5,038 research outputs found
Regulation of NKG2D-Dependent NK Cell Functions: The Yin and the Yang of Receptor Endocytosis.
Natural-killer receptor group 2, member D (NKG2D) is a well characterized natural killer (NK) cell activating receptor that recognizes several ligands poorly expressed on healthy cells but up-regulated upon stressing stimuli in the context of cancer or viral infection. Although NKG2D ligands represent danger signals that render target cells more susceptible to NK cell lysis, accumulating evidence demonstrates that persistent exposure to ligand-expressing cells causes the decrease of NKG2D surface expression leading to a functional impairment of NKG2D-dependent NK cell functions. Upon ligand binding, NKG2D is internalized from the plasma membrane and sorted to lysosomes for degradation. However, receptor endocytosis is not only a mechanism of receptor clearance from the cell surface, but is also required for the proper activation of signalling events leading to the functional program of NK cells. This review is aimed at providing a summary of current literature relevant to the molecular mechanisms leading to NKG2D down-modulation with particular emphasis given to the role of NKG2D endocytosis in both receptor degradation and signal propagation. Examples of chronic ligand-induced down-regulation of NK cell activating receptors other than NKG2D, including natural cytotoxicity receptors (NCRs), DNAX accessory molecule-1 (DNAM1) and CD16, will be also discussed
PRM102 Budget Impact Analysis of Delayed-Release Dimethylfumarate In The Treatment of Relapsing-Remitting Multiple Sclerosis In Italy
INTRODUCTION: Multiple Sclerosis (MS) is a condition with a significant economic and social burden that affects young adults, in their active working phase. The most recent evaluations show an annual average social cost of € 38-39 thousand per patient. Today the approval of the new oral therapies allows physicians to select further options that can meet patients’ clinical unmet needs.
OBJECTIVES: To evaluate the economic impact of a recently approved therapy, delayed-release dimethyl-fumarate (DMF; also known as gastro-resistant DMF), on the overall management costs of relapsing-remitting multiple sclerosis (RRMS) in Italy.
METHODS: A budget impact model, adopting the perspective of the Italian National Healthcare Service (NHS), was used to compare healthcare costs of two different treatment scenarios: a) base-case, where DMF is not available for RRMS patients (Scenario A), vs. b) alternative-case, where DMF is available for RRMS patients (Scenario B). Healthcare costs sustained by the Italian NHS to manage the RRMS population (drug treatment, administration, therapy and disease monitoring, relapse management, treatment-related adverse events) have been calculated over 3 years and compared for the two scenarios. Impact of relapses for the disease modifying therapies (DMTs) included in the analysis was estimated using an elaboration of the results from published mixed treatment comparison. RRMS population treated with DMTs was estimated using Italian prevalence and incidence data. According to these estimates, the number of treated patients amounted to 36,078 at Year 1, 38,832 at Year 2, and 40,673 at Year 3.
RESULTS: According to the current price and to the assumptions reported in the methodology section, it was estimated that the introduction of DMF (Scenario B) determines a decrease of the budget impact, if compared with the base case (Scenario A) in the perspective of Italian NHS. Over three years, the budget impact would be € 1,376 mln in the Scenario A and € 1,354 mln in the Scenario B (-22.18 mln €; -1.61% relative budget variation). The main drivers for cost-saving were pharmacological treatment costs and reduced burden of relapses (corresponding to more than 1,800 avoided relapses).
CONCLUSIONS: At the current cost conditions applied in Italy and according to the described assumptions, the use of DMF is economically sustainable for the Italian NHS. Plausibly, the introduction and usage of this new therapy in RRMS patients will ensure clinical benefits for patients without resulting in additional costs for the Italian NHS.
[In Italian
Effective Field Theory for the perturbations of a slowly rotating black hole
We develop the effective theory for perturbations around black holes with scalar hair, in two directions. First, we show that the scalar-Gauss-Bonnet theory, often used as an example exhibiting scalar black hole hair, can be deformed by galileon operators leading to order unity changes to its predictions. The effective theory for perturbations thus provides an efficient framework for describing and constraining broad classes of scalar-tensor theories, of which the addition of galileon operators is an example. Second, we extend the effective theory to perturbations around an axisymmetric, slowly rotating black hole, at linear order in the black hole spin. We also discuss the inclusion of parity-breaking operators in the effective theory.We develop the effective theory for perturbations around black holes with scalar hair, in two directions. First, we show that the scalar-Gauss-Bonnet theory, often used as an example exhibiting scalar black hole hair, can be deformed by galileon operators leading to order unity changes to its predictions. The effective theory for perturbations thus provides an efficient framework for describing and constraining broad classes of scalar-tensor theories, of which the addition of galileon operators is an example. Second, we extend the effective theory to perturbations around an axisymmetric, slowly rotating black hole, at linear order in the black hole spin. We also discuss the inclusion of parity-breaking operators in the effective theory
Immigrant entrepreneurs, diasporas, and exports
This paper demonstrates the positive effect of immigrant entrepreneurs on manufacturing exports over and above that of diasporas. Using small\u2010scale regional administrative data, our instrumental variable estimates of export gravity models imply that ceteris paribus, that is, holding constant the total number of immigrants, the expected protrade effect of a migrant becoming an entrepreneur amounts to an average increase of US$5,946 in the export flows toward her country of origin. Besides these dyadic effects, immigrant entrepreneurs unlike nonentrepreneurial immigrants raise a region's overall competitiveness and export flows toward other destinations as well
Network Analysis of World Trade using the BACI-CEPII dataset
In this paper we explore the BACI-CEPII database using Network Analysis. Starting from the visualization of the World Trade Network, we then define and describe the topology of the network, both in its binary version and in its weighted version, calculating and discussing some of the commonly used network's statistics. We finally discuss some specic topics that can be studied using Network Analysis and International Trade data, both at the aggregated and sectoral level. The analysis is done using multiple software (Stata, R, and Pajek). The scripts to replicate part of the analysis are included in the appendix, and can be used as an handson tutorial. Moreover,the World Trade Network local and global centrality measures, for the unweighted and the weighted version of the Network, calculated using the bilateral aggregate trade data for each country (178 in total) and each year (from 1995 to 2010,) can be downloaded from the CEPII webpage
Static response and Love numbers of Schwarzschild black holes
We derive the quadratic action for the physical degrees of freedom of massless spin-0, spin-1, and spin-2 perturbations on a Schwarzschild-(A)dS background in arbitrary dimensions. We then use these results to compute the static response of asymptotically flat Schwarzschild black holes to external fields. Our analysis reproduces known facts about black hole Love numbers-in particular that they vanish for all types of perturbation in four spacetime dimensions-but also leads to new results. For instance, we find that neutral Schwarzschild black holes polarize in the presence of an electromagnetic background in any number of spacetime dimensions except four. Moreover, we calculate for the first time black hole Love numbers for vector-type gravitational perturbations in higher dimensions and find that they generically do not vanish. Along the way, we shed some light on an apparent discrepancy between previous results in the literature, and clarify some aspects of the matching between perturbative calculations of static response on a Schwarzschild background and the point-particle effective theory.</p
Cu-catalyzed Si-NWS grown on “carbon paper” as anodes for Li-ion cells
The very high theoretical capacity of the silicon (4200mAh/g more than 10 times larger than graphite), environmental-friendly, abundant and low-cost, makes it a potential candidate to replace graphite in high energy density Li-ion batteries. As a drawback, silicon suffers from huge volume changes (300%) on alloying and dealloying with Li, leading a structural deformation that induces disruption. The use of nanostructured silicon materials has been shown to be an effective way to avoid this mechanical degradation of the active material. In this paper the synthesis of silicon nanowires, grown on a highly porous 3D-like carbon paper substrate by CVD using Cu as the catalyst, is presented. The use of carbon paper allows to achieve remarkable loadings of active material (2-5 mg/cm2) and, consequently, high capacity densities. The silicon electrode was investigated both morphologically and electrochemically. To improve the electrochemical performance various strategies have been carried out. It was observed that a very slow first cycle (C/40), which helps the formation of a stable solid electrolyte interphase on the silicon surface, improves the performance of the cells; nevertheless, their cycle life has been found not fully satisfactory. Morphological analysis of the Si-NWs electrodes before and after cycling showed the presence of a dense silicon layer below the nanowires which could reduce the electrical contact between the active material and the substrate
Tinjauan Geografis Perumahan Gading Jaya Kotabaru Kecamatan Tanjung Karang Timur Bandar Lampung Tahun 2016
The research aimed to find out geographical review of Gading Jaya Residence Kotabaru, East Tanjung Karang Sub-district, Bandar Lampung in 2016.The data collecting technique was done through field observation technique and documentation.The research method used in the research was explorative description. Results of the research showed that: (1) the topography of Gading Jaya Residence is appropriate since its height difference is 18 mand its slope is 2% - 15%, (2) the soil type of Gading Jaya Residence is Mediterranean (lime) and Latosol which are appropriate for residence construction, (3) the average rainfall at Gading Jaya residence is average since yearly average rainfall is below 4.000 mm, (4) the land use for housing at Gading Jaya is based on the criteria issued by PU (Pekerjaan Umum) department, and (5) the depth of ground water at Gading Jaya Residence is 100% or entirely considered deep.Penelitian ini dilakukan bertujuan untuk mengetahui tinjauan geografis Perumahan Gading Jaya Kotabaru Kecamatan Tanjung Karang Timur Bandar LampungTahun 2016. Pengumpulan data dilakukan dengan menggunakan teknik observasi lapangan dan dokumentasi.Teknik analisis deskriptif eksploratif. Hasil penelitian menunjukan bahwa: (1) Topografi Perumahan Gading Jaya sesuai karena memiliki beda tinggi 18 meter serta memiliki kemiringan lereng 2% - 15%. (2) Jenis tanah Perumahan Gading Jaya adalah mediteranian (kapur) dan latosol sesuai untuk dibangun Perumahan. (3) Rata-rata curah hujan di Perumahan Gading Jaya sesuai karena rata-rata curah hujan per tahunnya < 4.000 mm. (4) Penggunaan lahan di Perumahan Gading Jaya sudah sesuai dengan kriteria penggunaan lahan untuk Perumahan yang dikeluarkan kementerian Pekerjaan Umum (PU) serta,(5) Kedalaman air tanah di Perumahan Gading Jaya 100% atau seluruhnya termasuk dalam kriteria dalam
Black hole superradiance with dark matter accretion
Studies of black hole superradiance often focus on the growth of a cloud in isolation, accompanied by the spin-down of the black hole. In this paper, we consider the additional effect of the accretion of matter and angular momentum from the environment. We show that, in many cases, the black hole evolves by drifting along the superradiance threshold, in which case the evolution of its parameters can be described analytically or semianalytically. We quantify the conditions under which accretion can serve as a mechanism to increase the cloud-to-black hole mass ratio, beyond the standard maximum of about 10%. This occurs by a process we call oversuperradiance, whereby accretion effectively feeds the superradiance cloud, by way of the black hole. We give two explicit examples: accretion from a vortex expected in wave dark matter and accretion from a baryonic disk. In the former case, we estimate the accretion rate by using an analytical fit to the asymptotic behavior of the confluent Heun function. Level transition, whereby one cloud level grows while the other shrinks, can be understood in a similar way
LEO object’s light-curve acquisition system and their inversion for attitude reconstruction
In recent years, the increase in space activities has brought the space debris issue to the top of the list of all space agencies. The fact of there being uncontrolled objects is a problem both for the operational satellites in orbit (avoiding collisions) and for the safety of people on the ground (re-entry objects). Optical systems provide valuable assistance in identifying and monitoring such objects. The Sapienza Space System and Space Surveillance (S5Lab) has been working in this field for years, being able to take advantage of a network of telescopes spread over different continents. This article is focused on the re-entry phase of the object; indeed, the knowledge of the state of the object, in terms of position, velocity, and attitude during the descent, is crucial in order to predict as accurately as possible the impact point on the ground. A procedure to retrieve the light curves of orbiting objects by means of optical data will be shown and a method to obtain the attitude determination from their inversion based on a stochastic optimization (genetic algorithm) will be proposed
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