Genetic analysis of foot-and-mouth disease virus serotype A of Indian origin and detection of positive selection and recombination in leader protease- and capsid-coding regions

The leader protease (L-pro) and capsid-coding sequences (P1) constitute approximately 3 kb of the foot-and-mouth disease virus (FMDV). We studied the phylogenetic relationship of 46 FMDV serotype A isolates of Indian origin collected during the period 1968-2005 and also eight vaccine strains using the neighbour-joining tree and Bayesian tree methods. The viruses were categorized under three major groups - Asian, Euro-South American and European. The Indian isolates formed a distinct genetic group among the Asian isolates. The Indian isolates were further classified into different genetic subgroups (<5% divergence). Post-1995 isolates were divided into two subgroups while a few isolates which originated in the year 2005 from Andhra Pradesh formed a separate group. These isolates were closely related to the isolates of the 1970s. The FMDV isolates seem to undergo reverse mutation or onvergent evolution wherein sequences identical to the ancestors are present in the isolates in circulation. The eight vaccine strains included in the study were not related to each other and belonged to different genetic groups. Recombination was detected in the L-pro region in one isolate (A IND 20/82) and in the VP1 coding 1D region in another isolate (A RAJ 21/96). Positive selection was identified at aa positions 23 in the L-pro (P<0.05; 0.046*) and at aa 171 in the capsid protein VP1 (P<0.01; 0.003**).

Expression of Cytochrome P-450 and Albumin Genes in Rat Liver: Effect of Xenobioticst

Thioacetamide, a hepatocarcinogen and an inhibitor of heme synthesis, blocks the phenobarbitone- mediated increase in the transcription of cytochrome P-450b+e messenger RNA in rat liver. This property is also shared by CoCl, and 3-amino-l,2,4-triazole, two other inhibitors of heme synthesis. Thus, it appears feasible that heme may serve as a positive regulator of cytochrome P-450b+e gene transcription. Thioacetamide enhances albumin messenger RNA concentration, whereas phenobarbitone decreases the same. However, these changes in albumin messenger RNA concentration are not accompanied by corresponding changes in the transcription rates. Therefore, drug-mediated changes in albumin messenger RNA concentration are due to posttranscriptional regulation. The property of thioacetamide to enhance the albumin messenger RNA concentration is not shared by CoC1, and 3-amino- 1,2,4-triazole. Therefore, heme does not appear to be a regulatory molecule mediating the reciprocal changes brought about in the concentrations of cytochrome P-450b+e and albumin messenger RNAs.

Modelling predicts positive and negative interactions between three Australian tropical tree species in monoculture and binary mixture

Computer modelling promises to be an important tool for analysing and predicting interactions between trees within mixed species forest plantations. This study explored the use of an individual-based mechanistic model as a predictive tool for designing mixed species plantations of Australian tropical trees. The `spatially explicit individually based-forest simulator' (SeXI-FS) modelling system was used to describe the spatial interaction of individual tree crowns within a binary mixed-species experiment. The three-dimensional model was developed and verified with field data from three forest tree species grown in tropical Australia. The model predicted the interactions within monocultures and binary mixtures of Flindersia brayleyana, Eucalyptus pellita and Elaeocarpus grandis, accounting for an average of 42% of the growth variation exhibited by species in different treatments. The model requires only structural dimensions and shade tolerance as species parameters. By modelling interactions in existing tree mixtures, the model predicted both increases and reductions in the growth of mixtures (up to +/-50% of stem volume at 7 years) compared to monocultures. This modelling approach may be useful for designing mixed tree plantations.

Speciation of Gram-positive bacteria in fresh and ambient-stored sub-tropical marine fish.

This study identified Gram-positive bacteria in three sub-tropical marine fish species: Pseudocaranx dentex (silver trevally), Pagrus auratus (snapper) and Mugil cephalus (sea mullet). It further elucidated the role played by fish habitat, fish body part and ambient storage on the composition of the Gram-positive bacteria. A total of 266 isolates of Gram-positive bacteria were identified by conventional biochemical methods, VITEK, PCR using genus- and species-specific primers and/or 16S rRNA gene sequencing. The isolates were found to fall into 13 genera and 30 species. In fresh fish, Staphylococcus epidermidis and Micrococcus luteus were the most frequent isolates. After ambient storage, S. epidermidis, S. xylosus and Bacillus megaterium were no longer present whereas S. warned, B. sphaericus, Brevibacillus borstelensis, Enterococcus faecium and Streptococcus uberis increased in frequency. Micrococcus luteus and S. warned were the most prevalent isolates from P. dentex, while E. faecium and Strep. uberis were the most frequent isolates from P. auratus and M. cephalus. With respect to different parts of the fish body. E. faecium, Strep. uberis and B. sphaericus were the most frequent isolates from the muscles, E. faecium, Strep. uberis from the gills and M. luteus from the gut. This study showed a diversity of Gram-positive bacteria in sub-tropical marine fish; however, their abundance was affected by fish habitat, fish body part and ambient storage.

Positive results in a real-time PCR for type A influenza associated with the use of an inactivated vaccine.

A real-time reverse transcription polymerase chain reaction (qRT-PCR) test for the matrix gene of type A influenza viruses was used during the 2007 Australian equine influenza (EI) outbreak in order to confirm diagnosis and, later, eradication of the virus. During the EI outbreak, horses being exported required vaccination and individual proof of freedom from EI. At the end of the outbreak, positive results were obtained from four horses destined for export, because of contamination of the samples with the vaccine. This report highlights the need for EI testing and vaccination to occur on separate days and with the collection of swabs for testing to precede vaccination.

Multiple instance dictionary learning for activity representation

This paper presents an effective feature representation method in the context of activity recognition. Efficient and effective feature representation plays a crucial role not only in activity recognition, but also in a wide range of applications such as motion analysis, tracking, 3D scene understanding etc. In the context of activity recognition, local features are increasingly popular for representing videos because of their simplicity and efficiency. While they achieve state-of-the-art performance with low computational requirements, their performance is still limited for real world applications due to a lack of contextual information and models not being tailored to specific activities. We propose a new activity representation framework to address the shortcomings of the popular, but simple bag-of-words approach. In our framework, first multiple instance SVM (mi-SVM) is used to identify positive features for each action category and the k-means algorithm is used to generate a codebook. Then locality-constrained linear coding is used to encode the features into the generated codebook, followed by spatio-temporal pyramid pooling to convey the spatio-temporal statistics. Finally, an SVM is used to classify the videos. Experiments carried out on two popular datasets with varying complexity demonstrate significant performance improvement over the base-line bag-of-feature method.

Positive associations of serum Perfluoroalkyl substances with uric acid and hyperuricemia in children from Taiwan

To investigate the risk of hyperuricemia in relation to Perfluoroalkyl substances (PFASs) in children from Taiwan, 225 Taiwanese children aged 12-15 years were recruited from 2009 to 2010. Linear and logistic regression models were employed to examine the influence of PFASs on serum uric acid levels. Findings revealed that eight of ten PFASs analyses were detected in > 94% of the participants' serum samples. Multivariate linear regression models revealed that perfluorooctanic acid (PFOA) was positively associated with serum uric acid levels (β=0.1463, p<0.05). Of all the PFASs analyses, only PFOA showed a significant effect on elevated levels of hyperuricemia (aOR=2.16, 95%CI: 1.29-3.61). When stratified by gender, the association between serum PFOA and uric acid levels was only evident among boys (aOR=2.76, 95%CI: 1.37-5.56). In conclusion, PFOA was found to be associated with elevated serum levels of uric acid in Taiwanese children, especially boys. Further research is needed to elucidate these links.

Identification and functional characterization of a cis-acting positive DNA element regulating CYP 2B1/B2 gene transcription in rat liver

A positive cis-acting DNA element in the near 5'-upstream region of the CYP2B1/B2 genes in rat liver was found to play an important role in the transcription of these genes. An oligonucleotide covering -69 to -98 nt mimicked the gel mobility shift pattern given by the fragment -179 to +29 nt, which was earlier found adequate to confer the regulatory features of this gene. Two major complexes were seen, of which the slower and faster moving complexes became intense under uninduced and Phenobarbitone-induced conditions respectively. Minigene cloned DNA plasmid covering -179 to +181 nt in pUC 19 and Bal 31 mutants derived from this parent were transcribed in whole nuclei and cell free transcription extracts and mutants containing only upto -75 nt of the upstream were poorly transcribed. Transcription extracts from phenobarbitone-injected rat liver nuclei were significantly more active than extracts from uninduced rats in transcribing the minigene constructs. Addition of the oligonucleotide (-69 to -98nt) specifically inhibited the transcription of the minigene construct (-179 to +181 nt) in the cell free transcription system. It is therefore, concluded that the region -69 to -98 nt acts as a positive cis-acting element in the transcription of the CYP2B1/B2 genes and in mediating the inductive effects of phenobarbitone.

High P-T granulite relicts from the Imjingang belt, South Korea:Tectonic significance

This study presents a detailed description on crustal metamorphic signatures of garnet-clinopyroxene-quartz-rutile-bearing high P-T granulites, Samgot unit, Imajingang belt, northwestern Korean Peninsula that formed during Permo-Triassic regional metamorphism related to the amalgamation of East Asian continental fragments. Lenses and blocks of high P-T granulites and garnet-bearing leucosomes occur within mafic metamorphic rocks (mainly amphibolites). The mafic blocks comprise relicts of granoblastic garnet and clinopyroxene with medium-grained quartz and rutile. These relict mineral assemblages are confined to local micro-domains and constitute remnants of peak metamorphism. Plagioclase and amphibole form only as retrograde phases in medium ton coarse-grained moats that rim grain boundaries between relict peak mineral assemblages. This microstructure represents the reaction between garnet, clinopyroxene, quartz and rutile in the presence of melt to form amphibole, plagioclase and titanite with minor biotite. The leucosome domains consist of euhedral garnets within the quartz-K feldspar-plagioclase (granitic) matrix, probably representing peritectic garnet growth along with melting. The rare earth element (REE) composition of minerals also support the peritectic garnet growth with a positive Eu/Eu* (positive Eu anomaly), while the relict garnet shows a slight negative anomaly typical for high-grade granulites. The peak-metamorphic conditions calculated from thermodynamic modeling and compositional isopleths indicate a temperature around c. 900 degrees C at a pressure around c. 20 kbar. The present P-T path indicates a clear multi-stage decompression history with initial decompression and cooling followed by a stage of decompression during hydration possibly during Late Triassic exhumation. The results from this study together with the presence of eclogites from the Hongsung area suggest that the Imjingang area and the western Gyeonggi massif likely resided at crustal levels deeper than those of the eastern and southern part of the Gyeonggi massif. (C) 2009 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial

Background The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and gefitinib in this setting. Methods This multicentre, international, open-label, exploratory, randomised controlled phase 2B trial (LUX-Lung 7) was done at 64 centres in 13 countries. Treatment-naive patients with stage IIIB or IV NSCLC and a common EGFR mutation (exon 19 deletion or Leu858Arg) were randomly assigned (1:1) to receive afatinib (40 mg per day) or gefitinib (250 mg per day) until disease progression, or beyond if deemed beneficial by the investigator. Randomisation, stratified by EGFR mutation type and status of brain metastases, was done centrally using a validated number generating system implemented via an interactive voice or web-based response system with a block size of four. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. Coprimary endpoints were progression-free survival by independent central review, time-to-treatment failure, and overall survival. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01466660. Findings Between Dec 13, 2011, and Aug 8, 2013, 319 patients were randomly assigned (160 to afatinib and 159 to gefitinib). Median follow-up was 27·3 months (IQR 15·3–33·9). Progression-free survival (median 11·0 months [95% CI 10·6–12·9] with afatinib vs 10·9 months [9·1–11·5] with gefitinib; hazard ratio [HR] 0·73 [95% CI 0·57–0·95], p=0·017) and time-to-treatment failure (median 13·7 months [95% CI 11·9–15·0] with afatinib vs 11·5 months [10·1–13·1] with gefitinib; HR 0·73 [95% CI 0·58–0·92], p=0·0073) were significantly longer with afatinib than with gefitinib. Overall survival data are not mature. The most common treatment-related grade 3 or 4 adverse events were diarrhoea (20 [13%] of 160 patients given afatinib vs two [1%] of 159 given gefitinib) and rash or acne (15 [9%] patients given afatinib vs five [3%] of those given gefitinib) and liver enzyme elevations (no patients given afatinib vs 14 [9%] of those given gefitinib). Serious treatment-related adverse events occurred in 17 (11%) patients in the afatinib group and seven (4%) in the gefitinib group. Ten (6%) patients in each group discontinued treatment due to drug-related adverse events. 15 (9%) fatal adverse events occurred in the afatinib group and ten (6%) in the gefitinib group. All but one of these deaths were considered unrelated to treatment; one patient in the gefitinib group died from drug-related hepatic and renal failure. Interpretation Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC compared with gefitinib, with a manageable tolerability profile. These data are potentially important for clinical decision making in this patient population.

Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials

Background We aimed to assess the effect of afatinib on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from two open-label, randomised, phase 3 trials. Methods Previously untreated patients with EGFR mutation-positive stage IIIB or IV lung adenocarcinoma were enrolled in LUX-Lung 3 (n=345) and LUX-Lung 6 (n=364). These patients were randomly assigned in a 2:1 ratio to receive afatinib or chemotherapy (pemetrexed-cisplatin [LUX-Lung 3] or gemcitabine-cisplatin [LUX-Lung 6]), stratified by EGFR mutation (exon 19 deletion [del19], Leu858Arg, or other) and ethnic origin (LUX-Lung 3 only). We planned analyses of mature overall survival data in the intention-to-treat population after 209 (LUX-Lung 3) and 237 (LUX-Lung 6) deaths. These ongoing studies are registered with ClinicalTrials.gov, numbers NCT00949650 and NCT01121393. Findings Median follow-up in LUX-Lung 3 was 41 months (IQR 35–44); 213 (62%) of 345 patients had died. Median follow-up in LUX-Lung 6 was 33 months (IQR 31–37); 246 (68%) of 364 patients had died. In LUX-Lung 3, median overall survival was 28·2 months (95% CI 24·6–33·6) in the afatinib group and 28·2 months (20·7–33·2) in the pemetrexed-cisplatin group (HR 0·88, 95% CI 0·66–1·17, p=0·39). In LUX-Lung 6, median overall survival was 23·1 months (95% CI 20·4–27·3) in the afatinib group and 23·5 months (18·0–25·6) in the gemcitabine-cisplatin group (HR 0·93, 95% CI 0·72–1·22, p=0·61). However, in preplanned analyses, overall survival was significantly longer for patients with del19-positive tumours in the afatinib group than in the chemotherapy group in both trials: in LUX-Lung 3, median overall survival was 33·3 months (95% CI 26·8–41·5) in the afatinib group versus 21·1 months (16·3–30·7) in the chemotherapy group (HR 0·54, 95% CI 0·36–0·79, p=0·0015); in LUX-Lung 6, it was 31·4 months (95% CI 24·2–35·3) versus 18·4 months (14·6–25·6), respectively (HR 0·64, 95% CI 0·44–0·94, p=0·023). By contrast, there were no significant differences by treatment group for patients with EGFR Leu858Arg-positive tumours in either trial: in LUX-Lung 3, median overall survival was 27·6 months (19·8–41·7) in the afatinib group versus 40·3 months (24·3–not estimable) in the chemotherapy group (HR 1·30, 95% CI 0·80–2·11, p=0·29); in LUX-Lung 6, it was 19·6 months (95% CI 17·0–22·1) versus 24·3 months (19·0–27·0), respectively (HR 1·22, 95% CI 0·81–1·83, p=0·34). In both trials, the most common afatinib-related grade 3–4 adverse events were rash or acne (37 [16%] of 229 patients in LUX-Lung 3 and 35 [15%] of 239 patients in LUX-Lung 6), diarrhoea (33 [14%] and 13 [5%]), paronychia (26 [11%] in LUX-Lung 3 only), and stomatitis or mucositis (13 [5%] in LUX-Lung 6 only). In LUX-Lung 3, neutropenia (20 [18%] of 111 patients), fatigue (14 [13%]) and leucopenia (nine [8%]) were the most common chemotherapy-related grade 3–4 adverse events, while in LUX-Lung 6, the most common chemotherapy-related grade 3–4 adverse events were neutropenia (30 [27%] of 113 patients), vomiting (22 [19%]), and leucopenia (17 [15%]). Interpretation Although afatinib did not improve overall survival in the whole population of either trial, overall survival was improved with the drug for patients with del19 EGFR mutations. The absence of an effect in patients with Leu858Arg EGFR mutations suggests that EGFR del19-positive disease might be distinct from Leu858Arg-positive disease and that these subgroups should be analysed separately in future trials.

Immigrant Associations in the Metropolitan Area of Finland : Forms of Mobilisation, Participation and Representation

This study examines the role of immigrant associations in the societal and political integration of immigrants into Finnish society. The societal focus is on the ability of immigrant associations to mobilise their ethnic group members to participate in the socio-economic, cultural and political domains of Finnish society and in certain cases even beyond. The political integrative aims are the opportunities of immigrant associations to participate and represent the interests of their ethnic group in local and national policy making. This study focuses on associations in the Metropolitan Area of Finland, (Espoo, Helsinki and Vantaa).The qualitative research consisted of 71 interviews conducted with members of immigrant associations and civil servants. These interviews were mainly semi-structured, including some additional open-ended questions. Additional data consisted of documents, planning reports and of follow-up enquiries. -- In the analysis of the data I categorised thirty-two immigrant associations according to the activity forms and the description of the goals by the members. The four categories consisted of integrative, societal, ethno-cultural and transnational immigrant associations. Most of the immigrant associations belonged to the integrative category (15 of 32 associations). On the one hand the aims of these associations are to provide access for their ethnic group members into Finnish society, while on the other to strengthen the ethnic identity of their members by organising ethno-cultural activities. The societal associations only focused on activities with the objective of including immigrants into the Finnish labour market and educational system. The goal of ethno-cultural associations was to strengthen the ethnic identity of their ethnic group members. The transnational associations aimed at improving the living conditions of women and children in the members' country of origin. The possibilities for immigrant associations to mobilise their members depends partly on external financing. Subsidies have been allocated for societal activities in particular. There remains a risk of the crowding out of ethno-cultural activities: something which has already taken place in several European countries. Immigrant associations aim to strengthen the identity of immigrants mainly by organising social and ethno-cultural activities. Another important target was to provide peer support and therapy courses. Additionally, immigrant women's associations offer assistance to women who have encountered violence by providing counselling and in some cases access to shelter. The data showed that there is an ever growing need to pay heed to the well-being of women, children and elderly immigrants. The participation of immigrant associations in the municipalities' integrative issues takes place mainly through cooperative projects. Until the end of the 1990s there had not been much cooperation. The problem with the projects was that they had mainly been managed by civil servants, whereas members from immigrant associations had remained in a more passive position. Representation of immigrant associations in councils has been fairly weak. Immigrant associations are included in the multicultural councils of Espoo and Vantaa, but only in the planning stages. The municipality of Helsinki does not include immigrant associations due to the large number of organisations which causes problems in finding fair, democratic representation. At the national level, the ‘Advisory Board for Ethnic Relations’ – ETNO didn’t chose its members based on membership of ethnic associations, but based on belongingness to one of the larger language groups spoken by the foreign population in Finland. Since ETNO’s third period (2005-2007), the representatives of immigrant associations and ethnic minority groups have been chosen from proposed candidates. Key words: immigrant associations, integration, mobilisation, participation, representation, the Metropolitan area of Finland, immigrant (women), civil servants

Two-way converter logic for positive and negative binary numbers

This paper describes a hardware implementation of a two-way converter logic by which conversion between numbers from positive to negative binary representation is possible. Index terms: (i) Negative radix, (ii) Positive radix, (iii) Two-way conversion.

Hardness of approximation results for the problem of finding the stopping distance in Tanner graphs

Tanner Graph representation of linear block codes is widely used by iterative decoding algorithms for recovering data transmitted across a noisy communication channel from errors and erasures introduced by the channel. The stopping distance of a Tanner graph T for a binary linear block code C determines the number of erasures correctable using iterative decoding on the Tanner graph T when data is transmitted across a binary erasure channel using the code C. We show that the problem of finding the stopping distance of a Tanner graph is hard to approximate within any positive constant approximation ratio in polynomial time unless P = NP. It is also shown as a consequence that there can be no approximation algorithm for the problem achieving an approximation ratio of 2(log n)(1-epsilon) for any epsilon > 0 unless NP subset of DTIME(n(poly(log n))).

NQR study of complexes between p-dichlorobenzene and some aromatic π acceptors

The charge-transfer complexes of p-dichlorobenzene (PDB) with some aromatic π acceptors such as m-nitrobenzaldehyde (MNB), picric acid (PA), p-nitrobenzoic acid (PNB), and m-dinitrobenzene (MDNB) were prepared by slowly adding the acceptor to the molten donor and then cooling the mass to 15°C. The NQR frequencies of these complexes were measured at room temperature. Contrary to the theoretical prediction, the NQR shift is positive, indicating that the NQR shift in donor-acceptor complexes is indirectly related to the charge-transfer interaction. Bond properties are discussed in terms of frequency shift.