Experimental Study of Second-Mode Instabilities on a 7-Degree Cone at Mach 6

Experiments have been carried out in the NASA Langley Research Center 20-Inch Mach 6 Air Tunnel to measure the second-mode boundary-layer instability on a 7deg half-angle cone using high-frequency pressure sensors. Data were obtained with both blunt and sharp nosetips installed on the cone. The second-mode wave amplitudes were observed to saturate and then begin to decrease in the Langley tunnels, indicating wave breakdown. Pressure fluctuation measurements and thermocouple data indicated the location of transition along the cone at the different conditions tested. Comparisons between the power density spectra obtained during the current test and previous data from the Langley 15-Inch Mach 6 High Temperature Tunnel and the Boeing/AFOSR Mach 6 Quiet tunnel illustrate the effect of tunnel noise on instability growth and transition

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

Measurements and Computations of Second-Mode Instability Waves in Three Hypersonic Wind Tunnels

High-frequency pressure-fluctuation measurements were made in AEDC Tunnel 9 at Mach 10 and the NASA Langley 15-Inch Mach 6 and 31-Inch Mach 10 tunnels. Measurements were made on a 7deg-half-angle cone model. Pitot measurements of freestream pressure fluctuations were also made in Tunnel 9 and the Langley Mach-6 tunnel. For the first time, second-mode waves were measured in all of these tunnels, using 1-MHz-response pressure sensors. In Tunnel 9, second-mode waves could be seen in power spectra computed from records as short as 80 micro-s. The second-mode wave amplitudes were observed to saturate and then begin to decrease in the Langley tunnels, indicating wave breakdown. Breakdown was estimated to occur near N approx. equals 5 in the Langley Mach-10 tunnel. The unit-Reynolds-number variations in the data from Tunnel 9 were too large to see the same processes. In Tunnel 9, the measured transition locations were found to be at N = 4.5 using thermocouples, and N = 5.3 using 50-kHz-response pressure sensors. What appears to be a very long transitional region was observed at a unit Reynolds number of 13.5 million per meter in Tunnel 9. These results were consistent with the high-frequency pressure fluctuation measurements. High-frequency pressure fluctuation measurements indicated that transition did occur in the Langley Mach-6 tunnel, but the location of transition was not precisely determined. Unit Reynolds numbers in the Langley Mach-10 tunnel were too low to observe transition. More analysis of this data set is expected in the future

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

The lattice of the CERN Large Hadron Collider

The lattice of the CERN Large Hadron Collider is designed with 23 regular cells per arc, each containing 6 tightly packed 14.2 m long dipoles. This allows to reach 7 TeV per beam with a dipole field of 8.4 Tesla. There are four experimental insertions, two of which are devoted to high luminosity experiments with ± 23 m of free space for the detector. The other two experimental insertions are combined with injection. The value of ß* at the interaction points is tunable from 6 m at injection to 0.5 m in collision. The energy deposition in the inner triplets is carefully reduced to sustain the nominal luminosity of 1034 cm-2s-1. Two insertions are devoted to collect the halo particles with large emittance and momentum spread surrounding the beam core: escaping rates of the protons are estimated to be less than 4·106 sec-1m-1. Finally, one insertion is used to extract the particles in the vertical direction with a minimized deflecting strength

Case Report: Stepwise Anti-Inflammatory and Anti-SARS-CoV-2 Effects Following Convalescent Plasma Therapy With Full Clinical Recovery.

In these times of COVID-19 pandemic, concern has been raised about the potential effects of SARS-CoV-2 infection on immunocompromised patients, particularly on those receiving B-cell depleting agents and having therefore a severely depressed humoral response. Convalescent plasma can be a therapeutic option for these patients. Understanding the underlying mechanisms of convalescent plasma is crucial to optimize such therapeutic approach. Here, we describe a COVID-19 patient who was deeply immunosuppressed following rituximab (anti-CD20 monoclonal antibody) and concomitant chemotherapy for chronic lymphoid leukemia. His long-term severe T and B cell lymphopenia allowed to evaluate the treatment effects of convalescent plasma. Therapeutic outcome was monitored at the clinical, biological and radiological level. Moreover, anti-SARS-CoV-2 antibody titers (IgM, IgG and IgA) and neutralizing activity were assessed over time before and after plasma transfusions, alongside to SARS-CoV-2 RNA quantification and virus isolation from the upper respiratory tract. Already after the first cycle of plasma transfusion, the patient experienced rapid improvement of pneumonia, inflammation and blood cell counts, which may be related to the immunomodulatory properties of plasma. Subsequently, the cumulative increase in anti-SARS-CoV-2 neutralizing antibodies due to the three additional plasma transfusions was associated with progressive and finally complete viral clearance, resulting in full clinical recovery. In this case-report, administration of convalescent plasma revealed a stepwise effect with an initial and rapid anti-inflammatory activity followed by the progressive SARS-CoV-2 clearance. These data have potential implications for a more extended use of convalescent plasma and future monoclonal antibodies in the treatment of immunosuppressed COVID-19 patients

Vaccination with LAG-3Ig (IMP321) and Peptides Induces Specific CD4 and CD8 T-Cell Responses in Metastatic Melanoma Patients-Report of a Phase I/IIa Clinical Trial.

PURPOSE: Cancer vaccines aim to generate and maintain antitumor immune responses. We designed a phase I/IIa clinical trial to test a vaccine formulation composed of Montanide ISA-51 (Incomplete Freund's Adjuvant), LAG-3Ig (IMP321, a non-Toll like Receptor agonist with adjuvant properties), and five synthetic peptides derived from tumor-associated antigens (four short 9/10-mers targeting CD8 T-cells, and one longer 15-mer targeting CD4 T-cells). Primary endpoints were safety and T-cell responses. EXPERIMENTAL DESIGN: Sixteen metastatic melanoma patients received serial vaccinations. Up to nine injections were subcutaneously administered in three cycles, each with three vaccinations every 3 weeks, with 6 to 14 weeks interval between cycles. Blood samples were collected at baseline, 1-week after the third, sixth and ninth vaccination, and 6 months after the last vaccination. Circulating T-cells were monitored by tetramer staining directly ex vivo, and by combinatorial tetramer and cytokine staining on in vitro stimulated cells. RESULTS: Side effects were mild to moderate, comparable to vaccines with Montanide alone. Specific CD8 T-cell responses to at least one peptide formulated in the vaccine preparation were found in 13 of 16 patients. However, two of the four short peptides of the vaccine formulation did not elicit CD8 T-cell responses. Specific CD4 T-cell responses were found in all 16 patients. CONCLUSIONS: We conclude that vaccination with IMP321 is a promising and safe strategy for inducing sustained immune responses, encouraging further development for cancer vaccines as components of combination therapies. Clin Cancer Res; 22(6); 1330-40. ©2015 AACR

IL-12 controls cytotoxicity of a novel subset of self-antigen-specific human CD28+ cytolytic T cells.

Activated CD8 T cells develop cytotoxicity against autologous cells bearing foreign Ags and self/tumor Ags. However, self-specific cytolysis needs to be kept under control to avoid overwhelming immunopathology. After peptide vaccination of melanoma patients, we studied molecular and functional properties of T cell subsets specific for the self/tumor Ag Melan-A/MART-1. Ex vivo analysis revealed three Ag-specific effector memory (EM) populations, as follows: CD28-negative EM (EM28(-)) T cells strongly expressing granzyme/perforin, and two EM28(+) subsets, one with high and the other with low level expression of these cytotoxic proteins. For further functional characterization, we generated 117 stable CD8 T cell clones by ex vivo flow cytometry-based sorting of these subsets. All EM28(-)-derived clones lysed target cells with high efficacy. In contrast, EM28(+)-derived clones were heterogenous, and could be classified in two groups, one with high and the other with low killing capacity, correlating with granzyme/perforin expression. High and low killer phenotypes remained surprisingly stable for several months. However, strongly increased granzyme expression and cytotoxicity were observed after exposure to IL-12. Thus, the data reveal a newly identified subset of CD28(+) conditional killer T cells. Because CD28 can mediate strong costimulatory signals, tight cytotoxicity control, as shown in this study through IL-12, may be particularly important for subsets of T cells expressing CD28