Dominant Effect Research Articles

Genetic Component and Character Association for Yield and Yield Component Traits in Bread Wheat (Triticum aestivum L.)

The current research involves the implementation of half diallel crosses between ten genotypes of bread wheat in 2018-2019. The parents and their F1 generation, excluding reciprocals, were then cultivated in the 2019-2020 growing season at the agriculture research farm, School of Agricultural Sciences and Engineering, IFTM University, Lodhipur Rajput, Moradabad (U.P.) and R.B. (PG) College, Mudi, Agra, using a randomized complete block design with three replications. Knowledge of type of gene action controlling target traits and genetic behaviour is a basic principle for designing an appropriate breeding procedure for the purpose of genetic improvement. Hence, the success of any selection or hybridization breeding program for developing varieties depends on precise estimates of genetic variation components for traits of interest which may be additive, dominant and non-allelic interaction effects. Significant genotype means squares and its components (parents and crosses) were obtained for all traits in both locations. Genetic components analysis found that additive (D) and Dominance (H1) was significant in all the traits. The value of mean degree of dominance was greater than additive, indicating availability of over dominance for all the traits. The present investigation revealed that grain yield was positively correlated with days to maturity, plant height, number of effective tillers per plant spike length, number of spikelets per spike, days to 50% heading and yield (q ha-1). Hence, more importance should be given to these traits while exercising selection. Based on the correlation and path studies it was reported that days to ear head emergence, days to maturity, plant height, number of effective tillers per plant, number of spikelets per spike, number of grains per spike, grain yield per plant and 1000 grain weight could be used as important selection traits in order of merit to improve productivity during designing a suitable breeding programme in wheat.

Three-dimensional discretization-based kinematic analyses of prestressed anchor cables reinforced rotational slopes subjected to earthquakes

Prestressed anchor cables are commonly utilized to reinforce slopes in earthquake-prone zones. The existing upper bound limit analyses of seismic slopes reinforced with prestressed anchor cables have the following limitations: (1) neglecting variable seismic excitations; (2) ignoring the three-dimensional spatial layout of cables because of using the plane-strain analysis. In this study, the time-space effects of seismic waves are analytically described by sin-cos functions incorporating wave amplification or soil damping. Based on the upper bound of plastic theory and a three-dimensional discretized failure mechanism, internal energy dissipation rate and work rates contributed by gravitational forces, variable seismic excitations, and prestressed anchor cables are computed. An energy-based function of dynamic factors of safety (DFS) is established, followed by a global optimization to identify the critical harmonic pattern of DFS. The accuracy is checked by numerical simulations where the seismic stability of an engineering slope adjacent to Yu-Huai railway is evaluated. Comparisons also show that the conventional simplified method not only cannot reflect the spatial layout of cables but also overestimate the mechanical contribution of cables. Finally, the dominant effects of the layout of cables, soil properties as well as physical parameters of seismic waves on the DFS and the critical failure mechanism are discussed.

Top quark mass calibration for Monte Carlo event generators — an update

We generalize and update our former top quark mass calibration framework for Monte Carlo (MC) event generators based on the e+e− hadron-level 2-jettiness τ2 distribution in the resonance region for boosted tt¯\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ t\\overline{t} $$\\end{document} production, that was used to relate the Pythia 8.205 top mass parameter mtMC\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {m}_t^{\ extrm{MC}} $$\\end{document} to the MSR mass mtMSRR\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {m}_t^{\ extrm{MSR}}(R) $$\\end{document} and the pole mass mtpole\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {m}_t^{\ extrm{pole}} $$\\end{document}. The current most precise direct top mass measurements specifically determine mtMC\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {m}_t^{\ extrm{MC}} $$\\end{document}. The updated framework includes the addition of the shape variables sum of jet masses τs and modified jet mass τm, and the treatment of two more gap subtraction schemes to remove the O\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ \\mathcal{O} $$\\end{document}(ΛQCD) renormalon related to large-angle soft radiation. These generalizations entail implementing a more versatile shape-function fit procedure and accounting for a certain type of (mt/Q)2 power corrections to achieve gap-scheme and observable independent results. The theoretical description employs boosted heavy-quark effective theory (bHQET) at next-to-next-to-logarithmic order (N2LL), matched to soft-collinear effective theory (SCET) at N2LL and full QCD at next-to-leading order (NLO), and includes the dominant top width effects. Furthermore, the software framework has been modernized to use standard file and event record formats. We update the top mass calibration results by applying the new framework to Pythia 8.305, Herwig 7.2 and Sherpa 2.2.11. Even though the hadron-level resonance positions produced by the three generators differ significantly for the same top mass parameter mtMC\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {m}_t^{\ extrm{MC}} $$\\end{document} value, the calibration shows that these differences arise from the hadronization modeling. Indeed, we find that mtMC\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {m}_t^{\ extrm{MC}} $$\\end{document} agrees with mtMSR\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {m}_t^{\ extrm{MSR}} $$\\end{document}(1 GeV) within 200 MeV for the three generators and differs from the pole mass by 350 to 600 MeV.

Oxidation-driven 2D LIPSS on amorphous Si films atop metal layers: The interplay of near-field and far-field effects

We investigate the formation of Laser-Induced Periodic Surface Structures (LIPSS) on amorphous Si films coated on Al using circularly polarized femtosecond lasers. By controlling laser fluence, we induce oxidation-based surface patterns, with their regularity governed by the interplay between near-field and far-field contributions. Achieving the right balance between these effects results in a consistent hexagonal pattern. Varying the underlying metal type further revealed its impact on pattern quality: strong far-field contributions led to irregular patterns, while dominant near-field effects resulted in extensive oxidation. Our study reveals the critical balance between near-field and far-field effects in optimizing 2D LIPSS patterns, emphasizing the role of the underlying metal.

Estimating bidirectional effects between social connectedness and mental health in adolescent students: Addressing biases due to endogeneity

Research on the bidirectional relationship between social connectedness and health/mental health in adolescents is scarce, with most studies on adults. Some of the existing studies exploited the availability of longitudinal data to provide evidence of the existence of a causal relationship, either from social connectedness to health or establish a bidirectional relationship. There are at least two weaknesses associated with earlier research to assess the size of the effects. As acknowledged in the literature, one relates to attributing causality to empirical findings, due to well-known but inadequately addressed endogeneity biases. The other relates to failure to account for potentially important covariates, sometimes due to data limitations, or because such variables are not frequently used in sociological research. Existing research predominantly finds that the strongest path is from social connectedness to health/mental health, with effect estimates modest in size. I followed a quasi-experimental strategy by modelling adolescent students’ perceptions of social connectedness and mental health perceptions as potentially endogenous variables when estimating bidirectional effects. An instrumental variables (IV) modelling approach was followed, supplemented with a recently developed alternative approach to testing the exclusion restrictions of individual instruments. I exploited the rich information available in the PISA 2018 multi-country dataset, which allows for conditioning for a wide array of information on adolescent students’ personal circumstances, self-reported personality-related attributes, relationships with parents; and school characteristics. I found that (1) accounting for endogeneity biases is important; and (2) as opposed to findings reported in the literature, the dominant effect is from mental health perceptions to social connectedness for both male and female participants. The policy relevance of the findings is that adolescent mental health should be the primary focus of interventions, i.e., identifying and treating mental health symptoms as a primary intervention and as a precursor to improving the social connectedness of adolescents.

Evaluating the cost utility of estradiol plus dydrogesterone for the treatment of menopausal women in China

AimEvaluate the cost utility of menopausal hormone therapy for women in China.Materials and methodsA bespoke Markov cost utility model was developed to evaluate a cohort of symptomatic perimenopausal women (>45 years) with intact uterus in China in accordance with China’s Pharmacoeconomic guideline. Short (5-year) and long (10-year) treatment durations were evaluated over a lifetime model time horizon with 12-month cycle duration. Societal and healthcare payer perspectives were evaluated in the context of a primary care provider/prescriber, outpatient setting with inpatient care for patients with chronic conditions. Disease risk and mortality parameters were derived from focused literature searches, and China Diagnosis-related Group cost data was included. Comprehensive scenario, univariate and probabilistic sensitivity analysis were undertaken along with independent validation. This is the first model to include MHT-related disease risks.ResultsAccording to base case results, the total cost for MHT was 22,516$ (150,106¥) and total quality adjusted life years 12.32 versus total cost of no MHT 30,824$ (205,495¥) and total quality adjusted life years 11.16 resulting in a dominant incremental cost effectiveness ratio of −7,184$ (−47,898¥) per QALY. Results hold true over a range of univariate deterministic sensitivity and scenario analyses. Probabilistic analysis showed a 91% probability of being cost effective at a willingness to pay threshold of three times Gross Domestic Product per capita in China.ConclusionContingent on the structure and assumptions of the model, combination of estradiol plus dydrogesterone MHT is potentially cost saving in symptomatic women over the age of 45 years in China.

The Effects of the Al and Zr Contents on the Microstructure Evolution of Light-Weight AlxNbTiVZry High Entropy Alloy.

To investigate the comprehensive effects of the Al and Zr element contents on the microstructure evolution of the AlNbTiVZr series light-weight refractory high entropy alloys (HEAs), five samples were studied. Samples with different compositions were designated Al1.5NbTiVZr, Al1.5NbTiVZr0.5, AlNbTiVZr, AlNbTiVZr0.5, and Al0.5NbTiVZr0.5. The results demonstrated that the actual density of the studied HEA samples ranged from 5.291 to 5.826 g·cm-3. The microstructure of these HEAs contains a solid solution phase with a BCC structure and a Laves phase. The Laves phase was further identified as the ZrAlV intermetallic compound by TEM observations. The microstructure of the AlNbTiVZr series HEAs was affected by both the Al and Zr element contents, whereas the Zr element showed a more dominant effect due to Zr atoms occupying the core position of the ZrAlV Laves phase (C14 structure). Therefore, the as-cast Al0.5NbTiVZr0.5 sample exhibits the best room temperature compression property with a compression strength (σp) of 1783 MPa and an engineering strain of 28.8% due to having the lowest ZrAlV intermetallic compound area fraction (0.7%), as characterized by the EBSD technique.

The quantitative genetics of human disease: 1. Foundations

In this the first of an anticipated four paper series, fundamental results of quantitative genetics are presented from a first principles approach. While none of these results are in any sense new, they are presented in extended detail to precisely distinguish between definition and assumption, with a further emphasis on distinguishing quantities from their usual approximations. Terminology frequently encountered in the field of human genetic disease studies will be defined in terms of their quantitive genetics form. Methods for estimation of both quantitative genetics and the related human genetics quantities will be demonstrated. The principal target audience for this work is trainees reasonably familiar with population genetics theory, but with less experience in its application to human disease studies. We introduce much of this formalism because in later papers in this series, we demonstrate that common areas of confusion in human disease studies can be resolved be appealing directly to these formal definitions. The second paper in this series will discuss polygenic risk scores. The third paper will concern the question of “missing” heritability and the role interactions may play. The fourth paper will discuss sexually dimorphic disease and the potential role of the X chromosome. Background: With over a hundred years of history, most fundamental results in quantitative genetics are well known to most population genetics students, yet there is often considerable confusion concerning precise definitions and assumptions, particularly when interactions may exist. The connections between quantitative genetics and human disease genetics can be obscure to many. Methods: Fundamental quantitative genetics quantities are derived as conditional expectations of phenotype. Genetic, environmental, additive, dominance and interaction effects and their associated variances are defined, with key results explicitly derived. The effects of linkage disequilibrium and methods to account for it are examined. Methods to estimate and interpret heritability are discussed. Results: Application of quantitative genetics quantities are extended to binary traits with special emphasis on translation between commonly estimated human disease genetics quantities and their corresponding quantitative genetics representations. Conclusions: The distinction between modeling definitions and assumptions is made clear. Methods to unite human disease genetics and quantitative genetics are elucidated. Methods to account for linkage disequilibrium and other forms of interaction are described.

Multiple NTS neuron populations cumulatively suppress food intake.

Several discrete groups of feeding-regulated neurons in the nucleus of the solitary tract (nucleus tractus solitarius; NTS) suppress food intake, including avoidance-promoting neurons that express Cck (NTSCck cells) and distinct Lepr- and Calcr-expressing neurons (NTSLepr and NTSCalcr cells, respectively) that suppress food intake without promoting avoidance. To test potential synergies among these cell groups, we manipulated multiple NTS cell populations simultaneously. We found that activating multiple sets of NTS neurons (e.g. NTSLepr plus NTSCalcr [NTSLC], or NTSLC plus NTSCck [NTSLCK]) suppressed feeding more robustly than activating single populations. While activating groups of cells that include NTSCck neurons promoted conditioned taste avoidance (CTA), NTSLC activation produced no CTA despite abrogating feeding. Thus, the ability to promote CTA formation represents a dominant effect but activating multiple non-aversive populations augments the suppression of food intake without provoking avoidance. Furthermore, silencing multiple NTS neuron groups augmented food intake and body weight to a greater extent than silencing single populations, consistent with the notion that each of these NTS neuron populations plays crucial and cumulative roles in the control of energy balance. We found that silencing NTSLCK neurons failed to blunt the weight-loss response to vertical sleeve gastrectomy (VSG) and that feeding activated many non-NTSLCK neurons, however, suggesting that as-yet undefined NTS cell types must make additional contributions to the restraint of feeding.

Topological-edge-state spin transport in asymmetric three-terminal silicenelike nanodevice

We theoretically investigate the topological-edge-state spin transport in asymmetric three-terminal silicene-like nanodevice. Since silicene-like materials are honeycomb structures with considerable spin-orbit interaction (SOI), they possess both Dirac electron and topology insulator behaviors. In the three-terminal silicene-like nanodevice, the SOI realizes helical edge state and brings fully spin polarization selectively without external field. Firstly, we find that the spin degeneracy breaking gives rise to spin-polarized transport, i.e., up-spin electron and down-spin electron propagating to different leads from the top lead. The distribution of edge-state spin-dependent current in the real space indicates that an up-/down-spin channel to the left/right lead is opened at the interface of the present nanodevice. Secondly, the spin-polarized transport behavior has a competition with the effect of asymmetric transport, which prefers propagating the up- and down-electrons from top lead to the same (right) lead. Interestingly, as the geometric size variation is considered, the results show that the width increase of the horizontal armchair (top vertical zigzag) lead reinforces the spin-polarized (asymmetric) transport. However, when both the armchair and zigzag leads increase simultaneously, the spin-polarized transport becomes the dominant effect. Therefore, this edge-state spin-polarized transport behavior is topologically protected and very robust as the whole geometric size of the nanodevice increases. These properties of the topological-edge-state spin transport enable the asymmetric three-terminal silicene-like nanodevice a spin filter or a spin valve, and might contribute to the silicene-like nanocircuit engineering and spintronics application.

Climate overtakes vegetation greening in regulating spatiotemporal patterns of soil moisture in arid Central Asia in recent 35 years

ABSTRACTSatellite datasets have revealed significant greening and soil drying in arid Central Asia. However, the influence mechanism of vegetation and climate on soil moisture dynamics is still unclear. In this study, we investigated the spatiotemporal consistency of vegetation and soil moisture changes, examined the controlling factors of soil moisture under different vegetation indices (normalized differential vegetation index, NDVI; leaf area index, LAI), and explored the time lag and accumulation effects of vegetation greening on the soil moisture in arid Central Asia in the period of 1985 to 2020. The results showed that the co-occurrence of vegetation greening and soil drying in 30.4% (NDVI) and 19.4% (LAI) of the study area spatially. Temporally, the soil moisture increased from 1985 to 1989, but decreased from 1989 or 1990 to 2020. In contrast, vegetation activity increased continuously during 1985–2020. Precipitation accounted for the most variance of the soil moisture. The vegetation greenness demonstrated positive correlations with soil moisture, representing 20.7% (for NDVI) and 39.3% (for LAI) of vegetated areas (areas with long-term mean NDVI ≥ 0.1 and LAI > 0), while negative correlations were observed in only 5.4% (for NDVI) and 3.3% (for LAI) of vegetated areas, respectively. Soil moisture exhibited varying time lag and accumulation effects in response to different vegetation indices, precipitation, and temperature. The main temporal effects of NDVI and temperature were simultaneous changes with no time lag or accumulation effects on soil moisture. In contrast, the main temporal effects of LAI and precipitation included 1-month lag in their influence on soil moisture. Considering the inconsistencies in spatiotemporal patterns between vegetation and soil moisture, as well as the dominance and time lag effects of precipitation on soil moisture variations, we concluded that climate, especially precipitation, rather than vegetation greening, regulates soil moisture in Central Asia. These findings provide a scientific basis for vegetation restoration or regional water resource management in drylands.

Allele-specific CRISPR-Cas9 editing of dominant epidermolysis bullosa simplex in human epidermal stem cells

Epidermolysis Bullosa Simplex (EBS) is a rare skin disease inherited mostly in an autosomal dominant manner. Patients display a skin fragility that leads to blisters and erosions caused by minor mechanical trauma. EBS phenotypic and genotypic variants are caused by genetic defects in intracellular proteins whose function is to provide the attachment of basal keratinocytes to the basement membrane zone and most of EBS cases display mutations in keratin 5 (KRT5) and keratin 14 (KRT14) genes. Besides palliative treatments, there is still no long-lasting effective cure to correct the mutant gene and abolish dominant negative effect of the pathogenic protein over its wild-type counterpart. Here, we propose a molecular strategy for EBS01 patient’s keratinocytes carrying a monoallelic c.475/495del21 mutation in KRT14 exon1. Through the CRISPR/Cas9 system we performed a specific cleavage only on the mutant allele and restore a normal cellular phenotype and a correct intermediate filament network, without affecting the epidermal stem cell, referred to as holoclones, which play a crucial role in epidermal regeneration.

Improving sulfate and chloride resistance in eco-friendly marine concrete: Alkali-activated slag system with mineral admixtures

This study investigates the effects of various mineral admixtures, such as fly ash, metakaolin, and limestone powder, on the mechanical, chloride, and sulfate resistance properties of alkali-activated slag (AAS). The resistance of alkali-activated concrete (AAC) to chloride and sulfate is evaluated using the rapid chloride migration (RCM), wetting-drying cycles, SEM and XRD, TG/DTG. The results reveal that introducing fly ash improves workability but degrades the strength and durability of AAS. The 15% slag substitution by metakaolin is recommended to improve durability. Incorporating 15% limestone powder increases the compressive strength and reduces porosity due to filling and nucleation effects. The replacement ratio of 30% for each mineral admixture induces a considerable Ca2+ dilution, resulting in reducing the strength and durability of AAC. Under short-term wetting-drying cycles, the continued hydration of raw materials under MgSO4 erosion and the subsequent production of gypsum, hydrotalcite, and brucite from the matrix initially increase the AAC strength. However, the continued substitution of calcium in the C-(A)-S-H gel by magnesium and precipitation of gypsum under excessive cycles adversely deteriorates the compressive strength. The chloride migration degree in AAC is closely related to the porosity. Although the porous gel N-A-S-H facilitates chlorine migration in accelerated tests, it prevents further chlorine penetration by adsorbing chloride ions in large quantities, exhibiting the dominant effect on chloride immobilization. The formation of Friedel's salt, stemming from the chemical bonding of chloride, is present only in the high-calcium specimen G100 and the highly reactive aluminum specimen G85M15. Improvements in the gel chemistry and porosity are key factors in bolstering the durability of AAC. The findings of this study contribute to advancing the application of eco-friendly AAC in marine environments.

Development of an improved three-dimensional rough discrete fracture network model: Method and application

Structure plane is one of the important factors affecting the stability and failure mode of rock mass engineering. Rock mass structure characterization is the basic work of rock mechanics research and the important content of numerical simulation. A new 3-dimensional rough discrete fracture network (RDFN3D) model and its modeling method based on the Weierstrass-Mandelbrot (W-M) function were presented in this paper. The RDFN3D model, which improves and unifies the modelling methods for the complex structural planes, has been realized. The influence of fractal dimension, amplitude, and surface precision on the modeling parameters of RDFN3D was discussed. The reasonable W-M parameters suitable for the roughness coefficient of JRC were proposed, and the relationship between the mathematical model and the joint characterization was established. The RDFN3D together with the smooth 3-dimensional discrete fracture network (DFN3D) models were successfully exported to the drawing exchange format, which will provide a wide application in numerous numerical simulation codes including both the continuous and discontinuous methods. The numerical models were discussed using the COMSOL Multiphysics code and the 3-dimensional particle flow code, respectively. The reliability of the RDFN3D model was preliminarily discussed and analyzed. The roughness and spatial connectivity of the fracture networks have a dominant effect on the fluid flow patterns. The research results can provide a new geological model and analysis model for numerical simulation and engineering analysis of jointed rock mass.

X‐chromosome wide association study for Alzheimer’s disease

AbstractBackgroundAlthough the X‐chromosome represents about 5% of the genome, it has been excluded from the major genome‐wide association studies on Alzheimer’s Disease (AD) due to its genetic specificities. We performed an in‐depth X‐Chromosome‐Wide Association Study (XWAS) to better characterize the genetic landscape of AD.MethodThe XWAS is based on 49,333 clinically diagnosed cases and 68,882 controls (including 31,314 female cases and 39,407 female controls) of European ancestry from 29 studies from the International Genomics of Alzheimer’s Project (IGAP) and the European Alzheimer & Dementia Biobank (EADB) consortia. 45,993 samples were imputed with the 1000G reference panel and 72,220 samples were imputed with the TOPMed panel.We considered three approaches to take into account the different inactivation scenarios on the X‐chromosome: 1) random X‐chromosome inactivation (r‐XCI) in females, equivalent to an additive genetic model with males coded as homozygous females; 2) skewed X‐chromosome inactivation in females, where a dominance effect was added to the r‐XCI model to capture the inactivation skewedness; 3) escape X‐chromosome inactivation in females, equivalent to an additive model with males coded as hemizygous. For each approach, we performed a single variant analysis with a meta‐analysis of the 29 studies, followed by a gene‐based analysis.ResultWe analyzed 404,688 variants, including 225,045 common variants (Minor Allele Frequency [MAF] > 1%). No genome‐wide significant signals were found in either approach, but three suggestive signals (p‐value < 1×10‐5) were identified in the r‐XCI approach. In one of these loci, we detected an X‐chromosome‐wide significant gene with the gene‐based analysis (p‐value = 5.45×10‐5). The top variant of this locus shows a similar effect in males and females (odds ratio [OR] = 0.93, 95% confidence interval [CI] = 0.90–0.96, p‐value = 8.63 × 10−6, and MAF = 32%, with OR[CI] in females = 0.86[0.79‐0.94], and OR[CI] in males = 0.92 [0.87‐0.97]).ConclusionWe identified promising genetic signals for AD on the X‐chromosome. To increase power, we are currently updating the imputation with TOPMed for all the studies and extending the analyses to large European biobanks.

Pengaruh Infrastruktur, Investasi, dan Pertumbuhan Ekonomi terhadap Kesejahteraan Masyarakat melalui Kesempatan Kerja di Kabupaten Tapin

This study's purpose is to determine the effect of infrastructure, investment, and economic growth on employment opportunities in Tapin Regency, assess the impact of infrastructure, investment, and economic growth on people's welfare, choose the direct and indirect effects of infrastructure, investment, and the economic growth on the interest of the community through employment opportunities in Tapin Regency. This study uses the Path Analysis method's time series data from 2011 to 2020. Results of this study indicate that infrastructure and investment have no significant effect on employment opportunities, while economic growth substantially impacts employment opportunities. Furthermore, infrastructure and investment do not considerably affect people's welfare; economic growth considerably affects community welfare in Tapin Regency. Lastly, the influence of infrastructure and buying on the people's interest in Tapin Regency is a more dominant indirect influence. Economic growth on the welfare of the people in Tapin Regency is a more dominant direct effect.

Modeling and Hover Flight Control of a Micromechanical Flapping-Wing Aircraft Inspired by Wing–Tail Interaction

This article intends to give a comprehensive model to a brand new micromechanical flapping-wing aircraft inspired by wing–tail interaction. In this aircraft, the flapping-wing induced flow contributes to the tail control torque generation. However, this also makes the wing–tail interaction nonnegligible, and this flow would be disturbed by the relative flow produced by the body motion. The dominant unsteady aerodynamic effects of the flapping wing are considered. The flapping-wing induced flow over the tail is included when analyzing the tail aerodynamics. Especially, the aerodynamic–dynamic coupling effect of both the wing and the tail is considered to account for the force due to the body motion. A nonlinear and time-periodic simulation model of the aircraft is, thus, established. The model is averaged and linearized around hover status. Because of the combination of the wing–tail interaction with the aerodynamic–dynamic coupling, the state and control matrixes, including both the induced flow effect and the body motion effect, can be obtained. The pitch dynamics are analyzed, and it is found that the tail can push the two unstable oscillatory poles closer to the imaginary axis. The role of the tail is fully demonstrated by considering the induced flow. Cascade controllers are also designed according to the root-locus plot based on the built model. Due to the inclusion of the wing–tail interaction and the aerodynamic–dynamic coupling, the controllers are proved to be efficient in the attitude stabilization during statistic hover, descent, and ascent flights. Our proposed model can be easily applied to the modeling of other flapping-wing aircraft with similar structures, and it makes the controller design process more efficient and targeted.

Estimating time-dependent solar gains through opaque building envelope parts: an explorative study on a test box

Accurate estimation of the energy gain from solar radiation in buildings is necessary for building energy performance characterization, model predictive control (MPC), fault detection and diagnostics, etc. Solar radiation affects the buildings’ internal air temperature dynamics, either (directly) by penetrating the glazing or (indirectly) through the opaque building envelope. Nevertheless, no research has investigated the on-site data-driven modelling of the indirect effects of solar radiation i.e., additional solar gain through the opaque building envelope, marked as indirect solar gain. Therefore, this work aims to develop grey-box model-based techniques to characterize the dynamics of indirect solar gain. A test box, with overall dimensions of 120*120*120 cm3, that represents a simplified scale model of a building is examined, to provide an initial understanding of this matter. This test box is south-north orientated and has only one window of 60*60 cm2, positioned on its southern wall. On-site data associated with this text box was recorded during the summer (June-July) in Almeria, Spain. This simplified reduced-size text box satisfies the research goal very well to serve as a pilot case study, since the indirect solar gain was the dominant effect of solar radiation. Based on the in-situ data from this case, a three-dimensionally decomposed solar irradiance integrated grey-box modelling technique is proposed for characterizing the dynamics of indirect solar gain. Preliminary results from this study show that this technique can effectively reveal the key dynamics of indirect solar gain and outperform the classic grey-box model, based on limited low-frequency on-site measured data.

Research and modeling of the ecological efficiency of drying refractory and building materials in vertical shaft furnaces

Based on the hypothesis of the dominant effect on the environmental efficiency of drying materials in shaft furnaces of the concentration, median diameter, dispersion, temperature and humidity of dust particles at the outlet of the dryer, a device for thermal aeration separation of dust is proposed. The analysis of mathematical modeling of aerothermodynamic processes in a two-phase medium asbestos dust ‒ gas flow confirmed the conclusions of industrial studies on the influence of aerothermodynamic parameters of direct flow on the temperature and humidity of asbestos dust in the pneumatic dryer. Based on the principle of additive classification, a mathematical model of aeration separation of dust particles directly in the dryer of the shaft furnace is constructed, depending on the parameters of the heat carrier and the proposed device.

One Year Follow-up on the First Patient Treated with Nula-Cel: An Autologous CRISPR/Cas9 Gene Corrected CD34+ Cell Product to Treat Sickle Cell Disease

Introduction Sickle cell disease (SCD) is the most common serious genetic disease in the world with over 500,000 births per year globally. It is estimated that there are >100,000 patients in the US with SCD and at least 20% have severe disease. Patients with SCD have at least one HBB gene with an adenine to thymidine variant at position 6 of the coding region resulting in a glutamic acid to valine amino acid change ( HbS). The success of allogeneic hematopoietic stem cell transplantation demonstrates that reconstitution of the hematopoietic compartment with HSCs that contain at least one non- HbS allele can cure the disease. Homology directed repair gene editing (HDR-editing) has achieved high frequencies of conversion of the thymidine to the non-pathologic adenine in CD34+ hematopoietic stem and progenitor cells from patients with SCD. Nulabeglogene autogedtemcel (nula-cel) is an investigational drug product in which HDR-editing of plerixafor-mobilized CD34+ HSPCs corrects the underlying variant that causes SCD. This is the first drug to directly correct a disease-causing variant. We report on the 1 year follow up of the first and only patient to receive nula-cel. Results Patient 1 is now a 23 year old female with homozygous SCD. She was consented and enrolled on a Phase I//II trial to test the safety and efficacy of nula-cel. In the 2 years prior to enrollment, the patient averaged 6 VOC's and 4 hospitalizations per year. Two aphereses of plerixafor-mobilized CD34+ cells were performed followed by fresh CD34+ cell purification. The purified CD34+ cells were pooled and cryopreserved. A 5-day manufacturing process starting with 9.3 x 10 6 cells/kg of cryopreserved CD34+ cells resulted in a yield of 8.75 x 10 6 CD34/kg with an on-target allele correction frequency of 33%. In August, 2022 the thawed drug product was infused after the patient received AUC-adjusted busulfan myeloablative conditioning chemotherapy. The initial cell viability was 77% giving a viable infused cell dose of 6.74 x 10 6 CD34/kg. Follow-up exploratory apoptois studies, however, showed the viable CD34+cell dose may have been as low as 3.5 x 10 6 CD34+/kg. Neutrophil engraftment occurred at transplant Day +40. Because of the lack of platelet recovery and continued platelet and RBC transfusion requirements, the patient was started on eltrombopag on day +106 (marrow cellularity of 5%). Since eltrombopag usage was not part of the protocol, its use prompted the reporting of an SAE but the trial was never put on FDA hold. The last dose of GCSF was D+140, the last platelet transfusion was D+181 and the last RBC transfusion was D+263. With rising platelet counts and hemoglobin and a stable ANC >1500, eltrombopag was discontinued on D+322. The blood counts have continued to slowly increase after discontinuation of the eltrombopag. On D+307, with a Hgb of 8.5 g/dl, hemoglobin electrophoresis demonstrated HgbA=12.5%, HgbF >78% and HgbS=4.5%. On D+349 the blood tests show Hgb=9.1 g/dl, Platelet=77,000/ul, ANC=1788/ul with an absolute reticulocyte count of 119,130/ul. There are no signs or symptoms of hemolysis. Table 1 shows the time course of gene marking with stable allele gene correction and INDEL frequencies since D+49. No change in off-target INDEL frequency nor change in on-target INDEL spectrum has occurred and no evidence of oligoclonal or clonal hematopoiesis has been observed. Clinically, the patient has shown marked improvement in quality of life with zero VOE's or other manifestations of SCD. The patient still has not reached a steady state and updated results will be presented. Conclusion We describe the clinical results of the first patient treated with an autologous cell product (nula-cel) in which the pathologic variant was directly corrected. The mechanism of action is fundamentally different than other clinical gene editing and gene therapy programs as the level of the pathologic HgbS is directly decreased thereby removing the dominant negative effect that HgbS has on red blood cells. The high HgbF is an unexpected but potentially effective mechanism of action for the clinical benefit and is being further studied. Longer follow up to assess the durability of the curative clinical impact is underway. Improvements in cell manufacturing are being implemented to shorten the duration of transfusion needs and increase the level of gene correction of engrafted cells. Plans to treat the next patients with an improved nula-cel product are in place.