Treedepth Parameterized by Vertex Cover Number

To solve hard graph problems from the parameterized perspective, structural parameters have commonly been used. In particular, vertex cover number is frequently used in this context. In this paper, we study the problem of computing the treedepth of a given graph G. We show that there are an O(tau(G)^3) vertex kernel and an O(4^{tau(G)}*tau(G)*n) time fixed-parameter algorithm for this problem, where tau(G) is the size of a minimum vertex cover of G and n is the number of vertices of G

An Improved Fixed-Parameter Algorithm for One-Page Crossing Minimization

Book embedding is one of the most well-known graph drawing models and is extensively studied in the literature. The special case where the number of pages is one is of particular interest: an embedding in this case has a natural circular representation useful for visualization and graphs that can be embedded in one page without crossings form an important graph class, namely that of outerplanar graphs. In this paper, we consider the problem of minimizing the number of crossings in a one-page book embedding, which we call one-page crossing minimization. Here, we are given a graph G with n vertices together with a non-negative integer k and are asked whether G can be embedded into a single page with at most k crossings. Bannister and Eppstein (GD 2014) showed that this problem is fixed-parameter tractable. Their algorithm is derived through the application of Courcelle\u27s theorem (on graph properties definable in the monadic second-order logic of graphs) and runs in f(L)n time, where L = 2^{O(k^2)} is the length of the formula defining the property that the one-page crossing number is at most k and f is a computable function without any known upper bound expressible as an elementary function. We give an explicit dynamic programming algorithm with a drastically improved running time of 2^{O(k log k)}n

Recombinant gamma T305A fibrinogen indicates severely impaired fibrin polymerization due to the aberrant function of hole 'a' and calcium binding sites

Introduction: We examined a 6-month-old girl with inherited fibrinogen abnormality and no history of bleeding or thrombosis. Routine coagulation screening tests showed a markedly low level of plasma fibrinogen determined by functional measurement and also a low level by antigenic measurement (functional/antigenic ratio = 0.295), suggesting hypodysfibrinogenemia. Materials and methods: DNA sequence analysis was performed, and gamma T305A fibrinogen was synthesized in Chinese hamster ovary cells based on the results. We then functionally analyzed and compared with that of nearby recombinant gamma N308K fibrinogen. Results: DNA sequence analysis revealed a heterozygous gamma T305A substitution (mature protein residue number). The gamma T305A fibrinogen indicated markedly impaired thrombin-catalyzed fibrin polymerization both in the presence or absence of 1 mM calcium ion compared with that of gamma N308K fibrinogen. Protection of plasmin degradation in the presence of calcium ion or Gly-Pro-Arg-Pro peptide (analogue for so-called knob 'A') and factor XIIIa-catalyzed fibrinogen crosslinking demonstrated that the calcium binding sites, hole 'a' and D:D interaction sites were all markedly impaired, whereas gamma N308K was impaired at the latter two sites. Molecular modeling demonstrated that gamma T305 is localized at a shorter distance than gamma N308 from the high affinity calcium binding site and hole 'a'. Conclusion: Our findings suggest that gamma T305 might be important for construction of the overall structure of the. module of fibrinogen. Substitution of gamma T305A leads to both dysfibrinogenemic and hypofibrinogenemic characterization, namely hypodysfibrinogenemia. We have already reported that recombinant gamma T305A fibrinogen was synthesized normally and secreted slightly, but was significantly reduced.ArticleTHROMBOSIS RESEARCH. 134(2):518-525 (2014)journal articl

gamma 375W fibrinogen-synthesizing CHO cells indicate the accumulation of variant fibrinogen within endoplasmic reticulum

Background: Hepatic endoplasmic reticulum (ER) storage disease (HERSD) associated with hypofibrinogenemia has been reported in patients with four types of heterozygous gamma-chain variant fibrinogen in the C terminal region. Of interest, substitution of gamma R375W induced hypofibrinogenemia and HERSD, whereas gamma R375G induced dysfibrinogenemia. Objectives: To analyze the synthesis of variant fibrinogen and morphological characteristics, we established variant fibrinogen-producing cells and compared them with wild-type fibrinogen-synthesizing cells. Methods: The fibrinogen gamma-chain expression vectors coding gamma 375W and gamma 375G were altered by oligonucleotide-directed mutagenesis and transfected into Chinese hamster ovary (CHO) cells. Synthesis of fibrinogen (media and cell lysates) was measured by ELISA for each cloned cell line and morphological characteristics were observed by immunofluorescence and transmission electron microscopy. Results: The medium/cell lysate fibrinogen ratio of gamma 375W-CHO cells was markedly lower than that of the normal cells and gamma 375G-CHO cells. Immunostaining with anti-fibrinogen antibody showed only gamma 375W-CHO cells, but revealed two types of cells containing cytoplasmic inclusion bodies, scattered large-granular bodies and fibrous forms. Observation by confocal microscopy indicated that both inclusion bodies were colocalized with fibrinogen and ER-membrane protein; furthermore, transmission electron microscopic observation demonstrated dilatation of the ER by large-granular inclusion bodies and fibrous forms filled with regularly structured fibular materials within the dilated ER. Conclusion: These results demonstrated that assembled and non-secreted gamma 375W fibrinogen was accumulated in the dilated ER and aggregated variant fibrinogen was seen as regularly structured fibular materials, which was similar to the fingerprint-like pattern observed at inclusion bodies in patients' hepatocytes affected with HERSD.ArticleTHROMBOSIS RESEARCH. 133(1):101-107 (2014)journal articl

Validation of oral fluid samples to monitor serological changes to Plasmodium falciparum: An observational study in southern Zambia

<p>Abstract</p> <p>Background</p> <p>In formerly endemic areas where malaria transmission has declined, levels of population immunity to <it>Plasmodium falciparum </it>provide information on continued malaria transmission and potentially susceptible populations. Traditional techniques for measuring serological responses to <it>P. falciparum </it>antigens use plasma or dried blood spots (DBS). These invasive procedures pose a biohazard and may be unacceptable to communities if performed frequently. The use of oral fluid (OF) samples to detect antibodies to <it>P. falciparum </it>antigens may be a more acceptable strategy to monitor changes in population immunity.</p> <p>Methods</p> <p>An enzyme immunoassay was optimized to detect antibodies to whole, asexual stage <it>P. falciparum </it>antigens. Optical density (OD) values from paired DBS and OF samples collected as part of a community-based survey of malaria parasitaemia were compared.</p> <p>Results</p> <p>Oral fluid and dried blood spot samples were collected from 53 participants in Southern Province, Zambia. Their ages ranged from 1 to 80 years and 45% were female. A statistically significant correlation (r = 0.79; P < 0.01) was observed between OD values from OF and DBS samples. The OF assay identified all DBS-confirmed positive and negative samples, resulting in 100% sensitivity and specificity.</p> <p>Conclusions</p> <p>Oral fluid is a valid alternative specimen for monitoring changes in antibodies to <it>P. falciparum </it>antigens. As OF collection is often more acceptable to communities, poses less of a biohazard than blood samples and can be performed by community volunteers, serological surveys using OF samples provide a strategy for monitoring population immunity in regions of declining malaria transmission.</p

Changing individual-level risk factors for malaria with declining transmission in southern Zambia: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Malaria elimination will require that both symptomatic- and asymptomatic-infected persons be identified and treated. However, well-characterized, individual-level risk factors for malaria may not be valid in regions with declining malaria transmission. Changes in individual-level correlates of malaria infection were evaluated over three years in a region of declining malaria transmission in southern Zambia.</p> <p>Methods</p> <p>Malaria surveys were conducted in two study areas within the catchment area of Macha Hospital, Zambia in 2007 and 2008/2009. A random sample of households was identified from a digitized satellite image of the study areas. Cross-sectional surveys were conducted approximately five times throughout the year in each of the two study areas. During study visits, adults and caretakers of children were administered questionnaires and a blood sample was obtained for a rapid diagnostic test (RDT) for malaria.</p> <p>Results</p> <p>In the 2007 study area, 330 individuals were surveyed. 40.9% of participants lived in a household with at least one insecticide-treated bed net (ITN); however, only 45.2% reported sleeping under the ITN. 23.9% of participants were RDT positive. Correlates of RDT positivity included younger age, the presence of symptoms, testing during the rainy season, using an open water source, and not sleeping under an ITN. In the 2008 study area, 435 individuals were surveyed. 77.0% of participants lived in a household with at least one ITN; however, only 56.4% reported sleeping under the ITN. 8.1% of participants were RDT positive. RDT positivity was negatively correlated with the presence of symptoms within the last two weeks but positively correlated with documented fever. In 2009, 716 individuals were surveyed in the same area as 2008. 63.7% of participants lived in a household with at least one ITN; however, only 57.7% reported sleeping under the ITN. 1.5% of participants were RDT positive. Only self-reported fever was significantly correlated with RDT positivity.</p> <p>Conclusions</p> <p>With declining malaria prevalence, few individual-level characteristics were correlated with RDT positivity. This lack of correlation with individual characteristics hampers identification of individuals infected with malaria. Strategies based on ecological or environmental risk factors may be needed to target control efforts and achieve further reductions and elimination.</p

Comparison of a PfHRP2-Based Rapid Diagnostic Test and Pcr for Malaria in a Low Prevalence Setting in Rural Southern Zambia: Implications for Elimination

Background: Rapid diagnostic tests (RDTs) detecting histidine-rich protein 2 (PfHRP2) antigen are used to identify individuals with Plasmodium falciparum infection even in low transmission settings seeking to achieve elimination. However, these RDTs lack sensitivity to detect low-density infections, produce false negatives for P. falciparum strains lacking pfhrp2 gene and do not detect species other than P. falciparum. Methods: Results of a PfHRP2-based RDT and Plasmodium nested PCR were compared in a region of declining malaria transmission in southern Zambia using samples from community-based, cross-sectional surveys from 2008 to 2012. Participants were tested with a PfHRP2-based RDT and a finger prick blood sample was spotted onto filter paper for PCR analysis and used to prepare blood smears for microscopy. Species-specific, real-time, quantitative PCR (q-PCR) was performed on samples that tested positive either by microscopy, RDT or nested PCR. Results: Of 3,292 total participants enrolled, 12 (0.4%) tested positive by microscopy and 42 (1.3%) by RDT. Of 3,213 (98%) samples tested by nested PCR, 57 (1.8%) were positive, resulting in 87 participants positive by at least one of the three tests. Of these, 61 tested positive for P. falciparum by q-PCR with copy numbers ≤ 2 × 103 copies/μL, 5 were positive for both P. falciparum and Plasmodium malariae and 2 were positive for P. malariae alone. RDT detected 32 (53%) of P. falciparum positives, failing to detect three of the dual infections with P. malariae. Among 2,975 participants enrolled during a low transmission period between 2009 and 2012, sensitivity of the PfHRP2-based RDT compared to nested PCR was only 17%, with specificity of \u3e99%. The pfhrp gene was detected in 80% of P. falciparum positives; however, comparison of copy number between RDT negative and RDT positive samples suggested that RDT negatives resulted from low parasitaemia and not pfhrp2 gene deletion. Conclusions: Low-density P. falciparum infections not identified by currently used PfHRP2-based RDTs and the inability to detect non-falciparum malaria will hinder progress to further reduce malaria in low transmission settings of Zambia. More sensitive and specific diagnostic tests will likely be necessary to identify parasite reservoirs and achieve malaria elimination