Preface

This series contain the summaries of the bachelor thesis of the MaRBLe + students of 2015, and represent the different strands of research in the various bachelor tracks of Health Sciences and Bio Medical Sciences programmes in the academic year 2014/15. It should be noted that some of the work is considered for publication in a peer reviewed scientific journal and therefore the content of the presented thesis summary may be altered to prevent double publication of scientific work. This publication could be the first step in a research career for students and is an ideal way to spread their research findings to a broader audience

Preface

This series contain the summaries of the bachelor thesis of the MaRBLe+ students of2014, and represent the different strands of research in the various bachelor tracks of Health Sciences and Bio Medical Sciences programs in the academic year 2013/14

The Breda Study: Search for genetic factors involved in type 2 diabetes mellitus in a defined Dutch population

Little is known about the nature of genetic variation underlying complex diseases in humans. The recognition that susceptibility to type 2 diabetes mellitus has a strong inherited component provides a mechanism for developing the molecular understanding of the pathogenesis of type 2 diabetes mellitus through various genetic approaches. The main aim of the Breda study described in this thesis was to identify genetic factors involved in type 2 diabetes mellitus in a defined Dutch population. This thesis gives gives an overview of the approaches that can be used to identify genetic factors in type 2 diabetes mellitus and, in particular, the role of candidate gene analysis and genome-wide scanning is emphasised. This thesis also describes the results of a genome-wide scan performed for type 2 diabetes mellitus in a defined Dutch population. The genome-wide scan was carried out using identity-by-descent analysis in affected sibpairs. Since obesity and type 2 diabetes mellitus are inter-related, the data set was stratified for the sub-phenotype body mass index (BMI), corrected for age and gender. This resulted in a suggestive maximum multi-point LOD score of 2.3 (p-value 9.7 x 10-4] for the most obese 20% pedigrees of the data set in the region flanked by marker loci D18S471 and D18S843 (chromosome region 18p11). We hereby confirmed the presence of a susceptibility locus on chromosome 18, reported earlier from a Finnish/Swedish population. This finding provided solid and independent evidence that the chromosome 18p11 locus is of definite interest for type 2 diabetes mellitus in connection with obesity in the Breda study cohort. In addition, we demonstrated that in the lowest 80% obese pedigrees ("lean" type 2 diabetes mellitus) two interesting loci on chromosomes 2 and 19 were found with LODs of 1.5 and 1.3, respectively (p-values 7.5 x 10-3 and 11.2 x 10-3]. Further more this thesis describes the analysis for linkage to loci influencing BMI (using quantitative trait locus (QTL) mapping) in 420 type 2 diabetes mellitus patients from the Breda cohort for which BMI values where available. Subsequently, the genotype data from the 20% most obese type 2 diabetes mellitus pedigrees ("obese" type 2 diabetes mellitus) was also analysed for linkage to type 2 diabetes mellitus using the ASP analysis. The QTL results support previous findings of a susceptibility locus (QTL) influencing BMI in type 2 diabetes mellitus residing on chromosome region 11q. In addition, suggestive evidence was found and previous findings confirmed for linkage with type 2 diabetes mellitus on chromosome regions 1q, 11p, and 12q. In general, it appears that the linkage found for type 2 diabetes mellitus in the present cohort is strongly influenced by obesity. This supports the notion that a genetic predisposition to obesity is closely intertwined with one predisposition to type 2 diabetes mellitus. However, our study fails to determine to what extent obesity and type 2 diabetes mellitus are genetically unique entities in their own right. Complementary to these approaches described above also candidate gene association studies were performed with the sulphonylurea receptor 1 (SUR1) gene and type 2 diabetes mellitus, and with the beta-adrenergic receptor-2 (B2ADR) gene and obesity in type 2 diabetes mellitus subjects from the Breda study cohort. In our cohort, no significant association was found with the SNP16 variant of the SUR1 gene in type 2 diabetes patients compared to controls. The genotypes of SNP27 variant in the B2ADR gene were matched to the BMI values of 542 patients in our cohort and were compared using ANOVA with age and gender as covariates. No statistically significant difference was observed between the various groups, implying that, in our cohort, this polymorphism has no important effect on body mass index. Also no effect was found for this polymorphism on either the age of diagnosis of diabetes or on plasma lipids levels. The results of this thesis will, together with previously reported results, help accelerate the efforts to identify susceptibility genes for type 2 diabetes mellitus located in the regions described above. Combined with new developments in the fields of bioinformatics, genomics and proteomics, this will lead to a greater understanding of the pathogenesis of type 2 diabetes mellitus. Identifying new pathways involved in the disease aetiology may help identify new therapeutic goals, and direct efforts to target therapies to relevant tissues. By improving the classification of type 2 diabetes, together with new insights in pharmacogenetics, this genetic information may form the basis for the development of new drug therapies and hopefully, in the future, will lead to the prevention of type 2 diabetes mellitus

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Study of forward Z + jet production in pp collisions at √s=7 TeV

A measurement of the $Z(\rightarrow\mu^+\mu^-)$+jet production cross-section in $pp$ collisions at a centre-of-mass energy $\sqrt{s} = 7$ TeV is presented. The analysis is based on an integrated luminosity of $1.0\,\text{fb}^{-1}$ recorded by the LHCb experiment. Results are shown with two jet transverse momentum thresholds, 10 and 20 GeV, for both the overall cross-section within the fiducial volume, and for six differential cross-section measurements. The fiducial volume requires that both the jet and the muons from the Z boson decay are produced in the forward direction ($2.0<\eta<4.5$). The results show good agreement with theoretical predictions at the second-order expansion in the coupling of the strong interaction.A measurement of the $Z(\rightarrow\mu^+\mu^-)$+jet production cross-section in $pp$ collisions at a centre-of-mass energy $\sqrt{s} = 7$ TeV is presented. The analysis is based on an integrated luminosity of $1.0\,\text{fb}^{-1}$ recorded by the LHCb experiment. Results are shown with two jet transverse momentum thresholds, 10 and 20 GeV, for both the overall cross-section within the fiducial volume, and for six differential cross-section measurements. The fiducial volume requires that both the jet and the muons from the Z boson decay are produced in the forward direction ($2.0<\eta<4.5$). The results show good agreement with theoretical predictions at the second-order expansion in the coupling of the strong interaction

A study of CP violation in B-+/- -&gt; DK +/- and B-+/- -&gt; D pi(+/-) decays with D -&gt; (KSK +/-)-K-0 pi(-/+) final states

A first study of CP violation in the decay modes $B^\pm\to [K^0_{\rm S} K^\pm \pi^\mp]_D h^\pm$ and $B^\pm\to [K^0_{\rm S} K^\mp \pi^\pm]_D h^\pm$, where $h$ labels a $K$ or $\pi$ meson and $D$ labels a $D^0$ or $\overline{D}^0$ meson, is performed. The analysis uses the LHCb data set collected in $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$. The analysis is sensitive to the CP-violating CKM phase $\gamma$ through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of $\gamma$ using other decay modes

Measurement of CP asymmetry in B-s(0) -&gt; D-s(-/+) K--/+ decays

We report on measurements of the time-dependent CP violating observables in $B^0_s\rightarrow D^{\mp}_s K^{\pm}$ decays using a dataset corresponding to 1.0 fb$^{-1}$ of pp collisions recorded with the LHCb detector. We find the CP violating observables $C_f=0.53\pm0.25\pm0.04$, $A^{\Delta\Gamma}_f=0.37\pm0.42\pm0.20$, $A^{\Delta\Gamma}_{\bar{f}}=0.20\pm0.41\pm0.20$, $S_f=-1.09\pm0.33\pm0.08$, $S_{\bar{f}}=-0.36\pm0.34\pm0.08$, where the uncertainties are statistical and systematic, respectively. We use these observables to make the first measurement of the CKM angle $\gamma$ in $B^0_s\rightarrow D^{\mp}_s K^{\pm}$ decays, finding $\gamma$ = (115$_{-43}^{+28}$)$^\circ$ modulo 180$^\circ$ at 68% CL, where the error contains both statistical and systematic uncertainties.We report on measurements of the time-dependent CP violating observables in B$_{s}^{0}$  → D$_{s}^{∓}$ K$^{±}$ decays using a dataset corresponding to 1.0 fb$^{−1}$ of pp collisions recorded with the LHCb detector. We find the CP violating observables C$_{f}$ = 0.53±0.25±0.04, A$_{f}^{ΔΓ}$  = 0.37 ± 0.42 ± 0.20, ${A}_{\overline{f}}^{\varDelta \varGamma }=0.20\pm 0.41\pm 0.20$ , S$_{f}$ = −1.09±0.33±0.08, ${S}_{\overline{f}}=-0.36\pm 0.34\pm 0.08$ , where the uncertainties are statistical and systematic, respectively. Using these observables together with a recent measurement of the B$_{s}^{0}$ mixing phase −2β$_{s}$ leads to the first extraction of the CKM angle γ from B$_{s}^{0}$  → D$_{s}^{∓}$ K$^{±}$ decays, finding γ = (115$_{− 43}^{+ 28}$ )° modulo 180° at 68% CL, where the error contains both statistical and systematic uncertainties.We report on measurements of the time-dependent CP violating observables in $B^0_s\rightarrow D^{\mp}_s K^{\pm}$ decays using a dataset corresponding to 1.0 fb$^{-1}$ of pp collisions recorded with the LHCb detector. We find the CP violating observables $C_f=0.53\pm0.25\pm0.04$, $A^{\Delta\Gamma}_f=0.37\pm0.42\pm0.20$, $A^{\Delta\Gamma}_{\bar{f}}=0.20\pm0.41\pm0.20$, $S_f=-1.09\pm0.33\pm0.08$, $S_{\bar{f}}=-0.36\pm0.34\pm0.08$, where the uncertainties are statistical and systematic, respectively. Using these observables together with a recent measurement of the $B^0_s$ mixing phase $-2\beta_s$ leads to the first extraction of the CKM angle $\gamma$ from $B^0_s \rightarrow D^{\mp}_s K^{\pm}$ decays, finding $\gamma$ = (115$_{-43}^{+28}$)$^\circ$ modulo 180$^\circ$ at 68% CL, where the error contains both statistical and systematic uncertainties

Measurement of Upsilon production in collisions at root s=2.76 TeV

The production of $\Upsilon(1S)$, $\Upsilon(2S)$ and $\Upsilon(3S)$ mesons decaying into the dimuon final state is studied with the LHCb detector using a data sample corresponding to an integrated luminosity of 3.3 $pb^{-1}$ collected in proton-proton collisions at a centre-of-mass energy of $\sqrt{s}=2.76$ TeV. The differential production cross-sections times dimuon branching fractions are measured as functions of the $\Upsilon$ transverse momentum and rapidity, over the ranges $p_{\rm T} Upsilon(1S) X) x B(Upsilon(1S) -> mu+mu-) = 1.111 +/- 0.043 +/- 0.044 nb, sigma(pp -> Upsilon(2S) X) x B(Upsilon(2S) -> mu+mu-) = 0.264 +/- 0.023 +/- 0.011 nb, sigma(pp -> Upsilon(3S) X) x B(Upsilon(3S) -> mu+mu-) = 0.159 +/- 0.020 +/- 0.007 nb, where the first uncertainty is statistical and the second systematic

Observation of the B0 → ρ0ρ0 decay from an amplitude analysis of B0 → (π+π−)(π+π−) decays

Proton–proton collision data recorded in 2011 and 2012 by the LHCb experiment, corresponding to an integrated luminosity of 3.0 fb−1 , are analysed to search for the charmless B0→ρ0ρ0 decay. More than 600 B0→(π+π−)(π+π−) signal decays are selected and used to perform an amplitude analysis, under the assumption of no CP violation in the decay, from which the B0→ρ0ρ0 decay is observed for the first time with 7.1 standard deviations significance. The fraction of B0→ρ0ρ0 decays yielding a longitudinally polarised final state is measured to be fL=0.745−0.058+0.048(stat)±0.034(syst) . The B0→ρ0ρ0 branching fraction, using the B0→ϕK⁎(892)0 decay as reference, is also reported as B(B0→ρ0ρ0)=(0.94±0.17(stat)±0.09(syst)±0.06(BF))×10−6