REGULATORY MECHANISMS IMPLICATED IN THE CONTROL OF NUMB ASYMMETRIC PARTITIONING AT MITOSIS OF ADULT MAMMARY STEM CELLS

The cell fate determinant Numb has been recently shown to control the asymmetric outcome of self-renewing divisions in the normal mammary stem cell (MaSC) compartment. Loss of Numb results in the appearance of stem cells (SCs) endowed with an enhanced symmetric self-renewal ability (leading to expansion of the SC compartment) and with tumorigenic potential. The role of Numb in MaSCs is linked to its ability to asymmetrically partition at mitosis into the progeny that retains the SC identity, where it sustains the tumour suppressor activity of p53. Phosphorylation of Numb by the Par Complex (Par3/Par6/atypical PKC) is an evolutionary conserved mechanism to specify Numb asymmetric partitioning at SC mitosis. In this thesis work, we used a molecular genetics approach to demonstrate that a proper cycle of Numb phosphorylation and de-phosphorylation is essential to guarantee the asymmetric partitioning of Numb at mitosis of MaSCs. We also propose a conserved role for the atypical PKC isoenzyme and Par3 in the regulation of these events. Moreover, our preliminary data show that Numb phosphorylation mediated by aPKC impairs Numb interaction with p53, suggesting that the regulation of Numb phosphorylation can be also linked to its tumour suppressor function

Conservative Space and Time Regularizations for the ICON Model

In this article, we consider two modified (regularized) versions of the shallow water equations which are of potential interest for the construction of global oceanic and atmospheric models. The first modified system is the Lagrangian averaged shallow water system, which involves the use of a regularized advection velocity and which has been recently proposed as a turbulence parametrization for ocean models in order to avoid an excessive damping of the computed solution. The second modified system is the pressure regularized shallow water system, which provides an alternative to traditional semi-implicit time integration schemes and which results in larger freedom in the design of the time integrator and in a better treatment of nearly geostrophic flows. The two modified systems are both nondissipative, in that they do not result in an increase of the overall dissipation of the flow. We first show how the numerical discretization of the two regularized equation sets can be constructed in a natural way within the finite difference formulation adopted for the ICON general circulation model currently under developed at the Max Planck Institute for Meteorology and at the German Weather Service. The resulting scheme is then validated on a set of idealized tests in both planar and spherical geometry, and the effects of the considered regularizations on the computed solution are analyzed concerning: stability properties and maximum allowable time steps, similarities and differences in the behavior of the solutions, discrete conservation of flow invariants such as total energy and enstrophy. Our analysis should be considered as a first step toward the use of the regularization ideas in the simulation of more complex and more realistic flows

An upper limb Functional Electrical Stimulation controller based on Reinforcement Learning: A feasibility case study.

Controllers for Functional Electrical Stimulation (FES) are still not able to restore natural movements in the paretic arm. In this work, Reinforcement Learning (RL) is used for the first time to control a hybrid upper limb robotic system for stroke rehabilitation in a real environment. The feasibility of the FES controller is tested on one healthy subject during elbow flex-extension in the horizontal plane. Results showed an absolute position error <1.2° for a maximum range of motion of 50°

Psychological impact and health-related quality-of-life outcomes of Mayer-Rokitansky-K&#252;ster-Hauser syndrome : A systematic review and narrative synthesis

Mayer-Rokitansky-K\ufcster-Hauser syndrome causes absence or underdevelopment of uterus and vagina, but women's subjective experience remains understudied. This systematic review was conducted to examine the psychological and health-related quality-of-life outcomes of Mayer-Rokitansky-K\ufcster-Hauser syndrome. In total, 22 articles identified through electronic search matched the inclusion criteria and were included in our review. Mayer-Rokitansky-K\ufcster-Hauser syndrome may be associated with psychological symptoms and impaired quality of life, but especially with poor sexual esteem and genital image. Women may experience difficulties managing intimacy and disclosing to partners. Mothers may be perceived as overinvolved, with consequent negative emotions in women with the disease

The presence of dominant follicles and corpora lutea does not perturb response to controlled ovarian stimulation in random start protocols

The advent of random start protocols to shorten the time needed to store oocytes in women with malignancies has represented an important improvement in the field of fertility preservation. However, Randomized Controlled Trials are difficult to implement in this area and available evidence that supports this approach remains modest. To shed more light on this issue, we compared the follicular development between the ovary carrying the dominant follicle or the corpus luteum and the contralateral resting ovary in 90 women who underwent random start controlled ovarian stimulation (COS). In fact, ovarian response did not differ between the two ovaries. Subgroup analyses according to the phase of the cycle at the initiation of COS, the type of malignancy, the use of letrozole and the magnitude of the ovarian response did not allow to identify any condition showing a difference in the follicular response between the active and the resting ovaries. In conclusion, follicular growth does not seem to be perturbed by the presence of a dominant follicle or a corpus luteum