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]

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

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

Long-term course and outcome of obsessive-compulsive patientsafter cognitive-behavioral therapy in combination with eitherfluvoxamine or placebo: A 7-year follow-up of a randomized double-blind trial

Longitudinal studies with very long follow-up periods of patients with obsessive-compulsive disorder (OCD) who have received adequate treatment are rare. In the current study, 30 of 37 inpatients (81%) with severe OCD were followed up 6-8 years after treatment with cognitive-behavioral therapy (CBT) in combination with either fluvoxamine or placebo in a randomized design. The significant improvements (with large effectsizes) in obsessive-compulsive symptoms from pre- to post-treatment (41% reduction on the Y-BOCS) remained stable at follow-up (45 %). Responder rates, defined as ≥35% reduction on the Y-BOCS, were 67% and 60%, respectively. Depressive symptoms decreased significantly not only from pre- to post-treatment but also during follow-up. Re-hospitalization, which occurred in 11 patients (37 %), was associated with more severe depressive symptoms at pre-treatment and living without a partner. Full symptom remission at follow-up, defined as both Y-BOCS total score ≤ 7 and no longer meeting diagnostic criteria for OCD, was achieved by 8 patients (27 %). Patients without full remission at follow-up had a significantly longer history of OCD, assessed at pretreatment, compared to remitted patients. The shortterm treatment outcome had no predictive value for the long-term course. Throughout the naturalistic follow-up, nearly all patients (29 patients) received additional psychotherapy and/or medication. This might indicate that such chronic OCD patients usually need additional therapeutic support after effective inpatient treatment to maintain their improvements over long period

Single cell analysis reveals similar functional competence of dominant and nondominant CD8 T-cell clonotypes.

Immune protection from infectious diseases and cancer is mediated by individual T cells of different clonal origin. Their functions are tightly regulated but not yet fully characterized. Understanding the contribution of each T cell will improve the prediction of immune protection based on laboratory assessment of T-cell responses. Here we developed techniques for simultaneous molecular and functional assessment of single CD8 T cells directly ex vivo. We studied two groups of patients with melanoma after vaccination with two closely related tumor antigenic peptides. Vaccination induced T cells with strong memory and effector functions, as found in virtually all T cells of the first patient group, and fractions of T cells in the second group. Interestingly, high functionality was not restricted to dominant clonotypes. Rather, dominant and nondominant clonotypes acquired equal functional competence. In parallel, this was also found for EBV- and CMV-specific T cells. Thus, the nondominant clonotypes may contribute similarly to immunity as their dominant counterparts

Adequacy of Maternal Iron Status Protects against Behavioral, Neuroanatomical, and Growth Deficits in Fetal Alcohol Spectrum Disorders

Fetal alcohol spectrum disorders (FASD) are the leading non-genetic cause of neurodevelopmental disability in children. Although alcohol is clearly teratogenic, environmental factors such as gravidity and socioeconomic status significantly modify individual FASD risk despite equivalent alcohol intake. An explanation for this variability could inform FASD prevention. Here we show that the most common nutritional deficiency of pregnancy, iron deficiency without anemia (ID), is a potent and synergistic modifier of FASD risk. Using an established rat model of third trimester-equivalent binge drinking, we show that ID significantly interacts with alcohol to impair postnatal somatic growth, associative learning, and white matter formation, as compared with either insult separately. For the associative learning and myelination deficits, the ID-alcohol interaction was synergistic and the deficits persisted even after the offsprings’ iron status had normalized. Importantly, the observed deficits in the ID-alcohol animals comprise key diagnostic criteria of FASD. Other neurobehaviors were normal, showing the ID-alcohol interaction was selective and did not reflect a generalized malnutrition. Importantly ID worsened FASD outcome even though the mothers lacked overt anemia; thus diagnostics that emphasize hematological markers will not identify pregnancies at-risk. This is the first direct demonstration that, as suggested by clinical studies, maternal iron status has a unique influence upon FASD outcome. While alcohol is unquestionably teratogenic, this ID-alcohol interaction likely represents a significant portion of FASD diagnoses because ID is more common in alcohol-abusing pregnancies than generally appreciated. Iron status may also underlie the associations between FASD and parity or socioeconomic status. We propose that increased attention to normalizing maternal iron status will substantially improve FASD outcome, even if maternal alcohol abuse continues. These findings offer novel insights into how alcohol damages the developing brain

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

Long-lasting stem cell-like memory CD8+ T cells with a naïve-like profile upon yellow fever vaccination.

Efficient and persisting immune memory is essential for long-term protection from infectious and malignant diseases. The yellow fever (YF) vaccine is a live attenuated virus that mediates lifelong protection, with recent studies showing that the CD8(+) T cell response is particularly robust. Yet, limited data exist regarding the long-term CD8(+) T cell response, with no studies beyond 5 years after vaccination. We investigated 41 vaccinees, spanning 0.27 to 35 years after vaccination. YF-specific CD8(+) T cells were readily detected in almost all donors (38 of 41), with frequencies decreasing with time. As previously described, effector cells dominated the response early after vaccination. We detected a population of naïve-like YF-specific CD8(+) T cells that was stably maintained for more than 25 years and was capable of self-renewal ex vivo. In-depth analyses of markers and genome-wide mRNA profiling showed that naïve-like YF-specific CD8(+) T cells in vaccinees (i) were distinct from genuine naïve cells in unvaccinated donors, (ii) resembled the recently described stem cell-like memory subset (Tscm), and (iii) among all differentiated subsets, had profiles closest to naïve cells. Our findings reveal that CD8(+) Tscm are efficiently induced by a vaccine in humans, persist for decades, and preserve a naïveness-like profile. These data support YF vaccination as an optimal mechanistic model for the study of long-lasting memory CD8(+) T cells in humans

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