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"Haider, Syed"
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Age influences on the molecular presentation of tumours
Cancer is often called a disease of aging. There are numerous ways in which cancer epidemiology and behaviour change with the age of the patient. The molecular bases for these relationships remain largely underexplored. To characterise them, we analyse age-associations in the nuclear and mitochondrial somatic mutational landscape of 20,033 tumours across 35 tumour-types. Age influences both the number of mutations in a tumour (0.077 mutations per megabase per year) and their evolutionary timing. Specific mutational signatures are associated with age, reflecting differences in exogenous and endogenous oncogenic processes such as a greater influence of tobacco use in the tumours of younger patients, but higher activity of DNA damage repair signatures in those of older patients. We find that known cancer driver genes such as
CDKN2A
and
CREBBP
are mutated in age-associated frequencies, and these alter the transcriptome and predict for clinical outcomes. These effects are most striking in brain cancers where alterations like
SUFU
loss and
ATRX
mutation are age-dependent prognostic biomarkers. Using three cancer datasets, we show that age shapes the somatic mutational landscape of cancer, with clinical implications.
Ageing is a known risk factor in the development of cancers, but its association with molecular alterations is not fully explored. Here, the authors analyse pan-cancer age-associated molecular alterations in datasets from the TCGA, PCAWG and AACR-GENIE projects and identify prognostic biomarkers.
Journal Article
Advancing energy integration: renewable sources, ancillary services, and stability
The paper discusses the recent developments and challenges in the energy sector, particularly focusing on the integration of renewable energy sources into microgrids and conventional power systems. It highlights the importance of predicting future energy generation for effective grid integration and discusses the use of Artificial Neural Network (ANN) and Auto-Regressive Moving Average (ARMA) models for this purpose. Additionally, it explores the role of distributed generation in providing ancillary services traditionally offered by conventional power systems and analyzes the impact of renewable energy sources on core parameters like frequency and voltage stability. It also discusses the rapid growth of solar photovoltaic (PV) systems and the need to assess their impacts on distribution networks. Furthermore, it addresses the ongoing energy crisis, particularly in South Asia, and proposes solutions such as power factor correction through technologies like Static VAR Compensators (SVCs) to enhance system stability and efficiency, especially in medium and long transmission lines.
Journal Article
Impairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis
Profiling studies have revealed considerable phenotypic heterogeneity in cancer-associated fibroblasts (CAFs) present within the tumour microenvironment, however, functional characterisation of different CAF subsets is hampered by the lack of specific markers defining these populations. Here we show that genetic deletion of the Endo180 (
MRC2
) receptor, predominantly expressed by a population of matrix-remodelling CAFs, profoundly limits tumour growth and metastasis; effects that can be recapitulated in 3D co-culture assays. This impairment results from a CAF-intrinsic contractility defect and reduced CAF viability, which coupled with the lack of phenotype in the normal mouse, demonstrates that upregulated Endo180 expression by a specific, potentially targetable CAF subset is required to generate a supportive tumour microenvironment. Further, characterisation of a tumour subline selected via serial in vivo passage for its ability to overcome these stromal defects provides important insight into, how tumour cells adapt to a non-activated stroma in the early stages of metastatic colonisation.
Endo180, a collagen binding receptor, is highly expressed in a subset of cancer-associated fibroblasts. The authors show, using knockout mice and 3D in vitro assays, that Endo180 depletion impairs tumour fibroblast contractility and viability resulting in reduced tumour growth and metastasis.
Journal Article
Moderating effect of hedonism on store environment-impulse buying nexus
PurposeAlthough the store environment-impulse buying nexus is well documented, the influence of consumer motivations on this nexus is still underexplored. Consequently, this paper aims at explaining the mediating effect of emotional states and the moderating effect of hedonic shopping motives on the relationship between store atmospherics and impulse buying behavior.Design/methodology/approachPrimary data from 437 customers were generated through a questionnaire developed for this study. Respondents were accessed using mall-intercept technique. Structural equation modeling (SEM) was done to empirically estimate the model.FindingsResults indicate that pleasure and shopping enjoyment mediate the effect of store atmospherics on the impulse purchase behavior. The findings also show that hedonic shopping motives moderate the relationship between the store atmospherics and impulse purchase.Originality/valueThis study contributes by introducing the moderating role played by the hedonic shopping motives on the relationship between store atmospherics and impulse purchase. In addition, it introduces that shopping enjoyment and pleasure mediate the effect of perceived store atmospherics on impulse purchase.
Journal Article
Towards Efficient Energy Management of Smart Buildings Exploiting Heuristic Optimization with Real Time and Critical Peak Pricing Schemes
The smart grid plays a vital role in decreasing electricity cost through Demand Side Management (DSM). Smart homes, a part of the smart grid, contribute greatly to minimizing electricity consumption cost via scheduling home appliances. However, user waiting time increases due to the scheduling of home appliances. This scheduling problem is the motivation to find an optimal solution that could minimize the electricity cost and Peak to Average Ratio (PAR) with minimum user waiting time. There are many studies on Home Energy Management (HEM) for cost minimization and peak load reduction. However, none of the systems gave sufficient attention to tackle multiple parameters (i.e., electricity cost and peak load reduction) at the same time as user waiting time was minimum for residential consumers with multiple homes. Hence, in this work, we propose an efficient HEM scheme using the well-known meta-heuristic Genetic Algorithm (GA), the recently developed Cuckoo Search Optimization Algorithm (CSOA) and the Crow Search Algorithm (CSA), which can be used for electricity cost and peak load alleviation with minimum user waiting time. The integration of a smart Electricity Storage System (ESS) is also taken into account for more efficient operation of the Home Energy Management System (HEMS). Furthermore, we took the real-time electricity consumption pattern for every residence, i.e., every home has its own living pattern. The proposed scheme is implemented in a smart building; comprised of thirty smart homes (apartments), Real-Time Pricing (RTP) and Critical Peak Pricing (CPP) signals are examined in terms of electricity cost estimation for both a single smart home and a smart building. In addition, feasible regions are presented for single and multiple smart homes, which show the relationship among the electricity cost, electricity consumption and user waiting time. Experimental results demonstrate the effectiveness of our proposed scheme for single and multiple smart homes in terms of electricity cost and PAR minimization. Moreover, there exists a tradeoff between electricity cost and user waiting.
Journal Article
Soil Organic Carbon Sequestration Potential and Its Sustainability Comparison Between Mango-based Agroforestry and Cropland Seeking Soil Fertility Parameters Under Climate Resilience
Soil organic carbon (SOC) storage is a critical ecosystem service for reducing CO2 emissions. Terrestrial ecosystems, including the agriculture lands, hold the second largest carbon reserves after oceans, containing 2,344 Gt of carbon. Agroforestry plays an important role in sequestering (SOC) which is essential for mitigating CO2. Due to increased anthropogenic activities, global CO2 emissions continue to rise. In agroecological zones, SOC serves as a key reservoir for atmospheric CO2. This research evaluates sustainability comparison between two land types for carbon sequestration potential and soil fertility parameters in District Multan, Pakistan; mango-based agroforestry (MBA) and cropland (CL) respectively. Soil samples were collected randomly at a depth of 20 cm from the locations; under tree shade in mango-based agroforestry (MBAUS), outside the tree shade (MBA), and cropland (CL). These samples were tested for analysis for (SOC), organic matter (OM %), nitrogen percentage (N %), saturation percentage (SP %), bulk density (BD), and carbon-to-nitrogen (C: N) ratio between mean values of agroforestry and CL. Results indicated that the amount of SOC was higher in agroforestry (0.64) compared to CL (0.43). Similarly, OM% was 1.15 in agroforestry and 0.75% in CL. N% was 0.055 in agroforestry and 0.037 in CL, C: N ratio (12:1) in agroforestry versus (11:1) in CL. SP was greater in CL (36.1) than in agroforestry (34.1), similarly, BD was higher in CL (1.361 g/cm3) and (1.077 g/cm3) in agroforestry. The study employed a completely randomized design (CRD) with three treatments and four replications. ANOVA was used for data analysis. According to the results, the carbon sequestration potential and fertility index of agroforestry was quite double that of cropland.
Journal Article
BioMart – biological queries made easy
Background
Biologists need to perform complex queries, often across a variety of databases. Typically, each data resource provides an advanced query interface, each of which must be learnt by the biologist before they can begin to query them. Frequently, more than one data source is required and for high-throughput analysis, cutting and pasting results between websites is certainly very time consuming. Therefore, many groups rely on local bioinformatics support to process queries by accessing the resource's programmatic interfaces if they exist. This is not an efficient solution in terms of cost and time. Instead, it would be better if the biologist only had to learn one generic interface. BioMart provides such a solution.
Results
BioMart enables scientists to perform advanced querying of biological data sources through a single web interface. The power of the system comes from integrated querying of data sources regardless of their geographical locations. Once these queries have been defined, they may be automated with its \"scripting at the click of a button\" functionality. BioMart's capabilities are extended by integration with several widely used software packages such as BioConductor, DAS, Galaxy, Cytoscape, Taverna. In this paper, we describe all aspects of BioMart from a user's perspective and demonstrate how it can be used to solve real biological use cases such as SNP selection for candidate gene screening or annotation of microarray results.
Conclusion
BioMart is an easy to use, generic and scalable system and therefore, has become an integral part of large data resources including Ensembl, UniProt, HapMap, Wormbase, Gramene, Dictybase, PRIDE, MSD and Reactome. BioMart is freely accessible to use at
http://www.biomart.org
.
Journal Article
PARP inhibition enhances tumor cell–intrinsic immunity in ERCC1-deficient non–small cell lung cancer
The cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway detects cytosolic DNA to activate innate immune responses. Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA repair deficiencies such as those caused by BRCA1 mutations or ERCC1 defects. Using isogenic cell lines and patient-derived samples, we showed that ERCC1-defective non-small cell lung cancer (NSCLC) cells exhibit an enhanced type I IFN transcriptomic signature and that low ERCC1 expression correlates with increased lymphocytic infiltration. We demonstrated that clinical PARPi, including olaparib and rucaparib, have cell-autonomous immunomodulatory properties in ERCC1-defective NSCLC and BRCA1-defective triple-negative breast cancer (TNBC) cells. Mechanistically, PARPi generated cytoplasmic chromatin fragments with characteristics of micronuclei; these were found to activate cGAS/STING, downstream type I IFN signaling, and CCL5 secretion. Importantly, these effects were suppressed in PARP1-null TNBC cells, suggesting that this phenotype resulted from an on-target effect of PARPi on PARP1. PARPi also potentiated IFN-γ-induced PD-L1 expression in NSCLC cell lines and in fresh patient tumor cells; this effect was enhanced in ERCC1-deficient contexts. Our data provide a preclinical rationale for using PARPi as immunomodulatory agents in appropriately molecularly selected populations.
Journal Article
Lovemarks and beyond: Examining the link between lovemarks and brand loyalty through customer advocacy in the automobile industry
Despite the potential for businesses, our understanding of lovemark brands and their consequences is limited. Numerous psychological and brand-related consequences are linked to lovemarks, but the role of influential underlining mechanisms is not fully understood. Inspired by the norms of reciprocity theory, the current study investigates the underlining role of customer advocacy in the relationship between perceived lovemarks and brand loyalty of customers in the automobile industry.
By adopting the survey method, a sample of 478 was drawn from Pakistani automobile customers. Structural equation modelling was used for the analysis. We conceptualised lovemarks and brand loyalty as reflective higher-order constructs that we analysed through a two-stage disjoint analysis.
Our results support the conceptualization of lovemarks and brand loyalty as higher-order constructs. The influence of lovemarks and customer advocacy on brand loyalty was statistically significant when we controlled for age, gender, and income. Our findings also reveal that customer advocacy, seen as a company's positive interactions, mediates and play a key role in influencing the relationship between lovemarks and brand loyalty.
This is among the first studies to examine the role of customer advocacy in the lovemarks-brand loyalty relationship. We examined these relationships in the automobile sector of Pakistan, which offers several theoretical and managerial implications for academia and practitioners. The implications are proposed and outlined in this study.
Journal Article