PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores.

The PAT family of lipid droplet proteins includes 5 members in mammals: perilipin, adipose differentiation-related protein (ADRP), tail-interacting protein of 47 kDa (TIP47), S3-12, and OXPAT. Members of this family are also present in evolutionarily distant organisms, including insects, slime molds and fungi. All PAT proteins share sequence similarity and the ability to bind intracellular lipid droplets, either constitutively or in response to metabolic stimuli, such as increased lipid flux into or out of lipid droplets. Positioned at the lipid droplet surface, PAT proteins manage access of other proteins (lipases) to the lipid esters within the lipid droplet core and can interact with cellular machinery important for lipid droplet biogenesis. Genetic variations in the gene for the best-characterized of the mammalian PAT proteins, perilipin, have been associated with metabolic phenotypes, including type 2 diabetes mellitus and obesity. In this review, we discuss how the PAT proteins regulate cellular lipid metabolism both in mammals and in model organisms

Effects of neighborhood disadvantage on problem gambling and alcohol abuse

Background and aims: Based on social disorganization theory, the present study examined the effects of neighborhood disadvantage on gambling behaviors and problems as well as on alcohol use and abuse. Methods: Findings were based on a combined sample of two representative U.S. telephone surveys of gambling and substance use. One survey (n = 2,631) included adults 18 years and older and the second survey (2,274) included young people aged 14–21 years old. Results: Neighborhood disadvantage had a highly significant effect on problem gambling over and above the significant individual effects of gender, age, race/ethnicity and socioeconomic status. Alcohol abuse did not show the same relationship to neighborhood disadvantage as did problem gambling. Furthermore, when neighborhood disadvantage was high and individual socioeconomic status was low, the highest levels of problem gambling were observed. Conclusions: This study provides strong evidence for the effects of neighborhood ecology on the occurrence of problem gambling

BED Estimates of HIV Incidence: Resolving the Differences, Making Things Simpler

Objective: Develop a simple method for optimal estimation of HIV incidence using the BED capture enzyme immunoassay. Design: Use existing BED data to estimate mean recency duration, false recency rates and HIV incidence with reference to a fixed time period, T. Methods: Compare BED and cohort estimates of incidence referring to identical time frames. Generalize this approach to suggest a method for estimating HIV incidence from any cross-sectional survey. Results: Follow-up and BED analyses of the same, initially HIV negative, cases followed over the same set time period T, produce estimates of the same HIV incidence, permitting the estimation of the BED mean recency period for cases who have been HIV positive for less than T. Follow-up of HIV positive cases over T, similarly, provides estimates of the false-recent rate appropriate for T. Knowledge of these two parameters for a given population allows the estimation of HIV incidence during T by applying the BED method to samples from cross-sectional surveys. An algorithm is derived for providing these estimates, adjusted for the false-recent rate. The resulting estimator is identical to one derived independently using a more formal mathematical analysis. Adjustments improve the accuracy of HIV incidence estimates. Negative incidence estimates result from the use of inappropriate estimates of the false-recent rate and/or from sampling error, not from any error in the adjustment procedure

Structural and kinetic profiling of allosteric modulation of duplex DNA induced by DNA-binding polyamide analogues

A combined structural and quantitative biophysical profile of the DNA binding affinity, kinetics and sequence-selectivity of hairpin polyamide analogues is described. DNA duplexes containing either target polyamide binding sites or mismatch sequences are immobilized on a microelectrode surface. Quantitation of the DNA binding profile of polyamides containing N-terminal 1-alkylimidazole (Im) units exhibit picomolar binding affinities for their target sequences, whereas 5-alkylthiazole (Nt) units are an order of magnitude lower (low nanomolar). Comparative NMR structural analyses of the polyamide series shows that the steric bulk distal to the DNA-binding face of the hairpin iPr-Nt polyamide plays an influential role in the allosteric modulation of the overall DNA duplex structure. This combined kinetic and structural study provides a foundation to develop next-generation hairpin designs where the DNA-binding profile of polyamides is reconciled with their physicochemical properties

Adaptive Storage Optimization Scheme for Blockchain-IIoT Applications Using Deep Reinforcement Learning

Blockchain-IIoT integration into industrial processes promises greater security, transparency, and traceability. However, this advancement faces significant storage and scalability issues with existing blockchain technologies. Each peer in the blockchain network maintains a full copy of the ledger which is updated through consensus. This full replication approach places a burden on the storage space of the peers and would quickly outstrip the storage capacity of resource-constrained IIoT devices. Various solutions utilizing compression, summarization or different storage schemes have been proposed in literature. The use of cloud resources for blockchain storage has been extensively studied in recent years. Nonetheless, block selection remains a substantial challenge associated with cloud resources and blockchain integration. This paper proposes a deep reinforcement learning (DRL) approach as an alternative to solving the block selection problem, which involves identifying the blocks to be transferred to the cloud. We propose a DRL approach to solve our problem by converting the multi-objective optimization of block selection into a Markov decision process (MDP). We design a simulated blockchain environment for training and testing our proposed DRL approach. We utilize two DRL algorithms, Advantage Actor-Critic (A2C), and Proximal Policy Optimization (PPO) to solve the block selection problem and analyze their performance gains. PPO and A2C achieve 47.8% and 42.9% storage reduction on the blockchain peer compared to the full replication approach of conventional blockchain systems. The slowest DRL algorithm, A2C, achieves a run-time 7.2 times shorter than the benchmark evolutionary algorithms used in earlier works, which validates the gains introduced by the DRL algorithms. The simulation results further show that our DRL algorithms provide an adaptive and dynamic solution to the time-sensitive blockchain-IIoT environment

Recommended practices for wind farm data collection and reliability assessment for O&M optimization

The paper provides a brief overview of the aims and main results of IEA Wind Task 33. IEA Wind Task 33 was an expert working group with a focus on data collection and reliability assessment for O & M optimization of wind turbines. The working group started in 2012 and finalized the work in 2016. The complete results of IEA Wind Task 33 are described in the expert group report on recommended practices for "Wind farm data collection and reliability assessment for O & M optimization" which will be published by IEA Wind in 2017. This paper briefly presents the background of the work, the recommended process to identify necessary data, and appropriate taxonomies structuring and harmonizing the collected entries. Finally, the paper summarizes the key findings and recommendations from the IEA Wind Task 33 work

Bidirectional lipid droplet velocities are controlled by differential binding strengths of HCV Core DII protein

Host cell lipid droplets (LD) are essential in the hepatitis C virus (HCV) life cycle and are targeted by the viral capsid core protein. Core-coated LDs accumulate in the perinuclear region and facilitate viral particle assembly, but it is unclear how mobility of these LDs is directed by core. Herein we used two-photon fluorescence, differential interference contrast imaging, and coherent anti-Stokes Raman scattering microscopies, to reveal novel core-mediated changes to LD dynamics. Expression of core protein’s lipid binding domain II (DII-core) induced slower LD speeds, but did not affect directionality of movement on microtubules. Modulating the LD binding strength of DII-core further impacted LD mobility, revealing the temporal effects of LD-bound DII-core. These results for DII-core coated LDs support a model for core-mediated LD localization that involves core slowing down the rate of movement of LDs until localization at the perinuclear region is accomplished where LD movement ceases. The guided localization of LDs by HCV core protein not only is essential to the viral life cycle but also poses an interesting target for the development of antiviral strategies against HCV

Sex-specific associations of comorbidome and pulmorbidome with mortality in chronic obstructive pulmonary disease : results from COSYCONET

In patients with COPD, it has not been comprehensively assessed whether the predictive value of comorbidities for mortality difers between men and women. We therefore aimed to examine sex diferences of COPD comorbidities in regard with prognosis by classifying comorbidities into a comorbidome related to extrapulmonary disorders and a pulmorbidome, referring to pulmonary disorders. The study population comprised 1044 women and 1531 men with the diagnosis of COPD from COSYCONET, among them 2175 of GOLD grades 1–4 and 400 at risk. Associations of comorbidities with mortality were studied using Cox regression analysis for men and women separately. During the follow-up (median 3.7 years) 59 women and 159 men died. In men, obesity, hypertension, coronary artery disease, liver cirrhosis, osteoporosis, kidney disease, anaemia and increased heart rate (HR) predict mortality, in women heart failure, hyperuricemia, mental disorders, kidney disease and increased HR (p< 0.05 each). Regarding the pulmorbidome, signifcant predictors in men were impairment in difusion capacity and hyperinfation, in women asthma and hyperinfation. Similar results were obtained when repeating the analyses in GOLD 1–4 patients only. Gender diferences should be considered in COPD risk assessment for a tailored approach towards the treatment of COPD