Augmented Genetic Algorithm V2 with Reinforcement Learning for PDN Decap Optimization

Genetic Algorithms (GAs) Use Many Hyperparameters, and Tuning These Parameters Can Determine the Optimization Performance. a GA with an Augmented Initial Population Was Proposed for Decap Optimization but It Had Convergence Issues by Getting Stuck in the Local Minimum. This Work Uses a Reinforcement Learning (RL) Approach to Adaptively Tune the Hyperparameters of GA during its Operation. with This Approach, the Agent Tries to Change the Parameters So that the GA Does Not Get Stuck in the Local Minimum. the Proposed Method Combining the RL Agent and Augmented GA Showed Better Performance in Terms of Solution Quality and Time Cost. overall, in All the Cases Tested, the Proposed Method Showed Better Performance Than the Augmented GA Without RL

An Analysis on the Effectiveness of 2 and 3 Terminal Capacitors in PDN Design

The Parasitic Inductance of a Capacitor Depends on its Physical Structure. Due to the Geometry of 3-Terminal Capacitors, They Boast a Lower Parasitic Inductance Compared to 2-Terminal Capacitors of the Same and Possibly Smaller Package Sizes. While the Parasitic Inductance of a Single 3-Terminal Capacitor May Be Lower, using Multiple 2-Terminal Capacitors May Result in Similar Performance. in This Work, the Inductance of 2-Terminal (0201, Nominal 2.2 UF) and 3-Terminal (0402, Nominal 4.3 UF) Capacitors is Extracted and Compared through Measurements. from Our De-Embedding Method and Characterized Capacitors, the Inductance of 2-Terminal Capacitors is Only About 20 PH Higher Than the Characterized 3terminal Capacitor. on a Power Net of a Real Product, 3-Terminal Capacitors of the Same Type as Characterized Were Replaced with 2-Terminal Capacitors of the Same Type as Characterized. from Measurement Results, the Measured Inductance at 100 MHz is Lower by Only About 3.45 PH, or 2.62%, When using 3-Terminal Capacitors

Germline Met Mutations in Mice Reveal Mutation- and Background-Associated Differences in Tumor Profiles

BACKGROUND: The receptor tyrosine kinase Met is involved in the progression and metastasis of numerous human cancers. Although overexpression and autocrine activation of the Met signaling pathway are commonly found in human cancers, mutational activation of Met has been observed in small cell and non-small cell lung cancers, lung adenocarcinomas, renal carcinomas, and mesotheliomas. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the influence of mutationally activated Met in tumorigenesis, we utilized a novel mouse model. Previously, we observed that various Met mutations developed unique mutation-specific tumor spectra on a C57BL/6 background. Here, we assessed the effect of genetic background on the tumorigenic potential of mutationally activated Met. For this purpose, we created congenic knock-in lines of the Met mutations D1226N, M1248T, and Y1228C on the FVB/N background. Consistent with the mutation-specific tumor spectra, several of the mutations were associated with the same tumor types as observed on C57BL/6 background. However, on the FVB/N background most developed a high incidence of mammary carcinomas with diverse histopathologies. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that on two distinct mouse backgrounds, Met is able to initiate tumorigenesis in multiple cell types, including epithelial, hematopoietic, and endothelial. Furthermore, these observations emphasize that even a modest increase in Met activation can initiate tumorigenesis with both the Met mutational spectra and host background having profound influence on the type of tumor generated. Greater insight into the interaction of genetic modifiers and Met signaling will significantly enhance our ability to tailor combination therapies for Met-driven cancers

Mapping Trachoma in the Solomon Islands: Results of Three Baseline Population-Based Prevalence Surveys Conducted with the Global Trachoma Mapping Project.

PURPOSE: We sought to complete the baseline trachoma map of the Solomon Islands by establishing prevalences of active trachoma and trichiasis in the provinces of Choiseul, Western, Rennell-Bellona, and Temotu. METHODS: Using the standardized methodology developed for the Global Trachoma Mapping Project, we conducted cross-sectional community-based surveys from September to November 2013. Choiseul and Western provinces were each mapped as separate evaluation units (EUs); Rennell-Bellona and Temotu were combined to form a third EU. RESULTS: A total of 9819 individuals were sampled for inclusion, with 9224 (93.3%) consenting to examination, of whom 4587 (46.3%) were female. Survey teams visited 82 villages, and surveyed 2448 households. Two EUs had prevalences of trachomatous inflammation - follicular (TF) in 1-9-year-olds over the 10% threshold at which WHO recommends mass distribution of azithromycin for at least 3 years (Western 20.4%, 95% confidence interval, CI 15.6-26.3%; Rennell-Bellona/Temotu 22.0%, 95% CI 18.5-26.0%). Choiseul had a TF prevalence of 6.1% (95% CI 4.1-8.6%), and met the criterion for a single round of mass antibiotic distribution before re-survey. The adjusted prevalences of trichiasis in those aged 15+ years were 0.0% (95% CI 0.0-0.2%) in Choiseul, 0.16% (95% CI 0.0-0.5%) in Western, and 0.10% (95% CI 0-0.3%) in Rennell-Bellona/Temotu provinces. All three EUs require implementation of the facial cleanliness and environmental improvement components of the trachoma elimination strategy. CONCLUSION: Active trachoma is prevalent in the Solomon Islands. However, there is little evidence of the blinding complications of trachoma being a public health problem there. Further research into the explanation for this phenomenon is warranted

Evaluation of an epigenetic assay for predicting repeat prostate biopsy outcome in African American men

OBJECTIVE: To evaluate an epigenetic assay performed on tissue from negative prostate biopsies in a group of African American (AA) men undergoing repeat biopsy, and to compare accuracy for predicting repeat biopsy outcome to prior studies conducted in predominantly Caucasian populations. MATERIALS AND METHODS: The study population consisted of 211 AA men from 7 urology centers across the United States; all of whom were undergoing 12-core transrectal ultrasound-guided repeat biopsy within 30 months from a negative index biopsy. All biopsy cores from the negative index biopsy were profiled for the epigenetic biomarkers GSTP1, APC, and RASSF1 using ConfirmMDx for Prostate Cancer (MDxHealth, Irvine, CA). RESULTS: Upon repeat biopsy, 130 of 211 subjects (62%) had no prostate cancer (PCa) detected and 81 of 211 (38%) were diagnosed with PCa. Of the subjects with PCa, 54 (67%) were diagnosed with Gleason score (GS) = 7 disease. For detection of PCa at repeat biopsy, ConfirmMDx sensitivity was 74.1% and specificity was 60.0%, equivalent to prior studies (P = .235 and .697, respectively). For detection of GS >= 7 PCa, sensitivity was 78% and specificity was 53%. The negative predictive values for detection of all PCa and GS >= 7 PCa were 78.8% and 94.2%, respectively. CONCLUSION: In this group of AA men, we successfully validated an epigenetic assay to assess the need for repeat biopsy. Results were consistent with previous studies from predominantly Caucasian populations. Therefore, the ConfirmMDx assay is a useful tool for risk stratification of AA men who had an initial negative biopsy

Active Trachoma Cases in the Solomon Islands Have Varied Polymicrobial Community Structures but Do Not Associate with Individual Non-Chlamydial Pathogens of the Eye.

BACKGROUND: Several non-chlamydial microbial pathogens are associated with clinical signs of active trachoma in trachoma-endemic communities with a low prevalence of ocular Chlamydia trachomatis (Ct) infection. In the Solomon Islands, the prevalence of Ct among children is low despite the prevalence of active trachoma being moderate. Therefore, we set out to investigate whether active trachoma was associated with a common non-chlamydial infection or with a dominant polymicrobial community dysbiosis in the Solomon Islands. METHODS: We studied DNA from conjunctival swabs collected from 257 Solomon Islanders with active trachoma and matched controls. Droplet digital PCR was used to test for pathogens suspected to be able to induce follicular conjunctivitis. Polymicrobial community diversity and composition were studied by sequencing of hypervariable regions of the 16S ribosomal ribonucleic acid gene in a subset of 54 cases and 53 controls. RESULTS: Although Ct was associated with active trachoma, the number of infections was low (cases, 3.9%; controls, 0.4%). Estimated prevalence (cases and controls, respectively) of each non-chlamydial infection was as follows: Staphylococcus aureus: 1.9 and 1.9%, Adenoviridae: 1.2 and 1.2%, coagulase-negative Staphylococcus: 5.8 and 4.3%, Haemophilus influenzae: 7.4 and 11.7%, Moraxella catarrhalis: 2.3 and 4.7%, and Streptococcus pneumoniae: 7.0 and 6.2%. There was no statistically significant association between the clinical signs of trachoma and the presence or load of any of the non-Ct infections that were assayed. Interindividual variations in the conjunctival microbiome were characterized by differences in the levels of Corynebacterium, Propionibacterium, Helicobacter, and Paracoccus, but diversity and relative abundance of these specific genera did not differ significantly between cases and controls. DISCUSSION: It is unlikely that the prevalent trachoma-like follicular conjunctivitis in this region of the Solomon Islands has a dominant bacterial etiology. Before implementing community-wide azithromycin distribution for trachoma, policy makers should consider that clinical signs of trachoma can be observed in the absence of any detectable azithromycin-susceptible organism

eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5′UTR

BackgroundRegulation of the mRNA life cycle is central to gene expression control and determination of cell fate. miRNAs represent a critical mRNA regulatory mechanism, but despite decades of research, their mode of action is still not fully understood.ResultsHere, we show that eIF4A2 is a major effector of the repressive miRNA pathway functioning via the Ccr4-Not complex. We demonstrate that while DDX6 interacts with Ccr4-Not, its effects in the mechanism are not as pronounced. Through its interaction with the Ccr4-Not complex, eIF4A2 represses mRNAs at translation initiation. We show evidence that native eIF4A2 has similar RNA selectivity to chemically inhibited eIF4A1. eIF4A2 exerts its repressive effect by binding purine-rich motifs which are enriched in the 5′UTR of target mRNAs directly upstream of the AUG start codon.ConclusionsOur data support a model whereby purine motifs towards the 3′ end of the 5′UTR are associated with increased ribosome occupancy and possible uORF activation upon eIF4A2 binding.</p

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy