Realization and characterization of graphitic contacts on diamond by means of laser

This work deals with the realization and characterization of integrated graphitic contacts on diamond by means of laser irradiation (graphitization), in order to obtain good quality ohmic electrodes for nuclear radiation detectors to be used in high energy physics experiments. Unlike the conventional method used for the electrode production, which requires numerous steps and very well controlled environmental conditions, this alternative technique presents many advantages: the contacts are realized in air at room temperature in a single step. In this study, the characteristics of several graphitic structures realized on a diamond surface by changing the radiation-matter interaction parameters have been evaluated in order to define the best experimental conditions to create graphitic electrodes with low resistivity. The obtained results are promising: contacts perfectly adherent, with good charge collection properties, stable and resistant to ionizing radiation

Performance of the diamond active target prototype for the PADME experiment at the DAΦ\PhiNE BTF

The PADME experiment at the DA$\Phi$NE Beam-Test Facility (BTF) is designed to search for the gauge boson of a new $\rm U(1)$ interaction in the process e$^+$e$^-\rightarrow\gamma$+$\rm A'$, using the intense positron beam hitting a light target. The $\rm A'$, usually referred as dark photon, is assumed to decay into invisible particles of a secluded sector and it can be observed by searching for an anomalous peak in the spectrum of the missing mass measured in events with a single photon in the final state. The measurement requires the determination of the 4-momentum of the recoil photon, performed by a homogeneous, highly segmented BGO crystals calorimeter. A significant improvement of the missing mass resolution is possible using an active target capable to determine the average position of the positron bunch with a resolution of less than 1 mm. This report presents the performance of a real size $\rm (2x2 cm^2)$ PADME active target made of a thin (50 $\mu$m) diamond sensor, with graphitic strips produced via laser irradiation on both sides. The measurements are based on data collected in a beam test at the BTF in November 2015.Comment: 7 pages, 10 figure

Cell cycle perturbations and apoptosis induced by isohomohalichondrin B (IHB), a natural marine compound

Isohomohalichondrin B (IHB), a novel marine compound with anti-tumoral activity, extracted from the Lissodendorix sponge, inhibits GTP binding to tubulin, preventing microtubule assembly. Cell cycle perturbations and apoptosis induced by IHB were investigated on selected human cancer cell lines by using flow cytometric and biochemical techniques. Monoparameter flow cytometric analysis showed that 1 h IHB exposure caused a delayed progression through S-phase, a dramatic block in G2M phase of the cell cycle and the appearance of tetraploid cell population in LoVo, LoVo/DX, MOLT-4 and K562 cells. At 24 h after IHB exposure, the majority of cells blocked in G2M were in prophase as assessed by morphological analysis and by the fact that they expressed high levels of cyclin A/cdc2 and cyclin B1/cdc2. At 48 h, all cells were tetraploid as assessed by biparameter cyclin A/DNA and cyclin B1/DNA content analysis. Apoptotic death was detected in both leukaemic MOLT-4 and K562 cells, which express wild-type and mutated p53 respectively, when the cells were blocked in mitotic prophase. In conclusion, IHB is a novel potent anti-tumour drug that causes delayed S-phase progression, mitotic block, tetraploidy and apoptosis in cancer cell lines. © 1999 Cancer Research Campaig

Both ghrelin deletion and unacylated ghrelin overexpression preserve muscles in aging mice

Sarcopenia, the decline in muscle mass and functionality during aging, might arise from age-associated endocrine dysfunction. Ghrelin is a hormone circulating in both acylated (AG) and unacylated (UnAG) forms with antiatrophic activity on skeletal muscle. Here, we show that not only lifelong overexpression of UnAG (Tg) in mice, but also the deletion of ghrelin gene (Ghrl KO) attenuated the age-associated muscle atrophy and functionality decline, as well as systemic inflammation. Yet, the aging of Tg and Ghrl KO mice occurs with different dynamics: while old Tg mice seem to preserve the characteristics of young animals, Ghrl KO mice features deteriorate with aging. However, young Ghrl KO mice show more favorable traits compared to WT animals that result, on the whole, in better performances in aged Ghrl KO animals. Treatment with pharmacological doses of UnAG improved muscle performance in old mice without modifying the feeding behavior, body weight, and adipose tissue mass. The antiatrophic effect on muscle mass did not correlate with modifications of protein catabolism. However, UnAG treatment induced a strong shift towards oxidative metabolism in muscle. Altogether, these data confirmed and expanded some of the previously reported findings and advocate for the design of UnAG analogs to treat sarcopenia

Diamond graphitization by laser-writing for all-carbon detector applications

The surface of a detector grade CVD polycrystalline diamond sample (5 × 5 × 0.05 mm3) was irradiated by an ArF excimer laser (λ = 193 nm, τ = 20 ns) to produce graphitic conductive layers. In particular, two sets of four parallel graphitic strip-like contacts, with 1 mm pitch, were created along the whole sample on the top and on the rear surfaces of the sample respectively. The two series of stripes lie normally to each other. Such a grid allows to obtain a segmented all-carbon device capable of giving bi-dimensional information on particle detection processes in nuclear applications. Afterwards, an extensive characterization of the samples was performed: SEM and micro-Raman investigations to study the morphological and structural evolution of the irradiated areas, EDS measurements to individuate any absorption phenomena from environment associated to laser treatment, and nanoindentation mapping to understand how the hard-soft transformation occurred depending on the locally transferred energy. Finally, current-voltage analyses were carried out checking the ohmic behavior of the diamond-graphite contact. By comparing the results of the different characterization analyses, a strong periodicity of the modified surface properties was found, confirming the reliability and reproducibility of the laser-induced graphitization process. The results demonstrate that the laser-writing technique is a good and fast solution to produce graphitic contacts on diamond surface and therefore represents a promising way to fabricate segmented all-carbon devices

NOXA-Induced Alterations in the Bax/Smac Axis Enhance Sensitivity of Ovarian Cancer Cells to Cisplatin

Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy

Frequency of left ventricular hypertrophy in non-valvular atrial fibrillation

Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 \ub1 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index 640.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc 652 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention

Adherence to antibiotic treatment guidelines and outcomes in the hospitalized elderly with different types of pneumonia

Background: Few studies evaluated the clinical outcomes of Community Acquired Pneumonia (CAP), Hospital-Acquired Pneumonia (HAP) and Health Care-Associated Pneumonia (HCAP) in relation to the adherence of antibiotic treatment to the guidelines of the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) in hospitalized elderly people (65 years or older). Methods: Data were obtained from REPOSI, a prospective registry held in 87 Italian internal medicine and geriatric wards. Patients with a diagnosis of pneumonia (ICD-9 480-487) or prescribed with an antibiotic for pneumonia as indication were selected. The empirical antibiotic regimen was defined to be adherent to guidelines if concordant with the treatment regimens recommended by IDSA/ATS for CAP, HAP, and HCAP. Outcomes were assessed by logistic regression models. Results: A diagnosis of pneumonia was made in 317 patients. Only 38.8% of them received an empirical antibiotic regimen that was adherent to guidelines. However, no significant association was found between adherence to guidelines and outcomes. Having HAP, older age, and higher CIRS severity index were the main factors associated with in-hospital mortality. Conclusions: The adherence to antibiotic treatment guidelines was poor, particularly for HAP and HCAP, suggesting the need for more adherence to the optimal management of antibiotics in the elderly with pneumonia