Caffeine use in sports, pharmacokinetics in man, and cellular mechanisms of action

Caffeine is the most widely consumed psychoactive 'drug' in the world and probably one of the most commonly used stimulants in sports. This is not surprising, since it is one of the few ergogenic aids with documented efficiency and minimal side effects. Caffeine is rapidly and completely absorbed by the gastrointestinal tract and is readily distributed throughout all tissues of the body. Peak plasma concentrations after normal consumption are usually around 50 microM, and half-lives for elimination range between 2.5-10 h. The parent compound is extensively metabolized in the liver microsomes to more than 25 derivatives, while considerably less than 5% of the ingested dose is excreted unchanged in the urine. There is, however, considerable inter-individual variability in the handling of caffeine by the body, due to both environmental and genetic factors. Evidence from in vitro studies provides a wealth of different cellular actions that could potentially contribute to the observed effects of caffeine in humans in vivo. These include potentiation of muscle contractility via induction of sarcoplasmic reticulum calcium release, inhibition of phosphodiesterase isoenzymes and concomitant cyclic monophosphate accumulation, inhibition of glycogen phosphorylase enzymes in liver and muscle, non-selective adenosine receptor antagonism, stimulation of the cellular membrane sodium/potassium pump, impairment of phosphoinositide metabolism, as well as other, less thoroughly characterized actions. Not all, however, seem to account for the observed effects in vivo, although a variable degree of contribution cannot be readily discounted on the basis of experimental data. The most physiologically relevant mechanism of action is probably the blockade of adenosine receptors, but evidence suggests that, at least under certain conditions, other biochemical mechanisms may also be operational.     

Using modern RF tools to detect chaotic behaviour of electronic circuits and systems

In this paper, a new approach in identifying chaotic behaviour of nonlinear circuits is presented. This approach could be very useful to circuit designers, whether they pursue a chaotic behaviour or not. Simulation tools used for radio-frequency circuit design (Cadence SpectreRF), initially developed to characterise harmonic oscillators, are now utilised to detect chaotic behaviour, as well as routes to chaotic mode of operation. Specifically, Periodic Steady State Convergence Norm is used for the first time for chaos detection in circuits. The advantages of this method (especially in terms of simulation time) are presented, together with an example of detection of chaotic route to chaos in the case of a chaotic-operating Colpitts oscillator.     

The nanometre-scale physiology of bone: steric modelling and scanning transmission electron microscopy of collagen�Cmineral structure

The nanometre-scale structure of collagen and bioapatite within bone establishes bone''s physical properties, including strength and toughness. However, the nanostructural organization within bone is not well known and is debated. Widely accepted models hypothesize that apatite mineral (‘bioapatite’) is present predominantly inside collagen fibrils: in ‘gap channels’ between abutting collagen molecules, and in ‘intermolecular spaces’ between adjacent collagen molecules. However, recent studies report evidence of substantial extrafibrillar bioapatite, challenging this hypothesis. We studied the nanostructure of bioapatite and collagen in mouse bones by scanning transmission electron microscopy (STEM) using electron energy loss spectroscopy and high-angle annular dark-field imaging. Additionally, we developed a steric model to estimate the packing density of bioapatite within gap channels. Our steric model and STEM results constrain the fraction of total bioapatite in bone that is distributed within fibrils at less than or equal to 0.42 inside gap channels and less than or equal to 0.28 inside intermolecular overlap regions. Therefore, a significant fraction of bone''s bioapatite (greater than or equal to 0.3) must be external to the fibrils. Furthermore, we observe extrafibrillar bioapatite between non-mineralized collagen fibrils, suggesting that initial bioapatite nucleation and growth are not confined to the gap channels as hypothesized in some models. These results have important implications for the mechanics of partially mineralized and developing tissues.     

Direct electron crystallographic determination of zeolite zonal structures

The prospect for improving the success of ab initio zeolite structure investigations with electron diffraction data is evaluated. First of all, the quality of intensities obtained by precession electron diffraction at small hollow cone illumination angles is evaluated for seven representative materials: ITQ-1, ITQ-7, ITQ-29, ZSM-5, ZSM-10, mordenite, and MCM-68. It is clear that, for most examples, an appreciable fraction of a secondary scattering perturbation is removed by precession at small angles. In one case, ZSM-10, it can also be argued that precession diffraction produces a dramatically improved 'kinematical' data set. There seems to no real support for application of a Lorentz correction to these data and there is no reason to expect for any of these samples that a two-beam dynamical scattering relationship between structure factor amplitude and observed intensity should be valid. Removal of secondary scattering by the precession mode appears to facilitate ab initio structure analysis. Most zeolite structures investigated could be solved by maximum entropy and likelihood phasing via error-correcting codes when precession data were used. Examples include the projected structure of mordenite that could not be determined from selected area data alone. One anomaly is the case of ZSM-5, where the best structure determination in projection is made from selected area diffraction data. In a control study, the zonal structure of SSZ-48 could be determined from selected area diffraction data by either maximum entropy and likelihood or traditional direct methods. While the maximum entropy and likelihood approach enjoys some advantages over traditional direct methods (non-dependence on predicted phase invariant sums), some effort must be made to improve the figures of merit used to identify potential structure solutions.     

Assessing farmers' practices on disposal of pesticide waste after use

Common practices of farmers on disposal of pesticide waste after use were surveyed in five regions of the rural area of Pieria in northern Greece using a structured questionnaire administered via personal interviews. Concerning leftover spray solutions, most farmers reported that they normally re-spray the treated field area until the spraying tank is empty (54.9%) or they apply the leftover spray solutions to another crop listed on the product label (30.2%). A minority of the farmers (4.3%) mentioned that they often release the leftover spray solutions near or into irrigation canals and streams. As regards rinsates generated from washing the application equipment, most farmers reported that they release the rinsates over a non-cropped area (45.7%) or they drop the rinsates near or into irrigation canals and streams (40.7%). Moreover, a great proportion of the farmers stated that they dump the empty containers by the field (30.2%) or they throw them near or into irrigation canals and streams (33.3%). Burning the empty containers in open fire (17.9%) or throwing the empty containers in common waste places (11.1%) was also reported. Several farmers stated that they continue to use old pesticides for spraying (35.8%). Training programs which raise awareness of farmers of the potential hazards of pesticide use and particularly of the proper management of waste products, recycling programs and collection systems for unwanted agricultural chemicals to prevent inappropriate waste disposal, as well as improving packaging of pesticides to minimize waste production are essential for promoting safety during all phases of pesticide handling.     

Kefir Immobilized on Corn Grains as Biocatalyst for Lactic Acid Fermentation and Sourdough Bread Making

Abstract: The natural mixed culture kefir was immobilized on boiled corn grains to produce an efficient biocatalyst for lactic acid fermentation with direct applications in food production, such as sourdough bread making. The immobilized biocatalyst was initially evaluated for its efficiency for lactic acid production by fermentation of cheese whey at various temperatures. The immobilized cells increased the fermentation rate and enhanced lactic acid production compared to free kefir cells. Maximum lactic acid yield (68.8 g/100 g) and lactic acid productivity (12.6 g/L per day) were obtained during fermentation by immobilized cells at 37 °C. The immobilized biocatalyst was then assessed as culture for sourdough bread making. The produced sourdough breads had satisfactory specific loaf volumes and good sensory characteristics. Specifically, bread made by addition of 60% w/w sourdough containing kefir immobilized on corn was more resistant regarding mould spoilage (appearance during the 11^th day), probably due to higher lactic acid produced (2.86 g/Kg of bread) compared to the control samples. The sourdough breads made with the immobilized biocatalyst had aroma profiles similar to that of the control samples as shown by headspace SPME GC‐MS analysis.     

Application of Kluyveromyces marxianus, Lactobacillus delbrueckii ssp. bulgaricus and L. helveticus for sourdough bread making

The application of Kluyveromyces marxianus (IFO 288), Lactobacillus delbrueckii ssp. bulgaricus (ATCC 11842) and Lactobacillus helveticus (ATCC 15009) as starter cultures for sourdough bread making was examined. Production of lactic and acetic acids, bread rising, volatile composition, shelf-life and organoleptic quality of the sourdough breads were evaluated. The amount of starter culture added to the flour, the dough fermentation temperature and the amount of sourdough used were examined in order to optimise the bread making process. The use of mixed cultures led to higher total titratable acidities and lactic acid concentrations compared to traditionally made breads. Highest acidity (3.41 g lactic acid/kg of bread) and highest resistance to mould spoilage were observed when bread was made using 50% sourdough containing 1% K. marxianus and 4% L. delbrueckii ssp. bulgaricus. The use of these cultures also improved the aroma of sourdough breads, as shown by sensory evaluations and as revealed by GC–MS analysis.     

A Pipeline Technique for Dynamic Data Transfer on a Multiprocessor Grid

This paper describes a pipeline technique which is used to redistribute data on a multiprocessor grid during runtime. The main purposes of the algorithm are to minimize the data transfer time, prevent congestion on the ports of the receiving processors, and minimize the number of idle processors. One of the key ideas for this algorithm is the creation of processor classes, firstly introduced by Desprez et al. [IEEE Transactions on Parallel and Distributed Systems 9(2):102 (1998).] Based on the idea of classes, we create the pipeline tasks used to organize the redistribution of data. Our experimental results show that this pipeline technique can significantly reduce the amount of time required to complete a dynamic data transfer task.     

Port site recurrences after laparoscopic surgery. A review

The diagnosis of meningeal carcinomatosis hinges on the cytologic examination of cerebrospinal fluid (CSF), which has a known low sensitivity for the identification of malignant cells. Often only 'suspicious' or 'atypical' diagnoses can be rendered, and specimens are commonly unsatisfactory for evaluation due to poor morphologic preservation. Telomerase is widely expressed in most brain metastases, medulloblastomas, lymphomas, oligodendrogliomas, and is expressed focally in glioblastomas. Little is known about the level of telomerase expression in these tumors, except for brain metastases, where a four-fold variation in telomerase levels exists. In our laboratory, as few as ten carcinoma cells can be detected by a sensitive polymerase chain reaction-based assay, the telomeric repeat amplification protocol (TRAP), for telomerase, but it was unclear whether varying levels of telomerase expressed by different types of metastases would influence detection. Using the TRAP protocol, we studied 281 CSF samples from a wide variety of patients with neurologic and non-neurologic conditions for telomerase expression. An adjusted specificity of 90% and a sensitivity of 64% were achieved for detection of malignant cells in CSF by telomerase expression. The TRAP assay for telomerase detection may serve as an adjunct to the traditional examination of CSF. Neither previously documented four-fold variation in the levels of telomerase expression in brain metastases, high CSF protein levels nor high white blood cell counts precluded detection of malignant cells in CSF.