gebhart/patrepeval huggingface dataset:
Melatonin Receptor Agonists: New Options for Insomnia and Depression Treatment (2010)

The circadian nature of melatonin (MLT) secretion, coupled with the localization of MLT receptors to the suprachiasmatic nucleus, has led to numerous studies of the role of MLT in modulation of the sleep-wake cycle and circadian rhythms in humans. Although much more needs to be understood about the various functions exerted by MLT and its mechanisms of action, three therapeutic agents (ramelteon, prolonged-release MLT, and agomelatine) are already in use, and MLT receptor agonists are now appearing as new promising treatment options for sleep and circadian-rhythm related disorders. In this review, emphasis has been placed on medicinal chemistry strategies leading to MLT receptor agonists, and on the evidence supporting therapeutic efficacy of compounds undergoing clinical evaluation. A wide range of clinical trials demonstrated that ramelteon, prolonged-release MLT and tasimelteon have sleep-promoting effects, providing an important treatment option for insomnia and transient insomnia, even if the improvements of sleep maintenance appear moderate. Well-documented effects of agomelatine suggest that this MLT agonist offers an attractive alternative for the treatment of depression, combining efficacy with a favorable side effect profile. Despite a large number of high affinity nonselective MLT receptor agonists, only limited data on MT₁ or MT₂ subtype-selective compounds are available up to now. Administration of the MT₂-selective agonist IIK7 to rats has proved to decrease NREM sleep onset latency, suggesting that MT₂ receptor subtype is involved in the acute sleep-promoting action of MLT; rigorous clinical studies are needed to demonstrate this hypothesis. Further clinical candidates based on selective activation of MT₁ or MT₂ receptors are expected in coming years.
ChemInform Abstract: Intramolecular Nitrone‐Quinone Cycloaddition. Formation of Isomeric Isoxazolidines by Kinetic and Thermodynamic Control. (1988)

Abstract The 2‐(2'‐formylbenzyl)‐p‐benzoquinones (I) react with N‐methylhydroxylamine (II) to give the nitrones (III).
A new algorithm for elimination of common subexpressions (1999)

The problem of an efficient hardware implementation of multiplications with one or more constants is encountered in many different digital signal-processing areas, such as image processing or digital filter optimization. In a more general form, this is a problem of common subexpression elimination, and as such it also occurs in compiler optimization and many high-level synthesis tasks. An efficient solution of this problem can yield significant improvements in important design parameters like implementation area or power consumption. In this paper, a new solution of the multiple constant multiplication problem based on the common subexpression elimination technique is presented. The performance of our method is demonstrated primarily on a finite-duration impulse response filter design. The idea is to implement a set of constant multiplications as a set of add-shift operations and to optimize these with respect to the common subexpressions afterwards. We show that the number of add/subtract operations can be reduced significantly this way. The applicability of the presented algorithm to the different high-level synthesis tasks is also indicated. Benchmarks demonstrating the algorithm's efficiency are included as well.
Linguistic Justice for Europe and for the World (2011)

Abstract In Europe and throughout the world, competence in English is spreading at a speed never achieved by any language in human history. This apparently irresistible growing dominance of English is frequently perceived and sometimes indignantly denounced as being grossly unjust. This book starts off arguing that the dissemination of competence in a common lingua franca is a process to be welcomed and accelerated, most fundamentally because it provides the struggle for greater justice in Europe and in the world with an essential weapon: a cheap medium of communication and of mobilisation. However, the resulting linguistic situation can plausibly be regarded as unjust in three distinct senses. Firstly, the adoption of one natural language as the lingua franca implies that its native speakers are getting a free ride by benefiting costlessly from the learning effort of others. Secondly, they gain greater opportunities as a result of competence in their native language becoming a more valuable asset. And thirdly the privilege systematically given to one language fails to show equal respect for the various languages with which different portions of the population concerned identify. This book spells out the corresponding interpretations of linguistic justice as cooperative justice, distributive justice and parity of esteem, respectively. It argues that linguistic diversity is not valuable in itself but it will nonetheless need to be protected as a by-product of the pursuit of linguistic diversity as parity of esteem.
hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway (2015)

The maintenance of genome stability is essential to prevent loss of genetic information and the development of diseases such as cancer. One of the most common forms of damage to the genetic code is the oxidation of DNA by reactive oxygen species (ROS), of which 8-oxo-7,8-dihydro-guanine (8-oxoG) is the most frequent modification. Previous studies have established that human single-stranded DNA-binding protein 1 (hSSB1) is essential for the repair of double-stranded DNA breaks by the process of homologous recombination. Here we show that hSSB1 is also required following oxidative damage. Cells lacking hSSB1 are sensitive to oxidizing agents, have deficient ATM and p53 activation and cannot effectively repair 8-oxoGs. Furthermore, we demonstrate that hSSB1 forms a complex with the human oxo-guanine glycosylase 1 (hOGG1) and is important for hOGG1 localization to the damaged chromatin. In vitro, hSSB1 binds directly to DNA containing 8-oxoguanines and enhances hOGG1 activity. These results underpin the crucial role hSSB1 plays as a guardian of the genome.
OUTILS ET MÉTHODOLOGIE D'ÉTUDE DES SYSTÈMES ÉLECTRIQUES POLYPHASÉS. GÉNÉRALISATION DE LA MÉTHODE DES VECTEURS D'ESPACE (2000)

La démarche générale du mémoire consiste à utiliser des outils mathématiques permettant d'élaborer un formalisme vectoriel applicable aux systèmes électriques au sens large. Ce formalisme bénéficie à la fois des propriétés graphiques et géométriques de la théorie des vecteurs d'espace qu'il généralise et de la puissance du calcul matriciel. Aussi, est-il tout particulièrement adapté à l'étude des systèmes polyphasés. Tout d'abord, on caractérise les modulateurs d'énergie indépendamment de leurs charges. Pour cela des espaces vectoriels leur sont associés ainsi que des familles de vecteurs qui les caractérisent. Il est possible alors de définir quel type de charge le modulateur est capable de contrôler. Les degrés de liberté de la commande trouvent également une formulation mathématique. Les exemples traités sont les onduleurs de tension monophasé et triphasé deux niveaux. L'approche conduit, dans le cas d'une commande aux valeurs moyennes, à un calcul original des durées de conduction des interrupteurs en utilisant la notion de barycentre.
Growth/differentiation factor 15 promotes EGFR signalling, and regulates proliferation and migration in the hippocampus of neonatal and young adult mice (2014)

The activation of epidermal growth factor receptor (EGFR) affects multiple aspects of neural precursor behaviour, including proliferation and migration. Telencephalic precursors acquire EGF responsiveness and upregulate EGFR expression at late stages of development. The events regulating this process and its significance are still unclear. We here show that in the developing and postnatal hippocampus (HP), growth/differentiation factor (GDF) 15 and EGFR are co-expressed in primitive precursors as well as in more differentiated cells. We also provide evidence that GDF15 promotes responsiveness to EGF and EGFR expression in hippocampal precursors through a mechanism that requires active CXC chemokine receptor (CXCR) 4. Besides EGFR expression, GDF15 ablation also leads to decreased proliferation and migration. In particular, lack of GDF15 impairs both processes in the cornu ammonis (CA) 1 and only proliferation in the dentate gyrus (DG). Importantly, migration and proliferation in the mutant HP were altered only perinatally, when EGFR expression was also affected. These data suggest that GDF15 regulates migration and proliferation by promoting EGFR signalling in the perinatal HP and represent a first description of a functional role for GDF15 in the developing telencephalon.
A Phase II Pharmacodynamic Study of Erlotinib in Patients with Advanced Non–Small Cell Lung Cancer Previously Treated with Platinum-Based Chemotherapy (2008)

In this study, EGFR FISH-positive status was associated with improved outcome after erlotinib therapy. Erlotinib led to reduced levels of p-EGFR, p-MAPK, and Ki-67, and stimulated apoptosis in tumor samples from patients with clinical benefit.
Facial Selectivity in the Diels–Alder Reactions of 2,2‐Disubstituted Cyclopent‐4‐ene‐1,3‐dione Derivatives and a Computational Examination of the Facial Selectivity of the Diels–Alder Reactions of Structurally Related Dienes and Dienophiles (2011)

Abstract The facial selectivity in the Diels–Alder reactions via endo transition states of the plane‐nonsymmetric dienophiles spiro[bicyclo[2.2.2]octane‐2,1′‐[3]cyclopentene]‐2′,5′‐dione ( 6 ) and spiro[bicyclo[2.2.1]heptane‐2,1′‐[3]cyclopentene]‐2′,5′‐dione ( 7 ) has been found to be very similar to the facial selectivity of reactions of cyclopentadienes fused to bicyclo[2.2.2]octane and bicyclo[2.2.1]heptane ( 4 and 5 ). This is strong evidence for steric control in their facial selectivities. Density functional computations involving the reactions of these compounds, as well as a series of conformationally locked model addends ( 26a – c and 27a – c ), revealed geometrical and energetic properties that confirmed that the facial selectivity is governed by steric effects. Steric interactions appeared to be the reason for the low endo / exo selectivity of dienophiles 6 , 7 , 2,2‐dimethylcyclopent‐4‐ene‐1,3‐dione ( 20 ), and spiro[5.4]dec‐8‐ene‐7,10‐dione ( 23 ).
ChemInform Abstract: COMPOUNDS WITH POTENTIAL ANTITUMOR ACTIVITY. III. 1‐SUBSTITUTED N,N′‐BIS‐2‐PYRIMIDINYL(OR PYRAZINYL)METHYLENEDIAMINES (1985)

A series of 1-substituted N,N'-di-2-pyrimidinyl (or pyrazinyl)methylenediamines were synthesized as potential antitumor agents. The compounds were tested on lymphocytic murine leukemia P 388. The active 1-(2-chlorophenyl)-N,N'-(2-pyrazinyl)methylenediamine (IX) was also tested on other experimental tumors.
Identification of candidates for tumor‐specific alternative splicing in the thyroid (2006)

Alternative splicing is the differential processing of exon junctions to produce a new transcript variant from one gene. Some aberrant splicing, however, has been shown to be cancer specific. Identification of these specific splice variations will provide important insight into the molecular mechanism of normal cellular physiology as well as the disease processes. To gain knowledge about whether alternative splicing is linked to thyroid tumorigenesis, we used our prediction database to select targets for analysis. Fifteen putatively new alternative splicing isoforms were selected on the basis of their expression in thyroid libraries and/or their origin in genes previously associated with carcinogenesis. Using a set of 66 normal, benign, and malignant thyroid tissue samples, new splicing events were confirmed by RT-PCR for 13 of 15 genes (a validation rate of 87%). In addition, new alternative splicing isoforms not predicted by the system and not previously described in public databases were identified. Five genes (PTPN18, ABI3BP, PFDN5, SULF2, and ST5) presented new and/or additional unpredicted isoforms differentially expressed between malignant and benign or normal thyroid tissues, confirmed by sequencing. PTPN18, ABI3BP, and PFDN5 revealed a statistically significant differential splicing profile. In addition, real-time PCR analysis revealed that expression of an alternative PFDN5 variant was higher in malignant lesions than in benign lesions or normal tissues.
A gelatin sponge implantation model in swine for the determination of local immune reactions. (2000)

For in vivo determination of innate and memory immune reactions we have implanted sterile gelatin sponges subcutaneously in swine for the monitoring of the following immunological parameters: 1. Analysis of local cell population phenotypes after vascularization of the gelatin sponges using flow cytometry. 2. Comparative analysis of sponge-infiltrating cells after loading with viral antigen in primed as well as naive animals. 3. Performance of reverse transcription quantitative competitive PCR (RT-qcPCR) for the detection of porcine cytokine mRNA indicative for IFN-gamma, IL-2, IL-4, IL-8 and IL-10. The in vitro analysis, e.g. by re-exposure to viral antigens, allows the determination of cytokine reaction patterns of sponge derived cells, draining lymph node cells as well as PBMC of the same individual. Studies of innate reactions and modulation of cellular infiltration in transplanted gelatin sponges are possible. Functional assays, e.g. cell-mediated cytotoxicity, antigen specific cell proliferation, using sponge-derived cells will provide additional information about the suitability of the model for example in vaccine potency tests.
Fabrication of large diameter TiO<SUB align="right">2 nanotube for bone morphogenetic protein-2 delivery (2014)

A localised and release-controlled carrier is essential to enhance the effectiveness of bone morphogenetic protein in bone regeneration and repair. In this work, TiO2 nanotubes with diameter larger than 350 nm were successfully fabricated for the first time by electrochemical method using diethylene glycol electrolyte. The diameter of the nanotubes reaches 550 nm and 680 nm at 90 V and 100 V, respectively. Their influences for bone morphogenetic protein-2 (BMP-2) delivery were investigated. In the study of protein release, fabricated TiO2 nanotubes have shown superhydrophilic properties that induce tight interaction with BMP-2. The release profile of the TiO2 nanotubes demonstrated a larger retention of protein, a more significant suppression of the initial burst and a better retardation of the release rate. Elution profile was also found to be dependent greatly on the density and the diameter of the nanotubes. Results have shown that the initial burst was larger for nanotubes with lower density and more proteins were released from nanotubes with larger diameter for the whole elution process.
Expression of Human CD4 and chemokine receptors in cotton rat cells confers permissiveness for productive HIV infection (2009)

These results further suggest that the development of transgenic cotton rats expressing human HIV-1 receptors may prove to be useful small animal model for HIV infection.
Efficient Sorting on the Tilera Manycore Architecture (2012)

We present an efficient implementation of the radix sort algorithm for the Tilera TILEPro64 processor. The TILEPro64 is one of the first successful commercial manycore processors. It is composed of 64 tiles interconnected through multiple fast Networks-on-chip and features a fully coherent, shared distributed cache. The architecture has a large degree of flexibility, and allows various optimization strategies. We describe how we mapped the algorithm to this architecture. We present an in-depth analysis of the optimizations for each phase of the algorithm with respect to the processor's sustained performance. We discuss the overall throughput reached by our radix sort implementation (up to 132 MK/s) and show that it provides comparable or better performance-per-watt with respect to state-of-the art implementations on x86 processors and graphic processing units.
Time-Resolved Numerical Study of Axial Gap Effects on Labyrinth-Seal Leakage and Secondary Flow in a LP Turbine (2013)

One of the most promising ways to improve the efficiency of modern turbomachinery is the reduction of secondary flow-structures and associated losses. A widely spread approach is the usage of shrouded airfoils in combination with labyrinth-seals. The disadvantage of this arrangement is a small but inevitable labyrinth-leakage flow that tends to increase the secondary-flow structures. The present work investigates how the axial gap of the blade rows and the corresponding shift of the labyrinth’s inlet and outlet influences leakage related effects on the flow-field and loss-generation. In order to capture the inter-blade and leakage interaction properly, time-resolved RANS computations of a 1 1/2 stage low pressure turbine have been performed. Besides accounting for labyrinth seals, fillets have been modeled. The axial gap is varied from 20% to 80% axial chord length. Clocking-effects induced by the axial gap variation are compensated. The leakage flow nearly retains the flow direction of the flow entering the blade row. In case of the largest axial gap, mixing causes the flow-angle of the leakage to tend towards that of the main-flow, thus reducing the incidence on the downstream blade row. Therefore, the turning of the low-momentum flow is increased compared to a small axial gap. This leads to a higher loading in the affected region and an increased passage vortex can be observed. By comparing the entropy generation of computations with and without labyrinth seals, the regions where leakage-related losses occur are identified and the relevant mechanisms are distinguished.
Personal Freedom and the Law in Tanzania (1977)

Journal Article Personal Freedom And The Law In Tanzania Get access Personal Freedom And The Law In Tanzania. By Martin Robert B.. Nairobi: Oxford University Press, 1974. Pp. 224. Robert B. Seidman Robert B. Seidman *Professor of Law, Boston University. Search for other works by this author on: Oxford Academic Google Scholar The American Journal of Comparative Law, Volume 25, Issue 3, Summer 1977, Pages 573–576, https://doi.org/10.2307/839695 Published: 01 July 1977
HIV-1 Ribonuclease H Inhibitory Phenolic Glycosides from <i>Eugenia hyemalis</i> (2008)

Three new galloyl arbutins, hyemalosides A-C (1-3), along with nine known compounds were isolated from the evergreen tree Eugenia hyemalis. The structures of compounds 1-3 were determined by analysis of NMR and MS data. Compounds 1-3 inhibited HIV-1 RNase H in vitro with IC50 values of 1.46, >18, and 1.19 microM, respectively. However, in a XTT-based cell viability assay using the human T-cell line CEM-SS infected with HIV-1 RT, none of the compounds inhibited the cytopathic effect of HIV-1 infection at the highest dose tested (20 microg/mL).
Accelerated deflation promotes homogeneous airspace liquid distribution in the edematous lung (2016)

Edematous lungs contain regions with heterogeneous alveolar flooding. Liquid is trapped in flooded alveoli by a pressure barrier-higher liquid pressure at the border than in the center of flooded alveoli-that is proportional to surface tension, <i>T</i> Stress is concentrated between aerated and flooded alveoli, to a degree proportional to <i>T</i> Mechanical ventilation, by cyclically increasing <i>T</i>, injuriously exacerbates stress concentrations. Overcoming the pressure barrier to redistribute liquid more homogeneously between alveoli should reduce stress concentration prevalence and ventilation injury. In isolated rat lungs, we test whether accelerated deflation can overcome the pressure barrier and catapult liquid out of flooded alveoli. We generate a local edema model with normal <i>T</i> by microinfusing liquid into surface alveoli. We generate a global edema model with high <i>T</i> by establishing hydrostatic edema, which does not alter <i>T</i>, and then gently ventilating the edematous lungs, which increases <i>T</i> at 15 cmH<sub>2</sub>O transpulmonary pressure by 52%. Thus ventilation of globally edematous lungs increases <i>T</i>, which should increase stress concentrations and, with positive feedback, cause escalating ventilation injury. In the local model, when the pressure barrier is moderate, accelerated deflation causes liquid to escape from flooded alveoli and redistribute more equitably. Flooding heterogeneity tends to decrease. In the global model, accelerated deflation causes liquid escape, but-because of elevated <i>T</i>-the liquid jumps to nearby, aerated alveoli. Flooding heterogeneity is unaltered. In pulmonary edema with normal <i>T</i>, early ventilation with accelerated deflation might reduce the positive feedback mechanism through which ventilation injury increases over time.<b>NEW & NOTEWORTHY</b> We introduce, in the isolated rat lung, a new model of pulmonary edema with elevated surface tension. We first generate hydrostatic edema and then ventilate gently to increase surface tension. We investigate the mechanical mechanisms through which <i>1</i>) ventilation injures edematous lungs and <i>2</i>) ventilation with accelerated deflation might lessen ventilation injury.
<i>Candida albicans</i>metabolite affects the cytoskeleton and phagocytic activity of murine macrophages (2008)

Candida albicans is the most common opportunistic fungal pathogen of humans, causing systemic disease in immunocompromised patients. Host resistance to C. albicans infections is mediated predominantly by neutrophils and monocytes/macrophages. We have previously shown that exposure of a human epithelial cell line (HEp2) to C. albicans or to a culture filtrate of C. albicans caused actin rearrangement in the HEp2 cells. Since shifting of actin from the filamentous to the globular form may be crucial to the activity of phagocytes, we assessed in the present study the effect of the C. albicans metabolite (lyophilized culture filtrate) on the cytoskeleton of murine peritoneal macrophages and on their phagocytic activity. Our results showed a significant decrease in phagocytosis of C. albicans, ranging from 53-63% and a 25% reduction for C. glabrata cells. Using confocal laser scanning microscopy an actin rearrangement in the macrophages could be demonstrated that may be associated with the decrease of phagocytosis. We also tested the effect of mannan and of the secreted aspartic proteinase (Sap) inhibitor--pepstatin, on the activity of the metabolite in order to define the putative component and found no influence. In conclusion, our data indicate that a C. albicans metabolite affects phagocytic activity of macrophages, probably by alterations in their cytoskeleton.
Team JSK at MBZIRC 2020: Interception of Fast Flying Target using Multilinked Aerial Robot (2021)

The JSK (Jouhou System Kougaku) team from The University of Tokyo was selected as one of the 32 finalist teams out of 134 applicants to participate in the second edition of the Mohamed Bin Zayed International Robotic Challenge (MBZIRC) held in 2020. One of the challenges (Challenge 1) required an aerial robot to detect, follow and catch a yellow ball hanging underneath a fast-moving drone. In this challenge, we developed an articulated aerial robot that could intercept the target. This study presents reliable vision-based detection, target-trajectory estimation, fast interception-planning, and -control. Furthermore, we discuss outdoor experiments for evaluating our hardware and software systems, as well as the competition results in Abu Dhabi. With our developed system, we achieved third place in Challenge 1, as one of only four teams in the entire competition to successfully intercept the moving target.