Ultrasonic Sizing of Voids Using Area Functions

We present a simple technique for determining the size of voids by the inversion of backscattered ultrasonic signals using the area function formula. The formulation of this method is based on the Born approximation, which is a weak scattering approximation, but the method works well for voids. The area function has been widely used as a method for determining the position of the flaw centroid to assist implementation of some inversion algorithms. The method has been reported in [6]. Here, we report some further studies, and more experimental results in detail

Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled randomized discontinuation study.

BackgroundCabozantinib, an orally bioavailable inhibitor of tyrosine kinases including MET, AXL, and VEGF receptors, was assessed in patients with hepatocellular carcinoma (HCC) as part of a phase 2 randomized discontinuation trial with nine tumor-type cohorts.Patients and methodsEligible patients had Child-Pugh A liver function and ≤1 prior systemic anticancer regimen, completed ≥4 weeks before study entry. The cabozantinib starting dose was 100 mg daily. After an initial 12-week cabozantinib treatment period, patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 were randomized to cabozantinib or placebo. The primary endpoint of the lead-in stage was objective response rate (ORR) at week 12, and the primary endpoint of the randomized stage was progression-free survival (PFS).ResultsAmong the 41 HCC patients enrolled, the week 12 ORR was 5%, with 2 patients achieving a confirmed partial response (PR). The week 12 disease control rate (PR or SD) was 66% (Asian subgroup: 73%). Of patients with ≥1 post-baseline scan, 78% had tumor regression, with no apparent relationship to prior sorafenib therapy. Alpha-fetoprotein (AFP) response (>50% reduction from baseline) occurred in 9 of the 26 (35%) patients with elevated baseline AFP and ≥1 post-baseline measurement. Twenty-two patients with SD at week 12 were randomized. Median PFS after randomization was 2.5 months with cabozantinib and 1.4 months with placebo, although this difference was not statistically significant. Median PFS and overall survival from Day 1 in all patients were 5.2 and 11.5 months, respectively. The most common grade 3/4 adverse events, regardless of attribution, were diarrhea (20%), hand-foot syndrome (15%), and thrombocytopenia (15%). Dose reductions were utilized in 59% of patients.ConclusionsCabozantinib has clinical activity in HCC patients, including objective tumor responses, disease stabilization, and reductions in AFP. Adverse events were managed with dose reductions.Trial registration numberNCT00940225

Interleukin-6 but not soluble adhesion molecules has short-term prognostic value on mortality in patients with acute ST-segment elevation myocardial infarction

Inflammatory responses represent an important element in all phases of the atherosclerotic process. This recognition has stimulated the evaluation of different inflammatory markers as potential predictors of cardiovascular risk. This study was designed to simultaneously measure serum levels of interleukin- 6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble P-selectin (sP-selectin) in patients with acute ST-segment elevation myocardial infarction (STEMI) and to evaluate their ability to predict short-term prognosis. We recruited 263 consecutive patients admitted to our institute within 6 h of symptoms onset with the diagnosis of first STEMI. Clinical data were recorded and serum admission levels of IL-6, sICAM-1, sVCAM-1 and sPselectin were measured. The patients were then followed prospectively for the occurrence of cardiovascular mortality for 4 weeks. Nineteen (7.2%) patients died during the 4 weeks. The admission levels of IL-6 were significantly higher in patients who died from cardiovascular causes, whereas sICAM-1, sVCAM-1, and sP-selectin were not. Kaplan–Meier plots demonstrated a significant increase in cardiovascular mortality with increasing IL-6 levels (P = 0.0060). Logistic regression analysis revealed that IL-6 was an independent predictor for cardiovascular mortality. The present study indicates that elevated admission level of IL-6 but not soluble adhesion molecules could provide valuable information for short-term risk stratification in patients with STEMI.Key words: Acute ST-segment elevation myocardial infarction, interleukin-6, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble P-selectin, cardiovascular mortality

Accurate reconstruction of insertion-deletion histories by statistical phylogenetics

The Multiple Sequence Alignment (MSA) is a computational abstraction that represents a partial summary either of indel history, or of structural similarity. Taking the former view (indel history), it is possible to use formal automata theory to generalize the phylogenetic likelihood framework for finite substitution models (Dayhoff's probability matrices and Felsenstein's pruning algorithm) to arbitrary-length sequences. In this paper, we report results of a simulation-based benchmark of several methods for reconstruction of indel history. The methods tested include a relatively new algorithm for statistical marginalization of MSAs that sums over a stochastically-sampled ensemble of the most probable evolutionary histories. For mammalian evolutionary parameters on several different trees, the single most likely history sampled by our algorithm appears less biased than histories reconstructed by other MSA methods. The algorithm can also be used for alignment-free inference, where the MSA is explicitly summed out of the analysis. As an illustration of our method, we discuss reconstruction of the evolutionary histories of human protein-coding genes.Comment: 28 pages, 15 figures. arXiv admin note: text overlap with arXiv:1103.434

Quantum gravity effects on statistics and compact star configurations

The thermodynamics of classical and quantum ideal gases based on the Generalized uncertainty principle (GUP) are investigated. At low temperatures, we calculate corrections to the energy and entropy. The equations of state receive small modifications. We study a system comprised of a zero temperature ultra-relativistic Fermi gas. It turns out that at low Fermi energy $\varepsilon_F$, the degenerate pressure and energy are lifted. The Chandrasekhar limit receives a small positive correction. We discuss the applications on configurations of compact stars. As $\varepsilon_F$ increases, the radius, total number of fermions and mass first reach their nonvanishing minima and then diverge. Beyond a critical Fermi energy, the radius of a compact star becomes smaller than the Schwarzschild one. The stability of the configurations is also addressed. We find that beyond another critical value of the Fermi energy, the configurations are stable. At large radius, the increment of the degenerate pressure is accelerated at a rate proportional to the radius.Comment: V2. discussions on the stability of star configurations added, 17 pages, 2 figures, typos corrected, version to appear in JHE

Predicting promoters in phage genomes using machine learning models

The renewed interest in phages as antibacterial agents has led to the exponentially growing number of sequenced phage genomes. Therefore, the development of novel bioinformatics methods to automate and facilitate phage genome annotation is of utmost importance. The most difficult step of phage genome annotation is the identification of promoters. As the existing methods for predicting promoters are not well suited for phages, we used machine learning models for locating promoters in phage genomes. Several models were created, using different algorithms and datasets, which consisted of known phage promoter and non-promoter sequences. All models showed good performance, but the ANN model provided better results for the smaller dataset (92% of accuracy, 89% of precision and 87% of recall) and the SVM model returned better results for the larger dataset (93% of accuracy, 91% of precision and 80% of recall). Both models were applied to the genome of Pseudomonas phage phiPsa17 and were able to identify both types of promoters, host and phage, found in phage genomes.This study was supported by the Portuguese Foundation for Science andTechnology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit and theProject POCI-01-0145-FEDER-029628. This work was also supported by BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fundunder the scope of Norte2020 - Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Developing and applying heterogeneous phylogenetic models with XRate

Modeling sequence evolution on phylogenetic trees is a useful technique in computational biology. Especially powerful are models which take account of the heterogeneous nature of sequence evolution according to the "grammar" of the encoded gene features. However, beyond a modest level of model complexity, manual coding of models becomes prohibitively labor-intensive. We demonstrate, via a set of case studies, the new built-in model-prototyping capabilities of XRate (macros and Scheme extensions). These features allow rapid implementation of phylogenetic models which would have previously been far more labor-intensive. XRate's new capabilities for lineage-specific models, ancestral sequence reconstruction, and improved annotation output are also discussed. XRate's flexible model-specification capabilities and computational efficiency make it well-suited to developing and prototyping phylogenetic grammar models. XRate is available as part of the DART software package: http://biowiki.org/DART .Comment: 34 pages, 3 figures, glossary of XRate model terminolog

Single feature polymorphisms (SFPs) for drought tolerance in pigeonpea (Cajanus spp.)

Single feature polymorphisms (SFPs) are microarray-based molecular markers that are detected by hybridization of DNA or cRNA to oligonucleotide probes. With an objective to identify the potential polymorphic markers for drought tolerance in pigeonpea [Cajanus cajan (L.) Millspaugh], an important legume crop for the semi-arid tropics but deficient in genomic resources, Affymetrix Genome Arrays of soybean (Glycine max), a closely related species of pigeonpea were used on cRNA of six parental genotypes of three mapping populations of pigeonpea segregating for agronomic traits like drought tolerance and pod borer (Helicoverpa armigiera) resistance. By using robustified projection pursuit method on 15 pair-wise comparisons for the six parental genotypes, 5,692 SFPs were identified. Number of SFPs varied from 780 (ICPL 8755 × ICPL 227) to 854 (ICPL 151 × ICPL 87) per parental combination of the mapping populations. Randomly selected 179 SFPs were used for validation by Sanger sequencing and good quality sequence data were obtained for 99 genes of which 75 genes showed sequence polymorphisms. While associating the sequence polymorphisms with SFPs detected, true positives were observed for 52.6% SFPs detected. In terms of parental combinations of the mapping populations, occurrence of true positives was 34.48% for ICPL 151 × ICPL 87, 41.86% for ICPL 8755 × ICPL 227, and 81.58% for ICP 28 × ICPW 94. In addition, a set of 139 candidate genes that may be associated with drought tolerance has been identified based on gene ontology analysis of the homologous pigeonpea genes to the soybean genes that detected SFPs between the parents of the mapping populations segregating for drought tolerance