Editing to Eulerian Graphs

We investigate the problem of modifying a graph into a connected graph in which the degree of each vertex satisfies a prescribed parity constraint. Let ea, ed and vd denote the operations edge addition, edge deletion and vertex deletion respectively. For any S subseteq {ea,ed,vd}, we define Connected Degree Parity Editing (S) (CDPE(S)) to be the problem that takes as input a graph G, an integer k and a function delta: V(G) -> {0,1}, and asks whether G can be modified into a connected graph H with d_H(v) = delta(v)(mod 2) for each v in V(H), using at most k operations from S. We prove that (*) if S={ea} or S={ea,ed}, then CDPE(S) can be solved in polynomial time; (*) if {vd} subseteq S subseteq {ea,ed,vd}, then CDPE(S) is NP-complete and W-hard when parameterized by k, even if delta = 0. Together with known results by Cai and Yang and by Cygan, Marx, Pilipczuk, Pilipczuk and Schlotter, our results completely classify the classical and parameterized complexity of the CDPE(S) problem for all S subseteq {ea,ed,vd}. We obtain the same classification for a natural variant of the cdpe(S) problem on directed graphs, where the target is a weakly connected digraph in which the difference between the in- and out-degree of every vertex equals a prescribed value. As an important implication of our results, we obtain polynomial-time algorithms for Eulerian Editing problem and its directed variant. To the best of our knowledge, the only other natural non-trivial graph class H for which the H-Editing problem is known to be polynomial-time solvable is the class of split graphs

M1 Resonances in Unstable Magic Nuclei

Within a microscopic approach which takes into account RPA configurations, the single-particle continuum and more complex $1p1h\otimes phonon$ configurations isoscalar and isovector M1 excitations for the unstable nuclei ${56,78}$Ni and ${100,132}$Sn are calculated. For comparison, the experimentally known M1 excitations in ${40}$Ca and $^{208}$Pb have also been calculated. In the latter nuclei good agreement in the centroid energy, the total transition strength and the resonance width is obtained. With the same parameters we predict the magnetic excitations for the unstable nuclei. The strength is sufficiently concentrated to be measurable in radioactive beam experiments. New features are found for the very neutron rich nucleus ${78}$Ni and the neutron deficient nucleus ${100}$Sn.Comment: 17 pages (LATEX), 12 figures (available from the authors), KFA-IKP(TH)-1993-0

Sub-barrier capture with quantum diffusion approach: actinide-based reactions

With the quantum diffusion approach the behavior of capture cross sections and mean-square angular momenta of captured systems are revealed in the reactions with deformed nuclei at subbarrier energies. The calculated results are in a good agreement with existing experimental data. With decreasing bombarding energy under the barrier the external turning point of the nucleusnucleus potential leaves the region of short-range nuclear interaction and action of friction. Because of this change of the regime of interaction, an unexpected enhancement of the capture cross section is expected at bombarding energies far below the Coulomb barrier. This effect is shown its worth in the dependence of mean-square angular momentum of captured system on the bombarding energy. From the comparison of calculated and experimental capture cross sections, the importance of quasifission near the entrance channel is shown for the actinide-based reactions leading to superheavy nuclei.Comment: 11 pages, 16 figures, Regular Articl

Gene expression signatures in motor neurone disease fibroblasts reveal dysregulation of metabolism, hypoxia-response and RNA processing functions

Aims Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are two syndromic variants within the motor neurone disease spectrum. As PLS and most ALS cases are sporadic (SALS), this limits the availability of cellular models for investigating pathogenic mechanisms and therapeutic targets. The aim of this study was to use gene expression profiling to evaluate fibroblasts as cellular models for SALS and PLS, to establish whether dysregulated biological processes recapitulate those seen in the central nervous system and to elucidate pathways that distinguish the clinically defined variants of SALS and PLS. Methods Microarray analysis was performed on fibroblast RNA and differentially expressed genes identified. Genes in enriched biological pathways were validated by quantitative PCR and functional assays performed to establish the effect of altered RNA levels on the cellular processes. Results Gene expression profiling demonstrated that whilst there were many differentially expressed genes in common between SALS and PLS fibroblasts, there were many more expressed specifically in the SALS fibroblasts, including those involved in RNA processing and the stress response. Functional analysis of the fibroblasts confirmed a significant decrease in miRNA production and a reduced response to hypoxia in SALS fibroblasts. Furthermore, metabolic gene changes seen in SALS, many of which were also evident in PLS fibroblasts, resulted in dysfunctional cellular respiration. Conclusions The data demonstrate that fibroblasts can act as cellular models for ALS and PLS, by establishing the transcriptional changes in known pathogenic pathways that confer subsequent functional effects and potentially highlight targets for therapeutic intervention

Alignment of inhaled chronic obstructive pulmonary disease therapies with published strategies :analysis of the Global Initiative for Chronic Obstructive Lung Disease recommendations in SpiroMics

Rationale: Despite awareness of chronic obstructive pulmonary disease (COPD) treatment recommendations, uptake is poor. The Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) spans 2010-2016, providing an opportunity to assess integration of 2011 Global Initiative for Obstructive Lung Disease (GOLD) treatment strategies over time in a large observational cohort study. Objectives: To evaluate how COPD treatment aligns with 2011 GOLD strategies and determine factors associated with failure to align with recommendations. Methods: Information on inhaled medication use collected via questionnaire annually for 4 years was compiled into therapeutic classes (long-acting antimuscarinic agent, long-acting b-agonist, inhaled corticosteroids [ICS], and combinations thereof). Medications were not modified by SPIROMICS investigators. 2011 GOLD COPD categories A, B, C, and D were assigned. Alignment of inhaler regimen with first-/second-line GOLD recommendations was determined, stratifying into recommendation aligned or nonaligned. Recommendation-nonaligned participants were further stratified into overuse and underuse categories. Results: Of 1,721 participants with COPD, at baseline, 52% of regimens aligned with GOLD recommendations. Among participants with nonaligned regimens, 46% reported underuse, predominately owing to lack of long-acting inhalers in GOLD category D. Of the 54% reporting overuse, 95% were treated with nonindicated ICS-containing regimens. Among 431 participants with 4 years of follow-up data, recommendation alignment did not change over time. When we compared 2011 and 2017 recommendations, we found that 47% did not align with either set of recommendations, whereas 35% were in alignment with both recommendations. Conclusions: Among SPIROMICS participants with COPD, nearly 50% reported inhaler regimens that did not align with GOLD recommendations. Nonalignment was driven largely by overuse of ICS regimens in milder disease and lack of long-acting inhalers in severe disease

Associations Among 25-Hydroxyvitamin D Levels, Lung Function, and Exacerbation Outcomes in COPD: An Analysis of the SPIROMICS Cohort

Background: The relationship between 25-hydroxyvitamin D (25-OH-vitamin D) and COPD outcomes remains unclear. Using the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), we determined associations among baseline 25-OH-vitamin D and cross-sectional and longitudinal lung function and COPD exacerbations. Methods: Serum 25-OH-vitamin D level was measured in stored samples from 1,609 SPIROMICS participants with COPD. 25-OH-vitamin D levels were modeled continuously and dichotomized as deficient (< 20 ng/mL) vs not deficient (≥ 20 ng/mL). Outcomes of interest included % predicted FEV1 (current and 1-year longitudinal decline) and COPD exacerbations (separately any and severe, occurring in prior year and first year of follow-up). Results: Vitamin D deficiency was present in 21% of the cohort and was more prevalent in the younger, active smokers, and blacks. Vitamin D deficiency was independently associated with lower % predicted FEV1 (by 4.11%) at enrollment (95% CI, –6.90% to –1.34% predicted FEV1; P =.004), 1.27% predicted greater rate of FEV1 decline after 1 year (95% CI, –2.32% to –0.22% predicted/y; P =.02), and higher odds of any COPD exacerbation in the prior year (OR, 1.32; 95% CI, 1.00-1.74; P =.049). Each 10-ng/mL decrease in 25-OH-vitamin D was associated with lower baseline lung function (–1.04% predicted; 95% CI, –1.96% to –0.12% predicted; P =.03) and increased odds of any exacerbation in the year before enrollment (OR, 1.11; 95% CI, 1.01-1.22; P =.04). Conclusions: Vitamin D deficiency is associated with worse cross-sectional and longitudinal lung function and increased odds of prior COPD exacerbations. These findings identify 25-OH-vitamin D levels as a potentially useful marker of adverse COPD-related outcomes

Aspirin Use and Respiratory Morbidity in COPD: A Propensity Score-Matched Analysis in Subpopulations and Intermediate Outcome Measures in COPD Study

Background: Aspirin use in COPD has been associated with reduced all-cause mortality in meta-regression analysis with few equivocal studies. However, the effect of aspirin on COPD morbidity is unknown. Methods: Self-reported daily aspirin use was obtained at baseline from SPIROMICS participants with COPD (FEV 1 /FVC < 70%). Acute exacerbations of COPD (AECOPD) were prospectively ascertained through quarterly structured telephone questionnaires up to 3 years and categorized as moderate (symptoms treated with antibiotics or oral corticosteroids) or severe (requiring ED visit or hospitalization). Aspirin users were matched one-to-one with nonusers, based on propensity score. The association of aspirin use with total, moderate, and severe AECOPD was investigated using zero-inflated negative binomial models. Linear or logistic regression was used to investigate the association with baseline respiratory symptoms, quality of life, and exercise tolerance. Results: Among 1,698 participants, 45% reported daily aspirin use at baseline. Propensity score matching resulted in 503 participant pairs. Aspirin users had a lower incidence rate of total AECOPD (adjusted incidence rate ratio [IRR], 0.78; 95% CI, 0.65-0.94), with similar effect for moderate but not severe AECOPD (IRR, 0.86; 95% CI, 0.63-1.18). Aspirin use was associated with lower total St. George's Respiratory Questionnaire score (β, –2.2; 95% CI, –4.1 to –0.4), reduced odds of moderate-severe dyspnea (modified Medical Research Council questionnaire score ≥ 2; adjusted odds ratio, 0.69; 95% CI, 0.51-0.93), and COPD Assessment Test score (β, –1.1; 95% CI, –1.9 to –0.2) but not 6-min walk distance (β, 0.7 m; 95% CI, –14.3 to 15.6). Conclusions: Daily aspirin use is associated with reduced rate of COPD exacerbations, less dyspnea, and better quality of life. Randomized clinical trials of aspirin use in COPD are warranted to account for unmeasured and residual confounding. Trial Registry: ClinicalTrials.gov; No.: NCT01969344; URL: www.clinicaltrials.go

Perspective Chapter: Microemulsion as a Game Changer to Conquer Cancer with an Emphasis on Herbal Compounds

Microemulsions are lipid based drug delivery system consisting of oil, water, surfactant and often a co-surfactant. They are prepared in order to deliver the drug in an effective manner so as to obtain the desired therapeutic activity. Compared to other conventional therapy, they can deliver the drug in an efficient manner because of their characteristics like reduced particles size, lipid based drug delivery system, thermodynamic stability and economical scale up. Anti-cancer drugs can be easily incorporated into microemulsion so as to target the cancer cells. This helps in increasing the solubility, permeability and absorption of the poorly soluble and poorly permeable drugs, thereby helping in enhancing the bioavailability of the drug. In this chapter, we are also focusing on the herbal based formulations that will be helpful in effectively fighting against cancer cells with less or no side effects. A light has also been shed on the advantages and disadvantages of the microemulsions that will be helpful in considering them as an effective model to conquer cancer and promote the same in the upcoming years