1,352 research outputs found

    The Complexity of Drawing Graphs on Few Lines and Few Planes

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    It is well known that any graph admits a crossing-free straight-line drawing in R3\mathbb{R}^3 and that any planar graph admits the same even in R2\mathbb{R}^2. For a graph GG and d{2,3}d \in \{2,3\}, let ρd1(G)\rho^1_d(G) denote the minimum number of lines in Rd\mathbb{R}^d that together can cover all edges of a drawing of GG. For d=2d=2, GG must be planar. We investigate the complexity of computing these parameters and obtain the following hardness and algorithmic results. - For d{2,3}d\in\{2,3\}, we prove that deciding whether ρd1(G)k\rho^1_d(G)\le k for a given graph GG and integer kk is R{\exists\mathbb{R}}-complete. - Since NPR\mathrm{NP}\subseteq{\exists\mathbb{R}}, deciding ρd1(G)k\rho^1_d(G)\le k is NP-hard for d{2,3}d\in\{2,3\}. On the positive side, we show that the problem is fixed-parameter tractable with respect to kk. - Since RPSPACE{\exists\mathbb{R}}\subseteq\mathrm{PSPACE}, both ρ21(G)\rho^1_2(G) and ρ31(G)\rho^1_3(G) are computable in polynomial space. On the negative side, we show that drawings that are optimal with respect to ρ21\rho^1_2 or ρ31\rho^1_3 sometimes require irrational coordinates. - Let ρ32(G)\rho^2_3(G) be the minimum number of planes in R3\mathbb{R}^3 needed to cover a straight-line drawing of a graph GG. We prove that deciding whether ρ32(G)k\rho^2_3(G)\le k is NP-hard for any fixed k2k \ge 2. Hence, the problem is not fixed-parameter tractable with respect to kk unless P=NP\mathrm{P}=\mathrm{NP}

    Crude incidence in two-phase designs in the presence of competing risks.

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    BackgroundIn many studies, some information might not be available for the whole cohort, some covariates, or even the outcome, might be ascertained in selected subsamples. These studies are part of a broad category termed two-phase studies. Common examples include the nested case-control and the case-cohort designs. For two-phase studies, appropriate weighted survival estimates have been derived; however, no estimator of cumulative incidence accounting for competing events has been proposed. This is relevant in the presence of multiple types of events, where estimation of event type specific quantities are needed for evaluating outcome.MethodsWe develop a non parametric estimator of the cumulative incidence function of events accounting for possible competing events. It handles a general sampling design by weights derived from the sampling probabilities. The variance is derived from the influence function of the subdistribution hazard.ResultsThe proposed method shows good performance in simulations. It is applied to estimate the crude incidence of relapse in childhood acute lymphoblastic leukemia in groups defined by a genotype not available for everyone in a cohort of nearly 2000 patients, where death due to toxicity acted as a competing event. In a second example the aim was to estimate engagement in care of a cohort of HIV patients in resource limited setting, where for some patients the outcome itself was missing due to lost to follow-up. A sampling based approach was used to identify outcome in a subsample of lost patients and to obtain a valid estimate of connection to care.ConclusionsA valid estimator for cumulative incidence of events accounting for competing risks under a general sampling design from an infinite target population is derived

    Загадки Велесової книги

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    Дана публікація розкриває помилки попередніх досліджень «Велесової книги» та надає пояснення важкодоступних висловів тексту.Данная публикация раскрывает ошибки предыдущих исследований «Велесовой книги» и дает объяснение труднодоступных выражений в тексте.This publication reveals the mistakes of the former researches on the «Veles-book» and gives the meanings of some hard-to-understand terms of the text

    The study of reproductive outcome and the health of offspring of UK veterans of the Gulf war: methods and description of the study population

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    BACKGROUND: The aim of this study is to determine whether Gulf war veterans and their partners are at increased risk of adverse reproductive events and whether their children have increased risk of serious health problems. Methods and response to the study are reported here. METHODS: This was a retrospective cohort study of reproduction among UK Gulf war veterans, with a comparison cohort of Armed Service personnel who were not deployed to the Gulf. Reproductive history and details of children's health was collected by means of a validated postal questionnaire. A separate study of non-responders was conducted. RESULTS: Questionnaires were returned by a total of 25,084 Gulf war veterans (24,379 men) and 19,003 (18,439 men) subjects in the comparison group. After adjusting for undelivered mail the response rate was 53% for Gulf war veterans and 42% for non-Gulf veterans among men, 72% and 60% among women. Data from the non-responder study suggests that failure to respond to the main survey was largely unrelated to reproduction. 11,155 (46%) male Gulf war veterans and 7,769 (42%) male non-Gulf war veterans had conceived, or attempted to conceive, since the Gulf war. They reported 16442 and 11517 pregnancies respectively in that period. For women, 313 (44%) Gulf veterans and 235 (42%) non-Gulf veterans reported 484 and 377 pregnancies respectively conceived since the Gulf war. CONCLUSIONS: This survey enabled collection of information on a range of reproductive outcomes from veterans of the Gulf war and a suitably matched comparison cohort. Although the response rate for men was disappointing, selection bias related to reproduction does not appear to be strong in these data

    Microscopic annealing process and its impact on superconductivity in T'-structure electron-doped copper oxides

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    High-transition-temperature superconductivity arises in copper oxides when holes or electrons are doped into the CuO2 planes of their insulating parent compounds. While hole-doping quickly induces metallic behavior and superconductivity in many cuprates, electron-doping alone is insufficient in materials such as R2CuO4 (R is Nd, Pr, La, Ce, etc.), where it is necessary to anneal an as-grown sample in a low-oxygen environment to remove a tiny amount of oxygen in order to induce superconductivity. Here we show that the microscopic process of oxygen reduction repairs Cu deficiencies in the as-grown materials and creates oxygen vacancies in the stoichiometric CuO2 planes, effectively reducing disorder and providing itinerant carriers for superconductivity. The resolution of this long-standing materials issue suggests that the fundamental mechanism for superconductivity is the same for electron- and hole-doped copper oxides.Comment: 23 pages, 3 figures, accepted for publication in Nature Material

    Interventions Delivered in Clinical Settings are Effective in Reducing Risk of HIV Transmission Among People Living with HIV: Results from the Health Resources and Services Administration (HRSA)’s Special Projects of National Significance Initiative

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    To support expanded prevention services for people living with HIV, the US Health Resources and Services Administration (HRSA) sponsored a 5-year initiative to test whether interventions delivered in clinical settings were effective in reducing HIV transmission risk among HIV-infected patients. Across 13 demonstration sites, patients were randomized to one of four conditions. All interventions were associated with reduced unprotected vaginal and/or anal intercourse with persons of HIV-uninfected or unknown status among the 3,556 participating patients. Compared to the standard of care, patients assigned to receive interventions from medical care providers reported a significant decrease in risk after 12 months of participation. Patients receiving prevention services from health educators, social workers or paraprofessional HIV-infected peers reported significant reduction in risk at 6 months, but not at 12 months. While clinics have a choice of effective models for implementing prevention programs for their HIV-infected patients, medical provider-delivered methods are comparatively robust

    O-GlcNAc-Specific Antibody CTD110.6 Cross-Reacts with N-GlcNAc2-Modified Proteins Induced under Glucose Deprivation

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    Modification of serine and threonine residues in proteins by O-linked β-N-acetylgulcosamine (O-GlcNAc) glycosylation is a feature of many cellular responses to the nutritional state and to stress. O-GlcNAc modification is reversibly regulated by O-linked β-N-acetylgulcosamine transferase (OGT) and β-D-N-acetylgulcosaminase (O-GlcNAcase). O-GlcNAc modification of proteins is dependent on the concentration of uridine 5′-diphospho-N-acetylgulcosamine (UDP-GlcNAc), which is a substrate of OGT and is synthesized via the hexosamine biosynthetic pathway. Immunoblot analysis using the O-GlcNAc-specific antibody CTD110.6 has indicated that glucose deprivation increases protein O-GlcNAcylation in some cancer cells. The mechanism of this paradoxical phenomenon has remained unclear. Here we show that the increased glycosylation induced by glucose deprivation and detected by CTD110.6 antibodies is actually modification by N-GlcNAc2, rather than by O-GlcNAc. We found that this induced glycosylation was not regulated by OGT and O-GlcNAcase, unlike typical O-GlcNAcylation, and it was inhibited by treatment with tunicamycin, an N-glycosylation inhibitor. Proteomics analysis showed that proteins modified by this induced glycosylation were N-GlcNAc2-modified glycoproteins. Furthermore, CTD110.6 antibodies reacted with N-GlcNAc2-modified glycoproteins produced by a yeast strain with a ts-mutant of ALG1 that could not add a mannose residue to dolichol-PP-GlcNAc2. Our results demonstrated that N-GlcNAc2-modified glycoproteins were induced under glucose deprivation and that they cross-reacted with the O-GlcNAc-specific antibody CTD110.6. We therefore propose that the glycosylation status of proteins previously classified as O-GlcNAc-modified proteins according to their reactivity with CTD110.6 antibodies must be re-examined. We also suggest that the repression of mature N-linked glycoproteins due to increased levels of N-GlcNAc2-modifed proteins is a newly recognized pathway for effective use of sugar under stress and deprivation conditions. Further research is needed to clarify the physiological and pathological roles of N-GlcNAc2-modifed proteins

    Immunobiological effects of gemcitabine and capecitabine combination chemotherapy in advanced pancreatic ductal adenocarcinoma

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    Background: Preclinical studies suggest that chemotherapy may enhance the immune response against pancreatic cancer. Methods: The levels of granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) and the associated inflammatory marker C-reactive protein (CRP) were assessed in 38 patients receiving gemcitabine and capecitabine combination chemotherapy for advanced pancreatic cancer within the TeloVac trial. Apoptosis (M30) and total immune response (delayed-type hypersensitivity and/or T-cell response) were also assessed and levels of apoptosis induction correlated with immune response. The telomerase GV1001 vaccine was given either sequentially (n=18) or concomitantly (n=24) with the combination chemotherapy. Results: There were no differences between baseline and post-treatment levels of CRP (P=0.19), IL-6 (P=0.19) and GM-CSF (P=0.71). There was a positive correlation between post-chemotherapy CRP and IL-6 levels (r=0.45, P=0.005) and between CRP with carbohydrate antigen-19-9 (CA19-9) levels at baseline (r=0.45, P=0.015) and post treatment (r=0.40, P=0.015). The change in CRP and IL-6 levels was positively correlated (r=0.40, P=0.012). Hazard ratios (95% CI) for baseline CA19-9 (1.30 (1.07–1.59), P=0.009) and CRP (1.55 (1.00–2.39), P=0.049) levels were each independently predictive of survival. The M30 mean matched differences between pre- and post-chemotherapy showed evidence of apoptosis in both the sequential (P=0.058) and concurrent (P=0.0018) chemoimmunotherapy arms. Respectively, 5 of 10 and 9 of 20 patients had a positive immune response but there was no association with apoptosis. Conclusions: Combination gemcitabine and capecitabine chemotherapy did not affect circulating levels of GM-CSF, IL-6 and CRP. Chemotherapy-induced apoptosis was not associated with the immunogenicity induced by the GV1001 vaccine in advanced pancreatic cancer

    Contribution of Cell Elongation to the Biofilm Formation of Pseudomonas aeruginosa during Anaerobic Respiration

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    Pseudomonas aeruginosa, a gram-negative bacterium of clinical importance, forms more robust biofilm during anaerobic respiration, a mode of growth presumed to occur in abnormally thickened mucus layer lining the cystic fibrosis (CF) patient airway. However, molecular basis behind this anaerobiosis-triggered robust biofilm formation is not clearly defined yet. Here, we identified a morphological change naturally accompanied by anaerobic respiration in P. aeruginosa and investigated its effect on the biofilm formation in vitro. A standard laboratory strain, PAO1 was highly elongated during anaerobic respiration compared with bacteria grown aerobically. Microscopic analysis demonstrated that cell elongation likely occurred as a consequence of defective cell division. Cell elongation was dependent on the presence of nitrite reductase (NIR) that reduces nitrite (NO2−) to nitric oxide (NO) and was repressed in PAO1 in the presence of carboxy-PTIO, a NO antagonist, demonstrating that cell elongation involves a process to respond to NO, a spontaneous byproduct of the anaerobic respiration. Importantly, the non-elongated NIR-deficient mutant failed to form biofilm, while a mutant of nitrate reductase (NAR) and wild type PAO1, both of which were highly elongated, formed robust biofilm. Taken together, our data reveal a role of previously undescribed cell biological event in P. aeruginosa biofilm formation and suggest NIR as a key player involved in such process
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