Predominant association of HLA-B*2704 with ankylosing spondylitis in Chinese Han patients

The HLA-B27 subtypes have a varied racial and ethnic prevalence throughout the world. However, the association of B27-subtypes with ankylosing spondylitis (AS) in the mainland China is unknown. To determine the association of B27-subtypes with AS in the Mainland Chinese Han population, a total of unrelated 153 patients with AS were enrolled in a large case-control association study, and 1545 unrelated, healthy, ethnically matched blood donors were included as controls. The genotyping of B27 and its subtypes was performed using the polymerase chain reaction with sequence specific primers (PCR-SSP). A total of 130 (84.97%) AS patients and 61 (3.95%) healthy controls were B27 positive. Three B27-subtypes, B*2704, B*2705 and B*2710, were further identified, of which both B*2704 and B*2705 were strongly AS associated. B*2710 was only detected in one AS patient and two other healthy controls. Considering only B27-positive cases and controls, a statistically different frequency of B27-subtypes was observed, with an over-representation of B*2704 (P = 0.018). B*2704 was clearly more strongly associated than B*2705 with AS [odds ratio (OR) = 2.4, P = 0.011]. Furthermore, a combined analysis including three previous studies of B27-subtype distributions in Chinese AS cases confirmed the stronger association of B*2704 with AS than B*2705 (OR = 2.5, P = 0.00094).

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

The ascidian natural product eusynstyelamide B is a novel topoisomerase II poison that induces DNA damage and growth arrest in prostate and breast cancer cells

As part of an anti-cancer natural product drug discovery program, we recently identified eusynstyelamide B (EB), which displayed cytotoxicity against MDA-MB-231 breast cancer cells (IC50 = 5 μM) and induced apoptosis. Here, we investigated the mechanism of action of EB in cancer cell lines of the prostate (LNCaP) and breast (MDA-MB-231). EB inhibited cell growth (IC50 = 5 μM) and induced a G2 cell cycle arrest, as shown by a significant increase in the G2/M cell population in the absence of elevated levels of the mitotic marker phospho-histone H3. In contrast to MDA-MB-231 cells, EB did not induce cell death in LNCaP cells when treated for up to 10 days. Transcript profiling and Ingenuity Pathway Analysis suggested that EB activated DNA damage pathways in LNCaP cells. Consistent with this, CHK2 phosphorylation was increased, p21CIP1/WAF1 was up-regulated and CDC2 expression strongly reduced by EB. Importantly, EB caused DNA double-strand breaks, yet did not directly interact with DNA. Analysis of topoisomerase II-mediated decatenation discovered that EB is a novel topoisomerase II poison.

Spatial B-jump at sudden channel enlargements with abrupt drop

An analytical and experimental study of the hydraulic jump in stilling basins with abrupt drop and sudden enlargement, called the spatial B-jump here, is carried out for finding the sequent depth ratio and resulting energy dissipation. The spatial B-jump studied has its toe downstream of the expansion section, and the stream lines at the toe are characterized by downward curvature. An expression is obtained for the sequent depth ratio based on the momentum equation with suitable assumptions for the extra pressure force term because of the abrupt drop in the bed and sudden enlargement in the basin width. Predictions compare favorably with experiments. It is shown that the spatial B-jump needs less tailwater depth, thereby enhancing the stability of the jump when compared either with spatial jump, which forms in sudden expanding channels, or with B-jump, which forms in a channel with an abrupt drop in bed. It is also shown that there is a significant increase in relative energy loss for the spatial B-jump compared to either the spatial jump or B-jump alone.

B- and T-cell epitopes of tropomyosin, the major shrimp allergen

Seafood allergy is often encountered on ingestion of crustaceans such as shrimp, lobster, crab, and crayfish (1). On eating cooked shrimp, sensitive individuals experience a wide spectrum of reactions ranging from abdominal discomfort to anaphylaxis. The presence of cross-reacting heat-stable allergens in crustacean food was first recognized by Hoffman et al. (2) and Lehrer et al. (3). Subsequently, the major allergen was isolated and characterized from the shrimp species Paneaus indicus (Pen i 1) (4) and I? aztecm (Pen a 1) (5). Pen i 1 (originally designated Sa-TI) and Pen a 1, with mol. mass of 34 and 36 kDa, respectively, contain 301 and 312 amino-acid residues with a predominance of gluta- mate/glutamine and asparatate/asparagine.

Effect of microstructure on the mechanical behavior of b-modified ti-6al-4v alloys

Small additions of B to Titanium alloys refine the as-cast microstructure significantly and hence improve their mechanical performance. In this work, tensile, fracture and fatigue properties of the as-cast and HIPed Ti-6Al-4V alloy with hypoeutectic wt.% of B additions have been examined, with particular emphasis on identifying the microstructural length scale that controls the mechanical properties of these alloys.

Polymorphism in B-DNA - X-ray-Diffraction Studies on Li-DNA Fibers

From X-ray diffraction studies it is generally believed that B-DNA has the structural parameters n = 10 and h = 3.4 Å. However, for the first time we report that polymorphism in the B-form can be observed in DNA fibres. This was achieved by the precise control of salt and humidity in fibres and by the application of the precession method of X-ray diffraction to DNA fibres. The significant result obtained is that n = 10 is not observed for crystalline fibre patterns. In fact, n = 10 and h = 3.4 Å are not found to occur simultaneously. Instead, a range of values, n = 9.6–10.0 and h = 3.35 Å–3.41 Å is observed.

Critical Cation Balance In B-]Z Transition - Role Of Li+

The sodium salt of poly(dG-dC) is known to exhibit a B + Z transition in the presence of various cations and 60% alcohol. We here show that the lithium salt of poly(dG-dC) does not undergo B 4 Z transition in the presence of 60% alcohol since Li’ with its large hydration shell cannot stabilize the Z-form. On the other hand, high concentrations of Mg2* or micromolar concentrations of the cobalt hexamine complex which are known to stabilize the Z-form can compete with Li+ for charge neutraIization and hence bring about a B--t Z transition in the same polymer. From the model building studies the mode of action of the cobalt-hexamine complex in stabilizing the Z-form is postulated.

La modernización entre cafetales : San José, Costa Rica, 1880-1930

This work examines the urban modernization of San José, Costa Rica, between 1880 and 1930, using a cultural approach to trace the emergence of the bourgeois city in a small Central American capital, within the context of order and progress. As proposed by Henri Lefebvre, Manuel Castells and Edward Soja, space is given its rightful place as protagonist. The city, subject of this study, is explored as a seat of social power and as the embodiment of a cultural transformation that took shape in that space, a transformation spearheaded by the dominant social group, the Liberal elite. An analysis of the product built environment allows us to understand why the city grew in a determined manner: how the urban space became organized and how its infrastructure and services distributed. Although the emphasis is on the Liberal heyday from 1880-1930, this study also examines the history of the city since its origins in the late colonial period through its consolidation as a capital during the independent era, in order to characterize the nineteenth century colonial city that prevailed up to 1890 s. A diverse array of primary sources including official acts, memoirs, newspaper sources, maps and plans, photographs, and travelogues are used to study the initial phase of San Jose s urban growth. The investigation places the first period of modern urban growth at the turn of the nineteenth century within the prevailing ideological and political context of Positivism and Liberalism. The ideas of the city s elite regarding progress were translated into and reflected in the physical transformation of the city and in the social construction of space. Not only the transformations but also the limits and contradictions of the process of urban change are examined. At the same time, the reorganization of the city s physical space and the beginnings of the ensanche are studied. Hygiene as an engine of urban renovation is explored by studying the period s new public infrastructure (including pipelines, sewer systems, and the use of asphalt pavement) as part of the Saneamiento of San José. The modernization of public space is analyzed through a study of the first parks, boulevards and monuments and the emergence of a new urban culture prominently displayed in these green spaces. Parks and boulevards were new public and secular places of power within the modern city, used by the elite to display and educate the urban population into the new civic and secular traditions. The study goes on to explore the idealized image of the modern city through an analysis of European and North American travelogues and photography. The new esthetic of theatrical-spectacular representation of the modern city constructed a visual guide of how to understand and come to know the city. A partial and selective image of generalized urban change presented only the bourgeois facade and excluded everything that challenged the idea of progress. The enduring patterns of spatial and symbolic exclusion built into Costa Rica s capital city at the dawn of the twentieth century shed important light on the long-term political social and cultural processes that have created the troubled urban landscapes of contemporary Latin America.

Fibre diffraction of lithium DNA shows structural variability and deviation from a regular helical structure for the B-form

Recently, reports have appeared which show structural variations in B-DNA and indicate deviations from a uniform helical structure. We report for the first time that these indications are also present in the B-form fibre diffraction patterns for the lithium salt of natural DNA. We have used an improved method of controlling the salt concentration in the fibres. Our results are based on the appearance and disappearance of meridional reflections on different layer lines depending upon the salt.

Observations sur les termes culinaires dans deux San-Antonio de Frédéric Dard

Pro gradu-työni aihe on ruokaterminologiaa käsittelevät ranskan puhekielen ja Pariisin slangin lainasanat sekä kirjailija Frédéric Dardin alias San-Antonion (1921-2000) luomat, ruokatermistöön kuuluvat uudissanat ja -sanonnat kahdessa San-Antonio-romaanissa C'est mort et ça ne sait pas sekä Le fil à couper le beurre. Näissä ns. kioskikirjallisuutta edustavissa rikosromaaneissa seikkailee puheenparttaan ruoka-alan termeillä höystävä, "erikoistehtäviä" hoitava komisario ja naistenmies, San-Antonio. Ranskankielisessä arjen kielenkäytössä vilisee ruokaan liittyviä sanoja ja sanontoja muissakin kuin varsinaisissa ruuanvalmistus- ja ateriointiyhteyksissä. Halusin tarkastella, millaisena tämä yleisesti havaitsemani ilmiö todentuu Frédéric Dardin kahdessa romaanissa, jotka olen valinnut aineistokseni. Frédéric Dard käyttää romaaneissaan varsin omaperäistä kieltä: sekä puhekieltä että Pariisin slangia. Korpukseni koostuu romaaneista poimimistani ruoka-alan termistöä sisältävistä esimerkeistä, joita valmiiseen työhön tuli 228 kappaletta. Jaoin kaikki korpuksesta löytämäni ruokatermit kahteen luokkaan sen mukaan, oliko kirjailija lainannut käyttämänsä sanan tai ilmauksen puhekielestä tai Pariisin slangista (lainatermit), vai oliko hän luonut termin tai ilmauksen itse (neologismit). Määrittelin termin tai ilmauksen neologismiksi, jos se ei esiintynyt joko laisinkaan tai ainakaan kirjailijan tarkoittamassa merkityksessä seuraavissa sanakirjoissa: Le Dictionnaire du français argotique, populaire et familier; Le Dictionnaire de l'argot moderne; Le Dictionnaire du français non conventionnel; Le Dictionnaire de l'argot; Le Dictionnaire du français argotique et populaire; L'argot chez les vrais de vrai ja Trésor de la langue française. Varsinainen tutkimus perustuu sanojen ja ilmausten merkitysten selvittämiseen ja analysointiin. Lainatermien analyysillä tarkoitan lainatermien merkitysten selvitystä em. sanakirjojen avulla. Neologismit analysoin tarkemmin käyttäen em. sanakirjoja sekä tukeutuen gastronomisten ja erityisesti kielitieteellisten lähdeteosteni tarjoamiin rakenteellisiin ja semanttisiin muodostustapoihin ja tekemällä niistä tarvittavat yhteenvedot oikean merkityksen selvittämiseksi. Käsittelin aineiston kaikki ruokatermit. Niiden valtavan lukumäärän vuoksi analysoitavien esimerkkien määrää piti rajoittaa niin, että valmiiseen työhön jäi jokaisesta termistä enintään kaksi esimerkkiä kummastakin korpuksen kirjasta eli yhteensä 228 esimerkkiä. Muut esimerkit luetteloin työn lopusta löytyvään liitteeseen. Neologismianalyysissä selvisi, että Frédéric Dard suosi erityisesti semanttisia muodostustapoja eli olemassa olevan merkityksen muuttamista metaforien ja kielikuvien avulla. Dardin rikas terminologia ja hänen humoristiset oivalluksensa ovat osaltaan rikastuttaneet ranskan puhekieltä.Työssäni totean, että Pariisin slangia ja puhekieltä on totuttu pitämään sosiaalisesti sopimattomana, marginaalisten ryhmien kielenä, vaikka sen ilmauksia saattaa nykyisin kuulla jopa akateemikkojen käyttävän, ja ilmauksia on siirtynyt slangi- ja puhekielestä yleiskieleen. Toivon työni edistävän kiinnostusta kielitaidon parantamiseen San-Antonion tyyliin tutustumisen avulla sekä herättävän mielenkiintoa ranskan kielen vivahteikkuuteen ja monimuotoisuuteen muullakin kuin yleiskielen tasolla. Kielessä ei mielestäni voi olla sellaisia osa-alueita, joiden opiskelu ja osaaminen olisi tarpeetonta.

Isänmaa ja Ranska : Suomalainen frankofilia 1880-1914

In Finland the period 1880 -1914 constituted an essential phase in the creation of the great national project as well as it was a golden time of Francophilia. With Francophilia, i.e. French-mindedness, is here understood a collectively upheld strong sympathy towards France and French culture. However, the Francophilia of late nineteenth century Finland was free from apparent political intentions and remained a chosen disposition. The strength of its drive was not only based on the older European admiration of everything French, but also on the growing fascination for a novelty emerging besides the traditional influences of the Germanic culture. In Finnish society Francophilia mostly worked as an opposite force to the most confined conceptions of what was considered national ; as a consequence France came to denote more than a country and Francophilia contained an important symbolical meaning in the construction of the Finnish nation. The main tasks of the study are to introduce as the first large historical presentation of the subject a covering examination of the many descriptions of Paris-phases of assorted artists, authors, and intellectuals, to clarify the mental relationship of the Finnish intelligentsia to France prior to national independence, and finally to provide these developments with case studies of certain life paths. However, the examination is not biographical, because the starting point remains within the rhetoric arguments of Francophilia and patriotism as these appeared within the public sphere. Historical persons have thus been dealt with primarily as reflectors of the then-current French-minded mentality. Such Francophiles in Finland were first and foremost Werner Söderhjelm, Juhani Aho, L. Onerva and V. A. Koskenniemi. The networks of the Finnish cultural field are mostly displayed through these examples. In previous research the intensive relationship of Finnish artists and authors with France has not been connected with actual concepts of nationalism. The respective periods of the intellectuals in Paris have simply been viewed as devoid of ideological links with the contemporary advancement of the fatherland, or even as opposites to the patriotic pursuits in Finland. From the viewpoint of this study these now canonized creators of a Finnish culture are primarily seen as patriots and fellow countrymen, and only secondly as artists and artist s colleagues. The dissertation is constructed as both a regional survey of the idealization of France and a study of Finnish history through the mirror of Francophilia. As such France only held an instrumental role for the receiving culture, i.e. for the construction of Finland, as no "objective truths" were sought for in France. Keywords: France, francophilia, Finnishness, national project, Paris

Competing A-site and B-site driven ferroelectric instabilities in the (1-x)PbTiO3-(x)BiAlO3 system

The system (1-x)PbTiO3-(x)BiAlO3 has been investigated with regard to its solid solubility, crystal structure, microstructure, and ferroelectric transition. The unit cell volume and the tetragonality exhibit anomalous behavior near x=0.10. The Curie point (T-C) of PbTiO3 was however found to be nearly unchanged. The study seems to suggest that the decrease in the stability of the ferroelectric state due to dilution of the Ti-sublattice by smaller sized Al+3 ions is compensated by the increase in the ferroelectric stability by the Bi+3 ions.