Expanding Thermal Plasma Deposition of a-Si:H Thin Films for Surface Passivation of c-Si Wafers,

We investigated the material properties of expanding thermal plasma deposited a-Si:H thin films, providing a record-low surface recombination velocity of 1.6 cm/s (at injection level of 1 1015 cm-3). a-Si:H thin films with different thicknesses have been deposited at a high deposition rate (1.2 nm/s) on both sides of low resistivity (1-5 Ohm cm), 260µm thick, n- and ptype c-Si FZ wafers. The material properties of a -Si:H films have been characterized by Fourier Transform Infrared diagnostic and Spectroscopic Ellipsometry. The surface passivation of the wafers has been determined by photoconductivity decay measurements of the effective carrier lifetime. The investigation points out that the growth of ETP a-Si:H films begins with the formation of a thin porous layer (<10 nm) with a refractive index of 3.9 (at 2 eV) and a microstructure parameter (R*) of 0.50. Despite the open network formation at the a-Si/c-Si interface, a 7 nm a-Si:H film achieves a recombination velocity as low as 12 cm/s (at 1·1015 cm-3 injection level on ntype wafers). The good passivation is probably due to the large hydrogen content of the a-Si:H film, which terminates dangling bonds present on the c-Si surface. After this initial growth, a dense a-Si:H network develops with a refractive index of 4.3 (at 2 eV) and R* = 0.03. The surface recombination velocity decresses linearly with the a-Si:H thickness, achieving a record value of 1.6 cm/s (at 1·1015 cm-3 injection level) for 90 nm thick a-Si film on n-type wafers. As compared to hot wire CVD and radiofrequency PECVD techniques, ETP is capable to deposit thin a-Si:H films with outstanding surface passivation at higher temperature (250° C) and higher deposition rate (1.2 nm/s). The stability in time of surface passivation has been investigated. Effective carrier lifetime is found to decrease following a stretched exponential. Photo-electronic properties of a-Si:H are know to relax in time in a similar fashion. These results therefore suggest a correlation between the photo-electronic roperties of the a-Si:H/c-Si interface and a-Si:H bulk material

Surface Passivation Mechanism of Atomic Layer Deposited Al2O3 Films on c-Si Studied by Optical Second-Harmonic Generation

Recently, it was shown that Al2O3 thin films synthesized by (plasmaassisted) atomic layer deposition (ALD) provide excellent surface passivation of n, p and p+ type c-Si as highly relevant for c-Si photovoltaics. It was found that a large negative fixed charge density (up to 1013 cm-2) in the Al2O3 film plays a key role in the passivation mechanism of Al2O3 [1, 2]. The surface passivation quality of Al2O3 strongly increases with film thickness before reaching saturation around 10 nm as determined by carrier lifetime spectroscopy. In this contribution a study into the thickness effect will be presented in order to distinguish between the influence of fieldeffect passivation, i.e. electrostatic shielding of charge carriers by the fixed negative charge, and chemical passivation, i.e. by a reduction of the interface defect density. To this goal the nonlinear optical technique of second-harmonic generation (SHG) has been utilized. SHG is highly surface and interface specific and allows for the contactless determination of internal electric fields (= 105 V/cm-1). Spectroscopic SHG, carried out with a femtosecond Ti:sapphire laser tunable in the 1.33-1.75 eV photon energy range, has revealed a thickness independent electric field for Al2O3 films with thicknesses ranging from 2 to 20 nm. This implies that the fieldeffect passivation is not affected by the film thickness and that the thickness dependence in passivation quality can be attributed to a changing level of chemical passivation. Moreover, this result confirms that the fixed negative charges are located at the Al2O3 interface as also indicated by conventional C-V measurements. In addition, SHG shows clear differences between measurements performed on Al2O3 films grown by thermal and plasmaassisted ALD. These are likely related to the properties of the interfacial SiOx induced by either growth process. The presence of this oxide is suggested to be responsible for the chemical passivation quality. Furthermore, the differences indicate a smaller contribution of field-effect passivation for the Al2O3 grown with thermal ALD compared to the film from the plasma-assisted process. These results have led to a deeper understanding of the c-Si surface passivation by Al2O3 as will be discussed

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Machine learning prediction models in orthopedic surgery: A systematic review in transparent reporting

Machine learning (ML) studies are becoming increasingly popular in orthopedics but lack a critically appraisal of their adherence to peer-reviewed guidelines. The objective of this review was to (1) evaluate quality and transparent reporting of ML prediction models in orthopedic surgery based on the transparent reporting of multivariable prediction models for individual prognosis or diagnosis (TRIPOD), and (2) assess risk of bias with the Prediction model Risk Of Bias ASsessment Tool. A systematic review was performed to identify all ML prediction studies published in orthopedic surgery through June 18th, 2020. After screening 7138 studies, 59 studies met the study criteria and were included. Two reviewers independently extracted data and discrepancies were resolved by discussion with at least two additional reviewers present. Across all studies, the overall median completeness for the TRIPOD checklist was 53% (interquartile range 47%-60%). The overall risk of bias was low in 44% (n = 26), high in 41% (n = 24), and unclear in 15% (n = 9). High overall risk of bias was driven by incomplete reporting of performance measures, inadequate handling of missing data, and use of small datasets with inadequate outcome numbers. Although the number of ML studies in orthopedic surgery is increasing rapidly, over 40% of the existing models are at high risk of bias. Furthermore, over half incompletely reported their methods and/or performance measures. Until these issues are adequately addressed to give patients and providers trust in ML models, a considerable gap remains between the development of ML prediction models and their implementation in orthopedic practice

Global Analysis of the Impact of Environmental Perturbation on cis-Regulation of Gene Expression

Genetic variants altering cis-regulation of normal gene expression (cis-eQTLs) have been extensively mapped in human cells and tissues, but the extent by which controlled, environmental perturbation influences cis-eQTLs is unclear. We carried out large-scale induction experiments using primary human bone cells derived from unrelated donors of Swedish origin treated with 18 different stimuli (7 treatments and 2 controls, each assessed at 2 time points). The treatments with the largest impact on the transcriptome, verified on two independent expression arrays, included BMP-2 (t = 2h), dexamethasone (DEX) (t = 24h), and PGE2 (t = 24h). Using these treatments and control, we performed expression profiling for 18,144 RefSeq transcripts on biological replicates of the complete study cohort of 113 individuals (ntotal = 782) and combined it with genome-wide SNP-genotyping data in order to map treatment-specific cis-eQTLs (defined as SNPs located within the gene ±250 kb). We found that 93% of cis-eQTLs at 1% FDR were observed in at least one additional treatment, and in fact, on average, only 1.4% of the cis-eQTLs were considered as treatment-specific at high confidence. The relative invariability of cis-regulation following perturbation was reiterated independently by genome-wide allelic expression tests where only a small proportion of variance could be attributed to treatment. Treatment-specific cis-regulatory effects were, however, 2- to 6-fold more abundant among differently expressed genes upon treatment. We further followed-up and validated the DEX–specific cis-regulation of the MYO6 and TNC loci and found top cis-regulatory variants located 180 kb and 250 kb upstream of the transcription start sites, respectively. Our results suggest that, as opposed to tissue-specificity of cis-eQTLs, the interactions between cellular environment and cis-variants are relatively rare (∼1.5%), but that detection of such specific interactions can be achieved by a combination of functional genomic approaches as described here

A whey protein-based multi-ingredient nutritional supplement stimulates gains in lean body mass and strength in healthy older men: A randomized controlled trial

Protein and other compounds can exert anabolic effects on skeletal muscle, particularly in conjunction with exercise. The objective of this study was to evaluate the efficacy of twice daily consumption of a protein-based, multi-ingredient nutritional supplement to increase strength and lean mass independent of, and in combination with, exercise in healthy older men. Forty-nine healthy older men (age: 73 ± 1 years [mean ± SEM]; BMI: 28.5 ± 1.5 kg/m2) were randomly allocated to 20 weeks of twice daily consumption of either a nutritional supplement (SUPP; n = 25; 30 g whey protein, 2.5 g creatine, 500 IU vitamin D, 400 mg calcium, and 1500 mg n-3 PUFA with 700 mg as eicosapentanoic acid and 445 mg as docosahexanoic acid); or a control (n = 24; CON; 22 g of maltodextrin). The study had two phases. Phase 1 was 6 weeks of SUPP or CON alone. Phase 2 was a 12 week continuation of the SUPP/CON but in combination with exercise: SUPP + EX or CON + EX. Isotonic strength (one repetition maximum [1RM]) and lean body mass (LBM) were the primary outcomes. In Phase 1 only the SUPP group gained strength (Σ1RM, SUPP: +14 ± 4 kg, CON: +3 ± 2 kg, P < 0.001) and lean mass (LBM, +1.2 ± 0.3 kg, CON: -0.1 ± 0.2 kg, P < 0.001). Although both groups gained strength during Phase 2, upon completion of the study upper body strength was greater in the SUPP group compared to the CON group (Σ upper body 1RM: 119 ± 4 vs. 109 ± 5 kg, P = 0.039). We conclude that twice daily consumption of a multi-ingredient nutritional supplement increased muscle strength and lean mass in older men. Increases in strength were enhanced further with exercise training

Maps of Open Chromatin Guide the Functional Follow-Up of Genome-Wide Association Signals: Application to Hematological Traits

Turning genetic discoveries identified in genome-wide association (GWA) studies into biological mechanisms is an important challenge in human genetics. Many GWA signals map outside exons, suggesting that the associated variants may lie within regulatory regions. We applied the formaldehyde-assisted isolation of regulatory elements (FAIRE) method in a megakaryocytic and an erythroblastoid cell line to map active regulatory elements at known loci associated with hematological quantitative traits, coronary artery disease, and myocardial infarction. We showed that the two cell types exhibit distinct patterns of open chromatin and that cell-specific open chromatin can guide the finding of functional variants. We identified an open chromatin region at chromosome 7q22.3 in megakaryocytes but not erythroblasts, which harbors the common non-coding sequence variant rs342293 known to be associated with platelet volume and function. Resequencing of this open chromatin region in 643 individuals provided strong evidence that rs342293 is the only putative causative variant in this region. We demonstrated that the C- and G-alleles differentially bind the transcription factor EVI1 affecting PIK3CG gene expression in platelets and macrophages. A protein–protein interaction network including up- and down-regulated genes in Pik3cg knockout mice indicated that PIK3CG is associated with gene pathways with an established role in platelet membrane biogenesis and thrombus formation. Thus, rs342293 is the functional common variant at this locus; to the best of our knowledge this is the first such variant to be elucidated among the known platelet quantitative trait loci (QTLs). Our data suggested a molecular mechanism by which a non-coding GWA index SNP modulates platelet phenotype

Unraveling the Regulatory Mechanisms Underlying Tissue-Dependent Genetic Variation of Gene Expression

It is known that genetic variants can affect gene expression, but it is not yet completely clear through what mechanisms genetic variation mediate this expression. We therefore compared the cis-effect of single nucleotide polymorphisms (SNPs) on gene expression between blood samples from 1,240 human subjects and four primary non-blood tissues (liver, subcutaneous, and visceral adipose tissue and skeletal muscle) from 85 subjects. We characterized four different mechanisms for 2,072 probes that show tissue-dependent genetic regulation between blood and non-blood tissues: on average 33.2% only showed cis-regulation in non-blood tissues; 14.5% of the eQTL probes were regulated by different, independent SNPs depending on the tissue of investigation. 47.9% showed a different effect size although they were regulated by the same SNPs. Surprisingly, we observed that 4.4% were regulated by the same SNP but with opposite allelic direction. We show here that SNPs that are located in transcriptional regulatory elements are enriched for tissue-dependent regulation, including SNPs at 3′ and 5′ untranslated regions (P = 1.84×10−5 and 4.7×10−4, respectively) and SNPs that are synonymous-coding (P = 9.9×10−4). SNPs that are associated with complex traits more often exert a tissue-dependent effect on gene expression (P = 2.6×10−10). Our study yields new insights into the genetic basis of tissue-dependent expression and suggests that complex trait associated genetic variants have even more complex regulatory effects than previously anticipated