On stable and explicit numerical methods for the advection–diffusion equation

In this paper two stable and explicit numerical methods to integrate the one-dimensional (1D) advection–diffusion equation are presented. These schemes are stable by design and follow the main general concept behind the semi-Lagrangian method by constructing a virtual grid where the explicit method becomes stable. It is shown that the new schemes compare well with analytic solutions and are often more accurate than implicit schemes. In particular, the diffusion-only case is explored in some detail. The error produced by the stable and explicit method is a function of the ratio between the standard deviation σ₀ of the initial Gaussian state and the characteristic virtual grid distance ΔS. Larger values of this ratio lead to very accurate results when compared to implicit methods, while lower values lead to less accuracy. It is shown that the σ₀/ΔS ratio is also significant in the advection–diffusion problem: it determines the maximum error generated by new methods, obtained with a certain combination of the advection and diffusion values. In addition, the error becomes smaller when the problem becomes more advective or more diffusive.     

Experimental and theoretical polarized Raman linear difference spectroscopy of small molecules with a new alignment method using stretched polyethylene film

This paper reports the development of the new technique of Raman linear difference (RLD) spectroscopy and its application to small molecules: anthracene and nucleotides adenosine-5'-monophosphate, thymidine-5'-monophosphate, guanosine-5'-monophosphate, and cytidine-5'-monophosphate. In this work we also present a new alignment method for Raman spectroscopy where stretched polyethylene films are used as the matrix. Raman spectra using light polarized along the orientation direction and perpendicular to it are reported. The polyethylene (PE) film spectra are consistent with powder samples and films deposited on quartz. RLD spectra determined from the difference of the parallel and perpendicular polarized light Raman spectra are also reported. The equations describing RLD are derived, and RLD spectra of anthracene and thymidine are calculated from these equations using Density Functional Theory and assuming perfect orientation of the samples. Because of the wealth of spectroscopic information in the vibrational spectra of biomolecules together with our ability to calculate spectra as a function of orientation, we conclude that RLD has the potential to provide structural information for biological samples that currently cannot be extracted from any other method.     

Dissociation constants of aromatic carboxylic acids spread at the air/water interface

The surface potential technique is employed to estimate the dissociation constant (K) of a series of aromatic carboxylic acids in the form of Langmuir monolayers. Using electric surface potential (ΔV) measurements of monolayers spread on aqueous subphases, containing different concentrations of Na⁺, and applying the Gouy–Chapman theory as well as the Henderson–Hasselbalch equation, the surface pK for the investigated compounds falls in the range of 4.5–5.6 with the mean value of 5.1. The other method, based on surface potential measurements of monolayers of the parent, unsubstituted compound (5′-phenyl-m-terphenyl-4-carboxylic acid) spread on aqueous solutions with distinct pHs, leads to a pK of ca. 6.5 which corresponds to the bulk conditions. This value is shifted towards neutral pH as compared to the one calculated with the Henderson–Hasselbalch equation (5.3), owing to the inhomogeneous distribution of hydrogen ions caused by partial ionization of carboxylic groups of the monolayer molecules.     

Molecular and Functional Analysis of Sunitinib-Resistance Induction in Human Renal Cell Carcinoma Cells

Resistance in clear cell renal cell carcinoma (ccRCC) against sunitinib is a multifaceted process encompassing numerous molecular aberrations. This induces clinical complications, reducing the treatment success. Understanding these aberrations helps us to select an adapted treatment strategy that surpasses resistance mechanisms, reverting the treatment insensitivity. In this regard, we investigated the dominant mechanisms of resistance to sunitinib and validated an optimized multidrug combination to overcome this resistance. Human ccRCC cells were exposed to single or chronic treatment with sunitinib to obtain three resistant clones. Upon manifestation of sunitinib resistance, morphometric changes in the cells were observed. At the molecular level, the production of cell membrane and extracellular matrix components, chemotaxis, and cell cycle progression were dysregulated. Molecules enforcing the cell cycle progression, i.e., cyclin A, B1, and E, were upregulated. Mass spectrometry analysis revealed the intra- and extracellular presence of N-desethyl sunitinib, the active metabolite. Lysosomal sequestration of sunitinib was confirmed. After treatment with a synergistic optimized drug combination, the cell metabolic activity in Caki-1-sunitinib-resistant cells and 3D heterotypic co-cultures was reduced by >80%, remaining inactive in non-cancerous cells. These results demonstrate geno- and phenotypic changes in response to sunitinib treatment upon resistance induction. Mimicking resistance in the laboratory served as a platform to study drug responses.     

PSA Depletion Induces the Differentiation of Immature Neurons in the Piriform Cortex of Adult Mice

Immature neurons are maintained in cortical regions of the adult mammalian brain. In rodents, many of these immature neurons can be identified in the piriform cortex based on their high expression of early neuronal markers, such as doublecortin (DCX) and the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). This molecule plays critical roles in different neurodevelopmental events. Taking advantage of a DCX-CreERT2/Flox-EGFP reporter mice, we investigated the impact of targeted PSA enzymatic depletion in the piriform cortex on the fate of immature neurons. We report here that the removal of PSA accelerated the final development of immature neurons. This was revealed by a higher frequency of NeuN expression, an increase in the number of cells carrying an axon initial segment (AIS), and an increase in the number of dendrites and dendritic spines on the immature neurons. Taken together, our results demonstrated the crucial role of the PSA moiety in the protracted development of immature neurons residing outside of the neurogenic niches. More studies will be required to understand the intrinsic and extrinsic factors affecting PSA-NCAM expression to understand how the brain regulates the incorporation of these immature neurons to the established neuronal circuits of the adult brain.     

Potential Biomarkers in Diagnosis of Renal Acanthamoebiasis

Recent studies indicate that Acanthamoeba spp. may play a significant role in kidney dysfunction. The aim of the study was to examine the levels of kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemotactic protein 1 (MCP-1), as well as an activity of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9, respectively) in the kidneys of immunocompetent and immunosuppressed mice infected with Acanthamoeba spp. The levels of KIM-1, NGAL, and MCP-1 were analyzed by enzyme-linked immunosorbent assay (ELISA), and the activity of MMPs was determined by gelatin zymography. The elevated KIM-1 level was found in the kidneys of immunocompetent mice at the beginning of Acanthamoeba spp. infection. In the immunosuppressed mice, the KIM-1 level was statistically different. The statistically decreased NGAL level was found in the kidneys of immunocompetent mice compared to the uninfected mice. In the immunocompromised mice, we found statistically significant differences in MCP-1 levels between the uninfected and infected groups. There was an increase in the expression of both MMP-2 and MMP-9 in the kidneys of immunocompetent and immunosuppressed mice infected with Acanthamoeba spp. compared to the uninfected mice. The results indicate that KIM-1, NGAL, MCP-1, MMP-2, MMP-9, and MMP-9/NGAL might be promising biomarkers of renal acanthamoebiasis.     

Preparation of conducting polysiloxane/polyaniline composites

Polysiloxane/polyaniline microcomposites were prepared, in which polyaniline particles act as filler, thus combining the mechanical properties of polysiloxane matrix with conductivity of polyaniline. Two syntheses were evaluated: (1) homogeneous dispersion of a polyaniline colloid in the reaction mixture from which the polysiloxane matrix subsequently formed, and (2) the blending of previously prepared dry polyaniline particles with a liquid oligomeric siloxane resin followed by cure (“heterogeneous method”). Both methods lead to composites with evenly distributed filler. Electrical conductivity was achieved above 40 wt % of polyaniline, which is better obtained by the “heterogeneous” method. During the composite cure, the polyaniline particles, which are softer than the matrix, act as a catalyst and cause more efficient matrix crosslinking, thus leading to somewhat raised moduli. Although particulate fillers usually deteriorate the impact toughness, in the case of the prepared composites, the impact toughness was preserved due to the softer consistence of the filler, which hinders crack propagation. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42429.     

Mitochondrial Oxidative Stress—A Causative Factor and Therapeutic Target in Many Diseases

The excessive formation of reactive oxygen species (ROS) and impairment of defensive antioxidant systems leads to a condition known as oxidative stress. The main source of free radicals responsible for oxidative stress is mitochondrial respiration. The deleterious effects of ROS on cellular biomolecules, including DNA, is a well-known phenomenon that can disrupt mitochondrial function and contribute to cellular damage and death, and the subsequent development of various disease processes. In this review, we summarize the most important findings that implicated mitochondrial oxidative stress in a wide variety of pathologies from Alzheimer disease (AD) to autoimmune type 1 diabetes. This review also discusses attempts to affect oxidative stress as a therapeutic avenue.     

Microfibril Associated Protein 5 (MFAP5) Is Related to Survival of Ovarian Cancer Patients but Not Useful as a Prognostic Biomarker

Ovarian cancer (OC) is usually diagnosed late due to its nonspecific symptoms and lack of reliable tools for early diagnostics and screening. OC studies concentrate on the search for new biomarkers and therapeutic targets. This study aimed to validate the MFAP5 gene, and its encoded protein, as a potential prognostic biomarker. In our previous study, we found that patients with high-grade serous OC who had higher MFAP5 mRNA levels had shorter survival, as compared with those with lower levels. Here, we used the Kaplan-Meier Plotter and CSIOVDB online tools to analyze possible associations of MFAP5 expression with survival and other clinico-pathological features. In these analyses, higher MFAP5 mRNA expression was observed in the more advanced FIGO stages and high-grade tumors, and was significantly associated with shorter overall and progression-free survival. Next, we analyzed the expression of the MFAP5 protein by immunohistochemistry (IHC) in 108 OC samples and tissue arrays. Stronger MFAP5 expression was associated with stronger desmoplastic reaction and serous vs. non-serous histology. We found no significant correlation between IHC results and survival, although there was a trend toward shorter survival in patients with the highest IHC scores. We searched for co-expressed genes/proteins using cBioPortal and analyzed potential MFAP5 interaction networks with the STRING tool. MFAP5 was shown to interact with many extracellular matrix proteins, and was connected to the Notch signaling pathway. Therefore, although not suitable as a prognostic biomarker for evaluation with a simple diagnostic tool like IHC, MFAP5 is worth further studies as a possible therapeutic target.     

Melatonin and Female Hormone Secretion in Postmenopausal Overweight Women

Estrogen deficiency is considered to be the main cause of increased appetite and increased weight in postmenopausal women. In this period, reduced secretion of melatonin (MEL) was also observed. The aim of the study was to evaluate the secretion of melatonin, 17-β estradiol and follicle-stimulating hormone (FSH) in relation to body mass index (BMI) in pre- and postmenopausal women. The study included 90 women divided into three equal groups: group I (control)—women without menstrual disorders, group II—postmenopausal women without change in appetite and body weight, group III—postmenopausal women experiencing increased appetite and weight gain. In each patient, serum melatonin, 17-β-estradiol, FSH and urine a 6-sulfatoxymelatonin (aMT6s) were determined. Compared to the control group, the level of melatonin and estradiol was statistically lower. The FSH level was higher than in the groups of postmenopausal women. No significant correlation was found in all groups between the level of melatonin and the levels of estradiol and FSH. A negative correlation was found between aMT6s excretion and BMI, and a positive correlation between the level of FSH and BMI, mainly in overweight women. The obtained results indicate a significant effect of melatonin deficiency on the process of weight gain in postmenopausal women and justify its use in treatment of these disorders.