Uniformity Of The 2000 Test Beam Module With The New Optimal Filtering Coefficients

An original method to reconstruct electron and pion signals in the Liquid ARGon barrel calorimeter (LARG) is applied to test beam data collected at the H8 line of the CERN North Area in July and August 2000. The method is based on the use of optimal filtering coefficients and takes into account the electrical description of the read-out electronics in the reconstruction of the physics pulses. Results on improvements in the LARG response and in particular on the energy uniformity of the calorimeter are shown

E-ABR in patients with cochlear implant: A comparison between patients with malformed cochlea and normal cochlea

OBJECTIVES: This study aims to compare the electrical auditory brainstem response (EABR) following cochlear implant (CI) surgery in pediatric subjects with cochlear malformation and a normal cochlea, in order to assess the sensitivity of EABR and to evaluate the surgery outcome. MATERIALS and METHODS: A total of 26 pediatric subjects who were deaf and scheduled for CI surgery were enrolled into this case control study. Group A (n=20) included subjects with a normo-conformed cochlea. Group B (n=6) included subjects with cochlear malformation. Subjects were evaluated with EABR immediately (T0) and 6 months (T1) post-CI surgery. The EABR Waves III and V average amplitude and latency were compared across time, separately for each group, and across groups, separately for each time. RESULTS: Auditory brainstem response (ABR) could only be recorded in Group A. We were able to record EABR from all subjects at T0 and T1, and waves III and V were present in all the recorded signals. There were no statistically significant differences between T0 and T1 in EABR Waves III and V in terms of average amplitude and latency in neither group. When comparing Groups A and B, the only statistically significant difference was the average amplitude of wave V, both at T0 and T1. CONCLUSION: EABR is a valid tool to measure the auditory nerve integrity after CI surgery in patients with a normal and malformed cochlea, as shown by its ability to measure waves III and V when ABR is absent. The EABR testing should be performed before and after CI surgery, and EABR should be used as a measure of outcome, especially in patients with a malformed cochlea

Neural basis of anticipatory multisensory integration

The brain is able to gather different sensory information to enhance salient event perception, thus yielding a unified perceptual experience of multisensory events. Multisensory integration has been widely studied, and the literature supports the hypothesis that it can occur across various stages of stimulus processing, including both bottom-up and top-down control. However, evidence on anticipatory multisensory integration occurring in the fore period preceding the presentation of the expected stimulus in passive tasks, is missing. By means of event-related potentials (ERPs), it has been recently proposed that visual and auditory unimodal stimulations are preceded by sensory-specific readiness activities. Accordingly, in the present study, we tested the occurrence of multisensory integration in the endogenous anticipatory phase of sensory processing, combining visual and auditory stimuli during unimodal and multimodal passive ERP paradigms. Results showed that the modality-specific pre-stimulus ERP components (i.e., the auditory positivity-aP-and the visual negativity-vN-) started earlier and were larger in the multimodal stimulation compared with the sum of the ERPs elicited by the unimodal stimulations. The same amplitude effect was also present for the early auditory N1 and visual P1 components. This anticipatory multisensory effect seems to influence stimulus processing, boosting the magnitude of early stimulus processing. This paves the way for new perspectives on the neural basis of multisensory integration

Role of fetal MRI in the evaluation of isolated and non-isolated corpus callosum dysgenesis: results of a cross-sectional study

PURPOSE: The aims of this study were to characterize isolated and non-isolated forms of corpus callosum dysgenesis (CCD) at fetal magnetic resonance imaging (MRI) and to identify early predictors of associated anomalies. METHODS: We retrospectively analyzed 104 fetuses with CCD undergoing MRI between 2006 and 2016. Corpus callosum, cavum septi pellucidi, biometry, presence of ventriculomegaly, gyration anomalies, cranio-encephalic abnormalities and body malformations were evaluated. Results of genetic tests were also recorded. RESULTS: At MRI, isolated CCD was 26.9%, the rest being associated to other abnormalities. In the isolated group, median gestational age at MRI was lower in complete agenesis than in hypoplasia (22 vs 28 weeks). In the group with additional findings, cortical dysplasia was the most frequently associated feature (P = 0.008), with a more frequent occurrence in complete agenesis (70%) versus other forms; mesial frontal lobes were more often involved than other cortical regions (P = 0.006), with polymicrogyria as the most frequent cortical malformation (40%). Multivariate analysis confirmed the association between complete agenesis and cortical dysplasia (odds ratio = 7.29, 95% confidence interval 1.51-35.21). CONCLUSIONS: CCD is often complicated by other intra-cranial and extra-cranial findings (cortical dysplasias as the most prevalent) that significantly affect the postnatal prognosis. The present study showed CCD with associated anomalies as more frequent than isolated (73.1%). In isolated forms, severe ventriculomegaly was a reliable herald of future appearance of associated features

Two semiotic shifts in the philosophy of norms: meaning shift and referent shift

In this introductory paper the guest editors (Paolo Di Lucia and Lorenzo Passerini Glazel) of the special issue \u201cNorm: What Is It? Ontological and Pragmatical Perspectives\u201d maintain that the word norm is subject to two kinds of semiotic shifts: shifts in the meaning and shifts in the referents. Philosophical research on norms and on the normative has, indeed, broadened its dominion of investigation in both directions. The phenomena of norms and normativity, intersecting different orders of phenomena, are investigated by different disciplines from different methodological perspectives

Selective targeting of HDAC1/2 elicits anticancer effects through Gli1 acetylation in preclinical models of SHH Medulloblastoma.

SHH Medulloblastoma (SHH-MB) is a pediatric brain tumor characterized by an inappropriate activation of the developmental Hedgehog (Hh) signaling. SHH-MB patients treated with the FDA-approved vismodegib, an Hh inhibitor that targets the transmembrane activator Smoothened (Smo), have shown the rapid development of drug resistance and tumor relapse due to novel Smo mutations. Moreover, a subset of patients did not respond to vismodegib because mutations were localized downstream of Smo. Thus, targeting downstream Hh components is now considered a preferable approach. We show here that selective inhibition of the downstream Hh effectors HDAC1 and HDAC2 robustly counteracts SHH-MB growth in mouse models. These two deacetylases are upregulated in tumor and their knockdown inhibits Hh signaling and decreases tumor growth. We demonstrate that mocetinostat (MGCD0103), a selective HDAC1/HDAC2 inhibitor, is a potent Hh inhibitor and that its effect is linked to Gli1 acetylation at K518. Of note, we demonstrate that administration of mocetinostat to mouse models of SHH-MB drastically reduces tumor growth, by reducing proliferation and increasing apoptosis of tumor cells and prolongs mouse survival rate. Collectively, these data demonstrate the preclinical efficacy of targeting the downstream HDAC1/2-Gli1 acetylation in the treatment of SHH-MB

Averaging lifetimes for B hadron species

The measurement of the lifetimes of the individual B species are of great interest. Many of these measurements are well below the 10 $\%$ level of precision. However, in order to reach the precision necessary to test the current theoretical predictions, the results from different experiments need to be averaged. Therefore, the relevant systematic uncertainties of each measurement need to be well defined in order to understand the correlations between the results from different experiments. \par In this paper we discuss the dominant sources of systematic errors which lead to correlations between the different measurements. We point out problems connected with the conventional approach of combining lifetime data and discuss methods which overcome these problems

Immunoglobulin free light chains and GAGs mediate multiple myeloma extracellular vesicles uptake and secondary NfkB nuclear traslocation

Multiplemyeloma(MM) is a hematological malignancy caused by a microenviromentally aided persistence of plasmacells in the bone marrow. Monoclonal plasmacells often secrete high amounts of immunoglobulin free light chains(FLCs)that could induce tissue damage. Recently, we showed that FLCs are internalized in endothelial and myocardial cell lines and secreted in extracellular vesicles(EVs). MM serum derived EVs presented phenotypic differences if compared with monoclonal gammopathy of undetermined significance (MGUS)serum derived EVs suggesting their involvement in MM pathogenesis or progression. To investigate the effect of circulating EVs on endothelial and myocardial cells, we purified MM and MGUS serum derived EVs with differential ultracentrifugation protocols and tested their biological activity. We found that MM and MGUS EVs induced different proliferation and internalization rates in endothelial and myocardial cells, thus we tried to find specific targets in MM EVs docking and processing. Pre-treatment of EVs withanti-FLCs antibodies or heparin blocked the MM EVs uptake, highlighting that FLCs and glycosaminoglycans are involved. Indeed, only MM EVs exposure induced a strong nuclear factor kappa B nuclear translocation that was completely abolished afteranti-FLCs antibodies and heparin pre-treatment. The protein tyrosine kinase c-src is present on MM circulating EVs and redistributes to the cell plasma membrane after MM EVs exposure.The anti-FLCs antibodies and heparin pre-treatments were able to block the intracellular redistribution of the c-src kinase and the subsequent c-src kinase containing EVs production. Our results open new insights in EVs cellular biology and in MM therapeutic and diagnostic approaches

Immunoglobulin free light chains and GAGs mediate multiple myeloma extracellular vesicles uptake and secondary NfkB nuclear traslocation

Multiplemyeloma(MM) is a hematological malignancy caused by a microenviromentally aided persistence of plasmacells in the bone marrow. Monoclonal plasmacells often secrete high amounts of immunoglobulin free light chains(FLCs)that could induce tissue damage. Recently, we showed that FLCs are internalized in endothelial and myocardial cell lines and secreted in extracellular vesicles(EVs). MM serum derived EVs presented phenotypic differences if compared with monoclonal gammopathy of undetermined significance (MGUS)serum derived EVs suggesting their involvement in MM pathogenesis or progression. To investigate the effect of circulating EVs on endothelial and myocardial cells, we purified MM and MGUS serum derived EVs with differential ultracentrifugation protocols and tested their biological activity. We found that MM and MGUS EVs induced different proliferation and internalization rates in endothelial and myocardial cells, thus we tried to find specific targets in MM EVs docking and processing. Pre-treatment of EVs withanti-FLCs antibodies or heparin blocked the MM EVs uptake, highlighting that FLCs and glycosaminoglycans are involved. Indeed, only MM EVs exposure induced a strong nuclear factor kappa B nuclear translocation that was completely abolished afteranti-FLCs antibodies and heparin pre-treatment. The protein tyrosine kinase c-src is present on MM circulating EVs and redistributes to the cell plasma membrane after MM EVs exposure.The anti-FLCs antibodies and heparin pre-treatments were able to block the intracellular redistribution of the c-src kinase and the subsequent c-src kinase containing EVs production. Our results open new insights in EVs cellular biology and in MM therapeutic and diagnostic approaches