Future Needs in Mast Cell Biology.

The pathophysiological roles of mast cells are still not fully understood, over 140 years since their description by Paul Ehrlich in 1878. Initial studies have attempted to identify distinct "subpopulations" of mast cells based on a relatively small number of biochemical characteristics. More recently, "subtypes" of mast cells have been described based on the analysis of transcriptomes of anatomically distinct mouse mast cell populations. Although mast cells can potently alter homeostasis, in certain circumstances, these cells can also contribute to the restoration of homeostasis. Both solid and hematologic tumors are associated with the accumulation of peritumoral and/or intratumoral mast cells, suggesting that these cells can help to promote and/or limit tumorigenesis. We suggest that at least two major subsets of mast cells, MC1 (meaning anti-tumorigenic) and MC2 (meaning pro-tumorigenic), and/or different mast cell mediators derived from otherwise similar cells, could play distinct or even opposite roles in tumorigenesis. Mast cells are also strategically located in the human myocardium, in atherosclerotic plaques, in close proximity to nerves and in the aortic valve. Recent studies have revealed evidence that cardiac mast cells can participate both in physiological and pathological processes in the heart. It seems likely that different subsets of mast cells, like those of cardiac macrophages, can exert distinct, even opposite, effects in different pathophysiological processes in the heart. In this chapter, we have commented on possible future needs of the ongoing efforts to identify the diverse functions of mast cells in health and disease

Reconfigurable photoinduced metamaterials in the microwave regime

We investigate optically reconfigurable dielectric metamaterials at gigahertz frequencies. More precisely, we study the microwave response of a subwavelength grating optically imprinted into a semiconductor slab. In the homogenized regime, we analytically evaluate the ordinary and extraordinary component of the effective permittivity tensor by taking into account the photo-carrier dynamics described by the ambipolar diffusion equation. We analyze the impact of semiconductor parameters on the gigahertz metamaterial response which turns out to be highly reconfigurable by varying the photogenerated grating and which can show a marked anisotropic behavior.Comment: 6 figures, 7 page

Using TWDP to Quantify Channel Performance with Frequency-Domain S-Parameter Data

This paper presents an approach to quantify channel performance using TWDP (Transmitter Waveform and Dispersion Penalty) with frequency-domain S-parameter data. TWDP is initially defined to characterize the performance of a transmitter in optical links. The same concept has been extended to quantify channel performance as well, especially in high-speed copper links. This paper focuses on channel characterization. Instead of using time-domain oscilloscope measurements as defined in the original approach, a new method is proposed by using the frequency-domain S-parameter data, obtained either from measurements or simulations. A parametric study on TWDP with respect to bit rate, number of samples per bit, rise/fall time, etc., is also presented with discussions

Full-wave EMC Simulations Using Maxwell Garnett Model For Composites With Cylindrical Inclusions

Four different models for effective dielectric properties of biphasic composite containing random or aligned cylindrical inclusions are considered in this paper. These models are based on the Maxwell Garnett (MG) mixing rule. The effects of distribution and orientation of cylindrical inclusions in a composite material is studied. An equivalent averaged material with Debye-like frequency characteristics, suitable for time-domain full-wave numerical electromagnetic simulations is retrieved. This Debye model is derived from the Maxwell Garnett formulation. The numerical model test structure consists of a composite slab inserted in a rectangular waveguide. Simulations are run for the frequency range above the cut-off frequency of the fundamental mode TE10. The differences between the proposed models are quantified using the Feature Selection Validation (FSV) tool. The comparison of the models provides an insight on the effect of inclusion orientation and distribution. © 2011 IEEE

Characterization of Serial Links at 5.5Gbps on FR4 Backplanes

Nowdays the fast and increased demand for bandwidth in the telecommunication world translates into the design of complex boards exchanging data at high bit rate in reduced design cycle. Sometimes it is impossible to spent time in setting pre-layout simulations, because they are not compatible with the design time schedule. In this scenario it is better to design the boards using experience and then make simulations in conjunction with measurements, using customized numerical tools which don\u27t need complex models

Analytical Evaluation of Via-Plate Capacitance for Multilayer Printed Circuit Boards and Packages

The via-plate capacitance for a via transition to a multilayer printed circuit board is evaluated analytically in terms of higher order parallel-plate modes. The Green\u27s function in a bounded coaxial cavity for a concentric magnetic ring current is first derived by introducing reflection coefficients for cylindrical waves at the inner and outer cavity walls. These walls can be perfect electric conductor (PEC)/perfect magnetic conductor(PMC) or a nonreflective perfectly matched layer. by further assuming a magnetic frill current on the via-hole in the metal plate, an analytical formula is derived for the via barrel-plate capacitance by summing the higher order modes in the bounded coaxial cavity. The convergence of the formula with the number of modes, as well as with the radius of the outer PEC/PMC wall is discussed. The analytical formula is validated by both quasi-static numerical methods and measurements. Furthermore, the formula allows the investigation of the frequency dependence of the via-plate capacitance, which is not possible with quasi-static methods

Cardiovascular abnormalities and impaired exercise performance in adolescents with congenital adrenal hyperplasia

Context: Patients with classic Congenital Adrenal Hyperplasia (CAH) are treated with lifelong glucocorticoids (GCS). Cardiovascular (CV) and metabolic effects of such therapy in adolescents have never been quantified. Objective: To investigate left ventricular (LV) morphology, function and exercise performance in adolescents with CAH. Design and Setting: cross-sectional and controlled study conducted at a tertiary referral centre. Patients: Twenty patients with classic CAH (10 females) aged 13.6±2.5 years and 20 healthy controls comparable for sex and pubertal status were enrolled in the study and compared to a group of 18 patients without CAH receiving a similar dose of GCS for Juvenile Idiopathic Arthritis (JIA). Main Outcomes Measures: Echocardiographic assessment and symptom-limited exercise testing were performed. Anthropometric, hormonal and biochemical parameters were also measured. Results: Compared to healthy controls, patients with CAH exhibited an increased BMI (p<0.001), waist-to-height ratio (p<0.001), percentage of body fat (p<0.001) as well as higher insulin concentrations and HOMA index even after adjustment for BMI (p=0.03 and p=0.05, respectively). Moreover, CAH patients exhibited an impaired exercise capacity as shown by reduced peak workload (99±27 vs 126±27 W, p<0.01) and higher systolic blood pressure response at peak (156±18 vs 132±11 mmHg, p<0.01; Δ=45±24 vs 22±10 mmHg, p=0.05) with respect to healthy controls. CAH males displayed mild LV diastolic dysfunction as documented by significant prolongation of both isovolumic relaxation time (IRT) (118±18 vs 98±11ms, p<0.05) and mitral deceleration time (MDT) (138±25 vs 111±15 ms, p<0.01). No significant differences in CV function were found between CAH and JIA patients. Conclusion: Adolescents with CAH exhibit impaired exercise performance and enhanced systolic blood pressure response during exercise. In our population, such abnormalities appear related to GCS therapy rather than CAH per se. CAH males, but no females, present mild LV diastolic dysfunction that correlates with testosterone concentrations suggesting a sex hormone related difference

Novel Therapeutic Approaches in Rheumatoid Arthritis: Role of Janus Kinases Inhibitors.

Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage and bone destruction and several systemic features. Cardiovascular, pulmonary, psychological, and muscle involvement are the main comorbidities of RA and are responsible for the severity of the disease and long-term prognosis. Pharmacological treatment of rheumatic diseases has evolved remarkably over the past years. In addition, the widespread adoption of treat to target and tight control strategies has led to a substantial improvement of outcomes, so that drug-free remission is nowadays a realistic goal in the treatment of RA. However, despite the availability of multiple therapeutic options, up to 40% of patients do not respond to current treatments, including biologics. Small-molecule therapies offer an alternative to biological therapies for the treatment of inflammatory diseases. In the past 5 years, a number of small-molecule compounds targeting Janus Kinases (JAKs) have been developed. Since JAKs are essential for cell signaling in immune cells, in particular controlling the response to many cytokines, their inhibitors quickly became a promising class of oral therapeutics that proved effective in the treatment of RA. Tofacitinib is the first Janus Kinase (JAK) inhibitor approved for the treatment of RA, followed more recently by baricitinib. Several other JAK inhibitors, are currently being tested in phase II and III trials for the treatment of a different autoimmune diseases. Most of these compounds exhibit an overall acceptable safety profile similar to that of biologic agents, with infections being the most frequent adverse event. Apart from tofacitinib, safety data on other JAK inhibitors are still limited. Long-term follow-up and further research are needed to evaluate the general safety profile and the global risk of malignancy of these small molecules, although no clear association with malignancy has been reported to date. Here, we will review the main characteristics of JAK inhibitors, including details on their molecular targets and on the clinical evidences obtained so far in the treatment of RA