Pair HMM based gap statistics for re-evaluation of indels in alignments with affine gap penalties: Extended Version

Although computationally aligning sequence is a crucial step in the vast majority of comparative genomics studies our understanding of alignment biases still needs to be improved. To infer true structural or homologous regions computational alignments need further evaluation. It has been shown that the accuracy of aligned positions can drop substantially in particular around gaps. Here we focus on re-evaluation of score-based alignments with affine gap penalty costs. We exploit their relationships with pair hidden Markov models and develop efficient algorithms by which to identify gaps which are significant in terms of length and multiplicity. We evaluate our statistics with respect to the well-established structural alignments from SABmark and find that indel reliability substantially increases with their significance in particular in worst-case twilight zone alignments. This points out that our statistics can reliably complement other methods which mostly focus on the reliability of match positions.Comment: 17 pages, 7 figure

Extreme bendability of DNA double helix due to bending asymmetry

Experimental data of the DNA cyclization (J-factor) at short length scales, as a way to study the elastic behavior of tightly bent DNA, exceed the theoretical expectation based on the wormlike chain (WLC) model by several orders of magnitude. Here, we propose that asymmetric bending rigidity of the double helix in the groove direction can be responsible for extreme bendability of DNA at short length scales and it also facilitates DNA loop formation at these lengths. To account for the bending asymmetry, we consider the asymmetric elastic rod (AER) model which has been introduced and parametrized in an earlier study (B. Eslami-Mossallam and M. Ejtehadi, Phys. Rev. E 80, 011919 (2009)). Exploiting a coarse grained representation of DNA molecule at base pair (bp) level, and using the Monte Carlo simulation method in combination with the umbrella sampling technique, we calculate the loop formation probability of DNA in the AER model. We show that, for DNA molecule has a larger J-factor compared to the WLC model which is in excellent agreement with recent experimental data.Comment: 8 pages, 9 figure

Anti-allodynic efficacy of NMDA antagonist peptide and noradrenaline alone and in combination in rodent neuropathic pain model

Background: The present experiment was conducted to identify the cooperative effect of serine histogranin (SHG) and noradrenaline in alleviating peripheral neuropathic pain. Methods: Chronic constriction injury of the right sciatic nerve was used to induce chronic neuropathic pain. For drug delivery, a PE10 tube was inserted into the subarachnoid space. Acetone drops and a 44°C water bath were used to evaluate the cold and heat allodynia, respectively. Placing and grasping reflexes were used to assess the locomotor system. Results: SHG at 0.5 and 1 μg significantly (P < 0.05) decreased the thermal allodynia. The cold allodynia was also significantly reduced by intrathecal injections of 0.5 (P < 0.05) and 1 μg (P < 0.001) of SHG. 1 μg of noradrenaline, but not 0.5 μg, significantly alleviated the cold (P < 0.01) and thermal (P < 0.05) allodynia. The ameliorating effect of noradrenaline or SHG disappeared when the two compounds were administrated in equal concentrations. A significant difference (P < 0.01 in the acetone and P < 0.05 in the heat) was observed in the groups under equal doses of the two compounds, with a lower effectiveness of the combination therapy. Conclusions: Our findings suggest that the simultaneous administrations of noradrenaline and SHG do not result in synergistic analgesia, and combination therapy may not be a good approach to the treatment of chronic neuropathic pain syndrome. © The Korean Pain Society, 2015

Numerical Modeling of Bistun Rock Slope Behavior in Grouting Using Discrete Element Method

The discrete element method is an established method for considering discontinuous deformation behavior of joint systems. This paper provides a description of this algorithm used to model coupled hydraulic and mechanical effects of joints on rock mass behavior. The paper also describes Bistun rock slope stability analysis using empirical (SMR) and numerical (D.E.) methods. The behavior of the rock slope and rock blocks containing Bistun epigraph in grouting and groundwater flow has successfully simulated using UDEC (Universal Distinct Element Code) program. Finally, results have been presented and discussed on slope stability condition and grouting pressure

Sparsification of RNA Structure Prediction Including Pseudoknots

Background: Although many RNA molecules contain pseudoknots, computational prediction of pseudoknottedRNA structure is still in its infancy due to high running time and space consumption implied by the dynamicprogramming formulations of the problem.Results: In this paper, we introduce sparsification to significantly speedup the dynamic programming approachesfor pseudoknotted RNA structure prediction, which also lower the space requirements. Although sparsification hasbeen applied to a number of RNA-related structure prediction problems in the past few years, we provide the firstapplication of sparsification to pseudoknotted RNA structure prediction specifically and to handling gappedfragments more generally - which has a much more complex recursive structure than other problems to whichsparsification has been applied. We analyse how to sparsify four pseudoknot structure prediction algorithms,among those the most general method available (the Rivas-Eddy algorithm) and the fastest one (Reeder-Giegerichalgorithm). In all algorithms the number of “candidate” substructures to be considered is reduced.Conclusions: Our experimental results on the sparsified Reeder-Giegerich algorithm suggest a linear speedup overthe unsparsified implementation

Fast prediction of RNA-RNA interaction

<p>Abstract</p> <p>Background</p> <p>Regulatory antisense RNAs are a class of ncRNAs that regulate gene expression by prohibiting the translation of an mRNA by establishing stable interactions with a target sequence. There is great demand for efficient computational methods to predict the specific interaction between an ncRNA and its target mRNA(s). There are a number of algorithms in the literature which can predict a variety of such interactions - unfortunately at a very high computational cost. Although some existing target prediction approaches are much faster, they are specialized for interactions with a single binding site.</p> <p>Methods</p> <p>In this paper we present a novel algorithm to accurately predict the minimum free energy structure of RNA-RNA interaction under the most general type of interactions studied in the literature. Moreover, we introduce a fast heuristic method to predict the specific (multiple) binding sites of two interacting RNAs.</p> <p>Results</p> <p>We verify the performance of our algorithms for joint structure and binding site prediction on a set of known interacting RNA pairs. Experimental results show our algorithms are highly accurate and outperform all competitive approaches.</p

Effects of Cadmium on Rumen Fermentation and Nutrient Digestibility Using Dual Flow Continuous Culture System

This experiment was conducted to investigate the effects of different doses of cadmium on fermentation characterization and nutrient digestibility using dual flow continuous culture system. Eight dual-flow, continuous culture fermenters were used in 2 replicated periods of 10 d (7 d of adaptation and 3 d of sampling). Fermenters were inoculated with a composited ruminal fluid from 3 beef steers fed a high concentrate diet for at least 2 mo before the beginning of the trial. Anaerobic conditions were maintained by the infusion of N2 at a rate of 40 mL/min. Temperature (38.5°C) and liquid (10%/h) and solid (5%/h) dilution rates were kept constant. Fermenters were fed daily with 120 g dry matter in three equal portions. Treatments arranged as complete randomized block design with control and addition three levels of cadmium (0.1, 1 and 10 mg/l) to the high concentrate diet (15:85 forage to concentrate ratio). Organic matter, dry matter, NDF and ADF digestibility significantly decreased with the addition of 1 and 10 mg/l cadmium to the culture media compered to control treatment (P<0.05). Cadmium significantly decreased total volatile fatty acids concentration, acetate proportion and acetate to propionate ratio. Propionate and butyrate proportion increased significantly in response to cadmium addition (P<0.05). Concentration of NH3-N was significantly decreased in 1 and 10 mg/l cadmium treatments compared with control treatment. The results of this study suggest that cadmium in doses of 1 mg/l or more had strong inhibitory effect on mixed rumen microorganisms

Socio-economic inequality and inequity in use of health care services in Kenya: evidence from the fourth Kenya household health expenditure and utilization survey

BACKGROUND: Kenya is experiencing persistently high levels of inequity in health and access to care services. In 2018, decades of sustained policy efforts to promote equitable, affordable and quality health services have culminated in the launch of a universal health coverage scheme, initially piloted in four Kenyan counties and planned for national rollout by 2022. Our study aims to contribute to monitoring and evaluation efforts alongside policy implementation, by establishing a detailed, baseline assessment of socio-economic inequality and inequity in health care utilization in Kenya shortly before the policy launch. METHODS: We use concentration curves and corrected concentration indexes to measure socio-economic inequality in care use and the horizontal inequity index as a measure of inequity in care utilization for three types of care services: outpatient care, inpatient care and preventive and promotive care. Further insights into the individual and household level characteristics that determine observed inequality are derived through decomposition analysis. RESULTS: We find significant inequality and inequity in the use of all types of care services favouring richer population groups, with particularly pronounced levels for preventive and inpatient care services. These are driven primarily by differences in living standards and educational achievement, while the region of residence is a key driver for inequality in preventive care use only. Pro-rich inequalities are particularly pronounced for care provided in privately owned facilities, while public providers serve a much larger share of individuals from lower socio-economic groups. CONCLUSIONS: Through its focus on increasing affordability of care for all Kenyans, the newly launched universal health coverage scheme represents a crucial step towards reducing disparities in health care utilization. However in order to achieve equity in health and access to care such efforts must be paralleled by multi-sectoral approaches to address all key drivers of inequity: persistent poverty, disparities in living standards and educational achievement, as well as regional differences in availability and accessibility of care