Saethre-Chotzen syndrome : cranofacial anomalies caused by genetic changes in the TWIST gene

In this thesis, one of the most frequently occurring and most variable craniosynostosis syndromes was investigated; Saethre-Chotzen syndrome. Craniosynostosis is the premature obliteration of cranial sutures in the developing embryo. It can also occur in the first few months of life. Saethre-Chotzen syndrome is, besides craniosynostosis, characterized by specific facial and limb abnormalities, of which the most frequently reported are ptosis, prominent crus helicis, cutaneous syndactyly of digit 2 and 3 on both hands and feet, and broad halluces. Saethre-Chotzen syndrome has been linked to the TWIST gene on chromosome 7p21.1. Mutations in and variably sized deletions of this gene can be found in patients with clinical features of Saethre-Chotzen syndrome. The latter, TWIST deletions, often also include part of the surrounding chromosome 7p and are reported to be associated with mental retardation. In Saethre-Chotzen patients, in whom neither a mutation nor a deletion of TWIST had been found, the FGFR3 P250R mutation was in some cases detected. This mutation has specifically been linked to Muenke syndrome that is characterized by unior bicoronal synostosis and slight facial dysmorphology. However, a Saethre-Chotzen like phenotype can also result from this mutation. Because of the possible overlap of Saethre-Chotzen with Muenke syndrome, these syndromes were studied in order to provide clinical criteria that discriminate between the two (chapter 4). Many phenotypic features occur in both syndromes. In addition, although unicoronal synostosis occurs slightly more frequently in Muenke syndrome, unicoronal and bicoronal synostosis are seen in both syndromes. The discrimination between Saethre-Chotzen and Muenke is often not made easily and the associated genes, TWIST and FGFR3, respectively, are simultaneously tested for pathogenic m

Search for charged Higgs bosons in decays of top quarks in p-pbar collisions at sqrt(s) = 1.96 TeV

7 pages, 2 figuresWe report the recent charged Higgs search in top quark decays in 2.2/fb CDF data. This is the first attempt to search for charged Higgs using fully reconstructed mass assuming H->c-sbar in small tan beta region. No evidence of a charged Higgs is observed in the CDF data, hence 95% upper limits are placed at B(t->H+b)We report on the first direct search for charged Higgs bosons decaying into cs̅ in tt̅ events produced by pp̅ collisions at √s=1.96  TeV. The search uses a data sample corresponding to an integrated luminosity of 2.2  fb-1 collected by the CDF II detector at Fermilab and looks for a resonance in the invariant mass distribution of two jets in the lepton+jets sample of tt̅ candidates. We observe no evidence of charged Higgs bosons in top quark decays. Hence, 95% upper limits on the top quark decay branching ratio are placed at B(t→H+b)< 0.1 to 0.3 for charged Higgs boson masses of 60 to 150  GeV/c2 assuming B(H+→cs̅ )=1.0. The upper limits on B(t→H+b) are also used as model-independent limits on the decay branching ratio of top quarks to generic scalar charged bosons beyond the standard model.Peer reviewe

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

Method of fuzzy structural analysis of ontology

Hассматривается представление знаний в виде онтологии для улучшения процесса обучения. В предлагаемом подходе к решению задачи, каждый обучаемый добавляет отредактированную онтологию относительно своего виденья структуры рассматриваемой информации. На основании онтологий, полученных сообществом обучаемых, формируется так называемая идеальная онтология представления информации. Для сравнения построенных онтологий с идеальной онтологией используются графы онтологий. Для построения графов онтологий, в данной работе предлагается использовать метод нечеткого структурного анализа онтологий.У роботі розглядається подання знань у вигляді онтології для поліпшення процесу навчання. У запропонованому підході до вирішення завдання, кожен учень додає відредаговану онтологію щодо свого бачення структури розглянутої інформації. На підставі онтологій, отриманих спільнотою тих, що навчаються, формується так звана ідеальна онтологія подання інформації. Для порівняння побудованих онтологій з ідеальною онтологію використовуються графи онтологій. Для побудови графів онтологій, в даній роботі пропонується використовувати метод нечіткого структурного аналізу онтологій.The representation of knowledge in the form of ontology to improve the learning process is considered in this article. In the proposed approach of solving the problem, each student adds the edited ontology about his vision of the structure under consideration of information. On the basis of ontology obtained by learners’ community, so-called ideal ontology of information representation is formed. To compare formed ontologies with ideal ontology the graphs of ontology are used. The method of fuzzy structural analysis of ontology is proposed to be used to construct graphs of ontologies

Crystal structure and functional analysis of human C1ORF123

10.7717/peerj.5377PeerJ20189e537

Impact of Climate Change on the Hydrology of the Upper Awash River Basin, Ethiopia

This study investigated the impacts of climate change on the hydrology of the Upper Awash Basin, Ethiopia. A soil and water assessment tool (SWAT) model was calibrated and validated against observed streamflow using SWAT CUP. The Mann–Kendall trend test (MK) was used to assess climate trends. Meteorological drought (SPEI) and hydrological drought (SDI) were also investigated. Based on the ensemble mean of five global climate models (GCMs), projected increases in mean annual maximum temperature over the period 2015–2100 (compared with a 1983–2014 baseline) range from 1.16 to 1.73 °C, while increases in minimum temperature range between 0.79 and 2.53 °C. Increases in mean annual precipitation range from 1.8% at Addis Ababa to 45.5% over the Hombole area. High streamflow (Q5) declines at all stations except Ginchi. Low flows (Q90) also decline with Q90 equaling 0 m3 s−1 (i.e., 100% reduction) at some gauging stations (Akaki and Hombole) for individual GCMs. The SPEI confirmed a significant drought trend in the past, while the frequency and severity of drought will increase in the future. The basin experienced conditions that varied from modest dry periods to a very severe hydrological drought between 1986 and 2005. The projected SDI ranges from modestly dry to modestly wet conditions. Climate change in the basin would enhance seasonal variations in hydrological conditions. Both precipitation and streamflow will decline in the wet seasons and increase in the dry seasons. These changes are likely to have an impact on agricultural activities and other human demands for water resources throughout the basin and will require the implementation of appropriate mitigation measures

Higgs Boson Studies at the Tevatron

We combine searches by the CDF and D0 Collaborations for the standard model Higgs boson with mass in the range 90--200 GeV$/c^2$ produced in the gluon-gluon fusion, $WH$, $ZH$, $t{\bar{t}}H$, and vector boson fusion processes, and decaying in the $H\rightarrow b{\bar{b}}$, $H\rightarrow W^+W^-$, $H\rightarrow ZZ$, $H\rightarrow\tau^+\tau^-$, and $H\rightarrow \gamma\gamma$ modes. The data correspond to integrated luminosities of up to 10 fb$^{-1}$ and were collected at the Fermilab Tevatron in $p{\bar{p}}$ collisions at $\sqrt{s}=1.96$ TeV. The searches are also interpreted in the context of fermiophobic and fourth generation models. We observe a significant excess of events in the mass range between 115 and 140 GeV/$c^2$. The local significance corresponds to 3.0 standard deviations at $m_H=125$ GeV/$c^2$, consistent with the mass of the Higgs boson observed at the LHC, and we expect a local significance of 1.9 standard deviations. We separately combine searches for $H \to b\bar{b}$, $H \to W^+W^-$, $H\rightarrow\tau^+\tau^-$, and $H\rightarrow\gamma\gamma$. The observed signal strengths in all channels are consistent with the presence of a standard model Higgs boson with a mass of 125 GeV/$c^2$