Integration of very Small Modular Reactors and Renewable Energy Resources in Microgrid

Hybrid microgrids, integrating local energy resources, present a promising but challenging solution, especially in areas with limited or no access to the national grid. Reliable operation of off-grid energy systems necessitates sustainable energy sources, given the intermittent nature of renewables. While fossil fuel diesel generators mitigate risks, they increase carbon emissions. This study assesses the viability of integrating a very small modular renewable energy reactor into a microgrid for replacing conventional diesel generators, substantially curbing greenhouse gas emissions. A comprehensive analysis, including design and economic evaluation, was conducted for an off-grid community microgrid with an annual generation and load of 8.5 GWh and 7.8 GWh, respectively. The proposed microgrid configurations incorporate very small modular reactors, alongside solar, wind, and battery storage systems. MATLAB modeling and simulation across eight cases, accounting for seasonal variations, demonstrate the technical and economic feasibility of case 7. This configuration, integrating modular reactors, photovoltaics, wind turbines, and battery storage, satisfactorily meets load demands. Notably, it boasts a high internal rate of return up to ∼31% and a shorter payback period of around 4 years compared to alternative scenarios

The Impact of Knowledge Management Success Factors on Electronic Business in Jordanian Telecom Companies

Abstract: The study aimed to identify the impact of knowledge management success factors represented (organizational culture, administrative leadership, organizational structure, information technology infrastructure, standards) on electronic business (electronic information, electronic communications, electronic work flow), and the study community included all employees in Jordanian telecom companies, where the three telecommunications companies (Umniah, Zain, Orange) agreed to participate in the study, and (240) questionnaires were distributed to employees in those companies, and (191) questionnaires were retrieved, of which (188) were valid questionnaires for analysis with an actual response amount of (78.3%), which is similar to the final study sample. The study used the descriptive analytical method, and assumed a positive impact of the factors of success of knowledge management on electronic business in Jordanian telecom companies. The results showed that there is an awareness of the factors of success of knowledge management among employees in Jordanian telecom companies, where the arithmetic averages for the organizational culture variables, information technology infrastructure and knowledge measures came within the level of high importance, and the variable of administrative leadership and the organizational structure variable came within the level of intermediate importance in the current study, as well all averages of e-business dimensions came within the high level of importance, as well as the overall e-business variable, in addition to that, the results indicated a positive impact of the factors of success of knowledge management on e-business in Jordanian telecom companies; as the variable of knowledge management success factors explained (65.7%) of the variance in e-business, and the results also indicated that the variable of information technology infrastructure was the most influencing electronic information, and the second ranked in the impact of organizational culture, while the variables of administrative leadership do not affect the organizational structure and measures of knowledge on electronic information, and the results also showed that the variable of the information technology infrastructure ranked first in the impact on electronic communications, followed by the effect of the variable of organizational culture, and then the organizational structure variable, while the administrative leadership and knowledge standards variables do not affect, finally it showed the results indicated that the variable of the IT infrastructure was the most influential in the electronic work flow, and came second in the organizational structure, and the organizational culture ranked third, and the fourth came the variable of administrative leadership, while the electronic work flow variable was not affected by knowledge measures. Based on the results, the study recommended the need to pay attention to the employees awareness of the importance of success factors Knowledge Management, given its impact on e-business, by maintaining the level of organizational culture, and constantly enhancing it, raising the level of awareness of managers and decision makers about the importance of knowledge management success factors and their impact on e-business, developing the capabilities of employees, and creating a special administrative unit, concerned with knowledge management and organization Its operations, in addition to adopting successful organizational structures that increase the level of knowledge, as well as the need to develop and promote electronic business in Jordanian telecom companies, by paying attention to the communication infrastructure, and providing modern electronic workflow systems, the study also recommended researchers to conduct other studies on management success factors Knowledge and e-business in other study societies and other organizational outputs

Neratinib plus trastuzumab is superior to pertuzumab plus trastuzumab in HER2-positive breast cancer xenograft models

Lapatinib (L) plus trastuzumab (T), with endocrine therapy for estrogen receptor (ER)+ tumors, but without chemotherapy, yielded meaningful response in HER2+ breast cancer (BC) neoadjuvant trials. The irreversible/pan-HER inhibitor neratinib (N) has proven more potent than L. However, the efficacy of N+T in comparison to pertuzumab (P) + T or L + T (without chemotherapy) remains less studied. To address this, mice bearing HER2+ BT474-AZ (ER+) cell and BCM-3963 patient-derived BC xenografts were randomized to vehicle, N, T, P, N+T, or P+T, with simultaneous estrogen deprivation for BT474-AZ. Time to tumor regression/progression and incidence/time to complete response (CR) were determined. Changes in key HER pathway and proliferative markers were assessed by immunohistochemistry and western blot of short-term-treated tumors. In the BT474-AZ model, while all N, P, T, N + T, and P + T treated tumors regressed, N + T-treated tumors regressed faster than P, T, and P + T. Further, N + T was superior to N and T alone in accelerating CR. In the BCM-3963 model, which was refractory to T, P, and P + T, while N and N + T yielded 100% CR, N + T accelerated the CR compared to N. Ki67, phosphorylated (p) AKT, pS6, and pERK levels were largely inhibited by N and N + T, but not by T, P, or P + T. Phosphorylated HER receptor levels were also markedly inhibited by N and N + T, but not by P + T or L + T. Our findings establish the efficacy of combining N with T and support clinical testing to investigate the efficacy of N + T with or without chemotherapy in the neoadjuvant setting for HER2+ BC

The Impact of COVID-19 on Physical (In)Activity Behavior in 10 Arab Countries.

Insufficient physical activity is considered a strong risk factor associated with non-communicable diseases. This study aimed to assess the impact of COVID-19 on physical (in)activity behavior in 10 Arab countries before and during the lockdown. A cross-sectional study using a validated online survey was launched originally in 38 different countries. The Eastern Mediterranean regional data related to the 10 Arabic countries that participated in the survey were selected for analysis in this study. A total of 12,433 participants were included in this analysis. The mean age of the participants was 30.3 (SD, 11.7) years. Descriptive and regression analyses were conducted to examine the associations between physical activity levels and the participants\u27 sociodemographic characteristics, watching TV, screen time, and computer usage. Physical activity levels decreased significantly during the lockdown. Participants\u27 country of origin, gender, and education were associated with physical activity before and during the lockdown (p \u3c 0.050). Older age, watching TV, and using computers had a negative effect on physical activity before and during the lockdown (p \u3c 0.050). Strategies to improve physical activity and minimize sedentary behavior should be implemented, as well as to reduce unhealthy levels of inactive time, especially during times of crisis. Further research on the influence of a lack of physical activity on overall health status, as well as on the COVID-19 disease effect is recommended

Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET transgenic mice

<p>Abstract</p> <p>Background</p> <p>The importance of cell-surface nucleolin in cancer biology was recently highlighted by studies showing that ligands of nucleolin play critical role in tumorigenesis and angiogenesis. By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, we recently reported that HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in the athymic nude mice without apparent toxicity.</p> <p>Methods</p> <p>The <it>in vivo </it>antitumoral action of HB-19 treatment was assessed on the spontaneous development of melanoma in the RET transgenic mouse model. Ten days old RET mice were treated with HB-19 in a prophylactic setting that extended 300 days. In parallel, the molecular basis for the action of HB-19 was investigated on a melanoma cell line (called TIII) derived from a cutaneous nodule of a RET mouse.</p> <p>Results</p> <p>HB-19 treatment of RET mice caused a significant delay in the onset of cutaneous tumors, several-months delay in the incidence of large tumors, a lower frequency of cutaneous nodules, and a reduction of visceral metastatic nodules while displaying no toxicity to normal tissue. Moreover, microvessel density was significantly reduced in tumors recovered from HB-19 treated mice compared to corresponding controls. Studies on the melanoma-derived tumor cells demonstrated that HB-19 treatment of TIII cells could restore contact inhibition, impair anchorage-independent growth, and reduce their tumorigenic potential in mice. Moreover, HB-19 treatment caused selective down regulation of transcripts coding matrix metalloproteinase 2 and 9, and tumor necrosis factor-α in the TIII cells and in melanoma tumors of RET mice.</p> <p>Conclusions</p> <p>Although HB-19 treatment failed to prevent the development of spontaneous melanoma in the RET mice, it delayed for several months the onset and frequency of cutaneous tumors, and exerted a significant inhibitory effect on visceral metastasis. Consequently, HB-19 could provide a novel therapeutic agent by itself or as an adjuvant therapy in association with current therapeutic interventions on a virulent cancer like melanoma.</p

Integrative pathway enrichment analysis of multivariate omics data

Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations

HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers

Amplification and oncogenic mutations of ERBB2, the gene encoding the HER2 receptor tyrosine kinase, promote receptor hyperactivation and tumor growth. Here we demonstrate that HER2 ubiquitination and internalization, rather than its overexpression, are key mechanisms underlying endocytosis and consequent efficacy of the anti-HER2 antibody-drug conjugates (ADCs) ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) in lung cancer cell lines and patient-derived xenograft models. These data translated into a 51% response rate in a clinical trial of T-DM1 in 49 patients with ERBB2/HER2-amplified or mutant lung cancers. We show that co-treatment with irreversible pan-HER inhibitors enhances receptor ubiquitination and consequent ADC internalization and efficacy. We also demonstrate that ADC switching to T-DXd, which harbors a different cytotoxic payload, achieves durable responses in a patient with lung cancer and corresponding xenograft model developing resistance to T-DM1. Our findings may help guide future clinical trials and expand the field of ADC as cancer therapy

Novel functional insights into ischemic stroke biology provided by the first genome-wide association study of stroke in indigenous Africans

\ua9 The Author(s) 2024. Background: African ancestry populations have the highest burden of stroke worldwide, yet the genetic basis of stroke in these populations is obscure. The Stroke Investigative Research and Educational Network (SIREN) is a multicenter study involving 16 sites in West Africa. We conducted the first-ever genome-wide association study (GWAS) of stroke in indigenous Africans. Methods: Cases were consecutively recruited consenting adults (aged &gt; 18 years) with neuroimaging-confirmed ischemic stroke. Stroke-free controls were ascertained using a locally validated Questionnaire for Verifying Stroke-Free Status. DNA genotyping with the H3Africa array was performed, and following initial quality control, GWAS datasets were imputed into the NIH Trans-Omics for Precision Medicine (TOPMed) release2 from BioData Catalyst. Furthermore, we performed fine-mapping, trans-ethnic meta-analysis, and in silico functional characterization to identify likely causal variants with a functional interpretation. Results: We observed genome-wide significant (P-value &lt; 5.0E−8) SNPs associations near AADACL2 and miRNA (MIR5186) genes in chromosome 3 after adjusting for hypertension, diabetes, dyslipidemia, and cardiac status in the base model as covariates. SNPs near the miRNA (MIR4458) gene in chromosome 5 were also associated with stroke (P-value &lt; 1.0E−6). The putative genes near AADACL2, MIR5186, and MIR4458 genes were protective and novel. SNPs associations with stroke in chromosome 2 were more than 77 kb from the closest gene LINC01854 and SNPs in chromosome 7 were more than 116 kb to the closest gene LINC01446 (P-value &lt; 1.0E−6). In addition, we observed SNPs in genes STXBP5-AS1 (chromosome 6), GALTN9 (chromosome 12), FANCA (chromosome 16), and DLGAP1 (chromosome 18) (P-value &lt; 1.0E−6). Both genomic regions near genes AADACL2 and MIR4458 remained significant following fine mapping. Conclusions: Our findings identify potential roles of regulatory miRNA, intergenic non-coding DNA, and intronic non-coding RNA in the biology of ischemic stroke. These findings reveal new molecular targets that promise to help close the current gaps in accurate African ancestry-based genetic stroke’s risk prediction and development of new targeted interventions to prevent or treat stroke