Comparison and analysis of current-mode logic circuits with differential and static CMOS

This thesis describes the analysis and comparison of Folded Source-Coupled Logic (FSCL) with standard static CMOS, cascode voltage-switch logic and differential split-level logic gates. The advantages of FSCL are low switching noise and high operating speed. The effect of voltage and device scaling on these topologies is evaluated in terms of average delay, power dissipation at maximum frequency, power-delay-product and current spike noise. Several two-summand adders are designed and simulated using MOSIS 1-μm CMOS process parameters and evaluations are performed in terms of area, delay, noise and power dissipation

SGBS cells as a model of human adipocyte browning: A comprehensive comparative study with primary human white subcutaneous adipocytes.

The Simpson Golabi Behmel Syndrome (SGBS) pre-adipocyte cell strain is widely considered to be a representative in vitro model of human white pre-adipocytes. A recent study suggested that SGBS adipocytes exhibit an unexpected transient brown phenotype. Here, we comprehensively examined key differences between SGBS adipocytes and primary human white subcutaneous (PHWSC) adipocytes. RNA-Seq analysis revealed that extracellular matrix (ECM)-receptor interaction and metabolic pathways were the top two KEGG pathways significantly enriched in SGBS adipocytes, which included positively enriched mitochondrial respiration and oxidation pathways. Compared to PHWSC adipocytes, SGBS adipocytes showed not only greater induction of adipogenic gene expression during differentiation but also increased levels of UCP1 mRNA and protein expression. Functionally, SGBS adipocytes displayed higher ISO-induced basal leak respiration and overall oxygen consumption rate, along with increased triglyceride accumulation and insulin-stimulated glucose uptake. In conclusion, we confirmed that SGBS adipocytes, which are considered of white adipose tissue origin can shift towards a brown/beige adipocyte phenotype. These differences indicate SGBS cells may help to identify mechanisms leading to browning, and inform our understanding for the use of SGBS vis-à-vis primary human subcutaneous adipocytes as a human white adipocyte model, guiding the selection of appropriate cell models in future metabolic research

Identification of methylation changes associated with positive and negative growth deviance in Gambian infants using a targeted methyl sequencing approach of genomic DNA.

Low birthweight and reduced height gain during infancy (stunting) may arise at least in part from adverse early life environments that trigger epigenetic reprogramming that may favor survival. We examined differential DNA methylation patterns using targeted methyl sequencing of regions regulating gene activity in groups of rural Gambian infants: (a) low and high birthweight (DNA from cord blood (n = 16 and n = 20, respectively), from placental trophoblast tissue (n = 21 and n = 20, respectively), and DNA from peripheral blood collected from infants at 12 months of age (n = 23 and n = 17, respectively)), and, (b) the top 10% showing rapid postnatal length gain (high, n = 20) and the bottom 10% showing slow postnatal length gain (low, n = 20) based on z score change between birth and 12 months of age (LAZ) (DNA from peripheral blood collected from infants at 12 months of age). Using BiSeq analysis to identify significant methylation marks, for birthweight, four differentially methylated regions (DMRs) were identified in trophoblast DNA, compared to 68 DMRs in cord blood DNA, and 54 DMRs in 12-month peripheral blood DNA. Twenty-five DMRs were observed to be associated with high and low length for age (LAZ) at 12 months. With the exception of five loci (associated with two different genes), there was no overlap between these groups of methylation marks. Of the 194 CpG methylation marks contained within DMRs, 106 were located to defined gene regulatory elements (promoters, CTCF-binding sites, transcription factor-binding sites, and enhancers), 58 to gene bodies (introns or exons), and 30 to intergenic DNA. Distinct methylation patterns associated with birthweight between comparison groups were observed in DNA collected at birth (at the end of intrauterine growth window) compared to those established by 12 months (near the infancy/childhood growth transition). The longitudinal differences in methylation patterns may arise from methylation adjustments, changes in cellular composition of blood or both that continue during the critical postnatal growth period, and in response to early nutritional and infectious environmental exposures with impacts on growth and longer-term health outcomes.The funding sources as follows: 1. The Bill and Melinda Gates Foundation (OPP1066932) 2. Core funding to the MRC Unit The Gambia at LSHTM (MC-A760-5QX00) by the UK MRC and the UK Department for the International Development (DFID) under the MRC/DFID Concordat agreemen

Reply to: ‘Browning capabilities of human primary adipose-derived stromal cells compared to SGBS cells’

10.1038/s41598-020-64706-wScientific Reports101963

Inclusion body myositis and dysphagia. Presentation, intervention and outcome at a swallowing clinic: assessment and management of dysphagia in IBM

Objective This study reviewed patients with inclusion body myositis who were referred for assessment of dysphagia at a tertiary swallow clinic. It describes symptoms at presentation, imaging and management strategies. Method A retrospective review of electronic patient records was performed between 2016 and 2020. Results Twenty-four patients were included, with a mean age of 72 years. Baseline modified Sydney Swallow Questionnaires identified problems with hard or dry food, food sticking, and repeated swallowing. Twenty-two patients had a Reflux Symptom Index score that could indicate significant reflux. Video swallow identified specific problems, including tongue base retraction (96 per cent) and residual pharyngeal pooling (92 per cent). Seven patients (30 per cent) had features of aspiration on imaging despite a median penetration-aspiration scale score of 2. Four patients received balloon dilatation, and two patients underwent cricopharyngeal myotomy. Conclusion This study helped to profile features of dysphagia in patients with inclusion body myositis. More evidence is needed to determine the most effective management pathway for these patients