Study of D J meson decays to D +π-, D 0π+ and D ∗+π- final states in pp collisions

A study of D +π−, D 0π+ and D ∗+π− final states is performed using pp collision data, corresponding to an integrated luminosity of 1.0 fb−1, collected at a centre-of-mass energy of 7 TeV with the LHCb detector. The D 1(2420)0 resonance is observed in the D ∗+π− final state and the D∗2(2460) resonance is observed in the D +π−, D 0π+ and D ∗+π− final states. For both resonances, their properties and spin-parity assignments are obtained. In addition, two natural parity and two unnatural parity resonances are observed in the mass region between 2500 and 2800 MeV. Further structures in the region around 3000 MeV are observed in all the D ∗+π−, D +π− and D 0π+ final states.

Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia.

We and others have reported mutations in LONP1, a gene coding for a mitochondrial chaperone and protease, as the cause of the human CODAS (cerebral, ocular, dental, auricular and skeletal) syndrome (MIM 600373). Here, we delineate a similar but distinct condition that shares the epiphyseal, vertebral and ocular changes of CODAS but also included severe microtia, nasal hypoplasia, and other malformations, and for which we propose the name of EVEN-PLUS syndrome for epiphyseal, vertebral, ear, nose, plus associated findings. In three individuals from two families, no mutation in LONP1 was found; instead, we found biallelic mutations in HSPA9, the gene that codes for mHSP70/mortalin, another highly conserved mitochondrial chaperone protein essential in mitochondrial protein import, folding, and degradation. The functional relationship between LONP1 and HSPA9 in mitochondrial protein chaperoning and the overlapping phenotypes of CODAS and EVEN-PLUS delineate a family of "mitochondrial chaperonopathies" and point to an unexplored role of mitochondrial chaperones in human embryonic morphogenesis.

Migration and horizontal gene transfer divide microbial genomes into multiple niches.

Horizontal gene transfer is central to microbial evolution, because it enables genetic regions to spread horizontally through diverse communities. However, how gene transfer exerts such a strong effect is not understood. Here we develop an eco-evolutionary model and show how genetic transfer, even when rare, can transform the evolution and ecology of microbes. We recapitulate existing models, which suggest that asexual reproduction will overpower horizontal transfer and greatly limit its effects. We then show that allowing immigration completely changes these predictions. With migration, the rates and impacts of horizontal transfer are greatly increased, and transfer is most frequent for loci under positive natural selection. Our analysis explains how ecologically important loci can sweep through competing strains and species. In this way, microbial genomes can evolve to become ecologically diverse where different genomic regions encode for partially overlapping, but distinct, ecologies. Under these conditions ecological species do not exist, because genes, not species, inhabit niches.

A mild form of SLC29A3 disorder: a frameshift deletion leads to the paradoxical translation of an otherwise noncoding mRNA splice variant

We investigated two siblings with granulomatous histiocytosis prominent in the nasal area, mimicking rhinoscleroma and Rosai-Dorfman syndrome. Genome-wide linkage analysis and whole-exome sequencing identified a homozygous frameshift deletion in SLC29A3, which encodes human equilibrative nucleoside transporter-3 (hENT3). Germline mutations in SLC29A3 have been reported in rare patients with a wide range of overlapping clinical features and inherited disorders including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, and Faisalabad histiocytosis. With the exception of insulin-dependent diabetes and mild finger and toe contractures in one sibling, the two patients with nasal granulomatous histiocytosis studied here displayed none of the many SLC29A3-associated phenotypes. This mild clinical phenotype probably results from a remarkable genetic mechanism. The SLC29A3 frameshift deletion prevents the expression of the normally coding transcripts. It instead leads to the translation, expression, and function of an otherwise noncoding, out-of-frame mRNA splice variant lacking exon 3 that is eliminated by nonsense-mediated mRNA decay (NMD) in healthy individuals. The mutated isoform differs from the wild-type hENT3 by the modification of 20 residues in exon 2 and the removal of another 28 amino acids in exon 3, which include the second transmembrane domain. As a result, this new isoform displays some functional activity. This mechanism probably accounts for the narrow and mild clinical phenotype of the patients. This study highlights the"rescue" role played by a normally noncoding mRNA splice variant of SLC29A3, uncovering a new mechanism by which frameshift mutations can be hypomorphic.

High connectivity in a long-lived High-Arctic seabird, the ivory gull Pagophila eburnea

Species may cope with rapid habitat changes by distribution shifts or adaptation to new conditions. A common feature of these responses is that they depend on how the process of dispersal connects populations, both demographically and genetically. We analyzed the genetic structure of a near-threatened high-Arctic seabird, the ivory gull (Pagophila eburnea) in order to infer the connectivity among gull colonies. We analyzed 343 individuals sampled from 16 localities across the circumpolar breeding range of ivory gulls, from northern Russia to the Canadian Arctic. To explore the roles of natal and breeding dispersal, we developed a population genetic model to relate dispersal behavior to the observed genetic structure of worldwide ivory gull populations. Our key finding is the striking genetic homogeneity of ivory gulls across their entire distribution range. The lack of population genetic structure found among colonies, in tandem with independent evidence of movement among colonies, suggests that ongoing effective dispersal is occurring across the Arctic Region. Our results contradict the dispersal patterns generally observed in seabirds where species movement capabilities are often not indicative of dispersal patterns. Model predictions show how natal and breeding dispersal may combine to shape the genetic homogeneity among ivory gull colonies separated by up to 2800 km. Although field data will be key to determine the role of dispersal for the demography of local colonies and refine the respective impacts of natal versus breeding dispersal, conservation planning needs to consider ivory gulls as a genetically homogeneous, Arctic-wide metapopulation effectively connected through dispersal.

Reframing video gaming and internet use addiction : empirical cross-national comparison of heavy use over time and addiction scales among young users

BACKGROUND AND AIMS: Evidence-based and reliable measures of addictive disorders are needed in general population-based assessments. One study suggested that heavy use over time (UOT) should be used instead of self-reported addiction scales (AS). This study compared UOT and AS regarding video gaming and internet use empirically, using associations with comorbid factors. DESIGN: Cross-sectional data from the 2011 French Survey on Health and Consumption on Call-up and Preparation for Defence-Day (ESCAPAD), cross-sectional data from the 2012 Swiss ado@internet.ch study and two waves of longitudinal data (2010-13) of the Swiss Longitudinal Cohort Study on Substance Use Risk Factors (C-SURF). SETTING: Three representative samples from the general population of French and Swiss adolescents and young Swiss men, aged approximately 17, 14 and 20 years, respectively. PARTICIPANTS: ESCAPAD: n =22 945 (47.4% men); ado@internet.ch: n =3049 (50% men); C-SURF: n =4813 (baseline + follow-up, 100% men). MEASUREMENTS: We assessed video gaming/internet UOT ESCAPAD and ado@internet.ch: number of hours spent online per week, C-SURF: latent score of time spent gaming/using internet] and AS (ESCAPAD: Problematic Internet Use Questionnaire, ado@internet.ch: Internet Addiction Test, C-SURF: Gaming AS). Comorbidities were assessed with health outcomes (ESCAPAD: physical health evaluation with a single item, suicidal thoughts, and appointment with a psychiatrist; ado@internet.ch: WHO-5 and somatic health problems; C-SURF: Short Form 12 (SF-12 Health Survey) and Major Depression Inventory (MDI). FINDINGS: UOT and AS were correlated moderately (ESCAPAD: r = 0.40, ado@internet.ch: r = 0.53 and C-SURF: r = 0.51). Associations of AS with comorbidity factors were higher than those of UOT in cross-sectional (AS: .005 ≤ |b| ≤ 2.500, UOT: 0.001 ≤ |b| ≤ 1.000) and longitudinal analyses (AS: 0.093 ≤ |b| ≤ 1.079, UOT: 0.020 ≤ |b| ≤ 0.329). The results were similar across gender in ESCAPAD and ado@internet.ch (men: AS: 0.006 ≤ |b| ≤ 0.211, UOT: 0.001 ≤ |b| ≤ 0.061; women: AS: 0.004 ≤ |b| ≤ 0.155, UOT: 0.001 ≤ |b| ≤ 0.094). CONCLUSIONS: The measurement of heavy use over time captures part of addictive video gaming/internet use without overlapping to a large extent with the results of measuring by self-reported addiction scales (AS). Measuring addictive video gaming/internet use via self-reported addiction scales relates more strongly to comorbidity factors than heavy use over time.

Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells

Identification of CD8+ cytotoxic T lymphocyte (CTL) epitopes has traditionally relied upon testing of overlapping peptide libraries for their reactivity with T cells in vitro. Here, we pursued deep ligand sequencing (DLS) as an alternative method of directly identifying those ligands that are epitopes presented to CTLs by the class I human leukocyte antigens (HLA) of infected cells. Soluble class I HLA-A*11:01 (sHLA) was gathered from HIV-1 NL4-3-infected human CD4+ SUP-T1 cells. HLA-A*11:01 harvested from infected cells was immunoaffinity purified and acid boiled to release heavy and light chains from peptide ligands that were then recovered by size-exclusion filtration. The ligands were first fractionated by high-pH high-pressure liquid chromatography and then subjected to separation by nano-liquid chromatography (nano-LC)–mass spectrometry (MS) at low pH. Approximately 10 million ions were selected for sequencing by tandem mass spectrometry (MS/MS). HLA-A*11:01 ligand sequences were determined with PEAKS software and confirmed by comparison to spectra generated from synthetic peptides. DLS identified 42 viral ligands presented by HLA-A*11:01, and 37 of these were previously undetected. These data demonstrate that (i) HIV-1 Gag and Nef are extensively sampled, (ii) ligand length variants are prevalent, particularly within Gag and Nef hot spots where ligand sequences overlap, (iii) noncanonical ligands are T cell reactive, and (iv) HIV-1 ligands are derived from de novo synthesis rather than endocytic sampling. Next-generation immunotherapies must factor these nascent HIV-1 ligand length variants and the finding that CTL-reactive epitopes may be absent during infection of CD4+ T cells into strategies designed to enhance T cell immunity.

Local map update for large scale SLAM

A technique for simultaneous localisation and mapping (SLAM) for large scale scenarios is presented. This solution is based on the use of independent submaps of a limited size to map large areas. In addition, a global stochastic map, containing the links between adjacent submaps, is built. The information in both levels is corrected every time a loop is closed: local maps are updated with the information from overlapping maps, and the global stochastic map is optimised by means of constrained minimisation

Two-photon excitation fluorometry in detection of infectious diseases

Because of the heavily overlapping symptoms, pathogen-specific diagnosis and treatment of infectious diseases is difficult based on clinical symptoms alone. Therefore, patients are often treated empirically. More efficient treatment and management of infectious diseases would require rapid point-of-care compatible in vitro diagnostic methods. However, current point-of-care methods are unsatisfactory in performance and in cost structure. The lack of pointof- care methods results in unnecessary use of antibiotics, suboptimal use of virus-specific drugs, and compromised patient care. In this thesis, the applicability of a two-photon excitation fluorometry is evaluated as a tool for rapid detection of infectious diseases. New separation-free immunoassay methodologies were developed and validated for the following application areas: general inflammation markers, pathogen-specific antibodies, pathogen-specific antigens, and antimicrobial susceptibility testing. In addition, dry-reagent methodology and nanoparticulate tracers are introduced in context to the technique. The results show that the new assay technique is a versatile tool for rapid detection of infectious diseases in many different application areas. One particularly attractive area is rapid multianalyte testing of respiratory infections, where the technique was shown to allow simple assay protocols and comparable performance to the state-of-the-art laboratory methods. If implemented in clinical diagnostic use, the new methods could improve diagnostic testing routines, especially in rapid testing of respiratory tract infections.

Akateemiset urapolut. Humanistisen, yhteiskuntatieteellisen ja kasvatustieteellisen alan generalistien urapolkujen alkuvaiheet 1980- ja 1990-luvuilla

Academic Career Paths. The early career phases of generalists in the fields of humanities, social science and education in the 1980’s and 1990’s This doctoral thesis analyses how generalist graduates of master’s degree have attached to the labour market in two different time periods, and how their career paths in the first eight years following graduation have shaped up. The thesis also analyses the channels of employment through which the generalists have got employed in their early career path. By generalists I am referring to graduates of studies in academic fields which have not qualified the person in a specific profession but rather offered a more general readiness for working life. I address two groups of generalist master’s degree graduates of The University of Turku; one including graduates of the year 1985 and the other consisting of graduates of 1995. All subjects have graduated in the field of humanities, social studies or education. 71 respondents from the group of 1985 and 80 respondents from the group of 1995 answered a survey, which provided the data for the thesis. I interpret the data through the theoretical approaches of changing working life, model of normal employment, transitional labour markets, linear life path, overlapping life courses, hidden labour market and social capital. The conclusion of the thesis is that societal era is connected with employment and career paths of academic generalists. Between the two groups there were differences especially in attachment to labor market, in forms of employment (permanent full-time job vs. temporary job) and in employment channels. Compared to the situation the 1985 group had been in after their graduation, the 1995 group - after getting their degree - became more often unemployed and/or employed in duties below their level of education. Their mobility was also greater and their contracts were often temporary, whereas the graduates of 1985 had been employed in more permanent positions. I demonstrate that the career paths of generalists can be categorized in five career types: steady state, transitory, linear, unsteady and diverging career. Graduates of 1985 have been treading on more stable paths than the latter group. The channels of employment they used were roughly equally divided between formal (e.g. newspaper advertisement and employment office) and informal (e.g. personal contacts and unprompted search for work) channels, whereas amongst the 1995 group employment happened through more varied channels and mostly through informal channels. Regardless of their year of graduation the generalists’ careers had begun to evolve already while they were still in the university and had started working at the same time. The thesis displays how the model of normal employment has weakened and career paths have become unsteady as a consequence of temporary positions. What is also evident in employment when turning from the 1980’s towards the succeeding decade is the rise of significance of the hidden labour market and social capital.

PK-YRITYKSET INNOVAATTOREINA : Satunnaisista parannuksista kohti innovaatioiden virtaa. Yhteenveto tutkimusraportista, 3/2009

Tämän tutkimuksen tarkoituksena oli selvittää, minkälaisia innovaatioita eri toimialojen pienissä yrityksissä on kehitetty ja minkälaisia kyvykkyyksiä se on edellyttänyt. Lisäksi tavoitteena oli selvittää, kuinka suotuisana ympäristönä yritykset kokivat oman alueensa ja miten alueiden kehittämistyö on vaikuttanut yritysten kykyyn kilpailla. Teoreettiset oletukset perustuvat aikaisempiin tutkimuksiin innovaatiojohtamisen, yrittäjyyden ja pk-yritysten liiketoiminnan kehittämisen alueilta. Empiirinen aineisto on kerätty sähköpostikyselyllä tuottaen 733 kriteerit täyttävää vastausta. Kyselytutkimusta edelsi neljän alueen tapaustutkimus, jonka aikana luotiin teoreettinen rakennelma pienten yritysten innovaatiokyvykkyyden arvioimiseksi. Tämän tutkimuksen aineisto ei tue yleistä väitettä, jonka mukaan innovaatiotoiminta olisi harvinaisempaa tai vähäisempää kooltaan pienemmissä yrityksissä. Kokoa enemmän näyttäisi vaikuttavan innovaatiotoiminnan luonne ja siihen kytkeytyvä kyvykkyys. Yritysten innovaatio-toiminnan luonteen ja laajuuden perusteella tuloksista nousee neljä erilaista innovaattoriprofiilia: satunnainen parantaja, jatkuva parantaja, radikaali uudistaja ja monipuolinen kehittäjä. Innovaatiokyvykkyyttä tutkittiin seitsemän eri osatekijän suhteen. Eri profiilit omaavien yritysten kyvykkyyden tasot erosivat toisistaan merkittävästi. Tulokset vahvistavat käsityksiä siitä, että yksittäisen kyvykkyystekijän sijaan kyvykkyyskombinaatio vaikuttaa enemmän innovatiotoiminnan monipuolisuuteen. Innovaatiotoiminnan lisääntyessä ja monipuolistuessa, yritysten kyvykkyys-vaatimukset kasvavat kaikkien osatekijöiden suhteen. Yritykset ovat tiedostaneet innovaatio-kyvykkyyden kehittämisen tarpeet. Kyvykkyys on ajuri, jonka kyydissä pienet ja suuret innovaatiot syntyvät. Tämä tutkimus suosittelee, että innovaatiokyvykkyyden kehittäminen nostetaan näkyväm-mäksi tavoitteeksi. Pienissä yrityksissä luontevin tapa vahvistaa kyvykkyyksiä on integroida se yrityksen kehittämistoimintaan johtaen itse itseään ruokkivaksi prosessiksi. Haasteelliset kehittämis-tavoitteet edellyttävät monipuolista kyvykkyyksien vahvistamista ja vahvistuneet kyvykkyydet mahdollistavat entistä haastavampien kehittämistavoitteiden asettamisen. Parhaimmillaan tämä prosessi johtaa pienelle yritykselle soveltuvaan onnistumisen spiraaliin, joka samanaikaisesti kiihdyttää sekä kyvykkyyksien että innovaatioiden kehittämistä - tuotoksena jatkuva ja monipuolinen innovaatioiden virta. Tulokset vahvistavat ensimmäisessa vaiheessa toteutetun tapaustutkimuksen havaintoja siitä, että alueiden kehittämistyöstä hyötyvät yritykset, joiden kyvykkyystekijät ovat entuudestaan korkeaa tasoa. Pitkälle tuotteistetut julkiset palvelut soveltuvat parhaiten suuremmille yrityksille, joissa kehittämistoiminta on projektoitu ja kehittämistyö tehdään erillisten resurssien turvin. Sitä vastoin, valtaosassa pieniä yrityksiä kehittämistyö tapahtuu tavanomaisen liiketoiminnan ohessa ja samoilla resursseilla. Alueet tarjoavat varsin runsaasti luonteeltaan epäjatkuvia palveluja kohdistuen yksittäisten kyvykkyystekijöiden parantamiseen tai prosessin yksittäiseen vaiheeseen, usein innovaatioprosessin alkupäähän radikaalin innovaation kehittämiseksi. Tämän kyselyn tulokset suosittelevat myös toista reittiä: vahvistetaan ensin yritysten innovaatiokyvykkyyttä jatkuvaan pieniä askelia ottavaan innovaatiotoimintaan, josta matka jatkuu radikaalien uudistusten kautta moni-puoliseksi kehittämiseksi.

Flavonóide e triterpenos de Stigmaphyllom paralias

Stigmaphyllom paralias is a herb belonging to the family Malpighiaceae that occurs in sand soil of brazilian " restinga". This is the first report regarding phytochemical study with this species. The hexane extract of the aerial parts of plant afforded the triterpenes friedelin, lupenone, 3-oxo-alpha-amirin and 3-oxo-beta-amirin, the mixture of alpha-amirinyl palmitate and stearate, lupeol and 3,4-seco-friedelan-3-oic acid. The AcOEt extract yielded the flavonoid luteolin-7-rutinoside. All compounds were characterized by analysis of spectrometric data and the fatty acids esterified with alpha-amirine were identified by GC/MS of methyl derivatives of transesterified products . This is the first natural occurence of 3,4-seco-friedelan-3-oic acid and the 13C NMR spectral data were inequivocally assigned by two-dimensional techniques. This work also permitted to correct the 13C NMR resonances attributed to methyl groups C-26 and C-27 of fridelin.

Sexual foraging segregation in South American sea lions increases during the pre-breeding period in the La Plata River plume

Stable carbon and nitrogen isotopes in skin and bone of South American sea lions from Brazil and Uruguay were analysed to test the hypothesis that trophic overlap between the sexes is lower during the pre-breeding season than throughout the rest of the year. The isotopic values of skin and bone were used to infer the trophic relationships between the sexes during the pre-breeding period and year round, respectively. Prey species were also analysed to establish a baseline necessary for interpreting the stable isotope ratios of skin and bone. Standard ellipse areas, estimated using Bayesian inference in the SIBER routine of the SIAR package in R, suggested that males and females used a wide diversity of foraging strategies throughout the year and that no differences existed between the sexes. However, the diversity of foraging strategies was largely reduced during the pre-breeding period, with all the individuals of each sex adopting similar strategies, but with the two sexes differing considerably in stable isotope values and the ellipse areas of males and females not overlapping at all. Nevertheless, the results revealed a general increase in the consumption of pelagic prey by both sexes during the pre-breeding period. The progressive crowding of individuals in the areas surrounding the breeding rookeries during the pre-breeding period could lead to an increase in the local population density, which could explain the above reported changes.

Complexation of enalapril maleate with beta-cyclodextrin: NMR spectroscopic study in solution

A detailed NMR (¹H , COSY, ROESY) spectroscopic study of complexation of enalapril maleate with beta-cyclodextrin was carried out. The ¹H NMR spectrum of enalapril maleate confirmed the existence of cis-trans equilibrium in solution, possibly due to hindered rotation along the amide bond. The cis-trans ratio remained almost the same in the presence of beta-cyclodextrin but in one case it was found significantly different which suggests a catalytic role of beta-cyclodextrin in the isomerization. ¹H NMR titration studies confirmed the formation of an enalapril-beta-cyclodextrin inclusion complex as evidenced by chemical shift variations in the proton resonances of both the host and the guest. The stoichiometry of the complex was determined to be 2:1 (guest: host). The mode of penetration of the guest into the beta-cyclodextrin cavity as well as the structure of the complex were established using ROESY spectroscopy.

Quantum magnetic deflagration in Mn12 acetate

We report controlled ignition of magnetization reversal avalanches by surface acoustic waves in a single crystal of Mn12 acetate. Our data show that the speed of the avalanche exhibits maxima on the magnetic field at the tunneling resonances of Mn12. Combined with the evidence of magnetic deflagration in Mn12 acetate [Y. Suzuki et al., Phys. Rev. Lett. 95, 147201 (2005)], this suggests a novel physical phenomenon: deflagration assisted by quantum tunneling.