Interactivity And User-heterogeneity In On Demand Broadcast Video

Video-On-Demand (VOD) has appeared as an important technology for many multimedia applications such as news on demand, digital libraries, home entertainment, and distance learning. In its simplest form, delivery of a video stream requires a dedicated channel for each video session. This scheme is very expensive and non-scalable. To preserve server bandwidth, many users can share a channel using multicast. Two types of multicast have been considered. In a non-periodic multicast setting, users make video requests to the server; and it serves them according to some scheduling policy. In a periodic broadcast environment, the server does not wait for service requests. It broadcasts a video cyclically, e.g., a new stream of the same video is started every t seconds. Although, this type of approach does not guarantee true VOD, the worst service latency experienced by any client is less than t seconds. A distinct advantage of this approach is that it can serve a very large community of users using minimal server bandwidth. In VOD System it is desirable to provide the user with the video-cassette-recorder-like (VCR) capabilities such as fast-forwarding a video or jumping to a specific frame. This issue in the broadcast framework is addressed, where each video and its interactive version are broadcast repeatedly on the network. Existing techniques rely on data prefetching as the mechanism to provide this functionality. This approach provides limited usability since the prefetching rate cannot keep up with typical fast-forward speeds. In the same environment, end users might have access to different bandwidth capabilities at different times. Current periodic broadcast schemes, do not take advantage of high-bandwidth capabilities, nor do they adapt to the low-bandwidth limitation of the receivers. A heterogeneous technique is presented that can adapt to a range of receiving bandwidth capability. Given a server bandwidth and a range of different client bandwidths, users employing the proposed technique will choose either to use their full reception bandwidth capability and therefore accessing the video at a very short time, or using part or enough reception bandwidth at the expense of a longer access latency

Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells

The anti-diabetic drug metformin regulates T-cell responses to immune activation and is proposed to function by regulating the energy-stress-sensing adenosine-monophosphate-activated protein kinase (AMPK). However, the molecular details of how metformin controls T cell immune responses have not been studied nor is there any direct evidence that metformin acts on T cells via AMPK. Here, we report that metformin regulates cell growth and proliferation of antigen-activated T cells by modulating the metabolic reprogramming that is required for effector T cell differentiation. Metformin thus inhibits the mammalian target of rapamycin complex I signalling pathway and prevents the expression of the transcription factors c-Myc and hypoxia-inducible factor 1 alpha. However, the inhibitory effects of metformin on T cells did not depend on the expression of AMPK in T cells. Accordingly, experiments with metformin inform about the importance of metabolic reprogramming for T cell immune responses but do not inform about the importance of AMPK

Dynamic Changes in the Spatiotemporal Localization of Rab21 in Live RAW264 Cells during Macropinocytosis

Rab21, a member of the Rab GTPase family, is known to be involved in membrane trafficking, but its implication in macropinocytosis is unclear. We analyzed the spatiotemporal localization of Rab21 in M-CSF-stimulated RAW264 macrophages by the live-cell imaging of fluorescent protein-fused Rab21. It was demonstrated that wild-type Rab21 was transiently associated with macropinosomes. Rab21 was recruited to the macropinosomes after a decrease in PI(4,5)P2 and PI(3,4,5)P3 levels. Although Rab21 was largely colocalized with Rab5, the recruitment of Rab21 to the macropinosomes lagged a minute behind that of Rab5, and preceded that of Rab7. Then, Rab21 was dissociated from the macropinosomes prior to the accumulation of Lamp1, a late endosomal/lysosomal marker. Our analysis of Rab21 mutants revealed that the GTP-bound mutant, Rab21-Q78L, was recruited to the macropinosomes, similarly to wild-type Rab21. However, the GDP-bound mutant, Rab21-T33N, did not localize on the formed macropinosomes, suggesting that the binding of GTP to Rab21 is required for the proper recruitment of Rab21 onto the macropinosomes. However, neither mutation of Rab21 significantly affected the rate of macropinosome formation. These data indicate that Rab21 is a transient component of early and intermediate stages of macropinocytosis, and probably functions in macropinosome maturation before fusing with lysosomal compartments

Study of pulsatile pressure-driven electroosmotic flows through an elliptic cylindrical microchannel with the Navier slip condition

This paper aims to study an unsteady electric field-driven and pulsatile pressure-driven flow of a Newtonian fluid in an elliptic cylindrical microchannel with Navier boundary wall slip. The governing equations of the slip flow and distributions of electric potential and charge densities are the modified Navier-Stokes equations, the Poisson equation and the Nernst-Planck equations, respectively. Analytical and numerical analyses based on the Mathieu and modified Mathieu equations are performed to investigate the interplaying effects of pulsatile pressure gradients and the slip lengths on the electroosmotic flow

High-spatial resolution functional chemistry of nitrogen compounds in the observed UK meteorite fall Winchcombe

Organic matter in extraterrestrial samples is a complex material that might have played an important role in the delivery of prebiotic molecules to the early Earth. We report here on the identification of nitrogen-containing compounds such as amino acids and N-heterocycles within the recent observed meteorite fall Winchcombe by high-spatial resolution spectroscopy techniques. Although nitrogen contents of Winchcombe organic matter are low (N/C ~ 1–3%), we were able to detect the presence of these compounds using a low-noise direct electron detector. These biologically relevant molecules have therefore been tentatively found within a fresh, minimally processed meteorite sample by high spatial resolution techniques conserving the overall petrographic context. Carbon functional chemistry investigations show that sizes of aromatic domains are small and that abundances of carboxylic functional groups are low. Our observations demonstrate that Winchcombe represents an important addition to the collection of carbonaceous chondrites and still preserves pristine extraterrestrial organic matter

Dynamic NF-κB and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation

© Ankers et al. Dynamic cellular systems reprogram gene expression to ensure appropriate cellular fate responses to specific extracellular cues. Here we demonstrate that the dynamics of Nuclear Factor kappa B (NF-κB) signalling and the cell cycle are prioritised differently depending on the timing of an inflammatory signal. Using iterative experimental and computational analyses, we show physical and functional interactions between NF-κB and the E2 Factor 1 (E2F-1) and E2 Factor 4 (E2F-4) cell cycle regulators. These interactions modulate the NF-κB response. In S-phase, the NF-κB response was delayed or repressed, while cell cycle progression was unimpeded. By contrast, activation of NF-κB at the G1/S boundary resulted in a longer cell cycle and more synchronous initial NF-κB responses between cells. These data identify new mechanisms by which the cellular response to stress is differentially controlled at different stages of the cell cycle

Runt-related transcription factor 3 reverses epithelial-mesenchymal transition in hepatocellular carcinoma

Loss or decreased expression of runt-related transcription factor 3 (RUNX3), a tumor suppressor gene involved in gastric and other cancers, has been frequently observed in hepatocellular carcinoma (HCC). The objective of this study was to identify the regulatory mechanism of the epithelialmesenchymal transition (EMT) by RUNX3 in HCC. Human HCC cell lines, Hep3B, Huh7, HLF and SK-Hep1, were divided into low- and high-EMT lines, based on their expression of TWIST1 and SNAI2, and were used in this in vitro study. Ectopic RUNX3 expression had an anti-EMT effect in low-EMT HCC cell lines characterized by increased E-cadherin expression and decreased N-cadherin and vimentin expression. RUNX3 expression has previously been reported to reduce jagged-1 (JAG1) expression; therefore, JAG1 ligand peptide was used to reinduce EMT in RUNX3-expressing low-EMT HCC cells. Immunohistochemical analyses were performed for RUNX3, E-cadherin, N-cadherin and TWIST1 in 33 human HCC tissues, also divided into low- and high-EMT HCC, based on TWIST1 expression. E-cadherin expression was correlated positively and N-cadherin expression was correlated negatively with RUNX3 expression in low-EMT HCC tissues. Correlations between EMT markers and RUNX3 mRNA expression were analyzed using Oncomine datasets. Similarly, mRNA expression of E-cadherin was also significantly correlated with that of RUNX3 in low-EMT HCC, while mRNA expression of JAG1 was negatively correlated with that of RUNX3. These results suggest a novel mechanism by which loss or decreased expression of RUNX3 induces EMT via induction of JAG1 expression in low-EMT HCC

Hepatitis B virus X protein impedes the DNA repair via its association with transcription factor, TFIIH

<p>Abstract</p> <p>Background</p> <p>Hepatitis B virus (HBV) infections play an important role in the development of hepatocellular carcinoma (HCC). HBV X protein (HBx) is a multifunctional protein that can modulate various cellular processes and plays a crucial role in the pathogenesis of HCC. HBx is known to interact with DNA helicase components of TFIIH, a basal transcriptional factor and an integral component of DNA excision repair.</p> <p>Results</p> <p>In this study, the functional relevance of this association was further investigated in the context to DNA repair. By site-directed mutagenesis HBx's critical residues for interaction with TFIIH were identified. Similarly, TFIIH mutants lacking ATPase domain and the conserved carboxyl-terminal domain failed to interact with HBx. Yeast and mammalian cells expressing HBx^wtconferred hypersensitivity to UV irradiation, which is interpreted as a basic deficiency in nucleotide excision repair. HBx^mut120(Glu to Val) was defective in binding to TFIIH and failed to respond to UV.</p> <p>Conclusions</p> <p>We conclude that HBx may act as the promoting factor by inhibiting DNA repair causing DNA damage and accumulation of errors, thereby contributing to HCC development.</p

Enforced PGC-1α expression promotes CD8 T cell fitness, memory formation and antitumor immunity.

Memory CD8 T cells can provide long-term protection against tumors, which depends on their enhanced proliferative capacity, self-renewal and unique metabolic rewiring to sustain cellular fitness. Specifically, memory CD8 T cells engage oxidative phosphorylation and fatty acid oxidation to fulfill their metabolic demands. In contrast, tumor-infiltrating lymphocytes (TILs) display severe metabolic defects, which may underlie their functional decline. Here, we show that overexpression of proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), the master regulator of mitochondrial biogenesis (MB), favors CD8 T cell central memory formation rather than resident memory generation. PGC-1α-overexpressing CD8 T cells persist and mediate more robust recall responses to bacterial infection or peptide vaccination. Importantly, CD8 T cells with enhanced PGC-1α expression provide stronger antitumor immunity in a mouse melanoma model. Moreover, TILs overexpressing PGC-1α maintain higher mitochondrial activity and improved expansion when rechallenged in a tumor-free host. Altogether, our findings indicate that enforcing mitochondrial biogenesis promotes CD8 T cell memory formation, metabolic fitness, and antitumor immunity in vivo

Distinct roles of the RasGAP family proteins in C. elegans associative learning and memory

The Ras GTPase activating proteins (RasGAPs) are regulators of the conserved Ras/MAPK pathway. Various roles of some of the RasGAPs in learning and memory have been reported in different model systems, yet, there is no comprehensive study to characterize all gap genes in any organism. Here, using reverse genetics and neurobehavioural tests, we studied the role of all known genes of the rasgap family in C. elegans in associative learning and memory. We demonstrated that their proteins are implicated in different parts of the learning and memory processes. We show that gap-1 contribute redundantly with gap-3 to the chemosensation of volatile compounds, gap-1 plays a major role in associative learning, while gap-2 and gap-3 are predominantly required for short- and long-term associative memory. Our results also suggest that the C. elegans Ras orthologue let-60 is involved in multiple processes during learning and memory. Thus, we show that the different classes of RasGAP proteins are all involved in cognitive function and their complex interplay ensures the proper formation and storage of novel information in C. elegans