Probabilistic estimation of microarray data reliability and underlying gene expression

Background: The availability of high throughput methods for measurement of mRNA concentrations makes the reliability of conclusions drawn from the data and global quality control of samples and hybridization important issues. We address these issues by an information theoretic approach, applied to discretized expression values in replicated gene expression data. Results: Our approach yields a quantitative measure of two important parameter classes: First, the probability $P(\sigma | S)$ that a gene is in the biological state $\sigma$ in a certain variety, given its observed expression $S$ in the samples of that variety. Second, sample specific error probabilities which serve as consistency indicators of the measured samples of each variety. The method and its limitations are tested on gene expression data for developing murine B-cells and a $t$-test is used as reference. On a set of known genes it performs better than the $t$-test despite the crude discretization into only two expression levels. The consistency indicators, i.e. the error probabilities, correlate well with variations in the biological material and thus prove efficient. Conclusions: The proposed method is effective in determining differential gene expression and sample reliability in replicated microarray data. Already at two discrete expression levels in each sample, it gives a good explanation of the data and is comparable to standard techniques.Comment: 11 pages, 4 figure

Drink wise, age well; reducing alcohol related harm among people over 50: a study protocol

Background: Evidence suggests that the use of alcohol among older adults (defined as those aged 50+) has increased in recent years, with people aged 55-64 now more likely to exceed the recommended weekly guidelines than any other age group. Methods/ design: This is a quasi-experimental study with a before-after design. A postal questionnaire will be sent to 76,000 people aged 50 and over registered with a general practice in five different 'demonstration' (intervention) and control areas in the UK. Multiple interventions will then be delivered in demonstration areas across the UK. At the end of the programme, a postal questionnaire will be sent to the same individuals who completed it pre-programme to establish if there has been a reduction in alcohol use, at-risk drinking and alcohol related problems. Qualitative interviews with clients and staff will explore how the interventions were experienced; how they may work to bring about change and to identify areas for practice improvements. Discussion: This study protocol describes a multi-level, multi-intervention prevention-to-treatment programme which aims to reduce alcohol-related harm in people aged 50 and over

Cross-adaptation and bitterness inhibition of L-Tryptophan, L-Phenylalanine and urea : further support for shared peripheral physiology

A previous study investigating individuals\u27 bitterness sensitivities found a close association among three compounds: L-tryptophan (L-trp), L-phenylalanine (L-phe) and urea (Delwiche et al., 2001, Percept. Psychophys. 63, 761-776). In the present experiment, psychophysical cross-adaptation and bitterness inhibition experiments were performed on these three compounds to determine whether the bitterness could be differentially affected by either technique. If the two experimental approaches failed to differentiate L-trp, L-phe and urea\u27s bitterness, then we may infer they share peripheral physiological mechanisms involved in bitter taste. All compounds were intensity matched in each of 13 subjects, so the judgments of adaptation or bitterness inhibition would be based on equal initial magnitudes and, therefore, directly comparable. In the first experiment, cross-adaptation of bitterness between the amino acids was high (&gt;80%) and reciprocal. Urea and quinine-HCl (control) did not cross-adapt with the amino acids symmetrically. In a second experiment, the sodium salts, NaCl and Na gluconate, did not differentially inhibit the bitterness of L-trp, L-phe and urea, but the control compound, MgSO4, was differentially affected. The bitter inhibition experiment supports the hypothesis that L-trp, L-phe and urea share peripheral bitter taste mechanisms, while the adaptation experiment revealed subtle differences between urea and the amino acids indicating that urea and the amino acids activate only partially overlapping bitter taste mechanisms.<br /

Modifying the bitterness of selected oral pharmaceuticals with cation and anion series of salts

Purpose. NaCl has proven to be an effective bitterness inhibitor, but the reason remains unclear. The purpose of this study was to examine the influence of a variety of cations and anions on the bitterness of selected oral pharmaceuticals and bitter taste stimuli: pseudoephedrine, ranitidine, acetaminophen, quinine, and urea.Method. Human psychophysical taste evaluation using a whole mouth exposure procedure was used.Results. The cations (all associated with the acetate anion) inhibited bitterness when mixed with pharmaceutical solutions to varying degrees. The sodium cation significantly (P &lt; 0.003) inhibited bitterness of the pharmaceuticals more than the other cations. The anions (all associated with the sodium cation) also inhibited bitterness to varying degrees. With the exception of salicylate, the glutamate and adenosine monophosphate anions significantly (P &lt; 0.001) inhibited bitterness of the pharmaceuticals more than the other anions. Also, there were several specific inhibitory interactions between ammonium, sodium and salicylate and certain pharmaceuticals.Conclusions. We conclude that sodium was the most successful cation and glutamate and AMP were the most successful anions at inhibiting bitterness. Structure forming and breaking properties of ions, as predicted by the Hofmeister series, and other physical-chemical ion properties failed to significantly predict bitterness inhibition.<br /

East Asia and the global/transatlantic/Western crisis

This paper introduces the special collection on East Asia and the Global Crisis. After justifying why a focus on East Asia is appropriate, it draws out the main themes that run through the individual contributions. These are the extent to which the region is decoupling from the global economy (or the West), the increasing legitimacy of statist alternatives to neoliberal development strategies, and the impact of crises on the definition of ―region‖ and the functioning of regional institutions and governance mechanisms

Who governs and how? Non-state actors and transnational governance in Southeast Asia

This special issue focuses on transnational governance, essentially cross-border networked forms of co-ordination in which non-state, or private, actors play important or leading roles in providing standards, rules and practices that other actors voluntarily abide by. While not denying the pre-eminent role of the state in governance, we nonetheless believe there is an under-estimation of transnational governance in Southeast Asia and the varied governance role played by non-state actors that go beyond that of simply acting as pressure or advisory groups lobbying or advising states and regional organisations. We provide five different case studies that explore in detail the varied governance roles played by non-state actors using the common analytical framework set out in this introduction. The case studies reveal interesting variations in the architecture of transnational governance, why they emerge, the modes of social co-ordination through which they work to shape actor behaviour and achieve impact, their normative implications, and how these governance schemes intersect with the state and national regulatory frameworks. This special issue, thus, highlights the variegated architecture of governance in this region in which non-state actors play substantial governance roles regulating the conduct of other actors

An overview of binary taste-taste interactions

The human gustatory system is capable of identifying five major taste qualities: sweet, sour, bitter, salty and savory (umami), and perhaps several sub-qualities. This is a relatively small number of qualities given the vast number and structural diversity of chemical compounds that elicit taste. When we consume a food, our taste receptor cells are activated by numerous stimuli via several transduction pathways. An important food-related taste question which remains largely unanswered is: How do taste perceptions change when multiple taste stimuli are presented together in a food or beverage rather than when presented alone? The interactions among taste compounds is a large research area that has interested electrophysiologists, psychophysicists, biochemists, and food scientists alike. On a practical level, taste interactions are important in the development and modification of foods, beverages or oral care products. Is there enhancement or suppression of intensity when adding stimuli of the same or different qualities together? Relevant psychophysical literature on taste&ndash;taste interactions along with selected psychophysical theory is reviewed. We suggest that the position of the individual taste stimuli on the concentration-intensity psychophysical curve (expansive, linear, or compressive phase of the curve) predicts important interactions when reporting enhancement or suppression of taste mixtures.<br /

Novel oncogenes and tumor suppressor genes in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a very deadly disease. HCC initiation and progression involve multiple genetic events, including the activation of proto-oncogenes and disruption of the function of specific tumor suppressor genes. Activation of oncogenes stimulates cell growth and survival, while loss-of-function mutations of tumor suppressor genes result in unrestrained cell growth. In this review, we summarize the new findings that identified novel proto-oncogenes and tumor suppressors in HCC over the past five years. These findings may inspire the development of novel therapeutic strategies to improve the outcome of HCC patients

The influence of sodium salts on binary mixtures of bitter-tasting compounds

In order to study potential mixture interactions among bitter compounds, selected sodium salts were added to five compounds presented either alone or as binary bitter- ompound mixtures. Each compound was tested at a concentration that elicited &lsquo;weak&rsquo; perceived bitterness. The bitter compounds were mixed at these concentrations to form a subset of possible binary mixtures. For comparison, the concentration of each solitary compound was doubled to measure bitterness inhibition at the higher intensity level elicited by the mixtures. The following sodium salts were tested for bitterness inhibition: 100 mM sodium chloride (salty), 100 mM sodium gluconate (salty), 100 and 20 mM monosodium glutamate (umami), and 50 mM adenosine monophosphate disodium salt (umami). Sucrose (sweet) was also employed as a bitterness suppressor. The sodium salts differentially suppressed the bitterness of compounds and their binary combinations. Although most bitter compounds were suppressed, the bitterness of tetralone was not suppressed, nor was the bitterness of the binary mixtures that contained it. In general, the percent suppression of binary mixtures of compounds was predicted by the average percent suppression of its two components. Within the constraints of the present study, the bitterness of mixtures was suppressed by sodium salts and sucrose independently, with few bitter interactions. This is consistent with observations that the bitter taste system integrates the bitterness of multi-compound solutions linearly.<br /

(-)-Oleocanthal rapidly and selectively induces cancer cell death via lysosomal membrane permeabilization

(-)-Oleocanthal (OC), a phenolic compound present in extra-virgin olive oil (EVOO), has been implicated in the health benefits associated with diets rich in EVOO. We investigated the effect of OC on human cancer cell lines in culture and found that OC induced cell death in all cancer cells examined as rapidly as 30 minutes after treatment in the absence of serum. OC treatment of non-transformed cells suppressed their proliferation but did not cause cell death. OC induced both primary necrotic and apoptotic cell death via induction of lysosomal membrane permeabilization (LMP). We provide evidence that OC promotes LMP by inhibiting acid sphingomyelinase (ASM) activity, which destabilizes the interaction between proteins required for lysosomal membrane stability. The data presented here indicate that cancer cells, which tend to have fragile lysosomal membranes compared to non-cancerous cells, are susceptible to cell death induced by lysosomotropic agents. Therefore, targeting lysosomal membrane stability represents a novel approach for the induction of cancer-specific cell death