Effects of the Representation of Convection on the Modelling of Hurricane Tomas (2010)

The cumulus parameterization is widely recognised as a crucial factor in tropical meteorology: this paper intends to shed further light on the effects of convection parameterization on tropical cyclones’ numerical predictions in the “grey zone” (10–1 km grid spacing). Ten experiments are devised by combining five different convection treatments over the innermost, 5 km grid spacing, domain, and two different global circulation model datasets (IFS and ERA-Interim). All ten experiments are finally analysed and compared to observations provided by the National Hurricane Center’s best track record and multisatellite rainfall measurements. Results manifestly point to the superiority of employing no convective parameterization at the scale of 5 km versus the usage of any of those provided by WRF to reproduce the case study of Hurricane Tomas, which hit the Lesser Antilles and Greater Antilles in late October and early November 2010

Oxidation of Long Chain Fatty Acids by Rat Liver Mitochondria

Abstract Long chain fatty acids are oxidized by rat liver mitochondria provided that endogenous adenosine triphosphate is not depleted. If endogenous ATP is depleted, e.g. by 2,4-dinitrophenol, external ATP as well as carnitine is required for fatty acid oxidation. Atractyloside does not block this reaction in media containing orthophosphate buffer. Oligomycin can substitute for carnitine, but the oligomycin-dependent route is inhibited by atractyloside. These experimental situations localize two ATP-dependent fatty acid-activating systems, one of which is linked to carnitine. The dinitrophenol-insensitive, GTP-specific fatty acyl coenzyme A synthetase is active only in the absence of orthophosphate. Inhibition of oxidation of fatty acids by atractylate in phosphate-free media is not relieved with oligomycin or carnitine

A Guanosine Triphosphate-dependent Acyl Coenzyme A Synthetase from Rat Liver Mitochondria

A guanosine triphosphate-specific acyl coenzyme A synthetase has been purified from extracts of sonically disrupted rat liver mitochondria. This enzyme, which is free of adenosine triphosphate-dependent activating systems and from succinyl-CoA synthetase activity, catalyzes the formation of CoA esters of both long and short chain fatty acids. GTP-specific fatty acid activation is inhibited by orthophosphate and fluoride

Impact-based flash-flood forecasting system: Sensitivity to high resolution numerical weather prediction systems and soil moisture

In recent years, continuous improvements have been made in weather forecasting and flood prediction with great benefit from Early Warning Systems (EWSs). Despite the continuous quest for innovation from the scientific and user communities, EWSs remain based mostly on hazard forecast, and the information on possible consequences and potential impacts is generally missing. In this work, a methodology for quantitative real-time impact assessment for flash floods is presented. The methodology uses a multi-model ensemble approach and considers soil moisture uncertainty. Moreover, the flood forecasting chain, which normally provides only the discharge probability of exceeding a given threshold, is extended to include a fully 2D hydraulic model and a damage estimation model to quantitatively assess impacts in terms of economic losses and the people involved. The procedure was tested on recent flood events occurring in Genoa in northwestern Italy. This paper discusses the potential challenges and opportunities offered by this approach in the decision-making workflow in an operational context

Adverse outcome pathways – development and potential regulatory application

Introduction: Over the last two decades, chemical safety assessment and regulatory toxicology have progressed from empirical science based on direct observation of apical adverse outcomes in whole organisms to a predictive practice that infers outcomes and risks on the basis of accumulated understanding of toxicological mechanisms and modes of action. Objective: To provide general  concepts on how Adverse Outcome Pathways (AOPs) are developed and examples related to skin sensitization, endocrine, disruption, and mitochondrial dysfunction. Method: Narrative review based on data of the scientific literature relevant to the theme addressed and on the experience of the authors. Results: An AOP framework provides a systematic approach to organize knowledge about mechanisms of toxicity that may inform analytical domains in regulatory decision-making. AOPs are open structures that may indicate not only data gaps in the understanding of a toxicity process, but also testing procedures that will generate the necessary knowledge to fill those gaps. Every AOP should be continuously refined through the collaborative efforts of the scientific community. Depending on the amount and detail of information that is successively inserted, AOP may progress from the stage of a putative AOP to the stages of qualitative and quantitative AOPs, which are more fit-for-purpose to support regulatory decision-making. Conclusions: Continuous collaboration between AOP developers within the scientific community and the  regulatory corps toward the development of this mechanistic structure will support the advancement of toxicological sciences, regardless of its immediate application for regulatory purposes.TÍTULO PT: Vias de desfecho adverso – desenvolvimento e potencial aplicação regulatória Introdução: Durante as duas últimas décadas, a avaliação da segurança química e a toxicologia regulatória evoluíram de uma ciência empírica em grande parte baseada na observação de desfechos adversos em órgãos e ou organismos inteiros para uma prática preditiva que infere desfechos e riscos a partir do conhecimento acumulado sobre mecanismos e modos de ação toxicológicos. Objetivo: Discorrer sobre como as AOPs são desenvolvidas e fornecer exemplos relacionados à sensibilização cutânea, desregulação endócrina e disfunção mitocondrial. Método: Revisão narrativa baseada em dados da literatura científica relevantes para o tema abordado e na experiência dos autores. Resultados: A estrutura conceitual denominada AOP (do inglês, Adverse Outcome Pathway) permite uma abordagem sistemática do conhecimento disponível sobre mecanismos de toxicidade que pode subsidiar a tomada de decisões regulatórias. AOPs são estruturas abertas que podem indicar lacunas de dados para a compreensão de determinada via patogenética de toxicidade, de modo que podem ser continuamente aperfeiçoadas por esforços da comunidade científica. Dependendo das informações sucessivamente inseridas, as AOPs podem passar do estágio de uma AOP hipotética para os estágios de AOP qualitativa e AOP quantitativa, sendo este último o mais adequado para subsidiar decisões regulatórias. Conclusões: A colaboração contínua entre os desenvolvedores de AOPs dentro da comunidade científica e os corpos regulatórios para o desenvolvimento dessa estrutura mecanicista apoiará o avanço das ciências toxicológicas, independente de sua aplicação imediata para fins normativos.

Regional stratigraphy of the south polar layered deposits (Promethei Lingula, Mars): “Discontinuity-bounded” units in images and radargrams

The Mars South Polar Layered Deposits (SPLD) are the result of depositional and erosional events, which are marked by different stratigraphic sequences and erosional surfaces. To unambiguously define the stratigraphic units at regional scale, we mapped the SPLD on the basis of observed discontinuities (i.e., unconformities, correlative discontinuities and conformities), as commonly done in terrestrial modern stratigraphy. This methodology is defined as “Discontinuity-Bounded Units” or allostratigraphy, and is complemented by geomorphological mapping. Our study focuses on Promethei Lingula (PL) and uses both high-resolution images (CTX, HiRISE) and radargrams (SHARAD) to combine surface and sub-surface observations and obtain a 3D geological reconstruction of the SPLD. One regional discontinuity (named AUR1) was defined within the studied stratigraphic succession and is exposed in several non-contiguous outcrops around PL as well as observed at depth within the ice sheet. This is the primary contact between two major depositional sequences, showing a different texture at CTX resolution. The lower sequence is characterized mainly by a “ridge and trough” morphology (Ridge and Trough Sequence; RTS) and the upper sequence shows mainly by a “stair-stepped” morphology (Stair-Stepped Sequence; SSS). On the basis of the observations, we defined two regional “discontinuity-bounded” units in PL, respectively coinciding with RTS and SSS sequences. Our stratigraphic reconstruction provides new hints on the major scale events that shaped this region. Oscillations in Martian axial obliquity could have controlled local climate conditions in the past, affecting the PL geological record

Triple positive breast cancer. A distinct subtype?

Breast cancer is a heterogeneous disease, and within the HER-2 positive subtype this is highly exemplified by the presence of substantial phenotypical and clinical heterogeneity, mostly related to hormonal receptor (HR) expression. It is well known how HER-2 positivity is commonly associated with a more aggressive tumor phenotype and decreased overall survival and, moreover, with a reduced benefit from endocrine treatment. Preclinical studies corroborate the role played by functional crosstalks between HER-2 and estrogen receptor (ER) signaling in endocrine resistance and, more recently, the activation of ER signaling is emerging as a possible mechanism of resistance to HER-2 blocking agents. Indeed, HER-2 positive breast cancer heterogeneity has been suggested to underlie the variability of response not only to endocrine treatments, but also to HER-2 blocking agents. Among HER-2 positive tumors, HR status probably defines two distinct subtypes, with dissimilar clinical behavior and different sensitivity to anticancer agents. The triple positive subtype, namely, ER/PgR/Her-2 positive tumors, could be considered the subset which most closely resembles the HER-2 negative/HR positive tumors, with substantial differences in biology and clinical outcome. We argue on whether in this subgroup the "standard" treatment may be considered, in selected cases, i.e., small tumors, low tumor burden, high expression of both hormonal receptors, an overtreatment. This article review the existing literature on biologic and clinical data concerning the HER-2/ER/PgR positive tumors, in an attempt to better define the HER-2 subtypes and to optimize the use of HER-2 targeted agents, chemotherapy and endocrine treatments in the various subsets

Genetic and virulence characterization of colistin-resistant and colistin-sensitive A. baumannii clinical isolates.

Treatment of infections caused by A. baumannii is becoming a challenge due to the ability to develop multidrug-resistance, virulence, and high mortality. We described the colistin resistance and virulence genes present in sixA. baumannii clinical isolates using WGS, expression by qPCR, and virulence in the Galleria mellonella model. The colistin-resistant isolates were assigned as ST233 and the colistin-susceptible isolates as ST236 and ST407. The colistin-resistant isolates contained mutations within PmrA/PmrB, and the pmrA showed up-regulation in all of them. Only one colistin-resistant isolate indicating virulence in G. mellonella. This particular isolate belonged to a different clone, and it was the only isolate that presented non-synonymous mutations in pmrB. Colistinresistance in A. baumannii isolates seems to be caused by up-regulation of pmrA gene. Only one isolate appeared to be virulent in the G. mellonella model. This finding indicating low virulence in isolates belonging to emerging clones circulating in our hospital