A DISTANCE MEASURE FOR CLASSIFYING ARIMA MODELS

Abstract. In a number of practical problems where clustering or choosing from a set of dynamic structures is needed, the introduction of a distance between the data is an early step in the application of multivariate statistical methods. In this paper a parametric approach is proposed in order to introduce a well-defined metric on the class of autoregressive integrated moving-average (ARIMA) invertible models as the Euclidean distance between their autoregressive expansions. Two case studies for clustering economic time series and for assessing the consistency of seasonal adjustment procedures are discussed. Finally, some related proposals are surveyed and some suggestions for further research are made.     

The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.     

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.     

Controlled Mesoporosity in SiOC via Chemically Bonded Polymeric “Spacers”

Silicon oxycarbides with controlled porosity in the mesopore range have been obtained through high‐temperature pyrolysis of newly developed reactive siloxane formulations. The starting gels have been synthesized via Pt catalyzed hydrosilylation reaction between polyhydromethylsiloxane (PHMS) and vinyl‐terminated polydimethylsiloxane (PDMS) of different molecular weights in the presence of tetravinyltetramethylcyclotetrasiloxane as a crosslinking enhancer. In our approach, the PDMS serves the double purpose of size‐controlling templating agent as well as solvent at the early stages of the synthesis. During the curing step, the vinyl‐terminated PDMS is chemically bonded to the preceramic network through the extremely efficient hydrosilylation reaction and “solidify.” Accordingly, its removal during pyrolysis occurs through decomposition of a solid phase with retention of the formed porosity. The structural and morphological evolution of the preceramic gels containing the molecular spacers have been investigated as a function of the thermal treatment temperature by N₂ physisorption measurements, thermogravimetry, and SEM analyses. The results show that the pore size distribution of the resulting SiOCs depends on the molecular weight of the PDMS and is directly related to the molecular volume assumimg that the PDMS chains are entangled into spheroidal shapes. The total pore volume is related to the initial amount of templating PDMS assuming its complete decomposition during pyrolysis.     

Wooden window frames with structural sealants: manufacturing improvements and experimental validation of a finite element model

This paper proposes a finite element (FE) model of a novel wooden window frame typology and validates it by experimental tests on window frames and corner joint specimens. The innovation consists of the application of the structural silicone sealant only at the interface between wood and one of the thin glass layers of the double-glazing glass, so achieving a low application depth. This technique reduces the sealant quantity and allows the disassembly and substitution of the glass from the frame in case of breakage. In order to inform the FE model of the whole frame, the dowelled butt corner joint strength is measured by specific experimental tests. The results show a good correlation between the FE model and the experimental results in the range of small frame deformations, which are of interest for the proposed application. In particular, the FE curve overestimates the bottom corner displacement of about 17% at 1000?N load, 7% at 2000?N and less than 5% at higher applied force on the upper corner. The model is then applied to various wooden frame geometries in order to evaluate if the proposed silicone application mode and dowelled corner joints type allow an acceptable stiffness of the frame, and, in particular, low deformations of the bottom corner joint, in order to maintain the wooden frame functionality when subject to external loads. The approach could be useful when assessing optimal sealing application modes, wood-sealant-glass joint geometries, corner joint geometries and window frame geometries to limit the bottom corner joint deformation within the required technical specifications.     

The L467F-F508del Complex Allele Hampers Pharmacological Rescue of Mutant CFTR by Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Patients: The Value of the Ex Vivo Nasal Epithelial Model to Address Non-Responders to CFTR-Modulating Drugs

Loss-of-function mutations of the CFTR gene cause cystic fibrosis (CF) through a variety of molecular mechanisms involving altered expression, trafficking, and/or activity of the CFTR chloride channel. The most frequent mutation among CF patients, F508del, causes multiple defects that can be, however, overcome by a combination of three pharmacological agents that improve CFTR channel trafficking and gating, namely, elexacaftor, tezacaftor, and ivacaftor. This study was prompted by the evidence of two CF patients, compound heterozygous for F508del and a minimal function variant, who failed to obtain any beneficial effects following treatment with the triple drug combination. Functional studies on nasal epithelia generated in vitro from these patients confirmed the lack of response to pharmacological treatment. Molecular characterization highlighted the presence of an additional amino acid substitution, L467F, in cis with the F508del variant, demonstrating that both patients were carriers of a complex allele. Functional and biochemical assays in heterologous expression systems demonstrated that the double mutant L467F-F508del has a severely reduced activity, with negligible rescue by CFTR modulators. While further studies are needed to investigate the actual prevalence of the L467F-F508del allele, our results suggest that this complex allele should be taken into consideration as plausible cause in CF patients not responding to CFTR modulators.     

Pectin: A Long-Neglected Broad-Spectrum Antibacterial

First reported in the late 1930s and partly explained in 1970, the antibacterial activity of pectin remained almost ignored until the late 1990s. The concomitant emergence of research on natural antibacterials and new usages of pectin polysaccharides, including those in medicine widely researched in Russia, has led to a renaissance of research into the physiological properties of this uniquely versatile polysaccharide ubiquitous in plants and fruits. By collecting scattered information, this study provides an updated overview of the subtle factors affecting the behaviour of pectin as an antimicrobial. Less-degraded pectin extracted by acid-free routes, we argue in the conclusions, will soon find applications from new treatments for polymicrobial infections to use as an implantable biomaterial in tissue and bone engineering.     

α–ω Alkenyl-bis-S-Guanidine Thiourea Dihydrobromide Affects HeLa Cell Growth Hampering Tubulin Polymerization

Cancer is going to be the first cause of mortality worldwide in the 21th century. It is considered a multifactorial disease that results from the combined influence of many genetic aberrations, leading to abnormal cell proliferation. As microtubules are strongly implicated in cellular growth, they represent an important target for cancer treatment. The well-known microtubule-targeting agents (MTAs) including paclitaxel, colchicine and vinca alkaloids are commonly used in the treatment of various cancers. However, adverse effects and drug resistance are major limitations in their clinical use. To find new candidates able to induce microtubule alteration with reduced toxic effects or drug resistance, we studied a small new series of derivatives that present imidazolinic, guanidinic, thioureidic and hydrazinic groups ( 1 – 9 ). All the compounds were tested for their antitumor activity against a panel of six tumoral cell models. In particular, compound 8 (nonane-1,9-diyl-bis-S-amidinothiourea dihydrobromide) showed the lowest IC₅₀ value against HeLa cells, together with a low cytotoxicity for normal cells. This compound was able to induce the apoptotic mitochondrial pathway and inhibited tubulin polymerization with a similar efficacy to vinblastine and nocodazole. Taken together, these promising biological properties make compound 8 useful for the development of novel therapeutic approaches in cancer treatment.