bluuebunny/crossref_metadata_2025_split huggingface dataset:
An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent
Authors: Willis Nicky J , Bayle Elliott D , Papageorgiou George , Steadman David , Aktinson Benjamin N , Mahy William , Fish Paul V 
Published: July 2019

Background: The carboxylesterase Notum has been shown to act as a key negative regulator of the Wnt signalling pathway by mediating the depalmitoleoylation of Wnt proteins. LP-922056 (1) is an orally active inhibitor of Notum. We are investigating the role of Notum in modulating Wnt signalling in the central nervous system and wished to establish if 1 would serve as a peripherally restricted control. An accessible and improved synthetic route would allow 1 to become more readily available as a chemical tool to explore the fundamental biology of Notum and build target validation to underpin new drug discovery programs.

Results: An improved, scalable synthesis of 1 is reported. Key modifications include: (1) the introduction of the C7-cyclopropyl group was most effectively achieved with a Suzuki–Miyaura cross-coupling reaction with MIDA-boronate 11 (5 → 6); and (2) C6 chlorination was performed with 1-chloro-1,2-benziodoxol-3-one (12) (6 → 7) as a mild selective electrophilic chlorination agent. This 7-step route has been reliably performed on large scale to produce multigram quantities of 1 in good efficiency and high purity. Pharmacokinetic studies in mouse showed CNS penetration of 1 is very low with brain:plasma concentration ratio of just 0.01. A small library of amides 17 were prepared from acid 1 to explore if 1 could be modified to deliver a CNS penetrant tool by capping off the acid as an amide. Although significant Notum inhibition activity could be achieved, none of these amides demonstrated the required combination of metabolic stability along with cell permeability without evidence of P-gp mediated efflux.

Conclusion: Mouse pharmacokinetic studies demonstrate that 1 is unsuitable for use in models of disease where brain penetration is an essential requirement of the compound but would be an ideal peripherally restricted control. These data will contribute to the understanding of drug levels of 1 to overlay with appropriate in vivo efficacy endpoints, i.e. the PK-PD relationship. The identification of a suitable analogue of 1 (or 17) which combines Notum inhibition with CNS penetration would be a valuable chemical probe for investigating the role of Notum in disease models.
Not a Simple Relationship between Neptune’s Migration Speed and Kuiper Belt Inclination Excitation
Authors: Volk Kathryn , Malhotra Renu 
Published: July 2019

Abstract
We present numerical simulations of giant planet migration in our solar system and examine how the speed of planetary migration affects inclinations in the resulting population of small bodies (test particles) scattered outward and subsequently captured into Neptune’s 3:2 mean motion resonance (the Plutinos), as well as the hot classical Kuiper Belt population. We do not find a consistent relationship between the degree of test particle inclination excitation and e-folding planet migration timescales in the range 5–50 Myr. Our results present a counterexample to Nesvorný's finding that the Plutino and hot classical inclinations showed a marked increase with increasing e-folding timescales for Neptune’s migration. We argue that these differing results are likely due to differing secular architectures of the giant planets during and after migration. Small changes in the planets’ initial conditions and differences in the numerical implementation of planet migration can result in different amplitudes of the planets’ inclination secular modes, and this can lead to different final inclination distributions for test particles in the simulations. We conclude that the observed large inclination dispersion of Kuiper Belt objects does not require Neptune’s migration to be slow; planetary migration with e-folding timescales of 5, 10, 30, and 50 Myr can all yield inclination dispersions similar to the observed Plutino and hot classical populations, with no correlation between the degree of inclination excitation and migration speed.
HATS-54b–HATS-58Ab: Five New Transiting Hot Jupiters Including One with a Possible Temperate Companion*
Authors: Espinoza N. , Hartman J. D. , Bakos G. Á. , Henning T. , Bayliss D. , Bento J. , Bhatti W. , Brahm R. , Csubry Z. , Suc V. , Jordán A. , Mancini L. , Tan T. G. , Penev K. , Rabus M. , Sarkis P. , de Val-Borro M. , Durkan S. , Lázár J. , Papp I. , Sári P. 
Published: July 2019

Abstract
We report the discovery by the HATSouth project of five new transiting hot Jupiters (HATS-54b through HATS-58Ab). HATS-54b, HATS-55b, and HATS-58Ab are prototypical short-period (P = 2.5–4.2 days, R

p
∼ 1.1–1.2

) hot Jupiters that span effective temperatures from 1350 to 1750 K, putting them in the proposed region of maximum radius inflation efficiency. The HATS-58 system is composed of two stars, HATS-58A and HATS-58B, which are detected thanks to Gaia DR2 data and which we account for in the joint modeling of the available data—with this, we are led to conclude that the hot Jupiter orbits the brighter HATS-58A star. HATS-57b is a short-period (2.35 day), massive (3.15

), 1.14

, dense (

) hot Jupiter orbiting a very active star (2% peak-to-peak flux variability). Finally, HATS-56b is a short-period (4.32 day), highly inflated hot Jupiter (1.7

, 0.6

), which is an excellent target for future atmospheric follow-up, especially considering the relatively bright nature (V = 11.6) of its F dwarf host star. This latter exoplanet has another very interesting feature: the radial velocities show a significant quadratic trend. If we interpret this quadratic trend as arising from the pull of an additional planet in the system, we obtain a period of

days for the possible planet HATS-56c, and a minimum mass of

. The candidate planet HATS-56c would have a zero-albedo equilibrium temperature of T
eq = 332 ± 50 K, and thus would be orbiting close to the habitable zone of HATS-56. Further radial-velocity follow-up, especially over the next two years, is needed to confirm the nature of HATS-56c.
Assessing the growth of Staphylococcus aureus and Escherichia coli on fruits and vegetables
Authors: Kothe Caroline I , Pessoa João P , Malheiros Patricia S , Tondo Eduardo C 
Published: July 2019

Introduction: The number of registered foodborne diseases involving fresh produce is a preoccupation in many countries. For this reason, the aim of this study was to better understand the growth of Staphylococcus aureus and Escherichia coli, two indicators of hygienic and sanitary conditions, on fruits and vegetables that were exposed at different temperatures.
Methodology: The main salads served at the buffets of commercial restaurants were artificially contaminated with separate pools of both pathogens and subsequently exposed at 10, 20 and 30 °C and at different time intervals. Then, the growth potential of S. aureus and E. coli on each fruit and vegetable was determined.
Results: There was no significant S. aureus and E. coli growth on all evaluated foods exposed at 10 °C until 6 hours. When comparing both microorganisms, E. coli demonstrated higher growth potential than S. aureus on all analysed salads. Peculiarly, E. coli had the highest growth rate for the tomato (α = 6.43 at 30 °C), a fruit with low pH.
Conclusion: We suggest that fruits and vegetables should be distributed at temperatures equal to or lower than 10 °C and should not be kept for more than 2 hours at room temperature.
Investigation of carbapenemase and mcr-1 genes in carbapenem-resistant Klebsiella pneumoniae isolates
Authors: Arabacı Çiğdem , Dal Tuba , Başyiğit Tuğcan , Genişel Neslihan , Durmaz Rıza 
Published: July 2019

Introduction: Carbapenem-resistant Klebsiella pneumoniae are a major problem. We aimed to investigate carbapenemase-encoding genes and transferable mcr-1 genes among 57 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from hospitalized patients.
Methodology: Antibiotic susceptibility tests were performed by Phoenix (BD). Results for ertapenem and colistin were confirmed by gradient diffusion and microdilution methods. Carbapenemase and mcr-1 genes were investigated by Polymerase Chain Reaction (PCR).
Results: Thirty-two (56.14%) isolates were from intensive care units (ICU). Antibiotic resistance rates by Phoenix: 52.63% for amikacin; 73.69% trimethoprim sulfamethoxazole; 91.23% cefepime; 82.46% tigecycline; 59.65% colistin. Carbapenemases positivity: 82.45% (47) for blaOXA-48, 40.35% (23) blaOXA-55, 3.50% (2) blaOXA-51, 1.75% (1) blaOXA-23, 1.75% (1) blaOXA-24, 1.75% (1) blaIMP. blaOXA-58, blaKPC, blaNDM-1, and blaVIM were not detected. Twenty (35.08%) isolates had both blaOXA-48 and blaOXA-55. Three isolates were mcr-1 (+) and blaOXA-48 (+). One mcr-1 (+) isolates was blaOXA-51 (+). One colistin sensitive isolate determined by Phoenix, was found colistin resistant by microdilution.
Conclusion: OXA-48 and OXA-55 co-harboring isolates and mcr-1 gene (+) isolates were spreading. Automated colistin susceptibility results should be confirmed by microdilution method. Resistance mechanisms in Enterobacteriaceae should be determined and the isolates should be monitored by molecular epidemiological methods. Effective infection control measures will contribute to reduce risk of antibiotic resistant bacterial infections and dissemination of antibiotic resistance.
IL-28B genotypes as predictors of long-term outcome in patients with hepatitis C-related severe liver injury
Authors: Jordovic Jelena , Simonovic-Babic Jasmina , Gasic Vladimir , Kotur Nikola , Zukic Branka , Pavlovic Sonja , Lazarevic Ivana , Karalic Danijela , Katanic Natasa , Nikolic Natasa , Urosevic Aleksandar , Nestorov Jelena , Delic Dragan , Bojovic Ksenija 
Published: July 2019

Introduction: Patients with severe fibrosis or cirrhosis are at high risk for liver-related complications, even after successful antiviral treatment and/or regression of fibrosis. These are the first published results concerning the role of IL-28B genotypes as predictors of the durability of sustained virological response (SVR) and long-term outcome, in patients with baseline severe fibrosis and cirrhosis caused by hepatitis C (HCV) infection.
Methodology: Genetic testing for three different single nucleotide polymorphisms (SNP) near the IL28B gene, rs12979860, rs12980275 and rs8099917, was performed in 42 patients with HCV-related advanced fibrosis and cirrhosis, who achieved SVR after successful interferon-based treatment. Baseline clinical and laboratory parameters were analysed, as well as IL28B genotype association with late virological relapse, fibrosis progression and clinical outcomes.
Results: The most prevalent genotypes in all three tested SNP positions were: CCrs12979860 genotype in 69% of patients, GTrs8099917 in 78.6% and GGrs12980275 in 47.6% of patients. The presence of IL28B CCrs12979860 genotype was identified as a negative predictor of late virological relapse. Further analysis did not confirm the association of other IL28B genotypes with the progression of fibrosis and clinical outcomes.
Conclusions: Varying long-term prognosis in patients with HCV-related severe fibrosis and cirrhosis is due to multiple interactions between host genetic factors, virus and environment. These are first published results demonstrating the significance of IL28B CCrs12979860 genotype as a negative predictor of late virological relapse. A further investigation concerning genetic factors is necessary to identify patients under risk for late relapse, complications and unfavorable outcomes, so that they can be reevaluated and offered new treatment options.
Près des pistes, la grande loterie de la justice
Authors: Barbe Faustin , Hergon Flora , Hugues Fanny , Geoffrenet Marceau , Le Lay Guillaume , Paja Alfrida 
Published: July 2019

« Victime », « Migrant », « Voyageur » : telles sont les catégories attribuées aux personnes étrangères dès leur arrivée à l’aéroport de Roissy, et qui vont déterminer leur destin. Suivant le profil qu’on leur accole, elles seront autorisées à séjourner en France, retenues en zone d’attente pour des examens complémentaires de leur situation, voire expulsées. Or ces catégories n’ont rien d’anodin ni de scientifique, mais tout à voir avec le « risque migratoire » que la police des frontières traque sans relâche.
Sufficientarian-Libertarianism and Basic Income
Authors: Fukuhara Akio 
Published: July 2019

Le présent essai soutient une position qui s’inscrit dans le courant dit « libertarien » tout en explorant les implications de la politique qui prône un revenu de base et suscite présentement un débat vivace à travers le monde, y compris au Japon. Il existe diverses formes d’éthique libertarienne. Ici, dans la lignée de Nozick, la « propriété de soi » et la clause lockéenne sont reconnus comme deux rouages essentiels de l’argumentation qui conduit à leur ajustement en vue d’une éthique spécifique. Nous examinons comment Nozick défend la « propriété de soi » : son argumentation respecte la séparabilité des personnalités et elle accorde une grande importance à l’élaboration libre par chacun d’un mode de vie lui convenant. Une fois révisées la nature du droit dit « d’appropriation » et de la clause dite « lockéenne », nous réinterprétons cette position centrale des libertariens en considérant la position fondamentale de Nozick comme prenant appui sur une conception égalitariste de la notion de dispositions suffisantes. Les avantages de cette position sont dus non seulement à l’adéquation entre la théorie et un principe de distribution, mais encore à l’image de l’individu doté d’une propriété de soi réaffirmée, dans la vision libertarienne que Nozick déploie. Cette approche fournit les bases de la morale d’une activité libre exercée sur les marchés : ce point est essentiel pour les auteurs libertariens, qui refusent toute aliénation de la propriété privée et toute redistribution. Une version simplifiée du revenu de base une fois définie en l’adaptant à des cadres variés, dont le cadre japonais nous mène à conclure que le revenu de base, quoique séduisant, est partiellement conforme aux thèses libertariennes et qu’une version minimale serait à retenir.
A Theory of Real Freedom: Toward a Growth-Oriented Liberalism
Authors: Hashimoto Tsutomu 
Published: July 2019

Quelle est la nature de la liberté réelle (réelle) dans notre société ? Je présenterai ici une nouvelle théorie du libéralisme que j’appelle « libéralisme orienté vers la croissance ». D’abord, j’examine le concept de liberté positive et négative d’Isaiah Berlin et je pose la question fondamentale en matière de liberté, à savoir que la liberté est un idéal paradoxal . J’identifierai deux paradoxes : l’un porte sur la liberté ordinaire et les valeurs sophistiquées, l’autre sur la question de la libération et de l’apathie des individus ou des populations. Comment pouvons-nous surmonter ces paradoxes ? Pour répondre à cette question, j’examinerai l’argument de Charles Taylor sur la liberté positive (liberté) et en élargirai les implications. Le paradoxe est d’autant plus lorsqu’il s’agit de communautés, comme la société japonaise. Au-delà du mode de pensée communautaire de Taylor, par exemple, je construis une nouvelle théorie de la liberté en proposant de suivre trois principes : le principe de la vertu (estime de soi), le principe du changement générateur et le principe de la différenciation. Je soutiens que la pierre de touche d’une société libre dépend de la façon dont nous concevons notre gouvernance sociale sur la base de ces principes. JEL Codes : Z10, B25.
Continuité et rupture dans les théories socio-économiques de Yasuma Takata
Authors: Kitajima Shigeru , Yokota Hiroki 
Published: July 2019

Nous avons trois objectifs dans cet article. Le premier est de montrer la pensée et le comportement de Yasuma Takata (1883-1972), auteur quasiment inconnu en Occident, mais qui donna pourtant au Japon ses premières théories sociologiques et socio-économiques générales. Le deuxième est d’examiner comment ces pensée et comportement sont liés à la responsabilité de la guerre dans la seconde guerre mondiale. Le troisième consiste à montrer que cette pensée est profondément connectée au courant de la pensée japonaise moderne à travers la théorie de Maruyama et des opinions des Ôe et Kawabata. Classification JEL : B15, B31, N45
À propos des errances dans la réception japonaise de l’œuvre d’Adam Smith
Authors: Muramatsu Masataka 
Published: July 2019

La réception d’Adam Smith au Japon est l’occasion d’expériences variées de comparaison internationale et interdisciplinaire. Smith paraît ce que l’on pourrait déjà nommer un « philosophe-économiste » tout en étant regardé comme « l’économiste par excellence » et, au Japon aussi, le « professeur de tous les économistes ». Il continue d’y être considéré comme un représentant du libéralisme économique, ce qui prête à des erreurs et des errances que cet essai entend dénoncer. L’objet principal de ce texte est de présenter comment la doctrine smithienne a été conceptualisée au Japon sur les plans historique, social et intellectuel : ce n’est pas seulement la réception de sa théorie économique, mais aussi la relation à sa philosophie qui est questionnée.
Quest for the Consciousness of Historicity by Kiyoshi Miki – Hermeneutical Anthropology and Philosophy of History
Authors: Yagi Kiichirô 
Published: July 2019

Kiyoshi Miki (1897-1945) fut le philosophe dominant des débuts de l’ère Showa (à partir de 1925) au Japon. Il entama sa réflexion en appliquant l’herméneutique phénoménologique aux pensées de Pascal et de Marx puis il se mit en quête d’une philosophie de l’histoire où la conscience présente de l’historicité est centrale. Il allait reconnaître un type d’humanité dotée à la fois de pathos et du logos qu’il réinteprétait. Son engagement dans le movement de la culture prolétarienne et dans les fondements philosophques du Mouvement de l’Ordre Nouveau fut un double échec. Dans sa poursuite d’une philosophie de l’histoire, qui donne sa place aux considerations économiques, en même temps que d’une anthropologie philosophique, Miki a reflété la difficulté de mener une réflexion philosophique sereine durant cette période au Japon. JEL Codes : B24, B31
High Temperature Memory Design, Implementation, and Characterization in 1μm SiC CMOS Technology
Authors: Abbasi Affan , Murphree Robert , Roy Sajib , Suggs Marvin , Fraley John , Mantooth H. Alan , Di Jia , Erlbacher Tobias 
Published: July 2019

Abstract
Electronic systems capable of withstanding high temperature environments are in high demand in various applications such as logging-while-drilling (LWD) systems and embedded electronics which are in the core of gas turbine engine controls. Designing memory that can process massive amounts of data in harsh environments while consuming low power opens doors for next generation, smart, high temperature electronic systems. In this work, a CMOS based six transistor (6T) static random-access memory (SRAM) cell is designed and implemented in a state-of-the-art SiC 1μm triple well CMOS process. The designed SiC SRAM cell performance has been characterized for different values of cell ratios (CR) [0.5, 0.6, 1, 1.5, 2, 2.5] and pull-up ratios (PR) [1, 2, 3, 4, 5, 6] to determine the cell size with optimal performance parameters. Static noise margin (SNM) values for the different combinations of CR and PR are calculated using the model developed by Seevinck, et. al. [13]. The highest SNM values observed at 25°C and 300°C are 4.71 V and 4.65 V, respectively. Read static noise margin (RSNM) values of 1.94 V and 1.90 V are achieved at 25°C and 300°C, respectively. Analysis of measured data shows that the optimum cell size is with a CR of 2.5 and a PR of 6. However, these results are significantly impacted by highly resistive ohmic contacts.
Strategies for ending tuberculosis in the South-East Asian Region
Authors: Arinaminpathy Nimalan , Mandal Sandip , Bhatia Vineet , McLeod Ross , Sharma Mukta , Swaminathan Soumya , Hyder Khurshid Alam , Mandal Partha Pratim , Sarkar Swarup Kumar , Singh Poonam Khetrapal 
Published: July 2019

Background & objectives:
To support recent political commitments to end tuberculosis (TB) in the World Health Organization South-East Asian Region (SEAR), there is a need to understand by what measures, and with what investment, these goals could be reached. These questions were addressed by using mathematical models of TB transmission by doing the analysis on a country-by-country basis in SEAR.

Methods:
A dynamical model of TB transmission was developed, in consultation with each of the 11 countries in the SEAR. Three intervention scenarios were examined: (i) strengthening basic TB services (including private sector engagement), (ii) accelerating TB case-finding and notification, and (iii) deployment of a prognostic biomarker test by 2025, to guide mass preventive therapy of latent TB infection. Each scenario was built on the preceding ones, in successive combination.

Results:
Comprehensive improvements in basic TB services by 2020, in combination with accelerated case-finding to increase TB detection by at least two-fold by 2020, could lead to a reduction in TB incidence rates in SEAR by 67.3 per cent [95% credible intervals (CrI) 65.3-69.8] and TB deaths by 80.9 per cent (95% CrI 77.9-84.7) in 2035, relative to 2015. These interventions alone would require an additional investment of at least US$ 25 billion. However, their combined effect is insufficient to reach the end TB targets of 80 per cent by 2030 and 90 per cent by 2035. Model projections show how additionally, deployment of a biomarker test by 2025 could end TB in the region by 2035. Targeting specific risk groups, such as slum dwellers, could mitigate the coverage needed in the general population, to end TB in the Region.

Interpretation & conclusions:
While the scale-up of currently available strategies may play an important role in averting TB cases and deaths in the Region, there will ultimately be a need for novel, mass preventive measures, to meet the end TB goals. Achieving these impacts will require a substantial escalation in funding for TB control in the Region.