The Role of SATB1 in Medial Ganglionic Eminence-derived Cortical Interneuron Differentiation.

Brain function depends on the activity of cortical γ-aminobutyric acid- producing (GABAergic) interneurons, which participate in the formation of inhibitory circuits and control the activity of excitatory glutamatergic pyramidal neurons. Cortical GABAergic interneurons are extremely diverse in morphology, electrophysiology and molecular marker expression. A plethora of transcription factors that control aspects of this diversity has now been identified. Among them, the LIM-homeodomain transcription factor LHX6 is required for the differentiation of parvalbumin+ (PV+) and somatostatin+ (SST+) cortical interneurons. However, little is known about the molecular cascades operating downstream of LHX6 to control the maturation of these two major interneuron subtypes. With a focus on identifying region- and stage-specific factors regulating interneuron maturation, a genome-wide gene expression analysis was conducted in our laboratory and identified the gene encoding the chromatin organiser protein SATB1 as an LHX6 target in the E15.5 mouse cortex. In this thesis, we investigate the in vivo role of SATB1 in cortical interneuron terminal differentiation. Using a constitutive Satb1-null mouse established in our laboratory we demonstrate that Satb1 regulates multiple aspects of SST+ interneuron maturation. In contrast, by generating mice with a specific deletion of Satb1 in PV+ interneurons (PV-Cre;Satb1-flox) we show that Satb1 is not required for the maturation of this group of inhibitory neurons. Moreover, interneuron-specific deletion of Satb1 with the Nkx2.1-Cre line reveals a disruption of the excitation/inhibition balance in the brain and a significant loss of both SST+ and PV+ interneurons. Finally, we show that SATB1 and the general neuronal maturation marker KCC2 are coexpressed in mature cortical interneurons. By performing overexpression experiments in brain slices we observed regulation of Kcc2 expression by SATB1, but failed to detect any reciprocal regulation of Satb1 by KCC2. Overall, our findings provide a basis for understanding the terminal differentiation of interneurons in the mammalian cortex

Exophthalmos as a First Manifestation of Small Cell Lung Cancer: A Long-Term Follow-Up

Small cell lung cancer is characterized by rapid growth and early metastasis. Despite its sensitivity to cytotoxic therapy, until now treatments have failed to control or cure this disease in most patients. Orbital metastases are a rare manifestation of systemic malignancies. Breast and lung cancers represent more than two thirds of the primary cancer sites. Metastases to the eye and orbit develop in approximately 0.7–12% of patients with lung cancer. Here, we report a rare case of exophthalmos as the first manifestation of a metastatic carcinoma due to small cell lung cancer, and a 6-months follow-up with complete exophthalmic response to chemotherapy

Biocompatibility of poly(lactic acid) with incorporated graphene-based materials

The incorporation of graphene-based materials has been shown to improve mechanical properties of poly(lactic acid) (PLA). In this work, PLA films and composite PLA films incorporating two graphene-based materials – graphene oxide (GO) and graphene nanoplatelets (GNP) – were prepared and characterized regarding not only biocompatibility, but also surface topography, chemistry and wettability. The presence of both fillers changed the films surface topography, increasing the roughness, and modified the wettability – the polar component of surface free energy increased 59% with GO and decreased 56% with GNP. Mouse embryo fibroblasts incubated with both fillers exceeded the IC50 in both cases with a concentration of 10 μg mL−1. No variations in cell proliferation at the surface of the composite films were observed, except for those containing GO after 24 h incubation, which presented higher cell proliferation than pristine PLA films. Platelet adhesion to PLA and PLA/GNP films was lower in the presence of plasma proteins than when no proteins were present. Furthermore, incorporation of GNP into PLA reduced platelet activation in the presence of plasma proteins. The results indicated that low concentrations of GO and GNP may be incorporated safely in PLA to improve aspects relevant for biomedical applications, such as mechanical properties.Funding for this work was partially provided by FEDER, through Programa Operacional Factores de Competitividade - COMPETE, and by National Funding through FCT - Fundacao para a Ciencia e a Tecnologia, in the framework of project PTDC/EME-PME/114808/2009 and of grant SFRH/BPD/63722/2009

Photocatalytic Degradation of Organic Pollutants in Water Using Graphene Oxide Composite

Developing sustainable and less-expensive technique is always challenging task in water treatment process. This chapter explores the recent development of photocatalysis technique in organic pollutant removal from the water. Particularly, advantages of graphene oxide in promoting the catalytic performance of semiconductor, metal nanoparticle and polymer based photocatalyst materials. Owing to high internal surface area and rapid electron conducting property of graphene oxide fostering as backbone scaffold for effective hetero-photocatalyst loading, and rapid photo-charge separation enables effective degradation of pollutant. This chapter summaries the recent development of graphene oxide composite (metal oxide, metal nanoparticle, metal chalcogenides, and polymers) in semiconductor photocatalysis process towards environmental remediation application

Studies of new Higgs boson interactions through nonresonant HH production in the b¯bγγ fnal state in pp collisions at √s = 13 TeV with the ATLAS detector

A search for nonresonant Higgs boson pair production in the b ¯bγγ fnal state is performed using 140 fb−1 of proton-proton collisions at a centre-of-mass energy of 13 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. This analysis supersedes and expands upon the previous nonresonant ATLAS results in this fnal state based on the same data sample. The analysis strategy is optimised to probe anomalous values not only of the Higgs (H) boson self-coupling modifer κλ but also of the quartic HHV V (V = W, Z) coupling modifer κ2V . No signifcant excess above the expected background from Standard Model processes is observed. An observed upper limit µHH < 4.0 is set at 95% confdence level on the Higgs boson pair production cross-section normalised to its Standard Model prediction. The 95% confdence intervals for the coupling modifers are −1.4 < κλ < 6.9 and −0.5 < κ2V < 2.7, assuming all other Higgs boson couplings except the one under study are fxed to the Standard Model predictions. The results are interpreted in the Standard Model efective feld theory and Higgs efective feld theory frameworks in terms of constraints on the couplings of anomalous Higgs boson (self-)interactions

Measurement of the H → γ γ and H → ZZ∗ → 4 cross-sections in pp collisions at √s = 13.6 TeV with the ATLAS detector

The inclusive Higgs boson production cross section is measured in the di-photon and the Z Z∗ → 4 decay channels using 31.4 and 29.0 fb−1 of pp collision data respectively, collected with the ATLAS detector at a centre of-mass energy of √s = 13.6 TeV. To reduce the model dependence, the measurement in each channel is restricted to a particle-level phase space that closely matches the chan nel’s detector-level kinematic selection, and it is corrected for detector effects. These measured fiducial cross-sections are σfid,γ γ = 76+14 −13 fb, and σfid,4 = 2.80 ± 0.74 fb, in agreement with the corresponding Standard Model predic tions of 67.6±3.7 fb and 3.67±0.19 fb. Assuming Standard Model acceptances and branching fractions for the two chan nels, the fiducial measurements are extrapolated to the full phase space yielding total cross-sections of σ (pp → H) = 67+12 −11 pb and 46±12 pb at 13.6 TeV from the di-photon and Z Z∗ → 4 measurements respectively. The two measure ments are combined into a total cross-section measurement of σ (pp → H) = 58.2±8.7 pb, to be compared with the Stan dard Model prediction of σ (pp → H)SM = 59.9 ± 2.6 p

Search for pairs of muons with small displacements in pp collisions at root s=13 TeV with the ATLAS detector

A search for new phenomena giving rise to pairs of opposite electrically charged muons with impact parameters in the millimeter range is presented, using 139 fb−1 of √s = 13 TeV pp collision data from the ATLAS detector at the LHC. The search targets the gap in coverage between existing searches targeting final states with leptons with large displacement and prompt leptons. No significant excess over the background expectation is observed and exclusion limits are set on the mass of long-lived scalar supersymmetric muon-partners (smuons) with much lower lifetimes than previously targeted by displaced muon searches. Smuon lifetimes down to 1 ps are excluded for a smuon mass of 100 GeV, and smuon masses up to 520 GeV are excluded for a proper lifetime of 10 ps, at 95% confidence level. Finally, model-independent limits are set on the contribution from new phenomena to the signal-region yield