In normal B-cells, Bruton tyrosine kinase (Btk), a non-receptor tyrosine kinase involved in B-cell receptor (BCR) signalling, is essential for cell survival and maturation. Not surprisingly, Btk is ...also implicated in the pathogenesis of B-cell lymphomas, like Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma (MCL) and Waldenström’s Macroglobulinemia (WM), which are driven by aberrant BCR signalling. Thus, targeting Btk represents a promising therapeutic strategy in the treatment of B-cell lymphoma patients. Ibrutinib, a selective Btk inhibitor, has already been approved as second-line treatment of CLL/SLL, MCL and WM patients, while more clinical studies of ibrutinib and novel Btk inhibitors are currently under way. In light of results of the RESONATE-2 trial, the approval of ibrutinib as a first-line treatment of CLL/SLL may well be approaching. Herein, we review Btk’s role in normal and malignant BCR signalling, as well as ibrutinib’s performance in B-cell lymphoma treatment and prognosis.
A new effort to model the flow in a 90° rectangular duct by adopting three low-Reynolds-number turbulence models, two eddy-viscosity models (a linear and a non-linear) and a Reynolds-stress model, is ...presented. The complex flow development is a challenge for the application of turbulence models in order to assess their capability to capture the secondary flow and the developing vortices due to curvature and strong pressure gradient effects. The numerical results show that both the non-linear eddy-viscosity and the Reynolds-stress models can provide good results, especially for the velocity distributions. The superiority of the Reynolds-stress model is shown primarily in the Reynolds-stress distributions, which have the best quality among the predictions from the other models. On the other hand, the main advantage of the non-linear model is its simplicity and the smaller needed CPU cost, compared to the Reynolds-stress model. Additionally, in some stations of the flow development, the non-linear model provides good velocity distributions. The linear model gives lower quality predictions for the Reynolds-stress distributions, although it is capable in providing quite satisfactory results for the velocity distributions.
In the first paper we use a natural experiment that relaxed class attendance requirements for one school year to explore students’ marginal propensity to skip class, and to examine the effects of ...their absences on scholastic outcomes. We exploit exogenous variation resulting from a one-time policy Greece implemented allowing high school students to miss 30 percent more class hours without penalty during the 2009-10 academic year, a period when officials feared outbreaks of swine flu. Using a new dataset, we analyze which students missed more classes, and the effect of these absences on scholastic outcomes across the distribution of student ability, income, and peer quality. We find that while the swine flu itself did not affect the student population, the relaxed class attendance policy caused an increase in absences of roughly 10 hours per student, with more absences taken by those who had higher academic performance records, have academically weaker peers in their classes, or who live in poorer neighborhoods. End-of-year exam results show a positive effect of absences on grades across the ability distribution. The magnitude of the positive effect of absences on grades increases as we move to right of the ability distribution. Our results suggest that students who may have the resources or the human capital accumulation to learn outside the classroom may have lower performance when a strict attendance policy forces them to stay in class. In the second chapter we study the effect of disclosing relative performance information (feed- back) on students’ performance in high-school, on subsequent university enrollment, and on expected subsequent earnings. We exploit a large-scale natural experiment in which students in some cohorts receive information about their relative performance within their schools and across the nation. Using unique primary data, we find an asymmetric response to feedback: high-achieving students improve their final-year performance by 0.15 of a standard deviation, whereas the final-year performance of low-achieving students drops by 0.3 of a standard deviation. The results are more pronounced for females, indicating greater sensitivity to feedback. We also document the long-term effects of feedback: high-achieving students reduce their repetition rate for the national exams; they enroll into university departments that are more selective by 0.15 of a standard deviation and their expected annual earnings increase by 0.17 of a standard deviation. By contrast, the results for low-achieving students are negative. We provide suggestive evidence that feedback encourages students from low-income neighborhoods to enroll in university and to study in higher-quality programs, which may, in the long run, reduce income inequality. In the third chapter we examine the extent to which college decisions among adolescents depend on the decisions of their peers. In particular, we ask whether individuals derive utility from conformity in college enrollment and academic mobility. We propose a new methodology in mit- igating reflection and endogeneity issues in identifying social interactions. We use the proportion of females in a student’s last year’s reference group (school and neighborhood) as an instrumental variable. We investigate utility spillovers from the educational choices of students in consecutive cohorts. Spatial variation allows us to identify social interactions in groups of various sizes. We use a new data set that spans the universe of high school graduates. We find positive and significant externalities in the decision to enroll in college and the decision to migrate to a different city among peers that belong to the same social group. Results indicate that students who are in a school or neighborhood with 100% more peers who enrolled in college last year are 29% or 9.6% more likely to themselves attend college. In the fourth chapter we consider how economic recessions alter the costs and expected returns of attaining college education in general and pursuing a specific college major. We examine how changes in the unemployment rate affect demand for college education, demand for different fields of university study and degrees’ admission thresholds. We use panel data for applications submitted to the universe of undergraduate programs in Greece that span seven rounds of admission cohorts combined with a degree-specific job insecurity index, and time series on youth (ages 18- 25) unemployment. We find that degree- and major-specific job insecurity turns applicants away from degrees and majors that are associated with poor employment prospects. Results indicate that the steep increase in the unemployment rate that started in 2009 is associated with an increase in the number of college applicants. The effect is heterogeneous across fields, with an increase in the demand for degrees in Psychology as well as for entrance to Naval, Police and Military Academies, and a decrease in the demand for degrees in Business and Management. We also find that the business cycle changes degrees’ admission thresholds by affecting their popularity.
Adrenal pseudocysts are rare entities and occurred in the 5th and the 6th decades of life. They are discovered accidentally, while appearing with nonspecific clinical and imaging findings. We report ...a case of a 28-year-old woman presented in our Emergency Department complaining about upper abdomen pain. Computed tomography revealed a hypodense cystic lesion containing hyperdense material. The size of a mass was 11. 7 × 9.3 × 6.6 cm in diameter close to the pancreas, but the origin was from the left adrenal gland. The mass was excised with surgical laparotomy. Giant adrenal pseudocysts are rare entities. Final diagnosis usually confirmed with the pathology examination. Management of such adrenal lesions depends on the unique characteristics, the surgeon’s experience, and local resources.
• The role of DUSP1 on acute inflammatory response was investigated. • p38 MAPK phosphorylation was limited by DUSP1. • DUSP1 inhibited IL-6, TNF and COX2 expression in macrophages. • ...Carrageenan-induced paw inflammation was enhanced in DUSP1 deficient mice. • DUSP1 suppresses acute inflammatory response by inhibition of p38 MAPK.
Dual specificity phosphatase 1 (DUSP1) dephosphorylates and, hence, regulates the activity of MAP kinases. The present study investigated the effect of DUSP1 on inflammatory gene expression and on the development of carrageenan-induced inflammation. It was found that DUSP1 expression was increased by LPS, and the down-regulation of DUSP1 by siRNA enhanced the phosphorylation of p38 MAPK, while JNK phosphorylation was not affected in murine macrophages. LPS-induced interleukin (IL)-6, tumor-necrosis factor (TNF) and cyclooxygenase-2 (COX2) expression were enhanced in bone marrow-derived macrophages (BMMs) from DUSP1(−/−) mice as compared to those from wild-type mice. In addition, down-regulation of DUSP1 by siRNA enhanced IL-6, TNF and COX2 expression in J774 macrophages, while p38 MAPK inhibitors SB202190 and BIRB 796 inhibited the expression of those inflammatory factors. In vivo, the intensity of the carrageenan-induced paw edema reaction was increased in DUSP1(−/−) mice as compared to the wild-type animals. In conclusion, DUSP1 is an important negative regulator of the acute inflammatory response by limiting p38 MAPK, and compounds which enhance DUSP1 expression or activity may hold a promise as anti-inflammatory drugs.
Hot-wire measurements in the wake of a flat plate delta wing, at a fixed angle of attack, were carried-out in order to investigate its turbulence kinetic energy budget. The purpose of this study is ...to help acquire more information about the vortex structure formed in the wake region of the delta wing and to provide data for turbulence models’ validation. Point measurements were conducted in five planes perpendicular to the flow, on a high spatial resolution two–dimensional measurement grid that allowed precise derivative calculations of the flow quantities needed for the derivation of the kinetic energy budget. The turbulence kinetic energy convection, production, viscous diffusion and turbulence diffusion terms were directly obtained from the experimental data, whereas dissipation and pressure diffusion terms were calculated indirectly using techniques presented and validated in previous studies. All of the terms of the turbulence kinetic energy budget, along with the velocity components and the Reynolds stresses, are presented and discussed.
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