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Due to growing consciousness and pressure from concerned stakeholders, organizations have started to prioritize green management practices (GMP); however, little is known about the critical role of organizational motives (OM) for achieving GMP. Following the stakeholder theory, this study intends to examine the relationship between stakeholders' pressure (STP), organizational motives (OM), and GMP in an encompassing model. Three hundred and eight responses were collected from the Pakistani manufacturing industry, and hypotheses were confirmed employing structural equation modeling (SEM). Empirical results indicate that primary and secondary stakeholders' pressure has a substantial effect on OM. Further, each motive, such as instrumental, relational, and moral, substantially impacts GMP. Besides, OM has been found to partially mediate the relationship. Importance-performance analysis specified that the importance and performance values of STP are higher than OM for GMP. The conclusion emphasizes the essential role that STP can play in realizing GMP in manufacturing industries through OM. These novel findings suggest worthy insights for managerial staff and policymakers on enhancing GMP adoption through OM in emerging economies. [ABSTRACT FROM AUTHOR]

Environmental administrative penalty is a powerful way for the government to realize environmental pollution control. When a firm is subjected to an environmental administrative penalty, how the penalty affects its equity cost is a hot issue in academia and industry. Using the ordinary least square method and the Bootstrap method, it is found that environmental penalties significantly increase corporate equity costs in the following year through their disclosure increments; the disclosure increment plays a mediating role in the positive effect. It is also found that the reduced negative information disclosures can increase the effect, while the increased positive information can reduce the effect. These findings help us understand environmental management's significance to a firm's financing sustainability and have practical enlightenment on environmental management and environmental pollution control. [ABSTRACT FROM AUTHOR]

This study is about the inspection of the multidimensional poverty level and changes with time. Three sample countries (Pakistan, Bangladesh, and India) are taken from the South Asian Region to measure the depth of multidimensional poverty and inequality among the deprived individuals by using Alkire and Foster (2011) "Dimension Adjusted" or headcount ratio measure, Rippin (2010) Class of Ordinal Poverty measures, and Chakravarty and D'Ambrosio (2006) Class of Poverty measures. These all three approaches are counting-based approaches that are used on ordinal variables. The data of three main dimensions (Education, Health and Standard of Living) which is further divided into ten indicators is used for this study. The secondary data is used, which is extracted from Demographic Health Surveys (DHS). The last three surveys of DHS is used in this study, which was conducted in different period. Results of all three countries are compared and showed that India is having more poverty followed by Bangladesh and Pakistan. Change in inequality component among deprived individuals is recorded almost similar in all three sample countries. The finding of this study shows that all three techniques are providing insightful information about the depth and component inequality among deprived individuals. [ABSTRACT FROM AUTHOR]

Considering the growing awareness about sustainable development among various stakeholders, the present study aims to examine the impact of employees' knowledge absorptive capacity (KAC) on firms' corporate social responsibility (CSR) practices for accomplishing corporate sustainability performance (CSP) goals by following the absorptive capacity and green theory. Data were collected using a convenience sampling technique from 587 ISO-certified manufacturing Multinational Corporations (MNCs) from the Asia Pacific region, including those from China, Malaysia, Pakistan, the Middle East, and Taiwan. It was analysed using partial least squares structural equation modeling and fuzzy set qualitative comparative analysis (fsQCA). As per the results, KAC is positively correlated with CSR activities and significantly impacts CSP. Second, CSR was found to have a considerable mediating impact. Third, importance-performance map analysis indicated that the performance of KAC is relatively higher than CSR for CSP. Furthermore, fsQCA results validate the robustness of constructs towards CSP. [ABSTRACT FROM AUTHOR]

The world has witnessed a rapid rise of online health communities (OHCs) where patients can create a powerful network of support and resources to make a meaningful difference in people’s health lives. Despite this rapid rise, healthcare authorities and organisations are under enormous pressure to create a sustainable environment for OHCs. Prior studies revealed that encouraging patient value co-creation behaviour (VCB) is substantially beneficial for successful OHCs; however, what factors influence these patient behaviours to co-create value is still unknown. To fill this gap, this study uses the service-dominant logic perspective of value co-creation theory and discloses how homophily between patient influencers and patients in OHCs effect VCB. The data was collected through a self-administered survey from 422 patients who are users of OHC in China and was analysed via partial least squares structural equation modelling and fuzzy set qualitative comparative analysis (fsQCA). The results revealed that homophily positively influences VCBs, i.e. participation behaviour (PB) and citizenship behaviour (CB). A parasocial relationship only moderates the relations between homophily and (PB), whereas the influencer ethical interaction capability significantly moderates the relationship of both homophily with patient PB and CB. Furthermore, the fsQCA findings signify the robustness of the study model. [ABSTRACT FROM AUTHOR]

Intellectual disability (ID), which affects around 2% to 3% of the population, accounts for 0.63% of the overall prevalence of neurodevelopmental disorders (NDD). ID is characterized by limitations in a person's intellectual and adaptive functioning, and is caused by pathogenic variants in more than 1000 genes. Here, we report a rare missense variant (c.350T>C; p.(Leu117Ser)) in HACE1 segregating with NDD syndrome with clinical features including ID, epilepsy, spasticity, global developmental delay, and psychomotor impairment in two siblings of a consanguineous Pakistani kindred. HACE1 encodes a HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1), which is involved in protein ubiquitination, localization, and cell division. HACE1 is also predicted to interact with several proteins that have been previously implicated in the ID phenotype in humans. The p.(Leu117Ser) variant replaces an evolutionarily conserved residue of HACE1 and is predicted to be deleterious by various in silico algorithms. Previously, eleven protein truncating variants of HACE1 have been reported in individuals with NDD. However, to our knowledge, p.(Leu117Ser) is the second missense variant in HACE1 found in an individual with NDD. [ABSTRACT FROM AUTHOR]

The article reports 7 pathogenic variants in five Hermansky-Pudlak syndrome (HPS) genes segregating with the phenotype in seven large consanguineous Pakistani families using whole-exome sequencing (WES). Detailed hematological examinations and chest computerized tomography (CT) scans were performed on the affective individuals. Data suggests a genotype-phenotype correlation where the missense alleles are hypomorphic and associated with a milder phenotype.

Melanocortin 1 receptor ( MC1R), a Gs protein-coupled receptor of the melanocyte's plasma membrane, is a major determinant of skin pigmentation and phototype. Upon activation by α-melanocyte stimulating hormone, MC1R triggers the cAMP cascade to stimulate eumelanogenesis. We used whole-exome sequencing to identify causative alleles in Pakistani families with skin and hair hypopigmentation. Six MC1R mutations segregated with the phenotype in seven families, including a p.Val174del in-frame deletion and a p.Tyr298* nonsense mutation, that were analyzed for function in heterologous HEK293 cells. p.Tyr298* MC1R showed no agonist-induced signaling to the cAMP or ERK pathways, nor detectable agonist binding. Conversely, signaling was comparable for p.Val174del and wild-type in HEK cells overexpressing the proteins, but binding analysis suggested impaired cell surface expression. Flow cytometry and confocal imaging studies revealed reduced plasma membrane expression of p.Val174del and p.Tyr298*. Therefore, p.Tyr298* was a total loss-of-function ( LOF) allele, while p.Val174del displayed a partial LOF attribute. [ABSTRACT FROM AUTHOR]

Face anti-spoofing is an important part of the face recognition algorithm that aims to prevent face presentation attacks. To facilitate face anti-spoofing research, this paper introduces a novel method in which a simple model provides enhanced performance on the RGB modality images of the CASIA-SURF dataset. Initially, a simple model based on ResNet-50 architecture is proposed that uses three residual layers of ResNet-50 along with a single neuron at the end for binary classification. Meanwhile, to judge the baseline performance, the proposed Resnet-50-based model is trained on the RGB and Depth images, separately. Later, to increase the performance of the proposed ResNet-50-based model on the RGB modality images, a novel Learning Using Privileged Information (LUPI) algorithm is applied. The LUPI contains Depth images and helps to train the inferior model with the help of a pre-trained superior model. Detailed simulations on the CASIA-SURF dataset reveal that an intelligent combination of the ResNet50 based model with the LUPI paradigm works exceptionally well and significantly improves the performance on the RGB modality of the images. The proposed model is less complex and can be deployed in resource-constrained environments. [ABSTRACT FROM AUTHOR]

Congenital disorders of glycosylation (CDG) are a large group of recessive multisystem disorders caused by impaired protein or lipid glycosylation. The CDG-I subgroup is characterized by protein N-glycosylation defects originating in the endoplasmic reticulum. The genetic defect is known for 17 different CDG-I subtypes. Patients in the few reported DPAGT1-CDG families exhibit severe intellectual disability (ID), epilepsy, microcephaly, severe hypotonia, facial dysmorphism and structural brain anomalies. In this study, we report a non-consanguineous family with two affected adults presenting with a relatively mild phenotype consisting of moderate ID, epilepsy, hypotonia, aggressive behavior and balance problems. Exome sequencing revealed a compound heterozygous missense mutation, c.85A>T (p.I29F) and c.503T>C (p.L168P), in the DPAGT1 gene. The affected amino acids are located in the first and fifth transmembrane domains of the protein. Isoelectric focusing and high-resolution mass spectrometry analyses of serum transferrin revealed glycosylation profiles that are consistent with a CDG-I defect. Our results show that the clinical spectrum of DPAGT1-CDG is much broader than appreciated so far. [ABSTRACT FROM AUTHOR]

Increasing the unplanned penetration of Distributed Generators (DGs) has spurred active and reactive power losses in the distribution system. This article suggests using a novel Strawberry Plant Propagation Algorithm (SPPA) for planning the placement of the DGs with the aim of reducing the network (active) power losses and improving the overall voltage profile. The proposed method (SPPA) has been tested on 33 and 69 node radial systems in MATLAB. A cost analysis was also performed and compared with other contemporary methods. The results for the considered variables show the significance of the proposed method in comparison to various other counterparts, including the Mine Blast Algorithm and Particle Swarm Optimization. [ABSTRACT FROM AUTHOR]

Considering the growing awareness and increased pressure from various stakeholders about sustainable development, organizations placed green initiatives among their top priority; however, in doing so, they are neglecting the role of knowledge resources. Taking the lead from the stakeholder theory, this research seeks to investigate the relations between stakeholders' pressure (SP), corporate social responsibility (CSR), green innovation (GI), and the knowledge management process (KMP). Data was gathered through a survey from 318 respondents of the manufacturing industries of Pakistan, and hypotheses were proved using structural equation modeling (SEM). The findings reveal that SP has a significant positive impact on the KMP, CSR, and GI. Further, KMP was found to partially mediates these relationships. The conclusion signifies the critical role that SP can play in attaining environmental protection outcomes through CSR and GI in manufacturing industries. This study suggests valuable insights to policymakers and practitioners as how to conserve and enhance the stability of the environment through KMP in emerging economies. • Stakeholders' pressure has a significant influence on CSR, GI, and KMP. • The KMP complementary partially mediates the relationship between stakeholders' pressure, CSR, and GI. • KMP is one of the significantly essential strategies for enhancing GI and CSR. • Drawing on the Stakeholder theory, the research framework was analyzed by PLS-SEM. [ABSTRACT FROM AUTHOR]

We report the underlying genetic causes of prelingual hearing loss (HL) segregating in eight large consanguineous families, ascertained from the Punjab province of Pakistan. Exome sequencing followed by segregation analysis revealed seven potentially pathogenic variants, including four novel alleles c.257G>A, c.6083A>C, c.89A>G, and c.1249A>G of CLPP, CDH23, COL4A5, and LARS2, respectively. We also identified three previously reported HL-causing variants (c.4528C>T, c.35delG, and c.1219T>C) of MYO15A, GJB2, and TMPRSS3 segregating in four families. All identified variants were either absent or had very low frequencies in the control databases. Our in silico analyses and 3-dimensional (3D) molecular modeling support the deleterious impact of these variants on the encoded proteins. Variants identified in MYO15A, GJB2, TMPRSS3, and CDH23 were classified as "pathogenic" or "likely pathogenic", while the variants in CLPP and LARS2 fall in the category of "uncertain significance" based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) variant pathogenicity guidelines. This paper highlights the genetic diversity of hearing disorders in the Pakistani population and reports the identification of four novel mutations in four HL families. [ABSTRACT FROM AUTHOR]

Although extensive studies have focused on the impact of different corporate social responsibility (CSR) activities on environmental sustainability, few studies investigated the effects of CSR activities on environmentally sustainable development and green innovation. Yet, as a determinant of environmental strategies, green innovation haven't received much attention. Therefore, this study explored how different CSR dimensions impacts on environmentally sustainable development and further on green innovation. Data were collected from 282 respondents belonging to the manufacturing industries of Pakistan from January 2019 to April 2019; and analyzed by adopting methods of partial least squares structural equation modeling (PLS-SEM) and grey relational analysis. As per study results, all dimensions of CSR were found positively significant towards environmentally sustainable development. Further, the environmentally sustainable development positively enhances green innovation. This research employed an innovative attempt to evaluate the ranking of these constructs by using grey relational analysis whereby it was found that CSR to environment had a stronger effect, whereas CSR to consumer had a weaker impact on environmentally sustainable development. The research findings suggest that CSR activities should be embedded in the organizational environmental strategies for green innovation, as all CSR dimensions had positive relations with environmentally sustainable development. • CSR practices have a significant influence on environmentally sustainable development. • CSR to environment have a stronger, and CSR to consumer have a weaker effect on environmentally sustainable development. • Environmentally sustainable development is one of the significantly important strategies for enhancing green innovation. • The theory of sustainable development was adopted for the research framework. • PLS-SEM and Grey relational analyses were employed to analyze the data of 282 respondents collected through questionnaire. [ABSTRACT FROM AUTHOR]

Purpose: Growing evidence asserts that individuals are inclined to buy impulsively in the social commerce environment due to interactive elements. However, extant literature does not reveal the influence of emerging digital celebrities and their communities on impulse buying, although users may encounter them synchronously. Hence, this study explores the impact of parasocial relationships and social climate on impulse buying following the stimulus–organism–response framework with the incorporation of the urge to buy. Besides, this research investigates the role of hedonic and utility gratification-seeking behavior in parasocial relationships following uses and gratifications theory (UGT). Design/methodology/approach: An empirical research study was conducted on Facebook, and data were collected from Pakistani users who followed digital celebrities. Partial least squares structural equation modeling (PLS-SEM) approach was employed to analyze the valid data of 231 respondents. Findings: The results indicate that integrated constructs significantly influence impulse buying with complementary partial mediation of urge to buy. Besides, social climate significantly interacts the relationship of parasocial relationships and impulse buying. Further, passing time, enjoyment and information seeking has a significant impact on parasocial relationships, except for self-presentation. Originality/value: This research provides key knowledge to comprehend the overall phenomenon of emerging digital celebrities through the integration of their parasocial relationships and the social climate of their communities, with potential intervening and interaction effects. This study also unveils the role of gratifications in building digital celebrities' parasocial relationships. [ABSTRACT FROM AUTHOR]

Fuzzy set theory is the most powerful tool to describe the process of uncertainty which exist in real world and fuzzy regression is an important research topic which can be used for prediction by establishing the functional relationship between fuzzy variables. Quantile regression is also a significant statistical method for estimating and drawing inferences about conditional quantile functions. This study introduced the idea of quantile regression with respect to fuzzy. The ordinary fuzzy regression is based on least square method but here we have introduced the idea of weighted least absolute deviation method in fuzzy regression. We have considered two different cases for the illustration of our proposed technique, firstly when the input and output are taken as fuzzy and secondly, the input and output are taken as fuzzy but the parameters are crisp. The algorithm for each case is based on linear programming problem (LPP). The LPP is constructed for individual case and solved it by the method of Simplex procedure. The proposed work is then compared with the conventional fuzzy regression by using AIC criterion. Empirical study shows that the proposed technique works best in every situation where the fuzzy regression fails and also provide the results in depth. [ABSTRACT FROM AUTHOR]

Nonsyndromic oculocutaneous Albinism (nsOCA) is clinically characterized by the loss of pigmentation in the skin, hair, and iris. OCA is amongst the most common causes of vision impairment in children. To date, pathogenic variants in six genes have been identified in individuals with nsOCA. Here, we determined the identities, frequencies, and clinical consequences of OCA alleles in 94 previously unreported Pakistani families. Combination of Sanger and Exome sequencing revealed 38 alleles, including 22 novel variants, segregating with nsOCA phenotype in 80 families. Variants of TYR and OCA2 genes were the most common cause of nsOCA, occurring in 43 and 30 families, respectively. Twenty-two novel variants include nine missense, four splice site, two non-sense, one insertion and six gross deletions. In vitro studies revealed retention of OCA proteins harboring novel missense alleles in the endoplasmic reticulum (ER) of transfected cells. Exon-trapping assays with constructs containing splice site alleles revealed errors in splicing. As eight alleles account for approximately 56% (95% CI: 46.52-65.24%) of nsOCA cases, primarily enrolled from Punjab province of Pakistan, hierarchical strategies for variant detection would be feasible and cost-efficient genetic tests for OCA in families with similar origin. Thus, we developed Tetra-primer ARMS assays for rapid, reliable, reproducible and economical screening of most of these common alleles. [ABSTRACT FROM AUTHOR]

Congenital idiopathic nystagmus (CIN) is an oculomotor disorder characterized by repetitive and rapid involuntary movement of the eye that usually develops in the first six months after birth. Unlike other forms of nystagmus, CIN is widely associated with mutations in the FRMD7 gene. This study involves the molecular genetic analysis of a consanguineous Pakistani family with individuals suffering from CIN to undermine any potential pathogenic mutations. Blood samples were taken from affected and normal individuals of the family. Genomic DNA was extracted using an in-organic method. Whole Exome Sequencing (WES) and analysis were performed to find any mutations in the causative gene. To validate the existence and co-segregation of the FRMD7 gene variant found using WES, sanger sequencing was also carried out using primers that targeted all of the FRMD7 coding exons. Additionally, the pathogenicity of the identified variant was assessed using different bioinformatic tools. The WES results identified a novel nonsense mutation in the FRMD7 (c.443T>A; p. Leu148 *) gene in affected individuals from the Pakistani family, with CIN resulting in a premature termination codon, further resulting in the formation of a destabilized protein structure that was incomplete. Co-segregation analysis revealed that affected males are hemizygous for the mutated allele c.443T>A; p. Leu148 * and the affected mother is heterozygous. Overall, such molecular genetic studies expand our current knowledge of the mutations associated with the FRMD7 gene in Pakistani families with CIN and significantly enhance our understanding of the molecular mechanisms involved in genetic disorders. [ABSTRACT FROM AUTHOR]

Renewable energy resources have gained considerable attention in recent years due to their efficiency and economic benefits. Their proportion of total energy use continues to grow over time. Photovoltaic (PV) cell and wind energy generation are the least-expensive new energy sources in most countries. Renewable energy technologies significantly contribute to climate mitigation and provide economic benefits. Apart from these advantages, renewable energy sources, particularly solar energy, have drawbacks, for instance restricted energy supply, reliance on weather conditions, and being affected by several kinds of faults, which cause a high power loss. Usually, the local PV plants are small in size, and it is easy to trace any fault and defect; however, there are many PV cells in the grid-connected PV system where it is difficult to find a fault. Keeping in view the aforedescribed facts, this paper presents an intelligent model to detect faults in the PV panels. The proposed model utilizes the Convolutional Neural Network (CNN), which is trained on historic data. The dataset was preprocessed before being fed to the CNN. The dataset contained different parameters, such as current, voltage, temperature, and irradiance, for five different classes. The simulation results showed that the proposed CNN model achieved a training accuracy of 97.64% and a testing accuracy of 95.20%, which are much better than the previous research performed on this dataset. [ABSTRACT FROM AUTHOR]

The proposed work uses fixed lag smoothing on the interactive multiple model-integrated probabilistic data association algorithm (IMM-IPDA) to enhance its performance. This approach makes use of the advantages of the fixed lag smoothing algorithm to track the motion of a maneuvering target while it is surrounded by clutter. The suggested method provides a new mathematical foundation in terms of smoothing for mode probabilities in addition to the target trajectory state and target existence state by including the smoothing advantages. The suggested fixed lag smoothing IMM-IPDA (FLs IMM-IPDA) method's root mean square error (RMSE), true track rate (TTR), and mode probabilities are compared to those of other recent algorithms in the literature in this study. The results clearly show that the proposed algorithm outperformed the already-known methods in the literature in terms of these above parameters of interest. [ABSTRACT FROM AUTHOR]

To delineate the genetic bases of primary congenital glaucoma (PCG), we ascertained a large cohort consisting of 48 consanguineous families. Of these, we previously reported 26 families with mutations in CYP1B1 and six families with LTBP2, whereas the genetic bases responsible for PCG in 16 families remained elusive. We employed next-generation whole exome sequencing to delineate the genetic basis of PCG in four of these 16 familial cases. Exclusion of linkage to reported PCG loci was established followed by next-generation whole exome sequencing, which was performed on 10 affected individuals manifesting cardinal systems of PCG belonging to four unresolved families along with four control samples consisting of genomic DNAs of individuals harboring mutations in CYP1B1 and LTBP2. The analyses of sequencing datasets failed to identify potential causal alleles in the 10 exomes whereas c.1169G > A (p. Arg390His) in CYP1B1 and c.3427delC (p.Gln1143Argfs*35) in LTBP2 were identified in the control samples. Taken together, next-generation whole exome sequencing failed to delineate the genetic basis of PCG in familial cases excluded from mutations in CYP1B1 and LTBP2. These data strengthen the notion that compound heterozygous coding variants or non-coding variants might contribute to PCG. [ABSTRACT FROM AUTHOR]

Surveillance of genetic diversity of the SARS‐CoV‐2 is extremely important to detect the emergence of more infectious and deadly strains of the virus. In this study, we evaluated mutational events in the SARS‐CoV‐2 genomes through whole genome sequencing. The samples were collected from COVID‐19 patients in different major cities of Pakistan during the four waves of the pandemic (May 2020 to July 2021) and subjected to whole genome sequencing. Using in silico and machine learning tools, the viral mutational events were analyzed, and variants of concern and of interest were identified during each of the four waves. The overall mutation frequency (mutations per genome) increased during the course of the pandemic from 12.19 to 23.63, 31.03, and 41.22 in the first, second, third, and fourth waves, respectively. We determined that the viral strains rose to higher frequencies in local transmission. The first wave had three most common strains B.1.36, B.1.160, and B.1.255, the second wave comprised B.1.36 and B.1.247 strains, the third wave had B.1.1.7 (Alpha variant) and B.1.36 strains, and the fourth waves comprised B.1.617.2 (Delta). Intriguingly, the B.1.36 variants were found in all the waves of the infection indicating their survival fitness. Through phylogenetic analysis, the probable routes of transmission of various strains in the country were determined. Collectively, our study provided an insight into the evolution of SARS‐CoV‐2 lineages in the spatiotemporal local transmission during different waves of the pandemic, which aided the state institutions in implementing adequate preventive measures. [ABSTRACT FROM AUTHOR]

Fiscal decentralization implies the transfer of fiscal and financial authority to local government, which is highly integrated with sustainable economic decisions. Against this backdrop, this research examines the asymmetric impact of fiscal decentralization, green investment, and renewable energy consumption on ecological footprints from the context of selected OECD member states during 1990–2019. Moreover, it also examines the moderating role of fiscal decentralization in promoting green investment and, subsequently, environmental sustainability. For this purpose, advanced panel data estimators are applied to confirm cross-sectional dependency, unit-roots, and cointegration among model variables. Besides linear heterogeneous estimators, this research uses methods of moments quantile regression (MMQR) to integrate asymmetric behaviors of regressors. The preliminary results confirm cross-sectional dependence, non-stationarity, and cointegration properties among the variables of interest. The overall findings report that fiscal decentralization, green investment, and renewable energy consumption play a significant role in reducing the ecological footprints; however, their effects significantly varied across lower, medium, and higher quantiles. Particularly, these effects are more pronounced from middle to highest quantiles. Moreover, the interactive effects of fiscal decentralization and green investment are strongly negative, implying a substantial decrease in the ecological footprints of sample countries. These results suggest that fiscal decentralization improves environmental sustainability through green investment and renewable energy transition. [Display omitted] [ABSTRACT FROM AUTHOR]

China's tourism industry is under transition towards sustainable tourism. This study's primary purpose is to propose a novel framework that green core competence enhances the tourism industry's green absorptive capacity and green innovation performance. Additionally, green absorptive capacity mediates the relationship between green core competence and green innovation. And finally, green organizational culture moderates the relationship between green absorptive capacity and green innovation. Data were collected from different hotels and restaurants in the North East of China, practicing environmentally friendly green practices through convenient sampling. The PLS-SEM technique was used to test each hypothesis. The results showed that green core competence positively and significantly affects green innovation performance, and green absorptive capacity mediates the relationship between green core competencies and green innovation performance. Moreover, green organizational culture partially moderates the relationship between green absorptive capacity and green innovation. [ABSTRACT FROM AUTHOR]

Genetic analysis of an inbred Pakistani family PKDF280, segregating prelingual severe to profound sensorineural hearing loss, provided evidence for a DFNB locus on human chromosome 9q34.3. Co-segregation of the deafness trait with marker D9SH159 was determined by a two-point linkage analysis (LOD score 9.43 at θ=0). Two additional large families, PKDF517 and PKDF741, co-segregate recessive deafness with markers linked to the same interval. Haplotype analyses of these three families refined the interval to 3.84 Mb defined by D9S1818 (centromeric) and D9SH6 (telomeric). This interval overlaps with the previously reported DFNB33 locus whose chromosomal map position has been recently revised and assigned to a new position on chromosome 10p11.23–q21.1. The nonsyndromic deafness locus on chromosome 9q segregating in family PKDF280 was designated DFNB79. We are currently screening the 113 candidate DFNB79 genes for mutations and have excluded CACNA1B, EDF1, PTGDS, EHMT1, QSOX2, NOTCH1, MIR126 and MIR602. [ABSTRACT FROM AUTHOR]

The role of environmental information disclosure (EID) in debt financing for penalized enterprises remains limited in the current literature. This research seeks to investigate this topic by focusing on manufacturing firms that have been penalized by the Chinese government for violating environmental rules and regulations. Further, it analyzes how environmental administrative penalties impact the debt cost in the following year. Based on our results, the environmental administrative penalty significantly increases the debt cost in the following year through the negative increment of the company's disclosure quality, and the incremental disclosure plays a mediating role in this relationship. Besides, it has also been found that environmental administrative penalties cannot affect the debt cost by changing the disclosure level. While the existing literature has established that environmental penalties can lead to changes in corporate information disclosure, this research contributes to this literature by revealing that the decline of environmental disclosure quality of penalized firms leads to the increase of financing costs. [Display omitted] • Environmental administrative penalty significantly increases the corporate debt cost in the following year. • The disclosure increment plays a mediating role in the relationship between environmental administrative penalty and the debt cost. • The environmental administrative penalty increases the debt cost through the negative increment of the company's disclosure quality. [ABSTRACT FROM AUTHOR]

Adaptor protein (AP) complexes mediate selective intracellular vesicular trafficking and polarized localization of somatodendritic proteins in neurons. Disease-causing alleles of various subunits of AP complexes have been implicated in several heritable human disorders, including intellectual disabilities (IDs). Here, we report two bi-allelic (c.737C>A [p.Pro246His] and c.1105A>G [p.Met369Val]) and eight de novo heterozygous variants (c.44G>A [p.Arg15Gln], c.103C>T [p.Arg35Trp], c.104G>A [p.Arg35Gln], c.229delC [p.Gln77Lys∗11], c.399_400del [p.Glu133Aspfs∗37], c.747G>T [p.Gln249His], c.928−2A>C [p.?], and c.2459C>G [p.Pro820Arg]) in AP1G1 , encoding gamma-1 subunit of adaptor-related protein complex 1 (AP1γ1), associated with a neurodevelopmental disorder (NDD) characterized by mild to severe ID, epilepsy, and developmental delay in eleven families from different ethnicities. The AP1γ1-mediated adaptor complex is essential for the formation of clathrin-coated intracellular vesicles. In silico analysis and 3D protein modeling simulation predicted alteration of AP1γ1 protein folding for missense variants, which was consistent with the observed altered AP1γ1 levels in heterologous cells. Functional studies of the recessively inherited missense variants revealed no apparent impact on the interaction of AP1γ1 with other subunits of the AP-1 complex but rather showed to affect the endosome recycling pathway. Knocking out ap1g1 in zebrafish leads to severe morphological defect and lethality, which was significantly rescued by injection of wild-type AP1G1 mRNA and not by transcripts encoding the missense variants. Furthermore, microinjection of mRNAs with de novo missense variants in wild-type zebrafish resulted in severe developmental abnormalities and increased lethality. We conclude that de novo and bi-allelic variants in AP1G1 are associated with neurodevelopmental disorder in diverse populations. [ABSTRACT FROM AUTHOR]

Peroxisomes, single-membrane intracellular organelles, play an important role in various metabolic pathways. The translocation of proteins from the cytosol to peroxisomes depends on peroxisome import receptor proteins and defects in peroxisome transport result in a wide spectrum of peroxisomal disorders. Here, we report a large consanguineous family with autosomal recessive congenital cataracts and developmental defects. Genome-wide linkage analysis localized the critical interval to chromosome 12p with a maximum two-point LOD score of 4.2 (θ = 0). Next-generation exome sequencing identified a novel homozygous missense variant (c.653 T > C; p.F218S) in peroxisomal biogenesis factor 5 (PEX5), a peroxisome import receptor protein. This missense mutation was confirmed by bidirectional Sanger sequencing. It segregated with the disease phenotype in the family and was absent in ethnically matched control chromosomes. The lens-specific knockout mice of Pex5 recapitulated the cataractous phenotype. In vitro import assays revealed a normal capacity of the mutant PEX5 to enter the peroxisomal Docking/Translocation Module (DTM) in the presence of peroxisome targeting signal 1 (PTS1) cargo protein, be monoubiquitinated and exported back into the cytosol. Importantly, the mutant PEX5 protein was unable to form a stable trimeric complex with peroxisomal biogenesis factor 7 (PEX7) and a peroxisome targeting signal 2 (PTS2) cargo protein and, therefore, failed to promote the import of PTS2 cargo proteins into peroxisomes. In conclusion, we report a novel missense mutation in PEX5 responsible for the defective import of PTS2 cargo proteins into peroxisomes resulting in congenital cataracts and developmental defects. [ABSTRACT FROM AUTHOR]

COCH is the most abundantly expressed gene in the cochlea. Unsurprisingly, mutations in COCH underly hearing loss in mice and humans. Two forms of hearing loss are linked to mutations in COCH, the well-established autosomal dominant nonsyndromic hearing loss, with or without vestibular dysfunction (DFNA9) via a gain-of-function/dominant-negative mechanism, and more recently autosomal recessive nonsyndromic hearing loss (DFNB110) via nonsense variants. Using a combination of targeted gene panels, exome sequencing, and functional studies, we identified four novel pathogenic variants (two nonsense variants, one missense, and one inframe deletion) in COCH as the cause of autosomal recessive hearing loss in a multi-ethnic cohort. To investigate whether the non-truncating variants exert their effect via a loss-of-function mechanism, we used minigene splicing assays. Our data showed both the missense and inframe deletion variants altered RNA splicing by creating an exon splicing silencer and abolishing an exon splicing enhancer, respectively. Both variants create frameshifts and are predicted to result in a null allele. This study confirms the involvement of loss-of-function mutations in COCH in autosomal recessive nonsyndromic hearing loss, expands the mutational landscape of DFNB110 to include coding variants that alter RNA splicing, and highlights the need to investigate the effect of coding variants on RNA splicing. [ABSTRACT FROM AUTHOR]

Intellectual disability (ID) is a genetically and clinically heterogeneous disorder, characterized by limited cognitive abilities and impaired adaptive behaviors. In recent years, exome sequencing (ES) has been instrumental in deciphering the genetic etiology of ID. Here, through ES of a large cohort of individuals with ID, we identified two bi-allelic frameshift variants in METTL5 , c.344_345delGA (p.Arg115Asnfs∗19) and c.571_572delAA (p.Lys191Valfs∗10), in families of Pakistani and Yemenite origin. Both of these variants were segregating with moderate to severe ID, microcephaly, and various facial dysmorphisms, in an autosomal-recessive fashion. METTL5 is a member of the methyltransferase-like protein family, which encompasses proteins with a seven-beta-strand methyltransferase domain. We found METTL5 expression in various substructures of rodent and human brains and METTL5 protein to be enriched in the nucleus and synapses of the hippocampal neurons. Functional studies of these truncating variants in transiently transfected orthologous cells and cultured hippocampal rat neurons revealed no effect on the localization of METTL5 but alter its level of expression. Our in silico analysis and 3D modeling simulation predict disruption of METTL5 function by both variants. Finally, mettl5 knockdown in zebrafish resulted in microcephaly, recapitulating the human phenotype. This study provides evidence that biallelic variants in METTL5 cause ID and microcephaly in humans and highlights the essential role of METTL5 in brain development and neuronal function. [ABSTRACT FROM AUTHOR]

Short moving primary and rigid low‐cost secondary are important requirements of linear machines designed for long stroke applications. In the race, linear permanent magnet flux switching machine (LPMFSM) is a competitive candidate by confining excitation sources to short mover, thus making stator robust and low cost (made of only iron). However, single‐sided LPMFSM exhibit a demerit of high normal (attraction) force due to its topology. In order to rectify the problem and enhance thrust force profile, two novel double‐sided LPMFSMs are proposed with dual stator and dual mover topologies. After stator pole study, both topologies with same design dimensions are analysed and compared by 2‐D finite element method here. Detailed analysis revealed that 12/14 DMLPMFSM exhibit low numerical values of thrust force ripples and detent force while maintaining average thrust force value. Hence, 12/14 DMLPMFSM is selected and optimised by structure‐based deterministic optimisation (SBDO) approach to further enhance thrust force profile. Finally, comparison of initial and optimised design of 12/14 DMLPMFSM is presented to validate optimisation procedure. [ABSTRACT FROM AUTHOR]

CIB2 and GJB2 genes variants contribute significantly in familial cases of prelingual recessive hearing loss (HL). This study was aimed to determine the CIB2 and GJB2 variants and associated phenotype in 150 non-familial individuals with HL. After getting informed consent, 150 non-familial deaf patients were enrolled and blood samples were obtained for DNA extraction. Pure tone air conduction audiometry was performed. Coding exons of CIB2 and GJB2 genes were Sanger sequenced. A tetra primer ARMS assay was developed for recurrent CIB2 variant. Four bi-allelic GJB2 variants, c.71G>A p.(Trp24*), c.231G>A p.(Trp77*), c.235delC p.(Leu79Cysfs3*) and c.35delG p.(Gly11Leufs24*), were found in nine hearing impaired individuals. We also found four homozygotes and five carriers of c.380G>A p. (Arg127His) variant of controversial clinical significance. CIB2 sequencing revealed single recurrent variant c.272T>C p. (Phe91Ser) segregating with HL in ten individuals. Among our patients, c.71G>A (p.Trp24*) was the most common variant, accounted for 45% of GJB2 variants. Two known GJB2 variants, c.235delC p. (Leu79Cysfs3*) and c.310del14 p. (Lys105Argfs2*), are reported here for the first time in Pakistani population. Our data further support the benign nature of c.380G>A p. (Arg127His) variant. For CIB2, c.272T>C p. (Phe91Ser) is the second common cause of HL among our sporadic cases. Phenotypically, in our patients, individuals homozygous for GJB2 variants had profound HL, whereas CIB2 homozygotes had severe to profound prelingual HL. Our results suggest that GJB2 and CIB2 are common cause of HL in different Pakistani ethnicities. [ABSTRACT FROM AUTHOR]

While there is growing adoption of social media by environmental stakeholders, whether and how social media green communities affect netizens' pro-environmental behavior is understudied. Underpinned by social learning theory, this study explores the relation of green community browsing to netizens' pro-environmental behavior, the underlying mechanisms, and the interactive role of a critical social cue. Results of structural equation modeling in a sample of 585 members of green communities indicate that green communities' browsing has a significant relationship with pro-environmental behavior through the sequential mediation of participation and environmental concern. The volume of likes strengthens the relationship between netizens' browsing of green communities and participation. This novel study offers valuable insights into the role of social media green communities. • Browsing of green communities is positively related to pro-environmental behavior. • Social learning theory is adopted for the proposed framework. • Participation and environmental concern are recognized as significant mediator. • PLS-SEM was employed to analyze the data of 585 followers of green communities. • Volume of likes strengthens the association between browsing and participation. [ABSTRACT FROM AUTHOR]

Chrysobacterium indologenes is an emerging MDR pathogen that belongs to the family Flavobacteriaceae. The genome of the C. indologenes, isolated from the nephrotic patient, was sequenced through Illumina MiSeq. The pangenomics of available 56 C. indologenes strains using BPGA revealed an open pangenome (n=5553 CDS), core genome (2141), and accessory genome (2013). The CEG/DEG database identified 662 essential genes that drastically reduced to 68 genes after non-homology analyses towards human and gut microbiome. Further filtering the data for other drug target prioritizing parameters resulted in 32 putative targets. Keeping in view the crucial role played in cell wall biosynthesis, dacB was selected as the final target that encodes D-alanyl- d -alanine carboxypeptidase/endopeptidase (DD-peptidase). The 3D structure of dacB was modelled and rendered to docking analyses against two compound libraries of African plants (n=6842) and Tibetan medicines (n=52). The ADMET profiling exhibited the physicochemical properties of final compounds. The MD simulations showed the stability of inhibitor-DD-peptidase complex and interactions in terms of RMSD, RMSF, binding free energy calculation and H-bonding. We propose that the novel compounds Leptopene and ZINC95486338 from our findings might be potent DD-peptidase inhibitors that could aid in the development of new antibiotic-resistant therapy for the emerging MDR C. indologenes. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NGS) of exomes and genomes has accelerated the identification of genes involved in Mendelian phenotypes. However, many NGS studies fall short of identifying causal variants, with estimates for success rates as low as 25% for uncovering the pathological variant underlying disease etiology. An important reason for such failures is familial locus heterogeneity, where within a single pedigree causal variants in two or more genes underlie Mendelian trait etiology. As examples of intra- and inter-sibship familial locus heterogeneity, we present 10 consanguineous Pakistani families segregating hearing impairment due to homozygous variants in two different hearing impairment genes and a European-American pedigree in which hearing impairment is caused by four variants in three different genes. We have identified 41 additional pedigrees with syndromic and nonsyndromic hearing impairment for which a single previously reported hearing impairment gene has been identified but only segregates with the phenotype in a subset of affected pedigree members. We estimate that locus heterogeneity occurs in 15.3% (95% confidence interval: 11.9%, 19.9%) of the families in our collection. We demonstrate novel approaches to apply linkage analysis and homozygosity mapping (for autosomal recessive consanguineous pedigrees), which can be used to detect locus heterogeneity using either NGS or SNP array data. Results from linkage analysis and homozygosity mapping can also be used to group sibships or individuals most likely to be segregating the same causal variants and thereby increase the success rate of gene identification. [ABSTRACT FROM AUTHOR]

Pathogenic mutations of MARVELD2, encoding tricellulin, a tricelluar tight junction protein, cause autosomal recessive non-syndromic hearing loss (DFNB49) in families of Pakistan and Czech Roma origin. In fact, they are a significant cause of prelingual hearing loss in the Czech Roma, second only to GJB2 variants. Previously, we reported that mice homozygous for p.Arg497* variant of Marveld2 had a broad phenotypic spectrum, where defects were observed in the inner ear, heart, mandibular salivary gland, thyroid gland and olfactory epithelium. The current study describes the types and frequencies of MARVELD2 alleles and clinically reexamines members of DFNB49 families. We found that MARVELD2 variants are responsible for about 1.5 % (95 % CI 0.8-2.6) of non-syndromic hearing loss in our cohort of 800 Pakistani families. The c.1331+2T>C allele is recurrent. In addition, we identified a novel large deletion in a single family, which appears to have resulted from non-allelic homologous recombination between two similar Alu short interspersed elements. Finally, we observed no other clinical manifestations co-segregating with hearing loss in DFNB49 human families, and hypothesize that the additional abnormalities in the Marveld2 mutant mouse indicates a critical non-redundant function for tricellulin in other organ systems. [ABSTRACT FROM AUTHOR]

We assessed a large consanguineous Pakistani family (PKAB157) segregating early onset low vision problems. Funduscopic and electroretinographic evaluation of affected individuals revealed juvenile cone-rod dystrophy (CRD) with maculopathy. Other clinical symptoms included loss of color discrimination, photophobia and nystagmus. Whole-exome sequencing, segregation and haplotype analyses demonstrated that a transition variant (c.955T>C; p.(Cys319Arg)) in CNGA3 co-segregated with the CRD phenotype in family PKAB157. The ability of CNGA3 channel to influx calcium in response to agonist, when expressed either alone or together with the wild-type CNGB3 subunit in HEK293 cells, was completely abolished due to p.Cys319Arg variant. Western blotting and immunolocalization studies suggest that a decreased channel density in the HEK293 cell membrane due to impaired folding and/or trafficking of the CNGA3 protein is the main pathogenic effect of the p.Cys319Arg variant. Mutant alleles of the human cone photoreceptor cyclic nucleotide-gated channel (CNGA3) are frequently associated with achromatopsia. In rare cases, variants in CNGA3 are also associated with cone dystrophy, Leber's congenital amaurosis and oligo cone trichromacy. The identification of predicted p.(Cys319Arg) missense variant in CNGA3 expands the repertoire of the known genetic causes of CRD and phenotypic spectrum of CNGA3 alleles. [ABSTRACT FROM AUTHOR]

Here we demonstrate association of variants in the mitochondrial asparaginyl-tRNA synthetase NARS2 with human hearing loss and Leigh syndrome. A homozygous missense mutation ([c.637G>T; p.Val213Phe]) is the underlying cause of nonsyndromic hearing loss (DFNB94) and compound heterozygous mutations ([c.969T>A; p.Tyr323*] + [c.1142A>G; p.Asn381Ser]) result in mitochondrial respiratory chain deficiency and Leigh syndrome, which is a neurodegenerative disease characterized by symmetric, bilateral lesions in the basal ganglia, thalamus, and brain stem. The severity of the genetic lesions and their effects on NARS2 protein structure cosegregate with the phenotype. A hypothetical truncated NARS2 protein, secondary to the Leigh syndrome mutation p.Tyr323* is not detectable and p.Asn381Ser further decreases NARS2 protein levels in patient fibroblasts. p.Asn381Ser also disrupts dimerization of NARS2, while the hearing loss p.Val213Phe variant has no effect on NARS2 oligomerization. Additionally we demonstrate decreased steady-state levels of mt-tRNAAsn in fibroblasts from the Leigh syndrome patients. In these cells we show that a decrease in oxygen consumption rates (OCR) and electron transport chain (ETC) activity can be rescued by overexpression of wild type NARS2. However, overexpression of the hearing loss associated p.Val213Phe mutant protein in these fibroblasts cannot complement the OCR and ETC defects. Our findings establish lesions in NARS2 as a new cause for nonsyndromic hearing loss and Leigh syndrome. [ABSTRACT FROM AUTHOR]

Backgrounds and Aims: Next generation sequencing (NGS) approaches have revolutionized the identification of mutations underlying genetic disorders. This technology is particularly useful for the identification of mutations in known and new genes for conditions with extensive genetic heterogeneity. In the present study we investigated a consanguineous Pakistani family with intellectual disability (ID). Methods: Genotyping was carried out using 250k and 6k SNP microarrays in order to perform homozygosity mapping and copy number variation (CNV) analysis. Targeted NGS was performed to identify the genetic defect in this family. qPCR was performed to validate and confirm the NGS result. Results: Homozygosity mapping positioned the causative defect on chromosome 2p25.3–p25.2. Subsequent targeted NGS revealed an intragenic deletion of five exons of the gene TPO. Conclusions: NGS is a powerful method to uncover submicroscopic structural variations. This result demonstrates that an unbiased screening approach such as NGS can help to identify even unexpected disease-causing mutations. [ABSTRACT FROM AUTHOR]

A missense mutation of Gipc3 was previously reported to cause age-related hearing loss in mice. Point mutations of human GIPC3 were found in two small families, but association with hearing loss was not statistically significant. Here, we describe one frameshift and six missense mutations in GIPC3 cosegregating with DFNB72 hearing loss in six large families that support statistically significant evidence for genetic linkage. However, GIPC3 is not the only nonsyndromic hearing impairment gene in this region; no GIPC3 mutations were found in a family cosegregating hearing loss with markers of chromosome 19p. Haplotype analysis excluded GIPC3 from the obligate linkage interval in this family and defined a novel locus spanning 4.08 Mb and 104 genes. This closely linked but distinct nonsyndromic hearing loss locus was designated DFNB81. [ABSTRACT FROM AUTHOR]

There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132 and PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively. Family PKDF740 is segregating congenital blindness, mild-to-profound progressive hearing loss that is characteristic of Norrie disease (MIM#310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c.49delG causing a frameshift and premature truncation (p.V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling and molecular epidemiology of hearing loss among Pakistanis. [ABSTRACT FROM AUTHOR]

Targeted genome capture combined with next-generation sequencing was used to analyze 2.9 Mb of the DFNB79 interval on chromosome 9q34.3, which includes 108 candidate genes. Genomic DNA from an affected member of a consanguineous family segregating recessive, nonsyndromic hearing loss was used to make a library of fragments covering the DFNB79 linkage interval defined by genetic analyses of four pedigrees. Homozygosity for eight previously unreported variants in transcribed sequences was detected by evaluating a library of 402,554 sequencing reads and was later confirmed by Sanger sequencing. Of these variants, six were determined to be polymorphisms in the Pakistani population, and one was in a noncoding gene that was subsequently excluded genetically from the DFNB79 linkage interval. The remaining variant was a nonsense mutation in a predicted gene, C9orf75, renamed TPRN. Evaluation of the other three DFNB79-linked families identified three additional frameshift mutations, for a total of four truncating alleles of this gene. Although TPRN is expressed in many tissues, immunolocalization of the protein product in the mouse cochlea shows prominent expression in the taper region of hair cell stereocilia. Consequently, we named the protein taperin. [ABSTRACT FROM AUTHOR]

Automatic License Plate Detection (ALPD) is an integral component of using computer vision approaches in Intelligent Transportation Systems (ITS). An accurate detection of vehicles' license plates in images is a critical step that has a substantial impact on any ALPD system's recognition rate. In this paper, we develop an efficient license plate detecting technique through the intelligent combination of Faster R-CNN along with digital image processing techniques. The proposed algorithm initially detects vehicle(s) in the input image through Faster R-CNN. Later, the located vehicle is analyzed by a robust License Plate Localization Module (LPLM). The LPLM module primarily uses color segmentation and processes the HSV image to detect the license plate in the input image. Moreover, the LPLM module employs morphological filtering and dimension analysis to find the license plate. Detailed trials on challenging PKU datasets demonstrate that the proposed method outperforms few recently developed methods by producing high license plates detection accuracy in much less execution time. The proposed work demonstrates a great feasibility for security and target detection applications. [ABSTRACT FROM AUTHOR]

Linear Flux Switching Machines (LFSMs) possess the capability to generate adhesive thrust force, thus problems associated with conventional rotatory electric machines and mechanical conversion assemblies can be eliminated. Additionally, the unique features of high force/power density, efficiency, and a robust secondary structure make LFSMs a suitable candidate for linear motion applications. However, deficiency of controllable air-gap flux, risk of PM demagnetization, and increasing cost of rare earth PM materials in case of PMLFSMs, and inherent low thrust force capability of Field Excited LFSMs compels researchers to investigate new hybrid topologies. In this paper, a novel Double-Sided Hybrid Excited LFSM (DSHELFSM) with all three excitation sources, i.e., PMs, DC, and AC windings confined to short moving primary and segmented secondary providing short flux paths is designed, investigated, and optimized. Secondly, unequal primary tooth width optimization and additional end-teeth at all four corners of the primary equip proposed design with balanced magnetic circuit and reduced end-effect and thrust force ripples. Thirdly, the measured experimental results of the manufactured proposed machine prototype are compared with corresponding simulated model results and shows good agreements, thus validating the theoretical study. [ABSTRACT FROM AUTHOR]

Melanin pigment helps protect our body from broad wavelength solar radiation and skin cancer. Among other pigmentation disorders in humans, albinism is reported to manifest in both syndromic and nonsyndromic forms as well as with varying inheritance patterns. Oculocutaneous albinism (OCA), an autosomal recessive nonsyndromic form of albinism, presents as partial to complete loss of melanin in the skin, hair, and iris. OCA has been known to be caused by pathogenic variants in seven different genes, so far, according to all the currently published population studies. However, the detection rate of alleles causing OCA varies from 50% to 90%. One of the significant challenges of uncovering the pathological variant underlying disease etiology is inter- and intra-familial locus heterogeneity. This problem is especially pertinent in highly inbred populations. As examples of such familial locus heterogeneity, we present nine consanguineous Pakistani families with segregating OCA due to variants in one or two different known albinism-associated genes. All of the identified variants are predicted to be pathogenic, which was corroborated by several in silico algorithms and association with diverse clinical phenotypes. We report an individual affected with OCA carries heterozygous, likely pathogenic variants in TYR and OCA2, raising the question of a possible digenic inheritance. Altogether, our study highlights the significance of exome sequencing for the complete genetic diagnosis of inbred families and provides the ramifications of potential genetic interaction and digenic inheritance of variants in the TYR and OCA2 genes. [ABSTRACT FROM AUTHOR]

Social commerce has altered the consumption experience due to various interactive factors. Growing evidence stated that users are prone to buy impulsively in such an environment. Prior studies were limited to demonstrate the emerging role of social media celebrities and embedded social interaction in the context of impulse buying though users encounter them concurrently and frequently while browsing. Hence, this study investigated the influence of celebrities' post authenticity, sentiment polarity, observational learning, and impulse buying tendency following the latent state-trait theory. We have used the data of 452 Pakistani respondents to empirically investigate the research model collected via an online questionnaire from celebrities' community on Facebook. This study employed partial least squares structural equation modeling (PLS-SEM) and fuzzy set qualitative comparative analysis (fsQCA) to analyze data. The findings revealed that proposed constructs significantly influence the urge to buy impulsively. Further, impulse buying tendency moderates all relationships except negative sentiments. Unexpectedly, the moderation effects of celebrities' authenticity are insignificant. Furthermore, fsQCA results show the robustness of constructs towards urge to buy impulsively. The theoretical and managerial implications with limitations are provided in the paper. • Social media celebrities post and contextual interaction have a significant impact on impulse buying. • Latent state-trait theory was adopted for the research framework. • PLS-SEM was employed to analyze the data of 452 respondents collected via online questionnaire from Facebook.com. • Impulse buying tendency significantly interacts all relationships except negative sentiments. [ABSTRACT FROM AUTHOR]

Human pathogenic variants of TBC1D24 are associated with clinically heterogeneous phenotypes, including recessive nonsyndromic deafness DFNB86, dominant nonsyndromic deafness DFNA65, seizure accompanied by deafness, a variety of isolated seizure phenotypes and DOORS syndrome, characterized by deafness, onychodystrophy, osteodystrophy, intellectual disability and seizures. Thirty-five pathogenic variants of human TBC1D24 associated with deafness have been reported. However, functions of TBC1D24 in the inner ear and the pathophysiology of TBC1D24-related deafness are unknown. In this study, a novel splice-site variant of TBC1D24 c.965 + 1G > A in compound heterozygosity with c.641G > A p.(Arg214His) was found to be segregating in a Pakistani family. Affected individuals exhibited, either a deafness-seizure syndrome or nonsyndromic deafness. In human temporal bones, TBC1D24 immunolocalized in hair cells and spiral ganglion neurons, whereas in mouse cochlea, Tbc1d24 expression was detected only in spiral ganglion neurons. We engineered mouse models of DFNB86 p.(Asp70Tyr) and DFNA65 p.(Ser178Leu) nonsyndromic deafness and syndromic forms of deafness p.(His336Glnfs*12) that have the same pathogenic variants that were reported for human TBC1D24. Unexpectedly, no auditory dysfunction was detected in Tbc1d24 mutant mice, although homozygosity for some of the variants caused seizures or lethality. We provide some insightful supporting data to explain the phenotypic differences resulting from equivalent pathogenic variants of mouse Tbc1d24 and human TBC1D24. [ABSTRACT FROM AUTHOR]

This paper aims to propose and compare three new structures of single-phase field excited flux switching machine for pedestal fan application. Conventional six-slot/three-pole salient rotor design has better performance in terms of torque, whilst also having a higher back-EMF and unbalanced electromagnetic forces. Due to the alignment position of the rotor pole with stator teeth, the salient rotor design could not generate torque (called dead zone torque). A new structure having sub-part rotor design has the capability to eliminate dead zone torque. Both the conventional eight-slot/four-pole sub-part rotor design and six-slot/three-pole salient rotor design have an overlapped winding arrangement between armature coil and field excitation coil that depicts high copper losses as well as results in increased size of motor. Additionally, a field excited flux switching machine with a salient structure of the rotor has high flux strength in the stator-core that has considerable impact on high iron losses. Therefore, a novel topology in terms of modular rotor of single-phase field excited flux switching machine with eight-slot/six-pole configuration is proposed, which enable non-overlap arrangement between armature coil and FEC winding that facilitates reduction in the copper losses. The proposed modular rotor design acquires reduced iron losses as well as reduced active rotor mass comparatively to conventional rotor design. It is very persuasive to analyze the range of speed for these rotors to avoid cracks and deformation, the maximum tensile strength (can be measured with principal stress in research) of the rotor analysis is conducted using JMAG. A deterministic optimization technique is implemented to enhance the electromagnetic performance of eight-slot/six-pole modular rotor design. The electromagnetic performance of the conventional sub-part rotor design, doubly salient rotor design, and proposed novel-modular rotor design is analyzed by 3D-finite element analysis (3D-FEA), including flux linkage, flux distribution, flux strength, back-EMF, cogging torque, torque characteristics, iron losses, and efficiency. [ABSTRACT FROM AUTHOR]

Double sided linear flux switching permanent magnet machines (DSLFSPMMs) exhibit high thrust force density, high efficiency, low cost and robust double salient secondary (stator) structures. The aforementioned unique features make DSLFSPMM suitable for long stroke applications. However, distorted flux linkage waveforms and high detent forces can exaggerate thrust force ripples and reduce their applicability in many areas. In order to enhance thrust force performance, reduce thrust force ripple ratio and total harmonic distortion (THD) of no-load flux linkages, two structure-based advancements are introduced in this work, i.e., asynchronous mover slot and stator tooth displacement technique (AMSSTDT) and the addition of an active permanent magnet end slot (APMES). Furthermore, single variable geometric optimization (SVGO) is carried out by the finite element method (FEM). [ABSTRACT FROM AUTHOR]