gebhart/patrepeval huggingface dataset:
Biological and small molecule strategies in migraine therapy with relation to the calcitonin gene‐related peptide family of peptides (2021)

Migraine is one of the most common of neurological disorders with a global prevalence of up to 15%. One in five migraineurs have frequent episodic or chronic migraine requiring prophylactic treatment. In recent years, specific pharmacological treatments targeting calcitonin gene-related peptide (CGRP) signalling molecules have provided safe and effective treatments, monoclonal antibodies for prophylaxis and gepants for acute therapy. Albeit beneficial, it is important to understand the molecular mechanisms of these new drugs to better understand migraine pathophysiology and improve therapy. Here, we describe current views on the role of the CGRP family of peptides - CGRP, calcitonin, adrenomedullin, amylin - and their receptors in the trigeminovascular system. All these molecules are present within the trigeminovascular system but differ in expression and localization. It is likely that they have different roles, which can be utilized in providing additional drug targets. LINKED ARTICLES: This article is part of a themed issue on Advances in Migraine and Headache Therapy (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.3/issuetoc.
Response of a Rod Stabilized, Premixed Flame to Longitudinal Acoustic Forcing (2006)

This paper describes an experimental investigation of the flame sheet dynamics of an acoustically forced bluff body flame over a range of perturbation frequencies and amplitudes. When acoustically excited, the flame sheet displays well defined, periodic corrugations, presumably due to flame sheet perturbations created at its attachment point that convect downstream, as well as the rollup of shear layer instabilities into large scale coherent structures. The dynamics of the flame front response, such as its growth and decay in the bluff body wake, disturbance convection velocity, sub-harmonic response, and total flame area is discussed.
El Teorema de Gödel y de la discusión sobre el carácter computacional de la mente humana (1999)

El Teorema de lncompletitud de Gbdel se considera hoy en dia uno de los mas importantes que ha dado el siglo XX y se lo compara, en cuanto a profundidad y consecuencias, con la relati vidad de Einstein o el principio de incertidumbre de Heisenberg. Como veremos mas adelante es un teorema que conlleva implicaciones fil osofi cas de todo tipo, desde la di scusion sobre la naturaleza de la verdad hasta aspectos re lacionados con la mente y el pensamiento. Este articul o pretende ser una breve exposicion de algunas ideas interesantes entorno al teorema, y en concreto de las ideas referidas a las implicaciones del teorema en las reflexiones sobre el pensamiento humano. Para ello, se explica brevemente quien fu e Kurt Gbdel, se ex ponen las ideas bas icas subyacentes al teorema, y finalmente se di scuten las consecuencias en lo referente a la fil osofia de la mente.
Induction of tolerance by allochimeric class I MHC molecules: evidence of immunoregulatory T cells and limited usage of T cell receptor Vβ genes (2000)

Ghobrial, Rafik MD, PhD1; Mhoyan, Anna MD1; Zhai, Yuan PhD1; Shen, Xiu-Da MD1; Zhao, Danyun MD1; Gao, Fang MD1; Reemtsen, Brian MD1; Singer, Jennifer MD1; Kahan, Barry MD, PhD1; Busuttil, Ronald W MD, PhD2; Kupiec-Weglinski, Jerzy W MD, PhD1 Author Information
A Highly Reliable 3-D Integrated SBT Ferroelectric Capacitor Enabling FeRAM Scaling (2005)

Ferroelectric random access memories (FeRAMs) combine very attractive properties such as low-voltage operation, fast write and nonvolatility. However, unlike Flash memories, FeRAMs are difficult to scale along with the CMOS technology roadmap, mainly because of the decrease of available signal with decreasing cell area. One solution for further scaling is to integrate three-dimensional (3-D) FeCAPs. In this paper, we have integrated a 3-D FeCAP structure in a 0.35-/spl mu/m CMOS technology whereby the effective area of <1 /spl mu/m/sup 2/ single FeCAPs is increased by a factor of almost two. We show that, after optimization of the metal-organic chemical vapor deposition (MOCVD) deposition and post-anneal steps of the Sr/sub 0.8/Bi/sub 2.2/Ta/sub 2/O/sub 9/ (SBT) layer, the sidewall SBT contributes to the polarization Pr, resulting in higher Pr values for 0.81-/spl mu/m/sup 2/ three-dimensional (3-D) capacitors (2Pr/spl ap/15 /spl mu/C/cm/sup 2/) than for 1000 /spl mu/m/sup 2/ 2-D capacitors (2Pr/spl ap/10 /spl mu/C/cm/sup 2/). Moreover, these 3-D capacitors are observed to be fatigue-free and imprint-free up to 10/sup 11/ cycles (5-V square pulses), and extrapolations of retention tests indicate less than 10% Pr loss after ten years at 85/spl deg/C, which shows that sidewall SBT retains the same excellent reliability properties as 2-D capacitors. We demonstrate in this paper that the negative signal-scaling trend can be halted using 3-D FeCAPs. To our knowledge, this paper is the first report on electrical and reliability properties of integrated 3-D FeCAPs, and is a starting point for future development work on densely scaled FeRAMs.
Trigger Factor-Mediated Prolyl Isomerization Influences Maturation of the <i>Streptococcus pyogenes</i> Cysteine Protease (2003)

Trigger factor, a ribosome-associated chaperone and peptidyl-prolyl cis-trans isomerase (PPIase), is essential for the secretion and maturation of the cysteine protease of the pathogenic gram-positive bacterium Streptococcus pyogenes. In the absence of trigger factor, the nascent protease polypeptide is not targeted to the secretory pathway. Some partial-function mutations restore targeting. However, the secreted protease does not efficiently mature into an enzymatically active form, suggesting that trigger factor has an additional role in protease biogenesis. Here, we show that, while not required for targeting, the PPIase activity of trigger factor is essential for maturation of the protease following its secretion from the bacterial cell. Site-specific mutations introduced into ropA, the gene which encodes trigger factor in S. pyogenes, produced mutant proteins deficient in PPIase activity. When these mutant alleles were used to replace the wild-type gene on the streptococcal chromosome, analysis of protease biogenesis revealed that, although the protease was secreted normally, it did not efficiently mature to an active form. Furthermore, mutation of a single proline residue in the protease prodomain suppressed the requirement for PPIase activity, suggesting that this residue is the target of trigger factor. These data support a model in which trigger factor-mediated prolyl isomerization influences the conformation of the prodomain, which in turn directs the protease into one of several alternative folding pathways.
An approach to chiral trisubstituted pyrrolidines by enolate Claisen rearrangement of azalactones derived from α-amino acids (1991)

Homologation of the β-amino acid derivatives 17a, 27a and 27b by N-alkylation using the cis-butenyl chloride 18 has been used to obtain the hydroxy acids 19b, 28c and 28d which were then converted into the 9-membered azalactones 20,29a and 29b using Mukaiyama's reagent, 2-chloro-1-methylpyridinium iodide. Enolate Claisen rearrangements of these macrolides were then effected using a ‘pre-mix’ method in which the base (LDA) and the trapping agent (TBDMSCI) were mixed at low temperature before addition of these substrates and took place on warming to ambient temperature. Rearrangement of the azalactone 20 gave only the cis-3,4-disubstituted pyrrolidine 21a while rearrangements of the chiral lactones 29 led to the chiral trisubstituted pyrrolidines 30 in an enantiospecific fashion, via a boat-like transition state (e.g. 31).
Accurate constrained pose estimation for small objects (2013)

The paper proposes a novel method for accurate pose estimation of small objects. A range sensor is used to find object orientation that constraints a PnP solver. The method finds the global minimum of a cost function (as opposed to traditional PnP algorithms) in closed form. This approach was used to enable robust robotic operation with sub millimeter precision.
The Impact of Amino Acid Variability Defines a Functional Distance Predictive of Permissive HLA-DPB1 Mismatches in Hematopoietic Cell Transplantation (2015)

A major challenge in unrelated hematopoietic cell transplantation (HCT) is the prediction of permissive HLA mismatches, i.e. those associated with lower clinical risks compared to their non-permissive counterparts. For HLA-DPB1, a clinically prognostic model has been shown to be matching for T-cell epitope (TCE) groups assigned by crossreactivity of T-cells alloreactive to HLA-DPB1*09:01, however the molecular basis of this observation is not fully understood. Here we have mutated amino acids (aa) in 10 positions of HLA-DPB1*09:01 to other naturally occurring variants, expressed them by lentiviral vectors in B cell lines and quantitatively measured allorecognition by 17 CD4+ T-cell effectors from 6 unrelated individuals. A significant impact on the median alloresponse was observed for peptide contact positions 9, 11, 35, 55, 69, 76 and 84, but not for positions 8, 56 and 57 pointing away from the groove. A score for the “functional distance” (FD) from HLA-DPB1*09:01 was defined as the sum of the median impact of polymorphic aa in a given HLA-DPB1 allele on T-cell alloreactivity. Established TCE group assignment of 23 alleles correlated with FD scores of ≤0.5, 0.6-1.9 and ≥2 for TCE groups 1, 2 and 3, respectively. Based on this, prediction of TCE group assignment will be possible for any given HLA-DPB1 allele. In silico TCE group classification was performed for currently 328 HLA-DPB1 alleles encoding distinct proteins for which T-cell crossreactivity patterns are unknown, with subsequent functional confirmation for 7/7 of them. These findings have practical implications for the applicability of TCE group matching in unrelated HCT, and provide new insights into the molecular mechanisms underlying this model. The innovative concept of FD opens new potential avenues for risk prediction in unrelated HCT.
Reaction of 5-trifluoromethyl-2′-deoxyuridine and 1-methyl-5-trifluoromethyluracil with methoxyamine: model studies for the interaction between thymidylate synthetase and 5-trifluoromethyl-2′-deoxyuridine 5′-phosphate (1987)

The reaction of 5-trifluoromethyl-2′-deoxyuridine (CF3dUR) and 5-trifluoromethyl-1-methyluracil (1-MCF3U) with methoxyamine in aqueous solution was studied to provide insight into the mechanism of inhibition of thymidylate synthetase by 5-trifluoromethyl-2′-deoxyuridine 5′-phosphate. 5-(Methoxyiminofluoromethyl)-2′-deoxyuridine (4b) and 5-(methoxyiminomethoxyaminomethyl)-2′-deoxyuridine (8b) were the products of the reactions of CF3dUR with methoxyamine. No other major product was detected by radiochromatography of [6-3H]CF3dUR after treatment with methoxyamine. The decrease in CF3dUR on treatment with methoxyamine followed pseudo-first-order kinetics, and (4b) and (8b) were formed sequentially, in that order. At pH 7.5 and 37 °C in 0.5M methoxyamine, the pseudo-first-order rate constant, kobs, for the decrease in CF3dUR (0.4 mM) was 0.355 h–1 and that for the decrease in (4b)(0.4 mM) was 0.06 h–1. The kobs for the decrease in CF3dUR at 37 °C had an optimum at pH 7.5; it was 0.355 h–1 with 0.5M methoxyamine. Increasing the concentration of methoxyamine at pH 7.5 resulted in greater increases in the rate of CF3dUR degradation than expected for a first-order reaction. This suggests that more than one molecule of methoxyamine participates in the degradation of CF3dUR. 1-MCF3U Reacted with methoxyamine to give 5-(methoxyiminofluoromethyl)-1-methyluracil (4a) and 5-(methoxyiminomethoxyaminomethyl)-1-methyluracil (8a) as products. Under acidic conditions, (4a) was converted into 5-(N-methoxycarbamoyl)-1-methyluracil. The formation of (4a) and (4b) as products of these reactions provides evidence for the formation of a highly reactive intermediate with an exocyclic difluoromethylene group at the 5 position which subsequently reacts with methoxyamine. An analogous mechanism was proposed for the inhibition of thymidylate synthetase by 5-trifluoromethyl-2′-deoxyuridine 5′-phosphate in which a nucleophilic group of the active site of the enzyme participates in the activation of the trifluoromethyl group.
High efficient integrated power receiver for a Qi compliant Wireless Power Transfer system (2016)

Wireless Power Transfer (WPT) is an emerging technology with a huge variety of possible applications, including wireless charging of mobile devices like smart-phones or tablet computers. In this work, a WPT receiver system integrated on a silicon chip is proposed to maximize the efficiency of the system. The presented chip is produced in a low cost standard 130 nm CMOS process with a high voltage extension. This enables the on-chip integration of a full bridge rectifier with 12V power MOSFETs. A prototype system, designed for the use in mobile applications, has been developed based on the Qi standard specifications. Different control strategies for the rectifier have been implemented and compared regarding their impact on the overall receiver system efficiency. The fully-active rectifier control technique enables the WPT system to decrease its losses and hence increase the system efficiency by more than 16% when compared to a passive approach. The experimental results confirm that the presented system is able to obtain a system efficiency of up to 88% at an output power of 1.8W.
Bounds on the belief propagation threshold of non-binary LDPC codes (2012)

We consider LDPC code ensembles over non-binary Galois fields, when used for transmission over arbitrary memoryless channels. Belief propagation decoding for these codes has been shown to achieve excellent results. However, computing the decoding threshold using density evolution is usually impractical, since one needs to propagate multi-dimensional probability distributions, and Monte Carlo simulations are required instead. By considering the evolution of the message Bhattacharyya parameter and the message expected value parameter we derive a simple lower bound on the performance of the algorithm. This bound applies for both regular and irregular non-binary LDPC ensembles.
Asymmetric Palladium-Catalyzed [3+2] Cycloaddition (2006)

[3+2] Cycloadditions provide a cyclopentane moiety that is present in a large number of natural products. Previously the formation of stereocenters utilizing palladium-catalyzed [3+2] cycloadditions relied on a chiral auxillary due to the distal location of the phosphine ligands to the enantiodetermining bond formation. Only one other case of asymmetric palladium-catalyzed [3+2] trimethylenemethane cycloaddition has been reported with ee values of 4-78% ( A. Yama­moto et al. Tetrahedron Lett. 1989, 30, 375-378).
Multicellular piezoelectric actuator for setting in motion fluids, and heat exchange enhancement (2013)

11th IEEE International Workshop of Electronics, Control, Measurement, Signals and their Application to Mechatronics (ECMSM), ENSEEIHT Engn Sch, Toulouse, FRANCE, JUN 24-26, 2013
High lytic activity against human leukemia cells after activation of allogeneic NK cells by IL-12 and IL-2. (1996)

IL-12 is a novel cytokine with interesting features regarding its potential usefulness in peripheral blood stem cell transplantation and leukemia immunotherapy. We used cryopreserved leukemia cells of 18 patients with acute myelogenous (n= 14) or lymphocytic (n= 4) leukemia to investigate the effect of IL-12, alone or in combination with IL-2, on the cytolytic activity of NK cells against human leukemia targets. Effector cells were peripheral blood mononuclear cells from healthy donors which were depleted from CD3+ T cells by immunomagnetic separation. CD3-negative effector cells (mainly CD56+ NK cells) were treated for 24 h with various concentrations of IL-2 (100 U/ml to 1000 U/ml) and IL-12 (1 U/ml to 100 U/ml). Cytotoxicity was measured in a 4 h 51Cr-release assay. Whereas a two-fold enhancement of cytotoxic activity was observed after incubation with optimal doses of IL-2 or IL-12, the combination of both cytokines (500 U/ml IL-2, 100 U/ml IL-12) increased the lytic activity more than six-fold. This effect was accompanied by increased expression of cellular adhesion molecules (CD2, CD18) and CD25 on CD56+ effector cells. Of 18 leukemias investigated, five were completely resistant to lysis by effector cells activated with IL-2 or IL-12 alone. In three of these five cases, however, high cytolytic activity was observed after coincubation with IL-2 and IL-12. In comparison to allogeneic NK cells, autologous cells of three patients in remission demonstrated significantly lower cytotoxic activity. No killing of nonmalignant cells (PHA blasts) by allogeneic NK cells was observed. Our data demonstrate that IL-12 can enhance or even induce MHC-unrestricted cytotoxicity of IL-2-activated allogeneic natural killer cells. Since IL-12 has also been shown to have stem-cell mobilizing capacities, it could be used for the recruitment of both stem cells and antileukemic effector cells in the context of peripheral blood stem cell transplantation.
Genetic, metabolomic and transcriptomic analyses of the de novo L-cysteine biosynthetic pathway in the enteric protozoan parasite Entamoeba histolytica (2017)

The de novo L-cysteine biosynthetic pathway is critical for the growth, antioxidative stress defenses, and pathogenesis of bacterial and protozoan pathogens, such as Salmonella typhimurium and Entamoeba histolytica. This pathway involves two key enzymes, serine acetyltransferase (SAT) and cysteine synthase (CS), which are absent in mammals and therefore represent rational drug targets. The human parasite E. histolytica possesses three SAT and CS isozymes; however, the specific roles of individual isoforms and significance of such apparent redundancy remains unclear. In the present study, we generated E. histolytica cell lines in which CS and SAT expression was knocked down by transcriptional gene silencing. The strain in which CS1, 2 and 3 were simultaneously silenced and the SAT3 gene-silenced strain showed impaired growth when cultured in a cysteine lacking BI-S-33 medium, whereas silencing of SAT1 and SAT2 had no effects on growth. Combined transcriptomic and metabolomic analyses revealed that, CS and SAT3 are involved in S-methylcysteine/cysteine synthesis. Furthermore, silencing of the CS1-3 or SAT3 caused upregulation of various iron-sulfur flavoprotein genes. Taken together, these results provide the first direct evidence of the biological importance of SAT3 and CS isoforms in E. histolytica and justify the exploitation of these enzymes as potential drug targets.
DYVERSO: A Versatile Multi‐Phase Position‐Based Fluids Solution for VFX (2016)

Abstract Many impressive fluid simulation methods have been presented in research papers before. These papers typically focus on demonstrating particular innovative features, but they do not meet in a comprehensive manner the production demands of actual VFX pipelines. VFX artists seek methods that are flexible, efficient, robust and scalable, and these goals often conflict with each other. In this paper, we present a multi‐phase particle‐based fluid simulation framework, based on the well‐known Position‐Based Fluids (PBF) method, designed to address VFX production demands. Our simulation framework handles multi‐phase interactions robustly thanks to a modified constraint formulation for density contrast PBF. And, it also supports the interaction of fluids sampled at different resolutions. We put special care on data structure design and implementation details. Our framework highlights cache‐efficient GPU‐friendly data structures, an improved spatial voxelization technique based on Z‐index sorting, tuned‐up simulation algorithms and two‐way‐coupled collision handling based on VDB fields. Altogether, our fluid simulation framework empowers artists with the efficiency, scalability and versatility needed for simulating very diverse scenes and effects.
A 78mW 11.1Gb/s 5-tap DFE receiver with digitally calibrated current-integrating summers in 65nm CMOS (2009)

Extending data rates to meet the I/O needs of future computing and network systems is complicated by limited channel bandwidth. While a DFE can be used to compensate channel distortion, its power dissipation reduces link energy efficiency, which is vitally important in complex systems. One way of reducing DFE power consumption is to use current-integrating summers. Previously published current-integrating DFEs operating above 5 Gb/s were demonstrated on simple test chips lacking support circuitry for CDR and DFE adaptation functions. The architecture presented here includes additional data paths based on current-integrating summers to realize a fully integrated RX with CDR and continuous DFE adaptation. The design also features a digital calibration loop for setting the summer bias currents so that high performance is achieved over process variations and different data rates.
Ruxolitinib treatment in a patient with neuromyelitis optica: A case report (2017)

Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune demyelinating disease of the CNS that predominantly affects the optic nerves and the spinal cord.1 Because of the severity and poor recovery of attacks, aggressive immunosuppressive agents are used early in the clinical course to reduce relapse frequency. Apart from classical immunosuppressant agents, biologicals such as rituximab, eculizumab, or tocilizumab have been used for relapse prevention.2 Based on retrospective data, 17–53% of patients have break-through relapses under the most commonly used treatments azathioprine, mycophenolate mofetil, or rituximab.3
Data from Precision Oncology Decision Support: Current Approaches and Strategies for the Future (2023)

&lt;div&gt;Abstract&lt;p&gt;With the increasing availability of genomics, routine analysis of advanced cancers is now feasible. Treatment selection is frequently guided by the molecular characteristics of a patient's tumor, and an increasing number of trials are genomically selected. Furthermore, multiple studies have demonstrated the benefit of therapies that are chosen based upon the molecular profile of a tumor. However, the rapid evolution of genomic testing platforms and emergence of new technologies make interpreting molecular testing reports more challenging. More sophisticated precision oncology decision support services are essential. This review outlines existing tools available for health care providers and precision oncology teams and highlights strategies for optimizing decision support. Specific attention is given to the assays currently available for molecular testing, as well as considerations for interpreting alteration information. This article also discusses strategies for identifying and matching patients to clinical trials, current challenges, and proposals for future development of precision oncology decision support. &lt;i&gt;Clin Cancer Res; 24(12); 2719–31. ©2018 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;