RMD-QOSM: The NSIS Quality-of-Service Model for Resource Management in Diffserv

This document describes a Next Steps in Signaling (NSIS) Quality-of- Service (QoS) Model for networks that use the Resource Management in Diffserv (RMD) concept. RMD is a technique for adding admission control and preemption function to Differentiated Services (Diffserv) networks. The RMD QoS Model allows devices external to the RMD network to signal reservation requests to Edge nodes in the RMD network. The RMD Ingress Edge nodes classify the incoming flows into traffic classes and signals resource requests for the corresponding traffic class along the data path to the Egress Edge nodes for each flow. Egress nodes reconstitute the original requests and continue forwarding them along the data path towards the final destination. In addition, RMD defines notification functions to indicate overload situations within the domain to the Edge nodes

Critical role of canonical transient receptor potential channel 7 in initiation of seizures

Status epilepticus (SE) is a life-threatening disease that has been recognized since antiquity but still causes over 50,000 deaths annually in the United States. The prevailing view on the pathophysiology of SE is that it is sustained by a loss of normal inhibitory mechanisms of neuronal activity. However, the early process leading to the initiation of SE is not well understood. Here, we show that, as seen in electroencephalograms, SE induced by the muscarinic agonist pilocarpine in mice is preceded by a specific increase in the gamma wave, and genetic ablation of canonical transient receptor potential channel (TRPC) 7 significantly reduces this pilocarpine-induced increase of gamma wave activity, preventing the occurrence of SE. At the cellular level, TRPC7 plays a critical role in the generation of spontaneous epileptiform burst firing in cornu ammonis (CA) 3 pyramidal neurons in brain slices. At the synaptic level, TRPC7 plays a significant role in the long-term potentiation at the CA3 recurrent collateral synapses and Schaffer collateral-CA1 synapses, but not at the mossy fiber-CA3 synapses. Taken together, our data suggest that epileptiform burst firing generated in the CA3 region by activity-dependent enhancement of recurrent collateral synapses may be an early event in the initiation process of SE and that TRPC7 plays a critical role in this cellular event. Our findings reveal that TRPC7 is intimately involved in the initiation of seizures both in vitro and in vivo. To our knowledge, this contribution to initiation of seizures is the first identified functional role for the TRPC7 ion channel.Fil: Phelan, K. D.. University of Arkansas for Medical Sciences; Estados UnidosFil: Shwe, U. T.. University of Arkansas for Medical Sciences; Estados UnidosFil: Abramowitz, J.. National Institute of Environmental Health Sciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences; Estados UnidosFil: Zheng, F.. University of Arkansas for Medical Sciences; Estados Unido

A snapshot of translation in Mycobacterium tuberculosis during exponential growth and nutrient starvation revealed by ribosome profiling

Mycobacterium tuberculosis, which causes tuberculosis, can undergo prolonged periods of non-replicating persistence in the host. The mechanisms underlying this are not fully understood, but translational regulation is thought to play a role. A large proportion of mRNA transcripts expressed in M. tuberculosis lack canonical bacterial translation initiation signals, but little is known about the implications of this for fine-tuning of translation. Here, we perform ribosome profiling to characterize the translational landscape of M. tuberculosis under conditions of exponential growth and nutrient starvation. Our data reveal robust, widespread translation of non-canonical transcripts and point toward different translation initiation mechanisms compared to canonical Shine-Dalgarno transcripts. During nutrient starvation, patterns of ribosome recruitment vary, suggesting that regulation of translation in this pathogen is more complex than originally thought. Our data represent a rich resource for others seeking to understand translational regulation in bacterial pathogens

Entrepreneurial Orientation in Public Schools: The View from New Jersey

We utilize a sample of New Jersey schools to explore the relationship between entrepreneurial orientation (EO) and school performance. The results indicate a significant relationship between several dimensions of EO and performance after controlling for a number of relevant variables. Charter schools were found to have higher EO than traditional schools. The implications of these findings for education and entrepreneurship research are discussed

Field-dependent heat transport in the Kondo insulator SmB6 : phonons scattered by magnetic impurities

The thermal conductivity $\kappa$ of the Kondo insulator SmB$_6$ was measured at low temperature, down to 70 mK, in magnetic fields up to 15 T, on single crystals grown using both the floating-zone and the flux methods. The residual linear term $\kappa_0/T$ at $T \to 0$ is found to be zero in all samples, for all magnetic fields, in agreement with previous studies. There is therefore no clear evidence of fermionic heat carriers. In contrast to some prior data, we observe a large enhancement of $\kappa(T)$ with increasing field. The effect of field is anisotropic, depending on the relative orientation of field and heat current (parallel or perpendicular), and with respect to the cubic crystal structure. We interpret our data in terms of heat transport predominantly by phonons, which are scattered by magnetic impurities.Comment: publish versio

Understanding Conformational Regulation of the Integrin I-domain for Design of Chimeric Protein Switches

Within all complex biological processes intricate proteins are expressed to complete every niche and necessary task. Many express multiple allosterically regulated conformational states, with protein function regulated by effector molecules and other ligands. One such protein is the LFA-1 surface integrin protein and its inserted domain, the I-domain. We Isolated the I-domain for investigation of determining binding properties and understanding conformational regulations of affinity changes to its target ligand ICAM-1, for further use in chimeric protein switch design. A large change in binding affinity was found through the deletion of a sub-sequence of amino acids in I-domain known as the α7 helix. Our investigation shows that, when the α7 helix is deleted, I-domain converts into a permanent high affinity state in which binding affinity to ICAM-1 was increased, and this state can be reversed by co-expression with soluble α7 helix peptide. These results conclude that the α7 helix stabilizes the I domain in its low affinity conformation in a ligand-like manner, allowing relaxation to the high affinity conformation upon disruption of α7 helix interaction. While deletion of the α7 helix yields higher binding affinity in I-domain it cannot be applied in design of chimeric protein switches due to its permanent conformational state. Because of this, our switch design has a focus of allosterically regulating the I-domain and α7 helix through utilizing on/off switching of conformational states. I-domain is fused with EF3 and EF4 hands of calmodulin, which then regulates binding affinity to ICAM-1 through interaction with α7 helix, when the EF hands’ natural ligand peptides are present. Currently, mutant switches are being developed to alter EF hand binding specificity which, when bound to new target ligands, will cause an increase in I-domain-ICAM-1 binding affinity in switch molecules. The results of these allosteric regulations highlight the potential of chimeric protein switches for design of environmentally responsive targeting agents and suggest that, through directed evolution, regulated binding to a range of novel targets could be achieved for therapeutic intervention