Comparison of formaldehyde and methanol fixatives used in the detection of ion channel proteins in isolated rat ventricular myocytes by immunofluorescence labelling and confocal microscopy

In this study, a fixation protocol using a 10% neutral buffered formalin (FA) solution and another protocol using a methanol (MeOH) solution were compared for detection of ion channels, Kv1.5, Kv4.2, Cav1.2, Kir6.2, Nav1.5 and Nav1.1 in rat myocytes by immunolabelling. Kv1.5 and Kv4.2 at intercalated discs and Cav1.2 at transverse tubules were not detected by FA but were detected by MeOH. Kir6.2 at transverse tubules and Nav1.5 at sarcolemma were detected by FA but not by MeOH. It is suggested that both FA and MeOH fixation protocols should be used for the detection of cardiac ion channels by immunolabellin

A comparison among different spectrum compatible earthquake simulation methods

The need for the simulation of spectrum compatible earthquake time histories has existed since earthquake engineering for complicated structures began. More than the safety of the main structure, the analysis of the equipment (piping, racks, etc.) can only be assessed on the basis of the time history of the floor in which they are contained. This paper presents several methods for calculating simulated spectrum compatible earthquakes as well as a comparison between them. As a result of this comparison, the use of the phase content in real earthquakes as proposed by Ohsaki appears as an effective alternative to the classical methods. With this method, it is possible to establish an approach without the arbitrary modulation commonly used in other methods. Different procedures are described as is the influence of the different parameters which appear in the analysis. Several numerical examples are also presented, and the effectiveness of Ohsaki's method is confirmed

Effect of Vitamin K Supplementation on Insulin Resistance in Older Men and Women

OBJECTIVE—Vitamin K has a potentially beneficial role in insulin resistance, but evidence is limited in humans. We tested the hypothesis that vitamin K supplementation for 36 months will improve insulin resistance in older men and women

Computer simulation of diffusion processes in tilt spatio-periodic potentials

Нещодавно було показано, що в істотно нерівноважних системах коефіцієнт дифузії може вести себе немонотонно з температурою. Одним із прикладів таких систем з аномальною температурної залежністю є рух броунівських часток в просторово-періодичних структурах. Метою статті було дослідження зміни температурної залежності дифузії в недодемпфованих системах з низьким коефіцієнтом тертя. В роботі методами комп'ютерного моделювання вивчено зміна коефіцієнта дифузії частинок в широкому діапазоні температур в нахилених просторово-періодичних потенціалах для різних значень коефіцієнта тертя. Показано, що дифузія досягає максимуму при певній величині зовнішньої сили. Її значення залежить від величини коефіцієнта тертя. Показано, що на відміну від звичайної залежності Аррениуса, в разі нахиленого періодичного потенціалу, максимальний коефіцієнт дифузії зростає, а не зменшується з пониженням температури експоненціальним чином. Встановлено, що така залежність характерна для всіх недодемпфованих систем. Показано, що для просторово-періодичних структур існує обмежена ділянка сил, в якому спостерігається зростання коефіцієнта дифузії зі зменшенням температури. Це область так званої температурно-аномальної дифузії (ТАД). Визначено ширина і положення області ТАД в залежності від коефіцієнта тертя γ і параметрів системи. Показано, що зі зменшенням γ, ширина області ТАД зменшується пропорційно γ. При цьому коефіцієнт дифузії в області ТАД, навпаки зростає ~γ. Отримані дані про температурно-аномальної дифузії мають важливе значення для різних областей фізики і техніки та відкривають перспективи створення новітніх технологій управління процесами дифузії.It was recently shown that in essentially nonequilibrium systems, the diffusion coefficient can behave nonmonotonically with temperature. One example of such systems with anomalous temperature dependence is the motion of Brownian particles in spatially periodic structures. The aim of the article was to study the change in the temperature dependence of diffusion in underdamped systems with a low coefficient of friction. In this paper, computer simulation methods are used to study the change in the diffusion coefficient of particles in a wide range of temperatures in oblique spatially periodic potentials for different values of the friction coefficient. It is shown that diffusion reaches a maximum at a certain external force. Its value depends on the coefficient of friction. It is shown that, in contrast to the usual Arrhenius dependence, in the case of an inclined periodic potential, the maximum diffusion coefficient increases while temperature is decreasing exponentially. It is established that such a dependence is common to all underdamped systems. It is shown that for spatially periodic structures there is a limited portion of forces in which an increase in the diffusion coefficient while decreasing temperature is observed. This is the area of the so-called temperature-anomalous diffusion (TAD). The width and position of the TAD region are determined depending on the friction coefficient γ and the system parameters. It has been shown that a decrease in γ, width TAD region decreases proportionally γ. In this case, the diffusion coefficient in the TAD region, on the contrary, increases ~γ. The data obtained on the temperature and the anomalous diffusion are important for various fields of physics and engineering, and opens new prospects for a diffusion process control technology

Analysis of epidermal growth factor receptor expression as a predictive factor for response to gefitinib (‘Iressa’, ZD1839) in non-small-cell lung cancer

Gefitinib ('Iressa', ZD1839) is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated antitumour activity and favourable tolerability in Phase II studies. We investigated whether EGFR expression levels could predict for response to gefitinib in patients with advanced non-small-cell lung cancer (NSCLC), who received gefitinib (250 mg day(-1)) as part of a worldwide compassionate-use programme. Tissue samples were analysed by immunohistochemistry to assess membrane EGFR immunoreactivity. Of 147 patients enrolled in our institution, 50 patients were evaluable for assessment of both clinical response and EGFR expression. The objective tumour response rate was 10% and disease control was achieved in 50% of patients. Although high EGFR expression was more common in squamous-cell carcinomas than adenocarcinomas, all objective responses were observed in patients with adenocarcinoma. Response and disease control with gefitinib were not associated with high EGFR expression. Overall, median survival was 4 months, and the 1-year survival rate was 18%. Strong EGFR staining correlated with shorter survival time for all patients. Gefitinib demonstrated promising clinical activity in this group of patients with NSCLC. These results have also shown that EGFR expression is not a significant predictive factor for response to gefitinib

Non-homologous DNA end joining in normal and cancer cells and its dependence on break structures

DNA double-strand breaks (DSBs) are a serious threat to the cell, for if not or miss-repaired, they can lead to chromosomal aberration, mutation and cancer. DSBs in human cells are repaired via non-homologous DNA end joining (NHEJ) and homologous recombination repair pathways. In the former process, the structure of DNA termini plays an important role, as does the genetic constitution of the cells, through being different in normal and pathological cells. In order to investigate the dependence of NHEJ on DSB structure in normal and cancer cells, we used linearized plasmids with various, complementary or non-complementary, single-stranded or blunt DNA termini, as well as whole-cell extract isolated from normal human lymphocytes, chronic myeloid leukemia K562 cells and lung cancer A549 cells. We observed a pronounced variability in the efficacy of NHEJ reaction depending on the type of ends. Plasmids with complementary and blunt termini were more efficiently repaired than the substrate with 3' protruding single-strand ends. The hierarchy of the effectiveness of NHEJ was on average, from the most effective to the least, A549/ normal lymphocytes/ K562. Our results suggest that the genetic constitution of the cells together with the substrate terminal structure may contribute to the efficacy of the NHEJ reaction. This should be taken into account on considering its applicability in cancer chemo- or radiotherapy by pharmacologically modulating NHEJ cellular responses