FIELD INVERSION AND MACHINE LEARNING STRATEGIES FOR IMPROVING RANS MODELLING IN TURBOMACHINERY

Turbulence and transition modelling are critical aspects in the prediction of the flow field in turbomachinery. Recently, several research efforts have been devoted to the use of machine learning techniques for improving Reynolds-averaged Navier-Stokes (RANS) models. In this framework, a promising technique is represented by field inversion which requires to find an optimal correction field that minimises the error between numerical predictions and experimental data. In this work, Artificial Neural Networks and Random Forests are investigated as tools to generalise the correction provided by field inversion. An approach to automatically identify the regions where the correction model should be computed is proposed: this improves the fitting and reduces the calls to the model during the predictions. Furthermore, a correction-based weighting of the database is introduced in order to improve the training performances. The potential and the issues of the methods are investigated on a high-lift gas turbine cascade at low Reynolds number

Conduction band spin splitting and negative magnetoresistance in A3B5{\rm A}_3{\rm B}_5 heterostructures

The quantum interference corrections to the conductivity are calculated for an electron gas in asymmetric quantum wells in a magnetic field. The theory takes into account two different types of the spin splitting of the conduction band: the Dresselhaus terms, both linear and cubic in the wave vector, and the Rashba term, linear in wave vector. It is shown that the contributions of these terms into magnetoconductivity are not additive, as it was traditionally assumed. While the contributions of all terms of the conduction band splitting into the D'yakonov--Perel' spin relaxation rate are additive, in the conductivity the two linear terms cancel each other, and, when they are equal, in the absence of the cubic terms the conduction band spin splitting does not show up in the magnetoconductivity at all. The theory agrees very well with experimental results and enables one to determine experimentally parameters of the spin-orbit splitting of the conduction band.Comment: 8 pages, RevTeX, 4 Postscript figure

High-density neutrophils in MGUS and multiple myeloma are dysfunctional and immune-suppressive due to increased STAT3 downstream signaling

To understand neutrophil impairment in the progression from MGUS through active MM, we investigated the function of mature, high-density neutrophils (HDNs), isolated from peripheral blood. In 7 MM, 3 MGUS and 3 healthy subjects by gene expression profile, we identified a total of 551 upregulated and 343 downregulated genes in MM-HDN, involved in chemokine signaling pathway and FC-gamma receptor mediated phagocytosis conveying in the activation of STAT proteins. In a series of 60 newly diagnosed MM and 30 MGUS patients, by flow-cytometry we found that HDN from MM, and to a lesser extend MGUS, had an up-regulation of the inducible FcγRI (also known as CD64) and a down-regulation of the constitutive FcγRIIIa (also known as CD16) together with a reduced phagocytic activity and oxidative burst, associated to increased immune-suppression that could be reverted by arginase inhibitors in co-culture with lymphocytes. In 43 consecutive newly-diagnosed MM patients, who received first-line treatment based on bortezomib, thalidomide and dexamethasone, high CD64 could identify at diagnosis patients with inferior median overall survival (39.5 versus 86.7 months, p = 0.04). Thus, HDNs are significantly different among healthy, MGUS and MM subjects. In both MGUS and MM neutrophils may play a role in supporting both the increased susceptibility to infection and the immunological dysfunction that leads to tumor progression

Phenotype of apoptotic lymphocytes in children with Down syndrome

<p>Abstract</p> <p>Background</p> <p>Down syndrome (DS) is the most common and best-known chromosomal disorder and is associated with several other pathologic conditions including immunodeficiency which makes a significant contribution to morbidity and mortality. Various immunological theories and observations to explain the predisposition of individuals with DS to various infections have been published, one of which is increased apoptotic cells.</p> <p>Aim</p> <p>The aim of this study was to identify the effect of apoptosis on both types of cells of specific immune response (T and B lymphocytes) in children with DS using Annexin V staining of phosphatidyserine (PS) as a specific marker of early apoptosis.</p> <p>Subjects and methods</p> <p>The study included 17 children with karyotypically ascertained DS (7 males and 10 females). Their ages ranged from 4 months to 14 years with mean age of 5.7 ± 4.35 years. Seventeen age and sex matched healthy children were included in the study as controls. Patients or controls with infections were excluded from the study. Complete blood picture, immunophenotyping, analysis of apoptosis using Annexin V was done at National cancer Institute to all children included in this study.</p> <p>Results</p> <p>Although CBC, differential count, relative and absolute number of CD³⁺and CD¹⁶⁺did not show significant differences between DS children and control group, the relative and the absolute size of apoptotic CD³⁺T lymphocytes, and the relative size of apoptotic CD¹⁹⁺B lymphocytes were significantly higher in DS children than in controls. On the other hand, no significant difference was detected as regards the absolute size of CD¹⁹⁺B lymphocytes in DS children and in controls</p> <p>Conclusion</p> <p>our finding of increased early apoptotic cells (especially T cells) in DS children may emphasize the fact that the function of cells- and not their number- is main mechanism responsible for the impairment of the immune system in DS children and may further add to the known fact that cellular immunity is more severely affected than humoral immunity in these children. Further studies on apoptotic cellular phenotype in larger number of DS are needed</p

Estudio gravi-magnetométrico del margen continental argentino a partir de métodos automáticos, borde continental

En este trabajo se presenta un análisis de datos de anomalías del Campo Magnético Total (CMT) compiladas a partir de campañas oceanográficas y grillas globales actualizadas en el margen continental argentino entre las latitudes 35°S y 51°S. Los datos fueron procesados matemáticamente a fin de caracterizar fuentes o límites magnéticos en el borde entre las cortezas continental y oceánica (COB). Fueron aplicados los métodos de la señal analítica (SA), el ángulo tilt (TDR), y la segunda derivada vertical (SDV) en 3D. Se calcularon la deconvolución de Werner (DW) y la señal analítica 2D (SA2D), en perfiles transversales al margen, con el propósito de hallar la profundidad de las fuentes. La señal analítica mostró fuentes profundas coincidiendo a lo largo de los alineamientos magnéticos del Mesozoico M0- M4. La segunda derivada vertical expuso fuentes someras sobre la faja de la anomalía magnética G y los alineamientos magnéticos M0-M4, los cuales se mostraron controlados por el sistema de transferencia Río de La Plata y las zonas de fractura de transferencia (ZFT) Salado y Colorado. La delineación del valor nulo del TDR se ajustó tanto al borde oriental como al occidental de las cuñas buzantes hacia el mar (SDRs). Las profundidades de las fuentes obtenidas a través de DW y SA2D se compararon con modelos gravimétricos 2D. El estudio integral de las anomalías gravimétricas junto a las magnéticas proporcionó aportes al conocimiento de la conformación del margen y reafirma sus características de gran actividad volcánica.Eje: Estudio del Interior Terrestre.Facultad de Ciencias Astronómicas y Geofísica

Space Flight Qualification on a Multi-Fiber Ribbon Cable and Array Connector Assembly

NASA's Goddard Space Flight Center (GSFC) cooperatively with Sandia National Laboratories completed a series of tests on three separate configurations of multi-fiber ribbon cable and MTP connector assemblies. These tests simulate the aging process of components during launch and long-term space environmental exposure. The multi-fiber ribbon cable assembly was constructed of non-outgassing materials, with radiation-hardened, graded index 100/140-micron optical fiber. The results of this characterization presented here include vibration testing, thermal vacuum monitoring, and extended radiation exposure testing data

Reduced BRCA1 expression due to promoter hypermethylation in therapy-related acute myeloid leukaemia

BRCA1 plays a pivotal role in the repair of DNA damage, especially following chemotherapy and ionising radiation. We were interested in the regulation of BRCA1 expression in acute myeloid leukaemia (AML), in particular in therapy-related forms (t-AML). Using real-time PCR and Western blot, we found that BRCA1 mRNA was expressed at barely detectable levels by normal peripheral blood granulocytes, monocytes and lymphocytes, whereas control BM-mononuclear cells and selected CD34+ progenitor cells displayed significantly higher BRCA1 expression (P=0.0003). Acute myeloid leukaemia samples showed heterogeneous BRCA1 mRNA levels, which were lower than those of normal bone marrows (P=0.0001). We found a high frequency of hypermethylation of the BRCA1 promoter region in AML (51/133 samples, 38%), in particular in patients with karyotypic aberrations (P=0.026), and in t-AML, as compared to de novo AML (76 vs 31%, P=0.0002). Examining eight primary tumour samples from hypermethylated t-AML patients, BRCA1 was hypermethylated in three of four breast cancer samples, whereas it was unmethylated in the other four tumours. BRCA1 hypermethylation correlated to reduced BRCA1 mRNA (P=0.0004), and to increased DNA methyltransferase DNMT3A (P=0.003) expression. Our data show that reduced BRCA1 expression owing to promoter hypermethylation is frequent in t-AML and that this could contribute to secondary leukaemogenesis

Second Revision of the International Staging System (R2-ISS) for Overall Survival in Multiple Myeloma: A European Myeloma Network (EMN) Report Within the HARMONY Project

PURPOSEPatients with newly diagnosed multiple myeloma (NDMM) show heterogeneous outcomes, and approximately 60% of them are at intermediate-risk according to the Revised International Staging system (R-ISS), the standard-of-care risk stratification model. Moreover, chromosome 1q gain/amplification (1q+) recently proved to be a poor prognostic factor. In this study, we revised the R-ISS by analyzing the additive value of each single risk feature, including 1q+.PATIENTS AND METHODSThe European Myeloma Network, within the HARMONY project, collected individual data from 10,843 patients with NDMM enrolled in 16 clinical trials. An additive scoring system on the basis of top features predicting progression-free survival (PFS) and overall survival (OS) was developed and validated.RESULTSIn the training set (N = 7,072), at a median follow-up of 75 months, ISS, del(17p), lactate dehydrogenase, t(4;14), and 1q+ had the highest impact on PFS and OS. These variables were all simultaneously present in 2,226 patients. A value was assigned to each risk feature according to their OS impact (ISS-III 1.5, ISS-II 1, del(17p) 1, high lactate dehydrogenase 1, and 1q+ 0.5 points). Patients were stratified into four risk groups according to the total additive score: low (Second Revision of the International Staging System [R2-ISS]-I, 19.2%, 0 points), low-intermediate (II, 30.8%, 0.5-1 points), intermediate-high (III, 41.2%, 1.5-2.5 points), high (IV, 8.8%, 3-5 points). Median OS was not reached versus 109.2 versus 68.5 versus 37.9 months, and median PFS was 68 versus 45.5 versus 30.2 versus 19.9 months, respectively. The score was validated in an independent validation set (N = 3,771, of whom 1,214 were with complete data to calculate R2-ISS) maintaining its prognostic value.CONCLUSIONThe R2-ISS is a simple prognostic staging system allowing a better stratification of patients with intermediate-risk NDMM. The additive nature of this score fosters its future implementation with new prognostic variables

Rasch analysis of the Multiple Sclerosis Impact Scale (MSIS-29)

<p>Abstract</p> <p>Background</p> <p>Multiple Sclerosis (MS) is a degenerative neurological disease that causes impairments, including spasticity, pain, fatigue, and bladder dysfunction, which negatively impact on quality of life. The Multiple Sclerosis Impact Scale (MSIS-29) is a disease-specific health-related quality of life (HRQoL) instrument, developed using the patient's perspective on disease impact. It consists of two subscales assessing the physical (MSIS-29-PHYS) and psychological (MSIS-29-PSYCH) impact of MS. Although previous studies have found support for the psychometric properties of the MSIS-29 using traditional methods of scale evaluation, the scale has not been subjected to a detailed Rasch analysis. Therefore, the objective of this study was to use Rasch analysis to assess the internal validity of the scale, and its response format, item fit, targeting, internal consistency and dimensionality.</p> <p>Methods</p> <p>Ninety-two persons with definite MS residing in the community were recruited from a tertiary hospital database. Patients completed the MSIS-29 as part of a larger study. Rasch analysis was undertaken to assess the psychometric properties of the MSIS-29.</p> <p>Results</p> <p>Rasch analysis showed overall support for the psychometric properties of the two MSIS-29 subscales, however it was necessary to reduce the response format of the MSIS-29-PHYS to a 3-point response scale. Both subscales were unidimensional, had good internal consistency, and were free from item bias for sex and age. Dimensionality testing indicated it was not appropriate to combine the two subscales to form a total MSIS score.</p> <p>Conclusion</p> <p>In this first study to use Rasch analysis to fully assess the psychometric properties of the MSIS-29 support was found for the two subscales but not for the use of the total scale. Further use of Rasch analysis on the MSIS-29 in larger and broader samples is recommended to confirm these findings.</p

Cardiovascular adverse events in modern myeloma therapy - incidence and risks. A review from European Myeloma Network (EMN) and Italian Society of Arterial Hypertension (SIIA)

Cardiovascular disease in myeloma patients may derive from factors unrelated to the disease (age, diabetes, dyslipidemia, obesity, prior cardiovascular diseases), related to the disease (cardiac AL-amyloidosis, hyperviscosity, high-output failure, arteriovenous shunting, anemia, renal dysfunction) and linked to antimyeloma treatment (anthracyclines, corticosteroids, alkylating agents, immunomodulatory drugs, proteasome inhibitors). An accurate knowledge of cardiovascular events, effective dose reductions, prevention and management of early and late cardiovascular side effects of chemotherapeutic agents are essential in current clinical practice. Myeloma experts are obliged to carefully balance drugs' efficacy and toxicity for each individual patient. This review summarizes current data and novel insights on cardiovascular adverse events of today's antimyeloma treatment, focusing on carfilzomib, which is the starting point to develop consensus recommendations on preventing and managing cardiovascular side effects in myeloma patients