Scheduling M2M traffic over LTE uplink of a dense small cell network

We present an approach to schedule Long Term Evolution (LTE) uplink (UL) Machine-to-Machine (M2M) traffic in a densely deployed heterogeneous network, over the street lights of a big boulevard for smart city applications. The small cells operate with frequency reuse 1, and inter-cell interference (ICI) is a critical issue to manage. We consider a 3rd Generation Partnership Project (3GPP) compliant scenario, where single-carrier frequency-division multiple access (SC-FDMA) is selected as the multiple access scheme, which requires that all resource blocks (RBs) allocated to a single user have to be contiguous in the frequency within each time slot. This adjacency constraint limits the flexibility of the frequency-domain packet scheduling (FDPS) and inter-cell interference coordination (ICIC), when trying to maximize the scheduling objectives, and this makes the problem NP-hard. We aim to solve a multi-objective optimization problem, to maximize the overall throughput, maximize the radio resource usage and minimize the ICI. This can be modelled through a mixed-integer linear programming (MILP) and solved through a heuristic implementable in the standards. We propose two models. The first one allocates resources based on the three optimization criteria, while the second model is more compact and is demonstrated through numerical evaluation in CPLEX, to be equivalent in the complexity, while it performs better and executes faster. We present simulation results in a 3GPP compliant network simulator, implementing the overall protocol stack, which support the effectiveness of our algorithm, for different M2M applications, with respect to the state-of-the-art approaches

Activation of transcription factors by extracellular nucleotides in immune and related cell types

Extracellular nucleotides, acting through P2 receptors, can regulate gene expression via intracellular signaling pathways that control the activity of transcription factors. Relatively little is known about the activation of transcription factors by nucleotides in immune cells. The NF-κB family of transcription factors is critical for many immune and inflammatory responses. Nucleotides released from damaged or stressed cells can act alone through certain P2 receptors to alter NF-κB activity or they can enhance responses induced by pathogen-associated molecules such as LPS. Nucleotides have also been shown to regulate the activity of other transcription factors (AP-1, NFAT, CREB and STAT) in immune and related cell types. Here, we provide an overview of transcription factors shown to be activated by nucleotides in immune cells, and describe what is known about their mechanisms of activation and potential functions. Furthermore, we propose areas for future work in this new and expanding field

Methamphetamine Causes Differential Alterations in Gene Expression and Patterns of Histone Acetylation/Hypoacetylation in the Rat Nucleus Accumbens

Methamphetamine (METH) addiction is associated with several neuropsychiatric symptoms. Little is known about the effects of METH on gene expression and epigenetic modifications in the rat nucleus accumbens (NAC). Our study investigated the effects of a non-toxic METH injection (20 mg/kg) on gene expression, histone acetylation, and the expression of the histone acetyltransferase (HAT), ATF2, and of the histone deacetylases (HDACs), HDAC1 and HDAC2, in that structure. Microarray analyses done at 1, 8, 16 and 24 hrs after the METH injection identified METH-induced changes in the expression of genes previously implicated in the acute and longterm effects of psychostimulants, including immediate early genes and corticotropin-releasing factor (Crf). In contrast, the METH injection caused time-dependent decreases in the expression of other genes including Npas4 and cholecystokinin (Cck). Pathway analyses showed that genes with altered expression participated in behavioral performance, cell-to-cell signaling, and regulation of gene expression. PCR analyses confirmed the changes in the expression of c-fos, fosB, Crf, Cck, and Npas4 transcripts. To determine if the METH injection caused post-translational changes in histone markers, we used western blot analyses and identified METH-mediated decreases in histone H3 acetylated at lysine 9 (H3K9ac) and lysine 18 (H3K18ac) in nuclear sub-fractions. In contrast, the METH injection caused time-dependent increases in acetylated H4K5 and H4K8. The changes in histone acetylation were accompanied by decreased expression of HDAC1 but increased expression of HDAC2 protein levels. The histone acetyltransferase, ATF2, showed significant METH-induced increased in protein expression. These results suggest that METH-induced alterations in global gene expression seen in rat NAC might be related, in part, to METH-induced changes in histone acetylation secondary to changes in HAT and HDAC expression. The causal role that HATs and HDACs might play in METH-induced gene expression needs to be investigated further

A Selective HDAC 1/2 Inhibitor Modulates Chromatin and Gene Expression in Brain and Alters Mouse Behavior in Two Mood-Related Tests

Psychiatric diseases, including schizophrenia, bipolar disorder and major depression, are projected to lead global disease burden within the next decade. Pharmacotherapy, the primary – albeit often ineffective – treatment method, has remained largely unchanged over the past 50 years, highlighting the need for novel target discovery and improved mechanism-based treatments. Here, we examined in wild type mice the impact of chronic, systemic treatment with Compound 60 (Cpd-60), a slow-binding, benzamide-based inhibitor of the class I histone deacetylase (HDAC) family members, HDAC1 and HDAC2, in mood-related behavioral assays responsive to clinically effective drugs. Cpd-60 treatment for one week was associated with attenuated locomotor activity following acute amphetamine challenge. Further, treated mice demonstrated decreased immobility in the forced swim test. These changes are consistent with established effects of clinical mood stabilizers and antidepressants, respectively. Whole-genome expression profiling of specific brain regions (prefrontal cortex, nucleus accumbens, hippocampus) from mice treated with Cpd-60 identified gene expression changes, including a small subset of transcripts that significantly overlapped those previously reported in lithium-treated mice. HDAC inhibition in brain was confirmed by increased histone acetylation both globally and, using chromatin immunoprecipitation, at the promoter regions of upregulated transcripts, a finding consistent with in vivo engagement of HDAC targets. In contrast, treatment with suberoylanilide hydroxamic acid (SAHA), a non-selective fast-binding, hydroxamic acid HDAC 1/2/3/6 inhibitor, was sufficient to increase histone acetylation in brain, but did not alter mood-related behaviors and had dissimilar transcriptional regulatory effects compared to Cpd-60. These results provide evidence that selective inhibition of HDAC1 and HDAC2 in brain may provide an epigenetic-based target for developing improved treatments for mood disorders and other brain disorders with altered chromatin-mediated neuroplasticity.Stanley Medical Research InstituteNational Institutes of Health (U.S.) (R01DA028301)National Institutes of Health (U.S.) (R01DA030321

Investigation of the Acetylation Mechanism by GCN5 Histone Acetyltransferase

The histone acetylation of post-translational modification can be highly dynamic and play a crucial role in regulating cellular proliferation, survival, differentiation and motility. Of the enzymes that mediate post-translation modifications, the GCN5 of the histone acetyltransferase (HAT) proteins family that add acetyl groups to target lysine residues within histones, has been most extensively studied. According to the mechanism studies of GCN5 related proteins, two key processes, deprotonation and acetylation, must be involved. However, as a fundamental issue, the structure of hGCN5/AcCoA/pH3 remains elusive. Although biological experiments have proved that GCN5 mediates the acetylation process through the sequential mechanism pathway, a dynamic view of the catalytic process and the molecular basis for hGCN5/AcCoA/pH3 are still not available and none of theoretical studies has been reported to other related enzymes in HAT family. To explore the molecular basis for the catalytic mechanism, computational approaches including molecular modeling, molecular dynamic (MD) simulation and quantum mechanics/molecular mechanics (QM/MM) simulation were carried out. The initial hGCN5/AcCoA/pH3 complex structure was modeled and a reasonable snapshot was extracted from the trajectory of a 20 ns MD simulation, with considering post-MD analysis and reported experimental results. Those residues playing crucial roles in binding affinity and acetylation reaction were comprehensively investigated. It demonstrated Glu80 acted as the general base for deprotonation of Lys171 from H3. Furthermore, the two-dimensional QM/MM potential energy surface was employed to study the sequential pathway acetylation mechanism. Energy barriers of addition-elimination reaction in acetylation obtained from QM/MM calculation indicated the point of the intermediate ternary complex. Our study may provide insights into the detailed mechanism for acetylation reaction of GCN5, and has important implications for the discovery of regulators against GCN5 enzymes and related HAT family enzymes

Characteristics of the memory sources of dreams: A new version of the content-matching paradigm to take mundane and remote memories into account

Several studies have demonstrated that dream content is related to the waking life of the dreamer. However, the characteristics of the memory sources incorporated into dreams are still unclear. We designed a new protocol to investigate remote memories and memories of trivial experiences, both relatively unexplored in dream content until now. Upon awakening, for 7 days, participants identified the waking life elements (WLEs) related to their dream content and characterized them and their dream content on several scales to assess notably emotional valence. Thanks to this procedure, they could report WLEs from the whole lifespan, and mundane ones before they had been forgotten. Participants (N = 40, 14 males, age = 25.2 ± 7.6) reported 6.2 ± 2.0 dreams on average. For each participant, 83.4% ± 17.8 of the dream reports were related to one or more WLEs. Among all the WLEs incorporated into dreams dated by the participants (79.3 ± 19%), 40.2 ± 30% happened the day before the dream, 26.1 ± 26% the month before (the day before excluded), 15.8 ± 21% the year before the dream (the month before excluded), and 17.9 ± 24% happened more than one year before the dream. As could be expected from previous studies, the majority of the WLEs incorporated into dreams were scored as important by the dreamers. However, this was not true for incorporated WLEs dating from the day before the dream. In agreement with Freud’s observations, the majority of the day residues were scored as mundane. Finally, for both positive and negative WLEs incorporated into dreams, the dreamt version of the WLE was rated as emotionally less intense than the original WLE. This result, showing that dreams tend to attenuate the emotional tone of waking-life memories towards a more neutral one, argues in favor of the emotional regulation hypothesis of dreaming

The Impact of Correlated Channel Fluctuations on the Connectivity of Wireless Ad-Hoc Networks

Channel fluctuations affecting links of ad-hoc and sensor networks show an evident spatial correlation, besides the random behavior. Nonetheless, the vast majority of models used in the literature assign edges between pairs of vertices of a graph according to either the deterministic disk model or some random connection model assuming i.i.d. fluctuations. We believe none of the approaches reflects the reality. In this paper we introduce a Correlated Random Connection Model (CRCM) which accounts for angular correlation, by means of a tunable parameter, in the fluctuations that affect two links sharing one of the endpoints. Assuming a constant average number of neighbors, we study the percolating properties of correlated footprints on random graphs by computing the relative size of the two largest components of the graph and the probability of the event of (almost) connectivity. We also compare it to the case of some non- probabilistic shapes of both theoretical and practical flavor. Our results show that the presence of correlation may be beneficial or detrimental, depending of whether one considers undirected or directed graphs, i.e., ultimately, on the application