CGHnormaliter: an iterative strategy to enhance normalization of array CGH data with imbalanced aberrations

Background: Array comparative genomic hybridization (aCGH) is a popular technique for detection of genomic copy number imbalances. These play a critical role in the onset of various types of cancer. In the analysis of aCGH data, normalization is deemed a critical pre-processing step. In general, aCGH normalization approaches are similar to those used for gene expression data, albeit both data-types differ inherently. A particular problem with aCGH data is that imbalanced copy numbers lead to improper normalization using conventional methods. Results: In this study we present a novel method, called CGHnormaliter, which addresses this issue by means of an iterative normalization procedure. First, provisory balanced copy numbers are identified and subsequently used for normalization. These two steps are then iterated to refine the normalization. We tested our method on three well-studied tumor-related aCGH datasets with experimentally confirmed copy numbers. Results were compared to a conventional normalization approach and two more recent state-of-the-art aCGH normalization strategies. Our findings show that, compared to these three methods, CGHnormaliter yields a higher specificity and precision in terms of identifying the 'true' copy numbers. Conclusion: We demonstrate that the normalization of aCGH data can be significantly enhanced using an iterative procedure that effectively eliminates the effect of imbalanced copy numbers. This also leads to a more reliable assessment of aberrations. An R-package containing the implementation of CGHnormaliter is available at http://www.ibi.vu.nl/programs/cghnormaliterwww. © 2009 van Houte et al; licensee BioMed Central Ltd

Review of Hardware for PTCA

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72432/1/j.1540-8183.1988.tb00408.x.pd

The use of the 1 mm laparoscope to assist in port insertion in pelvic oncological surgery

BACKGROUND: A 1 mm minilaparoscope (Lifeline Biotechnoligies, Florida, USA) was assessed for aiding port site insertions. METHODS: Ten consecutive patients having laparoscopic procedures in a gynaecological oncology unit were included. Minilaparoscopy was feasible in all cases and was used to insert the umbilical port under direct vision in all patients. In one case, a thick band of abdominal adhesions was identified and a further lateral port site was inserted to aid their dissection. RESULTS: The minilaparoscope correctly identified all 10 patients with peritoneal disease and identified all patients who were suitable for debulking procedures. CONCLUSION: Minilaparoscopy with the 1 mm endoscope appears to be safe and accurate and we feel that it has a place in helping the surgeon identify adhesions and peritoneal disease as well as assisting further port site insertion safely and with minimal complications

Discrete wavelet transform de-noising in eukaryotic gene splicing

<p>Abstract</p> <p>Background</p> <p>This paper compares the most common digital signal processing methods of exon prediction in eukaryotes, and also proposes a technique for noise suppression in exon prediction. The specimen used here which has relevance in medical research, has been taken from the public genomic database - GenBank.</p> <p>Methods</p> <p>Here exon prediction has been done using the digital signal processing methods viz. binary method, EIIP (electron-ion interaction psuedopotential) method and filter methods. Under filter method two filter designs, and two approaches using these two designs have been tried. The discrete wavelet transform has been used for de-noising of the exon plots.</p> <p>Results</p> <p>Results of exon prediction based on the methods mentioned above, which give values closest to the ones found in the NCBI database are given here. The exon plot de-noised using discrete wavelet transform is also given.</p> <p>Conclusion</p> <p>Alterations to the proven methods as done by the authors, improves performance of exon prediction algorithms. Also it has been proven that the discrete wavelet transform is an effective tool for de-noising which can be used with exon prediction algorithms.</p

Multiple Neural Oscillators and Muscle Feedback Are Required for the Intestinal Fed State Motor Program

After a meal, the gastrointestinal tract exhibits a set of behaviours known as the fed state. A major feature of the fed state is a little understood motor pattern known as segmentation, which is essential for digestion and nutrient absorption. Segmentation manifests as rhythmic local constrictions that do not propagate along the intestine. In guinea-pig jejunum in vitro segmentation constrictions occur in short bursts together with other motor patterns in episodes of activity lasting 40–60 s and separated by quiescent episodes lasting 40–200 s. This activity is induced by luminal nutrients and abolished by blocking activity in the enteric nervous system (ENS). We investigated the enteric circuits that regulate segmentation focusing on a central feature of the ENS: a recurrent excitatory network of intrinsic sensory neurons (ISNs) which are characterized by prolonged after-hyperpolarizing potentials (AHPs) following their action potentials. We first examined the effects of depressing AHPs with blockers of the underlying channels (TRAM-34 and clotrimazole) on motor patterns induced in guinea-pig jejunum, in vitro, by luminal decanoic acid. Contractile episode durations increased markedly, but the frequency and number of constrictions within segmenting bursts and quiescent period durations were unaffected. We used these observations to develop a computational model of activity in ISNs, excitatory and inhibitory motor neurons and the muscle. The model predicted that: i) feedback to ISNs from contractions in the circular muscle is required to produce alternating activity and quiescence with the right durations; ii) transmission from ISNs to excitatory motor neurons is via fast excitatory synaptic potentials (EPSPs) and to inhibitory motor neurons via slow EPSPs. We conclude that two rhythm generators regulate segmentation: one drives contractions within segmentation bursts, the other the occurrence of bursts. The latter depends on AHPs in ISNs and feedback to these neurons from contraction of the circular muscle

Anemia is an independent risk for mortality after acute myocardial infarction in patients with and without diabetes

INTRODUCTION: Anemia and diabetes are risk factors for short-term mortality following an acute myocardial infarction(AMI). Anemia is more prevalent in patients with diabetes. We performed a retrospective study to assess the impact of the combination of diabetes and anemia on post-myocardial infarction outcomes. METHODS: Data relating to all consecutive patients hospitalized with AMI was obtained from a population-based disease-specific registry. Patients were divided into 4 groups: diabetes and anemia (group A, n = 716), diabetes and no anemia (group B, n = 1894), no diabetes and anemia (group C, n = 869), and no diabetes and no anemia (group D, n = 3987). Mortality at 30 days and 31 days to 36 months were the main outcome measures. RESULTS: 30-day mortality was 32.3% in group A, 16.1% in group B, 21.5% in group C, 6.6% in group D (all p < 0.001). 31-day to 36-month mortality was 47.6% in group A, 20.8% in group B, 34.3% in group C, and 10.4% in group D (all p < 0.001). Diabetes and anemia remained independent risk factors for mortality with odds ratios of 1.61 (1.41–1.85, p < 0.001) and 1.59 (1.38–1.85, p < 0.001) respectively at 36 months. Cardiovascular death from 31-days to 36-months was 43.7% of deaths in group A, 54.1% in group B, 47.0% in group C, 50.8% group D (A vs B, p < 0.05). INTERPRETATION: Patients with both diabetes and anemia have a significantly higher mortality than those with either diabetes or anemia alone. Cardiovascular death remained the most likely cause of mortality in all groups

Consistency and diversity of spike dynamics in the neurons of bed nucleus of Stria Terminalis of the rat: a dynamic clamp study

Neurons display a high degree of variability and diversity in the expression and regulation of their voltage-dependent ionic channels. Under low level of synaptic background a number of physiologically distinct cell types can be identified in most brain areas that display different responses to standard forms of intracellular current stimulation. Nevertheless, it is not well understood how biophysically different neurons process synaptic inputs in natural conditions, i.e., when experiencing intense synaptic bombardment in vivo. While distinct cell types might process synaptic inputs into different patterns of action potentials representing specific "motifs'' of network activity, standard methods of electrophysiology are not well suited to resolve such questions. In the current paper we performed dynamic clamp experiments with simulated synaptic inputs that were presented to three types of neurons in the juxtacapsular bed nucleus of stria terminalis (jcBNST) of the rat. Our analysis on the temporal structure of firing showed that the three types of jcBNST neurons did not produce qualitatively different spike responses under identical patterns of input. However, we observed consistent, cell type dependent variations in the fine structure of firing, at the level of single spikes. At the millisecond resolution structure of firing we found high degree of diversity across the entire spectrum of neurons irrespective of their type. Additionally, we identified a new cell type with intrinsic oscillatory properties that produced a rhythmic and regular firing under synaptic stimulation that distinguishes it from the previously described jcBNST cell types. Our findings suggest a sophisticated, cell type dependent regulation of spike dynamics of neurons when experiencing a complex synaptic background. The high degree of their dynamical diversity has implications to their cooperative dynamics and synchronization

The Role of Biomethylation in Toxicity and Carcinogenicity of Arsenic: A Research Update

Recent research of the metabolism and biological effects of arsenic has profoundly changed our understanding of the role of metabolism in modulation of toxicity and carcinogenicity of this metalloid. Historically, the enzymatic conversion of inorganic arsenic to mono- and dimethylated species has been considered a major mechanism for detoxification of inorganic arsenic. However, compelling experimental evidence obtained from several laboratories suggests that biomethylation, particularly the production of methylated metabolites that contain trivalent arsenic, is a process that activates arsenic as a toxin and a carcinogen. This article summarizes this evidence and provides new data on a) the toxicity of methylated trivalent arsenicals in mammalian cells, b) the effects of methylated trivalent arsenicals on gene transcription, and c) the mechanisms involved in arsenic methylation in animal and human tissues