gebhart/patrepeval huggingface dataset:
Evidence of the extrathymic development of tyrosinase‐related protein‐2‐recognizing CD8<sup>+</sup> T cells with low avidity (2001)

The majority of the human tumour-associated antigens characterized to date are derived from non-mutated self-proteins. However, nothing is known about the development of autoreactive and tumour-associated antigen-recognizing T cells. Tyrosinase-related protein (TRP)-2 is a non-mutated melanocyte differentiation antigen and TRP-2-recognizing CD8+ T cells are known to show responses to melanoma both in humans and mice. In addition, TRP-2-reactive T cells with low avidity have been suggested to be readily induced from the spleen cells of naïve mice. On the other hand, recent reports suggest that self antigen-reactive CD8+ T cells can be positively selected in the periphery. In this study, we tested the possibility that TRP-2-reactive CD8+ T cells in naïve mice could develop via the extrathymic pathway. As a consequence, TRP-2-reactive CD8+ T cell precursors in naïve C57BL/6 mice were suggested to express both interleukin-2 (IL-2) receptor beta chain (IL-2Rbeta) and CD44 molecules, in a manner similar to that of extrathymically developed T cells. Furthermore, IL-2Rbeta+ CD44+ CD8+ T cells were detected in the adult thymectomized and bone marrow-reconstituted mice, and functional TRP-2-reactive T cells were generated from their spleen cells. Overall, these results suggest that low avidity CD8+ T cells recognizing TRP-2 can be developed extrathymically.
Structural insights into the mechanism of action of a biparatopic anti-HER2 antibody (2018)

Pathways of human epidermal growth factor (EGF) receptors are activated upon ligand-dependent or -independent homo- or heterodimerization and their subsequent transphosphorylation. Overexpression of these receptors positively correlates with transphosphorylation rates and increased tumor growth rates. MEDI4276, an anti-human epidermal growth factor receptor 2 (HER2) biparatopic antibody-drug conjugate, has two paratopes within each antibody arm. One, 39S, is aiming at the HER2 site involved in receptor dimerization and the second, single chain fragment (scFv), mimicking trastuzumab. Here we present the cocrystal structure of the 39S Fab-HER2 complex and, along with biophysical and functional assays, determine the corresponding epitope of MEDI4276 and its underlying mechanism of action. Our results reveal that MEDI4276's uniqueness is based first on the ability of its 39S paratope to block HER2 homo- or heterodimerization and second on its ability to cluster the receptors on the surface of receptor-overexpressing cells.
Vigabatrin and depression. (1993)

Ten patients who developed a major depressive episode in association with vigabatrin treatment for intractable epilepsy are reported. The depression usually occurred early in the course of treatment, but when delayed followed a recent increase in dose. Depressive symptoms occurred at doses varying between 1.5 g and 4 g a day, often but not always when patients were experiencing a decrease in their seizure frequency. Most patients had a history of affective disturbance, sometimes in association with other GABAergic drugs. The observations support a possible role for GABAergic mechanisms in the biology of mood disorders.
Detection and dissipation of road traffic congestion using vehicular communication (2009)

Thanks to the advances in wireless technologies, mobile vehicular networks are likely to become the most relevant form of mobile ad hoc networks (MANET). Vehicular communication which facilitates the exchange of information between vehicles is the prerequisite not only for extending the access to Internet while on the road, but also to cater for special applications such as of road traffic and travel management. However despite the increasing studies on vehicular routing protocols, the support to applications other than the access the internet remains limited. In this paper we propose a novel vehicular communication system for road congestion detection and dissipation by disseminating and exploiting road information. The system is an integrated solution for sharing congestion information using a simple geocast protocol and a Dynamic Dijkstra algorithm for planning and computing least congested travel itineraries. In this paper, through simulation results, we show that the proposed solution not only allows vehicles to detect road congestion ahead of time, but also contributes to reducing it by allowing vehicles to avoid congestion points.
Time-dependent failure of amorphous polylactides in static loading conditions (2009)

Polylactides are commonly praised for their excellent mechanical properties (e.g. a high modulus and yield strength). In combination with their bioresorbability and biocompatibility, they are considered prime candidates for application in load-bearing biomedical implants. Unfortunately, however, their long-term performance under static load is far from impressive. In a previous in vivo study on degradable polylactide spinal cages in a goat model it was observed that, although short-term mechanical and real-time degradation experiments predicted otherwise, the implants failed prematurely under the specified loads. In this study we demonstrate that this premature failure is attributed to the time-dependent character of the material used. The phenomenon is common to all polymers, and finds its origin in stress-activated segmental molecular mobility leading to a steady rate of plastic flow. The stress-dependence of this flow-rate is well captured by Eyring's theory of absolute rates, as demonstrated on three amorphous polylactides of different stereoregularity.We show that the kinetics of the three materials are comparable and can be well described using the proposed modeling framework. The main conclusion is that knowledge of the instantaneous strength of a polymeric material is insufficient to predict its long-term performance.
1A1-O08 A hand exoskeleton robot for rehabilitation using a three-layered sliding spring mechanism(Rehabilitation Robotics and Mechatronics(1)) (2012)

In this study, a hand exoskeleton robot for rehabilitation using a three-layered sliding spring mechanism is presented. The advantage of the proposed mechanism compared to previously presented studies, is compact, light weight and high output force due to the compliant structure using the layered springs. In this paper, we introduce the mechanical structure of the proposed mechanism.
Intraocular T Cells of Patients with Herpes Simplex Virus (HSV)–Induced Acute Retinal Necrosis Recognize HSV Tegument Proteins VP11/12 and VP13/14 (2000)

It has previously been shown that T cells specific for the triggering virus infiltrate the eye of patients with herpes simplex virus type 1 (HSV-1)-induced acute retinal necrosis (ARN). The T cells were mainly directed against 0.67-0.73 HSV-1 map region encoded antigens. The fine specificities of genetically different T cell clones (TCC), obtained from affected eyes of 3 patients with HSV-induced ARN and reactive toward this genomic region of HSV-1, were analyzed with recombinant HSV viruses and synthetic peptides. For 1 patient, the HSV-1 UL46 gene encoded tegument protein VP11/12 was identified as the target antigen. Two separate CD4(+) T cell epitopes were defined in VP11/12. TCC from the other 2 patients recognized the HSV-1 UL47 gene encoded tegument protein VP13/14. Two separate CD4(+) VP13/14 T cell epitopes were identified in these patients. Analysis of the data indicates that HSV-1 VP11/12 and VP13/14 are major target antigens for T cells obtained from vitreous fluid samples of the HSV-induced ARN patients studied.
Pembrolizumab-triggered Uveitis: An Additional Surrogate Marker for Responders in Melanoma Immunotherapy? (2016)

Immunotherapy leads to significantly prolonged survival of patients with metastatic melanoma. Autoimmune side effects including colitis, dermatitis, and endocrine abnormalities are common in patients treated with ipilimumab [anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4)]. Antibodies such as pembrolizumab that interfere with the PD-1 (programmed cell death 1)/PD-L1 pathway show greater efficacy and less toxicity than ipilimumab. Here we report 2 cases of pembrolizumab-induced uveitis associated with complete or partial tumor response. We suggest that uveitis may serve as a surrogate marker for a tumor response to therapy with pembrolizumab.
On-board correction of systematic error of Earth sensors (1989)

Infrared Earth sensors are used in spacecraft for attitude sensing. Their accuracy is limited by systematic and random errors. Dominant sources of systematic errors are analyzed for a typical scanning infrared Earth sensor used in a remote-sensing satellite in a 900-km Sun-synchronous orbit. The errors considered arise from seasonable variation of infrared radiation; oblate shape of the Earth; ambient temperature of sensors; changes in spin/scan period; and misalignment of the axis of the sensors. Simple relations are derived using least-squares curve fitting for onboard correction of these errors. With these, it is possible to improve the accuracy of attitude determination by eight fold and achieve performance comparable to ground-based post-facto attitude computation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
A Memory-Efficient Unified Early Z-Test (2010)

The Unified Early Z-Test (U-EZT) is proposed to examine the visibility of pixels during tile-based rasterization in a mobile 3D graphics processor. U-EZT combines the advantages of the Z-max and Z-min EZT algorithms: the Z-max algorithm is improved by the independently updatable z-max tiles and the use of mask bits; and the Z-min algorithm is improved by reusing the mask bits from the z-max test to update the z-min tiles after tile rasterizing. As a result, storage requirements are reduced to 3 bits per pixel, and simulations suggest that U-EZT requires 20 percent to 57 percent less memory bandwidth than previous EZT algorithms.
Feasibility of Tool Condition Monitoring on Micro-Milling Using Current Signals (2011)

This paper reviewed existing studies in the area of tool condition monitoring. The review revealed the substantial amount of works that have been done in the area of tool condition monitoring in machine tool. However, it was observed that investigating the feasibility of using the main spindle and feed motor currents for tool condition monitoring in micromachining has not been carried out despite their advantage of low cost and simplicity. Therefore this study went further to investigate spindle and feed motor current signals as to their ability for sensing and monitoring tool wear progression on a micro milling machine. This initial investigation revealed some promising process signals for monitoring tool wear progression in micro milling.
Characterization of the<i>Staphylococcus epidermidis</i>Accessory‐Gene Regulator Response: Quorum‐Sensing Regulation of Resistance to Human Innate Host Defense (2006)

Staphylococci are important opportunistic pathogens. However, there is a lack of information on how these bacteria survive inside the human body during infection. This study demonstrates that quorum-sensing regulation in Staphylococcus epidermidis protects it from key mechanisms of human innate host defense. To gain a better understanding of the basis of the observed phenotype, the agr quorum-sensing regulon of S. epidermidis was characterized by a genomewide analysis of gene expression. The gene-expression data indicate that agr adapts bacterial physiology to stationary growth and, furthermore, that it controls a series of virulence factors, including degradative exoenzymes possibly involved in resistance to antimicrobial peptides. Remarkably, agr also regulates general and oxidative stress-response factors, including detoxifying enzymes of reactive oxygen species. Taken together, the results of this study indicate that quorum-sensing regulation in staphylococci has important, previously unknown functions that contribute to protection from mechanisms of human innate host defense--and, therefore, to the pathogen's survival in the human host.
Microglial Dynamics and Role in the Healthy and Diseased Brain (2014)

The study of the dynamics and functions of microglia in the healthy and diseased brain is a matter of intense scientific activity. The application of new techniques and new experimental approaches has allowed the identification of novel microglial functions and the redefinition of classic ones. In this review, we propose the study of microglial functions, rather than their molecular profiles, to better understand and define the roles of these cells in the brain. We review current knowledge on the role of surveillant microglia, proliferating microglia, pruning/neuromodulatory microglia, phagocytic microglia, and inflammatory microglia and the molecular profiles that are associated with these functions. In the remodeling scenario of microglial biology, the analysis of microglial functional states will inform about the roles in health and disease and will guide us to a more precise understanding of the multifaceted roles of this never-resting cells.
Fast recombination processes in lead chalcogenide semiconductors studied via transient optical nonlinearities (1995)

Third-order optical nonlinearities and recombination processes of photoexcited electron-hole plasma in PbSe and PbTe are directly monitored by picosecond pump-probe experiments in the wavelength range from 3 to 10 μm. After excitation, a strong blue shift of the absorption edge and large changes of the refractive index are found. Time-resolved studies of the absorption changes at lattice temperatures between 70 and 160 K reveal a fast partial decrease of the carrier density within 100 ps at excitation densities exceeding 7×1017 cm−3. Comparative emission spectra demonstrate that this behavior is due to recombination by stimulated emission. At room temperature the nonradiative Auger recombination dominates on a 0.5–2 ns time scale below the threshold of stimulated emission. The overall Auger coefficients for carrier densities of about 1018 cm−3 are derived from the data and have values of cAPbSe=1.1±0.3×10−28 cm6/s and cAPbTe=2.5±1.3×10−28 cm6/s.
Motor evoked potentials recorded from normal and spinal cord-injured rats (1987)

A need exists for an accurate neurophysiological technique that monitors the motor tracts of the cord in patients with spinal cord injury or other cord lesions and for the evaluation of experimental models of cord injury. We have recorded and characterized the motor evoked potentials (MEPs) from 10 normal rats and from 10 rats with the following cord lesions at C-8: 4 animals with complete cord transection and 6 with clip compression injury: 2 at 56.0 g, 2 at 20.0 g, and 2 at 1.5 g. MEPs were elicited by applying constant current anodal stimuli to the sensorimotor cortex with the responses recorded from microelectrodes in the spinal cord at T-10. The MEP consisted of an initial D wave (mean latency, 1.22 +/- 0.09 ms) and 4 subsequent I waves, I1 to I4. The D wave was elicited at stimulation frequencies exceeding 100 Hz, consistent with the hypothesis that it results from direct pyramidal cell excitation. The 56.0-g clip compression injuries and the cord transections abolished the MEP distal to the lesion, whereas the 20.0- and 1.5-g injuries resulted in a latency shift and amplitude decrement of the MEP peaks. These experiments suggest that the recording of MEPs will be an extremely useful and accurate method of monitoring the functional integrity of the cord, of value in patients with cord injury.
A context-aware augmented reality assisted maintenance system (2014)

Augmented reality (AR) provides a seamless interface between the virtual and real worlds, and it has been applied to various domains, e.g., product design, manufacturing, maintenance and repair, etc. In these AR systems, 3D graphics or other contents can be registered in the real environment to provide information to the users. Context-awareness can improve the usability of such AR systems through adapting the information rendered to the contexts so that the provided information can be more useful to the users. However, many AR product maintenance systems lack an authoring system that requires little programming skills to create context-aware AR contents. In this paper, an authoring system, authoring for context-aware AR (ACAAR), which provides concepts and techniques to author AR contents for context-aware AR applications, is proposed. Using ACAAR, the users can add and arrange various contents spatially, e.g., texts, images and computer-aided design (CAD) models, and specify the logical relationships between the AR contents and the maintenance contexts. In addition, a user study has been conducted to demonstrate the usability of the proposed system.
Inhibition of FK506 Binding Proteins Reduces α-Synuclein Aggregation and Parkinson's Disease-Like Pathology (2010)

alpha-Synuclein (alpha-SYN) is a key player in the pathogenesis of Parkinson's disease (PD). In pathological conditions, the protein is present in a fibrillar, aggregated form inside cytoplasmic inclusions called Lewy bodies. Members of the FK506 binding protein (FKBP) family are peptidyl-prolyl isomerases that were shown recently to accelerate the aggregation of alpha-SYN in vitro. We now established a neuronal cell culture model for synucleinopathy based on oxidative stress-induced alpha-SYN aggregation and apoptosis. Using high-content analysis, we examined the role of FKBPs in aggregation and apoptotic cell death. FK506, a specific inhibitor of this family of proteins, inhibited alpha-SYN aggregation and neuronal cell death in this synucleinopathy model dose dependently. Knockdown of FKBP12 or FKBP52 reduced the number of alpha-SYN aggregates and protected against cell death, whereas overexpression of FKBP12 or FKBP52 accelerated both aggregation of alpha-SYN and cell death. Thus, FK506 likely targets FKBP members in the cell culture model. Furthermore, oral administration of FK506 after viral vector-mediated overexpression of alpha-SYN in adult mouse brain significantly reduced alpha-SYN aggregate formation and neuronal cell death. Our data explain previously described neuroregenerative and neuroprotective effects of immunophilin ligands and validate FKBPs as a novel drug target for the causative treatment of PD.
Shaping single walled nanotubes with an electron beam (2008)

We show that electron irradiation in a dedicated scanning transmission microscope can be used as a nano-electron-lithography technique allowing the controlled reshaping of single walled carbon and boron nitride nanotubes. The required irradiation conditions have been optimized on the basis of total knock-on cross sections calculated within density functional based methods. It is then possible to induce morphological modifications, such as a local change of the tube chirality, by sequentially removing several tens of atoms with a nanometrical spatial resolution. We show that electron beam heating effects are limited. Thus, electron beam induced vacancy migration and nucleation might be excluded. These irradiation techniques could open new opportunities for nanoengineering a large variety of nanostructured materials.
Organization and nucleotide sequences of two lactococcal bacteriocin operons (1991)

Two distinct regions of the Lactococcus lactis subsp. cremoris 9B4 plasmid p9B4-6, each of which specified bacteriocin production as well as immunity, have been sequenced and analyzed by deletion and frameshift mutation analyses. On a 1.8-kb ScaI-ClaI fragment specifying low antagonistic activity, three open reading frames (ORFs) were present, which were organized in an operon. The first two ORFs, containing 69 and 77 codons, respectively, were involved in bacteriocin activity, whereas the third ORF, containing 154 codons, was essential for immunity. Primer extension analysis indicated the presence of a promoter upstream of the ORFs. Two ORFs were present on a 1.3-kb ScaI-HindII fragment specifying high antagonistic activity. The first ORF, containing 75 codons, specified bacteriocin activity. The second ORF, containing 98 codons, specified immunity. The nucleotide sequences of both fragments upstream of the first ORFs as well as the first 20 bp of the first ORF of both bacteriocin operons appeared to be identical.
High-density grids for efficient data collection from multiple crystals (2015)

Higher throughput methods to mount and collect data from multiple small and radiation-sensitive crystals are important to support challenging structural investigations using microfocus synchrotron beamlines. Furthermore, efficient sample-delivery methods are essential to carry out productive femtosecond crystallography experiments at X-ray free-electron laser (XFEL) sources such as the Linac Coherent Light Source (LCLS). To address these needs, a high-density sample grid useful as a scaffold for both crystal growth and diffraction data collection has been developed and utilized for efficient goniometer-based sample delivery at synchrotron and XFEL sources. A single grid contains 75 mounting ports and fits inside an SSRL cassette or uni-puck storage container. The use of grids with an SSRL cassette expands the cassette capacity up to 7200 samples. Grids may also be covered with a polymer film or sleeve for efficient room-temperature data collection from multiple samples. New automated routines have been incorporated into the Blu-Ice/DCSS experimental control system to support grids, including semi-automated grid alignment, fully automated positioning of grid ports, rastering and automated data collection. Specialized tools have been developed to support crystallization experiments on grids, including a universal adaptor, which allows grids to be filled by commercial liquid-handling robots, as well as incubation chambers, which support vapor-diffusion and lipidic cubic phase crystallization experiments. Experiments in which crystals were loaded into grids or grown on grids using liquid-handling robots and incubation chambers are described. Crystals were screened at LCLS-XPP and SSRL BL12-2 at room temperature and cryogenic temperatures.
Surface Structure of Binary Self-Assembled Monolayers Formed by Electrochemical Selective Replacement of Adsorbed Thiols (1999)

Nanometer-scale structure of binary thiol self-assembled monolayers (SAMs) prepared by the electrochemical selective replacement of adsorbed thiols in phase-separated binary SAMs has been studied by scanning tunneling microscopy (STM) and cyclic voltammetry. A phase-separated binary SAM of 1-undecanethiol (UDT) and 3-mercaptopropionic acid (MPA) is used as a starting system. MPA, which has a less negative desorption potential, is selectively removed by controlling the electrode potential, and replaced with 1-hexadecanethiol (HDT) or 11-mercaptoundecanoic acid (MUA). STM images of the UDT layer remaining after the selective removal of MPA exhibit two types of domains: domains with striped structure and domains where thiol molecules are densely packed, suggesting that some UDT molecules are reoriented and form low-density regions where the molecules are aligned flat on the surface. STM images of UDT-HDT and UDT-MUA binary SAMs formed by the replacement show surfaces which are phase-separated in nanometer scale. The size of the domains after the replacement is approximately equal to that of the initial phase-separated UDT-MPA SAM, indicating that the domain size is not significantly affected by the replacement.