PLXNA4 is associated with Alzheimer disease and modulates tau phosphorylation

OBJECTIVE: Much of the genetic basis for Alzheimer disease (AD) is unexplained. We sought to identify novel AD loci using a unique family-based approach that can detect robust associations with infrequent variants (minor allele frequency < 0.10). METHODS: We conducted a genome-wide association study in the Framingham Heart Study (discovery) and NIA-LOAD (National Institute on Aging-Late-Onset Alzheimer Disease) Study (replication) family-based cohorts using an approach that accounts for family structure and calculates a risk score for AD as the outcome. Links between the most promising gene candidate and AD pathogenesis were explored in silico as well as experimentally in cell-based models and in human brain. RESULTS: Genome-wide significant association was identified with a PLXNA4 single nucleotide polymorphism (rs277470) located in a region encoding the semaphorin-3A (SEMA3A) binding domain (meta-analysis p value [meta-P] = 4.1 × 10(-8) ). A test for association with the entire region was also significant (meta-P = 3.2 × 10(-4) ). Transfection of SH-SY5Y cells or primary rat neurons with full-length PLXNA4 (TS1) increased tau phosphorylation with stimulated by SEMA3A. The opposite effect was observed when cells were transfected with shorter isoforms (TS2 and TS3). However, transfection of any isoform into HEK293 cells stably expressing amyloid β (Aβ) precursor protein (APP) did not result in differential effects on APP processing or Aβ production. Late stage AD cases (n = 9) compared to controls (n = 5) had 1.9-fold increased expression of TS1 in cortical brain tissue (p = 1.6 × 10(-4) ). Expression of TS1 was significantly correlated with the Clinical Dementia Rating score (ρ = 0.75, p = 2.2 × 10(-4) ), plaque density (ρ = 0.56, p = 0.01), and Braak stage (ρ = 0.54, p = 0.02). INTERPRETATION: Our results indicate that PLXNA4 has a role in AD pathogenesis through isoform-specific effects on tau phosphorylation

Do Delays in Banks’ Loan Loss Provisioning Affect Economic Downturns? Evidence from the U.S. Housing Market

I study whether banks’ loan loss provisioning contributed to economic downturns by examining the U.S. housing market. Specifically, I examine the influence of delayed loan loss recognition (DLR) on bank lending and risk-taking in the U.S. mortgage market and the aggregate effects of DLR on house prices and household consumption during the Great Recession. I first examine the effects of DLR on individual banks’ behavior. Then I construct ZIP code-level exposure to banks’ DLR to examine the aggregate effects of banks’ DLR on the housing market. I find high DLR banks reduced mortgage supply, leading high exposure ZIP codes to experience larger decreases in mortgage supply during the crisis. Mortgages from high DLR banks were also more likely to become distressed, leading to more foreclosures and short sales in high exposure ZIP codes during the crisis. Consequently, banks’ DLR negatively affected house prices during the crisis, implying a significant decrease in household consumption. These findings suggest banks’ loan loss provisioning affected loan supply and risk-taking, exacerbating the economic downturn via the household channel

Techno-economic analysis (TEA) for CO2 reforming of methane in a membrane reactor for simultaneous CO2 utilization and ultra-pure H-2 production

Techno-economic analysis (TEA) for CO2 reforming of methane in a membrane reactor (MR) was conducted by using process simulation and economic analysis. Parametric studies for key operating conditions like a H-2 permeance, a H2O sweep gas flow rate, operating temperature, and a CO2/CH4 ratio were carried out for a conventional packed-bed reactor (PBR) and a MR using Aspen HYSYS (R), a commercial process simulator program and some critical design guidelines for a MR in terms of a H2O sweep gas flow rate and a CO2/CH4 ratio were obtained. Further economic analysis based on process simulation results showed about 42% reduction in a unit H-2 production cost in a MR (6.48 $kgH(2)(-1)) than a PBR (11.18$ kgH(2)(-1)) mostly due to the elimination of a pressure swing adsorption (PSA) system in a MR. In addition, sensitivity analysis (SA) revealed that reactant price and labor were the most influential economic factors to determine a unit H-2 production cost for both a PBR and a MR. Lastly, profitability analysis (PA) from cumulative cash flow diagram (CCFD) in Korea provided positive net present value (NPV) of $443,760-$240,980, discounted payback period (DPBP) of 3.03-3.18 y, and present value ratio (PVR) of 7.51-4.97 for discount rates from 2 to 10% showing economic feasibility of the use of a MR as simultaneous CO2 utilization and ultra-pure H-2 production

Deep Learning with Multimodal Integration for Predicting Recurrence in Patients with Non-Small Cell Lung Cancer

Due to high recurrence rates in patients with non-small cell lung cancer (NSCLC), medical professionals need extremely accurate diagnostic methods to prevent bleak prognoses. However, even the most commonly used diagnostic method, the TNM staging system, which describes the tumor-size, nodal-involvement, and presence of metastasis, is often inaccurate in predicting NSCLC recurrence. These limitations make it difficult for clinicians to tailor treatments to individual patients. Here, we propose a novel approach, which applies deep learning to an ensemble-based method that exploits patient-derived, multi-modal data. This will aid clinicians in successfully identifying patients at high risk of recurrence and improve treatment planning

Techno-economic analysis of a biological desulfurization process for a landfill gas (LFG) in Korea

We report techno-economic analysis of a biological desulfurization process to remove H2S and to produce sulfur from a landfill gas (2000 m3 h&amp;#8722;1) produced in Korea. With a process simulation model developed using Aspen Plus??, parametric assessment to determine the effect of various operating parameters such as a NaOH flow rate, a NaOH concentration, and a recycle ratio has been carried out. Based on results from process simulation, economic analysis was conducted to evaluate feasibility of this technology in Korea through a cash flow diagram, net present value (NPV), and discounted payback period (DPBP). It was demonstrated that DPBP of 6.9 years and NPV of 0.39 MM$ were obtained with a 10% discount rate

A Secure and Lightweight Approach for Routing Optimization in Mobile IPv6

Mobility support is an essential part of IPv6 because we have recently seen sharp increases in the number of mobile users. A security weakness in mobility support has a direct consequence on the security of users because it obscures the distinction between devices and users. Unfortunately, a malicious and unauthenticated message in mobility support may open a security hole for intruders by supplying an easy mean to launch an attack that hijacks an ongoing session to a location chosen by the intruder. In this paper, we show how to thwart such a session hijacking attack by authenticating a suspicious message. Although much research has been directed toward addressing similar problems, we contend that our proposed protocol would outperform other proposals that have been advanced. This claim is based on observations that the proposed protocol has strengths such as light computational load, backward compatibility, and dependable operation. The results of in-depth performance evaluation show that our protocol achieves strong security and at the same time requires minimal computational overhead