Healthy women and patients with endometriosis show high concentrations of inhibin A, inhibin B, and activin A in peritoneal fluid throughout the menstrual cycle

Inhibin A, inhibin B, and activin A are growth factors which play local autocrine/paracrine roles in reproductive tissues. Since peritoneal fluid hormone content may reflect in part ovarian and endometrial secretory activities, the present study aimed to evaluate: (i) whether inhibin alpha-, activin betaA- and betaB-subunits, and activin receptor type II and type IIB mRNA are expressed in peritoneal tissues; (ii) expression and secretion of inhibin A and B, and activin A in cultured endometriotic cells; and (iii) concentrations of inhibin A and B, and activin A in serum and in peritoneal fluid in healthy women and in patients with endometriosis throughout the menstrual cycle. A group of women (n = 72) was recruited at laparoscopy for infertility investigation and divided into two groups: (i) control healthy women (n = 35), (ii) women with endometriosis (n = 37). Both groups were subdivided according to the follicular and luteal phase of the menstrual cycle. At the time of laparoscopy, specimens of peritoneal tissues were collected from three healthy women, while endometriotic tissue samples were collected and cultured from three women with endometriosis. Peritoneal tissues and cultured endometriotic cells expressed inhibin alpha-, activin betaA-, and betaB-subunits, and activin receptors mRNAs; in addition, inhibin-related proteins were measurable in culture medium. In healthy women, inhibin A and B, and activin A concentrations in peritoneal fluid were significantly higher than in serum (P < 0.001), at both phases of the menstrual cycle. Peritoneal inhibin A and B, and activin A concentrations were not significantly different between healthy women and patients with endometriosis, either when evaluated according to the degree of the disease and/or to the phase of the menstrual cycle. In conclusion, the findings that high concentrations are present in peritoneal fluid and that menstrual cycle-related changes occur suggest that reproductive organs may contribute to inhibin-related proteins in peritoneal fluid.     

A generalization of the Curtis–Hedlund theorem

Let A be a set and let G be a group, and equip A^G with its prodiscrete uniform structure. Let τ:A^G→A^G be a map. We prove that τ is a cellular automaton if and only if τ is uniformly continuous and G-equivariant. We also give an example showing that a continuous and G-equivariant map τ:A^G→A^G may fail to be a cellular automaton when the alphabet set A is infinite.     

Platelet-Derived miR-126-3p Directly Targets AKT2 and Exerts Anti-Tumor Effects in Breast Cancer Cells: Further Insights in Platelet-Cancer Interplay

Among the surrounding cells influencing tumor biology, platelets are recognized as novel players as they release microvesicles (MVs) that, once delivered to cancer cells, modulate signaling pathways related to cell growth and dissemination. We have previously shown that physiological delivery of platelet MVs enriched in miR-126 exerted anti-tumor effects in different breast cancer (BC) cell lines. Here, we seek further insight by identifying AKT2 kinase as a novel miR-126-3p direct target, as assessed by bioinformatic analysis and validated by luciferase assay. Both ectopic expression and platelet MV-mediated delivery of miR-126-3p downregulated AKT2 expression, thus suppressing proliferating and invading properties, in either triple negative (BT549 cells) or less aggressive Luminal A (MCF-7 cells) BC subtypes. Accordingly, as shown by bioinformatic analysis, both high miR-126 and low AKT2 levels were associated with favorable long-term prognosis in BC patients. Our results, together with the literature data, indicate that miR-126-3p exerts suppressor activity by specifically targeting components of the PIK3/AKT signaling cascade. Therefore, management of platelet-derived MV production and selective delivery of miR-126-3p to tumor cells may represent a useful tool in multimodal therapeutic approaches in BC patients.     

A project scheduling approach to production planning with feeding precedence relations

In Manufacturing-to-Order or Engineering-to-Order systems producing complex and highly customised items, each item has its own characteristics that are often tailored for a specific customer. Project scheduling approaches are suitable for production planning in such environments. However, when we consider the production of complex items, the distinct production operations are often aggregated into activities representing whole production phases. In such cases, the planning and scheduling problem works on the aggregate activities, considering that, in most cases, such activities also have to be manually executed. Moreover, simple finish-to-start precedence relations no longer correctly represent the real production process, but overlapping among activities should be allowed. In this paper, a project scheduling approach is proposed for production planning in Manufacturing-to-Order systems. The Variable Intensity formulation is used to allow the effort committed to the execution of activities to vary over time. Feeding precedences are developed to model generalised precedence relations when the execution mode of activities is not known a priori. Two mathematical formulations of these precedence relations are proposed. The formulations are applied both to randomly generated instances and to an industrial system producing machining centres and are compared in terms of computational efficiency.     

Design of flexible transfer lines: A case-based reconfiguration cost assessment

Shortening product life cycles leads competing companies to continually release new products or modifying the existing ones; this is one of the major issues in production systems design. According to the changes in product features, production systems need to be properly configured or reconfigured to efficiently tackle new production requirements. A configuration approach for multi-product flexible transfer lines is presented which aims at minimizing the equipment cost. The approach is applied to a manufacturing case in the automotive sector. The robustness of the solution is tested against changes that affect the products to highlight reconfiguration costs and the penalty associated to the lack of a pro-active configuration approach.     

Obstacle Modelling Oriented to Safe Motion Planning and Control for Planar Rigid Robot Manipulators

Trajectory planning and tracking are crucial tasks in any application using robot manipulators. These tasks become particularly challenging when obstacles are present in the manipulator workspace. In this paper a n-joint planar robot manipulator is considered and it is assumed that obstacles located in its workspace can be approximated in a conservative way with circles. The goal is to represent the obstacles in the robot configuration space. The representation allows to obtain an efficient and accurate trajectory planning and tracking. A simple but effective path planning strategy is proposed in the paper. Since path planning depends on tracking accuracy, in this paper an adequate tracking accuracy is guaranteed by means of a suitably designed Second Order Sliding Mode Controller (SOSMC). The proposed approach guarantees a collision-free motion of the manipulator in its workspace in spite of the presence of obstacles, as confirmed by experimental results.     

Improved atrial function in bicaval versus standard orthotopic techniques in cardiac transplantation

Atrial geometry is preserved in the bicaval technique of cardiac transplantation. Using Doppler echocardiography, we investigated the impact of this technique on preservation of atrial function and found that echocardiographic indexes of atrial function are improved in bicaval cardiac transplants versus the standard orthotopic transplants.