A quantitative systems view of the spindle assembly checkpoint

The idle assembly checkpoint acts to delay chromosome segregation until all duplicated sister chromatids are captured by the mitotic spindle. This pathway ensures that each daughter cell receives a complete copy of the genome. The high fidelity and robustness of this process have made it a subject of intense study in both the experimental and computational realms. A significant number of checkpoint proteins have been identified but how they orchestrate the communication between local spindle attachment and global cytoplasmic signalling to delay segregation is not yet understood. Here, we propose a systems view of the spindle assembly checkpoint to focus attention on the key regulators of the dynamics of this pathway. These regulators in turn have been the subject of detailed cellular measurements and computational modelling to connect molecular function to the dynamics of spindle assembly checkpoint signalling. A review of these efforts reveals the insights provided by such approaches and underscores the need for further interdisciplinary studies to reveal in full the quantitative underpinnings of this cellular control pathway

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Hypertension and cerebrovascular diseases: a specific role of vascular protection for the prevention of dementia

IF 1,55

Fatty acid composition of spermatozoa and immature germ cells”. MOLECULAR HUMAN REPRODUCTION

A great deal of attention has recently been given to the essential role of polyunsaturated fatty acids (PUFA) of sperm membranes. We studied the fatty acid composition of the immature germ cells (IGC) and of the sperm populations separated by Percoll gradient in the ejaculate of normozoospermic patients. Fatty acid pattern was analysed by combined gas chromatography-mass spectrometry on a capillary column. In IGC, differences were found compared with mature spermatozoa, with a higher percentage of saturated fatty acids and of essential fatty acids. On the contrary, the long-chain PUFA were significantly lower in IGC. The highest concentration of n3 PUFA docohexaenoic acid (DHA) was detected in the spermatozoa deriving from 70-100% Percoll layers and a direct linear correlation was found between the increase of DHA and increased percentage of Percoll gradient. An inverse relationship between the percentage of atypical sperm forms in each layer and the percentage of DHA was also observed. This study demonstrates that the human germ cell line can elongate and desaturate essential fatty acids and that the percentage of long-chain PUFA is correlated with the normal morphology of sperm cells

An electro-thermal SPICE model for Reverse Conducting IGBT: Simulation and experimental validation

The compact SPICE modeling of Reverse Conducting IGBTs is presented in this paper. The proposed approach is based on a quasi-2D formulation with the joint use of IGBT and PiN diode sub-circuits. Lateral currents paths and turn-on forward delay are considered into the model. Self-heating effect for both IGBT and diode regions is take into account, enabling reliable electro-thermal analysis. The model is calibrated to fit experimental data of a commercial 20 A-1.2 kV rated device. As a compelling example to prove the effectiveness of the model, the results of an electro-thermal simulation on a quasi-resonant converter are compared with experiments. © 2016 IEEE