Field Emission from Self-Assembled Arrays of Lanthanum Monosulfide Nanoprotrusions

The field emission properties of LaS nanoprotrusions called nanodomes, formed by pulsed laser deposition on porous anodic alumina films, have been analyzed with scanning anode field emission microscopy. The voltage necessary to produce a given field emission current is 3.5 times less for nanodomes than for thin films. Assuming the same work function for LaS thin films and nanoprotrusions, that is, 1 eV, a field enhancement factor of 5.8 is extracted for the nanodome emitters from Fowler-Nordheim plots of the field emission data. This correlates well with the aspect ratio of the tallest nanodomes observed in atomic force micrograph measurements

Phase 2 Study of Pomalidomide (CC-4047) Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors

INTRODUCTION: Treatment of recurrent primary pediatric brain tumors remains a major challenge, with most children succumbing to their disease. We conducted a prospective phase 2 study investigating the safety and efficacy of pomalidomide (POM) in children and young adults with recurrent and progressive primary brain tumors. BACKGROUND: METHODS: Patients with recurrent and progressive high-grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), ependymoma, or medulloblastoma received POM 2.6 mg/m2/day (the recommended phase 2 dose [RP2D]) on days 1-21 of a 28-day cycle. A Simon’s Optimal 2-stage design was used to determine efficacy. Primary endpoints included objective response (OR) and long-term stable disease (LTSD) rates. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 46 patients were evaluable for response (HGG, n = 19; DIPG, ependymoma, and medulloblastoma, n = 9 each). Two patients with HGG achieved OR or LTSD (10.5% [95% CI, 1.3%-33.1%]; 1 partial response and 1 LTSD) and 1 patient with ependymoma had LTSD (11.1% [95% CI, 0.3%-48.2%]). There were no ORs or LTSD in the DIPG or medulloblastoma cohorts. The median PFS for patients with HGG, DIPG, ependymoma, and medulloblastoma was 7.86, 11.29, 8.43, and 8.43 weeks, respectively. Median OS was 5.06, 3.78, 12.02, and 11.60 months, respectively. Neutropenia was the most common grade 3/4 adverse event. CONCLUSIONS: Treatment with POM monotherapy did not meet the primary measure of success in any cohort. Future studies are needed to evaluate if POM would show efficacy in tumors with specific molecular signatures or in combination with other anticancer agents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03257631; EudraCT, identifier 2016-002903-25

Search for neutrinos from the tidal disruption events AT2019dsg and AT2019fdr with the ANTARES telescope

The authors acknowledge the financial support of the funding agencies: Centre National de la Recherche Scientifique (CNRS), Commissariat a l'energie atomique et aux energies alternatives (CEA), Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), Region Ile-de-France (DIM-ACAV), Region Alsace (contrat CPER), Region Provence-Alpes-Cote d'Azur, Departement du Var and Ville de La Seyne-sur-Mer, France; Bundesministerium fur Bildung und Forschung (BMBF), Germany; Istituto Nazionale di Fisica Nucleare (INFN), Italy; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; Council of the President of the Russian Federation for young scientists and leading scientific schools supporting grants, Russia; Executive Unit for Financing Higher Education, Research, Development and Innovation (UEFISCDI), Romania; Ministerio de Ciencia e Innovacion (MCI) and Agencia Estatal de Investigacion: Programa Estatal de Generacion de Conocimiento (refs. PGC2018-096663-B-C41, -A-C42, -B-C43, -B-C44) (MCI/FEDER), Severo Ochoa Centre of Excellence and MultiDark Consolider, Junta de Andalucia (ref. SOMM17/6104/UGR and A-FQM-053-UGR18), Generalitat Valenciana: Grisolia (ref. GRISOLIA/2018/119) and GenT (ref. CIDEGENT/2018/034) programs, Spain; Ministry of Higher Education, Scientific Research and Professional Training, Morocco. We also acknowledge the technical support of Ifremer, AIM and Foselev Marine for the sea operation and the CC-IN2P3 for the computing facilities.On October 1, 2019, the IceCube Collaboration detected a muon track neutrino with high probability of being of astrophysical origin, IC191001A. After a few hours, the tidal disruption event (TDE) AT2019dsg, observed by the Zwicky Transient Facility (ZTF), was indicated as the most likely counterpart of the IceCube track. More recently, the followup campaign of the IceCube alerts by ZTF suggested a second TDE, AT2019fdr, as a promising counterpart of another IceCube muon track candidate, IC200530A, detected on May 30, 2020. These are the second and third associations between astrophysical sources and high-energy neutrinos after the compelling identification of the blazar TXS 0506+056. Here, the search for ANTARES neutrinos from the directions of AT2019dsg and AT2019fdr using a time-integrated approach is presented. As no significant evidence for space clustering is found in the ANTARES data, upper limits on the one-flavour neutrino flux and fluence are set.Centre National de la Recherche Scientifique (CNRS)French Atomic Energy CommissionCommission Europeenne (FEDER fund and Marie Curie Program)Institut Universitaire de France (IUF)LabEx UnivEarthS ANR-10-LABX-0023 ANR-18-IDEX-0001Region Ile-de-FranceRegion Grand-EstRegion Provence-Alpes-Cote d'AzurFederal Ministry of Education & Research (BMBF)Istituto Nazionale di Fisica Nucleare (INFN)Netherlands Organization for Scientific Research (NWO)Netherlands GovernmentCouncil of the President of the Russian Federation for young scientists and leading scientific schools supporting grants, RussiaConsiliul National al Cercetarii Stiintifice (CNCS)Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (UEFISCDI)Spanish GovernmentAgencia Estatal de Investigacion (MCI/FEDER) PGC2018-096663-B-C41 PGC2018-096663-A-C42 PGC2018-096663-B-C43 PGC2018-096663-B-C44Severo Ochoa Centre of Excellence and MultiDark Consolider, Junta de Andalucia SOMM17/6104/UGR A-FQM-053-UGR18Generalitat Valenciana GRISOLIA/2018/119 CIDEGENT/2018/034Ministry of Higher Education, Scientific Research and Professional Training, Morocc

Limits on the nuclearite flux using the ANTARES neutrino telescope

In this work, a search for nuclearites of strange quark matter by using nine years of ANTARES data taken in the period 2009–2017 is presented. The passage through matter of these particles is simulated taking into account a detailed description of the detector response to nuclearites and of the data acquisition conditions. A down-going flux of cosmic nuclearites with Galactic velocities (ß = 10-3) was considered for this study. The mass threshold for detecting these particles at the detector level is 4 × 1013 GeV/c2. Upper limits on the nuclearite flux for masses up to 1017 GeV/c2 at the level of ~ 5 × 10-17 cm-2 s-1 sr-1 are obtained. These are the first upper limits on nuclearites established with a neutrino telescope and the most stringent ever set for Galactic velocitiesPeer ReviewedPostprint (author's final draft

Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference

BACKGROUND: Equine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causes respiratory disease, neurological disorders and abortions. The virus is a significant equine pathogen, but current EHV-1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interfering RNAs (siRNA's), delivered intranasally, could prove a valuable alternative for infection control. siRNA's against two essential EHV-1 genes, encoding the viral helicase (Ori) and glycoprotein B, were evaluated for their potential to decrease EHV-1 infection in a mouse model. METHODOLOGY/PRINCIPAL FNDINGS: siRNA therapy in vitro significantly reduced virus production and plaque size. Viral titers were reduced 80-fold with 37.5 pmol of a single siRNA or with as little as 6.25 pmol of each siRNA when used in combination. siRNA therapy in vivo significantly reduced viral replication and clinical signs. Intranasal treatment did not require a transport vehicle and proved effective when given up to 12 h before or after infection. CONCLUSIONS/SIGNIFICANCE: siRNA treatment has potential for both prevention and early treatment of EHV-1 infections

Field Emission from Self-Assembled Arrays of Lanthanum Monosulfide Nanoprotrusions

The field emission properties of LaS nanoprotrusions called nanodomes, formed by pulsed laser deposition on porous anodic alumina films, have been analyzed with scanning anode field emission microscopy. The voltage necessary to produce a given field emission current is ∼3.5 times less for nanodomes than for thin films. Assuming the same work function for LaS thin films and nanoprotrusions, that is, ∼1 eV, a field enhancement factor of ∼5.8 is extracted for the nanodome emitters from Fowler-Nordheim plots of the field emission data. This correlates well with the aspect ratio of the tallest nanodomes observed in atomic force micrograph measurements

Field Emission from Self-Assembled Arrays of Lanthanum Monosulfide Nanoprotrusions

The field emission properties of LaS nanoprotrusions called nanodomes, formed by pulsed laser deposition on porous anodic alumina films, have been analyzed with scanning anode field emission microscopy. The voltage necessary to produce a given field emission current is ∼3.5 times less for nanodomes than for thin films. Assuming the same work function for LaS thin films and nanoprotrusions, that is, ∼1 eV, a field enhancement factor of ∼5.8 is extracted for the nanodome emitters from FowlerNordheim plots of the field emission data. This correlates well with the aspect ratio of the tallest nanodomes observed in atomic force micrograph measurements. The promise of producing extremely high current densities in near-vacuum with no external source (such as heater, primary electron-beam, or intense light source) has generated significant interest in robust, reproducible, and fieldemission-based cold cathodes Recently, we reported the first successful deposition of lanthanum monosulfide (LaS) thin films on Si substrates using pulsed laser deposition (PLD) The nanodomes are cone-shaped LaS structures with base diameter 2r ranging from 50 to 100 nm and height h ranging from 100 to 150 nm. They were found to grow on the boundaries separating regions of the anodic alumina film that have near perfect pore ordering. Their density is ∼10 9 /cm 2 , as extracted from the field emission-scanning electron micrographs (FE-SEM) and atomic force micrographs (AFM) such as those shown in The SAFEM technique was used to measure the FE current-voltage (I-V) characteristics at different surface locations. As the nanowires are buried inside the pores, they contribute very little, if any at all, to the net FE current. Moreover, FE measurements from the arrays of nanodomes and nanodots were possible because the regions joining adjacent nanodomes and nanodots are covered with a thin percolating network of LaS over the entire array. Its presence was confirmed by measuring a low resistance value of about 2 Ohms between two electrical contacts about 1 cm apart. For each location, a full set of I-V characteristics (total measured current versus applied voltage) for different values of d, the distance between the cathode surface and the probe ball, was measured. This set of measurements was then analyzed in order to extract the apparent current density αJ versus actual applied local field γF, where γ is the local geometrical field enhancement at the surface of the cathode In order to assess the FE properties from LaS nanoprotrusions, we have compared the FE from nanodome cathodes with that from planar thin film LaS cathodes. This comparative methodology was chosen because a precise quantitative estimation of γ from topographic measurements is still subject to controversy, except for a flat surface. These experimental measurements were performed for both LaS thin films of 100 nm thickness on Si wafers and LaS nanodomes on anodic alumina films. The analysis consisted of the following steps. (1) In order to restrict the analysis of the differences in the I-V data to the surface morphology of the cathodes, both SAFEM measurements were performed with the same probe ball-to-cathode distance d = 3.65 μm. Typical I-V characteristics are shown in (2) The total FE current versus applied voltage (I-V) characteristics were measured for different values of the probe-ball-to-cathode-surface distance d. From these data, the apparent current densities (α t f J and α nd J) as a a function of the applied local field were extracted ACKNOWLEDGMEN

Correlation Between Anti-TNF Serum Levels and Endoscopic Inflammation in Inflammatory Bowel Disease Patients

Objectives: (a) To evaluate the diagnostic accuracy of anti-TNF trough levels to predict mucosal healing in inflammatory bowel disease (IBD); (b) to determine the best cut-off point to predict mucosal healing in IBD patients treated with anti-TNF. Methods: This is a multicenter, prospective study. IBD patients under anti-TNF treatment for at least 6 months that had to undergo an endoscopy were included. Mucosal healing was defined as: Simple endoscopic score for Crohn’s Disease < 3 for Crohn’s disease (CD), Rutgeerts score < i2 for CD in postoperative setting, or Mayo endoscopic score = 1 for ulcerative colitis (UC). Anti-TNF concentrations were measured using SMART ELISAs at trough. Results: A total of 182 patients were included. Anti-TNF trough levels were significantly higher among patients that had mucosal healing than among those who did not. The area under the curve of infliximab for mucosal healing was 0.63 (best cutoff value 3.4 µg/mL), and for adalimumab 0.60 (best cutoff value 7.2 µg/mL). In the multivariate analysis, having anti-TNF drug levels above the cutoff values [odds ratio (OR) 3.1]) and having UC instead of CD (OR 4) were associated with a higher probability of having mucosal healing. Additionally, the need for an escalated dosage (OR 0.2) and current smoking habit (OR 0.2) were also associated with a lower probability of mucosal healing. Conclusions: There was an association between anti-TNF trough levels and mucosal healing in IBD patients; however, the accuracy of the determination of infliximab and adalimumab concentrations able to predict mucosal healing was suboptimal

The Lsm1-7/Pat1 complex binds to stress-activated mRNAs and modulates the response to hyperosmotic shock

RNA-binding proteins (RBPs) establish the cellular fate of a transcript, but an understanding of these processes has been limited by a lack of identified specific interactions between RNA and protein molecules. Using MS2 RNA tagging, we have purified proteins associated with individual mRNA species induced by osmotic stress, STL1 and GPD1. We found members of the Lsm1-7/Pat1 RBP complex to preferentially bind these mRNAs, relative to the non-stress induced mRNAs, HYP2 and ASH1. To assess the functional importance, we mutated components of the Lsm1-7/Pat1 RBP complex and analyzed the impact on expression of osmostress gene products. We observed a defect in global translation inhibition under osmotic stress in pat1 and lsm1 mutants, which correlated with an abnormally high association of both non-stress and stress-induced mRNAs to translationally active polysomes. Additionally, for stress-induced proteins normally triggered only by moderate or high osmostress, in the mutants the protein levels rose high already at weak hyperosmosis. Analysis of ribosome passage on mRNAs through co-translational decay from the 5' end (5P-Seq) showed increased ribosome accumulation in lsm1 and pat1 mutants upstream of the start codon. This effect was particularly strong for mRNAs induced under osmostress. Thus, our results indicate that, in addition to its role in degradation, the Lsm1-7/Pat1 complex acts as a selective translational repressor, having stronger effect over the translation initiation of heavily expressed mRNAs. Binding of the Lsm1-7/Pat1p complex to osmostress-induced mRNAs mitigates their translation, suppressing it in conditions of weak or no stress, and avoiding a hyperresponse when triggered

Computational approaches to explainable artificial intelligence: Advances in theory, applications and trends

Deep Learning (DL), a groundbreaking branch of Machine Learning (ML), has emerged as a driving force in both theoretical and applied Artificial Intelligence (AI). DL algorithms, rooted in complex and non-linear artificial neural systems, excel at extracting high-level features from data. DL has demonstrated human-level performance in real-world tasks, including clinical diagnostics, and has unlocked solutions to previously intractable problems in virtual agent design, robotics, genomics, neuroimaging, computer vision, and industrial automation. In this paper, the most relevant advances from the last few years in Artificial Intelligence (AI) and several applications to neuroscience, neuroimaging, computer vision, and robotics are presented, reviewed and discussed. In this way, we summarize the state-of-the-art in AI methods, models and applications within a collection of works presented at the 9th International Conference on the Interplay between Natural and Artificial Computation (IWINAC). The works presented in this paper are excellent examples of new scientific discoveries made in laboratories that have successfully transitioned to real-life applications.MCIU - Nvidia(UMA18-FEDERJA-084