Precision Medicine for Frontotemporal Dementia

Frontotemporal dementia (FTD) is a common young-onset dementia presenting with heterogeneous and distinct syndromes. It is characterized by progressive deficits in behavior, language, and executive function. The disease may exhibit similar characteristics to many psychiatric disorders owing to its prominent behavioral features. The concept of precision medicine has recently emerged, and it involves neurodegenerative disease treatment that is personalized to match an individual's specific pattern of neuroimaging, neuropathology, and genetic variability. In this paper, the pathophysiology underlying FTD, which is characterized by the selective degeneration of the frontal and temporal cortices, is reviewed. We also discuss recent advancements in FTD research from the perspectives of clinical, imaging, molecular characterizations, and treatment. This review focuses on the approach of precision medicine to manage the clinical and biological complexities of FTD

Novel CMOS RFIC Layout Generation with Concurrent Device Placement and Fixed-Length Microstrip Routing

With advancing process technologies and booming IoT markets, millimeter-wave CMOS RFICs have been widely developed in re- cent years. Since the performance of CMOS RFICs is very sensi- tive to the precision of the layout, precise placement of devices and precisely matched microstrip lengths to given values have been a labor-intensive and time-consuming task, and thus become a major bottleneck for time to market. This paper introduces a progressive integer-linear-programming-based method to gener- ate high-quality RFIC layouts satisfying very stringent routing requirements of microstrip lines, including spacing/non-crossing rules, precise length, and bend number minimization, within a given layout area. The resulting RFIC layouts excel in both per- formance and area with much fewer bends compared with the simulation-tuning based manual layout, while the layout gener- ation time is significantly reduced from weeks to half an hour.Comment: ACM/IEEE Design Automation Conference (DAC), 201

Is deck B a disadvantageous deck in the Iowa Gambling Task?

BACKGROUND: The Iowa gambling task is a popular test for examining monetary decision behavior under uncertainty. According to Dunn et al. review article, the difficult-to-explain phenomenon of "prominent deck B" was revealed, namely that normal decision makers prefer bad final-outcome deck B to good final-outcome decks C or D. This phenomenon was demonstrated especially clearly by Wilder et al. and Toplak et al. The "prominent deck B" phenomenon is inconsistent with the basic assumption in the IGT; however, most IGT-related studies utilized the "summation" of bad decks A and B when presenting their data, thereby avoiding the problems associated with deck B. METHODS: To verify the "prominent deck B" phenomenon, this study launched a two-stage simple version IGT, namely, an AACC and BBDD version, which possesses a balanced gain-loss structure between advantageous and disadvantageous decks and facilitates monitoring of participant preferences after the first 100 trials. RESULTS: The experimental results suggested that the "prominent deck B" phenomenon exists in the IGT. Moreover, participants cannot suppress their preference for deck B under the uncertain condition, even during the second stage of the game. Although this result is incongruent with the basic assumption in IGT, an increasing number of studies are finding similar results. The results of the AACC and BBDD versions can be congruent with the decision literatures in terms of gain-loss frequency. CONCLUSION: Based on the experimental findings, participants can apply the "gain-stay, loss-shift" strategy to overcome situations involving uncertainty. This investigation found that the largest loss in the IGT did not inspire decision makers to avoid choosing bad deck B

Toward Optimal Resource Allocation of Virtualized Network Functions for Hierarchical Datacenters

Telecommunications service providers (TSPs) previously provided network functions to end users with dedicated hardware, but they are resorting to virtualized infrastructure for reducing costs and increasing flexibility in resource allocation. A representative case is the Central Office Re-architected as Datacenter (CORD) project from AT&T, which aims to deploy virtualized network functions (VNFs) to over 4000 central offices (COs) across the U.S. However, there is a wide spectrum of options for deploying VNFs over the COs, varying from highly distributed to highly centralized manners. The former benefits end users with short response time but has its inherent limitation on utilizing geographically dispersed resources, while the latter allows resources to be better utilized at a cost of longer response time. In this work, we model the TSP's virtualized infrastructure as hierarchical datacenters, namely hierarchical CORD, and provide a resource allocation solution to strike the optimal balance between the two extreme options. Our evaluations reveal that in general, the 3-tier architecture incurs the least cost in case of deploying VNFs under moderate or loose delay constraints. Furthermore, the margin of improvement on the resource allocation cost increases inversely with the overall system utilization rate. Our results also suggest that as heavy request load overwhelms the network infrastructure, the relevant VNFs shall be migrated to lower-tier edge datacenters or to some nearby datacenters with superior network capacity. The evaluations also demonstrate that the proposed model allows highly adaptive VNF deployment in the hierarchical architecture under various conditions.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 Grant MOST-106-2218-E-009-018 and Grant MOST-106-2221-E-194-021-MY3

The effect of network template from normal subjects in the detection of network impairment

This study aimed to provide a simple way to approach group differences by independent component analysis when researching functional connectivity changes of resting‑state network in brain disorders. We used baseline resting state functional magnetic resonance imaging from the Alzheimer's disease neuroimaging initiative dataset and performed independent component analysis based on different kinds of subject selection, by including two downloaded templates and single‑subject independent component analysis method. All conditions were used to calculate the functional connectivity of the default mode network, and to test group differences and evaluate correlation with cognitive measurements and hippocampal volume. The default mode network functional connectivity results most fitting clinical evaluations were from templates based on young healthy subjects and the worst results were from heterogeneous or more severe disease groups or single‑subject independent component analysis method. Using independent component analysis network maps derived from normal young subjects to extract all individual functional connectivities provides significant correlations with clinical evaluations

Asiatic acid, a triterpene, induces apoptosis and cell cycle arrest through activation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways in human breast cancer cells

ABSTRACT This study first investigates the anticancer effect of asiatic acid in two human breast cancer cell lines, MCF-7 and MDA-MB-231. Asiatic acid exhibited effective cell growth inhibition by inducing cancer cells to undergo S-G2/M phase arrest and apoptosis. Blockade of cell cycle was associated with increased p21/ WAF1 levels and reduced amounts of cyclinB1, cyclinA, Cdc2, and Cdc25C in a p53-independent manner. Asiatic acid also reduced Cdc2 function by increasing the association of p21/WAF1/Cdc2 complex and the level of inactivated phospho-Cdc2 and phospho-Cdc25C. Asiatic acid treatment triggered the mitochondrial apoptotic pathway indicated by changing Bax/Bcl-2 ratios, cytochrome c release, and caspase-9 activation, but it did not act on Fas/Fas ligand pathways and the activation of caspase-8. We also found that mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK1/2), and p38, but not c-Jun NH 2 -terminal kinase (JNK), are critical mediators in asiatic acid-induced cell growth inhibition. U0126 [1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene] or SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole], specific inhibitors of mitogen-activated protein kinase kinase and p38 kinase activities, significantly decreased or delayed apoptosis. Asiatic acid was likely to confine the breast cancer cells in the S-G2/M phase mainly through the p38 pathway, because both SB203580 and p38 small interfering RNA (siRNA) inhibition significantly attenuated the accumulation of inactive phospho-Cdc2 and phospho-Cdc25C proteins and the cell numbers of S-G2/M phase. Moreover, U0126 and ERK siRNA inhibition completely suppressed asiatic acid-induced Bcl-2 phosphorylation and Bax up-regulation, and caspase-9 activation. Together, these results imply a critical role for ERK1/2 and p38 but not JNK, p53, and Fas/Fas ligand in asiatic acid-induced S-G2/M arrest and apoptosis of human breast cancer cells