Development and simulation of an active target detector with GEM foil readout

At CERN, radioactive ion beams with energies of up to 10 MeV/u can be pro- duced by a newly commissioned post-accelerator, HIE-ISOLDE, which expands the possibilities for nuclear reaction studies. To investigate the collision properties of the ion beam with a target, an active gas–target detector is under development by the Reactions Group at the Nuclear Physics Division in Lund. The existing detector setup was further investigated in this thesis. Experimental tests of the gain and stability of the detector were performed with the simulation package Garfield++ for a 82/18 Ar/CO 2 gas mixture and a 55 Fe source. The results were compared to results obtained from an earlier project. Simulations of electron drift were performed for different drift distances to characterize the spread of an electron cloud to design a new backgammon shaped readout plane to investigate the electron diffusion. First tests of new readout electronics have been performed and a C++ file has been written to investigate cross talk of the used Kapton cables.Simulations of heavy element synthesis How to improve on the knowledge of heavy element production using a gas box The creation of elements, the basis for life on earth, is a topic of long standing interest and it is particularly interesting for the production of heavy elements above iron. Stars that gain energy by fusion reactions can produce elements up to iron. Heavier stable and radioactive nuclei are supposed to be created in star explosions. To simulate the reactions that occur in such environments, collisions between a gas and radioactive atomic nuclei can be used. For this purpose, radioactive particles can be shot into a gas that acts as target and detector at the same time. The reaction products reveal proper- ties of the interaction, which then helps to improve the understanding of heavy element synthesis. At the ISOLDE facility at CERN, such experiments take place. The active gas-target detector developed in this thesis is planned to be used in these experiments. In this thesis tests have been performed with a specific type of detector, based on Gas Electron Multiplier (GEM) foils for this purpose. The detector contains a gas filled volume, to which a drift potential is applied via a drift cathode. When a charged particle enters the gas, it will kick out electrons from the gas atom shell. This ionization process is used to track the particles path and recreate the reaction. Due to the electric field, the electrons produce will drift towards the anode readout plane and ionize further gas atoms in collisions. To see the signal, the electrons are multiplied by the GEM foils. These foils are thin polymer foils coated with copper and perforated with small holes. Depending on where a radioactive particle moves through the gas, a trace of electrons is created and the particle can be tracked. From the length of the track and the amplitude of the produced signals, the energy of the reaction products can be determined. More- over, the detected particles can be identified by their specific energy loss in the gas.With the help of a gas filled GEM detector box, one can therefore investigate super element synthesis and uncover the secrets of stars interior

Onco-miR-155 targets SHIP1 to promote TNFalpha-dependent growth of B cell lymphomas.

Non-coding microRNAs (miRs) are a vital component of post-transcriptional modulation of protein expression and, like coding mRNAs harbour oncogenic properties. However, the mechanisms governing miR expression and the identity of the affected transcripts remain poorly understood. Here we identify the inositol phosphatase SHIP1 as a bonafide target of the oncogenic miR-155. We demonstrate that in diffuse large B cell lymphoma (DLBCL) elevated levels of miR-155, and consequent diminished SHIP1 expression are the result of autocrine stimulation by the pro-inflammatory cytokine tumour necrosis factor a (TNFalpha). Anti-TNFalpha regimen such as eternacept or infliximab were sufficient to reduce miR-155 levels and restored SHIP1 expression in DLBCL cells with an accompanying reduction in cell proliferation. Furthermore, we observed a substantial decrease in tumour burden in DLBCL xenografts in response to eternacept. These findings strongly support the concept that cytokine-regulated miRs can function as a crucial link between inflammation and cancer, and illustrate the feasibility of anti-TNFalpha therapy as a novel and immediately accessible (co)treatment for DLBCL

A Census of Early-phase High-mass Star Formation in the Central Molecular Zone

We present new observations of the C-band continuum emission and masers to assess high-mass (>8 ${M}_{\odot }$) star formation at early evolutionary phases in the inner 200 pc of the Central Molecular Zone (CMZ) of the Galaxy. The continuum observation is complete to free–free emission from stars above 10–11 ${M}_{\odot }$ in 91% of the covered area. We identify 104 compact sources in the continuum emission, among which five are confirmed ultracompact H ii regions, 12 are candidates of ultracompact H ii regions, and the remaining 87 sources are mostly massive stars in clusters, field stars, evolved stars, pulsars, extragalactic sources, or of unknown nature that is to be investigated. We detect class ii CH3OH masers at 23 positions, among which six are new detections. We confirm six known H2CO masers in two high-mass star-forming regions and detect two new H2CO masers toward the Sgr C cloud, making it the ninth region in the Galaxy that contains masers of this type. In spite of these detections, we find that current high-mass star formation in the inner CMZ is only taking place in seven isolated clouds. The results suggest that star formation at early evolutionary phases in the CMZ is about 10 times less efficient than expected from the dense gas star formation relation, which is in line with previous studies that focus on more evolved phases of star formation. This means that if there will be any impending, next burst of star formation in the CMZ, it has not yet begun

Advancing Radiation-Detected Resonance Ionization towards Heavier Elements and More Exotic Nuclides

RAdiation-Detected Resonance Ionization Spectroscopy (RADRIS) is a versatile method for highly sensitive laser spectroscopy studies of the heaviest actinides. Most of these nuclides need to be produced at accelerator facilities in fusion-evaporation reactions and are studied immediately after their production and separation from the primary beam due to their short half-lives and low production rates of only a few atoms per second or less. Only recently, the first laser spectroscopic investigation of nobelium (Z=102) was performed by applying the RADRIS technique in a buffer-gas-filled stopping cell at the GSI in Darmstadt, Germany. To expand this technique to other nobelium isotopes and for the search for atomic levels in the heaviest actinide element, lawrencium (Z=103), the sensitivity of the RADRIS setup needed to be further improved. Therefore, a new movable double-detector setup was developed, which enhances the overall efficiency by approximately 65% compared to the previously used single-detector setup. Further development work was performed to enable the study of longer-lived (t₁/₂>1 h) and shorter-lived nuclides (t₁/₂<1 s) with the RADRIS method. With a new rotatable multi-detector design, the long-lived isotope 254Fm (t₁/₂=3.2 h) becomes within reach for laser spectroscopy. Upcoming experiments will also tackle the short-lived isotope 251No (t₁/₂=0.8 s) by applying a newly implemented short RADRIS measurement cycle

Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, which antagonizes B cell receptor (BCR) signals, demonstrates remarkable clinical activity in chronic lymphocytic leukemia (CLL). The lymphocytosis experienced by most patients under ibrutinib has previously been attributed to inhibition of BTK-dependent integrin and chemokine cues operating to retain the tumor cells in nodal compartments. Here, we show that the VLA-4 integrin, as expressed by CD49d-positive CLL, can be inside-out activated upon BCR triggering, thus reinforcing the adhesive capacities of CLL cells. In vitro and in vivo ibrutinib treatment, although reducing the constitutive VLA-4 activation and cell adhesion, can be overcome by exogenous BCR triggering in a BTK-independent manner involving PI3K. Clinically, in three independent ibrutinib-treated CLL cohorts, CD49d expression identifies cases with reduced lymphocytosis and inferior nodal response and behaves as independent predictor of shorter progression-free survival, suggesting the retention of CD49d-expressing CLL cells in tissue sites via activated VLA-4. Evaluation of CD49d expression should be incorporated in the characterization of CLL undergoing therapy with BCR inhibitors

The Survey of Water and Ammonia in the Galactic Center (SWAG): Molecular Cloud Evolution in the Central Molecular Zone

The Survey of Water and Ammonia in the Galactic Center (SWAG) covers the Central Molecular Zone (CMZ) of the Milky Way at frequencies between 21.2 and 25.4 GHz obtained at the Australia Telescope Compact Array at $\sim 0.9$ pc spatial and $\sim 2.0$ km s$^{-1}$ spectral resolution. In this paper, we present data on the inner $\sim 250$ pc ($1.4^\circ$) between Sgr C and Sgr B2. We focus on the hyperfine structure of the metastable ammonia inversion lines (J,K) = (1,1) - (6,6) to derive column density, kinematics, opacity and kinetic gas temperature. In the CMZ molecular clouds, we find typical line widths of $8-16$ km s$^{-1}$ and extended regions of optically thick ($\tau > 1$) emission. Two components in kinetic temperature are detected at $25-50$ K and $60-100$ K, both being significantly hotter than dust temperatures throughout the CMZ. We discuss the physical state of the CMZ gas as traced by ammonia in the context of the orbital model by Kruijssen et al. (2015) that interprets the observed distribution as a stream of molecular clouds following an open eccentric orbit. This allows us to statistically investigate the time dependencies of gas temperature, column density and line width. We find heating rates between $\sim 50$ and $\sim 100$ K Myr$^{-1}$ along the stream orbit. No strong signs of time dependence are found for column density or line width. These quantities are likely dominated by cloud-to-cloud variations. Our results qualitatively match the predictions of the current model of tidal triggering of cloud collapse, orbital kinematics and the observation of an evolutionary sequence of increasing star formation activity with orbital phase

A Census of Early Phase High-Mass Star Formation in the Central Molecular Zone

We present new observations of C-band continuum emission and masers to assess high-mass ($>$8 $M_\odot$) star formation at early evolutionary phases in the inner 200 pc of the Central Molecular Zone (CMZ) of the Galaxy. The continuum observation is complete to free-free emission from stars above 10-11 $M_\odot$ in 91% of the covered area. We identify 104 compact sources in the continuum emission, among which five are confirmed ultracompact H II regions, 12 are candidates of ultra-compact H II regions, and the remaining 87 sources are mostly massive stars in clusters, field stars, evolved stars, pulsars, extragalactic sources, or of unknown nature that is to be investigated. We detect class II CH$_3$OH masers at 23 positions, among which six are new detections. We confirm six known H$_2$CO masers in two high-mass star forming regions, and detect two new H$_2$CO masers toward the Sgr C cloud, making it the ninth region in the Galaxy that contains masers of this type. In spite of these detections, we find that current high-mass star formation in the inner CMZ is only taking place in seven isolated clouds. The results suggest that star formation at early evolutionary phases in the CMZ is about 10 times less efficient than expected by the dense gas star formation relation, which is in line with previous studies that focus on more evolved phases of star formation. This means that if there will be any impending, next burst of star formation in the CMZ, it has not yet begun

Onco‐miR‐155 targets SHIP1 to promote TNFα‐dependent growth of B cell lymphomas

Non-coding microRNAs (miRs) are a vital component of post-transcriptional modulation of protein expression and, like coding mRNAs harbour oncogenic properties. However, the mechanisms governing miR expression and the identity of the affected transcripts remain poorly understood. Here we identify the inositol phosphatase SHIP1 as a bonafide target of the oncogenic miR-155. We demonstrate that in diffuse large B cell lymphoma (DLBCL) elevated levels of miR-155, and consequent diminished SHIP1 expression are the result of autocrine stimulation by the pro-inflammatory cytokine tumour necrosis factor α (TNFα). Anti-TNFα regimen such as eternacept or infliximab were sufficient to reduce miR-155 levels and restored SHIP1 expression in DLBCL cells with an accompanying reduction in cell proliferation. Furthermore, we observed a substantial decrease in tumour burden in DLBCL xenografts in response to eternacept. These findings strongly support the concept that cytokine-regulated miRs can function as a crucial link between inflammation and cancer, and illustrate the feasibility of anti-TNFα therapy as a novel and immediately accessible (co)treatment for DLBCL