Targeting subtypes of breast cancer with Palbociclib, a cyclin-dependent Kinase inhibitor

Background: Breast cancer is the leading cause of cancer death in women. Despite major advances in breast cancer research, the recurrence of cancer represents a serious obstacle to successful treatment; deregulation in cell cycle proteins have been implicated in different cancers including breast. A pharmacological approach to inhibit cyclin - dependent kinases 4 and 6 (CDK 4/6) using Palbociclib, a highly selective small molecule inhibitor, was used to evaluate the effects of this inhibitor on cell proliferation of 4 different breast cancer cells subtypes (MCF-7, MDA-MB-231,BT474Z, MCF-7/her2 transfected). Methods: ERα and Cyclin D1 expression has been evaluated on 34 breast cancer specimens; 4 human immortalized breast cancer cell lines (BT474Z, MCF-7, MCF7/her2 transfected, MDA-MB-231) and one cell line derived from breast cancer tissue patient (K90) have been treated with increasing concentrations of Palbociclib (cyclin D1-CDK4/6 inhibitor); cell proliferation was evaluate by MTT assay and cell count. Cell cycle analysis and protein expression have been performed by Facs and WB. Results: ERα-positive MCF-7 cells are more sensitive to Palbociclib compared to the other breast cancer cell subtypes; Palbociclib displays a cytostatic effect by inhibiting cell viability and proliferation; the inhibitory effect of Palbociclib is based on breast cancer cells subtypes through modulation of expression of G0/G1 regulators (cyclin D1, p27, Rb and phospo-Rb). Conclusion: This study suggests a potential role of CDK 4/6 inhibitor Palbociclib on different breast cancer subtypes and identifies Luminal A and Luminal B breast cancer as possible target of Palbociclib in clinical setting

On prospective teachers' evaluations of freshman students' written arguments

n this paper we present a qualitative study in which we analyse how a group of prospective mathematics teachers evaluates written arguments produced by freshman students solving a problem involving graphs. The prospective teachers were attending a course of Mathematics Education for the second year of a master degree in Mathematics. In particular we focus on how prospective teachers in their evaluations look at mathematical content, language, and argumentative structure. The outcomes show, on the one hand, a certain attention to some linguistic aspects, on the other hand, a greater attention to the content than to the argumentative structure of the texts. We suggest that prospective teachers' models for linguistic education are often the standard ones, based on conformity to grammar or style rather than on adequacy with respect to goals

Random-Parameters Behavioral Models to Investigate Determinants of Perceived Safety in Railway Stations

Recent studies have highlighted the existence of a gap between actual and perceived safety and have shown that feelings of insecurity can affect individuals? travel behavior before and during the journey. In this paper, a methodology is proposed for assessing determinants of travelers? perception of safety and security in railway stations. The methodological approach includes focus groups, stated preference (SP) surveys, and the estimation of behavioral models with fixed parameters (Binomial Logit) and random parameters (Mixed Logit). The estimation results for a medium-sized railway station (Frosinone, Italy) confirmed that safety and security measures are not equally perceived by individuals and the use of random-parameters models leads to more robust estimates. The proposed modeling approach allows the identification of the interventions that should be prioritized to increase travelers? perceived levels of safety, highlighting those factors, such as, for the considered case study, the presence of security personnel and the level of decorum and maintenance, which are perceived by users as more important than others (e.g., surveillance cameras)

Evaluation of the environmental impact of harbour activities: problem analisys and possible solutions

A relevant problem is a main subject of this work: the pollution in ports close to inhabited zones where, due to the contemporaneous presence of many cruise ships, the contents of noxious elements in the air are excessive and the quality of life risks to become unsustainable. The impact of the operations of cruise ships in port has been analysed together with the possible consequences of their impact on the human health and the rules that attempt to reduce the effects of the pollution on it. Some possible solutions were proposed; first of all, the so called “cold ironing” consisting in a connection between the electric system of the ship and a shore system providing the ship with the electric energy to be used onboard. The major characteristics of the cold ironing were analysed together with its main problems; among them, the need of integrate this practice in a more wide scene, combining it with the microgrids in order to not to solve the problem simply by moving the production of electric energy from one site to another

Urothelial bladder carcinoma metastasizing to the eye: a systematic review and case report

The eye is a rare site for disseminated malignancies; nevertheless, several tumors may metastasize to ocular structures. Few cases of urothelial and bladder cancer with eye involvement have been described in the literature thus far. The rarity of metastatic ocular localization implies an accurate differential diagnosis among the possible primary tumor sites. However, a specific diagnostic algorithm is not currently available, nor a defined therapeutic approach. Eye metastases are associated with advanced disease and poor prognosis. Physicians should be made aware of the possibility of eye involvement in patients with a past medical history of urothelial bladder cancer associated with ocular symptoms. The present case reports discusses the first documented case, to the best of our knowledge, of an urothelial bladder cancer metastasizing to the retro bulbar region that infiltrates the lacrimal gland. Furthermore, the report provides a systematic qualitative review of the current literature on eye metastases from urothelial bladder cancer using the Preferred Reporting Items for Systematic Reviews and Meta Analyses

Numerically stable formulations of convective terms for turbulent compressible flows

A systematic analysis of the discrete conservation properties of non-dissipative, central-difference approximations of the compressible Navier-Stokes equations is reported. A general triple splitting of the nonlinear convective terms is considered, and energy-preserving formulations are fully characterized by deriving a two-parameter family of split forms. Previously developed formulations reported in literature are shown to be particular members of this family; novel splittings are introduced and discussed as well. Furthermore, the conservation properties yielded by different choices for the energy equation (i.e. total and internal energy, entropy) are analyzed thoroughly. It is shown that additional preserved quantities can be obtained through a suitable adaptive selection of the split form within the derived family. Local conservation of primary invariants, which is a fundamental property to build high-fidelity shock-capturing methods, is also discussed in the paper. Numerical tests performed for the Taylor-Green Vortex at zero viscosity fully confirm the theoretical findings, and show that a careful choice of both the splitting and the energy formulation can provide remarkably robust and accurate results

Fuzzy-Based Variable Speed Limits System Under Connected Vehicle Environment: A Simulation-Based Case Study in the City of Naples

This paper handles the problem of controlling speed limits on freeways in a connected traffic environment to reduce traffic congestion and improve both the operational and environmental performance of the road network. In order to achieve this objective, we present a Variable Speed Limit (VSL) system that utilizes fuzzy logic, which adjusts the speed limits that connected vehicles must comply with by leveraging traffic data such as vehicle flow, occupancy, and speed obtained from loop detectors installed along the road. To evaluate the effectiveness of the proposed Fuzzy-based VSL system and its potential benefits compared to the conventional rule-based VSL system in terms of traffic congestion and environmental impact, we conducted a simulation analysis using the microscopic traffic simulator, VISSIM. Specifically, three simulation scenarios are taken into account: i) no VSL, where the VSL system is not enabled; ii) Rule-based VSL system, where a typical a decision tree-based system is considered; iii) Fuzzy-based VSL system, where the herein proposed approach is appraised. The results demonstrate that the proposed approach enhances road efficiency by decreasing speed variation, increasing average speed and vehicle volume, and reducing fuel consumption

Asymmetric MSM sub-bandgap all-silicon photodetector with low dark current

Design, fabrication, and characterization of an asymmetric metal-semiconductor-metal photodetector, based on internal photoemission effect and integrated into a silicon-on-insulator waveguide, are reported. For this photodetector, a responsivity of 4.5 mA/W has been measured at 1550 nm, making it suitable for power monitoring applications. Because the absorbing metal is deposited strictly around the vertical output facet of the waveguide, a very small contact area of about 3 µm2 is obtained and a transit-time-limited bandwidth of about 1 GHz is demonstrated. Taking advantage of this small area and electrode asymmetry, a significant reduction in the dark current (2.2 nA at -21 V) is achieved. Interestingly, applying reverse voltage, the photodetector is able to tune its cut-off wavelength, extending its range of application into the MID infrared regime