The potential impact of climate change on the efficiency and reliability of solar, hydro, and wind energy sources

Climate change impacts the electric power system by affecting both the load and generation. It is paramount to understand this impact in the context of renewable energy as their market share has increased and will continue to grow. This study investigates the impact of climate change on the supply of renewable energy through applying novel metrics of intermittency, power production and storage required by the renewable energy plants as a function of historical climate data variability. Here we focus on and compare two disparate locations, Palma de Mallorca in the Balearic Islands and Cordova, Alaska. The main results of this analysis of wind, solar radiation and precipitation over the 1950–2020 period show that climate change impacts both the total supply available and its variability. Importantly, this impact is found to vary significantly with location. This analysis demonstrates the feasibility of a process to evaluate the local optimal mix of renewables, the changing needs for energy storage as well as the ability to evaluate the impact on grid reliability regarding both penetration of the increasing renewable resources and changes in the variability of the resource. This framework can be used to quantify the impact on both transmission grids and microgrids and can guide possible mitigation paths.P.C. and D.G. acknowledge financial support from Ministerio de Ciencia e Innovación (Spain), the Agencia Estatal de Investigación (AEI, Spain), and the Fondo Europeo de Desarrollo Regional (FEDER, EU) under grant PACSS (RTI2018-093732-B-C22) and the Maria de Maeztu program for Units of Excellence in R&D (MDM-2017-0711). D.N. gratefully acknowledges support from DOE Project GMLC 1.5.02—Resilient Alaskan Distribution system Improvements using Automation, Network analysis, Control, and Energy storage (RADIANCE). U.S.B. acknowledges support from the National Science Foundation under award #OIA-1753748 and by the State of Alaska for material which this work is based upon

Unique features of the mode of action of ET-743

This paper describes the current knowledge of the primary mode of action of a natural product, ecteinascidin 743 (ET-743), derived from the marine tunicate Ecteinascidia turbinata. ET-743 was initially selected for preclinical development because of its potent antitumor activity observed against several human solid tumor types. In vitro, the drug is cytotoxic in the nanomolar range, and in the case of some very sensitive cell lines, in the picomolar range. The large potency differences observed among several solid tumor types indicate that this compound possesses some tumor selectivity, but the molecular basis of these differential effects remains to be elucidated. The present studies were undertaken to evaluate the mechanism of action of ET-743 in this context. The available information on ET-743 binding to DNA and its effects on transcriptional regulation point to a unique behavior of this drug, as it independently affects specific gene transcription in a promoter-dependent way. In addition, ET-743 shows a peculiar pattern of selectivity in cells with different defects in their DNA-repair pathways. These results highlight a unique property of ET-743, possibly explaining why it possesses antitumor activity against tumors that are refractory to standard anticancer drugs, all of which certainly act by mechanisms that are different from that of ET-743

Changes of salivary biomarkers under different storage conditions : Effects of temperature and length of storage

Introduction: In this report, we aimed to examine the stability of various analytes in saliva under different storage conditions. Materials and methods: Alpha-amylase (AMY), cholinesterase (CHE), lipase (Lip), total esterase (TEA), creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LD), lactate (Lact), adenosine deaminase (ADA), Trolox equivalent antioxidant capacity (TEAC), ferric reducing ability (FRAS), cupric reducing antioxidant capacity (CUPRAC), uric acid (UA), catalase (CAT), advanced oxidation protein products (AOPP) and hydrogen peroxide (H O) were colorimetrically measured in saliva obtained by passive drool from 12 healthy voluntary donors at baseline and after 3, 6, 24, 72 hours, 7 and 14 days at room temperature (RT) and 4 ºC, and after 14 days, 1, 3 and 6 months at - 20 ºC and - 80 ºC. Results: At RT, changes appeared at 6 hours for TEA and H O; 24 hours for Lip, CK, ADA and CUPRAC; and 72 hours for LD, Lact, FRAS, UA and AOPP. At 4 ºC changes were observed after 6 hours for TEA and H O; 24 hours for Lip and CUPRAC; 72 hours for CK; and 7 days for LD, FRAS and UA. At - 20 ºC changes appeared after 14 days for AST, Lip, CK and LD; and 3 months for TEA and H O. At - 80 ºC observed changes were after 3 months for TEA and H O. Conclusions: In short-term storage, the analytes were more stable at 4 ºC than at room temperature, whereas in long-term storage they were more stable at -80 ºC than at - 20 ºC

Genomic instability in human cancer: molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition

Genomic instability can initiate cancer, augment progression, and influence the overall prognosis of the affected patient. Genomic instability arises from many different pathways, such as telomere damage, centrosome amplification, epigenetic modifications, and DNA damage from endogenous and exogenous sources, and can be perpetuating, or limiting, through the induction of mutations or aneuploidy, both enabling and catastrophic. Many cancer treatments induce DNA damage to impair cell division on a global scale but it is accepted that personalized treatments, those that are tailored to the particular patient and type of cancer, must also be developed. In this review, we detail the mechanisms from which genomic instability arises and can lead to cancer, as well as treatments and measures that prevent genomic instability or take advantage of the cellular defects caused by genomic instability. In particular, we identify and discuss five priority targets against genomic instability: (1) prevention of DNA damage; (2) enhancement of DNA repair; (3) targeting deficient DNA repair; (4) impairing centrosome clustering; and, (5) inhibition of telomerase activity. Moreover, we highlight vitamin D and B, selenium, carotenoids, PARP inhibitors, resveratrol, and isothiocyanates as priority approaches against genomic instability. The prioritized target sites and approaches were cross validated to identify potential synergistic effects on a number of important areas of cancer biology

Credit bureaus between risk-management, creditworthiness assessment and prudential supervision

"This text may be downloaded for personal research purposes only. Any additional reproduction for other purposes, whether in hard copy or electronically, requires the consent of the author. If cited or quoted, reference should be made to the full name of the author, the title, the working paper or other series, the year, and the publisher."This paper discusses the role and operations of consumer Credit Bureaus in the European Union in the context of the economic theories, policies and law within which they work. Across Europe there is no common practice of sharing the credit data of consumers which can be used for several purposes. Mostly, they are used by the lending industry as a practice of creditworthiness assessment or as a risk-management tool to underwrite borrowing decisions or price risk. However, the type, breath, and depth of information differ greatly from country to country. In some Member States, consumer data are part of a broader information centralisation system for the prudential supervision of banks and the financial system as a whole. Despite EU rules on credit to consumers for the creation of the internal market, the underlying consumer data infrastructure remains fragmented at national level, failing to achieve univocal, common, or defined policy objectives under a harmonised legal framework. Likewise, the establishment of the Banking Union and the prudential supervision of the Euro area demand standardisation and convergence of the data used to measure debt levels, arrears, and delinquencies. The many functions and usages of credit data suggest that the policy goals to be achieved should inform the legal and institutional framework of Credit Bureaus, as well as the design and use of the databases. This is also because fundamental rights and consumer protection concerns arise from the sharing of credit data and their expanding use

The impact of pre-transplantation nephrectomy on quality of life in patients with autosomal dominant polycystic kidney disease

PURPOSE: In selected ADPKD patients, a nephrectomy is required in the work-up for a kidney transplantation. Because the impact of this procedure is unknown, we investigated the effect of pre-transplantation nephrectomy on quality of life in this group.METHODS: In this retrospective cohort study all ADPKD patients, ≥ 18 years, who received a kidney transplantation in 2 ADPKD expertise centers between January 2000 and January 2016, were asked to participate. Quality of life was assessed using three validated questionnaires on three time points. Nephrectomy was performed in preparation for transplantation.RESULTS: Two hundred seventy-six ADPKD patients (53 ± 9 years, 56.2% male) were included. 98 patients (35.5%) underwent native nephrectomy in preparation for transplantation, of which 43 underwent bilateral nephrectomy. Pre-transplantation, ADPKD-IS scores were worse in the nephrectomy group vs. no-nephrectomy group (physical: 2.9 vs. 2.3, p &lt; 0.001; emotional: 2.0 vs. 1.8, p = 0.03; fatigue: 3.0 vs. 2.3, p = 0.01). Post-transplantation and post-nephrectomy, ADPKD-IS scores improved significantly in both groups, with a significantly higher improvement in the nephrectomy group. During follow-up, all scores were still better compared to pre-transplantation. Observed physical QoL (ADPKD-IS physical 1.3 vs. 1.7, p = 0.04; SF-36 physical 50.0 vs. 41.3, p = 0.03) was better post-transplantation after bilateral nephrectomy compared to unilateral nephrectomy. In retrospect, 19.7% of patients would have liked to undergo a nephrectomy, while the decision not to perform nephrectomy was made by the treating physician.CONCLUSION: This study shows that pre-transplantation nephrectomy improves quality of life in selected ADPKD patients. Bilateral nephrectomy may be preferred, although the risk of additional complications should be weighted.</p

Characterization of a new trabectedin-resistant myxoid liposarcoma cell line that shows collateral sensitivity to methylating agents

Myxoid Liposarcomas (MLS), characterized by the expression of FUS-CHOP fusion gene are clinically very sensitive to the DNA binding antitumor agent, trabectedin. However, resistance eventually occurs, preventing disease eradication. To investigate the mechanisms of resistance, a trabectedin resistant cell line, 402-91/ET, was developed. The resistance to trabectedin was not related to the expression of MDR related proteins, uptake/efflux of trabectedin or GSH levels that were similar in parental and resistant cells. The 402-91/ET cells were hypersensitive to UV light because of a nucleotide excision repair defect: XPG complementation decreased sensitivity to UV rays, but only partially to trabectedin. 402-91/ET cells showed collateral sensitivity to temozolomide due to the lack of O(6) -methylguanine-DNA-methyltransferase (MGMT) activity, related to the hypermethylation of MGMT promoter. In 402-91 cells chromatin immunoprecipitation (ChIP) assays showed that FUS-CHOP was bound to the PTX3 and FN1 gene promoters, as previously described, and trabectedin caused FUS-CHOP detachment from DNA. Here we report that, in contrast, in 402-91/ET cells, FUS-CHOP was not bound to these promoters. Differences in the modulation of transcription of genes involved in different pathways including signal transduction, apoptosis and stress response between the two cell lines were found. Trabectedin activates the transcription of genes involved in the adipogenic-program such as c/EBPα and β, in 402-91 but not in 402-91/ET cell lines. The collateral sensitivity of 402-91/ET to temozolomide provides the rationale to investigate the potential use of methylating agents in MLS patients resistant to trabectedin

100 key questions to guide hydropeaking research

As the share of renewable energy grows worldwide, flexible energy production from peak-operating hydropower and the phenomenon of hydropeaking have received increasing attention. In this study, we collected open research questions from 220 experts in river science, practice, and policy across the globe using an online survey available in six languages related to hydropeaking. We used a systematic method of determining expert consensus (Delphi method) to identify 100 high-priority questions related to the following thematic fields: (a) hydrology, (b) physico-chemical properties of water, (c) river morphology and sediment dynamics, (d) ecology and biology, (e) socio-economic topics, (f) energy markets, (g) policy and regulation, and (h) management and mitigation measures. The consensus list of high-priority questions shall inform and guide researchers in focusing their efforts to foster a better science-policy interface, thereby improving the sustainability of peak-operating hydropower in a variety of settings. We find that there is already a strong understanding of the ecological impact of hydropeaking and efficient mitigation techniques to support sustainable hydropower. Yet, a disconnect remains in its policy and management implementation.publishedVersio

Соотношение токсичности и преимуществ использования бевацизумаба при метастатическом раке толстой кишки: метаанализ рандомизированных клинических испытаний

Проведен систематический обзор и метаанализ, изучающий использование бевацизумаба (Бев) при метастатическом колоректальном раке. В анализ включены данные исследований, в которых принимали участие 3385 пациентов. Первичной конечной точкой была безопасность терапии, вторичными конечными точками — общая выживаемость и выживаемость без прогрессирования заболевания. Относительные риски (ОР) для побочных эффектов расчитывали с 95% доверительным интервалом (ДИ), с использованием метода обратной дисперсии. Для статистически значимых ОР определяли число обследуемых, которых необходимо дополнительно включить в группу Бев для нанесения вреда одному дополнительному пациенту в сравнении с контролем (number needed to harm — NNH). Значимое повышение ОР наблюдалось только для гипертензии (относительный риск 2,98, 95% ДИ 2,32–3,84), гастроинтестинальных перфораций (5,04, 95% ДИ 1,72–14,79) и кровотечений (2,07, 95% ДИ 1,19–3,62). Бев значимо улучшал как общую (ОР 0,80, 95% ДИ 0,71–0,91), так и беспрогрессивную выживаемость (ОР 0,62, 95% ДИ 0,52–0,74). Количество пациентов, которых необходимо дополнительно пролечить (number needed to treat — NNT) в группе Бев для достижения 1 дополнительного случая ОВ в сравнении с контролем составило 12, в то время как показатель NNH для разных побочных эффектов колебался в пределах 2–124. Полученные результаты демонстрируют, что преимущества терапии Бев перевешивают его возможную токсичность. Данных достаточно для подтверждения целесообразности использования Авастина при метастатическом колоректальном раке.A systematic review and meta-analysis investigating bevacizumab in metastatic colorectal cancer were performed. The primary endpoint was safety and secon dary endpoints were overall survival and progression-free survival. The relative risks for side effects were calcula ted with their 95% confidence interval (CI) using the inverse of variance method. For statistically significant relative risks, number needed to harm were calculated. Authors retrieved 6 out of 17 eligible papers encompassing 3385 patients. Only hypertension (relative risk 2,98 95% CI 2,32-3,84), gastrointestinal perforations (relative risk 5,04 95% CI 1,72–14,79) and bleeding (relative risk 2,07 95% CI 1,19–3.62) were significantly increased. Bevacizumab significantly improved both overall survival (HR 0,80 95% CI 0,71–0,91) and progression-free survival (hazard ratio (HR) 0,62 95% CI 0,52–0,74). Number needed to treat for overall survival is 12, whilst number needed to harms ranges from 2 to 14,286

ZNF93 Increases Resistance to ET-743 (Trabectedin; Yondelis®) and PM00104 (Zalypsis®) in Human Cancer Cell Lines

ET-743 (trabectedin, Yondelis) and PM00104 (Zalypsis) are marine derived compounds that have antitumor activity. ET-743 and PM00104 exposure over sustained periods of treatment will result in the development of drug resistance, but the mechanisms which lead to resistance are not yet understood.Human chondrosarcoma cell lines resistant to ET-743 (CS-1/ER) or PM00104 (CS-1/PR) were established in this study. The CS-1/ER and CS-1/PR exhibited cross resistance to cisplatin and methotrexate but not to doxorubicin. Human Affymetrix Gene Chip arrays were used to examine relative gene expression in these cell lines. We found that a large number of genes have altered expression levels in CS-1/ER and CS-1/PR when compared to the parental cell line. 595 CS-1/ER and 498 CS-1/PR genes were identified as overexpressing; 856 CS-1/ER and 874 CS-1/PR transcripts were identified as underexpressing. Three zinc finger protein (ZNF) genes were on the top 10 overexpressed genes list. These genes have not been previously associated with drug resistance in tumor cells. Differential expressions of ZNF93 and ZNF43 genes were confirmed in both CS-1/ER and CS-1/PR resistant cell lines by real-time RT-PCR. ZNF93 was overexpressed in two ET-743 resistant Ewing sarcoma cell lines as well as in a cisplatin resistant ovarian cancer cell line, but was not overexpressed in paclitaxel resistant cell lines. ZNF93 knockdown by siRNA in CS-1/ER and CS-1/PR caused increased sensitivity for ET-743, PM00104, and cisplatin. Furthermore, ZNF93 transfected CS-1 cells are relatively resistant to ET-743, PM00104 and cisplatin.This study suggests that zinc finger proteins, and ZNF93 in particular, are involved in resistance to ET-743 and PM00104