Passive components used in power converters

In power converters, passive components play an important role, and have in general specific nature and properties. The goal of this tutorial is to give an overview, first on inductive components for power conversion, and second on dedicated power capacitors. In a third part, new components— supercapacitors—will be presented. Generally, inductors for power applications must be custom designed. In this tutorial, the most important effects encountered when realising inductive components will be presented in the first part, without entering into the detailed design of such components. For that purpose, the referenced documents that have served as a base for this tutorial must be consulted [1], [2], and mainly [3]. The second part of this tutorial (Capacitors used in power electronics) is dedicated to power capacitors. Unlike inductors, capacitors cannot be specifically designed, but must be selected from a manufacturer’s list of components. Here, the documentation corresponds to a subset of Ref. [4] that has been translated by Dr. Martin Veenstra. The third part of the tutorial (Supercapacitors and applications) presents supercapacitors, new components that have very high energy density and high power density. Modelling and design rules for several applications are presented. This part of the document uses as a base the study made by Dr. Philippe Barrade [5]. Finally, it must be noted that, even with a correct selection or design of passive elements, there can be parasitic effects caused by interactions between components of the same or different nature. As an example, by designing filters combining several passives like inductors and capacitors, the primary specification may be modified by the interaction of parasitics, typically a mutual coupling between the parasitic inductances of neighbouring capacitors. A good description of such effects can be found in Ref. [6]

A First-Tier Framework for Assessing Toxicological Risk from Vaporized Cannabis Concentrates

Vaporization is an increasingly prevalent means to consume cannabis, but there is little guidance for manufacturers or regulators to evaluate additive safety. This paper presents a first-tier framework for regulators and cannabis manufacturers without significant toxicological expertise to conduct risk assessments and prioritize additives in cannabis concentrates for acceptance, elimination, or further evaluation. Cannabinoids and contaminants (e.g., solvents, pesticides, etc.) are excluded from this framework because of the complexity involved in their assessment; theirs would not be a first-tier toxicological assessment. Further, several U.S. state regulators have provided guidance for major cannabinoids and contaminants. Toxicological risk assessment of cannabis concentrate additives, like other types of risk assessment, includes hazard assessment, dose–response, exposure assessment, and risk characterization steps. Scarce consumption data has made exposure assessment of cannabis concentrates difficult and variable. Previously unpublished consumption data collected from over 54,000 smart vaporization devices show that 50th and 95th percentile users consume 5 and 57 mg per day on average, respectively. Based on these and published data, we propose assuming 100 mg per day cannabis concentrate consumption for first-tier risk assessment purposes. Herein, we provide regulators, cannabis manufacturers, and consumers a preliminary methodology to evaluate the health risks of cannabis concentrate additives

Facharztweiterbildung Psychiatrie und Psychotherapie: Problemorientiertes Lernen - Evaluation eines Modellprojekts

Zusammenfassung: Die Betonung individueller Lernbedürfnisse, der Fähigkeit zur Lösung komplexer klinischer Probleme sowie einer von interkollegialer Kommunikation geprägten professionellen Grundhaltung durch das problemorientierte Lernen (POL) spricht für dessen Eignung als didaktisches Format in der Facharztweiterbildung. Dennoch wurde es bisher selten hierfür eingesetzt. Im Rahmen dieses Modellprojektes wurde das POL in das Kurrikulum der strukturierten Facharztweiterbildung Psychiatrie und Psychotherapie aufgenommen und über einen Zeitraum von 12Monaten mittels strukturierter Fragebögen evaluiert. Es fanden im Evaluationszeitraum 41POL-Kurse statt, an denen insgesamt 447 Assistenzärzte teilnahmen. Die Teilnehmer und die Tutoren bewerteten 19 von 21 erfragten Aspekten der POL-Kurse als gut bis sehr gut (Mittelwert auf einer 5-stufigen Likert-Skala >4). Insgesamt wurde das POL als besonders geeignet für die Weiterbildung eingeschätzt (Teilnehmer 4,5±0,8; Tutoren 5,0±0,2). Die Ergebnisse dieses Modellprojekts sprechen für die Eignung des POL als Teil eines vielfältigen Weiterbildungsangebots, um den Praxisbezug und die Anwendbarkeit des Wissens im klinischen Alltag zu stärke

Dissociation and symptom dimensions of obsessive-compulsive disorder: A replication study

Background: Obsessive-compulsive disorder (OCD) is a phenotypically very heterogeneous disease with high rates of comorbid psychiatric pathology. Previous studies have indicated that OCD is associated with higher levels of dissociation. The aims of the present study were to replicate and extend previous findings of a significant link between certain OCD symptom dimensions and dissociation. Methods: The study sample comprised 50 patients with OCD, as confirmed by the Mini International Neuropsychiatric Interview,who had a score of at least 16 on the Yale-Brown Obsessive-Compulsive Scale. All patients were assessed with the short version of the Hamburg Obsessive-Compulsive Inventory and the Dissociative Experience Scale (DES). Correlation analyses and multiple regression analyses were performed to evaluate the relationship between OCD symptom dimensions and dissociation. Results: The checking dimension was most strongly related to dissociation, followed by the symmetry/ordering and obsessive thoughts dimensions. In contrast, no significant relationship was found between dissociation and the washing/cleaning, counting/touching, and aggressive impulses/fantasies dimensions. Multiple regression analyses revealed that: (1) only the checking dimension showed an independent positive correlation with dissociation, and (2) only higher scores on the DES subscale "amnestic dissociation" were associated with higher scores for checking compulsions. Conclusions: Our results suggest that there might be a specific link between checking behavior and dissociation in OCD. Moreover, checking compulsions seem to be particularly associated with amnestic dissociation. Further studies focusing on amnestic dissociation as a potentially important determinant of checking compulsions are warrante

Pharmacological Analysis of Dopamine Modulation in the \u3cem\u3eDrosophila melanogaster\u3c/em\u3e Larval Heart

Dopamine (DA) and other neurotransmitters affect nonneuronal tissues in insects by circulating in the hemolymph. In several organisms, DA has been shown to modulate distinct aspects of cardiac function but the signal transduction pathways that mediate dopaminergic effects on the heart are not well characterized. Here, we used a semiintact Drosophila melanogaster larva preparation and drugs targeting DA receptors and canonical second messenger pathways to identify signaling cascades that mediate the effect of DA on a myogenic heart. DA has a positive chronotropic effect that is mimicked by SKF38393 (type‐1 DA receptor agonist) and quinpirole (type‐2 DA receptor agonist). SCH23390 and spiperone (type‐1 and type‐2 DA receptor antagonists) are moderately effective at inhibiting DA\u27s effect. An adenylate cyclase inhibitor (SQ,22536) is also effective at blocking the stimulatory effect of DA but the drug has its own dose‐dependent effect. Activation of protein kinase C with a diacylglycerol analog has a stimulatory effect on heart rate (HR). These results suggest that (1) both DA receptor subtypes are expressed in third instar larva cardiac myocytes to increase HR in response to rising levels of DA in the hemolymph, and (2) canonical second messenger pathways modulate HR in D. melanogaster larvae. Having these disparate signaling cascades converge toward a common modulatory function appears redundant, but in the context of multiple cardioactive chemicals this redundancy is likely to increase the fidelity of signal transduction

Profile of a Serial Killer: Cellular and Molecular Approaches to Study Individual Cytotoxic T-Cells following Therapeutic Vaccination

T-cell vaccination may prevent or treat cancer and infectious diseases, but further progress is required to increase clinical efficacy. Step-by-step improvements of T-cell vaccination in phase I/II clinical studies combined with very detailed analysis of T-cell responses at the single cell level are the strategy of choice for the identification of the most promising vaccine candidates for testing in subsequent large-scale phase III clinical trials. Major aims are to fully identify the most efficient T-cells in anticancer therapy, to characterize their TCRs, and to pinpoint the mechanisms of T-cell recruitment and function in well-defined clinical situations. Here we discuss novel strategies for the assessment of human T-cell responses, revealing in part unprecedented insight into T-cell biology and novel structural principles that govern TCR-pMHC recognition. Together, the described approaches advance our knowledge of T-cell mediated-protection from human diseases

Lebensqualität und alexithyme Merkmale bei Patienten mit somatoformer Schmerzstörung

Zusammenfassung: Hintergrund: Patienten mit einer somatoformen Schmerzstörung weisen häufig eine schlechte gesundheitsbezogene Lebensqualität (QoL) und Schwierigkeiten in der Affektregulation (Alexithymie) auf. Ziel dieser Studie war es, den Zusammenhang zwischen QoL und alexithymen Merkmalen zu untersuchen. Patienten und Methoden: Bei 51Patienten mit somatoformer Schmerzstörung (durchschnittliche Erkrankungsdauer: 11,6Jahre) wurden Alexithymie (TAS-20), QoL (WHOQOL-BREF), psychische Belastung und Somatisierung (SCL-90-R) und depressive Symptome (MADRS) erhoben. Ergebnisse: Es fand sich eine signifikante negative Korrelation zwischen QoL und alexithymen Persönlichkeitsmerkmalen, insbesondere der psychischen QoL und dem TAS-20-Gesamtwert (r=−0,63, p<0,001). Die Alexithymiesubskala "Schwierigkeiten, Gefühle zu beschreiben" erwies sich als signifikanter Einflussfaktor für die psychische QoL (β=−0,34, p<0,01), auch nach Kontrolle von Depression, Somatisierung und Geschlecht. Schlussfolgerung: Für die insgesamt sehr niedrige QoL von Patienten mit somatoformer Schmerzstörung scheinen auch alexithyme Charakteristika eine wichtige Rolle zu spielen. Dies sollte sowohl diagnostisch als auch in der therapeutischen Zielsetzung berücksichtigt werde

Fine-Tuning of Optimal TCR Signaling in Tumor-Redirected CD8 T Cells by Distinct TCR Affinity-Mediated Mechanisms

Redirecting CD8 T cell immunity with self/tumor-specific affinity-matured T cell receptors (TCRs) is a promising approach for clinical adoptive T cell therapy, with the aim to improve treatment efficacy. Despite numerous functional-based studies, little is known about the characteristics of TCR signaling (i.e., intensity, duration, and amplification) and the regulatory mechanisms underlying optimal therapeutic T cell responses. Using a panel of human SUP-T1 and primary CD8 T cells engineered with incremental affinity TCRs against the cancer-testis antigen NY-ESO-1, we found that upon activation, T cells with optimal-affinity TCRs generated intense and sustained proximal (CD3 zeta, LCK) signals associated with distal (ERK1/2) amplification-gain and increased function. In contrast, in T cells with very high affinity TCRs, signal initiation was rapid and strong yet only transient, resulting in poor MAPK activation and low proliferation potential even at high antigen stimulation dose. Under resting conditions, the levels of surface TCR/CD3e, CD8 beta, and CD28 expression and of CD3. phosphorylation were significantly reduced in those hypo-responsive cells, suggesting the presence of TCR affinity-related activation thresholds. We also show that SHP phosphatases were involved along the TCR affinity gradient, but displayed spatially distinct regulatory roles. While PTPN6/SHP-1 phosphatase activity controlled TCR signaling initiation and subsequent amplification by counteracting CD3. and ERK1/2 phosphorylation, PTPN11/SHP-2 augmented MAPK activation without affecting proximal TCR signaling. Together, our findings indicate that optimal TCR signaling can be finely tuned by TCR affinity-dependent SHP-1 and SHP-2 activity, and this may readily be determined at the TCR/CD3 complex level. We propose that these TCR affinity-associated regulations represent potential protective mechanisms preventing high affinity TCR-mediated autoimmune diseases

SHP-1 phosphatase activity counteracts increased T cell receptor affinity.

Anti-self/tumor T cell function can be improved by increasing TCR-peptide MHC (pMHC) affinity within physiological limits, but paradoxically further increases (K(d) &lt; 1 μM) lead to drastic functional declines. Using human CD8(+) T cells engineered with TCRs of incremental affinity for the tumor antigen HLA-A2/NY-ESO-1, we investigated the molecular mechanisms underlying this high-affinity-associated loss of function. As compared with cells expressing TCR affinities generating optimal function (K(d) = 5 to 1 μM), those with supraphysiological affinity (K(d) = 1 μM to 15 nM) showed impaired gene expression, signaling, and surface expression of activatory/costimulatory receptors. Preferential expression of the inhibitory receptor programmed cell death-1 (PD-1) was limited to T cells with the highest TCR affinity, correlating with full functional recovery upon PD-1 ligand 1 (PD-L1) blockade. In contrast, upregulation of the Src homology 2 domain-containing phosphatase 1 (SHP-1/PTPN6) was broad, with gradually enhanced expression in CD8(+) T cells with increasing TCR affinities. Consequently, pharmacological inhibition of SHP-1 with sodium stibogluconate augmented the function of all engineered T cells, and this correlated with the TCR affinity-dependent levels of SHP-1. These data highlight an unexpected and global role of SHP-1 in regulating CD8(+) T cell activation and responsiveness and support the development of therapies inhibiting protein tyrosine phosphatases to enhance T cell-mediated immunity