Process planning and metallurgical issues for laser asisted spin froming of dual phase automotive steel

Postprint (published version

Eugenia:towards disciplined and automated development of GMF-based graphical model editors

EMF and GMF are powerful frameworks for implementing tool support for modelling languages in Eclipse. However, with power comes complexity, implementing a graphical editor for a modelling language using EMF and GMF requires developers to handcraft and maintain several detailed interconnected models through a loosely guided, labour-intensive, and error-prone process. We demonstrate how the application of metamodel annotation and model transformation techniques can help to manage the complexity of GMF and EMF and deliver significant productivity, quality, and maintainability benefits. We present Eugenia, an open-source tool that implements the proposed approach, illustrate its functionality with an example, evaluate it through an empirical study, and report on the community’s response to the tool

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

The Flipped Learning: Guía "gamificada" para novatos y no tan novatos

Si estás interesado en el libro consíguelo en www.amazon.esExplica Javier Tourón en el prólogo de "The Flipped Learning" que la escuela y el aprendizaje ya no pueden seguir siendo lo que eran, pues las necesidades de la sociedad y del entorno laboral han cambiado enormemente. La escuela y las demás instituciones educativas deben adaptarse para mantener su funcionalidad y su capacidad de anticipación. Es necesario, pues, redefinir el aprendizaje y determinar qué deben saber y saber hacer los alumnos. Y, para lograrlo, "The Flipped Learning" se presenta como una estupenda herramienta que puede ayudar a los profesores a mejorar sus tareas diarias. “Este es un libro de gran valor pedagógico y tecnológico porque son los mismos profesores los que hablan a sus colegas –desde su propia experiencia, desde quien lo tiene sabido como propio– y les explican cómo es posible hacer lo que parece imposible. Con un lenguaje directo y sencillo este grupo de profesores entusiastas, de innovadores inconformistas, ha decidido sacar adelante un proyecto del máximo interés, pues apoyándose en un enfoque pedagógico acertado (el flipped classroom) han decidido poner a disposición de los demás, con espíritu de servicio y afán de mejora, su conocimiento y experiencia. Han seleccionado con acierto las mejores aplicaciones que permitan llevar a la práctica lo señalado más arriba: hacer del alumno un protagonista de su propio aprendizaje

Combined vaccination with idiotype-pulsed allogeneic dendritic cells and soluble protein idiotype for multiple myeloma patients relapsing after reduced-intensity conditioning allogeneic stem cell transplantation.

BACKGROUND AND OBJECTIVE: To combine the use of idiotype-pulsed allogeneic dendritic cells (alloDC) and soluble protein Id conjugated with KLH (Id-KLH) in a vaccine strategy for multiple myeloma (MM). DESIGN AND METHODS: Four MM patients received the combined vaccine after having experienced disease relapse/progression following reduced intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) and failure to rescue therapy with donor lymphocyte infusion or chemotherapy (CHT). RESULTS: Vaccination was well tolerated and induced an anti-KLH antibody response in all 4 patients as well as substantial cell proliferation. In contrast, no case showed similar effects against either tumor-specific Id or irrelevant isotype control immunoglobulins (Ig). In turn, vaccination was associated with modulation of biological responses linked to both inflammatory and T-cell activation, with secretion of effector Th1 cytokines. In particular, an important increase in the spontaneous ex vivo secretion of TNFalpha, IL-6 and IFNgamma as well as IL-2 and IL-10 was frequently observed prior to the fourth vaccination. Moreover, in vitro stimulation with Id-KLH and Id-KLH plus alloDC, but not with alloDC alone was associated with an enhanced number of TNF-alpha+ T-cells and an increased secretion of IFNgamma and IL-2 before the third and fourth vaccination. From a clinical standpoint, 2 patients had a transient response and 1 has stable disease after stopping vaccination, while 3 of them ultimately progressed. INTERPRETATION AND CONCLUSIONS: The results show for the first time that the use of Id-pulsed alloDC following RIC alloSCT is safe and feasible. However, crucial strategy improvements are warranted to possibly achieve clinical benefit

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor-Associated Myocarditis.

BACKGROUND: Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited. OBJECTIVES: This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis. METHODS: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. RESULTS: Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction CONCLUSIONS: The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor-Associated Myocarditis.

Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE.The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis