gebhart/patrepeval huggingface dataset:
Association of diversity and composition of the gut microbiome with differential responses to PD-1 based therapy in patients with metastatic melanoma. (2017)

2 Background: Tremendous advances have been made in cancer therapy through the use of immune checkpoint blockade, although responses are not always durable. There is a growing appreciation of the role of the microbiome in cancer-related outcomes and recent evidence in murine models suggests that modulation of the gut microbiome may enhance responses to immune checkpoint blockade in melanoma. However this has not been investigated in patients. Here, we demonstrate that differential bacterial “signatures” exist in the gut microbiome of responders (R) and non-responders (NR) to anti-PD1 therapy at baseline, and that insights gained could be used to derive actionable strategies to enhance responses. Methods: We collected oral (n = 222) and gut microbiome (n = 113) samples on a large cohort of patients with metastatic melanoma (n = 228), with a majority treated with anti-PD1 therapy (n = 110). Patients were classified as either R or NR based on RECIST criteria, and 16S rRNA gene sequencing was performed to characterize the diversity and composition of the microbiomes. Immune profiling (via 7-marker IHC panel of CD3, CD8, PD-1, PD-L1, Granzyme B, RORγT and FoxP3) was performed in available tumors at baseline. Results: In these studies, we observed significant differences in the diversity and composition of the gut microbiome in R versus NR to PD1 blockade at baseline, but no clear differences in oral microbiomes. Specifically, R had a significantly higher alpha diversity compared to NR (p = 0.017). Notable differences were also seen in the composition of the gut microbiome of R versus NR. Immune profiling demonstrated significantly increased immune infiltrates in baseline tumor samples of R, with a positive correlation between CD8, CD3, PD1 and FoxP3 T-cell density and abundance of specific bacteria enriched in R (e.g. Faecalibacterium). Conclusions: Differences exist in the diversity and composition of the gut microbiome in R vs NR to anti-PD1 therapy. These results have far-reaching implications and suggest that modifications to the gut microbiome could potentially enhance therapeutic responses to immune checkpoint blockade.
New micromachined microstrip transmission lines for application in millimeter‐wave circuits (2003)

Abstract In this paper, we describe a new GaAs‐based micromachined microstrip line, supported by an electrically supported air‐gapped microstrip line (DAML) structure and developed using RF MEMS techniques to achieve low losses at millimeter‐wave frequency bands with wide impedance ranges. The measured DAML with a 10‐μm post height shows less than 1.5‐dB/cm attenuation at 50 GHz with 20–100Ω, which agrees well with the simulated results. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 6–9, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11270
Chaperonin Containing T-Complex Polypeptide Subunit Eta (CCT-eta) Is a Specific Regulator of Fibroblast Motility and Contractility (2010)

Integumentary wounds in mammalian fetuses heal without scar; this scarless wound healing is intrinsic to fetal tissues and is notable for absence of the contraction seen in postnatal (adult) wounds. The precise molecular signals determining the scarless phenotype remain unclear. We have previously reported that the eta subunit of the chaperonin containing T-complex polypeptide (CCT-eta) is specifically reduced in healing fetal wounds in a rabbit model. In this study, we examine the role of CCT-eta in fibroblast motility and contractility, properties essential to wound healing and scar formation. We demonstrate that CCT-eta (but not CCT-beta) is underexpressed in fetal fibroblasts compared to adult fibroblasts. An in vitro wound healing assay demonstrated that adult fibroblasts showed increased cell migration in response to epidermal growth factor (EGF) and platelet derived growth factor (PDGF) stimulation, whereas fetal fibroblasts were unresponsive. Downregulation of CCT-eta in adult fibroblasts with short inhibitory RNA (siRNA) reduced cellular motility, both basal and growth factor-induced; in contrast, siRNA against CCT-beta had no such effect. Adult fibroblasts were more inherently contractile than fetal fibroblasts by cellular traction force microscopy; this contractility was increased by treatment with EGF and PDGF. CCT-eta siRNA inhibited the PDGF-induction of adult fibroblast contractility, whereas CCT-beta siRNA had no such effect. In each of these instances, the effect of downregulating CCT-eta was to modulate the behavior of adult fibroblasts so as to more closely approximate the characteristics of fetal fibroblasts. We next examined the effect of CCT-eta modulation on alpha-smooth muscle actin (alpha-SMA) expression, a gene product well known to play a critical role in adult wound healing. Fetal fibroblasts were found to constitutively express less alpha-SMA than adult cells. Reduction of CCT-eta with siRNA had minimal effect on cellular beta-actin but markedly decreased alpha-SMA; in contrast, reduction of CCT-beta had minimal effect on either actin isoform. Direct inhibition of alpha-SMA with siRNA reduced both basal and growth factor-induced fibroblast motility. These results indicate that CCT-eta is a specific regulator of fibroblast motility and contractility and may be a key determinant of the scarless wound healing phenotype by means of its specific regulation of alpha-SMA expression.
Fibroblast growth factor 2 (FGF-2) is a novel substrate for arginine methylation by PRMT5 (2008)

Fibroblast growth factor 2 (FGF-2) is expressed in isoforms of different molecular masses from one mRNA species by alternative start of translation. The higher molecular mass isoforms (FGF-2(21) and (23)) contain an arginine-rich N-terminus organized in RG-motifs followed by the 18 kDa FGF-2 (FGF-2(18)) core which is common to all isoforms. Both isoforms localize differentially to the nucleus. Here, we analyzed the nuclear localization of FGF-2(21). Surprisingly, the lack of one RG-motif in FGF-2(21) resulted in the nucleolar distribution characteristic of FGF-2(18). We have previously shown that 23 kDa FGF-2 (FGF-2(23)) interacts specifically with the survival of motoneuron (SMN) protein, an assembly protein for small nuclear ribonucleoprotein particles. For this assembly, Sm-proteins methylated by protein arginine methyltransferase 5 (PRMT5) are required. In our study, we aimed to analyze whether FGF-2(23) is also a substrate for symmetrical methylation by PRMT5. We could confirm that both proteins exist in a common complex. Moreover, PRMT5 methylates FGF-2(23) in vitro, whereas mutated inactive PRMT5 does not. FGF-2(23) is therefore a new substrate of PRMT5. With regard to function, inhibition of methyltransferase activity in HEK293T cells leads to cytoplasmic enrichment of FGF-2, indicating the importance of arginine methylation for shuttling of FGF-2(23) to the nucleus.
Robust MMSE Beamforming for Multiuser MISO Systems With Limited Feedback (2009)

This letter considers minimum mean square error beamforming (MMSEBF) for the downlink of a multiuser multiple-input single-output (MISO) system with limited feedback, where the transmitter only has quantized information regarding the direction of the channel. We present an improved approach which is robust to the channel uncertainties arising from the quantization errors and the lack of channel magnitude information. Simulation results show that the proposed robust MMSEBF scheme provides improved performance over the conventional beamforming schemes in limited feedback systems.
Pathologie tumorale du massif facial: point de vue du clinicien, les résections cranio-faciales (1997)

Les tumeurs du massif facial nécessitent une approche pluridisciplinaire, aussi bien diagnostique que thérapeutique. La prise en charge du patient implique aussi une bonne intégration de l'équipe avec les anesthésistes et la réhabilitation postopératoire (kinésistes, logopèdes, psychothérapeutes). Un grand nombre de patients sont généralement référés après avoir déjà subi des traitements antérieurs, ce qui rend le traitement plus difficile et le pronostic plus sombre. Néanmoins, un maximum d'efforts doit être mis au service du patient afin de permettre une résection et une reconstruction qui assurent une qualité de vie optimale. Notre expérience confrontée avec celles de la littérature montre que les marges de résection du spécimen opératoire sont difficiles à évaluer, le grading histologique de la tumeur est important ainsi que l'existence d'une invasion de la dure-mère ou/et de l'orbite. On note une grande proportion de complications (de 30 à 50 % avec deux tiers de complications majeures, les plus importantes étant des infections et des troubles de la recouvrance neurologique). Le traitement chirurgical comporte un abord cervico-facial, un abord neurochirurgical de la fosse antérieure et une reconstruction par une équipe de chirurgiens plasticiens rompus à la microchirurgie pour amener in situ des lambeaux libres microvascularisés qui améliorent nettement la rapidité d'une reconstruction fonctionnelle et permettent une irradiation complémentaire dans des délais de 30 à 40 jours après l'intervention. La survie actuarielle à 5 ans pour ces tumeurs dépend essentiellement de l'histologie, du grading de la tumeur et du fait que celle-ci ait ou non été traitée antérieurement et qu'il s'agisse alors de rattrapage. Dans les meilleurs cas, cette survie actuarielle à 5 ans est de l'ordre de 55 %.
WDM/TDM-PON technologies for future flexible optical access networks (2010)

A WDM/TDM-PON system employing a dynamic wavelength and bandwidth-allocation technique is proposed for future flexible optical-access networks. The system achieves high utilization efficiency for the total bandwidth and smooth upgrade to higher bandwidth-guaranteed services.
Oncostatin M Receptor-β Signaling Limits Monocytic Cell Recruitment in Acute Inflammation (2008)

Although the IL-6-related cytokine oncostatin M (OSM) affects processes associated with disease progression, the specific function of OSM in the face of an inflammatory challenge remains unclear. In this report, a peritoneal model of acute inflammation was used to define the influence of OSM on chemokine-mediated leukocyte recruitment. When compared with wild-type and IL-6-deficient mice, peritoneal inflammation in oncostatin M receptor-beta-deficient (OSMR-KO) mice resulted in enhanced monocytic cell trafficking. In contrast to IL-6-deficient mice, OSMR-KO mice displayed no difference in neutrophil and lymphocyte migration. Subsequent in vitro studies using human peritoneal mesothelial cells and an in vivo appraisal of inflammatory chemokine expression after peritoneal inflammation identified OSM as a prominent regulator of CCL5 expression. Specifically, OSM inhibited IL-1beta-mediated NF-kappaB activity and CCL5 expression in human mesothelial cells. This was substantiated in vivo where peritoneal inflammation in OSMR-KO mice resulted in a temporal increase in both CCL5 secretion and NF-kappaB activation. These findings suggest that IL-6 and OSM individually affect the profile of leukocyte trafficking, and they point to a hitherto unidentified interplay between OSM signaling and the inflammatory activation of NF-kappaB.
Cytotoxic T‐cell responses to <i>Mycobacterium bovis</i> during experimental infection of cattle with bovine tuberculosis (2003)

Cytotoxic T-cell responses are thought to play a significant role in the host defence against mycobacterial infections. Little is understood about such responses of cattle to Mycobacterium bovis, the causative agent of bovine tuberculosis. The work described in this report demonstrates the activity of cytotoxic cells during experimental infection of cattle with M. bovis. The cytotoxic cells were found to have the ability to specifically lyse macrophages infected with M. bovis and were detected in peripheral blood lymphocytes after in vitro re-exposure to M. bovis. Cytotoxic activity was detected 4 weeks after experimental infection with M. bovis; a similar level of activity was maintained during the infection and it was mediated by both WC1+gammadelta and CD8+ T cells. In addition, inhibition of the growth of M. bovis within infected macrophages was detected when they were exposed to cultures containing M. bovis-specific cytotoxic cells. The ability to detect cytotoxic cells after infection of cattle with M. bovis will allow their activity to be measured during vaccination trials. Correlation of cytotoxic activity with disease outcome may aid in the design of new vaccines and vaccination strategies.
Motion-Still Segmentation Algorithm for VTC/VT Objective Quality Assessment (1991)

The ability of the human eye to resolve detail in a video scene is related to how much motion is present at the point of focus and whether or not the eye can track the motion. Thus, stationary portions of the video scene can be resolved in great detail by the eye, while moving portions of the video scene are normally resolved in less detail (provided the eye cannot fully track the motion). Low bit-rate digital video channels (e.g., video teleconferencing) determine how many bits are used for each local area of the video scene. Since the time averaged information content of a still video scene is much less than the time averaged information content of a moving scene, typical video teleconferencing channels can have very different static and dynamic responses. The dynamic response of the channel is also a function of the video scene and can vary on a frame-by-frame basis. Thus, it is desirable to have a general algorithm (applicable to any test waveform or test scene) that can separate the dynamic response from the static response on a frame by frame basis. This contribution describes one such algorithm. The motion-still segmentation algorithm presented here can be applied to any test waveform or test scene in order to separate the moving portions from the still portions of the video scene. A detailed description of the motion-still segmentation algorithm and its theoretical basis is given first. Then, a typical application of the algorithm is presented: measuring the increased spatial blurring of moving objects in an actual video teleconferencing scene.
The functions of the fibre bundles of the anterior cruciate ligament in anterior drawer, rotational laxity and the pivot shift (2012)

This paper reviews the functional anatomy of the anterior cruciate ligament (ACL), which has a parallel array of collagen fascicles that have usually been divided into two 'fibre bundles': anteromedial (AM) and posterolateral (PL), according to their tibial attachment sites. The PL bundle has shorter fibres, and so it is subjected to greater tensile strains than the AM bundle when the whole ACL is stretched; its oblique orientation in the coronal plane imbues it with greater ability to resist tibial rotation than the more vertical AM fibre bundle. Most studies have found that the AM bundle is close to isometric when the knee flexes, while the PL bundle slackens approximately 6 mm. There is little evidence of significant fibre bundle elongation in response to tibial rotation. Selective bundle cutting studies have been performed, allowing both the bundle tensions and their contributions to resisting tibial anterior translation and tibial rotation to be calculated. These show that the function of the PL bundle was dominant near knee extension in some studies, particularly when resisting anterior drawer and that its contribution reduced rapidly with knee flexion through 30 degrees. There has been little study of the contributions of the fibre bundles in control of tibial internal-external rotation or the pivot shift: one study found that the AM bundle had larger tensions than the PL bundle during a simulated pivot shift, but another study found that cutting the PL bundle allowed a larger increase in coupled tibial anterior translation than cutting the AM bundle. It was concluded that the AM bundle is most important for resisting tibial anterior drawer-the primary function of the ACL-while the PL bundle is tight near knee extension, when it has a role in control of tibial rotational laxity. There is a clear need for further study of dynamic knee instability, to gain better understanding of how best to reconstruct the ACL and associated tissues.
Baseball4D: A tool for baseball game reconstruction &amp; visualization (2014)

While many sports use statistics and video to analyze and improve game play, baseball has led the charge throughout its history. With the advent of new technologies that allow all players and the ball to be tracked across the entire field, it is now possible to bring this understanding to another level. From discrete positions across time, we present techniques to reconstruct entire baseball games and visually explore each play. This provides opportunities to not only derive new metrics for the game, but also allow us to investigate existing measures with targeted visualizations. In addition, our techniques allow users to filter on demand so specific situations can be analyzed both in general and according to those situations. We show that gameplay can be accurately reconstructed from the raw position data and discuss how visualization and statistical methods can combine to better inform baseball analyses.
Kinetics of the Oxygenation of Unsaturated Organics with Singlet Oxygen Generated from H<sub>2</sub>O<sub>2</sub> by a Heterogeneous Molybdenum Catalyst (2007)

A heterogeneous catalyst containing MoO42- exchanged on layered double hydroxides (Mo-LDHs) is used to produce 1O2 from H2O2, and with this dark 1O2, unsaturated hydrocarbons are oxidized in allylic peroxides. The oxidation kinetics are studied in detail and are compared with the kinetics of oxidation by 1O2, formed from H2O2 by a homogeneous catalyst. A model is proposed for the heterogeneously catalyzed 1O2 generation and peroxide formation. The model divides the reaction suspension in two compartments: (1) the intralamellar and intragranular zones of the LDH catalyst; (2) the bulk solution. The 2-compartment model correctly predicts the oxidant efficiency and peroxide yield for a series of olefin peroxidation reactions. 1O2 is generated at a high rate by the heterogeneous catalyst, but somewhat more 1O2 is lost by quenching with the heterogeneous catalyst than using the homogeneous catalyst. Quenching occurs mainly as a result of collision with the LDH hydroxyl surface, as is evidenced by using LDH supports containing strong 1O2 deactivators such as Ni2+. A total of 15 organic substrates were peroxidized on a preparative scale using the best Mo-LDH catalyst under optimal conditions.
The absolute oral bioavailability of selected drugs. (1989)

Oral bioavailability is best defined as the rate and extent to which an active drug substance is absorbed and becomes available to the general circulation. This concept is discussed, along with several popular methods for determining absolute oral bioavailability. The absolute oral bioavailability of numerous drugs is reviewed and interspecies comparisons are made. In general, absolute oral bioavailability does not correlate well between species, though relative comparisons might be made.
Atom transfer radical polymerization of <i>n</i>‐butyl acrylate catalyzed by CuBr/<i>N</i>‐(<i>n</i>‐hexyl)‐2‐pyridylmethanimine (2002)

Abstract The homogeneous atom transfer radical polymerization (ATRP) of n ‐butyl acrylate with CuBr/ N ‐( n ‐hexyl)‐2‐pyridylmethanimine as a catalyst and ethyl 2‐bromoisobutyrate as an initiator was investigated. The kinetic plots of ln([M] 0 /[M]) versus the reaction time for the ATRP systems in different solvents such as toluene, anisole, N,N ‐dimethylformamide, and 1‐butanol were linear throughout the reactions, and the experimental molecular weights increased linearly with increasing monomer conversion and were very close to the theoretical values. These, together with the relatively narrow molecular weight distributions (polydispersity index ∼ 1.40 in most cases with monomer conversion > 50%), indicated that the polymerization was living and controlled. Toluene appeared to be the best solvent for the studied ATRP system in terms of the polymerization rate and molecular weight distribution among the solvents used. The polymerization showed zero order with respect to both the initiator and the catalyst, probably because of the presence of a self‐regulation process at the beginning of the reaction. The reaction temperature had a positive effect on the polymerization rate, and the optimum reaction temperature was found to be 100 °C. An apparent enthalpy of activation of 81.2 kJ/mol was determined for the ATRP of n ‐butyl acrylate, corresponding to an enthalpy of equilibrium of 63.6 kJ/mol. An apparent enthalpy of activation of 52.8 kJ/mol was also obtained for the ATRP of methyl methacrylate under similar reaction conditions. Moreover, the CuBr/ N ‐( n ‐hexyl)‐2‐pyridylmethanimine‐based system was proven to be applicable to living block copolymerization and living random copolymerization of n ‐butyl acrylate with methyl methacrylate. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3549–3561, 2002
Design and Implementation of a 125kW T-NPC PV Inverter (2015)

Yuelin, Wu, National Active Distribution Network Technology Research Center (Beijing Jiaotong University), Beijing, China, 13121480@bjtu.edu.cn Guohong, Zeng, National Active Distribution Network Technology Research Center (Beijing Jiaotong University), Beijing, China, ghzeng@bjtu.edu.cn Jingdou, Liu, National Active Distribution Network Technology Research Center (Beijing Jiaotong University), Beijing, China, jdliu@bjtu.edu.cn Gaosheng, Song, MITSUBISHI ELECTRIC&ELECTRONICS (SHANGHAI) CO., LTD., Shanghai, China, SongGS@mesh.china.meap.com Jian, Sun, MITSUBISHI ELECTRIC&ELECTRONICS (SHANGHAI) CO., LTD., Shanghai, China, SunJian@mesh.china.meap.com
Use of self assembled magnetic beads for on-chip protein digestion (2005)

The use of grafted trypsin magnetic beads in a microchip for performing protein digestion is described. The PDMS device uses strong magnets to create a magnetic field parallel to the flow with a strong gradient pointing through the center of the chip channel. This allows for the formation of a low-hydrodynamic resistance plug of magnetic trypsin beads that serves as a matrix for protein digestion. This device represents an inexpensive way of fabricating a multi open-tubular-like column with an appropriate pore size for proteins. Kinetics studies of the hydrolysis of a model peptide show a 100-fold increase in digestion speed obtained by the microsystem when compared to a batch wise system. This system also offers the great advantage of easy replacement, as the bead matrix is easily washed out and replaced. High performance and reproducibility for digesting recombinant human growth hormone are confirmed by analysing the digest products in both CE and MALDI-TOF MS. Similar sequence coverage (of about 44%) is obtained from MS analysis of products after 10 minutes on-chip and 4 h with soluble trypsin in bulk.
Multiple aberrant splicing of the p53 transcript without genomic mutations around exon‐intron junctions in a case of chronic myelogenous leukaemia in blast crisis: a possible novel mechanism of p53 inactivation (1994)

We found three truncated p53 transcripts in a patient with chronic myelogenous leukaemia in blast crisis carrying chromosome 17 abnormalities. Sequencing of these transcripts revealed complete absence of the entire exons 7, 8 and 9 in one, exons 8 and 9 in another, and exon 10 in the other. Sequencing analysis of genomic DNA, however, revealed no mutation in exons 6-10 and their flanking introns. These results suggest that the aberrant p53 transcripts in this case might not result from splicing mutations but from an unknown affected splicing process.