Analysis of LGV usage for the improvement of a customized production

The paper describes an approach for analyzing the use of a Laser-Guided Vehicle (LGV) in the context of the small and medium-sized enterprise. The use of LGVs is an efficient solution to provide more flexibility in the context of Just-In-Time production; however, the investment cost can limit this application. A methodology has been proposed in this work to analyze the technical feasibility of using an LGV in the manufacturing industry of customized products. The test case focuses on the study of a laser-guided system to optimize the handling of molds for customized production. In this scenario, an LGV is proposed to substitute manual carts used for moving molds from the warehouse to the injection machines. The traditional path included an intermediate station for pre-heating the molds in hot-air ovens. The proposed solution includes the study of an induction heating system on the LGV to optimize time and energy consumption

The RCK2 domain of the human BKCa channel is a calcium sensor

Large conductance voltage and Ca2+-dependent K+ channels (BKCa) are activated by both membrane depolarization and intracellular Ca2+. Recent studies on bacterial channels have proposed that a Ca2+-induced conformational change within specialized regulators of K+ conductance (RCK) domains is responsible for channel gating. Each pore-forming α subunit of the homotetrameric BKCa channel is expected to contain two intracellular RCK domains. The first RCK domain in BKCa channels (RCK1) has been shown to contain residues critical for Ca2+ sensitivity, possibly participating in the formation of a Ca2+-binding site. The location and structure of the second RCK domain in the BKCa channel (RCK2) is still being examined, and the presence of a high-affinity Ca2+-binding site within this region is not yet established. Here, we present a structure-based alignment of the C terminus of BKCa and prokaryotic RCK domains that reveal the location of a second RCK domain in human BKCa channels (hSloRCK2). hSloRCK2 includes a high-affinity Ca2+-binding site (Ca bowl) and contains similar secondary structural elements as the bacterial RCK domains. Using CD spectroscopy, we provide evidence that hSloRCK2 undergoes a Ca2+-induced change in conformation, associated with an α-to-β structural transition. We also show that the Ca bowl is an essential element for the Ca2+-induced rearrangement of hSloRCK2. We speculate that the molecular rearrangements of RCK2 likely underlie the Ca2+-dependent gating mechanism of BKCa channels. A structural model of the heterodimeric complex of hSloRCK1 and hSloRCK2 domains is discussed

Kinetics of the oxygen evolution reaction on rhodium electrodes with different electrocatalytic activity

It has recently been demonstrated that the potentiodynamic behaviour of Rh/H2SO4(aq) interphases in the potential range of the thermodynamic stability of bulk water is associated with at least two-well defined and different electrochemical characteristics of rhodium, which were referred to as Aand B-type Rh electrodes. The aim of the present report is to show the electrocatalytic difference of A- and B-type electrodes for the 02 evolution reaction, on the basis that the corresponding structures of the electrodes remain stable during the time the electrochemical measurements last.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Unusual Skin Toxicity after a Chemotherapic Combination

As known calciphylaxis (CPX) is a rare condition involving subcutaneous vascular calcification and cutaneous necrosis, mostly observed in patients with renal failure. However CPX may also appear in patients affected by polymyositis, Sjogren syndrome, Lupus Erythematosus systemicus, Sarcoidosis and rheumatoid arthritis, especially in children. Clinically CPX can present itself as subcutaneous nodules, infiltrate plaques or purpuric-like and livedo-like plaques, while in the late stages necrotic ulcers (with a bizarre shape and severe pain) may be the main cutaneous manifestations

Effect of Probiotic Administration on Serum Tryptophan Metabolites in Pediatric Type 1 Diabetes Patients

Type 1 diabetes (T1D) is characterized by anomalous functioning of the immuno regulatory, tryptophan-catabolic enzyme indoleamine 2,3 dioxygenase 1 (IDO1). In T1D, the levels of kynurenine—the first byproduct of tryptophan degradation via IDO1—are significantly lower than in nondiabetic controls, such that defective immune regulation by IDO1 has been recognized as potentially contributing to autoimmunity in T1D. Because tryptophan catabolism—and the production of immune regulatory catabolites—also occurs via the gut microbiota, we measured serum levels of tryptophan, and metabolites thereof, in pediatric, diabetic patients after a 3-month oral course of Lactobacillus rhamnosus GG. Daily administration of the probiotic significantly affected circulating levels of tryptophan as well as the qualitative pattern of metabolite formation in the diabetic patients, while it decreased inflammatory cytokine production by the patients. This study suggests for the first time that a probiotic treatment may affect systemic tryptophan metabolism and restrain proinflammatory profile in pediatric T1D

Identification of a 2-propanol analogue modulating the non-enzymatic function of indoleamine 2,3-dioxygenase 1

Abstract Indoleamine 2,3 dioxygenase 1 (IDO1) is a metabolic enzyme that catalyzes the conversion of the essential amino acid tryptophan (Trp) into a series of immunoactive catabolites, collectively known as kynurenines. Through the depletion of Trp and the generation of kynurenines, IDO1 represents a key regulator of the immune responses involved in physiologic homeostasis as well as in neoplastic and autoimmune pathologies. The IDO1 enzyme has been described as an important immune checkpoint to be targeted by catalytic inhibitors in the treatment of cancer. In contrast, a defective expression/activity of the enzyme has been demonstrated in autoimmune diseases. Beside its catalytic activity, the IDO1 protein is endowed with an additional function associated with the presence of two immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which, once phosphorylated, bind SHP phosphatases and mediate a long-term immunoregulatory activity of IDO1. Herein, we report the screening of a focused library of molecules bearing a propanol core by a protocol combining microscale thermophoresis (MST) analysis and a cellular assay. As a result, the combined screening identified a 2-propanolol analogue, VIS351, as the first potent activator of the ITIM-mediated function of the IDO1 enzyme. VIS351 displayed a good dissociation constant (Kd = 1.90 μM) for IDO1 and a moderate cellular inhibitor activity (IC50 = 11.463 μM), although it did not show any catalytic inhibition of the recombinant IDO1 enzyme. Because we previously demonstrated that the enzymatic and non-enzymatic (i.e., ITIM-mediated) functions of IDO1 reside in different conformations of the protein, we hypothesized that in the cellular system VIS351 may shift the dynamic conformational balance towards the ITIM-favoring folding of IDO1, resulting in the activation of the signaling rather than catalytic activity of IDO1. We demonstrated that VIS351 activated the ITIM-mediated signaling of IDO1 also in mouse plasmacytoid dendritic cells, conferring those cells an immunosuppressive phenotype detectable in vivo. Thus the manuscript describes for the first time a small molecule as a positive modulator of IDO1 signaling function, paving the basis for an innovative approach to develop first-in-class drugs acting on the IDO1 target

Putting families of origin into the queer picture : introducing this special issue

In undertaking our own separate research projects and in our crosscontinental comparative analyses of those projects, we became aware of the gaps between the richness of research on GLBT lives, including experiences of intimacy and parenthood, and the paucity of research on their relations with their families of origin. Still marginal is, in particular, research on the perspectives of the families of origin themselves: parents, but also siblings, grandparents, and other members of extended families. For the purposes of this special issue, we are deploying the term families of origin to mean heterosexual-identifying family members (at least as they publicly perform and display their sexualities), living within a heteronormative socio-politicocultural system. As we will argue in this introduction, however, there is a need to document and research, and thereby historically situate, family diversity, including the increasing shifting discourses and lived experiences of same-sex and other queer families of origin

A comparison of calcium-activated potassium channel currents in cell- attached and excised patches

Single channel currents from Ca-activated K channels were recorded from cell-attached patches, which were then excised from 1321N1 human astrocytoma cells. Cells were depolarized with K (110 mM) so that the membrane potential was known in both patch configurations, and the Ca ionophore A23187 or ionomycin (20-100 microM) was used to equilibrate intracellular and extracellular [Ca] (0.3 or 1 microM). Measurements of intracellular [Ca] with the fluorescent Ca indicator quin2 verified that [Ca] equilibration apparently occurred in our experiments. Under these conditions, where both membrane potential and intracellular [Ca] were known, we found that the dependence of the channel percent open time on membrane potential and [Ca] was similar in both the cell- attached and excised patch configuration for several minutes after excision. Current-voltage relations were also similar, and autocorrelation functions constructed from the single channel currents revealed no obvious change in channel gating upon patch excision. These findings suggest that the results of studies that use excised membrane patches can be extrapolated to the K-depolarized cell-attached configuration, and that the relation between [Ca] and channel activity can be used to obtain a quantitative measure of [Ca] near the membrane intracellular surface