A two-stage approach to locate and size PV sources in distribution networks for annual grid operative costs minimization

This paper contributes with a new two-stage optimization methodology to solve the problem of the optimal placement and sizing of solar photovoltaic (PV) generation units in mediumvoltage distribution networks. The optimization problem is formulated with a mixed-integer nonlinear programming (MINLP) model, where it combines binary variables regarding the nodes where the PV generators will be located and continuous variables associated with the power flow solution. To solve the MINLP model a decoupled methodology is used where the binary problem is firstly solved with mixed-integer quadratic approximation; and once the nodes where the PV sources will be located are known, the dimensioning problem of the PV generators is secondly solved through an interior point method applied to the classical multi-period power flow formulation. Numerical results in the IEEE 33-bus and IEEE 85-bus systems demonstrate that the proposed approach improves the current literature results reached with combinatorial methods such as the Chu and Beasley genetic algorithm, the vortex search algorithm, the Newton-metaheuristic algorithm as well as the exact solution of the MINLP model with the GAMS software and the BONMIN solver. All the numerical simulations are implemented in the MATLAB programming environment and the convex equivalent models are solved with the CVX tool

Dissecting the role of TP53 alterations in del(11q) chronic lymphocytic leukemia

© 2021 The Authors.[Background]: Several genetic alterations have been identified as driver events in chronic lymphocytic leukemia (CLL) pathogenesis and oncogenic evolution. Concurrent driver alterations usually coexist within the same tumoral clone, but how the cooperation of multiple genomic abnormalities contributes to disease progression remains poorly understood. Specifically, the biological and clinical consequences of concurrent high-risk alterations such as del(11q)/ATM-mutations and del(17p)/TP53-mutations have not been established.[Methods]: We integrated next-generation sequencing (NGS) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 techniques to characterize the in vitro and in vivo effects of concurrent monoallelic or biallelic ATM and/or TP53 alterations in CLL prognosis, clonal evolution, and therapy response.[Results]: Targeted sequencing analysis of the co-occurrence of high-risk alterations in 271 CLLs revealed that biallelic inactivation of both ATM and TP53 was mutually exclusive, whereas monoallelic del(11q) and TP53 alterations significantly co-occurred in a subset of CLL patients with a highly adverse clinical outcome. We determined the biological effects of combined del(11q), ATM and/or TP53 mutations in CRISPR/Cas9-edited CLL cell lines. Our results showed that the combination of monoallelic del(11q) and TP53 mutations in CLL cells led to a clonal advantage in vitro and in in vivo clonal competition experiments, whereas CLL cells harboring biallelic ATM and TP53 loss failed to compete in in vivo xenotransplants. Furthermore, we demonstrated that CLL cell lines harboring del(11q) and TP53 mutations show only partial responses to B cell receptor signaling inhibitors, but may potentially benefit from ATR inhibition.[Conclusions]: Our work highlights that combined monoallelic del(11q) and TP53 alterations coordinately contribute to clonal advantage and shorter overall survival in CLL.Spanish Fondo de Investigaciones Sanitarias, Grant/Award Numbers: PI15/01471, PI18/01500); Fundación Memoria Don Samuel Solórzano Barruso, Grant/Award Number: RD12/0036/006

Acoustic and optical variations during rapid downward motion episodes in the deep north-western Mediterranean Sea

An Acoustic Doppler Current Profiler (ADCP) was moored at the deep-sea site of the ANTARES neutrino telescope near Toulon, France, thus providing a unique opportunity to compare high-resolution acoustic and optical observations between 70 and 170 m above the sea bed at 2475 m. The ADCP measured downward vertical currents of magnitudes up to 0.03 m s-1 in late winter and early spring 2006. In the same period, observations were made of enhanced levels of acoustic reflection, interpreted as suspended particles including zooplankton, by a factor of about 10 and of horizontal currents reaching 0.35 m s-1. These observations coincided with high light levels detected by the telescope, interpreted as increased bioluminescence. During winter 2006 deep dense-water formation occurred in the Ligurian subbasin, thus providing a possible explanation for these observations. However, the 10-20 days quasi-periodic episodes of high levels of acoustic reflection, light and large vertical currents continuing into the summer are not direct evidence of this process. It is hypothesized that the main process allowing for suspended material to be moved vertically later in the year is local advection, linked with topographic boundary current instabilities along the rim of the 'Northern Current'.Comment: 30 pages, 7 figure

Status and Recent Results of the Acoustic Neutrino Detection Test System AMADEUS

The AMADEUS system is an integral part of the ANTARES neutrino telescope in the Mediterranean Sea. The project aims at the investigation of techniques for acoustic neutrino detection in the deep sea. Installed at a depth of more than 2000m, the acoustic sensors of AMADEUS are based on piezo-ceramics elements for the broad-band recording of signals with frequencies ranging up to 125kHz. AMADEUS was completed in May 2008 and comprises six "acoustic clusters", each one holding six acoustic sensors that are arranged at distances of roughly 1m from each other. The clusters are installed with inter-spacings ranging from 15m to 340m. Acoustic data are continuously acquired and processed at a computer cluster where online filter algorithms are applied to select a high-purity sample of neutrino-like signals. 1.6 TB of data were recorded in 2008 and 3.2 TB in 2009. In order to assess the background of neutrino-like signals in the deep sea, the characteristics of ambient noise and transient signals have been investigated. In this article, the AMADEUS system will be described and recent results will be presented.Comment: 7 pages, 8 figures. Proceedings of ARENA 2010, the 4th International Workshop on Acoustic and Radio EeV Neutrino Detection Activitie

Tau Structures

Tau is a microtubule-associated protein that plays an important role in axonal stabilization, neuronal development, and neuronal polarity. In this review, we focus on the primary, secondary, tertiary, and quaternary tau structures. We describe the structure of tau from its specific residues until its conformation in dimers, oligomers, and larger polymers in physiological and pathological situations

A method for detection of muon induced electromagnetic showers with the ANTARES detector

The primary aim of ANTARES is neutrino astronomy with upward going muons created in charged current muon neutrino interactions in the detector and its surroundings. Downward going muons are background for neutrino searches. These muons are the decay products of cosmic-ray collisions in the Earth's atmosphere far above the detector. This paper presents a method to identify and count electromagnetic showers induced along atmospheric muon tracks with the ANTARES detector. The method is applied to both cosmic muon data and simulations and its applicability to the reconstruction of muon event energies is demonstrated.Comment: 20 pages, 7 figure

Measurement of the Group Velocity of Light in Sea Water at the ANTARES Site

The group velocity of light has been measured at eight different wavelengths between 385 nm and 532 nm in the Mediterranean Sea at a depth of about 2.2 km with the ANTARES optical beacon systems. A parametrisation of the dependence of the refractive index on wavelength based on the salinity, pressure and temperature of the sea water at the ANTARES site is in good agreement with these measurements.Comment: 14 pages, 5 figure

A Two-Stage Approach to Locate and Size PV Sources in Distribution Networks for Annual Grid Operative Costs Minimization

This paper contributes with a new two-stage optimization methodology to solve the problem of the optimal placement and sizing of solar photovoltaic (PV) generation units in medium-voltage distribution networks. The optimization problem is formulated with a mixed-integer nonlinear programming (MINLP) model, where it combines binary variables regarding the nodes where the PV generators will be located and continuous variables associated with the power flow solution. To solve the MINLP model a decoupled methodology is used where the binary problem is firstly solved with mixed-integer quadratic approximation; and once the nodes where the PV sources will be located are known, the dimensioning problem of the PV generators is secondly solved through an interior point method applied to the classical multi-period power flow formulation. Numerical results in the IEEE 33-bus and IEEE 85-bus systems demonstrate that the proposed approach improves the current literature results reached with combinatorial methods such as the Chu and Beasley genetic algorithm, the vortex search algorithm, the Newton-metaheuristic algorithm as well as the exact solution of the MINLP model with the GAMS software and the BONMIN solver. All the numerical simulations are implemented in the MATLAB programming environment and the convex equivalent models are solved with the CVX tool

Deregulation of genes related to iron and mitochondrial metabolism in refractory anemia with ring sideroblasts

The presence of SF3B1 gene mutations is a hallmark of refractory anemia with ring sideroblasts (RARS). However, the mechanisms responsible for iron accumulation that characterize the Myelodysplastic Syndrome with ring sideroblasts (MDS-RS) are not completely understood. In order to gain insight in the molecular basis of MDS-RS, an integrative study of the expression and mutational status of genes related to iron and mitochondrial metabolism was carried out. A total of 231 low-risk MDS patients and 81 controls were studied. Gene expression analysis revealed that iron metabolism and mitochondrial function had the highest number of genes deregulated in RARS patients compared to controls and the refractory cytopenias with unilineage dysplasia (RCUD). Thus mitochondrial transporters SLC25 (SLC25A37 and SLC25A38) and ALAD genes were over-expressed in RARS. Moreover, significant differences were observed between patients with SF3B1 mutations and patients without the mutations. The deregulation of genes involved in iron and mitochondrial metabolism provides new insights in our knowledge of MDS-RS. New variants that could be involved in the pathogenesis of these diseases have been identified

DNA damage response-related alterations define the genetic background of patients with chronic lymphocytic leukemia and chromosomal gains

The presence of chromosomal gains other than trisomy 12 suggesting a hyperdiploid karyotype is extremely rare in chronic lymphocytic leukemia (CLL) and is associated with a dismal prognosis. However, the genetic mechanisms and mutational background of these patients have not been fully explored. To improve our understanding of the genetic underpinnings of this subgroup of CLL, seven CLL patients with several chromosomal gains were sequenced using a next-generation sequencing (NGS)-targeted approach. The mutational status of 54 genes was evaluated using a custom-designed gene panel including recurrent mutated genes observed in CLL and widely associated with CLL pathogenesis. A total of 21 mutations were detected; TP53 (42.8%), ATM (28.5%), SF3B1 (28.5%), and BRAF (28.5%) were the most recurrently mutated genes. Of these mutations, 61.9% were detected in genes previously associated with a poor prognosis in CLL. Interestingly, five of the seven patients exhibited alterations in TP53 or ATM (deletion and/or mutation), genes involved in the DNA damage response (DDR), which could be related to a high genetic instability in this subgroup of patients. In conclusion, CLL patients with several chromosomal gains exhibit high genetic instability, with mutations in CLL driver genes and high-risk genetic alterations involving ATM and/or TP53 genes.This work was supported by grants from the Spanish Fondo de Investigaciones Sanitarias (PI15/01471, PI18/01500); by the Instituto de Salud Carlos III (ISCIII), European Regional Development Fund (ERDF) “Una manera de hacer Europa”; and by grants from Red Temática de Investigación Cooperativa en Cáncer (RTICC) and Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) (RD12/0036/0069). MH-S is supported by FEHH-Janssen (“Sociedad Española de Hematología y Hemoterapia”). AER-V and JMH-S are supported by a research grant from FEHH (Fundación Española de Hematología y Hemoterapia). MQ-Á is supported by a grant from “Ayuda Predoctoral de la Junta de Castilla y León” (JCYL-EDU/529/2017)