Engineering Parallel String Sorting

We discuss how string sorting algorithms can be parallelized on modern multi-core shared memory machines. As a synthesis of the best sequential string sorting algorithms and successful parallel sorting algorithms for atomic objects, we first propose string sample sort. The algorithm makes effective use of the memory hierarchy, uses additional word level parallelism, and largely avoids branch mispredictions. Then we focus on NUMA architectures, and develop parallel multiway LCP-merge and -mergesort to reduce the number of random memory accesses to remote nodes. Additionally, we parallelize variants of multikey quicksort and radix sort that are also useful in certain situations. Comprehensive experiments on five current multi-core platforms are then reported and discussed. The experiments show that our implementations scale very well on real-world inputs and modern machines.Comment: 46 pages, extension of "Parallel String Sample Sort" arXiv:1305.115

Crucial Role of Reactive Oxygen Species (ROS) for the Proapoptotic Effects of Indirubin Derivatives in Cutaneous SCC Cells

Efficient drugs are needed for countering the worldwide high incidence of cutaneous squamous cell carcinoma (cSCC) and actinic keratosis. Indirubin derivatives represent promising candidates, but their effects in cSCC cells have not been reported before. Here, we investigated the efficacy of three indirubin derivatives (DKP-071, -073 and -184) in four cSCC cell lines. High efficacy was seen in SCL-I, SCL-II, SCC-12 and SCC-13, resulting in up to 80% loss of cell proliferation, 60% loss of cell viability and 30% induced apoptosis (10 µM). Apoptosis was further enhanced in combinations with TNF-related apoptosis-inducing ligand (TRAIL). Induction of reactive oxygen species (ROS) appeared as critical for these effects. Thus, antioxidative pretreatment completely abolished apoptosis as well as restored cell proliferation and viability. Concerning the pathways, complete activation of caspases cascades (caspases-3, -4, -6, -7, -8 and -9), loss of mitochondrial membrane potential, activation of proapoptotic PKCδ (protein kinase C delta), inhibition of STAT3 (signal transducer and activator of transcription 3), downregulation of antiapoptotic XIAP (X-linked inhibitor of apoptosis protein) and survivin as well as upregulation of the proapoptotic Bcl-2 protein Puma and the cell cycle inhibitor p21 were obtained. Importantly, all activation steps were prevented by antioxidants, thus proving ROS as a master regulator of indirubins’ antitumor effects. ROS induction presently develops as an important issue in anticancer therapy

Crucial Role of Reactive Oxygen Species (ROS) for the Proapoptotic Effects of Indirubin Derivatives in Cutaneous SCC Cells

Efficient drugs are needed for countering the worldwide high incidence of cutaneous squamous cell carcinoma (cSCC) and actinic keratosis. Indirubin derivatives represent promising candidates, but their effects in cSCC cells have not been reported before. Here, we investigated the efficacy of three indirubin derivatives (DKP-071,-073 and-184) in four cSCC cell lines. High efficacy was seen in SCL-I, SCL-II, SCC-12 and SCC-13, resulting in up to 80% loss of cell proliferation, 60% loss of cell viability and 30% induced apoptosis (10 µM). Apoptosis was further enhanced in com-binations with TNF-related apoptosis-inducing ligand (TRAIL). Induction of reactive oxygen species (ROS) appeared as critical for these effects. Thus, antioxidative pretreatment completely abol-ished apoptosis as well as restored cell proliferation and viability. Concerning the pathways, com-plete activation of caspases cascades (caspases-3,-4,-6,-7,-8 and-9), loss of mitochondrial membrane potential, activation of proapoptotic PKCδ (protein kinase C delta), inhibition of STAT3 (sig-nal transducer and activator of transcription 3), downregulation of antiapoptotic XIAP (X-linked inhibitor of apoptosis protein) and survivin as well as upregulation of the proapoptotic Bcl-2 protein Puma and the cell cycle inhibitor p21 were obtained. Importantly, all activation steps were pre-vented by antioxidants, thus proving ROS as a master regulator of indirubins’ antitumor effects. ROS induction presently develops as an important issue in anticancer therapy. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Methodology for the numerical prediction of pollutant formation in gas turbine combustors and associated validation experiments

International audienceFor aircraft engine manufacturers the formation of pollutants such as NOx or soot particles is an important issue because the regulations on pollutant emissions are becoming increasingly stringent. In order to comply with these regulations, new concepts of gas turbine combustors must be developed with the help of simulation tools. In this paper we present two different strategies, proposed by ONERA and DLR respectively, to simulate soot or NOx formation in combustors. The first one is based on simple chemistry models allowing significant effort to be spent on the LES description of the flow, while the second one is based on more accurate, but also more expensive, models for soot chemistry and physics. Combustion experiments dedicated to the validation of these strategies are described next: The first one, performed at DLR, was operated at a semi-technical scale and aimed at very accurate and comprehensive information on soot formation and oxidation under well-defined experimental conditions; the second one, characterized at ONERA, was aimed at reproducing the severe conditions encountered in realistic gas turbine combustors. In the third part of the paper the results of combustion simulations are compared to those of the validation experiments. It is shown that a fine description of the physics and chemistry involved in the pollutant formation is necessary but not sufficient to obtain quantitative predictions of pollutant formation. An accurate calculation of the turbulent reactive flow interacting with pollutant formation and influencing dilution, oxidation and transport is also required: when the temperature field is correctly reproduced, as is the case of the ONERA simulation of the DLR combustor, the prediction of soot formation is quite satisfactory while difficulty in reproducing the temperature field in the TLC combustor leads to overestimations of NOx and soot concentrations.Pour les constructeurs de moteurs d’avion, la formation de polluants comme les NOx ou les particules de suies est une question importante car la réglementation sur les émissions polluantes est de plus en plus sévère. Pour respecter cette réglementation, de nouveaux concepts de foyers de turbine à gaz doivent être développés avec l’aide d’outils de simulation. Dans cet article, nous présentons deux stratégies différentes proposées par l’ONERA et le DLR pour simuler la formation des suies et des NOx dans les chambres de combustion. La première est basée sur des modèles chimiques simples permettant de faire porter l’effort de calcul sur la description LES de l’écoulement, tandis que la seconde est basée sur des modèles physico-chimiques de formation des suies plus précis mais aussi plus coûteux en temps de calcul. Des expériences de combustion conçues pour la validation de ces stratégies sont ensuite décrites : La première, réalisée au DLR, reproduit la combustion à une échelle semi-industrielle et a pour but de donner une information très précise et complète sur les mécanismes de formation des suies et leur oxydation dans des conditions expérimentales parfaitement maîtrisées ; la seconde, réalisée à l’ONERA, a pour but de reproduire de façon réaliste les conditions sévères rencontrées dans les foyers de turbine à gaz industrielles. Dans la troisième partie du papier, les résultats des simulations de combustion sont comparés à ceux des expériences de validation. Il est démontré que la description précise de la physique et de la chimie intervenant dans la formation des polluants est nécessaire mais non suffisante pour simuler correctement les quantités de polluants formés. Un calcul précis de l’écoulement turbulent réactif interagissant avec les mécanismes de formation, de dilution, d’oxydation et de transport des polluants est également nécessaire : Lorsque le champ de température est correctement reproduit comme c’est le cas pour la simulation ONERA du foyer DLR, la simulation de la formation des suies est assez satisfaisante, alors qu’une difficulté pour reproduire le champ de température dans le foyer TLC conduit à une surestimation des concentrations de NOx et de suies

Transcranial Doppler-detected cerebral embolic load during transcatheter aortic valve implantation†

OBJECTIVES Transcatheter aortic valve implantation (TAVI) is an alternative to surgery for high-risk patients with severe aortic valve stenosis. Periprocedural stroke is reported at an incidence up to 10%. Magnetic resonance imaging studies have identified new onset of clinically silent ischaemic cerebral lesions more frequently (68-84%). So far, few data are available about cerebral embolism during TAVI. The aim of this study was to determine the frequency of high-intensity transient signals (HITS) and to explore differences in the HITS pattern between transfemoral and transapical access and between self-expanding (SE) and balloon-expandable (BE) deployment technique. METHODS Transcranial Doppler (TCD) ultrasound recordings of 44 patients undergoing TAVI (age 78±6 years; logistic EuroSCORE 28±15%; transfemoral access, n=32; transapical access, n=12; SE, n=27; BE, n=17) were analysed for HITS during the following intervals: (i) instrumentation prior to valvuloplasty, (ii) balloon valvuloplasty, (iii) prosthesis deployment (DP) and (iv) post-implantation (PI) including any re-dilatation episodes. The total procedural load of HITS and HITS frequency in procedural intervals were compared between different access routes and DP techniques. Periprocedural neurocognitive impairment was assessed clinically and by the confusion assessment method (CAM) prior to TAVI and on post-procedural days 1 and 4-6. RESULTS TCD recordings demonstrated the occurrence of HITS in all patients. DP was associated with the highest load of HITS. Access route did not significantly influence the total burden of periprocedural HITS. During procedures using the SE type, a slightly larger total load of HITS was observed than with the BE type (P=0.024). This was mainly due to more HITS during the DP (P=0.027) and the PI interval (P=0.002). No incidence of delirium was detected by CAM ratings. Two patients suffered a new onset of stroke within the 2 weeks following the procedure. In-hospital death and 30-day mortality were 0/44. CONCLUSIONS HITS are observed during all procedural intervals in TAVI. The embolic events appear to peak during DP. In our series, the overall cerebral embolic load did not differ between the transfemoral and the transapical access route. TCD monitoring in TAVI is useful to identify periods and manipulations associated with an increased cerebral embolic load and may help to further enhance the safety of this procedur

Strengthening health data on a rare and heterogeneous disease: sarcoma incidence and histological subtypes in Germany

Background: The population-based incidence of sarcoma and its histological subtypes in Germany is unknown. Up-to-date information on a disease with an incidence comparable to other cancer entities is of high public health relevance. The aim of this study was to determine this incidence and to detect significant changes in incidence trends using data from German epidemiological cancer registries. Methods: Pooled data from the German Centre for Cancer Registry Data with a primary diagnosis occurring in 2013 were used. To date, this is the latest data on cancer incidence available for Germany. All German cancer registries with sufficient completeness were included (10 out of 11), covering a population of 70.0 million people, representing 87% of the German population. All malignant sarcomas according to the RARECARE Project and the WHO classification 2002 were considered for analysis and, above all, gastrointestinal stromal tumours (GIST) of uncertain behaviour. Sensitivity analysis was performed excluding certain histologies. Results: The analysis included 3404 cases in men and 3442 cases in women diagnosed in 2013. The age adjusted sarcoma incidence (European standard) was 7.4 (men) and 6.6 (women) per 100,000 inhabitants. About 70% of sarcomas were soft tissue sarcomas, about 22% GIST, and about 9% bone sarcomas. The most common histological subtypes besides GIST were fibrosarcomas (14%) and liposarcomas (12%) in men and complex mixed and stromal neoplasms (22%), non-uterine leiomysarcomas (10%) and fibrosarcomas (9%) in women. Considering the trend for the years of diagnosis 2004 to 2013, there was a significant increase in incidence for GIST while the incidence of soft tissue sarcomas (only men) as well as of bone sarcoma stayed constant over time. As to soft tissue sarcoma in women, the incidence stayed constant up to the year 2009 and significantly decreased afterwards. Conclusion: This study is the first detailed analysis of a German-wide population-based sarcoma incidence showing results comparable to the incidence detected in the RARECARE Project

Mitochondrial DNA Content in Human Omental Adipose Tissue

Background: Impairment of mitochondrial function plays an important role in obesity and the development of insulin resistance. The aim of this project was to investigate the mitochondrial DNA copy number in human omental adipose tissue with respect to obesity. Methods: The mitochondrial DNA (mtDNA) content per single adipocyte derived from abdominal omental adipose tissue was determined by quantitative RT-PCR in a group of 75 patients, consisting of obese and morbidly obese subjects, as well as non-obese controls. Additionally, basal metabolic rate and fat oxidation rate were recorded and expressed as total values or per kilogram fat mass. Results: MtDNA content is associated with obesity. Higher body mass index (BMI) resulted in a significantly elevated mtDNA count (ratio = 1.56; p = 0.0331) comparing non-obese (BMI < 30) to obese volunteers (BMI ≥ 30). The mtDNA count per cell was not correlated with age or gender. Diabetic patients showed a trend toward reduced mtDNA content. A seasonal change in mtDNA copy number could not be identified. In addition, a substudy investigating the basal metabolic rate and the fasting fat oxidation did not reveal any associations to the mtDNA count. Conclusions: The mtDNA content per cell of omental adipose tissue did not correlate with various clinical parameters but tended to be reduced in patients with diabetes, which may partly explain the impairment of mitochondrial function observed in insulin resistance. Furthermore, the mtDNA content was significantly increased in patients suffering from obesity (BMI above 30). This might reflect a compensatory response to the development of obesity, which is associated with impairment of mitochondrial functio

The Bax/Bcl-2 Ratio Determines the Susceptibility of Human Melanoma Cells to CD95/Fas-Mediated Apoptosis

Defective cytochrome c release and the resulting loss of caspase-3 activation was recently shown to be essential for the susceptibility of human melanoma cells to CD95/Fas-induced apoptosis. Cytochrome c release from mitochondria is regulated by the relative amounts of apoptosis-promoting and apoptosis-inhibiting Bcl-2 proteins in the outer membrane of these organelles. The assignment of Bax/Bcl-2 ratios by quantitative Western blotting in 11 melanoma cell populations revealed a relation to the susceptibility to CD95-mediated apoptosis. We could show that a low Bax/Bcl-2 ratio was characteristic for resistant cells and a high Bax/Bcl-2 ratio was characteristic for sensitive cells. Low Bax expression was not a consequence of mutations in the p53 coding sequence. The Bax/Bcl-2 ratio was also in clear correlation with sensitivity to another cell death inducer, N-acetylsphingosine. Furthermore, Bcl-2 overexpression abolished apoptosis triggered by both apoptotic stimuli, confirming the critical role of the Bax/Bcl-2 ratio as a rheostat that determines the susceptibility to apoptosis in melanoma cells by regulating mitochondrial function. Interestingly, some chemotherapeutics lead to the activation of death pathways by CD95L upregulation, ceramide generation, direct activation of upstream caspases, or upregulation of proapoptotic genes. Taken together, these signals enter the apoptotic pathway upstream of mitochondria, resulting in activation of this central checkpoint. We therefore assumed that apoptosis deficiency of malignant melanoma can be circumvented by drugs directly influencing mitochondrial functions. For this purpose we used betulinic acid, a cytotoxic agent selective for melanoma, straightly perturbing mitochondrial functions. In fact, betulinic acid induced mitochondrial cytochrome c release and DNA fragmentation in both CD95-resistant and CD95-sensitive melanoma cell populations, independent of the Bax/Bcl-2 ratio

COMPUCEA 2nd generation performance evaluation

COMPUCEA (Combined Procedure for Uranium Concentration and Enrichment Assay) is used for on-site analytical measurements in support of joint Euratom-IAEA inspections during physical inventory verification (PIV) campaigns in European Low-Enriched Uranium (LEU) fuel fabrication plants. The analyses provided on site during the PIV involve the accurate determination of the uranium element content and of the U-235 enrichment in verification samples (uranium product samples of solid form , i.e. powders, pellets) selected by the Safeguards inspectors. These samples are dissolved and then measured by energy-dispersive X-ray absorption edge spectrometry (L-edge densitometry) to obtain the uranium elemental content and gamma spectrometry with a Lanthanum-bromide detector for the U-235 abundance determination. The second generation of COMPUCEA equipment is compact, rugged and ready-to use directly after transport, no cooling of the detectors with liquid nitrogen is required. A software package for comfortable instrument control and data handling has been implemented. The paper describes the technique, setup and calibration procedure of the instrument. Results from PIV campaigns and comparisons between COMPUCEA results with data obtained by remote analysis with a qualified primary analytical method are presented, which demonstrate the performance of the technique. The achieved uncertainties are well within the international target values. First results obtained with a sandwich detector configuration for enhanced detection efficiency of the passive gamma spectrometry and a small separate X-ray fluorescence unit for the pre-screening of the samples for their Gd content are discussed.JRC.E.7-Nuclear Safeguards and Forensic