63 research outputs found
PyPSA-GB: An open-source model of Great Britainās power system for simulating future energy scenarios
This paper presents PyPSA-GB, a dataset and model of Great Britainās (GB) power system encompassing historical years and the future energy scenarios developed by National Grid. It is the first fully open-source model implementation of the future GB power system with high spatial and temporal resolution, and data for future years up to 2050. Two power dispatch formulations can be optimised: (i) single bus unit commitment problem, and (ii) network constrained linear optimal power flow. The model is showcased through an example analysis of quantifying future wind curtailment in Scotland. PyPSA-GB provides an open-source basis for GB operational and planning studies, e.g., sector coupling and flexibility options
The Impact of the Time Interval Between Radiation and Hyperthermia on Clinical Outcome in Patients With Locally Advanced Cervical Cancer
A Causal Discovery Approach To Learn How Urban Form Shapes Sustainable Mobility Across Continents
Global sustainability requires low-carbon urban transport systems, shaped by
adequate infrastructure, deployment of low-carbon transport modes and shifts in
travel behavior. To adequately implement alterations in infrastructure, it's
essential to grasp the location-specific cause-and-effect mechanisms that the
constructed environment has on travel. Yet, current research falls short in
representing causal relationships between the 6D urban form variables and
travel, generalizing across different regions, and modeling urban form effects
at high spatial resolution. Here, we address all three gaps by utilizing a
causal discovery and an explainable machine learning framework to detect urban
form effects on intra-city travel based on high-resolution mobility data of six
cities across three continents. We show that both distance to city center,
demographics and density indirectly affect other urban form features. By
considering the causal relationships, we find that location-specific influences
align across cities, yet vary in magnitude. In addition, the spread of the city
and the coverage of jobs across the city are the strongest determinants of
travel-related emissions, highlighting the benefits of compact development and
associated benefits. Differences in urban form effects across the cities call
for a more holistic definition of 6D measures. Our work is a starting point for
location-specific analysis of urban form effects on mobility behavior using
causal discovery approaches, which is highly relevant for city planners and
municipalities across continents.Comment: 22 pages, 13 figures, 4 table
PyPSA-Earth. A New Global Open Energy System Optimization Model Demonstrated in Africa
Macro-energy system modelling is used by decision-makers to steer the global
energy transition toward an affordable, sustainable and reliable future.
Closed-source models are the current standard for most policy and industry
decisions. However, open models have proven to be competitive alternatives that
promote science, robust technical analysis, collaboration and transparent
policy decision-making. Yet, two issues slow the adoption: open models are
often designed with limited geographic scope, hindering synergies from
collaboration, or are based on low spatially resolved data, limiting their use.
Here we introduce PyPSA-Earth, the first open-source global energy system model
with data in high spatial and temporal resolution. It enables large-scale
collaboration by providing a tool that can model the world energy system or any
subset of it. This work is derived from the European PyPSA-Eur model using new
data and functions. It is suitable for operational as well as combined
generation, storage and transmission expansion studies. The model provides two
main features: (1) customizable data extraction and preparation scripts with
global coverage and (2) a PyPSA energy modelling framework integration. The
data includes electricity demand, generation and medium to high-voltage
networks from open sources, yet additional data can be further integrated. A
broad range of clustering and grid meshing strategies help adapt the model to
computational and practical needs. A data validation for the entire African
continent is performed and the optimization features are tested with a 2060
net-zero planning study for Nigeria. The demonstration shows that the presented
developments can build a highly detailed energy system model for energy
planning studies to support policy and technical decision-making. We welcome
joining forces to address the challenges of the energy transition together.Comment: 36 pages, 14 figures, 3 table
Radiosensitization with Hyperthermia and Chemotherapeutic Agents: Effects on Linear-Quadratic Parameters of Radiation Cell Survival Curves
Analysis of Gene Expression Using Gene Sets Discriminates Cancer Patients with and without Late Radiation Toxicity
BACKGROUND: Radiation is an effective anti-cancer therapy but leads to severe late radiation toxicity in 5%ā10% of patients. Assuming that genetic susceptibility impacts this risk, we hypothesized that the cellular response of normal tissue to X-rays could discriminate patients with and without late radiation toxicity. METHODS AND FINDINGS: Prostate carcinoma patients without evidence of cancer 2 y after curative radiotherapy were recruited in the study. Blood samples of 21 patients with severe late complications from radiation and 17 patients without symptoms were collected. Stimulated peripheral lymphocytes were mock-irradiated or irradiated with 2-Gy X-rays. The 24-h radiation response was analyzed by gene expression profiling and used for classification. Classification was performed either on the expression of separate genes or, to augment the classification power, on gene sets consisting of genes grouped together based on function or cellular colocalization. X-ray irradiation altered the expression of radio-responsive genes in both groups. This response was variable across individuals, and the expression of the most significant radio-responsive genes was unlinked to radiation toxicity. The classifier based on the radiation response of separate genes correctly classified 63% of the patients. The classifier based on affected gene sets improved correct classification to 86%, although on the individual level only 21/38 (55%) patients were classified with high certainty. The majority of the discriminative genes and gene sets belonged to the ubiquitin, apoptosis, and stress signaling networks. The apoptotic response appeared more pronounced in patients that did not develop toxicity. In an independent set of 12 patients, the toxicity status of eight was predicted correctly by the gene set classifier. CONCLUSIONS: Gene expression profiling succeeded to some extent in discriminating groups of patients with and without severe late radiotherapy toxicity. Moreover, the discriminative power was enhanced by assessment of functionally or structurally related gene sets. While prediction of individual response requires improvement, this study is a step forward in predicting susceptibility to late radiation toxicity
Sensitizing thermochemotherapy with a PARP1-inhibitor
Cis-diamminedichloroplatinum(II) (cisplatin, cDDP) is an effective chemotherapeutic agent that induces DNA double strand breaks (DSBs), primarily in replicating cells. Generally, such DSBs can be repaired by the classical or backup non-homologous end joining (c-NHEJ/b-NHEJ) or homologous recombination (HR). Therefore, inhibiting these pathways in cancer cells should enhance the efficiency of cDDP treatments. Indeed, inhibition of HR by hyperthermia (HT) sensitizes cancer cells to cDDP and in the Netherlands this combination is a standard treatment option for recurrent cervical cancer after previous radiotherapy. Additionally, cDDP has been demonstrated to disrupt c-NHEJ, which likely further increases the treatment efficacy. However, if one of these pathways is blocked, DSB repair functions can be sustained by the Poly-(ADP-ribose)-polymerase1 (PARP1)-dependent b-NHEJ. Therefore, disabling b-NHEJ should, in principle, further inhibit the repair of cDDP-induced DNA lesions and enhance the toxicity of thermochemotherapy. To explore this hypothesis, we treated a panel of cancer cell lines with HT, cDDP and a PARP1-i and measured various end-point relevant in cancer treatment. Our results demonstrate that PARP1-i does not considerably increase the efficacy of HT combined with standard, commonly used cDDP concentrations. However, in the presence of a PARP1-i, ten-fold lower concentration of cDDP can be used to induce similar cytotoxic effects. PARP1 inhibition may thus permit a substantial lowering of cDDP concentrations without diminishing treatment efficacy, potentially reducing systemic side effects
Enhancing synthetic lethality of PARP-inhibitor and cisplatin in BRCA-proficient tumour cells with hyperthermia
Background: Poly-(ADP-ribose)-polymerase1 (PARP1) is involved in repair of DNA single strand breaks. PARP1-inhibitors (PARP1-i) cause an accumulation of DNA double strand breaks, which are generally repaired by homologous recombination (HR). Therefore, cancer cells harboring HR deficiencies are exceptionally sensitive to PARP1-i. For patients with HR-proficient tumors, HR can be temporarily inhibited by hyperthermia, thereby inducing synthetic lethal conditions in every tumor type. Since cisplatin is successfully used combined with hyperthermia (thermochemotherapy), we investigated the effectiveness of combining PARP1-i with thermochemotherapy. Results: The in vitro data demonstrate a decreased in cell survival after addition of PARP1-i to thermochemotherapy, which can be explained by increased DNA damage induction and less DSB repair. These in vitro findings are in line with in vivo model, in which a decreased tumor growth is observed upon addition of PARP1-i. Materials and Methods: Survival of three HR-proficient cell lines after cisplatin, hyperthermia and/or PARP1-i was studied. Cell cycle analyses, quantification of Ī³-H2AX foci and apoptotic assays were performed to understand these survival data. The effects of treatments were further evaluated by monitoring tumor responses in an in vivo rat model. Conclusions: Our results in HR-proficient cell lines suggest that PARP1-i combined with thermochemotherapy can be a promising clinical approach for all tumors independent of HR status
How does it scale? Comparing quantum and classical nonlinear optical processes in integrated devices
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