Memory leak detection in Plumbr

Platforms with automatic memory management, such as the JVM, are usually considered free of memory leaks. However, memory leaks can happen in such environments, as the garbage collector cannot free objects, which are not used by the application anymore, but are still referenced. Such unused objects can eventually fill up the heap and crash the application. Although this problem has been studied extensively, nevertheless, there are still many rooms for improvement in this area. This paper describes the statistical approach for memory leak detection, as an alternative, along with a commercial tool, Plumbr, which is based on the method. The tool is later analyzed with three case studies of real applications and in the process also analyzes strengths and weaknesses of the statistical approach for memory leak detection. Copyright © 2014 John Wiley & Sons, Ltd.     

Biosynthesis of zinc oxide nanoparticles by petals extract of Rosa indica L., its formulation as nail paint and evaluation of antifungal activity against fungi causing onychomycosis

Aim: The authors report the biological synthesis of zinc oxide nanoparticles (ZnO‐NPs) from the petals extract of Rosa indica L. (rose). Its efficacy was evaluated against two dermatophytes: namely: Trichophyton mentagrophytes and Microsporum canis which cause onychomycosis. The activity of antibiotics against the tested dermatophytes was enhanced, when evaluated in combination with ZnO‐NPs. Methods and results: The synthesised ZnO‐NPs were preliminary detected by using ultraviolet UV visible spectroscopy, which showed specific absorbance. The ZnO‐NPs were further characterised by nanoparticle tracking analysis (NTA), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X‐ray diffraction and Zetasizer. Moreover, nanoparticles containing nail paint (nanopaint) was formulated and its antifungal activity was also assessed against T. mentagrophytes and M. canis. ZnO‐NPs and formulated nanopaint containing ZnO‐NPs, both showed significant antifungal activity. The maximum activity was noted against M. canis and lesser against T. mentagrophytes. Minimum inhibitory concentration of ZnO‐NPs was also determined against the dermatophytes causing onychomycosis infection. Conclusion: ZnO‐NPs can be utilised as a potential antifungal agent for the treatment of onychomycosis after more experimental trials.Inspec keywords: diseases, zinc compounds, nanoparticles, nanofabrication, antibacterial activity, microorganisms, nanomedicine, ultraviolet spectra, visible spectra, Fourier transform infrared spectra, transmission electron microscopy, X‐ray diffraction, biomedical materials, patient treatmentOther keywords: zinc oxide nanoparticle biosynthesis, Rosa indica L petals extract, nail paint, antifungal activity evaluation, dermatophyte, Trichophyton mentagrophytes, Microsporum canis, antibiotics activity, ultraviolet‐visible spectroscopy, nanoparticle tracking analysis, Fourier transform infrared spectroscopy, transmission electron microscopy, X‐ray diffraction, zetasizer, antifungal agent, onychomycosis treatment     

A Novel Photoswitchable Azobenzene-Containing Local Anesthetic Ethercaine with Light-Controlled Biological Activity In Vivo

Pain is a common symptom that impairs the quality of life for people around the world. Local anesthetics widely used for pain relief have a number of side effects, which makes the development of both new drugs and new ways to control their activity particularly important. Photopharmacology makes it possible to reduce the side effects of an anesthetic and control its biological activity in the body. The purpose of this work was to create a new light-controlled local anesthetic and study its biological activity in animals. A compound with a simple scheme of synthesis was chosen to shift the UV-Vis absorption band towards the visible range of the spectrum and was synthesized for the first time. Some computer calculations were performed to make sure that the aforementioned changes would not lead to loss of biological activity. The micellar form of the new compound was prepared, and in vivo biological studies were carried out in rabbits. The existence of a local anesthetic effect, which disappeared almost completely on irradiation with light (λ = 395 nm), was shown using the surface anesthesia model. Moreover, the possibility of multiple reversible changes in the biological activity of ethercaine under the action of light was demonstrated. The latter compound manifests no local irritating effect, either. The data obtained indicate the prospects for the development of new compounds based on azobenzene for light-controlled local anesthesia.     

Structural and Molecular Kinetic Features of Activities of DNA Polymerases

DNA polymerases catalyze DNA synthesis during the replication, repair, and recombination of DNA. Based on phylogenetic analysis and primary protein sequences, DNA polymerases have been categorized into seven families: A, B, C, D, X, Y, and RT. This review presents generalized data on the catalytic mechanism of action of DNA polymerases. The structural features of different DNA polymerase families are described in detail. The discussion highlights the kinetics and conformational dynamics of DNA polymerases from all known polymerase families during DNA synthesis.     

Tumor-Stroma Ratio and Programmed Cell Death Ligand 1 Expression in Preoperative Biopsy and Matched Laryngeal Carcinoma Surgical Specimen

Programmed cell death ligand 1 (PD-L1) seems to rely on close relations between neoplastic and immune cells in the tumor microenvironment. Tumor to stroma ratio (TSR) has been associated with prognosis in different malignancies. The aims of this exploratory investigation were to analyze for the first time the: (i) association between TSR, PD-L1 expression and other clinical–pathological features in laryngeal squamous cell carcinoma (LSCC) biopsies and paired surgical specimens; (ii) prognostic and predictive role of TSR and PD-L1. TSR, PD-L1 expression (in terms of combined positive score [CPS]), and other clinical–pathological features were analyzed in biopsies and surgical specimens of 43 consecutive LSCC cases. A CPS < 1 evaluated on surgical specimens was associated with a low TSR (stroma rich) on both biopsies and surgical specimens (p = 0.0143 and p = 0.0063). Low TSR showed a significant negative prognostic value when evaluated on both biopsies and surgical specimens (HR = 8.808, p = 0.0003 and HR = 11.207, p = 0.0002). CPS ≥ 1 appeared to be a favorable prognostic factor (HR = 0.100, p = 0.0265). The association between bioptic and surgical specimen TSR and PD-L1 expression should be further investigated for a potential impact on targeted treatments, also with regard to immunotherapeutic protocols.     

Assessment of potential bioenergy from coppice forests trough the integration of remote sensing and field surveys

A spatially explicit knowledge of forest resources is essential to support the sustainable use of wood as a fuel for producing energy (firewood).This paper describes the integrated use of remotely sensed data and sample based forest inventories to derive a biomass map for coppice forest, resulted estimated potential biomass available is contrasted with local domestic consumptions at the municipality level. The test was carried out in an environmentally and socially homogeneous district of Apennine Mountains (Alto Molise, south-central Italy) coupling multispectral high resolution Landsat 7 ETM+ satellite imagery and a local forest inventory trough the application of the non-parametric estimation procedure k-Nearest Neighbours (k-NN). Several forest management scenarios were applied in order to evaluate their impact on the potential availability of firewood from coppice forests.The paper introduces data and methods used and presents the achieved results both in terms of the accuracy of the biomass map produced by k-NN and of the relationship between the potential availability and demand for firewood.These results demonstrated that k-NN is able to estimate the biomass of coppice forest in the test area with an accuracy level comparable with recent similar application of k-NN carried out in Boreal regions (RMSE of 25.6%).The application of different forest management scenarios have a significant impact on local estimated firewood balance between potential supply from coppice forests and demand for domestic consumption, depending of the scenarios the net balance changed up to 84%.     

The Role of Altered Mitochondrial Metabolism in Thyroid Cancer Development and Mitochondria-Targeted Thyroid Cancer Treatment

Thyroid cancer (TC) is the most common type of endocrine malignancy. Tumour formation, progression, and metastasis greatly depend on the efficacy of mitochondria—primarily, the regulation of mitochondria-mediated apoptosis, Ca²⁺ homeostasis, dynamics, energy production, and associated reactive oxygen species generation. Recent studies have successfully confirmed the mitochondrial aetiology of thyroid carcinogenesis. In this review, we focus on the recent progress in understanding the molecular mechanisms of thyroid cancer relating to altered mitochondrial metabolism. We also discuss the repurposing of known drugs and the induction of mitochondria-mediated apoptosis as a new trend in the development of anti-TC therapy.     

AICAR Protects Vascular Endothelial Cells from Oxidative Injury Induced by the Long-Term Palmitate Excess

Hyperlipidemia manifested by high blood levels of free fatty acids (FFA) and lipoprotein triglycerides is critical for the progression of type 2 diabetes (T2D) and its cardiovascular complications via vascular endothelial dysfunction. However, attempts to assess high FFA effects in endothelial culture often result in early cell apoptosis that poorly recapitulates a much slower pace of vascular deterioration in vivo and does not provide for the longer-term studies of endothelial lipotoxicity in vitro. Here, we report that palmitate (PA), a typical FFA, does not impair, by itself, endothelial barrier and insulin signaling in human umbilical vein endothelial cells (HUVEC), but increases NO release, reactive oxygen species (ROS) generation, and protein labeling by malondialdehyde (MDA) hallmarking oxidative stress and increased lipid peroxidation. This PA-induced stress eventually resulted in the loss of cell viability coincident with loss of insulin signaling. Supplementation with 5-aminoimidazole-4-carboxamide-riboside (AICAR) increased endothelial AMP-activated protein kinase (AMPK) activity, supported insulin signaling, and prevented the PA-induced increases in NO, ROS, and MDA, thus allowing to maintain HUVEC viability and barrier, and providing the means to study the long-term effects of high FFA levels in endothelial cultures. An upgraded cell-based model reproduces FFA-induced insulin resistance by demonstrating decreased NO production by vascular endothelium.