17 research outputs found
Design, synthesis and biological evaluation of biphenylamide derivatives as Hsp90 C-terminal inhibitors
No full textModulation of Hsp90 C-terminal function represents a promising
therapeutic approach for the treatment of cancer and neurodegenerative
diseases. Current drug discovery efforts toward Hsp90 C-terminal
inhibition focus on novobiocin, an antibiotic that was transformed into
an Hsp90 inhibitor. Based on structural information obtained during the
development of novobiocin derivatives and molecular docking studies,
scaffolds containing a biphenyl moiety in lieu of the coumarin ring
present in novobiocin were identified as new Hsp90 C-terminal
inhibitors. Structure activity relationship studies produced new
derivatives that inhibit the proliferation of breast cancer cell lines
at nanomolar concentrations, which corresponded directly with Hsp90
inhibition. (C) 2014 Elsevier Masson SAS. All rights reserved
Qing jing ye chu 清浄業処 in the Guan-Wu-Liang-Shou-Jing
No full textScholarly opinion differ as to whether the Guan wu liang shou jing was composed in India, China or Central Asia. The sutra's use of the term qing jing ye chu is cited as one evidence for the sutra's Indian origin. However, there are different position concerning the interpretation of this term, and no definitive theory has emerged. In my paper, I consider the various points of contention concerning this term. Dr. Hayashima Kyosho was the first to focus on the term qing jing ye chu to discuss the composition of the Guan jingo He took qing jing ye chu as being related to the term kammatthana (ye chu) used in Pali Buddhism to refer to the object of meditation or the method of meditative contemplation. For this reason, he argued that the sutra was composed in India. His theory was supported by Dr. Hirakawa Akira. In contrast, Dr. Fujita K6tatsu questioned the views of Drs. Hayashima and Hirakawa, arguing that there is no proof that ye chu is a translation of kammatthana, technical term distinctive to Pali Buddhism, and hence that it is impossible to argue for the Indian origin of the sutra on the basis of this term alone. The present author agrees with Dr. Fujita's view. To be more specific, there is no example of the Pali Buddhist term kammatthana, which refers to the object of meditation or its method, being translated as ye chu. It is quite possible that it is nothing more than the modern Japanese translation of kammatthana. In my paper, I consider the Guan jing's qing jing ye chu from the following four perspectives: (1) the usage of the terms qing jing ye and jing ye, (2) the usage of the term chu, (3) the context in which the term is used, and (4) the usage of the terms guan, jian 見 and xiang 想. My conclusion is as follows. When considering the Guan jing's qing jing ye chu, there is no need to stick to the Pali Buddhist kammatthana (object of meditation), as Drs. Hayashima and Hirakawa do. This is because the same meaning can be drawn from among the examples of the Guan jing. Therefore, it is impossible to use the term qing jing ye chu as evidence for the Indian origin of the Guan jingo But on the other hand, this is not to say that qing jing ye chu cannot be understood to mean the object of meditation. Thus, apart from the method of Drs. Hayashima and Hirakawa, it is possible to interpret qing jing ye chu as object of meditation from the examples of the Guan jingo In any case, it is not necessary to consider the Pali Buddhist term kammatthana as corresponding to the Guan jing's qing jing ye chu
Native vegetation of the southern forests : south-east highlands, Australian alps, south-west Slopes, and SE Corner bioregions
No full textThe Southern Forests study area covers an area of about six million hectares of south-eastern New South Wales, south of Oberon and Kiama and east of Albury and Boorowa (latitude 33° 02’–37 ° 06’ S; longitude 146° 56’ – 147° 06’ E). The total area of existing vegetation mapped was three million hectares (3 120 400 hectares) or about 50% of the study area. Terrestrial, wetland and estuarine vegetation of the Southern Forests region were classified into 206 vegetation groups and mapped at a scale between 1: 25 000 and 1: 100 000. The classification was based on a cluster analysis of detailed field surveys of vascular plants, as well as field knowledge in the absence of field survey data. The primary classification was based on 3740 vegetation samples with full floristics cover abundance data. Additional classifications of full floristics presence-absence and tree canopy data were carried out to guide mapping in areas with few full floristic samples. The mapping of extant vegetation was carried out by tagging vegetation polygons with vegetation codes, guided by expert knowledge, using field survey data classified into vegetation groups, remote sensing, and other environmental spatial data. The mapping of pre-1750 vegetation involved tagging of soils mapping with vegetation codes at 1: 100 000 scale, guided by spatial modelling of vegetation groups using generalised additive statistical models (GAMS), and expert knowledge. Profiles of each of the vegetation groups on the CD-ROM* provide key indicator species, descriptions, statistics and lists of informative plant species.
The 206 vegetation groups cover the full range of natural vegetation, including rainforests, moist eucalypt forests, dry shrub forests, grassy forests, mallee low forests, heathlands, shrublands, grasslands and wetlands. There are 138 groups of Eucalyptus forests or woodlands, 12 rainforest groups, and 46 non-forest groups. Of the 206 groups, 193 were classified and mapped in the study area. Thirteen vegetation groups were not mapped because of their small size and lack of samples, or because they fell outside the study area.
Updated regional extant and pre-1750 vegetation maps of southern New South Wales have been produced in 2005, based on those originally prepared in 2000 for the southern Regional Forest Agreement (RFA). Further validation and remapping of extant vegetation over 10% of the study area has subsequently improved the quality of the vegetation map, and removed some of the errors in the original version. The revised map provides a reasonable representation of native vegetation at a scale between 1: 25 000 and 1: 100 000 across the study area.
In 2005 native vegetation covers 50% of the study area. Environmental pressures on the remaining vegetation include clearing, habitat degradation from weeds and nutrification, severe droughts, changing fire regimes, and urbanisation. Grassy woodlands and forests, temperate grasslands, and coastal and riparian vegetation have been the most reduced in areal extent. Over 90% of the grassy woodlands and temperate grasslands have been lost. Conservation of the remaining vegetation in these formations is problematic because of the small, discontinuous, and degraded nature of the remaining patches of vegetation
Fantastická společnost: Společenská témata v zeměplošských knihách Terryho Pratchetta
No full textTerry Pratchett je známý především jako autor Úžasné Zeměplochy, což je řada čítající více než čtyřicet knih a několik povídek, které jsou zasazené do světa často popisovaného jako humoristická fantasy. Pratchett nicméně využívá tohoto žánru a jeho možností pro představivost a satiru, nejen aby vyprávěl příběhy, ale také aby zprostředkoval své vlastní názory na některá z největších společenských témat, jako je feminismus, náboženství nebo rasismus. Využívá stereotypních rolí a prostředí žánru fantasy a převrací je, aby ukázal na problémy skutečného světa. Nárůst obliby žánru fantasy, obzvláště satirické či humoristické, umožňuje Pratchettovi předkládat své názory širšímu publiku a vytvořit svět, který odráží a pokřivuje ten skutečný, aby ukázal důležitost a dopad těchto témat na společnost. Zasazení do fantasy světa navíc umožňuje Pratchettovi vytvořit svět, v němž tato témata mohou být volně ukázána a diskutována. První kapitola představuje Zeměplochu jakožto druhotný svět a představuje témata, která budou probírána. Druhá kapitola se zabývá mnoha formami rasismu na Zeměploše. První část kapitoly rozebírá standardní typ rasismu mezi člověkem a člověkem, což je ilustrováno na knize Jingo. Další podkapitola je pak věnována rasismu mezi lidmi a nelidmi a mezi trolly a trpaslíky, který je ilustrován...Terry Pratchett is best known as the author of Discworld, a series of more than forty books and several short stories set in a world that is often described as humorous fantasy. Pratchett, however, uses this genre and its imaginative and satiric opportunities not only to tell stories, but also to mediate his own views on some of the major social themes such as feminism, religion, or racism. He uses the stereotypical fantasy roles and settings and subverts them to point out real world problems and issues. The rise of popularity of the fantasy genre, especially satirical or humorous enables Pratchett to present his views to a broader audience, and to create a world mirroring and distorting the real one as to show the importance and impact of these issues on society. The fantasy setting also gives Pratchett the opportunity to create a world in which these themes can be illustrated and discussed freely. The first chapter sets up Discworld as a Secondary World and presents the topics that will be discussed. The second chapter deals with the many forms of racism in Discworld. The first part of the chapter discusses the standard, human-human type of racism, which is illustrated in the book Jingo. A subchapter is then dedicated to human-nonhuman and dwarf-troll racism, illustrated in Thud!, where Pratchett...Ústav anglofonních literatur a kulturDepartment of Anglophone Literatures and CulturesFaculty of ArtsFilozofická fakult
Fantastic Society: Social Themes in Terry Pratchett's Discworld
No full textTerry Pratchett is best known as the author of Discworld, a series of more than forty books and several short stories set in a world that is often described as humorous fantasy. Pratchett, however, uses this genre and its imaginative and satiric opportunities not only to tell stories, but also to mediate his own views on some of the major social themes such as feminism, religion, or racism. He uses the stereotypical fantasy roles and settings and subverts them to point out real world problems and issues. The rise of popularity of the fantasy genre, especially satirical or humorous enables Pratchett to present his views to a broader audience, and to create a world mirroring and distorting the real one as to show the importance and impact of these issues on society. The fantasy setting also gives Pratchett the opportunity to create a world in which these themes can be illustrated and discussed freely. The first chapter sets up Discworld as a Secondary World and presents the topics that will be discussed. The second chapter deals with the many forms of racism in Discworld. The first part of the chapter discusses the standard, human-human type of racism, which is illustrated in the book Jingo. A subchapter is then dedicated to human-nonhuman and dwarf-troll racism, illustrated in Thud!, where Pratchett..
The general as statesman : exploring the professional need for commanders to support viable political outcomes in peace and stability operations as typified by the UK military approach
No full textThe problem of theatre level politico-military arrangements during peace and stability operations is important because the intervening actors, working in complex and often ambiguous circumstances, need to calibrate the application of military and political means as a coherent interdependent whole. This is necessary in order to build peace, secure viable political outcomes and hence strategic successes; however it is not easy in practice. This thesis examines the hypothesis that, beyond their security-related tasks, military commanders should provide direct support to civilian interlocutors in order to facilitate and sustain the local political process. This requires military co-operation with other relevant actors, responsiveness to political direction and the specific shaping of military operations to impact decisively on political outcomes.
This work establishes that Western and United Nations doctrinal guidance extols political primacy and civil-military cooperation but does not fully explain the central importance of the political process, nor does it capture the potential peace building role of the military component. Analysis of practice in Kosovo, Iraq and Afghanistan, suggests that military commanders retain a uniquely influential position and have generally used their military means to positively influence political progress and help coordinate multi-dimensional plans. On occasion, to secure momentum and fill a void, commanders have quietly assumed a political function. Doctrine now needs to be refreshed to reflect practice. It should explain the military role in supporting the political process, elaborate the politico-military relationship as the inner core of a comprehensive approach to peace building and provide candid guidance on the difficulties to be expected where politico-military and coordination arrangements are incoherent. Moreover further work is needed on the wider application of this doctrine by the United Nations and the preparation of civilian leaders for politico-military relationships
Protocol for a multicentre, prospective observational study of elective neck dissection for clinically node-negative oral tongue squamous cell carcinoma (END-TC study)
No full textIntroduction In early-stage oral tongue squamous cell carcinoma (OTSCC), elective neck dissection (END) is recommended when occult lymph node metastasis is
suspected; however, there is no unanimous consensus on the risks and benefits of END in such cases. The management of clinically node-negative (cN0) OTSCC
remains controversial. This study, therefore, aimed to evaluate the efficacy of END and its impact on the quality of life (QoL) of patients with cN0 OTSCC.
Methods and analysis This is a prospective, multicentre, nonrandomised observational study. The choice of whether to perform END at the same time as resection of the primary tumour is based on institutional policy and patient preference. The primary endpoint of this study is 3-year overall survival. The secondary endpoints are
3-year disease-specific survival, 3-year relapse-free survival and the impact on patient QoL. Propensity score-matching analysis will be performed to reduce selection bias.
Ethics and dissemination This study was approved by the Clinical Research Review Board of the Nagasaki University. The protocol of this study was registered at the University Hospital Medical Information Network Clinical Trials Registry. The datasets generated during the current study will be available from the corresponding
author on reasonable request. The results will be disseminated internationally, through scientific and professional conferences and in peer-reviewed medical journals.BMJ open, 12 (9), art. no. e059615; 2022journal articl
« Retour à la France » et « Plus grande France »: Le fait colonial, composante de l’éblouissement tricolore et du malaise alsacien (à travers le cas de l’Exposition coloniale de Strasbourg en 1924)
No full textInternational audience„Erhänge dich, tapferer Joseph, wir haben in Douaumont gesiegt, während Du in Tuyen-Quang Siesta hieltest.“So beschreibt Jean Egen in „Die Linden von Lautenbach“ eine paradoxale Situation: sein Vater fahnenflüchtig von der deutschen Armee wird in das 3. Zouavenregiment eingezogen und in Indochina eingesetzt. Im Dorf erlebt er nicht die selbe Anerkennung wie die „Poilus“ die an der Westfront gekämpft haben. Die koloniale Gegebenheit ist ein Bestandteil der Nachkriegszeit im Elsass.Ziel der Ausstellung von 1924 ist es, die Elsässer davon zu überzeugen dass sie zu Frankreich gehören, da viele die sich 1870 für Frankreich entschieden hatten an den Überseeeroberungen beteiligt waren, und zusätzlich allen Franzosen die Reichtümer dieses Imperiums näher zu bringen. Denn es ist einer der Schlüssel zum Sieg und Frieden über Deutschland und bringt Paris keineswegs dazu seinen Blick von der „blauen Linie der Vogesen“ abzuwenden.Diese trikolore Exotik ruft heutzutage Unbehagen hervor. Die Ausstellung, aufgebaut wie menschlicher Zoo, hätte ein kollektives Unterbewusstsein herausgebildet das zum Ursprung eines elsässischen Rassismus geworden ist (Bourdieu 1999). Die koloniale Tatsache ist jedoch nicht neu im Elsass und auch eine deutsche Angelegenheit.Sie ist aber Teil des elsässischen Unmuts der Nachkriegszeit. Die „Wiederkehrer“ sind oft ehemalige Kolonisten, überzeugte Parteigänger der Assimilierung und geprägt von Stereotypen (mitunter ausgelöst durch Ausstellungen von Elsässern! - wie in Nancy 1909).“Go to hell, good old Joseph, we won the war while you were having a nap in Tuyen-Quang”.This is how in “Les tilleuls de Lautenbach” (1979) Jean Egen, the author, points out a real paradox; his father, who had deserted the German forces, had joined a French zouave regiment and been sent to Tonkin, was not considered a “genuine” combatant in his native village, contrary to those coming back from the European front.This shows that colonialism did play a role in after-war Alsace.Concerning that point, the 1924 Exhibition was meant to demonstrate the Alsatians’ belonging to France, many of those who had opted for France (after 1870) had participated in the conquest of overseas territories. It was also meant to raise public French awareness on the Empire’s resources. Far from distracting the Paris authorities from the Vosges borderline, it was one of the key factors of victory and peace for a province facing Germany.This sort of “jingo exoticism” is still inspiring a malaise. The 1924 Exhibition which appeared to be a “human zoo” is said (by sociologist Bourdieu in 1999) to have been the source of a collective subconscious leading to a form of “Alsatian racism”. And yet colonialism had existed in Alsace and in Germany previously.However, it was related to the Alsatian after-war malaise. Many a veteran was a former supporter of colonial assimilation based on stereotypes (sometimes due to exhibitions organized by Alsatians! e.g. in Nancy in 1909.« Pends-toi, brave Joseph, nous avons vaincu à Douaumont pendant que tu faisais la sieste à Tuyen-Quang ! »C’est ainsi que, dans Les Tilleuls de Lautenbach (1979), Jean Egen illustre un paradoxe : son père déserteur de l’armée allemande, versé au 3e Zouaves et affecté au Tonkin, n’apparaît pourtant pas un aussi « authentique » poilu dans son village que les combattants du front occidental. Aussi le fait colonial est une composante de l’après-guerre en Alsace.À ce titre, l’Exposition de 1924 veut convaincre les Alsaciens de leur appartenance à la France, nombre d’optants ayant participé aux conquêtes outre-mer, et sensibiliser tous les Français aux richesses de l’Empire. Loin de détourner Paris de la ligne bleue des Vosges, il est une des clés de la Victoire et de la paix face à l’Allemagne.Cet exotisme tricolore inspire aujourd’hui un malaise. L’Exposition, présentée comme un zoo humain, aurait formé un inconscient collectif source d’un racisme alsacien (Bourdieu, 1999). Le fait colonial est pourtant antérieur en Alsace, et aussi allemand.En revanche, il concerne un aspect du malaise alsacien d’après-guerre. Les « revenants » sont souvent d’anciens coloniaux tenants de l’assimilation et marqués par des stéréotypes (parfois d’ailleurs formés par des expositions d’Alsaciens ! – Nancy, 1909)
Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.
No full textThe prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity
The -ray spectrum of the core of Centaurus A as observed with H.E.S.S. and Fermi-LAT
No full textInternational audienceCentaurus A (Cen A) is the nearest radio galaxy discovered as a very-high-energy (VHE; 100 GeV–100 TeV) γ-ray source by the High Energy Stereoscopic System (H.E.S.S.). It is a faint VHE γ-ray emitter, though its VHE flux exceeds both the extrapolation from early Fermi-LAT observations as well as expectations from a (misaligned) single-zone synchrotron-self Compton (SSC) description. The latter satisfactorily reproduces the emission from Cen A at lower energies up to a few GeV. New observations with H.E.S.S., comparable in exposure time to those previously reported, were performed and eight years of Fermi-LAT data were accumulated to clarify the spectral characteristics of the γ-ray emission from the core of Cen A. The results allow us for the first time to achieve the goal of constructing a representative, contemporaneous γ-ray core spectrum of Cen A over almost five orders of magnitude in energy. Advanced analysis methods, including the template fitting method, allow detection in the VHE range of the core with a statistical significance of 12σ on the basis of 213 hours of total exposure time. The spectrum in the energy range of 250 GeV–6 TeV is compatible with a power-law function with a photon index Γ = 2.52 ± 0.13stat ± 0.20sys. An updated Fermi-LAT analysis provides evidence for spectral hardening by ΔΓ ≃ 0.4 ± 0.1 at γ-ray energies above 2.8+1.0−0.6 GeV at a level of 4.0σ. The fact that the spectrum hardens at GeV energies and extends into the VHE regime disfavour a single-zone SSC interpretation for the overall spectral energy distribution (SED) of the core and is suggestive of a new γ-ray emitting component connecting the high-energy emission above the break energy to the one observed at VHE energies. The absence of significant variability at both GeV and TeV energies does not yet allow disentanglement of the physical nature of this component, though a jet-related origin is possible and a simple two-zone SED model fit is provided to this end.Key words: gamma rays: galaxies / radiation mechanisms: non-thermal⋆ Corresponding author: H.E.S.S. and LAT Collaborations, e-mail: [email protected]; [email protected].† Funded by EU FP7 Marie Curie, grant agreement No. PIEF-GA-2012-332350
