gebhart/patrepeval huggingface dataset:
Tremelimumab in Combination With Microwave Ablation in Patients With Refractory Biliary Tract Cancer (2018)

Treatment options for patients with advanced biliary tract cancer are limited. Dysregulation of the immune system plays an important role in the pathogenesis of biliary tract cancer (BTC). This study aimed to investigate whether tremelimumab, an anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) inhibitor, could be combined safely with microwave ablation to enhance the effect of anti-CTLA4 treatment in patients with advanced BTC. Patients were enrolled to receive monthly tremelimumab (10 mg/kg, intravenously) for six doses, followed by infusions every 3 months until off-treatment criteria were met. Thirty-six days after the first tremelimumab dose, patients underwent subtotal microwave ablation. Interval imaging studies were performed every 8 weeks. Adverse events (AEs) were noted and managed. Tumor and peripheral blood samples were collected to perform immune monitoring and whole-exome sequencing (WES). Twenty patients with refractory BTC were enrolled (median age, 56.5 years). No dose-limiting toxicities were encountered. The common treatment-related AEs included lymphopenia, diarrhea, and elevated transaminases. Among 16 patients evaluable for efficacy analysis, 2 (12.5%) patients achieved a confirmed partial response (lasting for 8.0 and 18.1 months, respectively) and 5 patients (31.3%) achieved stable disease. Median progression free survival (PFS) and overall survival (OS) were 3.4 months (95% confidence interval [CI], 2.5-5.2) and 6.0 months (95% CI, 3.8-8.8), respectively. Peripheral blood immune cell subset profiling showed increased circulating activated human leukocyte antigen, DR isotype ([HLA-DR] positive) CD8<sup>+</sup> T cells. T-cell receptor (TCR)β screening showed tremelimumab expanded TCR repertoire, but not reaching statistical significance (P = 0.057). Conclusion: Tremelimumab in combination with tumor ablation is a potential treatment strategy for patients with advanced BTC. Increased circulating activated CD8<sup>+</sup> T cells and TCR repertoire expansion induced by tremelimumab may contribute to treatment benefit.
Attenuation of inflammatory mediator production by the NF-κB member RelB is mediated by microRNA-146a in lung fibroblasts (2013)

Lung inflammation can result from exposure to multiple types of inflammatory stimuli. Fibroblasts, key structural cells in the lung that are integral to inflammation and wound healing, produce inflammatory mediators after exposure to stimuli such as IL-1β. We and others have shown that the NF-κB member RelB has anti-inflammatory properties in mice. Little is known, however, about the anti-inflammatory role of RelB in human cells and how it functions. MicroRNAs (miRNAs), a novel class of small, noncoding RNAs, can mediate inflammatory signaling pathways, including NF-κB, through regulation of target gene expression. Our goal was to analyze the anti-inflammatory properties of RelB in human lung fibroblasts. We hypothesized that RelB regulates inflammatory mediator production in lung fibroblasts in part through a mechanism involving miRNAs. To accomplish this, we transfected human lung fibroblasts with a plasmid encoding RelB and small interfering (si)RNA targeting RelB mRNA to overexpress and downregulate RelB, respectively. IL-1β, a powerful proinflammatory stimulus, was used to induce NF-κB-driven inflammatory responses. RelB overexpression reduced IL-1β-induced cyclooxygenase (Cox)-2, PGE₂, and cytokine production, and RelB downregulation increased Cox-2 expression and PGE₂ production. Furthermore, RelB overexpression increased IL-1β-induced expression of miRNA-146a, an NF-κB-dependent miRNA with anti-inflammatory properties, whereas RelB downregulation reduced miRNA-146a. miR-146a overexpression ablated the effects of RelB downregulation on IL-1β-induced Cox-2, PGE₂, and IL-6 production, suggesting that RelB mediates IL-1β-induced inflammatory mediator production in lung fibroblasts through miRNA-146a. RelB and miRNA-146a may therefore be new therapeutic targets in the treatment of lung inflammation caused by various agents and conditions.
Synthesis and Biological Evaluation of an Indomethacin Library Reveals a New Class of Angiogenesis‐Related Kinase Inhibitors (2004)

In der Zuschrift „Synthesis and Biological Evaluation of an Indomethacin Library Reveals a New Class of Angiogenesis-Related Kinase Inhibitors” von A. Giannis, H. Waldmann et al. (1) wurden die Adressdaten der Autoren vertauscht. Die richtigen Adressen lauten: Prof. Dr. H. Waldmann, Dr. C. Rosenbaum Max-Planck-Institut für molekulare Physiologie Abteilung Chemische Biologie Otto-Hahn-Strasse 11, 44227 Dortmund (Germany) and Universität Dortmund, Fachbereich 3, Organische Chemie Fax: (+49) 231-133-2499 E-mail: herbert.waldmann@mpi-dortmund.mpg.de Dr. R. Matzitschek, Dipl.-Chem. P. Baumhof, Prof. Dr. A. Giannis Universität Leipzig Institut für Organische Chemie Johannisallee 29, 04103 Leipzig (Germany) Fax: (+49) 341-9736-599 E-mail: giannis@chemie.uni-leipzig.de
Intermodulation Distortion Characteristics of High-temperature Superconducting Dual-band (2011)

This paper presents the intermodulation distortion (IMD) characteristics of a high-temperature superconducting (HTS) dual-band bandpass filter (DBPF) comprising coplanar- waveguide quarter-wavelength resonator with odd- and even- mode resonant frequencies. The IMD characteristics are one of the most significant factors in order to elucidate the power handling capability (PHC) of HTS filters. The IMD measurements for HTS single-band filters have been reported, while those for HTS-DBPFs have not. This paper introduces the IMD characteristics of the HTS-DBPF when lower band and upper band signals are individually and simultaneously input to each passband, respectively. A 2.0-/3.5-GHz band HTS-DBPF is designed and fabricated as an example for the evaluation of the PHC. Experimental investigations confirm that the proposed HTS-DBPF is effective in achieving both flexible passband control and low IMD generation.
VeNAS: Versatile Negotiating Agent Strategy via Deep Reinforcement Learning (Student Abstract) (2022)

Existing research in the field of automated negotiation considers a negotiation architecture in which some of the negotiation components are designed separately by reinforcement learning (RL), but comprehensive negotiation strategy design has not been achieved. In this study, we formulated an RL model based on a Markov decision process (MDP) for bilateral multi-issue negotiations. We propose a versatile negotiating agent that can effectively learn various negotiation strategies and domains through comprehensive strategies using deep RL. We show that the proposed method can achieve the same or better utility than existing negotiation agents.
Static and Dynamic Error of a Biplanar Videoradiography System Using Marker-Based and Markerless Tracking Techniques (2011)

The use of biplanar videoradiography technology has become increasingly popular for evaluating joint function in vivo. Two fundamentally different methods are currently employed to reconstruct 3D bone motions captured using this technology. Marker-based tracking requires at least three radio-opaque markers to be implanted in the bone of interest. Markerless tracking makes use of algorithms designed to match 3D bone shapes to biplanar videoradiography data. In order to reliably quantify in vivo bone motion, the systematic error of these tracking techniques should be evaluated. Herein, we present new markerless tracking software that makes use of modern GPU technology, describe a versatile method for quantifying the systematic error of a biplanar videoradiography motion capture system using independent gold standard instrumentation, and evaluate the systematic error of the W.M. Keck XROMM Facility's biplanar videoradiography system using both marker-based and markerless tracking algorithms under static and dynamic motion conditions. A polycarbonate flag embedded with 12 radio-opaque markers was used to evaluate the systematic error of the marker-based tracking algorithm. Three human cadaveric bones (distal femur, distal radius, and distal ulna) were used to evaluate the systematic error of the markerless tracking algorithm. The systematic error was evaluated by comparing motions to independent gold standard instrumentation. Static motions were compared to high accuracy linear and rotary stages while dynamic motions were compared to a high accuracy angular displacement transducer. Marker-based tracking was shown to effectively track motion to within 0.1 mm and 0.1 deg under static and dynamic conditions. Furthermore, the presented results indicate that markerless tracking can be used to effectively track rapid bone motions to within 0.15 deg for the distal aspects of the femur, radius, and ulna. Both marker-based and markerless tracking techniques were in excellent agreement with the gold standard instrumentation for both static and dynamic testing protocols. Future research will employ these techniques to quantify in vivo joint motion for high-speed upper and lower extremity impacts such as jumping, landing, and hammering.
Features of the choriocapillaris in myopic maculopathy identified by optical coherence tomography angiography (2017)

OCTA visualised the choriocapillaris clearly. The choriocapillaris features differed depending to the category of myopic maculopathy. In eyes with lacquer cracks, choriocapillaris rupture might be less advanced than the breaks in Bruch's membrane and retinal pigment epithelium.
Response of septal cholinergic neurons to axotomy (1987)

In the present study we employed quantitative morphometric techniques to assay the response of septal cholinergic neurons following unilateral transection of the fimbria/fornix and supracallosal stria. Analysis of 50-micron-thick tissue sections with a Quantimet 920 image analysis system demonstrated a reduction in ChAT immunoreactivity as early as 1 day following denervation. This decrease was associated with a drop in the number of labeled cells ipsilateral to the lesion and a decrease in the area of cholinergic perikarya on the lesioned and nonlesioned side of the septum. The response at 1 day, however, was transient, and at 4 days the number of labeled neurons was not significantly different from controls. By 8 days we observed a dramatic reduction in the number and size of ChAT-positive cells ipsilateral to the lesion and a reduction in the size of cholinergic perikarya on the contralateral (i.e., nonlesioned) side. These values persisted throughout the remainder of the study. To assess more completely the morphologic response of neurons to axotomy than can be determined in 50-micron-thick tissue sections, we embedded the adjacent immunolabeled tissue section in Epon and then serially sectioned it to a thickness of 0.75-1.0 micron. By using this method, we were able to measure the area, length, and width of the cell, the area of the nucleus and nucleolus, and the position of the nucleus (i.e., eccentricity). Measurements were performed on ChAT-labeled and nonlabeled cells. The results of our studies demonstrate that cholinergic and noncholinergic cells responded to axotomy in a characteristic yet different fashion from each other and that this response could be quantitatively assayed. In general, labeled and nonlabeled cells on the lesioned side of the septum shrink in response to denervation. This shrunken state was reflected in measurements of cellular area, length, width, and nuclear area. Moreover, other measurements of cellular morphology (i.e., area of the nucleolus, position of the nucleus) indicate that none of the neuronal populations examined in the present study displayed morphologic evidence of regeneration. Our results indicate a dramatic loss of cholinergic perikarya ipsilateral to the lesion. Moreover, although a few neurons do persist they do so in a shrunken state. These data provide an essential baseline for the second study in this series, which will evaluate the effect of nerve growth factor on the survival of denervated septal neurons.
Synthesis and Characterization of Bis-azo 1,2,4,5-Tetrazine Dyestuff (2018)

The design, synthesis and characterization of symmetrical 3,6-Bis(2-(4-(dodecyloxy)phenyl)-1-(4-(phenyl)diazene)-1,2,4,5-tetrazine are described. The novel sym-tetrazine was prepared by addition reaction of 4-(2-(4-decyloxyphenyl)diazenyl)benzonitrile with hydrazine monohydrate followed by oxidation reaction to afford the corresponding bis(azo)-1,2,4,5-tetrazine. The chemical structure of the sym-tetrazine compound was confirmed by elemental analysis, fourier-transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance (1H and 13C NMR) spectral measurements. The design, synthesis and characterization of symmetrical 3,6-Bis(2-(4-(dodecyloxy)phenyl)-1-(4-(phenyl)diazene)-1,2,4,5-tetrazine are described. The novel sym-tetrazine was prepared by addition reaction of 4-(2-(4-decyloxyphenyl)diazenyl)benzonitrile with hydrazine monohydrate followed by oxidation reaction to afford the corresponding bis(azo)-1,2,4,5-tetrazine. The chemical structure of the sym-tetrazine compound was confirmed by elemental analysis, fourier-transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance (1H and 13C NMR) spectral measurements.
Acoustic modes and elastic properties of polymeric nanostructures (2005)

Phonon spectra of polymeric linear nanostructures have been characterized using Brillouin light scattering. In addition to phonon modes similar to those present in uniform thin films, the phonon spectra of the nanolines reveal a new mode with a lower frequency that depends on the width of the nanolines. Classic wave theory and finite element analysis were combined to identify this new mode as a flexural vibration of the nanolines. Analysis of the phonon spectra gave estimates of elastic constants in the nanostructures and indicated that there is no significant deviation from bulk mechanical properties and no mechanical anisotropy in structures as small as 88nm.
QuantumKeyDistribution forReconfigurable Optical Networks (invited) (2006)

Recent advances inquantum keydistribution (QKD)systems foroptical networks arepresented including asystem that iscompatible withdynamic reconfiguration ofthequantum channel using optical switches. © 2006Optical Society ofAmerica OCIScodes: (060.2330) Fiber Optics Communications; (270.5570) Quantum Detectors Introduction. Security isbecoming animportant factor indataservices andnetwork architectures, whichis increasing theimportance ofencryption techniques forproviding secure communications. Themostwidely implemented approach today usesPublic KeyInfrastructure (PKI), acombination ofpublic andprivate keysto encrypt data toavoid thedifficulties withsharing orexchanging private (symmetric) keys. Thesecurity ofthefinal PKIkeysandencrypted data depends onthecomplexity ofthealgorithm andonthelimitations ofthecomputational capability ofapotential eavesdropper. However, thedifficulty inpredicting future breakthroughs inmathematics andadvances incomputing maylimit theapplicability oftoday's cryptographic techniques forfuture security needs. QKD takes adifferent approach, focusing onthesecure distribution ofsecret keysacross anetwork, sothat encryption cantake place withfinal keyswhosesecurity isassured bythelawsofphysics, rather thancomputational ormathematical complexity. Thesecurity inQKD isachieved byencoding information inthequantum states of single photons, transmitting thephotons overaquantum channel (such asanoptical fiber), andperforming a protocol fordistilling afinal, shared secret key(1). Since QKD isbased onthetransfer ofnon-orthogonal quantum states, theexistence ofaneavesdropper's measurement onthecommunications canbedetected. 150
Mechanism of Eosinophil Infiltration in the Patient with Subcutaneous Angioblastic Lymphoid Hyperplasia with Eosinophilia (Kimura’s Disease) (1994)

Kimura's disease is a chronic granulomatous disease of unknown etiology. Although eosinophilia is one of the characteristic features in this disease, little is known about the mechanism of eosinophilia. In the present study it was demonstrated that interleukin-5 (IL-5) was produced and released from the site of a granuloma and lymph nodes after stimulation with candida antigen. It was also shown that peripheral blood eosinophils from patients with Kimura's disease contained a large proportion of hypodense eosinophils and that their viability was prolonged. These results strongly suggest that locally produced IL-5 induced by candida antigen contributes to the eosinophilia in this disease.
Three-dimensional pattern transfer and nanolithography: modified soft molding (2002)

One-step transfer of molded three-dimensional polymer structures into underlying substrate is reported. The one-step transfer is made possible by a molding technique presented here in the form of modified soft molding. Formation of a desired three-dimensional structure in a polymer film by this method, followed by one-step reactive ion etching, is utilized for the transfer. The technique is also shown to be effective in transferring sub-100-nm features.
Stabilities of leucine zipper dimers estimated by an empirical free energy method (1991)

The leucine zipper motif is a characteristic amino acid sequence found in dimeric DNA-binding proteins. Computer-generated models for leucine zippers were constructed as alpha-helical coiled dimers with leucine repeated every seventh residue. An empirical Gibbs free energy, delta G, function which incorporates hydrophobic force, electrostatic interactions, and conformational entropy loss as the major intermolecular interactions was used to estimate the delta G of dimer formation in fos, jun, and GCN4 zipper sequences. The calculations showed that complexes known to form stable homo- or heterodimers have favorable (negative) delta G, while other less stable complexes have unfavorable (positive) delta G. Leucines in position d of the coiled coil contribute large hydrophobic stabilization energies while residues in the a position contribute less to dimer stability. Hydrophobic contributions show little sequence specificity, however, and do not contribute significantly to homo/heterodimer preference. Charged residues in the e and g positions, on the other hand, determine homo/heterodimer specificity. In GCN4 homodimers, residues GLU el, Glu b2, Lys g2, and Lys e4 greatly contribute to dimer stability. The preferential stability of fos-jun heterodimer over the jun-jun and fos-fos homodimers is primarily due to the side chains Asp b1, Glu g1, Asp b2, Glu e2, Glu g2, Glu g3, and Lys a5 of the fos helix, and Arg c1, Lys g1, Lys b2, Lys e2, Arg e4, and Glu g4 of the jun helix.
Handling RF Power: The Latest Advances in RF-MEMS Tunable Filters (2013)

RF-MEMS technology permits practical implementations of high-Q (Q from 300 to over 1,000) tunable microwave filters with power handling in the >;1-10 W range, with significant tuning range (>;50% to 100%), and ultra-low power consumption. Continuously frequency-tunable filters with mechanical actuation in the opposite direction of RF-inducted pressure can reach powers up to several watts, using a variable compensation bias. Very high Q, and large tuning range can be achieved with this technology, both in planar and cavity tunable filters. Using several devices in parallel, RF-MEMS capacitor arrays can handle RF-powers better than 1 watt, without the need for any compensation tuning.
System-level power exploration for MPEG-2 decoder on embedded cores: a systematic approach (2002)

The paper describes the impact of our system level data transfer and storage exploration methodology-as proposed in our mbox-ATOMIUM approach-in a software development context on embedded processors. The effectiveness of this methodology on power reduction is demonstrated by optimizing a public domain MPEG-2 video decoder program for an embedded processor. The result is an average factor 3.7 gained on simulated power reduction for the memory transfers. These transfers represent the dominant power consumption source. The presented optimizations can also improve the overall performance of the MPEG-2 algorithm due to the better data caching behaviour. For MPEG-2, additional code transformations were performed to reduce the cycle overhead initially induced by the optimization.
Control of TH17 cells occurs in the small intestine (2020)

Interleukin (IL)-17-producing T helper cells (TH17) are a recently identified CD4+ T cell subset distinct from T helper type 1 (TH1) and T helper type 2 (TH2) cells1. TH17 cells can drive antigen specific autoimmune diseases and are considered the main population of pathogenic T cells driving experimental autoimmune encephalomyelitis (EAE)2, the mouse model for multiple sclerosis. The factors that are needed for the generation of TH17 cells have been well-characterized3–6. However, where and how the immune system controls TH17 cells in vivo remains unclear.Here, by using a model of tolerance induced by CD3-specific antibody, a model of sepsis and influenza A viral infection (H1N1), we show that pro-inflammatory TH17 cells can be redirected to and controlled in the small intestine. TH17-specific IL-17A secretion induced expression of the chemokine CCL20 in the small intestine, facilitating the migration of these cells specifically to the small intestine via the CCR6/CCL20 axis. Moreover, we found that TH17 cells are controlled by two different mechanisms in the small intestine: first, they are eliminated via the intestinal lumen and simultaneously pro-inflammatory TH17 cells acquire a regulatory phenotype with in vitro and in vivo immune-suppressive properties (rTH17). These results identify mechanisms limiting TH17 cell pathogenicity and implicate the gastrointestinal tract as a site for control of TH17 cells.
RapidNano: towards 20nm Particle Detection on EUV Mask Blanks (2016)

Cleanliness is a prerequisite for obtaining economically feasible yield levels in the semiconductor industry. For the next generation of lithographic equipment, EUV lithography, the size of yield-loss inducing particles for the masks will be smaller than 20 nm. Consequently, equipment for handling EUV masks should not add particles larger than 20 nm. Detection methods for 20 nm particles on large area surfaces are needed to qualify the equipment for cleanliness. Detection of 20 nm particles is extremely challenging, not only because of the particle size, but also because of the large surface area and limited available time. In 2002 TNO developed the RapidNano, a platform that is capable of detecting nanoparticles on flat substrates. Over the last decade, the smallest detectable particle size was decreased while the inspection rate was increased. This effort has led to a stable and affordable detection platform that is capable of inspecting the full surface of a mask blank. The core of RapidNano is a dark-field imaging technique. Every substrate type has a typical background characteristic, which strongly affects the size of the smallest detectable particle. The noise level is induced by the speckle generated by the surface roughness of the mask. The signal-to-noise ratio can be improved by illuminating the inspection area from nine different angles. This improvement was first shown on test bench level and then applied in the RapidNano3. The RapidNano3 is capable of detecting 42nm latex sphere equivalents (and larger) on silicon surfaces. RapidNano4, the next generation, will use 193 nm light and the same nine angle illumination mode. Camera sensitivity and available laser power determine the achievable throughput. Therefore, special care was given to the optical design, particularly the optical path. With RapidNano4, TNO will push the detection limit of defects on EUV blanks to below 20nm.