On LOS Contribution to Ultra-Dense Network

Ultra-dense networks (UDNs) are widely considered as an effective solution to greatly improve coverage by shortening the communication distance between user equipments (UEs) and base stations (BSs). The reality of UDN is that line-of-sight (LOS) communication becomes more likely to occur but this desirable result also complicates the performance analysis of random UDNs and puts an obstacle on the design and optimization of UDNs. The aim of this paper is to derive analytical results that take into account the phenomenon of having mixed LOS and non line-of-sight (NLOS) links in UDNs. In particular, the use of an arbitrary shaped thinning process to model the LOS wireless links allowed us to investigate a wide set of scenarios for what concerns the desired and interfering power levels. Our contribution is an accurate approximation in closed form for the success content delivery probability (SCDP) that decouples the contribution from LOS and NLOS links. Simulation results corroborate the accuracy of the proposed approximation

Ultra Dense Edge Caching Networks With Arbitrary User Spatial Density

Cache-enabled small cells can be an effective solution to deliver contents to mobile users with much lower power and latency. While the trend for getting smaller and denser cells is clear, interference will soon become unmanageable and an obstacle when the number of content requests is massive. Moreover, content request is seldom a spatially homogeneous process due to physical impediments (e.g., buidings) and social activities, which makes resource allocation for content delivery more challenging. In this paper, we consider an ultra-dense network (UDN) in which content requests are served by cache-enabled access nodes which can either be active for delivering contents to users, or inactive to reduce interference and network energy consumption. Our aim is to devise an approach that can locally adapt the caching node density and content caching probabilities to accommodate any arbitrary user density and content request for maximizing the network’s successful content delivery probability (SCDP). With a non-homogeneous spatial distribution for user equipments (UEs), we find that user-load, a parameter at the access node, plays a major role in the overall optimization. Simulation results illustrate that the proposed method can obtain superior performance against the considered benchmarks, with up to 150-160% increase, and our optimized solutions effectively adapt to the spatial-dependent user density

BAFF regulates B cell survival by downregulating the BH3-only family member Bim via the ERK pathway

The B cell activating factor belonging to the tumor necrosis factor family (BAFF) is required for B cell survival and maturation. The mechanisms by which BAFF mediates B cell survival are less understood. We found that BAFF and a proliferation-inducing ligand (APRIL), which are related, block B cell antigen receptor (BCR)–induced apoptosis upstream of mitochondrial damage, which is consistent with a role for Bcl-2 family proteins. BCR ligation strongly increased expression of the proapoptotic Bcl-2 homology 3–only Bcl-2 protein Bim in both WEHI-231 and splenic B cells, and increases in Bim were reversed by BAFF or APRIL. Small interfering RNA vector–mediated suppression of Bim blocked BCR-induced apoptosis. BAFF also induced Bim phosphorylation and inhibited BCR-induced association of Bim with Bcl-2. BAFF induced delayed but sustained stimulation of extracellular signal–regulated kinase (ERK) and its activators, mitogen-activated protein kinase/ERK activating kinase (MEK) and c-Raf, and MEK inhibitors promoted accumulation and dephosphorylation of Bim. These results suggest that BAFF inhibits BCR-induced death by down-regulating Bim via sustained ERK activation, demonstrating that BAFF directly regulates Bim function. Although transitional immature type 1 (T1) B cell numbers are normal in Bim−/− mice, T2 and follicular mature B cells are elevated and marginal zone B cells are reduced. Our results suggest that mature B cell homeostasis is maintained by BAFF-mediated regulation of Bim

Adsorption Capabilities of Fungoid Chitosan Toward Organic Acids in Model Solutions and White Wine

In oenology, fungoid chitosan (CH) can be used as an adjuvant for microbial control, haziness prevention, metal chelation, and ochratoxin removal. In acidic media (such as wine), CH can ionise and interact with charged compounds, giving rise to a series of adsorption and/or removal phenomena, some of which potentially impairing the overall quality of wines. In this context, it is worth noting that the interaction between CH and acidic components of wines has been poorly studied so far, and detailed information on this subject is still lacking. To study those interactions, different doses of chitosan (0.5; 1.0; 2.0 g/L) were dispersed in hydro-alcoholic solution (HS), synthetic wine solution (SW), and white wine (W). Results demonstrated that the remotion of tartaric acid and the change of pH were strongly affected by the matrix and dosage. In W and SW, chitosan was found to adsorb tartaric acid up to about 200 mg/g and 350 mg/g CH, respectively. Accordingly, pH values increased; however, the magnitude depended on the matrix as a consequence of different buffer capacities. Interestingly, even in the absence of tartaric acid (e.g. in HS samples) CH addition caused a pH increase (up to 1.2 units for 2 g/L CH addition) which demonstrated that pH variations may not only depend on the amount of organic acids adsorbed. The chitosan dispersed in W showed the highest average diameter D [3,2] (127.96 μm) compared to the ones dispersed in SW (120.81 μm) and in HS (116.26 μm), probably due to the presence of organic acids on the polymer surface. The minor removal of tartaric acid in W compared to SW could probably depend on the competitive adsorption onto chitosan of other families of compounds present in wine such as polyphenols. The data suggested that chitosan addition could affect the pH and organic acid concentration of all matrices, depending on the doses and composition of the solutions

IL-10 Producing B Cells Dampen Protective T Cell Response and Allow Chlamydia muridarum Infection of the Male Genital Tract

A significant proportion of individuals develop chronic, persistent and recurrent genital tract infections with Chlamydia trachomatis, which has been attributed to the numerous strategies that the bacterium uses to subvert host immune responses. Animal chlamydia models have demonstrated that protective immune response is mediated by CD4+ Th1 cytokine responses. Herein, we demonstrate that early after infecting the male genital tract, C. muridarum triggers the production of IL-10 by splenic and lymph node cells. In addition, C. muridarum triggers IL-6 and TNFα secretion. Data obtained from in vitro and in vivo experiments revealed B cells as the major IL-10 contributors. Indeed, purified B cells produced high amounts of IL-10 and also exhibited enhanced expression of inhibitory molecules such as CD39, PD-L1 and PD1 after C. muridarum stimulation. In vitro experiments performed with sorted cell subsets revealed that Marginal Zone B cells were the main IL-10 producers. In vitro and in vivo studies using TLR-deficient mice indicated that TLR4 signaling pathway was essential for IL-10 production. In addition, in vivo treatments to neutralize IL-10 or deplete B cells indicated that IL-10 and B cells played a significant role in delaying bacterial clearance ability. Moreover, the latter was confirmed by adoptive cell transfer experiments in which the absence of IL-10-producing B cells conferred the host a greater capability to induce Th1 responses and clear the infection. Interestingly, NOD mice, which were the least efficient in clearing the infection, presented much more Marginal Zone B counts and also enhanced TLR4 expression on Marginal Zone B cells when compared to B6 and BALB/c mice. Besides, treatment with antibodies that selectively deplete Marginal Zone B cells rendered mice more capable of inducing enhanced IFNγ responses and clearing the infection. Our findings suggest that B cells play a detrimental role in C. muridarum infection and that activation by innate receptors like TLR4 and IL-10 production by these cells could be used by Chlamydia spp. as a strategy to modulate the immune response establishing chronic infections in susceptible hosts

Dietary Supplementation with Probiotics Improves Hematopoiesis in Malnourished Mice

BACKGROUND: Lactobacillus rhamnosus CRL1505 (Lr) administered during the repletion of immunocompromised-malnourished mice improves the resistance against intestinal and respiratory infections. This effect is associated with an increase in the number and functionality of immune cells, indicating that Lr could have some influence on myeloid and lymphoid cell production and maturation. OBJECTIVE: This study analyzed the extent of the damage caused by malnutrition on myeloid and lymphoid cell development in the spleen and bone marrow (BM). We also evaluated the impact of immunobiotics on the recovery of hematopoiesis affected in malnourished mice. METHODS: Protein malnourished mice were fed on a balanced conventional diet for 7 or 14 consecutive d with or without supplemental Lr or fermented goat's milk (FGM). Malnourished mice and well-nourished mice were used as controls. Histological and flow cytometry studies were carried out in BM and spleen to study myeloid and lymphoid cells. RESULTS: Malnutrition induced quantitative alterations in spleen B and T cells; however, no alteration was observed in the ability of splenic B cells to produce immunoglobulins after challenge with LPS or CpG. The analysis of BM B cell subsets based on B220, CD24, IgM and IgD expression showed that malnutrition affected B cell development. In addition, BM myeloid cells decreased in malnourished mice. On the contrary, protein deprivation increased BM T cell number. These alterations were reverted with Lr or FGM repletion treatments since normal numbers of BM myeloid, T and B cells were observed in these groups. CONCLUSIONS: Protein malnutrition significantly alters B cell development in BM. The treatment of malnourished mice with L. rhamnosus CRL1505 was able to induce a recovery of B cells that would explain its ability to increase immunity against infections. This work highlights the possibility of using immunobiotics to accelerate the recovery of lymphopoyesis in immunocompromised-malnourished hosts

Dynamics of circulating follicular helper T cell subsets and follicular regulatory T cells in rheumatoid arthritis patients according to HLA-DRB1 locus

B cells, follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are part of a circuit that may play a role in the development or progression of rheumatoid arthritis (RA). With the aim of providing further insight into this topic, here we evaluated the frequency of different subsets of Tfh and Tfr in untreated and long-term treated RA patients from a cohort of Argentina, and their potential association with particular human leukocyte antigen (HLA) class-II variants and disease activity. We observed that the frequency of total Tfh cells as well as of particular Tfh subsets and Tfr cells were increased in seropositive untreated RA patients. Interestingly, when analyzing paired samples, the frequency of Tfh cells was reduced in synovial fluid compared to peripheral blood, while Tfr cells levels were similar in both biological fluids. After treatment, a decrease in the CCR7loPD1hi Tfh subset and an increase in the frequency of Tfr cells was observed in blood. In comparison to healthy donors, seropositive patients with moderate and high disease activity exhibited higher frequency of Tfh cells while seropositive patients with low disease activity presented higher Tfr cell frequency. Finally, we observed that HLA-DRB1*09 presence correlated with higher frequency of Tfh and Tfr cells, while HLA-DRB1*04 was associated with increased Tfr cell frequency. Together, our results increase our knowledge about the dynamics of Tfh and Tfr cell subsets in RA, showing that this is altered after treatment

BAFF Mediates Splenic B Cell Response and Antibody Production in Experimental Chagas Disease

Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Central and South America. It affects 20 million people and about 100 million people are at risk of infection in endemic areas. Some cases have been identified in non-endemic countries as a consequence of blood transfusion and organ transplantation. Chagas disease presents three stages of infection. The acute phase appears one to two weeks after infection and includes fever, swelling around the bite site, enlarged lymph glands and spleen, and fatigue. This stage is characterized by circulating parasites and many immunological disturbances including a massive B cell response. In general, the acute episode self-resolves in about 2 months and is followed by a clinically silent indeterminate phase characterized by absence of circulating parasites. In about one-third of the cases, the indeterminate phase evolves into a chronic phase with clinically defined cardiac or digestive disturbances. Current knowledge suggests that the persistence of parasites coupled with an unbalanced immune response sustain inflammatory response in the chronic stage. We believe that an effective treatment for chronic Chagas disease should combine antiparasitic drugs with immunomodulators aimed at reducing inflammation and autoreactive response. Our findings enlighten a new role of BAFF-BAFF-R signaling in parasite infection that partially controls polyclonal B cell response but not parasitespecific class-switched primary effectors B cells

SUPREMATISMO Y REVOLUCIÓN. ARTE MODERNO Y POLÍTICA CONTEMPORÁNEA

RESUMEN Este artículo examina la estética suprematista en relación con teorías políticas contemporáneas sobre la revolución y la transformación social. El punto de partida del suprematismo es la destrucción de la realidad objetiva como acto liberador. Aunque diversos autores contemporáneos del campo de la teoría política conciben el arte tcomo producción de sentimientos que actúan como puntos de partida de la acción y el compromiso. Ambas perspectivas se entrelazan en el concepto de 'revolución': la liberación de la representación totalitaria y la creación de una nueva sociedad

The Molecular Chaperone Hsp90α Is Required for Meiotic Progression of Spermatocytes beyond Pachytene in the Mouse

The molecular chaperone Hsp90 has been found to be essential for viability in all tested eukaryotes, from the budding yeast to Drosophila. In mammals, two genes encode the two highly similar and functionally largely redundant isoforms Hsp90α and Hsp90β. Although they are co-expressed in most if not all cells, their relative levels vary between tissues and during development. Since mouse embryos lacking Hsp90β die at implantation, and despite the fact that Hsp90 inhibitors being tested as anti-cancer agents are relatively well tolerated, the organismic functions of Hsp90 in mammals remain largely unknown. We have generated mouse lines carrying gene trap insertions in the Hsp90α gene to investigate the global functions of this isoform. Surprisingly, mice without Hsp90α are apparently normal, with one major exception. Mutant male mice, whose Hsp90β levels are unchanged, are sterile because of a complete failure to produce sperm. While the development of the male reproductive system appears to be normal, spermatogenesis arrests specifically at the pachytene stage of meiosis I. Over time, the number of spermatocytes and the levels of the meiotic regulators and Hsp90 interactors Hsp70-2, NASP and Cdc2 are reduced. We speculate that Hsp90α may be required to maintain and to activate these regulators and/or to disassemble the synaptonemal complex that holds homologous chromosomes together. The link between fertility and Hsp90 is further supported by our finding that an Hsp90 inhibitor that can cross the blood-testis barrier can partially phenocopy the genetic defects