The Role of NLRP3 Inflammasome Activation and Oxidative Stress in Varicocele-Mediated Male Hypofertility

Varicocele (VC) is the most common abnormality identified in men evaluated for hypofertility. Increased levels of reactive oxygen species (ROS) and reduced antioxidants concentrations are key contributors in varicocele-mediated hypofertility. Moreover, inflammation and alterations in testicular immunity negatively impact male fertility. In particular, NLRP3 inflammasome activation was hypothesized to lead to seminal inflammation, in which the levels of specific cytokines, such as IL-1β and IL-18, are overexpressed. In this review, we described the role played by oxidative stress (OS), inflammation, and NLRP3 inflammasome activation in VC disease. The consequences of ROS overproduction in testis, including inflammation, lipid peroxidation, mitochondrial dysfunction, chromatin damage, and sperm DNA fragmentation, leading to abnormal testicular function and failed spermatogenesis, were highlighted. Finally, we described some therapeutic antioxidant strategies, with recognized beneficial effects in counteracting OS and inflammation in testes, as possible therapeutic drugs against varicocele-mediated hypofertility.     

Focused Design of Novel Cyclic Peptides Endowed with GABARAP-Inhibiting Activity

(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and K_d values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules.     

A real time FFT-based impedance meter with bias compensation

A real time FFT-based impedance meter is here presented. It is realized simply by a standard PC in addition to a low cost two channels hardware device, and is based on a cost-effective algorithm to meaningfully reduce the known problem of the bias introduced by the relative phase and amplitude error between channels. The impedance meter exploits the implementation of an ad hoc cost-effective algorithm and a synchronous sampling allows eliminating the leakage error. The aliasing and the spectral interference are eliminated by means of an anti-aliasing filter and the use of very low distortion sinusoidal signals. Automatic measurements can be managed too, capturing different measures at different test frequencies and displaying them graphically on the PC screen. To validate the measured results comparative test were performed with respect to certified and calibrated commercially available multimeters known with good accuracies.Finally, this novel impedance meter integrates a home-made software, previously reported [1] capable to implement real time virtual instruments.     

Measurement involving human perception and interpretation

The measurement of features related to human perception and interpretation is discussed. After a brief review of the historical framework, the state of the art is presented on the basis of the authors’ experience in the field and their participation in related European projects, with development of experiments, and co-ordination activities. Future research needs and challenges are then addressed.     

The relationship between scientists’ research performance and the degree of internationalization of their research

Policy makers, at various levels of governance, generally encourage the development of research collaboration. However the underlying determinants of collaboration are not completely clear. In particular, the literature lacks studies that, taking the individual researcher as the unit of analysis, attempt to understand if and to what extent the researcher’s scientific performance might impact on his/her degree of collaboration with foreign colleagues. The current work examines the international collaborations of Italian university researchers for the period 2001–2005, and puts them in relation to each individual’s research performance. The results of the investigation, which assumes co-authorship as proxy of research collaboration, show that both research productivity and average quality of output have positive effects on the degree of international collaboration achieved by a scientist.     

Disturbed Exploitation compact Differential Evolution for limited memory optimization problems

This paper proposes a novel and unconventional Memetic Computing approach for solving continuous optimization problems characterized by memory limitations. The proposed algorithm, unlike employing an explorative evolutionary framework and a set of local search algorithms, employs multiple exploitative search within the main framework and performs a multiple step global search by means of a randomized perturbation of the virtual population corresponding to a periodical randomization of the search for the exploitative operators. The proposed Memetic Computing approach is based on a populationless (compact) evolutionary framework which, instead of processing a population of solutions, handles its statistical model. This evolutionary framework is based on a Differential Evolution which cooperatively employs two exploitative search operators: the first is based on a standard Differential Evolution mutation and exponential crossover, and the second is the trigonometric mutation. These two search operators have an exploitative action on the algorithmic framework and thus contribute to the rapid convergence of the virtual population towards promising candidate solutions. The action of these search operators is counterbalanced by a periodical stochastic perturbation of the virtual population, which has the role of “disturbing” the excessively exploitative action of the framework and thus inhibits its premature convergence. The proposed algorithm, namely Disturbed Exploitation compact Differential Evolution, is a simple and memory-wise cheap structure that makes use of the Memetic Computing paradigm in order to solve complex optimization problems. The proposed approach has been tested on a set of various test problems and compared with state-of-the-art compact algorithms and with some modern population based meta-heuristics. Numerical results show that Disturbed Exploitation compact Differential Evolution significantly outperforms all the other compact algorithms present in literature and reaches a competitive performance with respect to modern population algorithms, including some memetic approaches and complex modern Differential Evolution based algorithms. In order to show the potential of the proposed approach in real-world applications, Disturbed Exploitation compact Differential Evolution has been implemented for performing the control of a space robot by simulating the implementation within the robot micro-controller. Numerical results show the superiority of the proposed algorithm with respect to other modern compact algorithms present in literature.     

Constrained scheduling of the inspection activities on semiconductor wafers grouped in families with sequence-dependent set-up times

The scheduling of families of semiconductor wafers within the inspection department of a company producing electronic devices is considered in this paper. Changing the family of wafers to be inspected by an inspection machine requires a sequence-dependent set-up time; furthermore, due to the limited space availability of the inspection area, the available interoperational buffer capacity between the inspection machines is finite. The objective of the scheduling is the maximization of inspection department productivity, measured through the sequence makespan. A permutational flowshop group-scheduling problem (GSP) with sequence-dependent set-up times and limited interoperational buffer capacity has been taken into account. A benchmark of process scenarios considering different numbers of inspection machines wafers codes and families to be inspected has been generated. A Genetic Algorithm is here proposed as an efficient tool to solve the investigated problem. A comparison with a tabu search and a Nawaz, Enscore, and Ham procedure improving the currently available scheduler tool within the inspection department has been performed on the benchmark of problems. Finally, the influence on line productivity due to the finite interoperational buffer capacity is investigated.     

MagIC system

In the health-care area, there is a growing demand for devices capable of monitoring cardiorespiratory function in a simple and comfortable way without interfering with the patient's behavior. Smart monitoring systems are also requested for the recording of vital signs in healthy subjects for research, assessment of performances, safety, and injury prevention purposes. Typical nonclinical areas of application include ergonomics, occupational medicine, wellness, and sport.