Molecular line and continuum studies of the early stages of star formation

New stars form in dense interstellar clouds of gas and dust called molecular clouds. The actual sites where the process of star formation takes place are the dense clumps and cores deeply embedded in molecular clouds. The details of the star formation process are complex and not completely understood. Thus, determining the physical and chemical properties of molecular cloud cores is necessary for a better understanding of how stars are formed. Some of the main features of the origin of low-mass stars, like the Sun, are already relatively well-known, though many details of the process are still under debate. The mechanism through which high-mass stars form, on the other hand, is poorly understood. Although it is likely that the formation of high-mass stars shares many properties similar to those of low-mass stars, the very first steps of the evolutionary sequence are unclear. Observational studies of star formation are carried out particularly at infrared, submillimetre, millimetre, and radio wavelengths. Much of our knowledge about the early stages of star formation in our Milky Way galaxy is obtained through molecular spectral line and dust continuum observations. The continuum emission of cold dust is one of the best tracers of the column density of molecular hydrogen, the main constituent of molecular clouds. Consequently, dust continuum observations provide a powerful tool to map large portions across molecular clouds, and to identify the dense star-forming sites within them. Molecular line observations, on the other hand, provide information on the gas kinematics and temperature. Together, these two observational tools provide an efficient way to study the dense interstellar gas and the associated dust that form new stars. The properties of highly obscured young stars can be further examined through radio continuum observations at centimetre wavelengths. For example, radio continuum emission carries useful information on conditions in the protostar+disk interaction region where protostellar jets are launched. In this PhD thesis, we study the physical and chemical properties of dense clumps and cores in both low- and high-mass star-forming regions. The sources are mainly studied in a statistical sense, but also in more detail. In this way, we are able to examine the general characteristics of the early stages of star formation, cloud properties on large scales (such as fragmentation), and some of the initial conditions of the collapse process that leads to the formation of a star. The studies presented in this thesis are mainly based on molecular line and dust continuum observations. These are combined with archival observations at infrared wavelengths in order to study the protostellar content of the cloud cores. In addition, centimetre radio continuum emission from young stellar objects (YSOs; i.e., protostars and pre-main sequence stars) is studied in this thesis to determine their evolutionary stages. The main results of this thesis are as follows: i) filamentary and sheet-like molecular cloud structures, such as infrared dark clouds (IRDCs), are likely to be caused by supersonic turbulence but their fragmentation at the scale of cores could be due to gravo-thermal instability; ii) the core evolution in the Orion B9 star-forming region appears to be dynamic and the role played by slow ambipolar diffusion in the formation and collapse of the cores may not be significant; iii) the study of the R CrA star-forming region suggests that the centimetre radio emission properties of a YSO are likely to change with its evolutionary stage; iv) the IRDC G304.74+01.32 contains candidate high-mass starless cores which may represent the very first steps of high-mass star and star cluster formation; v) SiO outflow signatures are seen in several high-mass star-forming regions which suggest that high-mass stars form in a similar way as their low-mass counterparts, i.e., via disk accretion. The results presented in this thesis provide constraints on the initial conditions and early stages of both low- and high-mass star formation. In particular, this thesis presents several observational results on the early stages of clustered star formation, which is the dominant mode of star formation in our Galaxy.

Abnormal levels of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in tumour tissue and blood samples from patients diagnosed with lung cancer

Lung cancer is the second most common type of cancer in the world and is the most common cause of cancer-related death in both men and women. Research into causes, prevention and treatment of lung cancer is ongoing and much progress has been made recently in these areas, however survival rates have not significantly improved. Therefore, it is essential to develop biomarkers for early diagnosis of lung cancer, prediction of metastasis and evaluation of treatment efficiency, as well as using these molecules to provide some understanding about tumour biology and translate highly promising findings in basic science research to clinical application. In this investigation, two-dimensional difference gel electrophoresis and mass spectrometry were initially used to analyse conditioned media from a panel of lung cancer and normal bronchial epithelial cell lines. Significant proteins were identified with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), pyruvate kinase M2 isoform (PKM2), Hsc-70 interacting protein and lactate dehydrogenase A (LDHA) selected for analysis in serum from healthy individuals and lung cancer patients. hnRNPA2B1, PKM2 and LDHA were found to be statistically significant in all comparisons. Tissue analysis and knockdown of hnRNPA2B1 using siRNA subsequently demonstrated both the overexpression and potential role for this molecule in lung tumorigenesis. The data presented highlights a number of in vitro derived candidate biomarkers subsequently verified in patient samples and also provides some insight into their roles in the complex intracellular mechanisms associated with tumour progression.

Disarming identities : Ethnic identities in conflict resolution: Hindrance or helpful resource?

This thesis proposes that national or ethnic identity is an important and overlooked resource in conflict resolution. Usually ethnic identity is seen both in international relations and in social psychology as something that fuels the conflict. Using grounded theory to analyze data from interactive problem-solving workshops between Palestinians and Israelis a theory about the role of national identity in turning conflict into protracted conflict is developed. Drawing upon research from, among others, social identity theory, just world theory and prejudice it is argued that national identity is a prime candidate to provide the justification of a conflict party’s goals and the dehumanization of the other necessary to make a conflict protracted. It is not the nature of national identity itself that lets it perform this role but rather the ability to mobilize a constituency for social action (see Stürmer, Simon, Loewy, & Jörger, 2003). Reicher & Hopkins (1996) have demonstrated that national identity is constructed by political entrepreneurs to further their cause, even if this construction is not a conscious one. Data from interactive problem-solving workshops suggest that the possibility of conflict resolution is actually seen by participants as a direct threat of annihilation. Understanding the investment necessary to make conflict protracted this reaction seems plausible. The justification for ones actions provided by national identity makes the conflict an integral part of a conflict party’s identity. Conflict resolution, it is argued, is therefore a threat to the very core of the current national identity. This may explain why so many peace agreements have failed to provide the hoped for resolution of conflict. But if national identity is being used in a constructionist way to attain political goals, a political project of conflict resolution, if it is conscious of the constructionist process, needs to develop a national identity that is independent of conflict and therefore able to accommodate conflict resolution. From this understanding it becomes clear why national identity needs to change, i.e. be disarmed, if conflict resolution is to be successful. This process of disarmament is theorized to be similar to the process of creating and sustaining protracted conflict. What shape and function this change should have is explored from the understanding of the role of national identity in supporting conflict. Ideas how track-two diplomacy efforts, such as the interactive problem-solving workshop, could integrate a process by both conflict parties to disarm their respective identities are developed.

Developmental origins of physiological stress reactivity

The model of developmental origins of health and disease proposes that organisms during fetal period utilize cues that enable their adaptation in the postnatal environment they are likely to live, having short-term advantages when trying to survive in environment but simultaneously in the long run have costs for health. A large body of epidemiological research has found that low birth weight, a marker of intrauterine conditions, is associated with cardiovascular (CV) disease. Since the reported associations of birth weight with normal variation in the resting blood pressure (BP), a major predictor of CV disease risk, have been modest, a key candidate mediating the link has been CV and hypothalamus-pituitary-adrenal axes (HPAA) reactivity to stress. In addition, not only weight at birth but also gestational age and early postnatal growth may have independent associations to stress reactivity. The aim of this thesis was to investigate whether pre- and postnatal growth and gestational age are associated with CV and HPAA activity before, during and after stress in childhood and in late adulthood. Altogether 287 men and women aged 60-70 and 299 boys and girls aged 7-9 underwent Trier Social Stress Test. Several indices of HPAA and CV were measured and birth size and gestational age were obtained from birth records. Results showed that low birth weight was associated with low HPAA activity during psychosocial stress, and rapid gain in BMI during years 7-11 was related to heightened stress reactivity to psychosocial stress. Size at birth in children and gestational age and early postnatal (0-2 years) gain in height in adults were associated with CV stress responses; however, in a sex-specific manner. Given that CV stress responses and HPAA activity are markers of CV disease vulnerability, our results may partly explain the associations between early environment and later CV disease.

Observation of exclusive charmonium production and gamma+gamma to mu+mu- in p+pbar collisions at sqrt{s} = 1.96 TeV

We have observed the reactions p+pbar --> p+X+pbar, with X being a centrally produced J/psi, psi(2S) or chi_c0, and gamma+gamma --> mu+mu-, in proton- antiproton collisions at sqrt{s} = 1.96 TeV using the Run II Collider Detector at Fermilab. The event signature requires two oppositely charged muons, each with pseudorapidity |eta| mu+mu-. Events with a J/psi and an associated photon candidate are consistent with exclusive chi_c0 production through double pomeron exchange. The exclusive vector meson production is as expected for elastic photo- production, gamma+p --> J/psi(psi(2S)) + p, which is observed here for the first time in hadron-hadron collisions. The cross sections ds/dy(y=0) for p + pbar --> p + X + pbar with X = J/psi, psi(2S) orchi_c0 are 3.92+/-0.62 nb, 0.53+/-0.14 nb, and 75+/-14 nb respectively. The cross section for the continuum, with |eta(mu+/-)|

Observation of exclusive charmonium production and gamma+gamma to mu+mu- in p+pbar collisions at sqrt{s} = 1.96 TeV

We have observed the reactions p+pbar --> p+X+pbar, with X being a centrally produced J/psi, psi(2S) or chi_c0, and gamma+gamma --> mu+mu-, in proton- antiproton collisions at sqrt{s} = 1.96 TeV using the Run II Collider Detector at Fermilab. The event signature requires two oppositely charged muons, each with pseudorapidity |eta| mu+mu-. Events with a J/psi and an associated photon candidate are consistent with exclusive chi_c0 production through double pomeron exchange. The exclusive vector meson production is as expected for elastic photo- production, gamma+p --> J/psi(psi(2S)) + p, which is observed here for the first time in hadron-hadron collisions. The cross sections ds/dy(y=0) for p + pbar --> p + X + pbar with X = J/psi, psi(2S) orchi_c0 are 3.92+/-0.62 nb, 0.53+/-0.14 nb, and 75+/-14 nb respectively. The cross section for the continuum, with |eta(mu+/-)|

Data integration from two microarray platforms identifies bi-allelic genetic inactivation of RIC8A in a breast cancer cell line

Background: Using array comparative genomic hybridization (aCGH), a large number of deleted genomic regions have been identified in human cancers. However, subsequent efforts to identify target genes selected for inactivation in these regions have often been challenging. Methods: We integrated here genome-wide copy number data with gene expression data and non-sense mediated mRNA decay rates in breast cancer cell lines to prioritize gene candidates that are likely to be tumour suppressor genes inactivated by bi-allelic genetic events. The candidates were sequenced to identify potential mutations. Results: This integrated genomic approach led to the identification of RIC8A at 11p15 as a putative candidate target gene for the genomic deletion in the ZR-75-1 breast cancer cell line. We identified a truncating mutation in this cell line, leading to loss of expression and rapid decay of the transcript. We screened 127 breast cancers for RIC8A mutations, but did not find any pathogenic mutations. No promoter hypermethylation in these tumours was detected either. However, analysis of gene expression data from breast tumours identified a small group of aggressive tumours that displayed low levels of RIC8A transcripts. qRT-PCR analysis of 38 breast tumours showed a strong association between low RIC8A expression and the presence of TP53 mutations (P = 0.006). Conclusion: We demonstrate a data integration strategy leading to the identification of RIC8A as a gene undergoing a classical double-hit genetic inactivation in a breast cancer cell line, as well as in vivo evidence of loss of RIC8A expression in a subgroup of aggressive TP53 mutant breast cancers.

Measurement of the top quark mass in the dilepton channel using mT2 at CDF

We present measurements of the top quark mass using the \mT2, a variable related to the transverse mass in events with two missing particles. We use the template method applied to t\tbar dilepton events produced in p\pbar collisions at Fermilab's Tevatron and collected by the CDF detector. From a data sample corresponding to an integrated luminosity of 3.4 \invfb, we select 236 t\tbar candidate events. Using the \mT2 distribution, we measure the top quark mass to be M_{Top} = 168.0^{+4.8}_{-4.0} $\pm$ {2.9} GeV/c^{2}. By combining the \mT2 with the reconstructed top mass distributions based on a neutrino weighting method, we measure M_{top}=169.3 $\pm$ 2.7 $\pm$ 3.2 GeV/c^{2}. This is the first application of the \mT2 variable in a mass measurement at a hadron collider.

Integrative functional genomics analysis of sustained polyploidy phenotypes in breast cancer cells identifies an oncogenic profile for GINS2

Aneuploidy is among the most obvious differences between normal and cancer cells. However, mechanisms contributing to development and maintenance of aneuploid cell growth are diverse and incompletely understood. Functional genomics analyses have shown that aneuploidy in cancer cells is correlated with diffuse gene expression signatures and that aneuploidy can arise by a variety of mechanisms, including cytokinesis failures, DNA endoreplication and possibly through polyploid intermediate states. Here, we used a novel cell spot microarray technique to identify genes with a loss-of-function effect inducing polyploidy and/or allowing maintenance of polyploid cell growth of breast cancer cells. Integrative genomics profiling of candidate genes highlighted GINS2 as a potential oncogene frequently overexpressed in clinical breast cancers as well as in several other cancer types. Multivariate analysis indicated GINS2 to be an independent prognostic factor for breast cancer outcome (p = 0.001). Suppression of GINS2 expression effectively inhibited breast cancer cell growth and induced polyploidy. In addition, protein level detection of nuclear GINS2 accurately distinguished actively proliferating cancer cells suggesting potential use as an operational biomarker.

Detection,amplification and sequence homology of sodC in clinical isolates of Salmonella sp

Background & objectives: Periplasmic copper and zinc superoxide dismutase (Cu,Zn-SOD or SodC) is an important component of the antioxidant shield which protects bacteria from the phagocytic oxidative burst. Cu,Zn-SODs protect Gram-negative bacteria against oxygen damage which have also been shown to contribute to the pathogenicity of these bacterial species. We report the presence of SodC in drug resistant Salmonella sp. isolated from patients suffering from enteric fever. Further sodC was amplified, cloned into Escherichia coli and the nucleotide sequence and amino acid sequence homology were compared with the standard strain Salmonella Typhimurium 14028. Methods: Salmonella enterica serovar Typhi (S. Typhi) and Salmonellaenterica serovar Paratyphi (S. Paratyphi) were isolated and identified from blood samples of the patients. The isolates were screened for the presence of Cu, Zn-SOD by PAGE using KCN as inhibitor of Cu,Zn-SOD. The gene (sodC) was amplified by PCR, cloned and sequenced. The nucleotide and amino acid sequences of sodC were compared using CLUSTAL X.Results: SodC was detected in 35 per cent of the Salmonella isolates. Amplification of the genomic DNA of S. Typhi and S. Paratyphi with sodC specific primers resulted in 519 and 515 bp amplicons respectively. Single mutational difference at position 489 was observed between thesodC of S. Typhi and S. Paratyphi while they differed at 6 positions with the sodC of S. Typhimurium 14028. The SodC amino acid sequences of the two isolates were homologous but 3 amino acid difference was observed with that of standard strain S. Typhimurium 14028.Interpretation & conclusions: The presence of SodC in pathogenic bacteria could be a novel candidate as phylogenetic marker.

Measurement of the Single Top Quark Production Cross Section at CDF

We report a measurement of the single top quark production cross section in 2.2 ~fb-1 of p-pbar collision data collected by the Collider Detector at Fermilab at sqrt{s}=1.96 TeV. Candidate events are classified as signal-like by three parallel analyses which use likelihood, matrix element, and neural network discriminants. These results are combined in order to improve the sensitivity. We observe a signal consistent with the standard model prediction, but inconsistent with the background-only model by 3.7 standard deviations with a median expected sensitivity of 4.9 standard deviations. We measure a cross section of 2.2 +0.7 -0.6(stat+sys) pb, extract the CKM matrix element value |V_{tb}|=0.88 +0.13 -0.12 (stat+sys) +- 0.07(theory), and set the limit |V_{tb}|>0.66 at the 95% C.L.

Measurement of the top quark mass with dilepton events selected using neuroevolution at CDF

We report a measurement of the top quark mass $M_t$ in the dilepton decay channel $t\bar{t}\to b\ell'^{+}\nu'_\ell\bar{b}\ell^{-}\bar{\nu}_{\ell}$. Events are selected with a neural network which has been directly optimized for statistical precision in top quark mass using neuroevolution, a technique modeled on biological evolution. The top quark mass is extracted from per-event probability densities that are formed by the convolution of leading order matrix elements and detector resolution functions. The joint probability is the product of the probability densities from 344 candidate events in 2.0 fb$^{-1}$ of $p\bar{p}$ collisions collected with the CDF II detector, yielding a measurement of $M_t= 171.2\pm 2.7(\textrm{stat.})\pm 2.9(\textrm{syst.})\mathrm{GeV}/c^2$.

Direct Top-Quark Width Measurement at CDF

We present a measurement of the top-quark width using $t\bar{t}$ events produced in $p\bar{p}$ collisions at Fermilab's Tevatron collider and collected by the CDF II detector. In the mode where the top quark decays to a $W$ boson and a bottom quark, we select events in which one $W$ decays leptonically and the other hadronically~(lepton + jets channel) . From a data sample corresponding to 4.3~fb$^{-1}$ of integrated luminosity, we identify 756 candidate events. The top-quark mass and the mass of $W$ boson that decays hadronically are reconstructed for each event and compared with templates of different top-quark widths~($\Gamma_t$) and deviations from nominal jet energy scale~($\Delta_{JES}$) to perform a simultaneous fit for both parameters, where $\Delta_{JES}$ is used for the {\it in situ} calibration of the jet energy scale. By applying a Feldman-Cousins approach, we establish an upper limit at 95$\%$ confidence level~(CL) of $\Gamma_t $

Measurement of the top quark mass in the dilepton channel using mT2 at CDF

We present measurements of the top quark mass using the \mT2, a variable related to the transverse mass in events with two missing particles. We use the template method applied to t\tbar dilepton events produced in p\pbar collisions at Fermilab's Tevatron and collected by the CDF detector. From a data sample corresponding to an integrated luminosity of 3.4 \invfb, we select 236 t\tbar candidate events. Using the \mT2 distribution, we measure the top quark mass to be M_{Top} = 168.0^{+4.8}_{-4.0} $\pm$ {2.9} GeV/c^{2}. By combining the \mT2 with the reconstructed top mass distributions based on a neutrino weighting method, we measure M_{top}=169.3 $\pm$ 2.7 $\pm$ 3.2 GeV/c^{2}. This is the first application of the \mT2 variable in a mass measurement at a hadron collider.

Search for Pair Production of Supersymmetric Top Quarks in Dilepton Events from pp̅ Collisions at √s=1.96 TeV

We present the results of a search for pair production of the supersymmetric partner of the top quark (the stop quark $\tilde{t}_{1}$) decaying to a $b$-quark and a chargino $\chargino$ with a subsequent $\chargino$ decay into a neutralino $\neutralino$, lepton $\ell$, and neutrino $\nu$. Using a data sample corresponding to 2.7 fb$^{-1}$ of integrated luminosity of $p\bar{p}$ collisions at $\sqrt{s} = 1.96$ TeV collected by the CDF II detector, we reconstruct the mass of candidate stop events and fit the observed mass spectrum to a combination of standard model processes and stop quark signal. We find no evidence for $\pairstop$ production and set 95% C.L. limits on the masses of the stop quark and the neutralino for several values of the chargino mass and the branching ratio ${\cal B}(\chargino\to\neutralino\ell^{\pm}\nu)$.