Development and commissioning of the ALICE pixel detector control system

The Silicon Pixel Detector (SPD) is the innermost detector of the ALICE Inner Tracking System and the closest one to the interaction point. In order to operate the detector in a safe way, a control system was developed in the framework of PVSS which allows to monitor and control a large number of parameters such as temperatures, currents, voltages, etc. The control system of the SPD implements interlock features to protect the detector against overheating and prevents operating it in case of malfunctions. The nearly 50,000 parameters required to fully configure the detector are stored in a database which employs automatic configuration versions after a new calibration run has been carried out. Several user interface panels were developed to allow experts and non-expert shifters to operate the detector in an easy and safe way. This contribution provides an overview of the SPD control system

Risk factors for abnormally invasive placenta: a systematic review and meta-analysis.

Purpose of the article. To explore the strength of association between different maternal and pregnancy characteristics and the occurrence of abnormally invasive placenta (AIP). MATERIALS AND METHODS: Pubmed, Embase, CINAHL databases were searched. The risk factors for AIP explored were: obesity, age > 35 years, smoking before or during pregnancy, placenta previa, prior cesarean section (CS), placenta previa and prior CS, prior uterine surgery, abortion and uterine curettage, in vitro fertilization (IVF) pregnancy and interval between a previous CS and a subsequent pregnancy. Random-effect head-to-head meta-analyses were used to analyze the data. RESULTS: Forty-six were included in the systematic review. Maternal obesity (Odd ratio, OR: 1.4, 95% CI 1.0-1.8), advanced maternal age (OR: 3.1, 95% CI 1.4-7.0) and parity (OR: 2.5, 95% CI 1.7-3.6), but not smoking were associated with a higher risk of AIP. The presence of placenta previa in women with at least a prior CS was associated with a higher risk of AIP compared to controls, with an OR of 12.0, 95% CI 1.6-88.0. Furthermore, the risk of AIP increased with the number of prior CS (OR of 2.6, 95% CI 1.6-4.4 and 5.4, 95% CI 1.7-17.4 for two and three prior CS respectively). Finally, IVF pregnancies were associated with a high risk of AIP, with an OR of 2.8 (95% CI 1.2-6.8). CONCLUSION: A prior CS and placenta previa are among the strongest risk factors for the occurrence of AIP

Prominent and regressive brain developmental disorders associated with nance-horan syndrome

Nance-Horan syndrome (NHS) is a rare X-linked developmental disorder caused mainly by loss of function variants in the NHS gene. NHS is characterized by congenital cataracts, dental anomalies, and distinctive facial features, and a proportion of the affected individuals also present intellectual disability and congenital cardiopathies. Despite identification of at least 40 distinct hemizygous variants leading to NHS, genotype-phenotype correlations remain largely elusive. In this study, we describe a Sicilian family affected with congenital cataracts and dental anomalies and diagnosed with NHS by whole-exome sequencing (WES). The affected boy from this family presented a late regression of cognitive, motor, language, and adaptive skills, as well as broad behavioral anomalies. Furthermore, brain imaging showed corpus callosum anomalies and periven-tricular leukoencephalopathy. We expand the phenotypic and mutational NHS spectrum and review potential disease mechanisms underlying the central neurological anomalies and the potential neu-rodevelopmental features associated with NHS

A homozygous MED11 C-terminal variant causes a lethal neurodegenerative disease

Purpose: The mediator (MED) multisubunit-complex modulates the activity of the transcriptional machinery, and genetic defects in different MED subunits (17, 20, 27) have been implicated in neurologic diseases. In this study, we identified a recurrent homozygous variant in MED11 (c.325C>T; p.Arg109Ter) in 7 affected individuals from 5 unrelated families. Methods: To investigate the genetic cause of the disease, exome or genome sequencing were performed in 5 unrelated families identified via different research networks and Matchmaker Exchange. Deep clinical and brain imaging evaluations were performed by clinical pediatric neurologists and neuroradiologists. The functional effect of the candidate variant on both MED11 RNA and protein was assessed using reverse transcriptase polymerase chain reaction and western blotting using fibroblast cell lines derived from 1 affected individual and controls and through computational approaches. Knockouts in zebrafish were generated using clustered regularly interspaced short palindromic repeats/Cas9. Results: The disease was characterized by microcephaly, profound neurodevelopmental impairment, exaggerated startle response, myoclonic seizures, progressive widespread neurodegeneration, and premature death. Functional studies on patient-derived fibroblasts did not show a loss of protein function but rather disruption of the C-terminal of MED11, likely impairing binding to other MED subunits. A zebrafish knockout model recapitulates key clinical phenotypes. Conclusion: Loss of the C-terminal of MED subunit 11 may affect its binding efficiency to other MED subunits, thus implicating the MED-complex stability in brain development and neurodegeneration

Dependence of atmospheric muon flux on seawater depth measured with the first KM3NeT detection units: The KM3NeT Collaboration

KM3NeT is a research infrastructure located in the Mediterranean Sea, that will consist of two deep-sea Cherenkov neutrino detectors. With one detector (ARCA), the KM3NeT Collaboration aims at identifying and studying TeV–PeV astrophysical neutrino sources. With the other detector (ORCA), the neutrino mass ordering will be determined by studying GeV-scale atmospheric neutrino oscillations. The first KM3NeT detection units were deployed at the Italian and French sites between 2015 and 2017. In this paper, a description of the detector is presented, together with a summary of the procedures used to calibrate the detector in-situ. Finally, the measurement of the atmospheric muon flux between 2232–3386 m seawater depth is obtained

Genotype-phenotype correlations and disease mechanisms in PEX13-related Zellweger spectrum disorders.

BACKGROUND: Pathogenic variants in PEX-genes can affect peroxisome assembly and function and cause Zellweger spectrum disorders (ZSDs), characterized by variable phenotypes in terms of disease severity, age of onset and clinical presentations. So far, defects in at least 15 PEX-genes have been implicated in Mendelian diseases, but in some of the ultra-rare ZSD subtypes genotype-phenotype correlations and disease mechanisms remain elusive. METHODS: We report five families carrying biallelic variants in PEX13. The identified variants were initially evaluated by using a combination of computational approaches. Immunofluorescence and complementation studies on patient-derived fibroblasts were performed in two patients to investigate the cellular impact of the identified mutations. RESULTS: Three out of five families carried a recurrent p.Arg294Trp non-synonymous variant. Individuals affected with PEX13-related ZSD presented heterogeneous clinical features, including hypotonia, developmental regression, hearing/vision impairment, progressive spasticity and brain leukodystrophy. Computational predictions highlighted the involvement of the Arg294 residue in PEX13 homodimerization, and the analysis of blind docking predicted that the p.Arg294Trp variant alters the formation of dimers, impairing the stability of the PEX13/PEX14 translocation module. Studies on muscle tissues and patient-derived fibroblasts revealed biochemical alterations of mitochondrial function and identified mislocalized mitochondria and a reduced number of peroxisomes with abnormal PEX13 concentration. CONCLUSIONS: This study expands the phenotypic and mutational spectrum of PEX13-related ZSDs and also highlight a variety of disease mechanisms contributing to PEX13-related clinical phenotypes, including the emerging contribution of secondary mitochondrial dysfunction to the pathophysiology of ZSDs

Phage-inducible chromosomal islands are ubiquitous within the bacterial universe

Phage-inducible chromosomal islands (PICIs) are a recently discovered family of pathogenicity islands that contribute substantively to horizontal gene transfer, host adaptation and virulence in Gram-positive cocci. Here we report that similar elements also occur widely in Gram-negative bacteria. As with the PICIs from Gram-positive cocci, their uniqueness is defined by a constellation of features: unique and specific attachment sites, exclusive PICI genes, a phage-dependent mechanism of induction, conserved replication origin organization, convergent mechanisms of phage interference, and specific packaging of PICI DNA into phage-like infectious particles, resulting in very high transfer frequencies. We suggest that the PICIs represent two or more distinct lineages, have spread widely throughout the bacterial world, and have diverged much more slowly than their host organisms or their prophage cousins. Overall, these findings represent the discovery of a universal class of mobile genetic elements

Long term monitoring of the optical background in the Capo Passero deep-sea site with the NEMO tower prototype

The NEMO Phase-2 tower is the first detector which was operated underwater for more than 1 year at the "record" depth of 3500 m. It was designed and built within the framework of the NEMO (NEutrino Mediterranean Observatory) project. The 380 m high tower was successfully installed in March 2013 80 km offshore Capo Passero (Italy). This is the first prototype operated on the site where the Italian node of the KM3NeT neutrino telescope will be built. The installation and operation of the NEMO Phase-2 tower has proven the functionality of the infrastructure and the operability at 3500 m depth. A more than 1 year long monitoring of the deep water characteristics of the site has been also provided. In this paper the infrastructure and the tower structure and instrumentation are described. The results of long term optical background measurements are presented. The rates show stable and low baseline values, compatible with the contribution of K-40 light emission, with a small percentage of light bursts due to bioluminescence. All these features confirm the stability and good optical properties of the site.Funded by SCOAP3Adrián Martínez, S.; Aiello, S.; Ameli, F.; Anghinolfi, M.; Ardid Ramírez, M.; Barbarino, G.; Barbarito, E.... (2016). Long term monitoring of the optical background in the Capo Passero deep-sea site with the NEMO tower prototype. European Physical Journal C: Particles and Fields. 76(68):1-11. https://doi.org/10.1140/epjc/s10052-016-3908-0S1117668M. Ageron et al., ANTARES: the first undersea neutrino telescope. Nucl. Instr. Methods A 656, 11 (2011)V. Aynutdnov for the Baikal Coll., The BAIKAL neutrino project: results and perspective. Nucl. Instr. Methods. A 628, 115 (2011)A. Achterberg et al., First year performance of the IceCube neutrino telescope. Astropart. Phys. 26, 155 (2006)M.G. Aartsen et al., Evidence for high-energy extraterrestrial neutrinos at the IceCube detector. Science 342, 1242856 (2013)M.G. Aartsen et al., Observation of high-energy astrophysical neutrinos in three years of IceCube data. Phys. Rev. Lett. 113, 101101 (2014)M.G. Aartsen et al., Evidence for astrophysical muon neutrinos from the northern sky with IceCube. Phys. Rev. Lett. 115, 081102 (2015)E. Migneco et al., Status of NEMO. Nucl. Instr. Methods A 567, 444 (2006)E. Migneco et al., Recent achievements of the NEMO project. Nucl. Instr. Methods A 588, 111 (2008)A. Capone et al., Recent results and perspectives od the NEMO project. Nucl. Instr. Methods A 602, 47 (2009)M. Taiuti et al., The NEMO project: a status report. Nucl. Instr. Methods A 626, S25 (2011)S. Aiello et al., Measurement of the atmospheric muon flux of the NEMO Phase-1 detector. Astropart. Phys. 33, 263 (2010)A. Capone et al., Measurements of light transmission in deep sea with the AC9 transmissometer. Nucl. Instr. Methods A 487, 423 (2002)G. Riccobene et al., Deep seawater inherent optical properties in the Southern Ionian Sea. Astropart. Phys. 27, 1 (2007)A. Rubino et al., Abyssal undular vortices in the Eastern Mediterranean basin. Nat. Commun. 3, 834 (2012)KM3NeT web site. www.km3net.orgM. Sedita for the NEMO collaboration, Electro-optical cable and power feeding system for the NEMO Phase-2 project. Nucl. Instr. Methods A 567, 531 (2006)R. Cocimano for the NEMO collaboration, A comparison of AC and DC power feeding systems based on the NEMO experiences. Nucl. Instr. Methods A 602, 171 (2009)A. Orlando for the NEMO collaboration, On line monitoring of the power control and engineering parameters systems of the NEMO Phase-2 tower. Nucl. Instr. Methods. A 602, 180 (2009)M. Musumeci for the NEMO collaboration, Construction and deployment issues for a km {3} 3 underwater detector. Nucl. Instr. Methods. A 567, 545 (2006)S. Aiello et al., The optical modules of the phase-2 of the NEMO project. JINST 8, P07001 (2013)E. Leonora, S. Aiello, Design and assembly of the optical modules for phase-2 of the NEMO project. Nucl. Instr. Methods A 725, 234 (2013)S. Aiello et al., Procedures and results of the measurements on large area photomultipliers for the NEMO project. Nucl. Instr. Methods A 614, 206 (2010)C.A. Nicolau for the NEMO collaboration, An FPGA-based readout electronics for neutrino telescopes. Nucl. Instr. Methods A 567, 552 (2006)M. Cordelli et al., PORFIDO: oceanographic data for neutrino telescopes. Nucl. Instr. Methods A 626–627, S109 (2011)F. Ameli, The data acquisition and transport design for NEMO Phase-1. IEEE Trans. Nucl. Sci. 55(1), 233 (2008)A. D’Amico for the NEMO collaboration, Design of the optical Raman amplifier for the shore station of NEMO Phase-2. Nucl. Instr. Methods A 626–627, S173 (2011)T. Chiarusi for the NEMO collaboration, Scalable TriDAS for the NEMO project. Nucl. Instr. Methods A 630, 107 (2011)S. Viola et al., NEMO-SMO acoustic array: a deep-sea test of a novel acoustic positioning system for a km $$^3$$ 3 -scale underwater neutrino telescope. Nucl. Instr. Methods A 725, 207 (2013)S. Viola et al., in Underwater acoustic positioning system for the SMO and KM3NeT-Italia projects. AIP Conference Proceedings 1630, 134 (2014)M. Circella for the NEMO collaboration, Time calibration of the NEutrino Mediterranean Observatory (NEMO). Nucl. Instr. Methods A 602, 187 (2009)S. Aiello et al., Measurement of the atmospheric muon depth intensity relation with the NEMO phase-2 tower. Astropart. Phys. 66, 1 (2015)C. Hugon for the ANTARES and KM3NeT collaborations, Step by step simulation of phototubes for the KM3NeT and ANTARES optical modules. Nucl. Instr. Methods A 787, 189 (2015)Ch. Tamburini et al., Deep-sea bioluminescence blooms after dense water formation at the ocean surface. PLOS One 8, e67523 (2013

Uncertainty Reasoning for the Semantic Web

Significant research activities have recently been directed towards the Semantic Web as a potential future substitute of the current World Wide Web. Many experts predict that the next huge step forward in Web information technology will be achieved by adding semantics to Web data. An important role in research towards the Semantic Web is played by formalisms and technologies for handling uncertainty and/or vagueness. In this paper, I first provide some motivating examples for handling uncertainty and/or vagueness in the Semantic Web. I then give an overview of some own recent formalisms for handling uncertainty and/or vagueness in the Semantic Web.</p

P16INK4a as a progression/regression tumour marker in LSIL cervix lesions: Our clinical experience

Purpose of investigation: The aim of this prospective study was the evaluation of low-grade intraepithelial lesion (LSIL) lesions evolvement in woman with evidence of high risk HPV infection and p16 INK4a negative expression. Materials and Methods: 150 women with cytological diagnosis of LSIL were selected to be underwent to three years of follow-up consisting in smear test, colposcopy, and protein p16 INK4a investigation every six months and HPV-test every 12 months. Result: Final follow-up showed 45 cases of spontaneous lesion regression and 42 cases of persistence with absence of protein p16 INK4a in all of them. There were three cases of disease progression to CIN2, two at 18-month follow-up and one at last follow-up. Disease progression was characterized of p16 INK4a expression. Conclusion: p16 INK4a should help to identify which LSIL cases are inclined to the progression of the disease and focalize which patients are eligible for specific treatment