FLUKA Simulations of Energy Density Deposition from a ILC Bunch in different Spoiler Designs

FLUKA is used to simulate the energy deposition due to a direct bunch impact of the ILC beam in various candidate spoiler designs. The conclusions extracted will contribute to the overall optimisation process and identify areas where additional experimental data would be beneficial

Staging the Sounds of the Nation: The Poetic Soundscapes of the USA

Staging the Sounds of the Nation: The Poetic Soundscapes of the US

Optimización del proceso kraft en maderas de Eucalyptus globulus

Se ha estudiado en maderas de E. globulus como afecta el factor H y la carga de álcali activo en cocción sobre la facilidad de la deslignificación, el contenido en carbohidratos y la eliminación de extractos de las pastas crudas obtenidas a un mismo nivel de lignina residual. Los resultados obtenidos mostraron que trabajar con bajas cargas de álcali activo y temperaturas en cocción más elevadas, aumenta el rendimiento de pasta en cocción y eliminan más sitosterol. Sin embargo, las blancuras más altas se obtienen trabajando con alta carga de álcali activo. Los xilanos son los compuestos más sensibles a la alta carga de álcali y se eliminan en gran extensión. Las pastas obtenidas con bajo álcali residual en cocción tienen mejor estallido y tracción pero peor drenabilidad, volumen, opacidad y porosidad.___________________________________This paper studies how H factor and active alkali loads in cooking affect E. globulus woods with regard to ease of delignification, carbohydrate content or removal of extractives. The results obtained demonstrated that working with low alkali loads and higher cooking temperatures increase pulp production and remove greater amounts of sitosterol. However, the greatest brightness is achieved by working with a high active alkali load. Xylans are the most sensitive compounds to high alkali loads and to a large extent are removed. Pulp produced with low residual alkali in the cooking stage has better burst index and tensile strength, but lower dewatering, bulk, opacity and air permeability

Increased expression levels of the pvcrt-o and pvmdr1 genes in a patient with severe Plasmodium vivax malaria

<p>Abstract</p> <p>Background</p> <p>There are increasing reports of severe clinical cases exclusively associated with <it>Plasmodium vivax </it>infections. Notably, this severity has been recently suggested to be associated with chloroquine resistance.</p> <p>Patients</p> <p>Two different patients presented at the Hospital Clinic in Barcelona with <it>P. vivax </it>malaria episodes. One patient had severe symptoms and the other mild symptoms. Both patients traveled through the Brazilian Amazon (Manaus) in 2007. For both patients the current diagnosis of malaria was the first. Two other patients with mild symptoms presented to the "Centro de Pesquisa em Medicina Tropical", also in the Brazilian Amazon (Rondônia) in 2000.</p> <p>Methods</p> <p>To exclude the possibility that the patient's severe symptoms were due to <it>Plasmodium falciparum</it>, a nested PCR was performed. A magnetic method was used to purify <it>P. vivax </it>free of human leukocytes. Quantitative real-time PCR was performed to compare the transcript levels of two main transporters likely to be involved in chloroquine resistance in <it>P. vivax</it>, namely the <it>P. vivax </it>chloroquine resistance transporter, <it>pvcrt-o</it>, and the <it>P. vivax </it>multidrug resistance transporter, <it>pvmdr 1</it>.</p> <p>Results</p> <p>Results demonstrated that the severe clinical symptoms were exclusively due to <it>P. vivax</it>. The patient presented acute respiratory conditions requiring admission to the intensive care unit. The magnetic method showed highly purified infected-reticulocytes with mature stages. In addition, it was found that parasites obtained from the severe patient had up to 2.9-fold increase in <it>pvmdr1 </it>levels and up to 21.9-fold increase in <it>pvcrt-o </it>levels compared to expression levels of parasites from the other patients with mild symptoms.</p> <p>Conclusion</p> <p>This is the first clinical case of severe disease exclusively associated with vivax malaria in Spain. Moreover, these findings suggest that clinical severity could be associated with increased expression levels of parasite genes likely involved in chloroquine resistance. It is necessary to further explore the potential of <it>pvmdr1 </it>and particularly <it>pvcrt-o </it>expression levels as molecular markers of severe disease in <it>P. vivax</it>.</p

Thermoremanence anomaly in Fe-Zr(B,Cu) Invar metallic glasses: Volume expansion induced ferromagnetism

We report the existence of a thermally induced sharp increase of thermoremanence around the Curie temperature of Invar-like Fe-Zr(B,Cu) soft magnetic glasses. Neutron-diffraction measurements indicate that a true enhancement of the average local magnetic moment, rather than only a change in the domain structure, occurs. Such enhancement has been tentatively attributed to the increasing volume expansion that takes place beyond the Curie temperature and reinforces ferromagnetism in some low-density clusters

Organocatalytically Generated Donor − Acceptor Cyclopropanes in Domino Reactions. One-Step Enantioselective Synthesis of Pyrrolo[1,2 ‑ a ]quinolines

An easy and straightforward procedure has been developed for the synthesis of highly enantioenriched pyrrolo-[1,2-a]quinolines through a one-pot process that comprises a domino cyclopropane ring opening/aza-Michael/aldol reaction followed by acid-promoted lactamization. The key feature of the synthetic approach relies on the ability of conveniently functionalized cyclopropaneacetaldehydes to undergo organocatalytic activation by a chiral secondary amine that enables the catalytic generation of a donor acceptor cyclopropane. This intermediate has the potential to undergo a ring opening that generates an electrophilic alpha,beta-unsaturated iminium ion that subsequently reacts through the already mentioned domino sequence and in which stereochemical information is very efficiently transferred from the amine catalyst to the final products. Moreover, one of the alkoxycarbonyl moieties can be easily removed by standard hydrolysis/decarboxylation, providing access to the target adducts as single stereoisomers.This research was supported by the Spanish MINECO (FEDER-CTQ2014-52107-P), the Basque Government (Grupos IT328-10), and UPV/EHU (fellowship to E.S. and UFI QOSYC 11/22). Membership in the COST action CM1407 (NatChemDrugs) is also acknowledged

Virtual reality-based early neurocognitive stimulation in critically ill patients: A pilot randomized clinical trial

This study focuses on the application of a non-immersive virtual reality (VR)-based neurocognitive intervention in critically ill patients. Our aim was to assess the feasibility of direct outcome measures to detect the impact of this digital therapy on patients’ cognitive and emotional outcomes. Seventy-two mechanically ventilated adult patients were randomly assigned to the “treatment as usual” (TAU, n = 38) or the “early neurocognitive stimulation” (ENRIC, n = 34) groups. All patients received standard intensive care unit (ICU) care. Patients in the ENRIC group also received adjuvant neurocognitive stimulation during the ICU stay. Outcome measures were a full neuropsychological battery and two mental health questionnaires. A total of 42 patients (21 ENRIC) completed assessment one month after ICU discharge, and 24 (10 ENRIC) one year later. At onemonth follow-up, ENRIC patients had better working memory scores (p = 0.009, d = 0.363) and showed up to 50% less non-specific anxiety (11.8% vs. 21.1%) and depression (5.9% vs. 10.5%) than TAU patients. A general linear model of repeated measures reported a main effect of group, but not of time or group–time interaction, on working memory, with ENRIC patients outperforming TAU patients (p = 0.008, ¿p2 = 0.282). Our results suggest that non-immersive VR-based neurocognitive stimulation may help improve short-term working memory outcomes in survivors of critical illness. Moreover, this advantage could be maintained in the long term. An efficacy trial in a larger sample of participants is feasible and must be conducted. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

p-SMAD2/3 and DICER promote pre-miR-21 processing during pressure overload-associated myocardial remodeling

AbstractTransforming growth factor-β (TGF-β) induces miR-21 expression which contributes to fibrotic events in the left ventricle (LV) under pressure overload. SMAD effectors of TGF-β signaling interact with DROSHA to promote primary miR-21 processing into precursor miR-21 (pre-miR-21). We hypothesize that p-SMAD-2 and -3 also interact with DICER1 to regulate the processing of pre-miR-21 to mature miR-21 in cardiac fibroblasts under experimental and clinical pressure overload. The subjects of the study were mice undergoing transverse aortic constriction (TAC) and patients with aortic stenosis (AS). In vitro, NIH-3T3 fibroblasts transfected with pre-miR-21 responded to TGF-β1 stimulation by overexpressing miR-21. Overexpression and silencing of SMAD2/3 resulted in higher and lower production of mature miR-21, respectively. DICER1 co-precipitated along with SMAD2/3 and both proteins were up-regulated in the LV from TAC-mice. Pre-miR-21 was isolated bound to the DICER1 maturation complex. Immunofluorescence analysis revealed co-localization of p-SMAD2/3 and DICER1 in NIH-3T3 and mouse cardiac fibroblasts. DICER1-p-SMAD2/3 protein–protein interaction was confirmed by in situ proximity ligation assay. Myocardial up-regulation of DICER1 constituted a response to pressure overload in TAC-mice. DICER mRNA levels correlated directly with those of TGF-β1, SMAD2 and SMAD3. In the LV from AS patients, DICER mRNA was up-regulated and its transcript levels correlated directly with TGF-β1, SMAD2, and SMAD3. Our results support that p-SMAD2/3 interacts with DICER1 to promote pre-miR-21 processing to mature miR-21. This new TGFβ-dependent regulatory mechanism is involved in miR-21 overexpression in cultured fibroblasts, and in the pressure overloaded LV of mice and human patients

Sudden spleen rupture in a Plasmodium vivax-infected patient undergoing malaria treatment

BACKGROUND: Splenomegaly is one of the most common features of malaria. However, spontaneous splenic rupture, although unusual, represents a severe complication often leading to death. It is mostly seen in acute infection and primary attack, and it is most commonly associated with Plasmodium vivax. Here, a case of spontaneous splenic rupture diagnosed with a portable ultrasound apparatus shortly after starting treatment and with recurrent parasitaemia after splenectomy, is reported. CASE DESCRIPTION: In November 2015, a 45-year-old Brazilian man presented to the hospital in Manaus with fever, headache and myalgia. He was diagnosed with P. vivax malaria and, after a normal G6PD test, he started treatment with chloroquine and primaquine and was discharged. Two days later, he went back to the hospital with abdominal pain, dyspnea, dry cough, pallor, oliguria and fever. Using a portable ultrasound, he was diagnosed of rupture of the spleen, which was removed by emergency surgery. After this episode, he suffered two more malaria episodes with high parasitaemia at approximately 2-month intervals. DNA from different portions of the spleen was extracted and a qualitative PCR was performed to detect P. vivax. CONCLUSIONS: The splenic rupture suffered by this patient occurred 2 days after starting the treatment. Having a portable ultrasound apparatus may have saved the patient's life, as it revealed a haemorrhage needing an urgent surgery. Parasites were detected by PCR in the extracted spleen. This patient suffered two more vivax malaria diagnosed episodes in spite of receiving and completing treatment with chloroquine and primaquine for each clinical attack. Splenic rupture during acute malaria is uncommon, but it is likely underdiagnosed and underreported, because the lack of means and equipment hinders diagnostic confirmation, especially in endemic areas

Characterization of Plasmodium vivax Proteins in Plasma-Derived Exosomes From Malaria-Infected Liver-Chimeric Humanized Mice

Exosomes are extracellular vesicles of endocytic origin containing molecular signatures implying the cell of origin; thus, they offer a unique opportunity to discover biomarkers of disease. Plasmodium vivax, responsible for more than half of all malaria cases outside Africa, is a major obstacle in the goal of malaria elimination due to the presence of dormant liver stages (hypnozoites), which after the initial infection may reactivate to cause disease. Hypnozoite infection is asymptomatic and there are currently no diagnostic tools to detect their presence. The human liver-chimeric (FRG huHep) mouse is a robust P. vivax infection model for exo-erythrocytic development of liver stages, including hypnozoites. We studied the proteome of plasma-derived exosomes isolated from P. vivax infected FRG huHep mice with the objective of identifying liver-stage expressed parasite proteins indicative of infection. Proteomic analysis of these exosomes showed the presence of 290 and 234 proteins from mouse and human origin, respectively, including canonical exosomal markers. Human proteins include proteins previously detected in liver-derived exosomes, highlighting the potential of this chimeric mouse model to study plasma exosomes derived unequivocally from human hepatocytes. Noticeably, we identified 17 parasite proteins including enzymes, surface proteins, components of the endocytic pathway and translation machinery, as well as uncharacterized proteins. Western blot analysis validated the presence of human arginase-I and an uncharacterized P. vivax protein in plasma-derived exosomes. This study represents a proof-of-principle that plasma-derived exosomes from P. vivax infected FRG-huHep mice contain human hepatocyte and P. vivax proteins with the potential to unveil biological features of liver infection and identify biomarkers of hypnozoite infection