Abstract: The present invention relates to nucleic acid sequences that encode hepatitis C viruses (HCV) that are useful in the fundamental research of HCV as well as in the search of a vaccine against HCV. In particular the present invention relates to nucleic acid sequences that comprises HCVs which are capable of expressing said virus when transfected into cells and are capable of infectivity in vivo.

Abstract: The present invention relates to methods for obtaining a whole virus vaccine candidate stock. The present invention also relates to an inactivated whole virus vaccine candidate stock that can be used for vaccination purposes as well as development of novel high titer virus, which is the preferred virus for this technique.

Abstract: The present invention relates to hepatitis C virus (HCV) culture systems of genotypes 1a, 3a, 4a, 5a, and 6a that directly contribute to HCV drug and vaccine development, to HCV basic research and better-individualized treatment of HCV infected patients.

Abstract: The present invention relates to nucleic acid sequences that encode hepatitis C viruses (HCV) of genotype 2b that are useful in the fundamental research of HCV as well as in the search of a vaccine against HCV. In particular the present invention relates to nucleic acid sequences that comprises HCVs, which are capable of expressing said virus when transfected into cells and are capable of infectivity in vivo.

Abstract: The present invention relates to molecular approaches to the production of nucleic acid sequences, which comprises the genome of infectious hepatitis C virus. In particular, the invention provides nucleic acid sequences which comprise the genomes of infectious hepatitis C viruses of either genotype 3a (strain S52) or genotype 4a (strain ED43). The invention therefore relates to the use of the nucleic acid sequences and polypeptides encoded by all or part of the sequences in the development of vaccines and diagnostic assays for HCV and in the development of screening assays for the identification of antiviral agents for HCV. The invention therefore also relates to the use of viral particles derived from laboratory animals infected with S52 and ED43 viruses.

Abstract: The present disclosure relates to ascoliosis monopiece plate, to fit tightly on the back of a user, comprising a lower section and an upper section, wherein the upper section is rounded in the sagittal plane, such that the plate is configured to force the thoracic spine of the user to bend forward in the sagittal plane. The disclosure furthermore relates to a method for manufacturing a scoliosis monopiece plate, to fit tightly on the back of a user, comprising a lower section and an upper section, wherein the upper section is rounded in the sagittal plane, such that the plate is configured to force the thoracic spine of the user to bend forward in the sagittal plane and a method for reducing risk and/or treating spinal deformities, such as scoliosis, of a patient by applying pressure to the thoracic spine of the patient, such that the thoracic spine of the patient is bent forward in the sagittal plane.

Abstract: The present invention relates to molecular approaches to the production of nucleic acid sequences, which comprises the genome of infectious hepatitis C virus. In particular, the invention provides nucleic acid sequences which comprise the genomes of infectious hepatitis C viruses of either genotype 3a (strain S52) or genotype 4a (strain ED43). The invention therefore relates to the use of the nucleic acid sequences and polypeptides encoded by all or part of the sequences in the development of vaccines and diagnostic assays for HCV and in the development of screening assays for the identification of antiviral agents for HCV. The invention therefore also relates to the use of viral particles derived from laboratory animals infected with S52 and ED43 viruses.

Abstract: The invention concerns a marker for low-grade inflammation and metabolic syndrome (MS) and MS-related diseases and/or low-grade inflammation-related diseases such as cardiovascular disease, ischemic heart disease and type 2 diabetes. More particularly it concerns the measurement of the concentration of soluble urokinase plasminogen activator receptor (suPAR) in human biological fluids (sputum, cystic fluid, ascites, serum, plasma, urine) as a tool of diagnosing and/or prognosticating low-grade inflammation and metabolic syndrome and the risk of development of the related diseases such as cancer, cardiovascular disease, ischemic heart disease and type 2 diabetes.

Abstract: The present inventors developed hepatitis C virus recombinants expressing NS5A from genotype 1a, 1b, 2a, 3a, 4a, 5a, 6a or 7a in the context of a genotype 2a backbone. Additional recombinants express NS5A and the structural proteins (Core, E1 and E2), p7 and NS2 from genotype 1a, 1b, 3a, 4a, 5a, 6a or 7a in the genotype 2a backbone. Sequence analysis of the recombinants recovered after viral passage in Huh7.5 cells revealed adaptive mutations in NS5A and/or NS3. The importance of these mutations for improved growth kinetics was shown in reverse genetic studies.

Abstract: The present invention relates to nucleic acid sequences that encode hepatitis C viruses (HCV) that are useful in the fundamental research of HCV as well as in the search of a vaccine against HCV. In particular the present invention relates to nucleic acid sequences that comprises HCVs which are capable of expressing said virus when transfected into cells and are capable of infectivity in vivo.

Abstract: The present invention relates to molecular approaches to the production of nucleic acid sequences, which comprises the genome of infectious hepatitis C virus. In particular, invention provides nucleic acid sequences which comprise the genomes of infectious hepatitis C viruses of either genotype 3a (strain S52) or genotype 4a (strain ED43). The invention therefore relates to the use of the nucleic acid sequences and polypeptides encoded by all or part of the sequences in the development of vaccines and diagnostic assays for HCV and in the development of screening assays for the identification of antiviral agents for HCV. The invention therefore also relates to the use of viral particles derived from laboratory animals infected with S52 and ED43 viruses.

Abstract: A robust and genetically stable cell culture system for Hepatitis C Virus (HCV) genotype 3a is provided. A genotype 3a/2a (S52/JFH1) recombinant containing the structural genes (Core, E1, E2), p7 and NS2 of strain S52 was constructed and characterized in Huh7.5 cells. S52/JFH1 and J6/JFH viruses passaged in cell culture had comparable growth kinetics and yielded similar peak HCV RNA titers and infectivity titers. Direct genome sequencing of cell culture derived S52/JFH1 viruses identified putative adaptive mutations in Core, E2, p7, NS3, and NS5A; clonal analysis revealed that all genomes analyzed exhibited different combinations of these mutations. Finally, viruses resulting from transfection with RNA transcripts of five S52/JFH1 recombinants containing these combinations of putative adaptive mutations performed as efficiently as J6/JFH viruses in Huh7.5 cells and were all genetically stable after viral passage.

Abstract: The present inventors used the previously developed H77/JFH 1T27OOC,A4O8OT (1a/2a), J4/JFH 1T2996C,A4827T,?HVRI (1b/2a), J6/JFH 1?HVRI (2a/2a), J8/JFH 1?HVRI (2b/2a), S52/JFH 1T27i8G,?7i6oc (3a/2a), SA13/JFH 1C34O5G,A3696G (5a/2a) and HK6a/JFH 1T1389c,A1590G (6a/2a) constructs for the deletion of Hypervariable Region 1 (HVR1) to construct viable, JFH 1 (genotype 2a) based, genomes. The present inventors serially passaged the viruses in cell culture obtaining relatively high HCV RNA titers and infectivity titers. Sequence analysis of the viruses identified mutations adapting H77/JFH 1T27OOC,A4O8OT,?HVR1 (1a/2a), J8/JFH 1?HVR1 (2b/2a), S52/JFH 1T2718G,T716OC,?HVR1 (3a/2a) and J4/JFH 1T2996C,A4827T,?HVR1 (1b/2a) to the HVR1 deletion.

Abstract: The invention concerns a marker for low-grade inflammation and metabolic syndrome (MS) and MS-related diseases and/or low-grade inflammation-related diseases such as cardiovasculardisease, ischemic heart disease and type 2 diabetes. More particularly it concerns the measurement of the concentration of soluble urokinase plasminogen activator receptor (suPAR) in human biological fluids (sputum, cystic fluid, ascites, serum, plasma, urine) as a tool of diagnosing and/or prognosticating low-grade inflammation and metabolic syndrome and the risk of development of the related diseases such as cancer, cardiovascular disease, ischemic heart disease and type 2 diabetes.

Abstract: Hepatitis C reporter viruses containing Core through NS2 of prototype isolates of all major HCV genotypes and the remaining genes of isolate JFH1, by insertion of reporter genes in domain III of HCV NS5A were developed. A deletion upstream of the inserted reporter gene sequence conferred favorable growth kinetics in Huh7.5 cells to these viruses. These reporter viruses can be used for high throughput analysis of drug and vaccine candidates as well as patient samples. JFH1-based intergenotypic recombinants with genotype specific homotypic 5?UTR, or heterotypic 5?UTR (either of genotype 1a (strain H77) or of genotype 3a (strain S52)) were also developed. The present inventors additionally developed J6/JFH1 recombinants with the 5?UTR of genotypes 1-6. These recombinants with different 5?UTRs are a useful to study the function of the 5?UTR in a genotype specific manner.

Abstract: The present invention relates to methods of diagnosing the presence of a non-specific disease or disorder in a subject, wherein a determined level of YKL-40 above a reference level indicates the presence of a non-specific disease or disorder. The subject may suffer from a variety of diseases or disorders. The reference level may be a reference level obtained from healthy individuals or it may be a previous measurement obtained from the same subject. The present invention furthermore relates to a method for classifying the severity of a non-specific disease or disorder in a subject, wherein a determined level of YKL-40 above or below one or more reference levels gives the severity of said non-specific disease or disorder. The present invention further relates to a kit and a device that may be used in the method of the present invention comprising means for measuring the level of YKL-40 in a sample; and means for comparing the measured level of YKL-40 with at least one reference level of YKL-40.

Abstract: The present invention relates to a method that enables simpler, easier and more accurate determination cell mediated immune (CMI) responses using the biomarker IP-10 together with a simple and safe “dried blood spot” filter paper method of storing and shipping samples. The method is useful for the diagnosis and prognostication of diseases and conditions that can be diagnosed and prognosticated by measuring correlates of IP-10.

Abstract: The present inventors developed hepatitis C virus 2b/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 2b reference strain J8. Sequence analysis of recovered 2b/2a recombinants from 2 transfection experiments revealed that 2b/2a was genetically stable. Conclusion: The developed 2b/2a viruses provide a robust in vitro tool for research in HCV genotype 2b, including vaccine studies and functional analysis.

Abstract: The present inventors developed 5a/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and all of or part of NS2 were replaced by the corresponding genes of the genotype 5a reference strain SA13. Compared to the J6/JFH control virus, after transfection of in vitro transcripts in Huh7.5 cells, production of infectious viruses was delayed. However, in subsequent viral passages efficient spread of infection and HCV RNA titers as high as for J6/JFH were obtained. Infectivity titers were at all time points analyzed comparable to J6/JFH control virus. Sequence analysis of recovered 5a/2a recombinants from 2 serial passages and subsequent reverse genetic studies revealed adaptive mutations in p7, NS2 and/or NS3. Infectivity of the 5a/2a viruses was CD81 and SR-BI dependant, and the recombinant viruses could be neutralized by chronic phase sera from patients infected with genotype 5a.

Abstract: The present invention relates to gastrointestinal cancers and methods for selecting a treatment for said gastrointestinal cancer in a subject. The present invention further relates to a methods of diagnosing the presence of and/or classifying the severity of a gastrointestinal cancer; together with methods for determining the effect of a therapy administered and/or the prognosis for a subject suffering from a gastrointestinal cancer, before, during or after administering the treatment. For all the methods applies that a determined level of YKL-40 above one or more reference levels indicates the treatment, the severity of the disease, the effect of the treatment and/or the prognosis of the subject. The reference level is typically a level obtained from healthy individuals or a level previously obtained from the same subject. The subject may suffer from any one or more gastrointestinal cancers, such as upper gastrointestinal cancers, and metastatic colorectal cancer.