Defining the role of IL-15 trans-presentation by distinct cell-types during the development and homeostasis of Natural Killer and invariant Natural Killer T cells

The immuno-regulatory functions displayed by NK and iNKT cells have highlighted their importance as key lymphocytes involved in innate and adaptive immunity. Therefore, understanding the dynamics influencing the generation of NK and iNKT cells is extremely important. IL-15 has been shown to provide a critical signal throughout the development and homeostasis of NK and iNKT cells; however, the cellular source of IL-15 has remained unclear. In this investigation, I provide evidence that the cell-type providing IL-15 to NK and iNKT cells via trans-presentation is determined by the tissue site and the maturation status of NK and iNKT cells. For NK cells, I revealed the non-hematopoietic compartment provides IL-15 to NK cells in the early stages of development while hematopoietic cells were crucial for the generation and maintenance of mature NK cells. Regarding iNKT cells in the thymus, IL-15 trans-presentation by non-hematopoietic cells was crucial for the survival of mature iNKT cells. In the liver, both hematopoietic and non-hematopoietic compartments provided IL-15 to both immature and mature iNKT cells. This IL-15 signal helped mediate the survival and proliferation of both NK and iNKT cells as well as induce the functional maturation of mature iNKT cells via enhanced T-bet expression. In conclusion, my work illustrates an important notion that the immunological niche of NK and iNKT cells is tightly regulated and that this regulation is meticulously influenced by the tissue microenvironment.

Transcriptional regulation of the invariant chain associated with MHC class II molecules

The invariant chain associated with the major histocompatibility complex (MHC) class II molecules is a non-polymorphic glycoprotein implicated in antigen processing and class II molecule intracellular transport. Class II molecules and invariant chain (In) are expressed primarily by B lymphocytes and antigen-presenting cells such as macrophages and can be induced by interferon gamma (IFN-$\gamma$) in a variety of cell types such as endothelial cells, fibroblasts, and astrocytes. In this study the cis-acting sequences involved in the constitutive, tissue-specific, and IFN-$\gamma$ induced expression of the human In gene were investigated and nuclear proteins which specifically bound these sequences were identified.^ To define promoter sequences involved in the regulation of the human In gene, 790 bp 5$\sp\prime$ to the initiation of transcription were subcloned upstream of the gene encoding chloramphenicol acetyl transferase (CAT). Transfection of this construct into In expressing and non-expressing cell lines demonstrated that this 790 bp In promoter sequence conferred tissue specificity to the CAT gene. Deletion mutants were created in the promoter to identify sequences important for transcription. Three regulatory regions were identified $-$396 to $-$241, $-$241 to $-$216, and $-$216 to $-$165 bp 5$\sp\prime$ to the cap site. Transfection into a human glioblastoma cell line, U-373 MG, and treatment with IFN-$\gamma$, demonstrated that this 5$\sp\prime$ region is responsive to IFN-$\gamma$. An IFN-$\gamma$ response element was sublocalized to the region $-$120 to $-$61 bp. This region contains homology to the interferon-stimulated response element (ISRE) identified in other IFN responsive genes. IFN-$\gamma$ induces a sequence-specific DNA binding factor which binds to an oligonucleotide corresponding to $-$107 to $-$79 bp of the In promoter. This factor also binds to an oligonucleotide corresponding to $-$91 to $-$62 of the interferon-$\beta$ gene promoter, suggesting this factor may be member of the IRF-1/ISGF2, IRF-2, ICSBP family of ISRE binding proteins. A transcriptional enhancer was identified in the first intron of the In gene. This element, located in a 2.6 kb BamHI/PstI fragment, enhances the IFN-$\gamma$ response of the promoter in U-373 MG. The majority of the In enhancer activity was sublocalized to a 550 bp region $\sim$1.6 kb downstream of the In transcriptional start site. ^

Search for Quantum Black Hole Production in High-Invariant-Mass Lepton plus Jet Final States Using pp Collisions at root s=8 TeV and the ATLAS Detector

This Letter presents a search for quantum black-hole production using 20.3 fb(-1) of data collected with the ATLAS detector in pp collisions at the LHC at root s = 8 TeV. The quantum black holes are assumed to decay into a final state characterized by a lepton (electron or muon) and a jet. In either channel, no event with a lepton-jet invariant mass of 3.5 TeV or more is observed, consistent with the expected background. Limits are set on the product of cross sections and branching fractions for the lepton + jet final states of quantum black holes produced in a search region for invariant masses above 1 TeV. The combined 95% confidence level upper limit on this product for quantum black holes with threshold mass above 3.5 TeV is 0.18 fb. This limit constrains the threshold quantum black-hole mass to be above 5.3 TeV in the model considered.

Enhanced Cold Tolerance in Transgenic Tobacco Expressing a Chloroplast Omega-3 Fatty Acid Desaturase Gene under the Control of a Cold-inducible Promoter

A new cold-inducible genetic construct was cloned using a chloroplast-specific omega-3-fatty acid desaturase gene (FAD7) under the control of a cold-inducible promoter (cor15a) from Arabidopsis thaliana. RT-PCR confirmed a marked increase in FAD7 expression, in young Nicotiana tabacum (cv. Havana) plants harboring cor15a-FAD7, after a short-term exposure to cold. When young, cold-induced tobacco seedlings were exposed to low-temperature (0.5, 2 or 3.5 degrees C) for up to 44 days, survival within independent cor15a-FAD7 transgenic lines (40.2-96%) was far superior to the wild type (6.7-10.2%). In addition, the major trienoic fatty acid species remained stable in cold-induced cor15a-FAD7 N. tabacum plants under prolonged cold storage while the levels of hexadecatrienoic acid (16:3) and octadecatrienoic acid (18:3) declined in wild type plants under the same conditions (79 and 20.7% respectively). Electron microscopy showed that chloroplast membrane ultrastructure in cor15a-FAD7 transgenic plants was unaffected by prolonged exposure to cold temperatures. In contrast, wild type plants experienced a loss of granal stacking and disorganization of the thylakoid membrane under the same conditions. Changes in membrane integrity coincided with a precipitous decline in leaf chlorophyll concentration and low survival rates in wild type plants. Cold-induced double transgenic N. alata (cv. Domino Mix) plants, harboring both the cor15a-FAD7 cold-tolerance gene and a cor15a-IPT dark-tolerance gene, exhibited dramatically higher survival rates (89-90%) than wild type plants (2%) under prolonged cold storage under dark conditions (2 degrees C for 50 days).

The effects of omega -3 fatty acid -enriched fish on C -reactive protein levels in postmenopausal women

Coronary heart disease (CHD) is the leading cause of death in women and rates markedly increase among women after 65 years of age. C-reactive protein (CRP) is a new clinical indicator of atherosclerotic-related inflammation with a direct pathogenic role. Studies show lifestyle factors can modulate CRP. Omega-3 fatty acids have anti-inflammatory properties and studies suggest that eating fish high in omega-3 fatty acids may lower CHD risk in women. This study sought to assess the possible role of omega-3 fatty acids in the reduction of CHD-related inflammation by investigating the effect of fish consumption on CRP levels. Methods. Twenty-four healthy postmenopausal women were randomly assigned to a fish group (usual diet plus two servings per week of enriched fish) or control group (usual diet with no fatty fish) for eight weeks. Omega-3 fatty acid-enriched fish developed by the West Virginia University Aquaculture Division was used. Serum CRP, serum interleukin-6 (IL-6), and the fatty acid content of red blood cells (RBC) were measured before and after the study. Women also completed food records. RESULTS: Baseline levels of CRP were low (85% of the fish group had normal levels) and few changes in CRP risk category were observed. Mean IL-6 levels were reduced by 27% and 35% in the fish and control groups, respectively (p for between-group difference = 0.60). Changes in RBC fatty acid composition were not statistically significant. Compared to control women, women in the fish group had greater reductions in mean triglycerides (p = 0.08), total cholesterol (P = 0.04), and LDL cholesterol levels (p = 0.06). Baseline dietary intake of total and monounsaturated fatty acids tended to be positively associated with baseline CRP, while vitamin E intake was inversely related. Saturated fat intake tended to have a positive association with IL-6. Conclusions. Findings regarding the effect of two servings of fish on CRP and IL-6 levels are inconclusive due to low baseline levels of CRP and IL-6. However, results indicate two servings of fatty fish have favorable effects on blood lipids. The relationship of dietary components with CRP and IL-6 is complex and further research is needed to determine the varying roles of diet on the inflammatory process. ^

Shape-invariant multibeam backscatter data of the eastern slope of the Porcupine Seabight (50 m grid size)

In this study multibeam angular backscatter data acquired in the eastern slope of the Porcupine Seabight are analysed. Processing of the angular backscatter data using the 'NRGCOR' software was made for 29 locations comprising different geological provinces like: carbonate mounds, buried mounds, seafloor channels, and inter-channel areas. A detailed methodology is developed to produce a map of angle-invariant (normalized) backscatter data by correcting the local angular backscatter values. The present paper involves detailed processing steps and related technical aspects of the normalization approach. The presented angle-invariant backscatter map possesses 12 dB dynamic range in terms of grey scale. A clear distinction is seen between the mound dominated northern area (Belgica province) and the Gollum channel seafloor at the southern end of the site. Qualitative analyses of the calculated mean backscatter values i.e., grey scale levels, utilizing angle-invariant backscatter data generally indicate backscatter values are highest (lighter grey scale) in the mound areas followed by buried mounds. The backscatter values are lowest in the inter-channel areas (lowest grey scale level). Moderate backscatter values (medium grey level) are observed from the Gollum and Kings channel data, and significant variability within the channel seafloor provinces. The segmentation of the channel seafloor provinces are made based on the computed grey scale levels for further analyses based on the angular backscatter strength. Three major parameters are utilized to classify four different seafloor provinces of the Porcupine Seabight by employing a semi-empirical method to analyse multibeam angular backscatter data. The predicted backscatter response which has been computed at 20° is the highest for the mound areas. The coefficient of variation (CV) of the mean backscatter response is also the highest for the mound areas. Interestingly, the slope value of the buried mound areas are found to be the highest. However, the channel seafloor of moderate backscatter response presents the lowest slope and CV values. A critical examination of the inter-channel areas indicates less variability within the estimated three parameters.

The effects of long (C20/22) and short (C18) chain omega-3 fatty acids on keel bone fractures, bone biomechanics, behavior, and egg production in free-range laying hens.

Keel fractures in the laying hen are the most critical animal welfare issue facing the egg production industry, particularly with the increased use of extensive systems in response to the 2012 EU directive banning conventional battery cages. The current study is aimed at assessing the effects of 2 omega-3 (n3) enhanced diets on bone health, production endpoints, and behavior in free-range laying hens. Data was collected from 2 experiments over 2 laying cycles, each of which compared a (n3) supplemented diet with a control diet. Experiment 1 employed a diet supplemented with a 60:40 fish oil-linseed mixture (n3:n6 to 1.35) compared with a control diet (n3:n6 to 0.11), whereas the n3 diet in Experiment 2 was supplemented with a 40:60 fish oil-linseed (n3:n6 to 0.77) compared to the control diet (n3:n6 to 0.11). The n3 enhanced diet of Experiment 1 had a higher n3:n6 ratio, and a greater proportion of n3 in the long chain (C20/22) form (0.41 LC:SC) than that of Experiment 2 (0.12 LC:SC). Although dietary treatment was successful in reducing the frequency of fractures by approximately 27% in Experiment 2, data from Experiment 1 indicated the diet actually induced a greater likelihood of fracture (odds ratio: 1.2) and had substantial production detriment. Reduced keel breakage during Experiment 2 could be related to changes in bone health as n3-supplemented birds demonstrated greater load at failure of the keel, and tibiae and humeri that were more flexible. These results support previous findings that n3-supplemented diets can reduce fracture likely by increasing bone strength, and that this can be achieved without detriment to production. However, our findings suggest diets with excessive quantities of n3, or very high levels of C20/22, may experience health and production detriments. Further research is needed to optimize the quantity and type of n3 in terms of bone health and production variables and investigate the potential associated mechanisms.

Communication-efficient and crash-quiescent Omega with unknown membership

The failure detector class Omega (Ω) provides an eventual leader election functionality, i.e., eventually all correct processes permanently trust the same correct process. An algorithm is communication-efficient if the number of links that carry messages forever is bounded by n, being n the number of processes in the system. It has been defined that an algorithm is crash-quiescent if it eventually stops sending messages to crashed processes. In this regard, it has been recently shown the impossibility of implementing Ω crash quiescently without a majority of correct processes. We say that the membership is unknown if each process pi only knows its own identity and the number of processes in the system (that is, i and n), but pi does not know the identity of the rest of processes of the system. There is a type of link (denoted by ADD link) in which a bounded (but unknown) number of consecutive messages can be delayed or lost. In this work we present the first implementation (to our knowledge) of Ω in partially synchronous systems with ADD links and with unknown membership. Furthermore, it is the first implementation of Ω that combines two very interesting properties: communication-efficiency and crash-quiescence when the majority of processes are correct. Finally, we also obtain with the same algorithm a failure detector () such that every correct process eventually and permanently outputs the set of all correct processes.

Explicitly Context-Aware Publish/Subscribe with Context-Invariant Subscriptions

Although context could be exploited to improve the performance, elasticity and adaptation in most distributed systems that adopt the publish/subscribe (P/S) model of communication, only very few works have explored domains with highly dynamic context, whereas most adopted models are context agnostic. In this paper, we present the key design principles underlying a novel context-aware content-based P/S (CA-CBPS) model of communication, where the context is explicitly managed, focusing on the minimization of network overhead in domains with recurrent context changes thanks to contextual scoping. We highlight how we dealt with the main shortcomings of most of the current approaches. Our research is some of the first to study the problem of explicitly introducing context-awareness into the P/S model to capitalize on contextual information. The envisioned CA-CBPS middleware enables the cloud ecosystem of services to communicate very efficiently, in a decoupled, but contextually scoped fashion.

Bandlimited Airy Pulses for Invariant Propagation in Single-Mode Fibers

By spectral analysis, and using joint time-frequency representations, we present the theoretical basis to design invariant bandlimited Airy pulses with an arbitrary degree of robustness and an arbitrary range of single-mode fiber chromatic dispersion. The numerically simulated examples confirm the theoretically predicted pulse partial invariance in the propagation of the pulse in the fiber.

On some sampling-related frames in U-invariant spaces

This paper concerns the characterization as frames of some sequences in U-invariant spaces of a separable Hilbert space H where U denotes an unitary operator defined on H ; besides, the dual frames having the same form are also found. This general setting includes, in particular, shift-invariant or modulation-invariant subspaces in L2 (R), where these frames are intimately related to the generalized sampling problem. We also deal with some related perturbation problems. In so doing, we need that the unitary operator U belongs to a continuous group of unitary operators.

Generalized sampling in U-invariant subspaces

In this work we carry out some results in sampling theory for U-invariant subspaces of a separable Hilbert space H, also called atomic subspaces. These spaces are a generalization of the well-known shift- invariant subspaces in L2 (R); here the space L2 (R) is replaced by H, and the shift operator by U. Having as data the samples of some related operators, we derive frame expansions allowing the recovery of the elements in Aa. Moreover, we include a frame perturbation-type result whenever the samples are affected with a jitter error.