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Nuclear power is typically deployed as a baseload generator. Increased penetration of variable renewables motivates combining nuclear and renewable technologies into Integrated Energy Systems (IES) to improve dispatchability, component synergies and, through cogeneration, address multiple markets. However, combining multiple energy resources heavily depends on the proper selection of each system’s location and design limitations. In this paper, co-siting options for IES that couple nuclear and concentrating solar power (CSP) with thermal desalination are investigated. A comprehensive siting analysis is performed that utilizes global information survey data to determine possible co-siting options for nuclear and solar thermal generation in the United States. Viable co-siting options are distributed across the Southwestern U.S., with the greatest concentration of siting options in the southern Great Plains, although siting with higher solar direct normal irradiance is possible in other states such as Arizona and New Mexico. Brackish water desalination is also attractive across the southwest U.S. due to high water stress, but for brackish water desalination reverse osmosis (an electricity driven process) is most cost- and energy-efficient, which does not require co-siting with the thermal generator. The most attractive state for nuclear and thermal desalination (which is more attractive when using seawater) is Texas, although other areas may become attractive as water stress increases over the coming decades. Co-siting of all CSP and thermal desalination is challenging as attractive CSP sites are not coastal.

Abstract Background Inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal soft tissue sarcomas that often present diagnostic challenges due to their wide and varied morphology. A subset of IMTs have fusions involving ALK or ROS1. The role of next‐generation sequencing (NGS) for classification of unselected sarcomas remains controversial. Methods and Results We report a case of a metastatic sarcoma in a 34‐year‐old female originally diagnosed as an unclassified spindle cell sarcoma with myofibroblastic differentiation and later reclassified as IMT after NGS revealed a TFG‐ROS1 rearrangement. Histologically, the neoplasm had spindle cell morphology with a lobulated to focally infiltrative growth pattern with scant inflammatory cell infiltrate. Immunohistochemistry demonstrated focal desmin and variable smooth muscle actin staining but was negative for SOX10, S100, and CD34. Fluorescence in situ hybridization was negative for USP6 or ALK gene rearrangements. NGS revealed a TFG‐ROS1 rearrangement and the patient was treated with crizotinib with clinical benefit. Conclusions We discuss the role of NGS as well as its potential benefit in patients with unresectable, ALK‐negative metastatic disease. Considering this case and previous literature, we support the use of NGS for patients requiring systemic treatment.

Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit).Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4–96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure.Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment.Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.

Abstract Background Malignant hemangioendothelioma is an endothelial cancer with heterogeneous clinical behavior that can range from indolent to aggressive, of which the majority are epithelioid (EHE). Its incidence and demographics have not been previously well defined in a large cohort. Methods This retrospective analysis used the US Cancer Statistics National Program of Cancer Registries – Surveillance Epidemiology End Results (SEER) combined database to identify patients in the US newly diagnosed with hemangioendothelioma between the years of 2001 and 2017 (n = 1986). Survival analyses were performed on a subset of patients within the SEER‐18 database with survival information available (n = 417). Outcomes included incidence, demographics of patients newly diagnosed with hemangioendothelioma, extent of disease at presentation, and overall survival. Results The incidence of hemangioendothelioma in the US is 0.4 cases per million person‐years. Although cases rose to 122 newly diagnosed in the year 2017 (90 EHE, 32 other hemangioendothelioma), incidence rates were stable. Skin and connective tissues were the most common presenting sites (33.4%), followed by liver (24.5%), lung (17.6%), and bone (12.5%). Median age at diagnosis was 55 years; 27.2% of patients were pediatric, adolescent, or young adult (

Future electrical grids will likely include a diverse group of power generation plants. With the growing list of new generation options comes many opportunities for more optimal energy production management and effective resource utilization. Microgrids are an ideal environment for research, development, and validation of those energy optimization strategies. This paper establishes a method for integrating a virtual thermal power plant model with a physical microgrid in a power hardware in the loop testbed. One advantage of these testbeds is their variety of configuration options. In this paper, the combined effects of photovoltaic and concentrating solar power generation are investigated. A conventional thermal power plant with components sized for CSP applications is modeled in the Simscape environment. Actual solar panels provide the photovoltaic element of this experiment. How the plant model and physical hardware interact is described in detail. A PV startup and shutdown event is simulated in real-time. The model responses are shown to be successfully and correctly coupled to electrical power flow in the testbed.

To make concentrating solar power (CSP) more cost competitive, rigourous optimizations must be run to improve plant design and operations. However, these optimizaitons rely on time consuming annual simulations that solve an electricity dispatch scheduling problem to maximize plant revenue. To reduce the runtime of annual dispatch simulations of CSP plants, a data clustering approach is utilized. This approach assumes that like days of revenue and electricity generation can be identified using weather and price data. Although weather and price are important factors for electricity production, this work investigates how thermal energy storage (TES) inventory at the beginning of a day, denoted as Si, can be used as a supplemental feature to group like days. A framework for creating and training a deep neural network to predict Si is proposed. This model is validated and assessed using eleven sets of testing data that were not used during training. Then, the data clustering approach is performed three seperate times with features of weather and price along with either Si from the neural network, Si from the full annual simulation, or no Si. Ultimately, the results suggest that using Si as an additional clustering feature improves the data clustering simulation accuracy by 1.4%.

Abstract The carbon net negative conversion of bio-char, the low value byproduct of pyrolysis bio-oil production from biomass, to high value, very high purity, highly crystalline flake graphite agglomerates with rationally designed shape and size tailored for lithium-ion battery energy storage material is reported. The process is highly efficient, 0.41 g/Wh; the energy content of its co-product of the process, bio-oil, exceeds that needed to power the process. It is shown that the shape of the starting material is retained during the transformation, allowing the ultimate morphology of the graphite agglomerates to be engineered from relatively malleable biomass. In contrast to commercial graphite production, the process can be performed at small scale with low equipment costs, enabling individual research laboratories to produce Li-ion grade graphite with customizable shape, size and porosity for Si/graphite composite and other graphite involved anodes. The mechanism of the graphitization of bio-char, a “non-graphitizable” carbon, is explored, suggesting the molten metal catalyst is absorbed into the pore structure, transported through and transforming the largely immobile biochar. Finally, the transformation of biomass to rationally designed graphite morphologies with Li-ion anode performance that closely mimic commercial shaped graphite is demonstrated.

In the field of printed electronics, there is a pressing need for printable resistors, particularly ones where the resistance can be varied without changing the size of the resistor. This work presents ink synthesis and printing results for variable resistance, inkjet-printed patterns of a novel and sustainable carbon nanomaterial—multilayer graphene nanoshells. Dispersed multilayer graphene nanospheres are sterically stabilized by a surfactant (Triton X100), and no post-process is required to achieve the resistive functionality. A surface tension-based adsorption analysis technique is used to determine the optimal surfactant dosage, and a geometric model explains the conformation of adsorbed surfactant molecules. The energetic interparticle potentials between approaching particles are modeled to assess and compare the stability of sterically and electrostatically stabilized multilayer graphene nanoshells. The multilayer graphene nanoshell inks presented here show a promising new pathway toward sustainable and practical printed resistors that achieve variable resistances within a constant areal footprint without post-processing.

Abstract Angiosarcoma is an aggressive malignancy of endothelial cells that carries a high mortality rate. Cytotoxic chemotherapy can elicit clinical responses, but the duration of response is limited. Sequencing reveals multiple mutations in angiogenesis pathways in angiosarcomas, particularly in vascular endothelial growth factor (VEGFR) and mitogen-activated protein kinase (MAPK) signaling. We aimed to determine the biological relevance of these pathways in angiosarcoma. Tissue microarray consisting of clinical formalin-fixed paraffin embedded tissue archival samples were stained for phospho- extracellular signal-regulated kinase (p-ERK) with immunohistochemistry. Angiosarcoma cell lines were treated with the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib, pan-VEGFR inhibitor cediranib, or combined trametinib and cediranib and viability was assessed. Reverse phase protein array (RPPA) was performed to assess multiple oncogenic protein pathways. SVR angiosarcoma cells were grown in vivo and gene expression effects of treatment were assessed with whole exome RNA sequencing. MAPK signaling was found active in over half of clinical angiosarcoma samples. Inhibition of MAPK signaling with the MEK inhibitor trametinib decreased the viability of angiosarcoma cells. Combined inhibition of the VEGF and MAPK pathways with cediranib and trametinib had an additive effect in in vitro models, and a combinatorial effect in an in vivo model. Combined treatment led to smaller tumors than treatment with either agent alone. RNA-seq demonstrated distinct expression signatures between the trametinib treated tumors and those treated with both trametinib and cediranib. These results indicate a clinical study of combined VEGFR and MEK inhibition in angiosarcoma is warranted.

Abstract Background Angiosarcoma is an aggressive tumor. Recent case series describe exceptional responses to checkpoint blockade in this disease. Methods Herein, we explored the genomic correlates of 48 angiosarcomas from the Angiosarcoma Project (12,499 variants analyzed in 6603 genes; whole-exome sequencing) versus 10,106 pan-cancer tumors in The Cancer Genome Atlas including 235 sarcomas but no angiosarcoma. Results At the molecular level, angiosarcomas were heterogeneous. Those located in the face and scalp presented high tumor mutation burden, missense amino acid variations biased towards more hydrophobic (and therefore more immunogenic) peptides, and ultra-violet mutational signature. Conclusions Angiosarcoma molecular features are similar to those observed in melanoma and other skin tumors and may explain comparable immunotherapy sensitivity of these tumor types.

Several types of benign and malignant neoplasms harboring GLI1 gene fusions with various partner genes, including ACTB, MALAT1 and PTCH1, have been described. These neoplasms show a spectrum of morphologic features and immunohistochemical profiles. However, the GLI1 gene fusion has not been described in soft tissue myoepithelial neoplasms previously. In this study, we reported a novel TUBA1A-GLI1 gene fusion in soft tissue neoplasm occurring in the chest wall of a 35-year-old male. The neoplasm shows morphologic features and immunophenotype of myoepithelial differentiation. FusionPlex analysis detected TUBA1A-GLI1 fusion in the neoplasm. The fusion transcript is comprised of 3′ end of exon 1 of TUBA1A and 5′ end of exon 6 of GLI1, retaining the FOXP coiled-coil domain and the DNA-binding zinc finger domains of GLI1. Promoter swapping with the TUBA1A (tubulin alpha 1a) gene likely leads to deregulation of GLI1 expression and its downstream targets. Despite the clinical presentation of multifocal disease and regional lymph node metastasis, the neoplasm in our case study appeared to be stable in a 10-month follow-up, suggesting that this neoplasm likely pursues an indolent clinical course. This study expands the morphologic and immunohistochemical spectrum of the neoplasms with GLI1 gene fusions and identifies a novel fusion in soft tissue myoepithelial neoplasms. As the TUBA1A-GLI1 fusion event likely results in activated GLI1 expression, targeting the Hedgehog pathway is a potential therapeutic option for treatment of patients with this neoplasm.

Variable renewable energy availability has increased the volatility in energy prices in most markets. Nuclear power plants, with a large ratio of capital to variable costs, have historically operated as base load energy suppliers but the need for more flexible operation is increasing. We simulate the techno-economic performance of a 950 MWt nuclear power plant, based on the Westinghouse lead-cooled fast reactor, coupled with molten salt thermal storage as a method for flexible energy dispatch. We use the System Advisor Model to model the nuclear reactor thermal power input and power cycle operating modes. We combine this robust engineering model with a mixed-integer linear program model for optimized dispatch scheduling. We then simulate the coupled nuclear and thermal storage system under different market scenarios with varying price volatility. We find that the coupled plant outperforms the base plant under markets where energy price peaks fluctuate by a factor of two or more about the mean price. We show that a calculated power purchase agreement price for the plant improves by up to 10% when operating under California energy market conditions. Sensitivity analysis on the thermal storage cost shows that the optimal design remains unchanged even when doubling costs.

Abstract Background Chondrosarcoma is one of the most common malignant bone tumors in adults. Conventional chondrosarcoma represents around 85% of all chondrosarcomas and is notoriously difficult to treat with chemotherapy. Case presentation We describe a 67-year-old man with metastatic conventional chondrosarcoma who was treated with nivolumab. Treatment was discontinued after restaging showed increased tumor burden, which later proved to be pseudoprogression. The patient restarted nivolumab and continues to have a near complete response. Conclusion Conventional chondrosarcoma may be sensitive to checkpoint inhibitors. Further, this case demonstrates clearly the phenomenon of pseudo-progression in this disease, a factor that must be considered in the design of clinical trials and clinical care. This case supports additional study of immunomodulatory agents in this deadly disease.

Abstract Endothelial cell malignancies are rare in the Western world and range from intermediate grade hemangioendothelioma to Kaposi sarcoma to aggressive high-grade angiosarcoma that metastasize early and have a high rate of mortality. These malignancies are associated with dysregulation of normal endothelial cell signaling pathways, including the vascular endothelial growth factor, angiopoietin, and Notch pathways. Discoveries over the past two decades related to mechanisms of angiogenesis have led to the development of many drugs that intuitively would be promising therapeutic candidates for these endothelial-derived tumors. However, clinical efficacy of such drugs has been limited. New insights into the mechanisms that lead to dysregulated angiogenesis such as mutation or amplification in known angiogenesis related genes, viral infection, and chromosomal translocations have improved our understanding of the pathogenesis of endothelial malignancies and how they evade anti-angiogenesis drugs. In this review, we describe the major molecular alterations in endothelial cell malignancies and consider emerging opportunities for improving therapeutic efficacy against these rare but deadly tumors.

Background Individuals with type 2 diabetes are at an increased risk of cardiovascular disease. Alterations in circulating lipid levels, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) are heritable risk factors for cardiovascular disease. Here we conduct a genome-wide association study (GWAS) of common and rare variants to investigate associations with baseline lipid levels in 7,844 individuals with type 2 diabetes from the ACCORD clinical trial. Methods DNA extracted from stored blood samples from ACCORD participants were genotyped using the Affymetrix Axiom Biobank 1 Genotyping Array. After quality control and genotype imputation, association of common genetic variants (CV), defined as minor allele frequency (MAF) ≥ 3%, with baseline levels of TC, LDL, HDL, and TG was tested using a linear model. Rare variant (RV) associations (MAF < 3%) were conducted using a suite of methods that collapse multiple RV within individual genes. Results Many statistically significant CV (p

Background. The prognosis and clinical characteristics of head and neck synovial sarcomas (HNSS) are unclear. Herein, we present an update using a cohort of patients treated at our institution. Methods. We performed a retrospective chart review of 44 patients diagnosed with primary HNSS between March 1990 and June 2012. Overall survival (OS) and progression-free survival (PFS) curves were estimated and hazard ratios (HRs) were calculated. Results. The entire cohort’s median PFS was 4.6 years, and 20 of the 44 (45%) patients developed either local or distant recurrence. Tumor size ≥ 5 cm (p=0.008, HR = 4.69; 95% CI = 1.34–16.38) and a primary presentation in the soft tissues of the neck (p=0.04, HR = 2.41; 95% CI = 1.003–5.82) were associated with significantly worse PFS. The OS and PFS of patients who received definitive local therapy versus those who received additional adjuvant systemic therapy did not differ significantly. Conclusion. Despite the treatment challenges associated with HNSS, our cohort of patients had a better prognosis than one might expect in this unfavorable anatomical location. Our findings suggest that tumor size and site are predictive of PFS and that wide surgical excision is of vital importance, since traditional cytotoxic chemotherapy has limited efficacy at this site.

Lithium-sulfur (Li-S) battery is a promising energy storage system due to its high energy density, cost effectiveness and environmental friendliness of sulfur. However, there are still a number of technical challenges, such as low Coulombic efficiency and poor long-term cycle life, impeding the commercialization of Li-S battery. The electrochemical performance of Li-S battery is closely related with the interfacial reactions occurring between hosting substrate and active sulfur species which are poorly conducting at fully oxidized and reduced states. Here, we correlate the relationship between the performance and interfacial reactions in the Li-S battery system, using a hollow carbon nanosphere (HCNS) with highly graphitic character as hosting substrate for sulfur. With an appropriate amount of sulfur loading, HCNS/S composite exhibits excellent electrochemical performance because of the fast interfacial reactions between HCNS and the polysulfides. However, further increase of sulfur loading leads to increased formation of highly resistive insoluble reaction products (Li2S2/Li2S) which limits the reversibility of the interfacial reactions and results in poor electrochemical performances. These findings demonstrate the importance of the interfacial reaction reversibility in the whole electrode system on achieving high capacity and long cycle life of sulfur cathode for Li-S batteries.

Background. Patients with recurrent synovial sarcomas have few options for systemic therapy. Since they express large amounts of endogenous CT (cancer testis) antigens such as NY-ESO-1, we investigated the clinical activity of single agent anti-CTLA4 antibody ipilimumab in patients with advanced or metastatic synovial sarcoma. Methods. A Simon two-stage phase II design was used to determine if there was sufficient activity to pursue further. The primary endpoint was tumor response rate by RECIST 1.0. Patients were treated with ipilimumab 3 mg/kg intravenously every 3 weeks for three cycles and then restaged. Retreatment was possible for patients receiving an extra three-week break from therapy. Sera and peripheral blood mononuclear cells were collected before and during therapy to assess NY-ESO-1-specific immunity. Results. Six patients were enrolled and received 1–3 cycles of ipilimumab. All patients showed clinical or radiological evidence of disease progression after no more than three cycles of therapy, for a RECIST response rate of 0%. The study was stopped for slow accrual, lack of activity, and lack of immune response. There was no evidence of clinically significant either serologic or delayed type hypersensitivity responses to NY-ESO-1 before or after therapy. Conclusion. Despite high expression of CT antigens by synovial sarcomas of patients treated in this study, there was neither clinical benefit nor evidence of anti-CT antigen serological responses. Assessment of the ability of synovial sarcoma cell lines to present cancer-germ cell antigens may be useful in determining the reason for the observed lack of immunological or clinical activity.