A Learning Framework for the YWCA Central Massachusetts

After meeting with the Director of Wellness and Health Equity at the YWCA Central Massachusetts (which will be referred to as the YWCA from here on out), we learned that as a non-profit gym and health center, it is heavily underfunded. The main focus of the project was to determine how to upkeep the facility while bringing in new customers with limited resources and budget. Due to the needs of the YWCA, our group focused on six aspects: revenue stream, donor retention, increasing membership, customer experience, social media marketing, and membership fee structure. After completing extensive research, we were able to make the following suggestions

Thermo-economic evaluation and optimization of solar-driven power-to-chemical systems with thermal, electricity, and chemical storage

This paper evaluates the thermo-economics of power-to-chemicals using solar energy, with the chemicals being methane, methanol, and gasoline. In addition to the optimal technology sizing and heat cascade utilization, this paper also considers the optimal molten-salt solar power tower (MSPT) design, as the MSPT significantly affects the levelized product cost. A bi-level optimization is proposed, employing mixed-integer linear programming at the lower level with heat and mass integration for optimizing sizes and operating strategies of technologies, and with heat cascade utilization and a genetic algorithm at the upper level for optimizing the MSPT design. In the upper level, the full-load storage hours, design direct normal irradiance, solar multiple, and sizes of the MSPT are optimized. The electricity sources considered are the MSPT, photovoltaic (PV) with daily electricity storage, and the electrical grid as a complementary technology to satisfy the targeted daily product demand. Cost-competitiveness of solar-driven chemical synthesis is thoroughly assessed via considering sensitivity analysis on 1) regional solar resource endowments and actual local demands; 2) electricity sources, that is, PV vs. MSPT; and 3) the scale effect represented by different chemicals’ yield. The results show that the levelized methane cost ranges from 4.5 to 8.5 €/kg, depending on the location, plant size, and annual power contribution of concentrated solar power. Due to the larger mass production, the levelized cost of methanol and gasoline is lower: 1.5–2.2 €/kg for methanol and 4–6 €/kg for gasoline. The findings highlight the significance of location choice, that is, natural endowment of solar radiation and carbon sources. Using the syngas co-electrolysis pathway and direct solar radiation 100 kWh/m2 higher, the methane production cost is decreased by 2.4 €/kg. Sensitivity analysis performed on plant scale reveals that a compact, small-scale system is far too expensive. The levelized cost of methane could be decreased by 1.2 €/kg when the plant is scaled up from 4,000 to 20,000 kg/day H2. Due to its expensive electricity storage and limited working hours, PV is typically not chosen as a power source. Overall, solar fuels are unlikely to be cost-competitive in the near future when compared to market prices for all three compounds under consideration

A Study on the Radiosensitivity of Radiation-Induced Lung Injury at the Acute Phase Based on Single-Cell Transcriptomics

Background and AimsRadiation-induced lung injury (RILI) is the most common complication associated with chest tumors, such as lung and breast cancers, after radiotherapy; however, the pathogenic mechanisms are unclear. Single-cell RNA sequencing has laid the foundation for studying RILI at the cellular microenvironmental level. This study focused on changes during the acute pneumonitis stage of RILI at the cellular microenvironmental level and investigated the interactions between different cell types.MethodsAn acute RILI model in mice and a single-cell transcriptional library were established. Intercellular communication networks were constructed to study the heterogeneity and intercellular interactions among different cell types.ResultsA single-cell transcriptome map was established in a mouse model of acute lung injury. In total, 18,500 single-cell transcripts were generated, and 10 major cell types were identified. The heterogeneity and radiosensitivity of each cell type or subtype in the lung tissues during the acute stage were revealed. It was found that immune cells had higher radiosensitivity than stromal cells. Immune cells were highly heterogeneous in terms of radiosensitivity, while some immune cells had the characteristics of radiation resistance. Two groups of radiation-induced Cd8+Mki67+ T cells and Cd4+Cxcr6+ helper T cells were identified. The presence of these cells was verified using immunofluorescence. The ligand-receptor interactions were analyzed by constructing intercellular communication networks. These explained the origins of the cells and revealed that they had been recruited from endothelial cells to the inflammatory site.ConclusionsThis study revealed the heterogeneity of in vivo radiosensitivity of different cell types in the lung at the initial stage post irradiatio

High-Power Electromagnetic Pulse Exposure of Healthy Mice: Assessment of Effects on Mice Cognitions, Neuronal Activities, and Hippocampal Structures

Electromagnetic pulse (EMP) is a high-energy pulse with an extremely rapid rise time and a broad bandwidth. The brain is a target organ sensitive to electromagnetic radiation (EMR), the biological effects and related mechanisms of EMPs on the brain remain unclear. The objectives of the study were to assess the effects of EMP exposure on mouse cognitions, and the neuronal calcium activities in vivo under different cases of real-time exposure and post exposure. EMP-treated animal model was established by exposing male adult C57BL/6N mice to 300 kV/m EMPs. First, the effects of EMPs on the cognitions, including the spatial learning and memory, avoidance learning and memory, novelty-seeking behavior, and anxiety, were assessed by multiple behavioral experiments. Then, the changes in the neuronal activities of the hippocampal CA1 area in vivo were detected by fiber photometry in both cases of during real-time EMP radiation and post-exposure. Finally, the structures of neurons in hippocampi were observed by optical microscope and transmission electron microscope. We found that EMPs under this condition caused a decline in the spatial learning and memory ability in mice, but no effects on the avoidance learning and memory, novelty-seeking behavior, and anxiety. The neuron activities of hippocampal CA1 were disturbed by EMP exposure, which were inhibited during EMP exposure, but activated immediately after exposure end. Additionally, the CA1 neuron activities, when mice entered the central area in an Open field (OF) test or explored the novelty in a Novel object exploration (NOE) test, were inhibited on day 1 and day 7 after radiation. Besides, damaged structures in hippocampal neurons were observed after EMP radiation. In conclusion, EMP radiation impaired the spatial learning and memory ability and disturbed the neuronal activities in hippocampal CA1 in mice

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Development of delivery strategies for CRISPR‐Cas9 genome editing

Abstract The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR‐related protein 9 (Cas9) genome editing system has attracted much attention due to its powerful genome editing capacity. However, CRISPR‐Cas9 components are easily degraded by acids, enzymes, and other substances in the body fluids after entering the organism, thus efficiently delivering the CRISPR‐Cas9 system into targeted organs or cells has been a central theme for promoting the application of CRISPR‐Cas9 technology. Although several physical methods and viral vectors have been developed for CRISPR‐Cas9 delivery, their clinical application still suffers from disadvantages, such as the risks of mutagenesis, cell damage, and poor specificity. As an alternative, non‐viral nanocarriers hold great promise for circumventing these challenges. Furthermore, with aim to realize more efficient and precise genome editing and reduce the undesirable side effects, stimuli‐responsive nanocarriers are designed for the spatiotemporal CRISPR‐Cas9 delivery in responsive to various stimuli. In this review, we will summarize the recent progress in delivery strategies for CRISPR‐Cas9 genome editing. The mechanisms and advantages of these strategies were reviewed, providing a comprehensive review of the rational design of materials and techniques for efficient and precise genome editing. At last, the potential challenges of current CRISPR‐Cas9 delivery are discussed

Discovery of novel and potent CDK8 inhibitors for the treatment of acute myeloid leukaemia

AbstractIt has been reported that CDK8 plays a key role in acute myeloid leukaemia. Here, a total of 40 compounds were rational designed and synthesised based on the previous SAR. Among them, compound 12 (3-(3-(furan-3-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide) showed the most potent inhibiting activity against CDK8 with an IC50 value of 39.2 ± 6.3 nM and anti AML cell proliferation activity (molm-13 GC50 = 0.02 ± 0.01 μM, MV4-11 GC50 = 0.03 ± 0.01 μM). Mechanistic studies revealed that this compound 12 could inhibit the phosphorylation of STAT-1 and STAT-5. Importantly, compound 12 showed relative good bioavailability (F = 38.80%) and low toxicity in vivo. This study has great significance for the discovery of more efficient CDK8 inhibitors and the development of drugs for treating AML in the future

Game-theory-based clustering scheme for energy balancing in underwater acoustic sensor networks

The underwater acoustic sensor network (UASN) is a specific deployment of Internet-of-Things (IoT) technology in the underwater environment, since energy constraints limit the lifetime of UASNs, effectively balancing the energy consumption of acoustic sensor nodes in UASNs is important to maximize the amount of information collected and to prolong the network lifetime. Node clustering is widely regarded as one of the most important energy-efficient schemes for UASNs. However, most existing clustering schemes focus on the cooperation-based election of cluster headers (CHs) in a centralized manner. Due to the limited energy capacity, acoustic sensor nodes are designed to save their own energy, hindering the realization of such cooperation. To address this issue in this article, game theory is applied to UASNs to balance network energy consumption and model acoustic sensor nodes as rational and selfish players. Specifically, a game-theory-based clustering (GTC) scheme for UASNs is developed. In the CH election phase, each node makes a decision in pursuit of a greater payoff based on the Nash equilibrium. An incentive mechanism is invented to induce nodes to make more beneficial collective decisions and plays a role in the CH rotation to effectively balance the energy consumption. Meanwhile, the network area is divided into nonuniform sectors to ensure the energy consumption of the CH is more evenly distributed. Simulation results show that the proposed GTC scheme can effectively balance network energy consumption and extend the network lifetime.This work was supported in part by the National Natural Science Foundation of China under Grant 61972424; in part by JSPS KAKENHI under Grant JP20F20080; and in part by the Special Fund for Basic Scientific Research of Central College, SCUEC, under Grant CZT20025