On pairwise distances and median score of three genomes under DCJ

In comparative genomics, the rearrangement distance between two genomes (equal the minimal number of genome rearrangements required to transform them into a single genome) is often used for measuring their evolutionary remoteness. Generalization of this measure to three genomes is known as the median score (while a resulting genome is called median genome). In contrast to the rearrangement distance between two genomes which can be computed in linear time, computing the median score for three genomes is NP-hard. This inspires a quest for simpler and faster approximations for the median score, the most natural of which appears to be the halved sum of pairwise distances which in fact represents a lower bound for the median score. In this work, we study relationship and interplay of pairwise distances between three genomes and their median score under the model of Double-Cut-and-Join (DCJ) rearrangements. Most remarkably we show that while a rearrangement may change the sum of pairwise distances by at most 2 (and thus change the lower bound by at most 1), even the most "powerful" rearrangements in this respect that increase the lower bound by 1 (by moving one genome farther away from each of the other two genomes), which we call strong, do not necessarily affect the median score. This observation implies that the two measures are not as well-correlated as one's intuition may suggest. We further prove that the median score attains the lower bound exactly on the triples of genomes that can be obtained from a single genome with strong rearrangements. While the sum of pairwise distances with the factor 2/3 represents an upper bound for the median score, its tightness remains unclear. Nonetheless, we show that the difference of the median score and its lower bound is not bounded by a constant.Comment: Proceedings of the 10-th Annual RECOMB Satellite Workshop on Comparative Genomics (RECOMB-CG), 2012. (to appear

Vascular device interaction with the endothelium

Copyright @ 2008 Elsevier. This is the post-print version of the article.Cerebral stents and Intra Aortic Balloon Pumps (IABP) are examples of mechanical devices that are inserted into arteries to restore flows to clinically healthy states. The stent and the IABP ‘correct’ the arterial flow by static dilation and by cyclical occlusion respectively. As this presentation shows, these functions are effectively modelled by current engineering practice. As interventions however, by their very nature they involve physical contact between a non-biological structure and the sensitive endothelial surface. The possible damage to the endothelium is not currently well addressed and we also consider this issue. Cerebral stents generally have two primary clinical objectives: to mechanically dilate a stenosed artery and to have minimal detrimental impact upon local blood flow characteristics. These objectives are well served at the arterial scale as these devices are evidently effective in opening up diseased arteries and restoring vital flows. However, at the near-wall micro-scale the picture is less satisfactory, as thin stent wires apply stresses to the endothelium and glycocalyx and the local flow is disturbed rather than being ideally streamlined. This causes further interaction with this endothelium topography. Wall Shear Stress (WSS) is the measure commonly used to indicate the interaction between fluid and wall but it is a broad brush approach that loses fidelity close to the wall. We will present simulation results of blood flow through a stented cerebral saccular aneurysm under these limitations of WSS. The Intra Aortic Balloon Pump (IABP) is a widely used temporary cardiac assist device. The balloon is usually inserted from the iliac artery, advanced in the aorta until it reaches the desired position; with its base just above the renal bifurcation and the tip approximately 10cm away from the aortic valve. The balloon is inflated and deflated every- (1:1), every other- (1:2) or every second (1:3) cardiac cycle. Balloon inflation, which takes place during early diastole, causes an increase in the pressure of the aortic root which leads to an increase in coronary flow. Balloon deflation which takes place during late diastole achieves one of the main IABP therapeutic effects by reducing left ventricular afterload. Unavoidably, the balloon contacts the inner wall of the aorta with every inflation/deflation cycle. This repeated event and possible contact with atherosclerotic plaque have been reported to be responsible for balloon rupture. However, there has not been a methodical study to investigate the mechanical effects of balloon-wall interaction. For example, during inflation the balloon approaches the endothelium as it displaces a volume of blood proximally and distally. This squeezing process generates shear stresses, which hasn't yet been quantified. Similarly, when the balloon moves away from the endothelium during deflation, it generates micro pressure differences that may impose stretching (pulling) stresses on the endothelium cells. Both of the above cases indicate that a very high spatial resolution is required in order to fully understand the process of interaction between device and endothelium, and to interpret the effects at the cellular level

Stability, Structure and Scale: Improvements in Multi-modal Vessel Extraction for SEEG Trajectory Planning

Purpose Brain vessels are among the most critical landmarks that need to be assessed for mitigating surgical risks in stereo-electroencephalography (SEEG) implantation. Intracranial haemorrhage is the most common complication associated with implantation, carrying signi cant associated morbidity. SEEG planning is done pre-operatively to identify avascular trajectories for the electrodes. In current practice, neurosurgeons have no assistance in the planning of electrode trajectories. There is great interest in developing computer assisted planning systems that can optimise the safety pro le of electrode trajectories, maximising the distance to critical structures. This paper presents a method that integrates the concepts of scale, neighbourhood structure and feature stability with the aim of improving robustness and accuracy of vessel extraction within a SEEG planning system. Methods The developed method accounts for scale and vicinity of a voxel by formulating the problem within a multi-scale tensor voting framework. Feature stability is achieved through a similarity measure that evaluates the multi-modal consistency in vesselness responses. The proposed measurement allows the combination of multiple images modalities into a single image that is used within the planning system to visualise critical vessels. Results Twelve paired datasets from two image modalities available within the planning system were used for evaluation. The mean Dice similarity coe cient was 0.89 ± 0.04, representing a statistically signi cantly improvement when compared to a semi-automated single human rater, single-modality segmentation protocol used in clinical practice (0.80 ±0.03). Conclusions Multi-modal vessel extraction is superior to semi-automated single-modality segmentation, indicating the possibility of safer SEEG planning, with reduced patient morbidity

Diffuse Gamma Rays: Galactic and Extragalactic Diffuse Emission

"Diffuse" gamma rays consist of several components: truly diffuse emission from the interstellar medium, the extragalactic background, whose origin is not firmly established yet, and the contribution from unresolved and faint Galactic point sources. One approach to unravel these components is to study the diffuse emission from the interstellar medium, which traces the interactions of high energy particles with interstellar gas and radiation fields. Because of its origin such emission is potentially able to reveal much about the sources and propagation of cosmic rays. The extragalactic background, if reliably determined, can be used in cosmological and blazar studies. Studying the derived "average" spectrum of faint Galactic sources may be able to give a clue to the nature of the emitting objects.Comment: 32 pages, 28 figures, kapproc.cls. Chapter to the book "Cosmic Gamma-Ray Sources," to be published by Kluwer ASSL Series, Edited by K. S. Cheng and G. E. Romero. More details can be found at http://www.gamma.mpe-garching.mpg.de/~aws/aws.htm

Flavonoid intake and the risk of age-related cataract in China’s Heilongjiang Province

Background/Objectives: Epidemiological evidence suggests that diets rich in flavonoids may reduce the risk of developing age-related cataract (ARC). Flavonoids are widely distributed in foods of plant origin and the objective of this study was to evaluate retrospectively the association between the intakes of the five flavonoid subclasses and the risk of ARC.  Subjects/Methods: A population-based case-control study (249 cases and 66 controls) was carried out in Heilongjiang province, which is located in the Northeast of China, and where intakes and availability of fresh vegetables and fruits can be limited. Dietary data gathered by food-frequency questionnaire (FFQ) were used to calculate flavonoid intake. Adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression.  Results: No linear associations between risk of developing ARC and intakes of total dietary flavonoids, anthocyanidins, flavon-3-ol, flavanone, total flavones or total flavonols were found, but quercetin and isorhamnetin intake was inversely associated with ARC risk (OR 11.78, 95% CI: 1.62-85.84, P<0.05, and OR 6.99, 95% CI:1.12-43.44, P<0.05, quartile 4 vs quartile 1, respectively).  Conclusion: As quercetin is contained in many plant foods and isorhamnetin is only contained in very few foods, we concluded that higher quercetin intake may be an important dietary factor in the reduction of risk of age-related cataract

Primary enucleation for group D retinoblastoma in the era of systemic and targeted chemotherapy: the price of retaining an eye

BACKGROUND: Chemotherapy is increasingly used as primary treatment for group D retinoblastoma, whereas primary enucleation is considered to have a diminishing role. This study aimed to compare the management course, including number of examinations under anaesthesia (EUAs), of group D patients treated by enucleation versus chemotherapy. METHODS: A retrospective analysis of 92 group D patients, of which 40 (37 unilateral) underwent primary enucleation and 52 (17 unilateral) were treated with intravenous chemotherapy. Number of EUAs was compared between the treatment groups with respect to the whole cohort, using univariate and multivariate analysis, and to unilateral cases only. RESULTS: Patients were followed up for a median of 61 months (mean: 66, range: 14-156), in which time primary enucleated patients had on average seven EUAs and chemotherapy-treated patients 21 EUAs (p<0.001). Chemotherapy, young age, bilateral disease, multifocal tumours, familial and germline retinoblastoma were found on univariate analysis to correlate with increased number of EUAs (p≤0.019). On multivariate analysis, however, only treatment type and presentation age were found significant (p≤0.001). On subanalysis of the unilateral cases, patients undergoing primary enucleation had in average seven EUAs, as compared with 16 in the chemotherapy group (p<0.001). Of the 55 unilateral-presenting patients, a new tumour developed in the fellow eye only in a single familial case. CONCLUSION: Group D patients' families should be counselled regarding the significant difference in number of EUAs following primary enucleation versus chemotherapy when deciding on a treatment strategy. In this regard, primary enucleation would be most beneficial for older patients with unilateral disease

Generating reversible circuits from higher-order functional programs

Boolean reversible circuits are boolean circuits made of reversible elementary gates. Despite their constrained form, they can simulate any boolean function. The synthesis and validation of a reversible circuit simulating a given function is a difficult problem. In 1973, Bennett proposed to generate reversible circuits from traces of execution of Turing machines. In this paper, we propose a novel presentation of this approach, adapted to higher-order programs. Starting with a PCF-like language, we use a monadic representation of the trace of execution to turn a regular boolean program into a circuit-generating code. We show that a circuit traced out of a program computes the same boolean function as the original program. This technique has been successfully applied to generate large oracles with the quantum programming language Quipper.Comment: 21 pages. A shorter preprint has been accepted for publication in the Proceedings of Reversible Computation 2016. The final publication is available at http://link.springer.co

Picosecond time-resolved resonance Raman observation of the iso-CH2Cl-I and iso-CH2I-Cl photoproducts from the "photoisomerization" reactions of CH 2ICl in the solution phase

A preliminary pecosecond Stokes time-resolved resonance Raman investigation was made of the initial formation and subsequent decay of the photoproduct produced following 267 nm excitaiton of CH 2ClI in acetonitrile solution. A coparision was made between density-functional theroy computations for portable photoproduct species and the results from a femtosecond transient absorption study to Raman spectra. This comparision indicated that the iso-CH 2ClI was aminly produced and associated with the 460 nm transient absorption band.published_or_final_versio