Melatonin Therapy Prevents Programmed Hypertension and Nitric Oxide Deficiency in Offspring Exposed to Maternal Caloric Restriction

Nitric oxide (NO) deficiency is involved in the development of hypertension, a condition that can originate early in life. We examined whether NO deficiency contributed to programmed hypertension in offspring from mothers with calorie-restricted diets and whether melatonin therapy prevented this process. We examined 3-month-old male rat offspring from four maternal groups: untreated controls, 50% calorie-restricted (CR) rats, controls treated with melatonin (0.01% in drinking water), and CR rats treated with melatonin (CR + M). The effect of melatonin on nephrogenesis was analyzed using next-generation sequencing. The CR group developed hypertension associated with elevated plasma asymmetric dimethylarginine (ADMA, a nitric oxide synthase inhibitor), decreased L-arginine, decreased L-arginine-to-ADMA ratio (AAR), and decreased renal NO production. Maternal melatonin treatment prevented these effects. Melatonin prevented CR-induced renin and prorenin receptor expression. Renal angiotensin-converting enzyme 2 protein levels in the M and CR + M groups were also significantly increased by melatonin therapy. Maternal melatonin therapy had long-term epigenetic effects on global gene expression in the kidneys of offspring. Conclusively, we attributed these protective effects of melatonin on CR-induced programmed hypertension to the reduction of plasma ADMA, restoration of plasma AAR, increase of renal NO level, alteration of renin-angiotensin system, and epigenetic changes in numerous genes

Multi-Operator Fairness in Transparent RAN Sharing by Soft-Partition With Blocking and Dropping Mechanism

Radio access network (RAN) sharing has attracted significant attention from telecom operators as a means of accommodating data surges. However, current mechanisms for RAN sharing ignore the fairness issue among operators, and hence the RAN may be under- or over-utilized. Furthermore, the fairness among different operators cannot be guaranteed, since the RAN resources are distributed on a first come, first served basis. Accordingly, the present study proposes a “soft-partition with blocking and dropping” (SBD) mechanism that offers inter-operator fairness using a “soft-partition” approach. In particular, the operator subscribers are permitted to overuse the resources specified in the predefined service-level-agreement when the shared RAN is under-utilized, but are blocked (or even dropped) when the RAN is over-utilized. The simulation results show that SBD achieves an inter-operator fairness of 0.997, which is higher than that of both a hard-partition approach (0.98) and a no-partition approach (0.6) while maintaining a shared RAN utilization rate of 98%. Furthermore, SBD reduces the blocking rate from 35% (hard partition approach) to almost 0%, whereas controlling the dropping rate at 5%. Notably, the dropping rate can be reduced to almost 0% using a newly proposed bandwidth scale down procedure.This work was supported in part by H2020 collaborative Europe/Taiwan research project 5G-CORAL under Grant 761586, and in part by the Ministry of Science and Technology, Taiwan under Contract MOST 106-2218- E-009-018

Three-Tier Capacity and Traffic Allocation for Core, Edges, and Devices for Mobile Edge Computing

In order to satisfy the 5G requirements of ultra-low latency, mobile edge computing (MEC)-based architecture, composed of three-tier nodes, core, edges, and devices, is proposed. In MEC-based architecture, previous studies focused on the controlplane issue, i.e., how to allocate traffic to be processed at different nodes to meet this ultra-low latency requirement. Also important is how to allocate the capacity to different nodes in the management plane so as to establish a minimal-capacity network. The objectives of this paper is to solve two problems: 1) to allocate the capacity of all nodes in MEC-based architecture so as to provide a minimal-capacity network and 2) to allocate the traffic to satisfy the latency percentage constraint, i.e., at least a percentage of traffic satisfying the latency constraint. In order to achieve these objectives, a two-phase iterative optimization (TPIO) method is proposed to try to optimize capacity and traffic allocation in MEC-based architecture. TPIO iteratively uses two phases to adjust capacity and traffic allocation respectively because they are tightly coupled. In the first phase, using queuing theory calculates the optimal traffic allocation under fixed allocated capacity, while in the second phase, allocated capacity is further reduced under fixed traffic allocation to satisfy the latency percentage constraint. Simulation results show that MEC-based architecture can save about 20.7% of capacity of two-tier architecture. Further, an extra 12.2% capacity must be forfeited when the percentage of satisfying latency is 90%, compared to 50%.This work was supported in part by H2020 collaborative Europe/Taiwan research project 5G-CORAL (grant number 761586), and Ministry of Science and Technology, Taiwan for financially supporting this research under Contract No. MOST 106-2218-E-009-018

A novel regulatory event-based gene set analysis method for exploring global functional changes in heterogeneous genomic data sets

<p>Abstract</p> <p>Background</p> <p>Analyzing gene expression data by assessing the significance of pre-defined gene sets, rather than individual genes, has become a main approach in microarray data analysis and this has promisingly derive new biological interpretations of microarray data. However, the detection power of conventional gene list or gene set-based approaches is limited on highly heterogeneous samples, such as tumors.</p> <p>Results</p> <p>We developed a novel method, the regulatory <b>e</b>vent-based <b>G</b>ene <b>S</b>et <b>A</b>nalysis (eGSA), which considers not only the consistently changed genes but also every gene regulation (event) of each sample to overcome the detection limit. In comparison with conventional methods, eGSA can detect functional changes in heterogeneous samples more precisely and robustly. Furthermore, by utilizing eGSA, we successfully revealed novel functional characteristics and potential mechanisms of very early hepatocellular carcinoma (HCC).</p> <p>Conclusion</p> <p>Our study creates a novel scheme to directly target the major cellular functional changes in heterogeneous samples. All potential regulatory routines of a functional change can be further analyzed by the regulatory event frequency. We also provide a case study on early HCCs and reveal a novel insight at the initial stage of hepatocarcinogenesis. eGSA therefore accelerates and refines the interpretation of heterogeneous genomic data sets in the absence of gene-phenotype correlations.</p

The Prescription Pattern of Chinese Herbal Products Containing Ginseng

Background. The purpose of our study is to analyze the association between prescribed Chinese herbal products (CHPs) containing Ginseng and the risk of endometrial cancer among tamoxifen (TMX) users and to identify any possible interactive effects between Ginseng and TMX with respect to preventing the development of subsequent endometrial cancer in an estrogen-dependent breast cancer population in Taiwan. Methods. All patients newly diagnosed with invasive breast cancer receiving tamoxifen treatment from January 1, 1998, to December 31, 2008, were selected from the National Health Insurance Research Database. The usage, frequency of service, and CHP-Ginseng prescribed across the 30,556 TMX-treated breast cancer (BC) survivors were evaluated. Logistic regression was employed to estimate the odds ratios (ORs) for the utilization of CHP-Ginseng. Cox’s proportional hazard regression was performed to calculate the hazard ratios (HRs) for endometrial cancer associated with Ginseng use among the TMX-treated BC cohort. Results. The HR for the development of endometrial cancer among breast cancer survivors who had ever taken Ginseng after TXM treatment was significantly decreased compared to those who never used CHP. Conclusion. A significant inhibitory relationship between Ginseng consumption and subsequent endometrial cancer less than 2 years after TMX treatment was detected among BC survivors