An efficient pseudomedian filter for tiling microrrays

<p>Abstract</p> <p>Background</p> <p>Tiling microarrays are becoming an essential technology in the functional genomics toolbox. They have been applied to the tasks of novel transcript identification, elucidation of transcription factor binding sites, detection of methylated DNA and several other applications in several model organisms. These experiments are being conducted at increasingly finer resolutions as the microarray technology enjoys increasingly greater feature densities. The increased densities naturally lead to increased data analysis requirements. Specifically, the most widely employed algorithm for tiling array analysis involves smoothing observed signals by computing pseudomedians within sliding windows, a <it>O</it>(<it>n</it>²log<it>n</it>) calculation in each window. This poor time complexity is an issue for tiling array analysis and could prove to be a real bottleneck as tiling microarray experiments become grander in scope and finer in resolution.</p> <p>Results</p> <p>We therefore implemented Monahan's HLQEST algorithm that reduces the runtime complexity for computing the pseudomedian of <it>n </it>numbers to <it>O</it>(<it>n</it>log<it>n</it>) from <it>O</it>(<it>n</it>²log<it>n</it>). For a representative tiling microarray dataset, this modification reduced the smoothing procedure's runtime by nearly 90%. We then leveraged the fact that elements within sliding windows remain largely unchanged in overlapping windows (as one slides across genomic space) to further reduce computation by an additional 43%. This was achieved by the application of skip lists to maintaining a sorted list of values from window to window. This sorted list could be maintained with simple <it>O</it>(log <it>n</it>) inserts and deletes. We illustrate the favorable scaling properties of our algorithms with both time complexity analysis and benchmarking on synthetic datasets.</p> <p>Conclusion</p> <p>Tiling microarray analyses that rely upon a sliding window pseudomedian calculation can require many hours of computation. We have eased this requirement significantly by implementing efficient algorithms that scale well with genomic feature density. This result not only speeds the current standard analyses, but also makes possible ones where many iterations of the filter may be required, such as might be required in a bootstrap or parameter estimation setting. Source code and executables are available at <url>http://tiling.gersteinlab.org/pseudomedian/</url>.</p

Material Strength Effect in the Shock Compression of Alumina

The Hugoniot elastic limits (HEL) of a high-density aluminum oxide ceramic (Lucalox) and a slightly lower-density ceramic (porosity approximately 4%) were determined to be 112±13 and 83±5 kbar, respectively. Above the HEL, the shock-stress-volume Hugoniot curves for both materials are offset by 40 kbar or more above their hydrostatic-pressure-volume curves. These results indicate that shear stresses with magnitudes of about 30–40 kbar persist in aluminum oxide to shock-pressure levels of at least 300 kbar

Synthesis, Electrochemistry, and Excited-State Properties of Three Ru(II) Quaterpyridine Complexes

The complexes [Ru(qpy)LL′]2+ (qpy = 2,2′:6′,2″:6″,2‴-quaterpyridine), with 1: L = acetonitrile, L′= chloride; 2: L = L′= acetonitrile; and 3: L = L′= vinylpyridine, have been prepared from [Ru(qpy) (Cl)2]. Their absorption spectra in CH3CN exhibit broad metal-to-ligand charge transfer (MLCT) absorptions arising from overlapping 1A1 → 1MLCT transitions. Photoluminescence is not observed at room temperature, but all three are weakly emissive in 4:1 ethanol/methanol glasses at 77 K with broad, featureless emissions observed between 600 and 1000 nm consistent with MLCT phosphorescence. Cyclic voltammograms in CH3CN reveal the expected RuIII/II redox couples. In 0.1 M trifluoroacetic acid (TFA), 1 and 2 undergo aquation to give [RuII(qpy)(OH2)2]2+, as evidenced by the appearance of waves for the couples [RuIII(qpy)(OH2)2]3+/[RuII(qpy)(OH2)2]2+, [RuIV(qpy)(O)(OH2)]2+/[RuIII(qpy)(OH2)2]3+, and [RuVI(qpy)(O)2]2+/[RuIV(qpy)(O)(OH2)]2+ in cyclic voltammograms

Prescription Drug Retail Sales in the Mountain West

This fact sheet synthesizes data on prescription drug retail sales in the Mountain West (Arizona, Colorado, Nevada, New Mexico, and Utah). Retail Sales for Prescription Drugs Filled at Pharmacies by Payer, a 2019 report by the Kaiser Family Foundation, includes data on the amount of retail sales for prescription drugs made in each state by dollar amount, along with the method of coverage, including commercial, Medicare, Medicaid and cash payment

A Phase-Field Model of Spiral Dendritic Growth

Domains of condensed-phase monolayers of chiral molecules exhibit a variety of interesting nonequilibrium structures when formed via pressurization. To model these domain patterns, we add a complex field describing the tilt degree of freedom to an (anisotropic) complex-phase-field solidification model. The resulting formalism allows for the inclusion of (in general, non-reflection symmetric) interactions between the tilt, the solid-liquid interface, and the bond orientation. Simulations demonstrate the ability of the model to exhibit spiral dendritic growth.Comment: text plus Four postscript figure file

Shorter Exposures to Harder X-Rays Trigger Early Apoptotic Events in Xenopus laevis Embryos

A long-standing conventional view of radiation-induced apoptosis is that increased exposure results in augmented apoptosis in a biological system, with a threshold below which radiation doses do not cause any significant increase in cell death. The consequences of this belief impact the extent to which malignant diseases and non-malignant conditions are therapeutically treated and how radiation is used in combination with other therapies. Our research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new parallel paradigm to the photoelectric effect in biological systems. embryo. Three different experimental scenarios were analyzed and morphological and biochemical hallmarks of apoptosis were evaluated. Initially, we examined cell death events in embryos exposed to increasing incident energies when the exposure time was preset. Then, we evaluated the embryo's response when the exposure time was augmented while the energy value remained constant. Lastly, we studied the incidence of apoptosis in embryos exposed to an equal total dose of radiation that resulted from increasing the incoming energy while lowering the exposure time. absorbed dose of radiation, the response is significantly increased when shorter bursts of more energetic photons are used. These results suggest that biological organisms display properties similar to the photoelectric effect in physical systems and provide new insights into how radiation-mediated apoptosis should be understood and utilized for therapeutic purposes

Use of anti-retroviral therapy in tuberculosis patients on second-line anti-TB regimens: a systematic review

Introduction: Use of antiretroviral therapy (ART) during treatment of drug susceptible tuberculosis (TB) improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB. Methods: We included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events. Results: Ten observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR) 3.4, 95% CI 1.6–7.4) and decreased likelihood of death (HR 0.4, 95% CI 0.3–0.6) during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm3 and less than 50 cells/mm3, and when correcting for drug resistance pattern. Limitations: We identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias. Discussion: While there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB

Male obesity associated gonadal dysfunction and the role of bariatric surgery

Obesity is an ever growing pandemic and a prevalent problem among men of reproductive age that can both cause and exacerbate male-factor infertility by means of endocrine abnormalities, associated comorbidities, and direct effects on the precision and throughput of spermatogenesis. Robust epidemiologic, clinical, genetic, epigenetic, and preclinical data support these findings. Clinical studies on the impact of medically induced weight loss on serum testosterone concentrations and spermatogenesis is promising but may show differential and unsustainable results. In contrast, literature has demonstrated that weight loss after bariatric surgery is correlated with an increase in serum testosterone concentrations that is superior than that obtained with only lifestyle modifications, supporting a further metabolic benefit from surgery that may be specific to the male reproductive system. The data on sperm and semen parameters is controversial to date. Emerging evidence in the burgeoning field of genetics and epigenetics has demonstrated that paternal obesity can affect offspring metabolic and reproductive phenotypes by means of epigenetic reprogramming of spermatogonial stem cells. Understanding the impact of this reprogramming is critical to a comprehensive view of the impact of obesity on subsequent generations. Furthermore, conveying the potential impact of these lifestyle changes on future progeny can serve as a powerful tool for obese men to modify their behavior. Healthcare professionals treating male infertility and obesity need to adapt their practice to assimilate these new findings to better counsel men about the importance of paternal preconception health and the impact of novel non-medical therapeutic interventions. Herein, we summarize the pathophysiology of obesity on the male reproductive system and emerging evidence regarding the potential role of bariatric surgery as treatment of male obesity-associated gonadal dysfunction