gebhart/patrepeval huggingface dataset:
Data from Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Ovarian carcinoma no longer responsive to surgery and chemotherapy remains an incurable disease. Alternative therapeutic options remain desperately needed.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Patients and Methods:&lt;/b&gt; We describe a heavily pretreated patient with ovarian cancer with recurrent disease experiencing a remarkable clinical response to treatment with the anti-PD1 immune checkpoint inhibitor pembrolizumab. The clinical, pathological, and genomic characteristics of this exceptional ovarian cancer responder were carefully investigated using immunohistochemistry (IHC), quantitative multiplex fluorescence methods (i.e., automated quantitative analysis, AQUA) and whole-exome sequencing (WES) techniques.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The patient harbored a recurrent/metastatic radiation and chemotherapy-resistant high-grade ovarian carcinoma with clear cell features. While progressing on any standard treatment modality, she demonstrated a remarkable complete response to the anti-PD1 immune checkpoint inhibitor pembrolizumab. WES results were notable for the presence a relative low number of mutations (tumor mutation load/Mb = 4.31, total mutations = 164) and a peculiar structural variant disrupting the 3′ region of the &lt;i&gt;PD-L1&lt;/i&gt; gene causing aberrant PD-L1 surface expression as confirmed by IHC and AQUA technology. Heavy infiltration of the PD-L1–mutated and PD-L1–overexpressing tumor with T-cell lymphocytes (i.e., CD4&lt;sup&gt;+&lt;/sup&gt;/CD8&lt;sup&gt;+&lt;/sup&gt; TIL), CD68&lt;sup&gt;+&lt;/sup&gt; macrophages, and CD20&lt;sup&gt;+&lt;/sup&gt; B cells was detected in the surgical specimen strongly suggesting immune evasion as a key mechanism of tumor growth and survival. Patient's complete clinical responses remain unchanged at the time of the writing of this report with no significant side effects reported to date.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Anti-PD1 inhibitors may represent a novel treatment option for recurrent/metastatic human tumors refractory to salvage treatment harboring &lt;i&gt;PD-L1&lt;/i&gt; gene structural variations causing aberrant PD-L1 expression. &lt;i&gt;Clin Cancer Res; 24(14); 3282–91. ©2018 AACR&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;i&gt;See related commentary by Lheureux, p. 3233&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;
Theoretical Study of the Mechanism of Zeolite-Catalyzed Isomerization Reactions of Linear Butenes (1998)

Density functional theory is used to study the mechanism of double-bond isomerization and skeletal isomerization of linear butenes catalyzed by a protonated zeolite, which is simulated by a cluster consisting of two Si and one Al tetrahedra. The study includes complete geometry optimization and characterization of reactants, products, reaction intermediates and transition states, and calculation of the activation energies for the different processes involved. It is shown that the double bond isomerization proceeds by a concerted mechanism which does not involve the formation of either ionic or covalent alkoxy intermediates. According to this concerted mechanism, in one step the acid OH group of the zeolite protonates the double bond of adsorbed but-1-ene and the basic neighboring O atom of the cluster abstracts a hydrogen from the olefin, restoring the zeolite active site and yielding adsorbed but-2-ene. However, the mechanism of skeletal isomerization of linear butenes consists of three elementary steps: protonation of adsorbed but-1-ene to give a secondary alkoxy intermediate, conversion of the secondary alkoxy intermediate into a branched primary one through a cyclic transition state in which the transferring methyl group is halfway between its position in the linear and in the branched species, and decomposition of the primary alkoxy intermediate to give adsorbed isobutene. The activation barriers calculated for the two reactions are in good agreement with experimental data.
CELLULAR SIGNALING IN DEVELOPMENTAL CHONDROGENESIS (2003)

Cartilage formation in the developing vertebrate embryonic limb consists of a highly coordinated and orchestrated series of events involving the commitment, condensation, and chondrogenic differentiation of mesenchymal cells and the production of the cartilaginous matrix 1. Endochondral ossification ensues upon maturation and hypertrophy of the cartilage, resulting in the formation of the osseous elements of the limb. The recapitulation of this sequence of events during skeletal wound-healing and fracture-healing in postnatal life underscores the importance of understanding the cellular and molecular mechanisms that are responsible for initiating and regulating the early steps of cartilage development.

Embryonic cartilage development has been shown to be under the regulation of a number of biological factors, including members of the transforming growth factor-β (TGF-β) superfamily such as the bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs), and the Wnt family of secreted glycoproteins as well as cell adhesion proteins (e.g., neural cadherin [N-cadherin] and neural cell adhesion molecule [N-CAM]) and extracellular matrix (ECM) molecules (e.g., fibronectin, proteoglycans, and various collagen types)1.

This paper briefly reviews our recent studies on the mechanisms responsible for mesenchymal condensation and chondrogenic differentiation, and the role of Wnt members, as related to N-cadherin-mediated functions and the action of BMP-2, in the regulation of these processes. The Wnts are a large family of cysteine-rich glycoproteins that have been shown to perform a wide variety of inductive and regulatory functions in both normal development and oncogenic transformations1-3. The expression of various Wnts has been identified in the developing limb bud 4,5, and it has been shown that some Wnts may act in a chondro-inhibitory fashion when introduced during limb development 6-8. Our recent studies have shown that the dual consequences of Wnt signaling on cadherin-mediated cell adhesion and/or gene expression through β-catenin provide at …
In Vitro

Characterization of Polymeric Membrane used for Controlled Release Application (1995)

The application of a polymer film coat is a common practice in the preparation of controlled release dosage forms. In vitro characterization of the polymeric membrane is essential for optimization of the membrane formulation. Polymers selected in this study were cellulose acetate (CA), ethylcellulose (EC) and copolymers of acrylic and methacrylic esters (Eudragit RL100). Plasticizers used in this study were dibutyl sebacate (DBS), triethyl citrate (TEC) and triacetin. Polymer dispersions containing different plasticizers were cast into membranes on a tefloncoated plate. The resulting membranes were evaluated for permeability and mechanical properties. Membrane permeability was determined by quantifying the transport of a model drug, theophylline, across a circular polymeric membrane mounted in a thermostatted, twocompartment horizontal diffusion cell. Mechanical properties of the membranes, such as tensile strength, percent elongation and modulus of elasticity, were determined using an Instron 4301. The results of this study indicate that the CA and EC membranes were found to be effective in preventing the diffusion of theophylline. The addition of Eudragit RL100 to the CA or EC membranes increased the permeability but decreased the mechanical strength of the resulting membrane(s). A significant increase in permeability was observed at a CA:Eudragit RL100 ratio of 60:40. This could be explained by a change in the mechanism of drug transport, principally from partitioning into the membrane to diffusing through the liquidfilled pores of the resulting membrane(s). The results of the mechanical deformation studies indicate that triacetin has a greater potential for partitioning into the CA polymer than does TEC or DBS. DBS has a greater potential for partitioning into the EC polymer than does TEC or triacetin. The addition of Eudragit RL100 to the CA membrane(s) caused a significant decrease in the tensile strength, percent elongation and modulus of elasticity, thus resulting in weaker and softer membranes. The results indicate that the test methods employed were sufficiently sensitive to quantify the test parameters for the changes in membrane compositions which could provide valuable information for optimization of the membrane formulation.
Multi-window Gabor schemes in signal and image representations (1998)

Motivated by biological vision, schemes of signal and image representation by localized Gabor-type functions are introduced and analyzed. These schemes, suitable for information representation in a combined frequency-position space are investigated through signal decomposition into a set of elementary functions. Utilizing the Piecewise Zak transform (PZT), the theory of the multi-window approach is given in detail based on the mathematical concept of frames. The advantages of using more than a single window are analyzed and discussed. Applications to image processing and computer vision are presented with regard to texture images, and considered in the context of two typical tasks: image representation by partial information and pattern recognition. In both cases the results indicate that the multi-window approach is efficient and superior in major aspects to previously available methods. It is concluded that the new multi-window Gabor approach could be integrated efficiently into practical techniques of signal and image representation.KeywordsSpatial FrequencyWindow FunctionImage RepresentationTight FrameDual FrameThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
A family of genus‐specific RNAs in tandem with DNA‐binding proteins control expression of the badA major virulence factor gene in Bartonella henselae (2016)

Abstract Bartonella henselae is a gram‐negative zoonotic bacterium that causes infections in humans including endocarditis and bacillary angiomatosis. B. henselae has been shown to grow as large aggregates and form biofilms in vitro. The aggregative growth and the angiogenic host response requires the trimeric autotransporter adhesin BadA. We examined the transcriptome of the Houston‐1 strain of B. henselae using RNA ‐seq revealing nine novel, highly‐expressed intergenic transcripts ( Bartonella regulatory transcript, Brt1‐9). The Brt family of RNA s is unique to the genus Bartonella and ranges from 194 to 203 nucleotides with high homology and stable predicted secondary structures. Immediately downstream of each of the nine RNA genes is a helix‐turn‐helix DNA ‐binding protein (transcriptional regulatory protein, Trp1‐9) that is poorly transcribed under the growth conditions used for RNA ‐seq. Using knockdown or overexpressing strains, we show a role of both the Brt1 and Trp1 in the regulation of badA and also in biofilm formation. Based on these data, we hypothesize that Brt1 is a trans ‐acting sRNA that also serves as a cis ‐acting riboswitch to control the expression of badA . This family of RNA s together with the downstream Trp DNA ‐binding proteins represents a novel coordinated regulatory circuit controlling expression of virulence‐associated genes in the bartonellae.
Experimental characterization of wavelength separation for "QKD+WDM" co-existence (2005)

The minimum wavelength separation for multiplexing 1.3 /spl mu/m QKD with 1.5 /spl mu/m classical optical channels is experimentally determined for impairment-free QKD+WDM transmission.
Differential requirement for A2a and A3 adenosine receptors for the protective effect of inosine in vivo (2003)

Inosine is an endogenous nucleoside with immunosuppressive properties that is known to inhibit the accumulation of proinflammatory cytokines and protect mice from endotoxin-induced inflammation and lung tissue damage. There are no known receptors specific for inosine, but A3 adenosine receptors (A3Rs) have been shown to bind inosine, resulting in mast cell degranulation and increased vascular permeability. The present study specifically addresses the requirement for A2aR and/or A3R for the protective effect of inosine in 2 experimental in vivo models of inflammatory disease. The data show that A3R is essential for protection against ConA-induced fulminant hepatitis since only A3R-expressing mice were protected by inosine whereas wild-type and A2aR-deficient mice exhibited severe liver damage even after administration of inosine. In addition, we show in a model of LPS-induced endotoxemia that inosine protected both A2aR-/- and A3R-/- mice from inflammation, but not A2aA3R double-null mice, indicating that in this model both A2aR and A3R were used by inosine. Thus, we demonstrate that A2a and A3 adenosine receptors are differentially utilized by inosine for the down-regulation of tissue damage under different inflammatory conditions in vivo.
Impact of involved free light chain (FLC) levels in patients achieving normal FLC ratio after initial therapy in light chain amyloidosis (AL) (2017)

Achievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10-year period (2006-2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1<sup>st</sup> reading of normal FLCr (hiFLC1; n = 166; 48.1%) were compared to those who did not (n = 179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi-organ involvement (63.3 vs 46.4%; P = .002) and patients in advanced Mayo stage (42.9 vs 32.2%; P = .04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; P = .0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; P < .0001] were lower in those who had hiFLC1. A more stringent comparison for patients with 2 consecutive hiFLC (hIFLC2; n = 111; 32.2%) versus not (n = 2234; 67.8%) showed consistent results [PFS; 27.1 (95%CI; 23, 53.8) vs 63.3 (95%CI; 55.4, 77) months; P < .0001 and OS; 78 (95% CI; 54.6, 98.8) vs NR (95%CI; NR, NR); P < .0001]. This poor prognostic impact of hiFLC on survival was independent of serum creatinine, Mayo stage, negative immunofixation status and inclusion of transplant in initial therapy on multivariate analysis. Hence, persistent elevation of iFLC predicts poor prognosis even among patients achieving normal ratio after initial therapy in AL.
Adaptive antenna array transmit diversity in FDD forwad link for W-CDMA and broadband packet wireless access (2002)

This article presents a transmitter antenna weight generation method in adaptive antenna array transmit diversity (AAA-TD) that focuses on the calibrations in wideband direct sequence code-division multiple access (W-CSDMA) and broadband packet wireless access in FDD systems. In our scheme, the adaptively generated receiver antenna weights of the reverse link in the coherent adaptive antenna array diversity receiver are used as transmitter antenna weights, however, with calibration of the phase/amplitude variations of the parallel radio frequency receiver/transmitter circuits corresponding to the number of array antennas (RF circuitry calibration) and with calibration of the transmitter beam pattern due to the difference in carrier frequency between the reverse and the forward links (carrier frequency calibration). The interference suppression effect of AAA-TD employing a carrier frequency calibration and RF circuitry calibration in the W-CDMA forward link is also investigated by laboratory experiments. The experimental results elucidate that in a four-user environment (three interfering users), although an error floor above BER of 10 -1 is observed with a one-antenna transmitter due to the severe multipath interference, average BER of below 10 -6 is achieved using AAA-TD with four antennas, when the ratio of the target signal energy per bit-to-interference plus background noise power spectrum density ratio (E b /I 0 ) of the desired user to interfering user for fast transmission power control is ΔE b /I 0 = -12 dB.
Insights into the role of C3d dimers in B cell activation and Staphylococcal immune evasion (2020)

Abstract Cleavage of C3 to C3a and C3b plays a central role in the generation of complement-mediated defences. Although the thioester-mediated surface deposition of C3b has been well-studied, fluid-phase dimers of C3 fragments remain largely unexplored. Here we present the first X-ray crystal structures of disulphide-linked human C3d dimers and show they undergo structurally-stabilising N-terminal domain swapping when in complex with the Staphylococcus aureus immunomodulator Sbi. Through binding studies and flow cytometric analyses we uncover the physiologically-relevant roles of these dimers in crosslinking complement receptor 2 and modulating B cell activation to potentially promote anergy. This potential induction of cellular tolerance by C3d dimers could contribute to Sbi-mediated S. aureus immune evasion as well as limit autoreactive immune responses under physiological conditions. Thus, insights gained from our findings could inform the design of novel therapies for autoimmune disorders and enhance our understanding surrounding the importance of complement in the fluid phase.
ChemInform Abstract: Cyclizations of Hydroxy Dithioketals. New Synthetic Technology for the Construction of Oxocenes and Related Medium‐Ring Systems. (1989)

Abstract Ag+‐induced ring closure of the hydroxy dithioketal (III) affords the oxacene (IV).
Effects of Pregermination of Pea and Cucumber Seeds and of Seed Treatment withEnterobacter cloacaeon Rots Caused byPythiumspp. (1983)

Effets de la pregermination sur la sensibilite des graines a la fonte des semis dans diverses conditions, notamment en aseptie ou non. Etude du role d'E.c. dans la prevention des infections
Monochromatic X-ray Source Based on Scattering from a Magnetic Nanoundulator (2020)

We present a novel design for an ultracompact, passive light source capable of generating ultraviolet and X-ray radiation, based on the interaction of free electrons with the magnetic near-field of a ferromagnet. Our design is motivated by recent advances in the fabrication of nanostructures, which allow the confinement of large magnetic fields at the surface of ferromagnetic nanogratings. Using ab initio simulations and a complementary analytical theory, we show that highly directional, tunable, monochromatic radiation at high frequencies could be produced from relatively low-energy electrons within a tabletop design. The output frequency is tunable in the extreme ultraviolet to hard X-ray range via electron kinetic energies from 1 keV to 5 MeV and nanograting periods from 1 μm to 5 nm. The proposed radiation source can achieve the tunability and monochromaticity of current free-electron-driven sources (free-electron lasers, synchrotrons, and laser-driven undulators), yet with a significantly reduced scale, cost, and complexity. Our design could help realize the next generation of tabletop or on-chip X-ray sources.
The mutual exclusion problem (1986)

A novel formal theory of concurrent systems that does not assume any atomic operations is introduced. The execution of a concurrent program is modeled as an abstract set of operation executions with two temporal ordering relations: “precedence” and “can causally affect”. A primitive interprocess communication mechanism is then defined. In Part II, the mutual exclusion is expressed precisely in terms of this model, and solutions using the communication mechanism are given.
Deep-Level Defects in High-Dose Proton Implanted and High-Temperature Annealed Silicon (2014)

We review the principal mechanisms of deep-level defect formation after proton irradiation and subsequent annealing of float zone grown crystalline silicon. Various reaction paths commonly related to vacancy-complexes, interstitial oxygen and hydrogen are discussed. In the experimental part DLTS results of proton-irradiated pn-diode structures are presented. It appears that some detected defects show a thermal stability differing from that reported in literature. Furthermore the metastability of two defects at 300 meV and 418 meV below the conduction band is examined. This behavior commonly designated to a negative-U defect is for the first time reported in a sample annealed at 350° C.
Taylor series expansions for the entropy rate of Hidden Markov Processes (2006)

Finding the entropy rate of Hidden Markov Processes is an active research topic, of both theoretical and practical importance. A recently used approach is studying the asymptotic behavior of the entropy rate in various regimes. In this paper we generalize and prove a previous conjecture relating the entropy rate to entropies of finite systems. We use the proof to establish series expansions for the entropy rate in two different regimes. We also study the radius of convergence of the two series expansions.
Factor Xa and Prothrombin: Mechanism of Action of FEIBA (1999)

A complex consisting of activated factor X (FX) (enzyme) and prothrombin (substrate), both highly purified from human plasma and virus inactivated, was formulated, characterised biochemically as well as in animal studies, and given the name Partial Prothrombinase (PPT). In vitro, PPT shortened the clotting time of a high-titre human factor VIII (FVIII) inhibitor plasma in a manner similar to that of the activated prothrombin complex concentrate FEIBA and triggered coagulation in plasma samples in which factor V (FV) is present. In vivo, the ability of PPT to activate coagulation in both chimpanzees and baboons was equivalent to that of FEIBA. PPT also triggered coagulation in a von Willebrand factor(vWF)-deficient dog and controlled bleeding in rabbits with antibody-induced haemophilia A. Thus, studying the mechanism of action of PPT also explains the therapeutic principle of FEIBA.
Scalability Of Plasma Damage With Gate Oxide Thickness (1997)

The effect of decreasing gate oxide thickness on the susceptibility to pre-metallization plasma damage is investigated for the range of 40-80A for both n and p type MOS capacitors. An antenna design, which intentionally uses an excessive number of contacts, has been used as a tool for excessive damage initiation to investigate the scalability of plasma damage with gate oxide thickness. Electrical reliability results indicate that susceptibility to damage increases with decreasing oxide thickness. Breakdown field was found to be an appropriate reliability criterion for comparing various oxide thicknesses.
A high-gain, compact, nonimaging concentrator: RXI (1995)

The design procedure of a new nonimaging concentrator (called an RXI) is explained. Rays that impinge on the concentrator aperture, within the acceptance angle, are directed to the receiver by means of one refraction, one reflection, and one total internal reflection. The concentrator can be made as a single dielectric piece (in which the receiver is immersed) whose aspect ratio (thickness/aperture diameter) is close to 1/3. Ray-tracing analysis of a rotational symmetric RXI shows total transmissions of greater than 94.5% (no absorption or reflection losses are considered) when the acceptance angle of the incoming rays is small (<3°) and when the receiver area is the smallest possible (maximal concentration.).