Crystallographic and superconducting properties of the fully-gapped noncentrosymmetric 5d-electron superconductors CaMSi3 (M=Ir, Pt)

We report crystallographic, specific heat, transport, and magnetic properties of the recently discovered noncentrosymmetric 5d-electron superconductors CaIrSi3 (Tc = 3.6 K) and CaPtSi3 (Tc = 2.3 K). The specific heat suggests that these superconductors are fully gapped. The upper critical fields are less than 1 T, consistent with limitation by conventional orbital depairing. High, non-Pauli-limited {\mu}0 Hc2 values, often taken as a key signature of novel noncentrosymmetric physics, are not observed in these materials because the high carrier masses required to suppress orbital depairing and reveal the violated Pauli limit are not present.Comment: 8 pages, 8 figure

Conversion of end-of-life household materials into building insulating low-cost solutions for the development of vulnerable contexts: Review and outlook towards a circular and sustainable economy

In a world increasingly aware of the environmental cost of the current production/ consumption model, the use of sustainable practices to reduce our environmental impact as a society becomes imperative. One way to reduce this impact is to increase the reuse of materials that are considered, by current definitions of ”waste”, at their end of life. End-of-Life Household Materials (EoLHM) can be defined as household waste materials that still possess exploitable properties, thus making them suitable for reuse. There are several studies in the literature that address the recycling of these materials. When it comes to their reuse, unfortunately, only a limited number of studies are available. This paper aims to fill this gap by investigating the possibility to convert EoLHM, such as clothes or packaging, into low-cost thermal insulating materials for the improvement of the indoor thermal comfort in buildings, especially for households at risk of suffering from energy poverty. For this purpose, a comprehensive literature review and a qualitative analysis of both commercial and EoLHM are proposed. Commercial thermal insulating materials analysis is used as a reference to measure the performance of EoLHM. Important aspects to be considered when choosing suitable EoLHM for a smart conversion and reuse are also investigated. The most important outcome of this investigation is the comprehension that the conversion of EoLHM into insulating material is possible, and it implies a direct reduction in waste production, with environmental benefits and positive social implications. However, some aspects such as adaptability, life expectancy, collection and storage are, at present, in need of further thinking and development to make the EoLHM reuse and re-conversion processes viable on a large (neighborhood/city) scale

Downregulation of 26S proteasome catalytic activity promotes epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) endows carcinoma cells with phenotypic plasticity that can facilitate the formation of cancer stem cells (CSCs) and contribute to the metastatic cascade. While there is substantial support for the role of EMT in driving cancer cell dissemination, less is known about the intracellular molecular mechanisms that govern formation of CSCs via EMT. Here we show that β2 and β5 proteasome subunit activity is downregulated during EMT in immortalized human mammary epithelial cells. Moreover, selective proteasome inhibition enabled mammary epithelial cells to acquire certain morphologic and functional characteristics reminiscent of cancer stem cells, including CD44 expression, self-renewal, and tumor formation. Transcriptomic analyses suggested that proteasome-inhibited cells share gene expression signatures with cells that have undergone EMT, in part, through modulation of the TGF-β signaling pathway. These findings suggest that selective downregulation of proteasome activity in mammary epithelial cells can initiate the EMT program and acquisition of a cancer stem cell-like phenotype. As proteasome inhibitors become increasingly used in cancer treatment, our findings highlight a potential risk of these therapeutic strategies and suggest a possible mechanism by which carcinoma cells may escape from proteasome inhibitor-based therapy

Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation

The force-dependent interaction between talin and vinculin plays a crucial role in the initiation and growth of focal adhesions. Here we use magnetic tweezers to characterise the mechano-sensitive compact N-terminal region of the talin rod, and show that the three helical bundles R1-R3 in this region unfold in three distinct steps consistent with the domains unfolding independently. Mechanical stretching of talin R1-R3 enhances its binding to vinculin and vinculin binding inhibits talin refolding after force is released. Mutations that stabilize R3 identify it as the initial mechano-sensing domain in talin, unfolding at ~5 pN, suggesting that 5 pN is the force threshold for vinculin binding and adhesion progression

Long-lived neutral-kaon flux measurement for the KOTO experiment

The KOTO ($K^0$ at Tokai) experiment aims to observe the CP-violating rare decay $K_L \rightarrow \pi^0 \nu \bar{\nu}$ by using a long-lived neutral-kaon beam produced by the 30 GeV proton beam at the Japan Proton Accelerator Research Complex. The $K_L$ flux is an essential parameter for the measurement of the branching fraction. Three $K_L$ neutral decay modes, $K_L \rightarrow 3\pi^0$, $K_L \rightarrow 2\pi^0$, and $K_L \rightarrow 2\gamma$ were used to measure the $K_L$ flux in the beam line in the 2013 KOTO engineering run. A Monte Carlo simulation was used to estimate the detector acceptance for these decays. Agreement was found between the simulation model and the experimental data, and the remaining systematic uncertainty was estimated at the 1.4\% level. The $K_L$ flux was measured as $(4.183 \pm 0.017_{\mathrm{stat.}} \pm 0.059_{\mathrm{sys.}}) \times 10^7$ $K_L$ per $2\times 10^{14}$ protons on a 66-mm-long Au target.Comment: 27 pages, 16 figures. To be appeared in Progress of Theoretical and Experimental Physic

Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia

BackgroundCritical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities.Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization.Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissues.MethodsBalb-c nude mice (n:24) were distributed in four different groups: healthy controls (C, n:4), shams (SH, n:4), and ischemic mice (after femoral ligation) that received either 50 mu l physiological serum (SC, n:8) or 5x10(5) human CACs (SE, n:8). Ischemic mice were sacrificed on days 2 and 4 (n:4/group/day), and immunohistochemistry assays and qPCR amplification of Alu-human-specific sequences were carried out for cell detection and vascular density measurements. Additionally, a label-free MS-based quantitative approach was performed to identify protein changes related.ResultsAdministration of CACs induced in the ischemic tissues an increase in the number of blood vessels as well as the diameter size compared to ischemic, non-treated mice, although the number of CACs decreased within time. The initial protein changes taking place in response to ischemia and more importantly, right after administration of CACs to CLI mice, are shown.ConclusionsOur results indicate that CACs migrate to the injured area; moreover, they trigger protein changes correlated with cell migration, cell death, angiogenesis, and arteriogenesis in the host. These changes indicate that CACs promote from the beginning an increase in the number of vessels as well as the development of an appropriate vascular network.Institute of Health Carlos III, ISCIII; Junta de Andaluci

Frequency analyses of CSF flow on cine MRI in normal pressure hydrocephalus

Abstract Our objective was to clarify intracranial cerebrospinal fluid (CSF) flow dynamics in normalpressure hydrocephalus (NPH). Frequency analyses of CSF flow measured with phase-contrast cine MRI were performed. The CSF flow spectra in the aqueduct were determined in patients (n=51) with NPH, brain atrophy or asymptomatic ventricular dilation (VD), and in healthy volunteers (control group; n=25). The changes in CSF flow spectra were also analyzed after intravenous injection of acetazolamide. Moreover, a phase transfer function (PTF) calculated from the spectra of the driving vascular pulsation and CSF flow in the aqueduct were assessed. These values were compared with the pressure volume response (PVR). The amplitude in the NPH group was significantly larger than that in the VD or control group because of a decrease in compliance. The phase in the NPH group was significantly different from that in either the VD or the control group, but no difference was found between the VD and control groups. The amplitude increased in all groups after acetazolamide injection. The PTF in the NPH group was significantly larger than in the control group, and a positive correlation was noted between PTF and PVR. Frequency analyses of CSF flow measured by cine MRI make it possible to noninvasively obtain a more detailed picture of the pathophysiology of NPH

Precocious Metamorphosis in the Juvenile Hormone–Deficient Mutant of the Silkworm, Bombyx mori

Insect molting and metamorphosis are intricately governed by two hormones, ecdysteroids and juvenile hormones (JHs). JHs prevent precocious metamorphosis and allow the larva to undergo multiple rounds of molting until it attains the proper size for metamorphosis. In the silkworm, Bombyx mori, several “moltinism” mutations have been identified that exhibit variations in the number of larval molts; however, none of them have been characterized molecularly. Here we report the identification and characterization of the gene responsible for the dimolting (mod) mutant that undergoes precocious metamorphosis with fewer larval–larval molts. We show that the mod mutation results in complete loss of JHs in the larval hemolymph and that the mutant phenotype can be rescued by topical application of a JH analog. We performed positional cloning of mod and found a null mutation in the cytochrome P450 gene CYP15C1 in the mod allele. We also demonstrated that CYP15C1 is specifically expressed in the corpus allatum, an endocrine organ that synthesizes and secretes JHs. Furthermore, a biochemical experiment showed that CYP15C1 epoxidizes farnesoic acid to JH acid in a highly stereospecific manner. Precocious metamorphosis of mod larvae was rescued when the wild-type allele of CYP15C1 was expressed in transgenic mod larvae using the GAL4/UAS system. Our data therefore reveal that CYP15C1 is the gene responsible for the mod mutation and is essential for JH biosynthesis. Remarkably, precocious larval–pupal transition in mod larvae does not occur in the first or second instar, suggesting that authentic epoxidized JHs are not essential in very young larvae of B. mori. Our identification of a JH–deficient mutant in this model insect will lead to a greater understanding of the molecular basis of the hormonal control of development and metamorphosis

Macrophage Inhibitory Cytokine 1 (MIC-1/GDF15) Decreases Food Intake, Body Weight and Improves Glucose Tolerance in Mice on Normal & Obesogenic Diets

Food intake and body weight are controlled by a variety of central and peripheral factors, but the exact mechanisms behind these processes are still not fully understood. Here we show that that macrophage inhibitory cytokine-1 (MIC-1/GDF15), known to have anorexigenic effects particularly in cancer, provides protection against the development of obesity. Both under a normal chow diet and an obesogenic diet, the transgenic overexpression of MIC-1/GDF15 in mice leads to decreased body weight and fat mass. This lean phenotype was associated with decreased spontaneous but not fasting-induced food intake, on a background of unaltered energy expenditure and reduced physical activity. Importantly, the overexpression of MIC-1/GDF15 improved glucose tolerance, both under normal and high fat-fed conditions. Altogether, this work shows that the molecule MIC-1/GDF15 might be beneficial for the treatment of obesity as well as perturbations in glucose homeostasis