NFKB1 regulates human NK cell maturation and effector functions

12siopenopenLougaris, Vassilios; Patrizi, Ornella; Baronio, Manuela; Tabellini, Giovanna; Tampella, Giacomo; Damiati, Eufemia; Frede, Natalie; van der Meer, Jos W.M.; Fliegauf, Manfred; Grimbacher, Bodo; Parolini, Silvia; Plebani, AlessandroLougaris, Vassilios; Patrizi, Ornella; Baronio, Manuela; Tabellini, Giovanna; Tampella, Giacomo; Damiati, Eufemia; Frede, Natalie; van der Meer, Jos W. M.; Fliegauf, Manfred; Grimbacher, Bodo; Parolini, Silvia; Plebani, Alessandr

MOONLIGHT: A NEW LUNAR LASER RANGING RETROREFLECTOR AND THE LUNAR GEODETIC PRECESSION

Since the 1970s Lunar Laser Ranging (LLR) to the Apollo Cube Corner Retroreflector (CCR) arrays (developed by the University of Maryland, UMD) supplied almost all significant tests of General Relativity (Alley et al., 1970; Chang et al., 1971; Bender et al.,1973): possible changes in the gravitational constant, gravitational self-energy, weak equivalence principle, geodetic precession, inverse-square force-law. The LNF group, in fact, has just completed a new measurement of the lunar geodetic precession with Apollo array, with accuracy of 9 × 10−3, comparable to the best measurement to date. LLR has also provided significant information on the composition and origin of the moon. This is the only Apollo experiment still in operation. In the 1970s Apollo LLR arrays contributed a negligible fraction of the ranging error budget. Since the ranging capabilities of ground stations improved by more than two orders of magnitude, now, because of the lunar librations, Apollo CCR arrays dominate the error budget. With the project MoonLIGHT (Moon Laser Instrumentation for General relativity High-accuracy Tests), in 2006 INFN-LNF joined UMD in the development and test of a new-generation LLR payload made by a single, large CCR (100mm diameter) unaffected by the effect of librations. With MoonLIGHT CCRs the accuracy of the measurement of the lunar geodetic precession can be improved up to a factor 100 compared to Apollo arrays. From a technological point of view, INFN-LNF built and is operating a new experimental apparatus (Satellite/lunar laser ranging Characterization Facility, SCF) and created a new industry-standard test procedure (SCF-Test) to characterize and model the detailed thermal behavior and the optical performance of CCRs in accurately laboratory-simulated space conditions, for industrial and scientific applications. Our key experimental innovation is the concurrent measurement and modeling of the optical Far Field Diffraction Pattern (FFDP) and the temperature distribution of retroreflector payloads under thermal conditions produced with a close-match solar simulator. The apparatus includes infrared cameras for non-invasive thermometry, thermal control and real-time payload movement to simulate satellite orientation on orbit with respect to solar illumination and laser interrogation beams. These capabilities provide: unique pre-launch performance validation of the space segment of LLR/SLR (Satellite Laser Ranging); retroreflector design optimization to maximize ranging efficiency and signal-to-noise conditions in daylight. Results of the SCF-Test of our CCR payload will be presented. Negotiations are underway to propose our payload and SCF-Test services for precision gravity and lunar science measurements with next robotic lunar landing missions. In particular, a scientific collaboration agreement was signed on Jan. 30, 2012, by D. Currie, S. Dell'Agnello and the Japanese PI team of the LLR instrument of the proposed SELENE-2 mission by JAXA (Registered with INFN Protocol n. 0000242-03/Feb/2012). The agreement foresees that, under no exchange of funds, the Japanese single, large, hollow LLR reflector will be SCF-Tested and that MoonLIGHT will be considered as backup instrument

MOONLIGHT: A NEW LUNAR LASER RANGING RETROREFLECTOR AND THE LUNAR GEODETIC PRECESSION

Since the 1970s Lunar Laser Ranging (LLR) to the Apollo Cube Corner Retroreflector (CCR) arrays (developed by the University of Maryland, UMD) supplied almost all significant tests of General Relativity (Alley et al., 1970; Chang et al., 1971; Bender et al.,1973): possible changes in the gravitational constant, gravitational self-energy, weak equivalence principle, geodetic precession, inverse-square force-law. The LNF group, in fact, has just completed a new measurement of the lunar geodetic precession with Apollo array, with accuracy of 9 × 10−3, comparable to the best measurement to date. LLR has also provided significant information on the composition and origin of the moon. This is the only Apollo experiment still in operation. In the 1970s Apollo LLR arrays contributed a negligible fraction of the ranging error budget. Since the ranging capabilities of ground stations improved by more than two orders of magnitude, now, because of the lunar librations, Apollo CCR arrays dominate the error budget. With the project MoonLIGHT (Moon Laser Instrumentation for General relativity High-accuracy Tests), in 2006 INFN-LNF joined UMD in the development and test of a new-generation LLR payload made by a single, large CCR (100mm diameter) unaffected by the effect of librations. With MoonLIGHT CCRs the accuracy of the measurement of the lunar geodetic precession can be improved up to a factor 100 compared to Apollo arrays. From a technological point of view, INFN-LNF built and is operating a new experimental apparatus (Satellite/lunar laser ranging Characterization Facility, SCF) and created a new industry-standard test procedure (SCF-Test) to characterize and model the detailed thermal behavior and the optical performance of CCRs in accurately laboratory-simulated space conditions, for industrial and scientific applications. Our key experimental innovation is the concurrent measurement and modeling of the optical Far Field Diffraction Pattern (FFDP) and the temperature distribution of retroreflector payloads under thermal conditions produced with a close-match solar simulator. The apparatus includes infrared cameras for non-invasive thermometry, thermal control and real-time payload movement to simulate satellite orientation on orbit with respect to solar illumination and laser interrogation beams. These capabilities provide: unique pre-launch performance validation of the space segment of LLR/SLR (Satellite Laser Ranging); retroreflector design optimization to maximize ranging efficiency and signal-to-noise conditions in daylight. Results of the SCF-Test of our CCR payload will be presented. Negotiations are underway to propose our payload and SCF-Test services for precision gravity and lunar science measurements with next robotic lunar landing missions. In particular, a scientific collaboration agreement was signed on Jan. 30, 2012, by D. Currie, S. Dell’Agnello and the Japanese PI team of the LLR instrument of the proposed SELENE-2 mission by JAXA (Registered with INFN Protocol n. 0000242-03/Feb/2012). The agreement foresees that, under no exchange of funds, the Japanese single, large, hollow LLR reflector will be SCF-Tested and that MoonLIGHT will be considered as backup instrument

MOONLIGHT: A NEW LUNAR LASER RANGING RETROREFLECTOR INSTRUMENT

Since 1969 Lunar Laser Ranging (LLR) to the Apollo Cube Corner Reflector (CCR) arrays has supplied several significant tests of gravity: Geodetic Precession, the Strong and Weak Equivalence Principle (SEP, WEP), the Parametrized Post Newtonian (PPN) parameter , the time change of the Gravitational constant (G), 1/r2 deviations and new gravitational theories beyond General Relativity (GR), like the unified braneworld theory (G. Dvali et al., 2003). Now a new generation of LLR can do better using evolved laser retroreflectors, developed from tight collaboration between my institution, INFN–LNF (Istituto Nazionale di Fisica Nucleare – Laboratori Nazionali di Frascati), and Douglas Currie (University of Maryland, USA), one of the fathers of LLR. The new lunar CCR is developing and characterizing at the "Satellite/Lunar laser ranging Characterization Facility" (SCF), in Frascati, performing our new industry standard space test procedure, the "SCF-Test"; this work contains the experimental results of the SCF-Test applied to the new lunar CCR, and all the new payload developments, including the future SCF tests. The International Lunar Network (ILN) research project considers our new retroreflector as one of the possible "Core Instruments

Reduced NK cell activity and abnormal expression of CCR7 and CXCR1 by NK cells analysis in patients with DOCK8 deficiency

DOCK8-deficiency is an autosomal recessive primary immunodeficiency that is characterized by multiple abnormalities of the immune system, including a defect of NK cell cytotoxicity which could not be restored after IL2 stimulation. Nevertheless, unanswered questions remain regarding how the absence of DOCK8 leads to predisposition for malignancy, viral, fungal, and bacterial infections. To address these questions we have analyzed NK cell phenotype and functions in patients with DOCK8 deficiency. We observed that NK cells derived from five DOCK8-deficient patients displayed dramatically reduced cytotoxicity which was partially restored after IL-2 stimulation. Analysis of activating and inhibitory NK receptors, including KIRs molecules, chemokine receptors and activation markers on gated CD56+cells by cytofluorimetric analysis showed a substantial defect of CCR7 expression by CD56bright NK cells. Noteworthy, we have also detected the expression of NKG2C and of the chemokine receptor CXCR1 on CD56dull NK cells in DOCK8-deficient cells. Because CCR7 expression by NK cells can be induced after cell culture with IL18 we stimulated NK cells from DOCK-8 deficient patients with IL18. Despite unstimulated CD56bright NK cells from DOCK8 patients showed reduced CCR7 expression, we could not detect any increase of CCR7 on CD56 dull and bright NK cells of DOCK8-deficient patients, whereas CCR7 expression on NK cells derived from healthy donors significantly increased from 5% to 17%.Taken together our results suggest that NK cells of DOCK-8 deficient patients show reduced cytotoxicity and abnormal expression of the chemokine receptors CXCR1 and CCR7 suggesting an abnormal recruitment of these cells to secondary lymphoid organs

Componentes da parede celular das silagens de seis genótipos de sorgo (Sorghum bicolor (L.) Moench).

Foram estudados os componentes da parede celular de seis genótipos de sorgo (Sorghum bicolor (L.) Moench) de porte alto e colmo seco para a produção de silagem. A colheita do material a ser ensilado foi realizada durante o estádio de grão leitoso/pastoso. Os híbridos 1 e 2 são as testemunhas comerciais (BRS610 e VOLUMAX, respectivamente), enquanto que os outros quatro são novos materiais desenvolvidos pela EMBRAPA Milho e Sorgo. Nas silagens utilizaram-se silos de laboratório, feitos de PVC. Foram avaliados oito períodos, sendo que um destes é a forragem antes de ensilar (PO). Os silos foram abertos com 1; 3; 5; 7; 14; 28 e 56 dias de fermentação, que correspondem a P1; P2; P3; P4; P5; P6 e P7, respectivamente. Utilizou-se o teste SNK para comparação entre médias, com um delineamento experimental inteiramente ao acaso. Os híbridos não apresentaram alterações dos componentes da parede celular com o processo de ensilagem. Todos os materiais se mostraram promissores para a confecção de silagens, pois os nutrientes dos híbridos em estudo se mostraram estáveis diante do processo de ensilagem

The Observation of Up-going Charged Particles Produced by High Energy Muons in Underground Detectors

An experimental study of the production of up-going charged particles in inelastic interactions of down-going underground muons is reported, using data obtained from the MACRO detector at the Gran Sasso Laboratory. In a sample of 12.2 10^6 single muons, corresponding to a detector livetime of 1.55 y, 243 events are observed having an up-going particle associated with a down-going muon. These events are analysed to determine the range and emission angle distributions of the up-going particle, corrected for detection and reconstruction efficiency. Measurements of the muon neutrino flux by underground detectors are often based on the observation of through-going and stopping muons produced in $\nu_\mu$ interactions in the rock below the detector. Up-going particles produced by an undetected down-going muon are a potential background source in these measurements. The implications of this background for neutrino studies using MACRO are discussed.Comment: 18 pages, 9 figures. Accepted by Astrop. Physic

WRAP53 Is Essential for Cajal Body Formation and for Targeting the Survival of Motor Neuron Complex to Cajal Bodies

The WRAP53 protein regulates the formation and maintenance of Cajal bodies (nuclear sub-organelles), as well as directs the recruitment of nuclear factors to Cajal bodies

Natural Killer Cells from Patients with Recombinase-Activating Gene and Non-Homologous End Joining Gene Defects Comprise a Higher Frequency of CD56bright NKG2A+++ Cells, and Yet Display Increased Degranulation and Higher Perforin Content.

Mutations of the recombinase Activating Genes 1 and 2 (RAG1, RAG2) in humans are associated with a broad range of phenotypes. For patients with severe clinical presentation, hematopoietic stem cell transplantation (HSCT) represents the only curative treatment, however high rates of graft failure and incomplete immune reconstitution have been observed, especially after unconditioned haploidentical transplantation. Studies in mice have shown that Rag-/- NK cells have a mature phenotype, reduced fitness and increased cytotoxicity. We aimed to analyze NK cell phenotype and function in patients with mutations in RAG and in non-homologous end joining (NHEJ) genes. Here we provide evidence that NK cells from these patients have an immature phenotype, with significant expansion of CD56bright CD16-/int CD57- cells, yet increased degranulation and high perforin content. Correlation was observed between in vitro recombinase activity of the mutant proteins, NK cell abnormalities, and in vivo clinical phenotype. Addition of serotherapy in the conditioning regimen, with the aim of depleting the autologous NK cell compartment, may be important to facilitate engraftment and immune reconstitution in patients with RAG and NHEJ defects treated by HSCT

EuPRAXIA - A compact, cost-efficient particle and radiation source

Plasma accelerators present one of the most suitable candidates for the development of more compact particle acceleration technologies, yet they still lag behind radiofrequency (RF)-based devices when it comes to beam quality, control, stability and power efficiency. The Horizon 2020-funded project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") aims to overcome the first three of these hurdles by developing a conceptual design for a first international user facility based on plasma acceleration. In this paper we report on the main features, simulation studies and potential applications of this future research infrastructure