77 research outputs found

    Ultra-thin oxide breakdown for OTP development in power technologies

    Get PDF
    AbstractOTP (One Time Programmable) memory in power technology enables electrical performance optimization together with area occupation reduction. In this paper, the aspects relative to the oxide breakdown (which is the key mechanism for memory programmability) are studied and applied to the development of an antifuse OTP cell in a 350 nm-CMOS power technology. The physical analysis of the degradation phases of an oxide layer is presented together with the physical models, exploited to foresee the device time-to-breakdown depending on applied voltage, oxide thickness etc. The achieved results are used in the development and reliable implementation of OTP cells in the target 350 nm-CMOS node

    Radiologic Cerebral Reperfusion at 24 h Predicts Good Clinical Outcome

    Get PDF
    Cerebral reperfusion and arterial recanalization are radiological features of the effectiveness of thrombolysis in acute ischemic stroke (AIS) patients. Here, an investigation of the prognostic role of early recanalization/reperfusion on clinical outcome was performed. In AIS patients (n = 55), baseline computerized tomography (CT) was performed 64 8 h from symptom onset, whereas CT determination of reperfusion/recanalization was assessed at 24 h. Multiple linear and logistic regression models were used to correlate reperfusion/recanalization with radiological (i.e., hemorrhagic transformation, ischemic core, and penumbra volumes) and clinical outcomes (assessed as National Institutes of Health Stroke Scale [NIHSS] reduction 65 8 points or a NIHSS 64 1 at 24 h and as modified Rankin Scale [mRS] < 2 at 90 days). At 24 h, patients achieving radiological reperfusion were n = 24, while the non-reperfused were n = 31. Among non-reperfused, n = 15 patients were recanalized. Radiological reperfusion vs. recanalization was also confirmed by early increased levels of circulating inflammatory biomarkers (i.e., serum osteopontin). In multivariate analysis, ischemic lesion volume reduction was associated with both recanalization (\u3b2 = 0.265; p = 0.014) and reperfusion (\u3b2 = 0.461; p < 0.001), but only reperfusion was independently associated with final infarct volume (\u3b2 = 12 0.333; p = 0.007). Only radiological reperfusion at 24 h predicted good clinical response at day 1 (adjusted OR 16.054 [1.423\u2013181.158]; p = 0.025) and 90-day good functional outcome (adjusted OR 25.801 [1.483\u2013448.840]; p = 0.026). At ROC curve analysis the AUC of reperfusion was 0.777 (p < 0.001) for the good clinical response at 24 h and 0.792 (p < 0.001) for 90-day clinical outcome. Twenty-four-hour radiological reperfusion assessed by CT is associated with good clinical response on day 1 and good functional outcome on day 90 in patients with ischemic stroke

    Characterization of the Santa Maria del Fiore Cupola construction tools using X-ray fluorescence

    Get PDF
    This paper presents the characterization of different tools employed in the construction of the Santa Maria del Fiore cathedral in Florence; they are part of the Opera di Santa Maria del Fiore collection and are currently exhibited in the Museo dell’Opera del Duomo. The analyzed objects are turnbuckles, pulleys, three-legged lewises, and pincers; indeed, despite their uniqueness and their importance from the historical point of view, this study is the first one that investigates their alloys composition. Actually, this information can be of great interest for curators to find the best conservation strategies and to have new insights on the production techniques typical of the Renaissance. The study was performed using X-Ray Fluorescence (XRF) in order to identify the materials constituting the objects. Then, XRF spectra were analyzed using chemometric techniques, namely Principal Components Analysis (PCA), in order to investigate possible similarities among different alloys and thus provide new indications to help collocating these tools in a specific historical period

    The C-Terminal Domain of CENP-C Displays Multiple and Critical Functions for Mammalian Centromere Formation

    Get PDF
    CENP-C is a fundamental component of functional centromeres. The elucidation of its structure-function relationship with centromeric DNA and other kinetochore proteins is critical to the understanding of centromere assembly. CENP-C carries two regions, the central and the C-terminal domains, both of which are important for the ability of CENP-C to associate with the centromeric DNA. However, while the central region is largely divergent in CENP-C homologues, the C-terminal moiety contains two regions that are highly conserved from yeast to humans, named Mif2p homology domains (blocks II and III). The activity of these two domains in human CENP-C is not well defined. In this study we performed a functional dissection of C-terminal CENP-C region analyzing the role of single Mif2p homology domains through in vivo and in vitro assays. By immunofluorescence and Chromatin immunoprecipitation assay (ChIP) we were able to elucidate the ability of the Mif2p homology domain II to target centromere and contact alpha satellite DNA. We also investigate the interactions with other conserved inner kinetochore proteins by means of coimmunoprecipitation and bimolecular fluorescence complementation on cell nuclei. We found that the C-terminal region of CENP-C (Mif2p homology domain III) displays multiple activities ranging from the ability to form higher order structures like homo-dimers and homo-oligomers, to mediate interaction with CENP-A and histone H3. Overall, our findings support a model in which the Mif2p homology domains of CENP-C, by virtue of their ability to establish multiple contacts with DNA and centromere proteins, play a critical role in the structuring of kinethocore chromatin

    Pseudo solid-appearing pancreatic serous microcystic adenomas: Histologic diagnosis with the EUS core biopsy fork-tip needle

    Get PDF
    Background and Objectives: Despite rarely, serous cystic adenoma (SCA) can assume a pseudo-solid aspect mimicking other pancreatic neoplasm as neuroendocrine tumor. EUS-FNA cytology has low diagnostic accuracy due to the scant cellularity of the collected samples. Histological diagnosis is usually made after resection. Recently, end-cutting needles for EUS-fine-needle biopsy (EUS-FNB), which obtain tissue cores by penetrating the lesions, have been developed. We aimed to assess the capability of EUS-FNB with SharkCore (TM) needles in the preoperative diagnosis of serous cystic adenoma pseudo-solid-appearing on imaging (Sa-SCA). Materials and Methods: Between January 2016 and January 2018, data from consecutive adult patients, who were referred for EUS-FNB of a solid pancreatic lesion and were diagnosed with having SCA, were retrieved from a single-center institutional database. Results: Two patients were excluded because of microcystic aspect at EUS. Histological diagnosis of SCA was made by EUS-FNB in the remaining 7 patients (5 females; mean age of 62.5 years). Lesions (mean size of 19.8 mm) were hypervascular on cross-sectional imaging, slightly hyperdense magnetic resonance imaging with T2-weighted images can, and negative at Ga-68-somatostatin receptor positron emission tomography and (18)fluoro-deoxyglucose positron emission tomography. EUS-FNB samples were judged adequate for a definitive diagnosis in all cases, achieving specimens suitable for histological evaluation and several ancillary stains. Histochemical positivity for periodic acid-Schiff (PAS) and PAS with diastase digestion was observed in 7/7 cases. Immunohistochemical positivity for alpha-inhibin (7/7), GLUT1 (6/6), MUC6 (5/5), and negativity for synaptophysin (7/7) and chromogranin A (2/2) favored SCA diagnosis. Conclusions: In the case of preoperative workup suspected for Sa-SCA, a "forward acquiring" needle could improve the rate of preoperative histological diagnosis

    Cerebral blood volume ASPECTS is the best predictor of clinical outcome in acute ischemic stroke: A retrospective, combined semi-quantitative and quantitative assessment

    Get PDF
    INTRODUCTION:The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned. METHODS:62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded. RESULTS:Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS ≤ 2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome. CONCLUSIONS:Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size

    Neuronopathic Gaucher disease models reveal defects in cell growth promoted by Hippo pathway activation

    Get PDF
    Gaucher Disease (GD), the most common lysosomal disorder, arises from mutations in the GBA1 gene and is characterized by a wide spectrum of phenotypes, ranging from mild hematological and visceral involvement to severe neurological disease. Neuronopathic patients display dramatic neuronal loss and increased neuroinflammation, whose molecular basis are still unclear. Using a combination of Drosophila dGBA1b loss-of-function models and GD patient-derived iPSCs differentiated towards neuronal precursors and mature neurons we showed that different GD- tissues and neuronal cells display an impairment of growth mechanisms with an increased cell death and reduced proliferation. These phenotypes are coupled with the downregulation of several Hippo transcriptional targets, mainly involved in cells and tissue growth, and YAP exclusion from nuclei. Interestingly, Hippo knock-down in the GBA-KO flies rescues the proliferative defect, suggesting that targeting the Hippo pathway can be a promising therapeutic approach to neuronopathic GD.A combination of Drosophila dGBA1b loss-of-function models and Gaucher Disease (GD) patient-derived iPSCs reveals an impairment in GD neuronal cell growth and that Hippo pathway hyperactivation contributes to the impairment

    Altered medial frontal feedback learning signals in anorexia nervosa

    Get PDF
    Background In their relentless pursuit of thinness, individuals with anorexia nervosa (AN) engage in maladaptive behaviors (restrictive food choices, over-exercising) which may originate in altered decision-making and learning. Methods In this fMRI study we employed computational modelling to elucidate the neural correlates of feedback learning and value-based decision making in 36 female AN patients and 36 age-matched healthy volunteers (12-24 years). Participants performed a decision task which required adaptation to changing reward contingencies. Data were analyzed within a hierarchical Gaussian filter model, which captures inter-individual variability in learning under uncertainty. Results Behaviorally, patients displayed an increased learning rate specifically after punishments. At the neural level, hemodynamic correlates for learning rate, expected value and prediction error did not differ between the groups. However, activity in the posterior medial frontal cortex was elevated in AN following punishment. Conclusion Our findings suggest that the neural underpinning of feedback learning is selectively altered for punishment in AN

    First Results of the &#8220;Carbonaceous Aerosol in Rome and Environs (CARE)&#8221; Experiment: Beyond Current Standards for PM10

    Get PDF
    In February 2017 the “Carbonaceous Aerosol in Rome and Environs (CARE)” experiment was carried out in downtown Rome to address the following specific questions: what is the color, size, composition, and toxicity of the carbonaceous aerosol in the Mediterranean urban background area of Rome? The motivation of this experiment is the lack of understanding of what aerosol types are responsible for the severe risks to human health posed by particulate matter (PM) pollution, and how carbonaceous aerosols influence radiative balance. Physicochemical properties of the carbonaceous aerosol were characterised, and relevant toxicological variables assessed. The aerosol characterisation includes: (i) measurements with high time resolution (min to 1–2 h) at a fixed location of black carbon (eBC), elemental carbon (EC), organic carbon (OC), particle number size distribution (0.008–10 μ m), major non refractory PM1 components, elemental composition, wavelength-dependent optical properties, and atmospheric turbulence; (ii) 24-h measurements of PM10 and PM2.5 mass concentration, water soluble OC and brown carbon (BrC), and levoglucosan; (iii) mobile measurements of eBC and size distribution around the study area, with computational fluid dynamics modeling; (iv) characterisation of road dust emissions and their EC and OC content. The toxicological assessment includes: (i) preliminary evaluation of the potential impact of ultrafine particles on lung epithelia cells (cultured at the air liquid interface and directly exposed to particles); (ii) assessment of the oxidative stress induced by carbonaceous aerosols; (iii) assessment of particle size dependent number doses deposited in different regions of the human body; (iv) PAHs biomonitoring (from the participants into the mobile measurements). The first experimental results of the CARE experiment are presented in this paper. The objective here is to provide baseline levels of carbonaceous aerosols for Rome, and to address future research directions. First, we found that BC and EC mass concentration in Rome are larger than those measured in similar urban areas across Europe (the urban background mass concentration of eBC in Rome in winter being on average 2.6 ± 2.5 μ g · m − 3 , mean eBC at the peak level hour being 5.2 (95% CI = 5.0–5.5) μ g · m − 3 ). Then, we discussed significant variations of carbonaceous aerosol properties occurring with time scales of minutes, and questioned on the data averaging period used in current air quality standard for PM 10 (24-h). Third, we showed that the oxidative potential induced by aerosol depends on particle size and composition, the effects of toxicity being higher with lower mass concentrations and smaller particle size. Albeit this is a preliminary analysis, findings reinforce the need for an urgent update of existing air quality standards for PM 10 and PM 2.5 with regard to particle composition and size distribution, and data averaging period. Our results reinforce existing concerns about the toxicity of carbonaceous aerosols, support the existing evidence indicating that particle size distribution and composition may play a role in the generation of this toxicity, and remark the need to consider a shorter averaging period (&lt;1 h) in these new standards
    corecore