Many breakthroughs in the laboratories often do not bridge the gap between research and commercialization. However, silicon photonics bucked the trend, with industry observers estimating the ...commercial market to close in on a billion dollars in 2020 <xref ref-type="bibr" rid="ref45">45 . Silicon photonics leverages the billions of dollars and decades of research poured into silicon semiconductor device processing to enable high yield, robust processing, and most of all, low cost. Silicon is also a good optical material, with transparency in the commercially important infrared wavelength bands, and is a suitable platform for large-scale photonic integrated circuits. Silicon photonics is therefore slated to address the world's ever-increasing needs for bandwidth. It is part of an emerging ecosystem which includes designers, foundries, and integrators. In this paper, we review most of the foundries that presently enable silicon photonics integrated circuits fabrication. Some of these are pilot lines of major research institutes, and others are fully commercial pure-play foundries. Since silicon photonics has been commercially active for some years, foundries have released process design kits (PDK) that contain a standard device library. These libraries represent optimized and well-tested photonic elements, whose performance reflects the stability and maturity of the integration platforms. We will document the early works in silicon photonics, as well as its commercial status. We will provide a comprehensive review of the development of silicon photonics and the foundry services which enable the productization, including various efforts to develop and release PDK devices. In this context, we will report the long-standing efforts and contributions that previously IME/A * STAR and now AMF has dedicated to accelerating this journey.
The causative virus of the COVID-19 pandemic, SARS-CoV-2, uses its nonstructural protein 1 (Nsp1) to suppress cellular, but not viral, protein synthesis through yet unknown mechanisms. We show here ...that among all viral proteins, Nsp1 has the largest impact on host viability in the cells of human lung origin. Differential expression analysis of mRNA-seq data revealed that Nsp1 broadly alters the cellular transcriptome. Our cryo-EM structure of the Nsp1-40S ribosome complex shows that Nsp1 inhibits translation by plugging the mRNA entry channel of the 40S. We also determined the structure of the 48S preinitiation complex formed by Nsp1, 40S, and the cricket paralysis virus internal ribosome entry site (IRES) RNA, which shows that it is nonfunctional because of the incorrect position of the mRNA 3′ region. Our results elucidate the mechanism of host translation inhibition by SARS-CoV-2 and advance understanding of the impacts from a major pathogenicity factor of SARS-CoV-2.
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•ORF screen identified Nsp1 as a major cellular pathogenicity factor of SARS-CoV-2•Nsp1 broadly alters the gene expression programs in human cells of lung origin•Nsp1 inhibits translation by blocking mRNA entry channel on the 40S ribosome•Nsp1 prevents physiological conformation of the 48S preinitiation complex (PIC)
Yuan et al. used functional and cryo-EM studies to show that SARS-CoV-2 Nsp1 significantly reduces cell viability, induces extensive transcriptome alteration, and blocks host mRNA access to the ribosome. These results help understand how Nsp1 suppresses host gene expression and its broad impact as a comorbidity-inducing factor.
Complex-valued neural networks have many advantages over their real-valued counterparts. Conventional digital electronic computing platforms are incapable of executing truly complex-valued ...representations and operations. In contrast, optical computing platforms that encode information in both phase and magnitude can execute complex arithmetic by optical interference, offering significantly enhanced computational speed and energy efficiency. However, to date, most demonstrations of optical neural networks still only utilize conventional real-valued frameworks that are designed for digital computers, forfeiting many of the advantages of optical computing such as efficient complex-valued operations. In this article, we highlight an optical neural chip (ONC) that implements truly complex-valued neural networks. We benchmark the performance of our complex-valued ONC in four settings: simple Boolean tasks, species classification of an Iris dataset, classifying nonlinear datasets (Circle and Spiral), and handwriting recognition. Strong learning capabilities (i.e., high accuracy, fast convergence and the capability to construct nonlinear decision boundaries) are achieved by our complex-valued ONC compared to its real-valued counterpart.
Air pollution is a major environmental concern during all seasons in the megacity of Beijing, China. Here we present the results from a winter study that was conducted from 21 November 2011 to 20 ...January 2012 with an Aerodyne Aerosol Chemical Speciation Monitor (ACSM) and various collocated instruments. The non-refractory submicron aerosol (NR-PM1) species vary dramatically with clean periods and pollution episodes alternating frequently. Compared to summer, wintertime submicron aerosols show much enhanced organics and chloride, which on average account for 52% and 5%, respectively, of the total NR-PM1 mass. All NR-PM1 species show quite different diurnal behaviors between summer and winter. For example, the wintertime nitrate presents a gradual increase during daytime and correlates well with secondary organic aerosol (OA), indicating a dominant role of photochemical production over gas–particle partitioning. Positive matrix factorization was performed on ACSM OA mass spectra, and identified three primary OA (POA) factors, i.e., hydrocarbon-like OA (HOA), cooking OA (COA), and coal combustion OA (CCOA), and one secondary factor, i.e., oxygenated OA (OOA). The POA dominates OA during wintertime, contributing 69%, with the other 31% being SOA. Further, all POA components show pronounced diurnal cycles with the highest concentrations occurring at nighttime. CCOA is the largest primary source during the heating season, on average accounting for 33% of OA and 17% of NR-PM1. CCOA also plays a significant role in chemically resolved particulate matter (PM) pollution as its mass contribution increases linearly as a function of NR-PM1 mass loadings. The SOA, however, presents a reverse trend, which might indicate the limited SOA formation during high PM pollution episodes in winter. The effects of meteorology on PM pollution and aerosol processing were also explored. In particular, the sulfate mass is largely enhanced during periods with high humidity because of fog processing of high concentration of precursor SO2. In addition, the increased traffic-related HOA emission at low temperature is also highlighted.
The E3 ubiquitin ligase adaptor speckle-type POZ protein (SPOP) is frequently dysregulated in prostate adenocarcinoma (PC), via either somatic mutations or mRNA downregulation, suggesting an ...important tumour suppressor function. To examine its physiologic role in the prostate epithelium in vivo, we generated mice with prostate-specific biallelic ablation of Spop. These mice exhibited increased prostate mass, prostate epithelial cell proliferation, and expression of c-MYC protein compared to littermate controls, and eventually developed prostatic intraepithelial neoplasia (PIN). We found that SPOP
can physically interact with c-MYC protein and, upon exogenous expression in vitro, can promote c-MYC ubiquitination and degradation. This effect was attenuated in PC cells by introducing PC-associated SPOP mutants or upon knockdown of SPOP via short-hairpin-RNA, suggesting that SPOP inactivation directly increases c-MYC protein levels. Gene Set Enrichment Analysis revealed enrichment of Myc-induced genes in transcriptomic signatures associated with SPOP
. Likewise, we observed strong inverse correlation between c-MYC activity and SPOP mRNA levels in two independent PC patient cohorts. The core SPOP
;MYC
transcriptomic response, defined by the overlap between the SPOP
and c-MYC transcriptomic programmes, was also associated with inferior clinical outcome in human PCs. Finally, the organoid-forming capacity of Spop-null murine prostate cells was more sensitive to c-MYC inhibition than that of Spop-WT cells, suggesting that c-MYC upregulation functionally contributes to the proliferative phenotype of Spop knock-out prostates. Taken together, our data highlight SPOP as an important regulator of luminal epithelial cell proliferation and c-MYC expression in prostate physiology, identify c-MYC as a novel bona fide SPOP substrate, and help explain the frequent inactivation of SPOP in human PC. We propose SPOP
-induced stabilization of c-MYC protein as a novel mechanism that can increase total c-MYC levels in PC cells, in addition to amplification of c-MYC locus.
Human leukocyte antigen B (HLA‐B) is responsible for presenting peptides to immune cells and plays a critical role in normal immune recognition of pathogens. A variant allele, HLA‐B*57:01, is ...associated with increased risk of a hypersensitivity reaction to the anti‐HIV drug abacavir. In the absence of genetic prescreening, hypersensitivity affects ~6% of patients and can be life‐threatening with repeated dosing. We provide recommendations (updated periodically at http://www.pharmkgb.org) for the use of abacavir based on HLA‐B genotype.
Clinical Pharmacology & Therapeutics (2012); 91 4, 734–738. doi:10.1038/clpt.2011.355
The three-dimensional fluorescence spectrum has a significantly greater amount of information than the single-stage scanning fluorescence spectrum. At the same time, the parallel factor (PARAFAC) ...analysis and neural network method can help explore the fluorescence characteristics further, thus could be used to analyse multiple sets of three-dimensional matrix data. In this study, the PARAFAC analysis and the self-organizing mapping (SOM) neural network method are firstly introduced comprehensively. They are then adopted to extract information of the three-dimensional fluorescence spectrum data set for fluorescence characteristics analysis of dissolved organic matter (DOM) in Taihu Lake water. Forty water samples with DOM species were taken from different seasons with the fluorescence information obtained through three-dimensional fluorescence spectrum analysis, PARAFAC analysis and SOM analysis. The PARAFAC analysis results indicated that the main fluorescence components of dissolved organic matter in Taihu Lake water were aromatic proteins, fulvic acids, and dissolved microorganisms. The SOM analysis results showed that the fluorescence characteristics of the dissolved organics in Taihu Lake varied seasonally. Therefore, the combined method of three-dimensional fluorescence spectrum analysis, PARAFAC and SOM analysis can provide important information for characterization of the fluorescence properties of dissolved organic matter in surface water bodies.
To our knowledge, no comprehensive meta-analysis has examined the association between sarcopenia and the risk of fractures. This systematic review and meta-analysis of prospective cohort studies aims ...to summarize whether sarcopenia is a risk factor for fractures among community-dwelling older adults. We searched four electronic literature databases (Ovid MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PubMed) for relevant publications from inception to December 2017, using relevant keywords. We conducted a pooled analysis of the association between sarcopenia and the risk of fractures by employing a random-effects model. Subgroup analyses were conducted based on definitions of sarcopenia and gender. In total, nine studies were included in our systematic review and meta-analysis. The prevalence of sarcopenia ranged from 4.3 to 33.1%. The pooled RR of fractures for the sarcopenic versus the nonsarcopenic was 1.34 (95% CI = 1.13–1.58,
P
= 0.001,
I
2
= 5.5%,
P
-heterogeneity = 0.391). Subgroup analyses showed that associations between sarcopenia and fractures were significant when using the AWGS definition (combined effect size = 1.78, 95% CI = 1.25–2.54,
P
= 0.001), and studies in males (combined effect size = 1.39, 95% CI = 1.13–1.71,
P
= 0.002). In conclusion, we found that compared to nonsarcopenic, the association between sarcopenia and fractures among community-dwelling older people was significant when using the AWGS definition, and only for males. Future studies are needed to establish a possible association between sarcopenia definitions and risk of fractures of different sites.
Objective
To understand the prevalence of sarcopenia in the Chengdu community, analyze the risk factors of sarcopenia, and provide a theoretical basis for further development of strategies for ...sarcopenia prevention and treatment.
Methods
A total of 938 individuals aged 60 years and above were recruited from the community of Chengdu. Skeletal muscle mass was measured by the bioelectrical impedance analysis (BIA), and sarcopenia was diagnosed according to the Asian Sarcopenia Working Group (AWGS) 2019 diagnostic criteria. A scale was generated to determine the age, living habits, and chronic diseases of enrolled subjects. The Mini Mental Examination Scale (MMSE) was used to assess their cognitive function, and the Geriatric Depression Scale (GDS-15) was used to identify depression.
Results
Among the 938 residents enrolled in the study, 172 (18.34%) had sarcopenia, including 48 (5.12%) with severe sarcopenia. The prevalence of sarcopenia in males was 19.91% and 16.81% in females. According to the binary logistic regression, older age (OR = 1.104, 95%CI: 1.059–1.151) and impaired cognitive function (OR = 2.251, 95%CI: 1.145–4.424) were independent risk factors for sarcopenia in females. Among the males, older age (OR = 1.079, 95%CI: 1.037–1.124) was the independent risk factor for sarcopenia. A moderate increase in BMI reduced the prevalence of sarcopenia in both females and males. Multi-category logistic regression analysis documented that females of older age were more likely to develop severe sarcopenia (χ
2
= 16.769, P < 0.01 vs. no sarcopenia), females with lower BMI were more likely to develop severe sarcopenia (χ
2
= 13.654, P < 0.01 vs. no sarcopenia), females with heart disease were more likely to develop severe sarcopenia (χ
2
= 5.786, P = 0.016 vs. no sarcopenia; χ
2
= 5.791, P = 0.016 vs. non-severe sarcopenia), and females with impaired cognitive function were more likely to develop severe sarcopenia (χ
2
= 13.381, P < 0.01 vs. no sarcopenia; χ
2
= 7.529, P = 0.006 vs. non-severe sarcopenia). Males were more likely to develop severe sarcopenia with older age (χ
2
= 18.435, P < 0.01 vs. no sarcopenia; χ
2
= 9.8011, P=0.002 vs. non-severe sarcopenia), lower BMI (χ
2
= 12.736, P < 0.01 vs. no sarcopenia), smoking (χ
2
= 4.68, P = 0.031 vs. no sarcopenia; χ
2
= 5.652, P = 0.017 vs. non-severe sarcopenia), and chronic obstructive pulmonary disease (COPD) (χ
2
= 5.517, P = 0.019 vs. no sarcopenia).
Conclusion
In the Chengdu community, the prevalence of sarcopenia among individuals 60 years of age or older was higher in males than in females. In elderly females, older age and impaired cognitive function were independent risk factors for sarcopenia. Women with more advanced age, decreased BMI, heart disease, and impaired cognitive function were more likely to develop severe sarcopenia. In elderly males, increased age was an independent risk factor for sarcopenia, and older age, decreased BMI, smoking, and COPD increased the probability of developing severe sarcopenia.
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