tracking of FEXT Transfer Functions in Downstream VDSL (2006)

With increasing bandwidths and decreasing loop lengths, crosstalk becomes the main impairment in VDSL systems. For downstream communication, crosstalk precompensation techniques have been designed to cope with this issue by using the collocation of the transmitters. These techniques naturally need an accurate estimation of the crosstalk channel impulse responses. We investigate the issue of tracking these channels. Due to the lack of coordination between the receivers, and because the amplitude levels of the remaining interference from crosstalk after precompensation are very low, blind estimation schemes are inefficient in this case. So some part of the upstream or downstream bit rate needs to be used to help the estimation. In this paper, we design a new algorithm to try to limit the bandwidth used for the estimation purpose by exploiting the collocation at the transmitter side. The principle is to use feedback from the receiver to the transmitter instead of using pilots in the downstream signal. It is justified by computing the Cramer-Rao lower bound on the estimation error variance and showing that, for the levels of power in consideration, and for a given bit rate used to help the estimation, this bound is effectively lower for the proposed scheme. A simple algorithm based on the maximum likelihood is proposed. Its performance is analyzed in detail and is compared to a classical scheme using pilot symbols. Finally, an improved but more complex version is proposed to approach the performance bound.
Peptides Constrained by an Aliphatic Linkage between Two C<i><sup>α</sup></i>Sites:  Design, Synthesis, and Unexpected Conformational Properties of an<i>i</i>,(<i>i</i><i>+</i>4)-Linked Peptide (2001)

A novel route for the synthesis of cyclic peptides constrained by an aliphatic bridge between two C(alpha)sites, using a triply orthogonal protecting group strategy, is described. The synthesis of the orthogonally protected bis-amino acid 1, via an enantioselective route utilizing the Schöllkopf and Evans methodologies, is first described. This is then incorporated into a short, alanine-rich peptide 13, using a novel triply orthogonal protecting group strategy to couple first one, then the other, amino acid moiety in such a way that an aliphatic bridge is formed between the i and i + 4 positions. Unexpectedly, the resulting constrained peptide does not adopt a helical conformation: instead, it is shown by CD at low temperature to adopt a left-handed type II beta-turn conformation in aqueous media and a right-handed type I beta-turn conformation in TFE.
Bounded-distortion piecewise mesh parameterization (2003)

Many computer graphics operations, such as texture mapping, 3D painting, remeshing, mesh compression, and digital geometry processing, require finding a low-distortion parameterization for irregular connectivity triangulations of arbitrary genus 2-manifolds. This paper presents a simple and fast method for computing parameterizations with strictly bounded distortion. The new method operates by flattening the mesh onto a region of the 2D plane. To comply with the distortion bound, the mesh is automatically cut and partitioned on-the-fly. The method guarantees avoiding global and local self-intersections, while attempting to minimize the total length of the introduced seams. To our knowledge, this is the first method to compute the mesh partitioning and the parameterization simultaneously and entirely automatically, while providing guaranteed distortion bounds. Our results on a variety of objects demonstrate that the method is fast enough to work with large complex irregular meshes in interactive applications.
Novel human light chain V kappa segment: serologic and structural analyses of the <i>kappa</i> III-like Bence Jones protein and IgG <i>kappa</i> light chain REE. (1986)

Immunochemical and sequence analyses of kappa light chain REE (Bence Jones protein REE and the light chain isolated from IgG kappa myeloma protein REE) revealed antigenic and structural features not previously described for human kappa-chains. Although closely related to proteins of the V kappa III subgroup, light chain REE is readily distinguished from light chains classified serologically as members of the kappa IIIa or kappa IIIb sub-subgroups. Light chains REE (Bence Jones protein REE and light chain REE) are identical in sequence and differ from kappa III proteins by at least 10 uncommon amino acid substitutions in the first three framework regions. Further, kappa-chain REE is unique by virtue of a four-residue deletion in the third complementarity-determining region. The deletion encompasses the three carboxyl-terminal residues in the V kappa-encoded segment and the first residue at the site of V-J recombination. Urine specimens from patient REE also contained a light chain fragment that lacked the first (amino-terminal) 85 residues of the native light chain but otherwise was identical in sequence to the light chain REE. The extensive amino acid differences and unique length of the V kappa segment in light chain REE indicate that this kappa-chain is the product of an unusual V kappa III gene or, alternatively, represents a rarely expressed and novel human V kappa gene.
The Manufacturing Knowledge Repository - Consolidating Knowledge to Enable Holistic Process Knowledge Management in Manufacturing (2014)

The manufacturing industry is faced with strong competition making the companiesâ knowledge resources and their systematic management a critical success factor. Yet, existing concepts for the management of process knowledge in manufacturing are characterized by major shortcomings. Particularly, they are either exclusively based on structured knowledge, e. g., formal rules, or on unstructured knowledge, such as documents, and they focus on isolated aspects of manufacturing processes. To address these issues, we present the Manufacturing Knowledge Repository, a holistic repository that consolidates structured and unstructured process knowledge to facilitate knowledge management and process optimization in manufacturing. First, we define requirements, especially the types of knowledge to be handled, e. g., data mining models and text documents. Next, we develop a conceptual repository data model associating knowledge items and process components such as machines and process steps. Furthermore, we discuss implementation issues including storage architecture variants and finally present a proof of concept based on a prototypical implementation.
Generation of hypoallergenic neoglycoconjugates for dendritic cell targeted vaccination: A novel tool for specific immunotherapy (2012)

The incidence of allergic disorders and asthma continuously increased over the past decades, consuming a considerable proportion of the health care budget. Allergen-specific subcutaneous immunotherapy represents the only intervention treating the underlying causes of type I allergies, but still suffers from unwanted side effects and low compliance. There is an urgent need for novel approaches improving safety and efficacy of this therapy. In the present study we investigated carbohydrate-mediated targeting of allergens to dermal antigen-presenting cells and its influence on immunogenicity and allergenicity. Mannan, high (40kDa) and low (6kDa) molecular weight dextran, and maltodextrin were covalently attached to ovalbumin and papain via mild carbohydrate oxidation resulting in neoglycocomplexes of various sizes. In particular, mannan-conjugates were efficiently taken up by dendritic cells in vivo leading to elevated humoral immune responses against the protein moiety and a shift from IgE to IgG. Beyond providing an adjuvant effect, papain glycocomplexes also proved to mask B-cell epitopes, thus rendering the allergen derivative hypoallergenic. The present data demonstrate that carbohydrate-modified allergens combine targeting of antigen presenting cells with hypoallergenicity, offering the potential for low dose allergen-specific immunotherapy while concomitantly reducing the risk of side effects.
In Search of the Genes of Asthma on the Island of Tristan da Cunha (1995)

Asthma, like several common diseases such as diabetes and atherosclerosis, occurs in families and thus probably has a complex polygenic basis, in which environmental factors also play a role. In trying to elucidate the genetic mechanism, studies of communities characterized by a high level of interbreeding and a high prevalence of asthma should be helpful. One such community has been described in the medical literature, the island of Tristan da Cunha. The University of Toronto Genetics of Asthma Project decided to study this community. It sent a team to the island to construct a geneology, obtain a history of respiratory and allergy symptoms by questionnaire, perform allergy skin testing and methocholine challenge, and obtain blood for white cell genetic studies. The initial results of this study are presented here, together with a historical perspective on the people of Tristan da Cunha.