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  • Publication . Article . Preprint . 2018
    Open Access English
    Authors: 
    Lu, Xuan; Cao, Yanbin; Chen, Zhenpeng; Liu, Xuanzhe;

    Emoji is becoming a ubiquitous language and gaining worldwide popularity in recent years including the field of software engineering (SE). As nonverbal cues, emojis are widely used in user understanding tasks such as sentiment analysis, but few work has been done to study emojis in SE scenarios. This paper presents a large scale empirical study on how GitHub users use emojis in development-related communications. We find that emojis are used by a considerable proportion of GitHub users. In comparison to Internet users, developers show interesting usage characteristics and have their own interpretation of the meanings of emojis. In addition, the usage of emojis reflects a positive and supportive culture of this community. Through a manual annotation task, we find that sentimental usage is a main intention of using emojis in issues, pull requests, and comments, while emojis are mainly used to emphasize important contents in README. These findings not only deepen our understanding about the culture of SE communities, but also provide implications on how to facilitate SE tasks with emojis such as sentiment analysis.

  • Open Access
    Authors: 
    Ahmad Fauzi Ismail; Mahesh Padaki; Nidal Hilal; Takeshi Matsuura; Woei Jye Lau;
    Publisher: Elsevier BV
    Country: United Kingdom

    This paper provides a review on the recent development of thin film composite (TFC) membrane, which has received increasing attention in the field of water desalination process. The development of new thin films and substrates, and the effect of additives are mostly focused in this review. In particular, nanotechnology has shown its impact on the development of TFC membranes by incorporating nanoparticles and nanofibers in the substrate as well as in the top thin film. The search for novel monomers and novel fabrication methods of thin film, modification of substrate, and optimization of operational conditions is also the topic of this review article. It still remains a challenge to produce high impact TFC membranes with antifouling and biofouling properties, chemical resistance, improved mechanical strength and thermal stability. For this purpose, further insights into the phase inversion and interfacial polymerization processes are necessary. Currently, it seems that there is no end in the near future for the further development of TFC membranes, which will be followed by the expansion of the scope of their applications in various chemical and biochemical industrial sectors.

  • Open Access
    Authors: 
    Carlevaro-Fita J.; Lanzos A.; Feuerbach L.; Hong C.; Mas-Ponte D.; Pedersen J. S.; Abascal F.; Amin S. B.; Bader G. D.; Barenboim J.; +127 more
    Publisher: Springer Science and Business Media LLC
    Countries: Belgium, Switzerland, Italy, Sweden, Denmark, Netherlands, Switzerland, Spain, United Kingdom

    Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis. Communications Biology, 3 (1) ISSN:2399-3642

  • Open Access
    Authors: 
    Hans P. Heinig;
    Publisher: Institute of Mathematics, Czech Academy of Sciences
    Project: NSERC
  • Open Access
    Authors: 
    Yanguang Yu; Jiangtao Xi; Enbang Li; Joe F. Chicharo;
    Publisher: SPIE

    Semiconductor lasers are very different from other lasers because refraction variation can't be avoided when the gain is changed. Refraction variation can be introduced the theory of semiconductor laser by a dimensional parameter. This parameter is called linewidth enhancement factor (LEF). The value of LEF is very important for many aspects of laser behavior. The LEF characterizes the linewidth broadening and chirp due to fluctuation in the carrier density. A simple method to measure the linewidth enhancement factor of laser diodes is presented in this paper. The method uses the self-mixing effect at a weak feedback level. An optical beam is reflected and injected into the laser diode cavity by an external target, and is then mixed with the light inside the cavity, causing variations of the optical output power. The waveform of the optical power is determined by the feedback factor C and the LEF. A theoretical formula to compute LEF is proposed for the case when the feedback level C is smaller than 1. The experimental results show this method is feasible and simple when a laser diode operates at single longitudinal mode.

  • Open Access
    Authors: 
    Elizabeth Bancroft; Elizabeth Page; Elena Castro; Hans Lilja; Andrew J. Vickers; Daniel Sjöberg; Melissa Assel; Christopher S. Foster; Gillian Mitchell; Kate Drew; +105 more
    Publisher: Elsevier BV
    Countries: Denmark, United Kingdom, Netherlands
    Project: NIH | Improving prostate cancer... (5R01CA175491-04), NIH | Prospective validation of... (5R01CA160816-02), NIH | RATIONAL DESIGN OF PROSTA... (5P50CA092629-10)

    Background Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. Objective To report the first year's screening results for all men at enrolment in the study. Design, setting and participants We recruited men aged 40–69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrolment, and those men with PSA >3 ng/ml were offered prostate biopsy. Outcome measurements and statistical analysis PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. Results and limitations We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%—double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups. Conclusions The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease. Patient summary In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment. Take Home Message This report demonstrates that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these higher-risk men resulted in the identification of tumours that were more likely to require treatment.

  • Open Access
    Authors: 
    Dennis, Jessica; Ghadirian, Parviz; Little, Julian; Lubinski, Jan; Gronwald, Jacek; Kim-Sing, Charmaine; Foulkes, William; Moller, Pal; Lynch, Henry T.; Neuhausen, Susan L.; +10 more
    Publisher: Elsevier BV
    Country: Canada

    Alcohol consumption increases the risk of breast cancer among women in the general population, but its effect on women who carry a BRCA gene mutation is unclear. We conducted a case-control study of 1925 matched pairs of predominantly premenopausal women who carry a BRCA1 or a BRCA2 mutation. Information on current alcohol consumption was obtained from a questionnaire administered during the course of genetic counselling or at the time of enrollment. A modest inverse association between breast cancer and reported current alcohol consumption was observed among women with a BRCA1 mutation (OR = 0.82, 95% CI 0.70-0.96), but not among women with a BRCA2 mutation (OR = 1.00; 95% CI 0.71-1.41). Compared to non-drinkers, exclusive consumption of wine was associated with a significant reduction in the risk of breast cancer among BRCA1 carriers (p-trend = 0.01). Alcohol consumption does not appear to increase breast cancer risk in women carrying a BRCA gene mutation.

  • Publication . Article . 2010
    Open Access
    Authors: 
    Rosanna W. Peeling; Harvey Artsob; José L. Pelegrino; Philippe Buchy; Mary Jane Cardosa; Shamala Devi; Delia Enria; Jeremy Farrar; Duane J. Gubler; María G. Guzmán; +9 more

    Dengue is an arthropod-borne flavivirus that comprises four distinct serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) that constitute an antigenic complex of the genus flavivirus, family Flaviviridae. Infection by one serotype induces life-long immunity against reinfection by the same serotype, but only transient and partial protection against infection with the other serotypes1,2. Dengue virus infections can result in a range of clinical manifestations from asymp tomatic infection to dengue fever (DF) and the severe disease dengue haemorrhagic fever/dengue shock syndrome (DHF/ DSS). Most dengue infections are asymptomatic or cause mild symptoms, which are characterized by undifferentiated fever with or without rash. Typical DF is characterized by high fever, severe headache, myalgia, arthralgia, retro-orbital pain and maculopapular rash. Some patients show petechiae, bruising or thrombocytopenia. The clinical presentation of acute dengue infection is non-specific but 5–10% of patients progress to severe DHF/DSS, which can result in death if it is not managed appropriately. Plasma extravasation is the main pathophysiological finding of DHF/ DSS, which differentiates it from DF. DHF/ DSS is characterized by high fever, bleeding, thrombocytopenia and haemoconcentration (an increase in the concentration of blood cells as a result of fluid loss). Approximately 3–4 days after the onset of fever, patients can present with petechiae, rash, epistaxis, and gingival and gastrointestinal bleeding. Pleural effusion and ascites are common. Some patients develop circulatory failure (DSS), presenting with a weak and fast pulse, narrowing of pulse pressure or hypotension, cold and moist skin and altered mental state. Although there are no specific antiviral treatments for dengue infection, patients usually recover when the need for fluid management is identified early and electrolytes are administered3. It has been proposed that the classification of dengue disease should be simplified as severe and non-severe dengue. This simplified classification would make patient management and surveillance easier4. There is a need for specific, inexpensive dengue diagnostic tests that can be used for clinical management, surveillance and outbreak investigations and would permit early intervention to treat patients and prevent or control epidemics. Progress is being made in primary prevention, with several candidate dengue vaccines in late phases of development as well as improved vector control measures. Additionally, new techniques for the early detection of severe disease such as the use of biomarkers have the potential to decrease morbidity and

  • Open Access English
    Authors: 
    Ondřej Kaplan; Jana Zarubova; Barbora Mikulová; Elena Filova; Jiřina Bártová; Lucie Bacakova; Eduard Brynda;
    Publisher: Public Library of Science (PLoS)

    We describe the production of a highly-active mutant VEGF variant, α2-PI1-8-VEGF121, which contains a substrate sequence for factor XIIIa at the aminoterminus designed for incorporation into a fibrin gel. The α2-PI1-8-VEGF121 gene was synthesized, cloned into a pET-32a(+) vector and expressed in Escherichia coli Origami B (DE3) host cells. To increase the protein folding and the solubility, the resulting thioredoxin-α2-PI1-8-VEGF121 fusion protein was co-expressed with recombinant molecular chaperones GroES/EL encoded by independent plasmid pGro7. The fusion protein was purified from the soluble fraction of cytoplasmic proteins using affinity chromatography. After cleavage of the thioredoxin fusion part with thrombin, the target protein was purified by a second round of affinity chromatography. The yield of purified α2-PI1-8-VEGF121 was 1.4 mg per liter of the cell culture. The α2-PI1-8-VEGF121 expressed in this work increased the proliferation of endothelial cells 3.9-8.7 times in comparison with commercially-available recombinant VEGF121. This very high mitogenic activity may be caused by co-expression of the growth factor with molecular chaperones not previously used in VEGF production. At the same time, α2-PI1-8-VEGF121 did not elicit considerable inflammatory activation of human endothelial HUVEC cells and human monocyte-like THP-1 cells.

  • Publication . Article . Other literature type . 2013
    Open Access English
    Authors: 
    Maimoona A. Zariwala; Heon Yung Gee; Małgorzata Kurkowiak; Dalal A. Al-Mutairi; Margaret W. Leigh; Toby W. Hurd; Rim Hjeij; Sharon D. Dell; Moumita Chaki; Gerard W. Dougherty; +48 more
    Countries: Croatia, Germany, France
    Project: NIH | Pathogenesis of PCD Lung ... (5R01HL071798-04), NIH | Genetic Disorder of Mucoc... (5U54HL096458-14), NIH | Identifying all Meckel-li... (1RC4DK090917-01), NIH | Novel genetics, pathobiol... (5R01DK068306-17), WT , NIH | Colorado Clinical and Tra... (3UL1TR000154-05S1)

    Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function. © 2013 The American Society of Human Genetics.

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Include:
The following results are related to Canada. Are you interested to view more results? Visit OpenAIRE - Explore.
12,205 Research products, page 1 of 1,221
  • Publication . Article . Preprint . 2018
    Open Access English
    Authors: 
    Lu, Xuan; Cao, Yanbin; Chen, Zhenpeng; Liu, Xuanzhe;

    Emoji is becoming a ubiquitous language and gaining worldwide popularity in recent years including the field of software engineering (SE). As nonverbal cues, emojis are widely used in user understanding tasks such as sentiment analysis, but few work has been done to study emojis in SE scenarios. This paper presents a large scale empirical study on how GitHub users use emojis in development-related communications. We find that emojis are used by a considerable proportion of GitHub users. In comparison to Internet users, developers show interesting usage characteristics and have their own interpretation of the meanings of emojis. In addition, the usage of emojis reflects a positive and supportive culture of this community. Through a manual annotation task, we find that sentimental usage is a main intention of using emojis in issues, pull requests, and comments, while emojis are mainly used to emphasize important contents in README. These findings not only deepen our understanding about the culture of SE communities, but also provide implications on how to facilitate SE tasks with emojis such as sentiment analysis.

  • Open Access
    Authors: 
    Ahmad Fauzi Ismail; Mahesh Padaki; Nidal Hilal; Takeshi Matsuura; Woei Jye Lau;
    Publisher: Elsevier BV
    Country: United Kingdom

    This paper provides a review on the recent development of thin film composite (TFC) membrane, which has received increasing attention in the field of water desalination process. The development of new thin films and substrates, and the effect of additives are mostly focused in this review. In particular, nanotechnology has shown its impact on the development of TFC membranes by incorporating nanoparticles and nanofibers in the substrate as well as in the top thin film. The search for novel monomers and novel fabrication methods of thin film, modification of substrate, and optimization of operational conditions is also the topic of this review article. It still remains a challenge to produce high impact TFC membranes with antifouling and biofouling properties, chemical resistance, improved mechanical strength and thermal stability. For this purpose, further insights into the phase inversion and interfacial polymerization processes are necessary. Currently, it seems that there is no end in the near future for the further development of TFC membranes, which will be followed by the expansion of the scope of their applications in various chemical and biochemical industrial sectors.

  • Open Access
    Authors: 
    Carlevaro-Fita J.; Lanzos A.; Feuerbach L.; Hong C.; Mas-Ponte D.; Pedersen J. S.; Abascal F.; Amin S. B.; Bader G. D.; Barenboim J.; +127 more
    Publisher: Springer Science and Business Media LLC
    Countries: Belgium, Switzerland, Italy, Sweden, Denmark, Netherlands, Switzerland, Spain, United Kingdom

    Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis. Communications Biology, 3 (1) ISSN:2399-3642

  • Open Access
    Authors: 
    Hans P. Heinig;
    Publisher: Institute of Mathematics, Czech Academy of Sciences
    Project: NSERC
  • Open Access
    Authors: 
    Yanguang Yu; Jiangtao Xi; Enbang Li; Joe F. Chicharo;
    Publisher: SPIE

    Semiconductor lasers are very different from other lasers because refraction variation can't be avoided when the gain is changed. Refraction variation can be introduced the theory of semiconductor laser by a dimensional parameter. This parameter is called linewidth enhancement factor (LEF). The value of LEF is very important for many aspects of laser behavior. The LEF characterizes the linewidth broadening and chirp due to fluctuation in the carrier density. A simple method to measure the linewidth enhancement factor of laser diodes is presented in this paper. The method uses the self-mixing effect at a weak feedback level. An optical beam is reflected and injected into the laser diode cavity by an external target, and is then mixed with the light inside the cavity, causing variations of the optical output power. The waveform of the optical power is determined by the feedback factor C and the LEF. A theoretical formula to compute LEF is proposed for the case when the feedback level C is smaller than 1. The experimental results show this method is feasible and simple when a laser diode operates at single longitudinal mode.

  • Open Access
    Authors: 
    Elizabeth Bancroft; Elizabeth Page; Elena Castro; Hans Lilja; Andrew J. Vickers; Daniel Sjöberg; Melissa Assel; Christopher S. Foster; Gillian Mitchell; Kate Drew; +105 more
    Publisher: Elsevier BV
    Countries: Denmark, United Kingdom, Netherlands
    Project: NIH | Improving prostate cancer... (5R01CA175491-04), NIH | Prospective validation of... (5R01CA160816-02), NIH | RATIONAL DESIGN OF PROSTA... (5P50CA092629-10)

    Background Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. Objective To report the first year's screening results for all men at enrolment in the study. Design, setting and participants We recruited men aged 40–69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrolment, and those men with PSA >3 ng/ml were offered prostate biopsy. Outcome measurements and statistical analysis PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. Results and limitations We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%—double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups. Conclusions The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease. Patient summary In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment. Take Home Message This report demonstrates that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these higher-risk men resulted in the identification of tumours that were more likely to require treatment.

  • Open Access
    Authors: 
    Dennis, Jessica; Ghadirian, Parviz; Little, Julian; Lubinski, Jan; Gronwald, Jacek; Kim-Sing, Charmaine; Foulkes, William; Moller, Pal; Lynch, Henry T.; Neuhausen, Susan L.; +10 more
    Publisher: Elsevier BV
    Country: Canada

    Alcohol consumption increases the risk of breast cancer among women in the general population, but its effect on women who carry a BRCA gene mutation is unclear. We conducted a case-control study of 1925 matched pairs of predominantly premenopausal women who carry a BRCA1 or a BRCA2 mutation. Information on current alcohol consumption was obtained from a questionnaire administered during the course of genetic counselling or at the time of enrollment. A modest inverse association between breast cancer and reported current alcohol consumption was observed among women with a BRCA1 mutation (OR = 0.82, 95% CI 0.70-0.96), but not among women with a BRCA2 mutation (OR = 1.00; 95% CI 0.71-1.41). Compared to non-drinkers, exclusive consumption of wine was associated with a significant reduction in the risk of breast cancer among BRCA1 carriers (p-trend = 0.01). Alcohol consumption does not appear to increase breast cancer risk in women carrying a BRCA gene mutation.

  • Publication . Article . 2010
    Open Access
    Authors: 
    Rosanna W. Peeling; Harvey Artsob; José L. Pelegrino; Philippe Buchy; Mary Jane Cardosa; Shamala Devi; Delia Enria; Jeremy Farrar; Duane J. Gubler; María G. Guzmán; +9 more

    Dengue is an arthropod-borne flavivirus that comprises four distinct serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) that constitute an antigenic complex of the genus flavivirus, family Flaviviridae. Infection by one serotype induces life-long immunity against reinfection by the same serotype, but only transient and partial protection against infection with the other serotypes1,2. Dengue virus infections can result in a range of clinical manifestations from asymp tomatic infection to dengue fever (DF) and the severe disease dengue haemorrhagic fever/dengue shock syndrome (DHF/ DSS). Most dengue infections are asymptomatic or cause mild symptoms, which are characterized by undifferentiated fever with or without rash. Typical DF is characterized by high fever, severe headache, myalgia, arthralgia, retro-orbital pain and maculopapular rash. Some patients show petechiae, bruising or thrombocytopenia. The clinical presentation of acute dengue infection is non-specific but 5–10% of patients progress to severe DHF/DSS, which can result in death if it is not managed appropriately. Plasma extravasation is the main pathophysiological finding of DHF/ DSS, which differentiates it from DF. DHF/ DSS is characterized by high fever, bleeding, thrombocytopenia and haemoconcentration (an increase in the concentration of blood cells as a result of fluid loss). Approximately 3–4 days after the onset of fever, patients can present with petechiae, rash, epistaxis, and gingival and gastrointestinal bleeding. Pleural effusion and ascites are common. Some patients develop circulatory failure (DSS), presenting with a weak and fast pulse, narrowing of pulse pressure or hypotension, cold and moist skin and altered mental state. Although there are no specific antiviral treatments for dengue infection, patients usually recover when the need for fluid management is identified early and electrolytes are administered3. It has been proposed that the classification of dengue disease should be simplified as severe and non-severe dengue. This simplified classification would make patient management and surveillance easier4. There is a need for specific, inexpensive dengue diagnostic tests that can be used for clinical management, surveillance and outbreak investigations and would permit early intervention to treat patients and prevent or control epidemics. Progress is being made in primary prevention, with several candidate dengue vaccines in late phases of development as well as improved vector control measures. Additionally, new techniques for the early detection of severe disease such as the use of biomarkers have the potential to decrease morbidity and

  • Open Access English
    Authors: 
    Ondřej Kaplan; Jana Zarubova; Barbora Mikulová; Elena Filova; Jiřina Bártová; Lucie Bacakova; Eduard Brynda;
    Publisher: Public Library of Science (PLoS)

    We describe the production of a highly-active mutant VEGF variant, α2-PI1-8-VEGF121, which contains a substrate sequence for factor XIIIa at the aminoterminus designed for incorporation into a fibrin gel. The α2-PI1-8-VEGF121 gene was synthesized, cloned into a pET-32a(+) vector and expressed in Escherichia coli Origami B (DE3) host cells. To increase the protein folding and the solubility, the resulting thioredoxin-α2-PI1-8-VEGF121 fusion protein was co-expressed with recombinant molecular chaperones GroES/EL encoded by independent plasmid pGro7. The fusion protein was purified from the soluble fraction of cytoplasmic proteins using affinity chromatography. After cleavage of the thioredoxin fusion part with thrombin, the target protein was purified by a second round of affinity chromatography. The yield of purified α2-PI1-8-VEGF121 was 1.4 mg per liter of the cell culture. The α2-PI1-8-VEGF121 expressed in this work increased the proliferation of endothelial cells 3.9-8.7 times in comparison with commercially-available recombinant VEGF121. This very high mitogenic activity may be caused by co-expression of the growth factor with molecular chaperones not previously used in VEGF production. At the same time, α2-PI1-8-VEGF121 did not elicit considerable inflammatory activation of human endothelial HUVEC cells and human monocyte-like THP-1 cells.

  • Publication . Article . Other literature type . 2013
    Open Access English
    Authors: 
    Maimoona A. Zariwala; Heon Yung Gee; Małgorzata Kurkowiak; Dalal A. Al-Mutairi; Margaret W. Leigh; Toby W. Hurd; Rim Hjeij; Sharon D. Dell; Moumita Chaki; Gerard W. Dougherty; +48 more
    Countries: Croatia, Germany, France
    Project: NIH | Pathogenesis of PCD Lung ... (5R01HL071798-04), NIH | Genetic Disorder of Mucoc... (5U54HL096458-14), NIH | Identifying all Meckel-li... (1RC4DK090917-01), NIH | Novel genetics, pathobiol... (5R01DK068306-17), WT , NIH | Colorado Clinical and Tra... (3UL1TR000154-05S1)

    Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function. © 2013 The American Society of Human Genetics.