Polycarbonate‐based composites reinforced by in situ polytetrafluoroethylene fibrillation: Preparation,thermal and rheological behavior

Fibrillar reinforced composites of polytetrafluoroethylene (PTFE) and polycarbonate (PC) were prepared by in situ fibrillation of PTFE into PC matrix using twin screw extruder. Different samples were obtained by varying the relative ratio between PC and PTFE. The rheological properties of the PC/PTFE composites were found to depend on concentration of the PTFE fibrils. The melt strength analysis in nonisothermal conditions was also studied. The increase in force and decrease in drawability with increasing the PTFE content are associated with the PTFE fibrils formed in situ during the thermomechanical process in twin screw extruder. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42401.     

Magnetic resonance image denoising using nonlocal maximum likelihood paradigm in DCT‐framework

The data acquired by magnetic resonance (MR) imaging system are inherently degraded by noise that has its origin in the thermal Brownian motion of electrons. Denoising can enhance the quality (by improving the SNR) of the acquired MR image, which is important for both visual analysis and other post processing operations. Recent works on maximum likelihood (ML) based denoising shows that ML methods are very effective in denoising MR images and has an edge over the other state‐of‐the‐art methods for MRI denoising. Among the ML based approaches, the Nonlocal maximum likelihood (NLML) method is commonly used. In the conventional NLML method, the samples for the ML estimation of the unknown true pixel are chosen in a nonlocal fashion based on the intensity similarity of the pixel neighborhoods. Euclidean distance is generally used to measure this similarity. It has been recently shown that computing similarity measure is more robust in discrete cosine transform (DCT) subspace, compared with Euclidean image subspace. Motivated by this observation, we integrated DCT into NLML to produce an improved MRI filtration process. Other than improving the SNR, the time complexity of the conventional NLML can also be significantly reduced through the proposed approach. On synthetic MR brain image, an average improvement of 5% in PSNR and 86%reduction in execution time is achieved with a search window size of 91 × 91 after incorporating the improvements in the existing NLML method. On an experimental kiwi fruit image an improvement of 10% in PSNR is achieved. We did experiments on both simulated and real data sets to validate and to demonstrate the effectiveness of the proposed method. © 2015 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 25, 256–264, 2015     

Additive Manufacturing of Ceramics Enabled by Flash Pyrolysis of Polymer Precursors with Nanoscale Layers

We show that a polymer‐based route to ceramics can be implemented into additive manufacturing by reducing the time for pyrolysis to about a second, which we call flash pyrolysis. Repetitive deposition of nanometer scale coatings of the ceramic, in this way, is employed to create defect‐free infiltrations of carbon fiber composites. The mechanical strength of the fibers is retained in the composite. Excellent wetting properties of the polymer precursor permits three‐dimensional, conformal coating through the three stages of infiltration: nanoscale coating of the single fibers, filling of interstitial spaces between the fibers, and a buildup of the coating over the entire composite. The flash pyrolysis method will enable a new genre of polymer‐derived ceramics made into net shape by this unusual method of additive manufacturing.     

Identification and Structure–Activity Relationship Studies of Small‐Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1

The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small‐molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure‐ and ligand‐based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds. Our in silico studies coupled with in vitro testing were successful in identifying novel Spindlin1 inhibitors. Several 4‐aminoquinazoline and quinazolinethione derivatives were among the active hit compounds, which indicated that these scaffolds represent promising lead structures for the development of Spindlin1 inhibitors. Subsequent lead optimization studies were hence carried out, and numerous derivatives of both lead scaffolds were synthesized. This resulted in the discovery of novel inhibitors of Spindlin1 and helped explore the structure–activity relationships of these inhibitor series.     

Novel Therapeutic Opportunities in Neoadjuvant Setting in Urothelial Cancers: A New Horizon Opened by Molecular Classification and Immune Checkpoint Inhibitors

Muscle invasive bladder cancer (MIBC) is a widespread malignancy with a worse prognosis often related to a late diagnosis. For early-stage MIBC pts, a multidisciplinary approach is mandatory to evaluate the timing of neoadjuvant chemotherapy (NAC) and surgery. The current standard therapy is platinum-based NAC (MVAC-methotrexate, vinblastine, doxorubicin, and cisplatin or Platinum–Gemcitabine regimens) followed by radical cystectomy (RC) with lymphadenectomy. However, preliminary data from Vesper trial highlighted that dose-dense NAC MVAC is endowed with a good pathological response but shows low tolerability. In the last few years, translational-based research approaches have identified several candidate biomarkers of NAC esponsiveness, such as ERCC2, ERBB2, or DNA damage response (DDR) gene alterations. Moreover, the recent consensus MIBC molecular classification identified six molecular subtypes, characterized by different sensitivity to chemo- or targeted or immunotherapy, that could open a novel procedure for patient selection and also for neoadjuvant therapies. The Italian PURE-01 phase II Trial extended data on efficacy and resistance to Immune Checkpoint Inhibitors (ICIs) in this setting. In this review, we summarize the most relevant literature data supporting NAC use in MIBC, focusing on novel therapeutic strategies such as immunotherapy, considering the better patient stratification and selection emerging from novel molecular classification.     

Platinum(II) Complexes Bearing Triphenylphosphine and Chelating Oximes: Antiproliferative Effect and Biological Profile in Resistant Cells

Platinum(II) complexes of the type [Pt(Cl)(PPh₃){(κ²-N,O)-(1{C(R)=N(OH)-2(O)C₆H₄})}] with R=Me, H, ( 1 and 2 ) were synthesized and characterized. Single-crystal X-ray diffraction confirmed the proposed (SP4-3) configuration for 1 . Study of the antiproliferative activity, performed on a panel of human tumor cell lines and on mesothelial cells, highlighted complex 2 as the more effective. In particular, it showed a remarkable cytotoxicity in ovarian carcinoma cells (A2780) and interestingly, a significant antiproliferative effect on cisplatin resistant cells (A2780cis). Investigation into the intracellular mechanism of action demonstrated that 2 had a lower ability to platinate DNA than did cisplatin, which was taken as reference, and a notably higher uptake in resistant cells. A significant accumulation in mitochondria, along with the ability to induce concentration-dependent mitochondrial membrane depolarization and intracellular reactive oxygen species production, allowed us to propose a mitochondrion-mediated pathway as responsible for the interesting cytotoxic profile of complex 2 .     

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.