Design of an ASIC Digital Clock Using VLSI Technology

We present the design of an Application Specific Integrated Circuit (ASIC) digital clock based on the 0.12 µm deep submicron technology node. The widths of the PMOS and NMOS transistors are 0.72 µm and 0.24 µm, respectively. The clock expresses time based on the 12-hour time notation. The gate-level schematic and the layout of the design are drawn and validated using DSCH3 and Microwind3 Lite. The key feature of the clock is constructed from 18 D-type flip-flops. Two modulo-60 counters and a modulo-12 counter are built from the flip-flops. The modulo-60 counters are used for the second and minute modules, while the modulo-12 flip-flop is for the hour module. The length and width of the layout are, respectively, 153.60 µm and 58.14 µm. This is to say that the size of the die is comparable with that of a human hair. The average static power dissipation is found to be 0.202 mW, which is reasonably low. Since the proposed design is in the form of an ASIC chip, the input and output pins merely require to be connected to an external power source, an oscillator, and displays, to allow the clock to operate properly. With its miniaturized size and low power consumption, the proposed design clearly exhibits advantages over those built using discrete components and general-purpose chips

Integrated Circuit Packaging Recognition with Tilt Auto Adjustment using Deep Learning Approach

A deep-learning-based approach for recognizing integrated circuit (IC) packaging type is presented in this paper. The objective of this work is to design a deep-learning method that can recognize multiple types of packaging per detection, performing counting operations, and calculating the centre location of an IC with its tilting angle. The transfer learning from model You-Only-Look-Once (YOLO) v5 was chosen because it has been trained with the coco dataset and has a more reliable feature extraction system than the other models. In order to extract data from images, OpenCV was used, which allows the deep learning model to perform more efficient analysis of the input data. Apart from that, the principal component analysis (PCA) was used to estimate the angle of the IC in order to determine the rotation of each IC for the purpose of tilting adjustment. The developed model has an average confidence score of 85% and is capable of operating in a variety of conditions, as demonstrated by ANOVA analysis

Mitochondrial Phenotypes in Purified Human Immune Cell Subtypes and Cell Mixtures

Using a high-throughput mitochondrial phenotyping platform to quantify multiple mitochondrial features among molecularly defined immune cell subtypes, we quantify the natural variation in mitochondrial DNA copy number (mtDNAcn), citrate synthase, and respiratory chain enzymatic activities in human neutrophils, monocytes, B cells, and naïve and memory T lymphocyte subtypes. In mixed peripheral blood mononuclear cells (PBMCs) from the same individuals, we show to what extent mitochondrial measures are confounded by both cell type distributions and contaminating platelets. Cell subtype-specific measures among women and men spanning four decades of life indicate potential age- and sex-related differences, including an age-related elevation in mtDNAcn, which are masked or blunted in mixed PBMCs. Finally, a proof-of-concept, repeated-measures study in a single individual validates cell type differences and also reveals week-to-week changes in mitochondrial activities. Larger studies are required to validate and mechanistically extend these findings. These mitochondrial phenotyping data build upon established immunometabolic differences among leukocyte subpopulations, and provide foundational quantitative knowledge to develop interpretable blood-based assays of mitochondrial health

Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites

Tissue-resident memory T cells (TRMs) in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRMs remain unclear. Here, we use a unique human tissue resource to determine whether human tissue memory T cells constitute a distinct subset in diverse mucosal and lymphoid tissues. We identify a core transcriptional profile within the CD69+ subset of memory CD4+ and CD8+ T cells in lung and spleen that is distinct from that of CD69− TEM cells in tissues and circulation and defines human TRMs based on homology to the transcriptional profile of mouse CD8+ TRMs. Human TRMs in diverse sites exhibit increased expression of adhesion and inhibitory molecules, produce both pro-inflammatory and regulatory cytokines, and have reduced turnover compared with circulating TEM, suggesting unique adaptations for in situ immunity. Together, our results provide a unifying signature for human TRM and a blueprint for designing tissue-targeted immunotherapies

AluScan: a method for genome-wide scanning of sequence and structure variations in the human genome

<p>Abstract</p> <p>Background</p> <p>To complement next-generation sequencing technologies, there is a pressing need for efficient pre-sequencing capture methods with reduced costs and DNA requirement. The Alu family of short interspersed nucleotide elements is the most abundant type of transposable elements in the human genome and a recognized source of genome instability. With over one million Alu elements distributed throughout the genome, they are well positioned to facilitate genome-wide sequence amplification and capture of regions likely to harbor genetic variation hotspots of biological relevance.</p> <p>Results</p> <p>Here we report on the use of inter-Alu PCR with an enhanced range of amplicons in conjunction with next-generation sequencing to generate an Alu-anchored scan, or 'AluScan', of DNA sequences between Alu transposons, where Alu consensus sequence-based 'H-type' PCR primers that elongate outward from the head of an Alu element are combined with 'T-type' primers elongating from the poly-A containing tail to achieve huge amplicon range. To illustrate the method, glioma DNA was compared with white blood cell control DNA of the same patient by means of AluScan. The over 10 Mb sequences obtained, derived from more than 8,000 genes spread over all the chromosomes, revealed a highly reproducible capture of genomic sequences enriched in genic sequences and cancer candidate gene regions. Requiring only sub-micrograms of sample DNA, the power of AluScan as a discovery tool for genetic variations was demonstrated by the identification of 357 instances of loss of heterozygosity, 341 somatic indels, 274 somatic SNVs, and seven potential somatic SNV hotspots between control and glioma DNA.</p> <p>Conclusions</p> <p>AluScan, implemented with just a small number of H-type and T-type inter-Alu PCR primers, provides an effective capture of a diversity of genome-wide sequences for analysis. The method, by enabling an examination of gene-enriched regions containing exons, introns, and intergenic sequences with modest capture and sequencing costs, computation workload and DNA sample requirement is particularly well suited for accelerating the discovery of somatic mutations, as well as analysis of disease-predisposing germline polymorphisms, by making possible the comparative genome-wide scanning of DNA sequences from large human cohorts.</p

Disparities of time trends and birth cohort effects on invasive breast cancer incidence in Shanghai and Hong Kong pre- and post-menopausal women

© 2017 The Author(s). Background: Breast cancer is the leading cause of cancer morbidity among Shanghai and Hong Kong women, which contributes to 20-25% of new female cancer incidents. This study aimed to describe the temporal trend of breast cancer and interpret the potential effects on the observed secular trends. Methods: Cancer incident data were obtained from the cancer registries. Age-standardized incidence rate was computed by the direct method using the World population of 2000. Average annual percentage change (AAPC) in incidence rate was estimated by the Joinpoint regression. Age, period and cohort effects were assessed by using a log-linear model with Poisson regression. Results: During 1976-2009, an increasing trend of breast cancer incidence was observed, with an AAPC of 1.73 [95% confidence interval (CI): 1.54-1.92)] for women in Hong Kong and 2.83 (95% CI, 2.26-3.40) in Shanghai. Greater upward trends were revealed in Shanghai women aged 50 years old or above (AAPC = 3.09; 95% CI, 1.48-4.73). Using age at 50 years old as cut-point, strong birth cohort effects were shown in both pre- and post-menopausal women, though a more remarkable effect was suggested in Shanghai post-menopausal women. No evidence for a period effect was indicated. Conclusions: Incidence rate of breast cancer has been more speedy in Shanghai post-menopausal women than that of the Hong Kong women over the past 30 years. Decreased birth rate and increasing environmental exposures (e.g., light-at-night) over successive generations may have constituted major impacts on the birth cohort effects, especially for the post-menopausal breast cancer; further analytic studies are warranted.Link_to_subscribed_fulltex

Bone Marrow Myeloid Cells Regulate Myeloid-Biased Hematopoietic Stem Cells via a Histamine-Dependent Feedback Loop

Myeloid-biased hematopoietic stem cells (MB-HSCs) play critical roles in recovery from injury, but little is known about how they are regulated within the bone marrow niche. Here we describe an auto-/paracrine physiologic circuit that controls quiescence of MB-HSCs and hematopoietic progenitors marked by histidine decarboxylase (Hdc). Committed Hdc+ myeloid cells lie in close anatomical proximity to MB-HSCs and produce histamine, which activates the H2 receptor on MB-HSCs to promote their quiescence and self-renewal. Depleting histamine-producing cells enforces cell cycle entry, induces loss of serial transplant capacity, and sensitizes animals to chemotherapeutic injury. Increasing demand for myeloid cells via lipopolysaccharide (LPS) treatment specifically recruits MB-HSCs and progenitors into the cell cycle; cycling MB-HSCs fail to revert into quiescence in the absence of histamine feedback, leading to their depletion, while an H2 agonist protects MB-HSCs from depletion after sepsis. Thus, histamine couples lineage-specific physiological demands to intrinsically primed MB-HSCs to enforce homeostasis. Chen et al. show that histidine decarboxylase (Hdc) marks quiescent myeloid-biased HSCs (MB-HSCs). Daughter myeloid cells form a spatial cluster with Hdc+ MB-HSCs and secrete histamine to enforce their quiescence and protect them from depletion, following activation by a variety of physiologic insults

Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese

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