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Book ; Online: Exploring the Tidal Response to Bathymetry Evolution and Present-Day Sea Level Rise in a Channel-Shoal Environment

Lepper, Robert / Jänicke, Leon / Hache, Ingo / Jordan, Christian / Kösters, Frank

eISSN:

2024

Abstract: Intertidal flats and salt marshes in channel-shoal environments are at severe risk from drowning under sea level rise (SLR) ultimately ceasing their function in coastal defense. Earlier studies indicated that these environments can be resilient against ... ...

Abstract	Intertidal flats and salt marshes in channel-shoal environments are at severe risk from drowning under sea level rise (SLR) ultimately ceasing their function in coastal defense. Earlier studies indicated that these environments can be resilient against moderate SLR as their mean height is believed to correlate with tidal amplitude and mean sea level. Recent morphological analyses in the German Wadden Sea on the Northwestern European Shelf contradicted this assumption as mean tidal flat accretion surpassed relative SLR; indicating that nonlinear feedback between SLR, coastal morphodynamics, and tidal dynamics played a role. We explored this relationship in the German Wadden Sea’s channel-shoal environment by revisiting the sensitivity of tidal dynamics to observed SLR and coastal bathymetry evolution over one nodal cycle (1997 to 2015) with a numerical model. We found a proportional response of tidal high and low water to SLR when the bathymetry was kept constant. In contrast, coastal bathymetry evolution caused a spatially-varying hydrodynamic reaction with both increases and decreases of tidal characteristic patterns within few kilometers. An explorative assessment of potential mechanisms suggested that energy dissipation declined near the coast which we related to decreasing tidal prism and declining tidal energy import. Our study stresses the fact that an accurate representation of coastal morphology in hind- and nowcasts and ensembles for bathymetry evolution to assess the impact of SLR are needed when using numerical models.
Subject code	551
Language	English
Publishing date	2024-02-02
Publishing country	de
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Process intensification strategies toward cell culture-based high-yield production of a fusogenic oncolytic virus.

Göbel, Sven / Jaén, Karim E / Dorn, Marie / Neumeyer, Victoria / Jordan, Ingo / Sandig, Volker / Reichl, Udo / Altomonte, Jennifer / Genzel, Yvonne

Biotechnology and bioengineering

2023 Volume 120, Issue 9, Page(s) 2639–2657

Abstract: We present a proof-of-concept study for production of a recombinant vesicular stomatitis virus (rVSV)-based fusogenic oncolytic virus (OV), rVSV-Newcastle disease virus (NDV), at high cell densities (HCD). Based on comprehensive experiments in 1 L ... ...

Abstract	We present a proof-of-concept study for production of a recombinant vesicular stomatitis virus (rVSV)-based fusogenic oncolytic virus (OV), rVSV-Newcastle disease virus (NDV), at high cell densities (HCD). Based on comprehensive experiments in 1 L stirred tank reactors (STRs) in batch mode, first optimization studies at HCD were carried out in semi-perfusion in small-scale cultivations using shake flasks. Further, a perfusion process was established using an acoustic settler for cell retention. Growth, production yields, and process-related impurities were evaluated for three candidate cell lines (AGE1.CR, BHK-21, HEK293SF)infected at densities ranging from 15 to 30 × 10
MeSH term(s)	Animals ; Oncolytic Viruses/genetics ; Cell Culture Techniques ; Bioreactors ; Cell Line ; Vesiculovirus/genetics ; Virus Cultivation
Language	English
Publishing date	2023-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	280318-5
ISSN	1097-0290 ; 0006-3592
ISSN (online)	1097-0290
ISSN	0006-3592
DOI	10.1002/bit.28353
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Article ; Online: Development of an efficient veterinary rabies vaccine production process in the avian suspension cell line AGE1.CR.pIX.

Trabelsi, Khaled / Zakour, Meriem Ben / Jordan, Ingo / Sandig, Volker / Rourou, Samia / Kallel, Hela

BMC biotechnology

2022 Volume 22, Issue 1, Page(s) 17

Abstract: Background: Mass vaccination of dogs as important rabies reservoir is proposed to most effectively reduce and eliminate rabies also in humans. However, a minimum coverage of 70% needs to be achieved for control of the disease in zoonotic regions. In ... ...

Abstract	Background: Mass vaccination of dogs as important rabies reservoir is proposed to most effectively reduce and eliminate rabies also in humans. However, a minimum coverage of 70% needs to be achieved for control of the disease in zoonotic regions. In numerous developing countries, dog vaccination rate is still dangerously low because of economic constraints and due to a high turnover in dog populations. Improved vaccine production processes may help to alleviate cost and supply limitations. In this work, we studied and optimized the replication and vaccine potency of PV rabies virus strain in the muscovy-duck derived AGE1.CR and AGE1.CR.pIX suspension cell lines. Results: The BHK-21-adapted PV rabies virus strain replicated efficiently in the avian cell lines without requirement for prior passaging. CR.pIX was previously shown to augment heat shock responses and supported slightly higher infectious titers compared to the parental CR cell line. Both cell lines allowed replication of rabies virus also in absence of recombinant IGF, the only complex component of the chemically defined medium that was developed for the two cell lines. After scale-up from optimization experiments in shake flask to production in 7-l bioreactors peak virus titers of 2.4 × 10 Conclusion: This study demonstrates that a rabies vaccine for animal vaccination can be produced efficiently in the AGE1.CR.pIX suspension cell line in a scalable process in chemically defined medium.
MeSH term(s)	Animals ; Bioreactors ; Cell Line ; Dogs ; Ducks ; Rabies/prevention & control ; Rabies/veterinary ; Rabies Vaccines
Chemical Substances	Rabies Vaccines
Language	English
Publishing date	2022-06-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2052746-9
ISSN	1472-6750 ; 1472-6750
ISSN (online)	1472-6750
ISSN	1472-6750
DOI	10.1186/s12896-022-00747-5
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Article ; Online: Transgene expression knock-down in recombinant Modified Vaccinia virus Ankara vectors improves genetic stability and sustained transgene maintenance across multiple passages.

Neckermann, Patrick / Mohr, Madlen / Billmeier, Martina / Karlas, Alexander / Boilesen, Ditte R / Thirion, Christian / Holst, Peter J / Jordan, Ingo / Sandig, Volker / Asbach, Benedikt / Wagner, Ralf

Frontiers in immunology

2024 Volume 15, Page(s) 1338492

Abstract: Modified vaccinia virus Ankara is a versatile vaccine vector, well suited for transgene delivery, with an excellent safety profile. However, certain transgenes render recombinant MVA (rMVA) genetically unstable, leading to the accumulation of mutated ... ...

Abstract	Modified vaccinia virus Ankara is a versatile vaccine vector, well suited for transgene delivery, with an excellent safety profile. However, certain transgenes render recombinant MVA (rMVA) genetically unstable, leading to the accumulation of mutated rMVA with impaired transgene expression. This represents a major challenge for upscaling and manufacturing of rMVA vaccines. To prevent transgene-mediated negative selection, the continuous avian cell line AGE1.CR pIX (CR pIX) was modified to suppress transgene expression during rMVA generation and amplification. This was achieved by constitutively expressing a tetracycline repressor (TetR) together with a rat-derived shRNA in engineered CR pIX PRO suppressor cells targeting an operator element (tetO) and 3' untranslated sequence motif on a chimeric poxviral promoter and the transgene mRNA, respectively. This cell line was instrumental in generating two rMVA (isolate CR19) expressing a
MeSH term(s)	Rats ; Animals ; Vaccinia virus/genetics ; Vaccines, Synthetic ; CD8-Positive T-Lymphocytes ; Transgenes
Chemical Substances	Vaccines, Synthetic
Language	English
Publishing date	2024-02-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1338492
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Article ; Online: A rapid, high-throughput, viral infectivity assay using automated brightfield microscopy with machine learning.

Dodkins, Rupert / Delaney, John R / Overton, Tess / Scholle, Frank / Frias-De-Diego, Alba / Crisci, Elisa / Huq, Nafisa / Jordan, Ingo / Kimata, Jason T / Findley, Teresa / Goldberg, Ilya G

SLAS technology

2023 Volume 28, Issue 5, Page(s) 324–333

Abstract: Infectivity assays are essential for the development of viral vaccines, antiviral therapies, and the manufacture of biologicals. Traditionally, these assays take 2-7 days and require several manual processing steps after infection. We describe an ... ...

Abstract	Infectivity assays are essential for the development of viral vaccines, antiviral therapies, and the manufacture of biologicals. Traditionally, these assays take 2-7 days and require several manual processing steps after infection. We describe an automated viral infectivity assay (AVIA
Language	English
Publishing date	2023-07-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2900310-6
ISSN	2472-6311 ; 2472-6303
ISSN (online)	2472-6311
ISSN	2472-6303
DOI	10.1016/j.slast.2023.07.003
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Article ; Online: Development of an efficient veterinary rabies vaccine production process in the avian suspension cell line AGE1.CR.pIX

Trabelsi, Khaled / Zakour, Meriem Ben / Jordan, Ingo / Sandig, Volker / Rourou, Samia / Kallel, Hela

BMC Biotechnol. 2022 Dec., v. 22, no. 1 p.17-17

2022

Abstract: BACKGROUND: Mass vaccination of dogs as important rabies reservoir is proposed to most effectively reduce and eliminate rabies also in humans. However, a minimum coverage of 70% needs to be achieved for control of the disease in zoonotic regions. In ... ...

Abstract	BACKGROUND: Mass vaccination of dogs as important rabies reservoir is proposed to most effectively reduce and eliminate rabies also in humans. However, a minimum coverage of 70% needs to be achieved for control of the disease in zoonotic regions. In numerous developing countries, dog vaccination rate is still dangerously low because of economic constraints and due to a high turnover in dog populations. Improved vaccine production processes may help to alleviate cost and supply limitations. In this work, we studied and optimized the replication and vaccine potency of PV rabies virus strain in the muscovy-duck derived AGE1.CR and AGE1.CR.pIX suspension cell lines. RESULTS: The BHK-21-adapted PV rabies virus strain replicated efficiently in the avian cell lines without requirement for prior passaging. CR.pIX was previously shown to augment heat shock responses and supported slightly higher infectious titers compared to the parental CR cell line. Both cell lines allowed replication of rabies virus also in absence of recombinant IGF, the only complex component of the chemically defined medium that was developed for the two cell lines. After scale-up from optimization experiments in shake flask to production in 7-l bioreactors peak virus titers of 2.4 × 10⁸ FFU/ml were obtained. The potency of inactivated rabies virus harvest according to the NIH test was 3.5 IU/ml. Perfusion with the chemically defined medium during the virus replication phase improved the potency of the vaccine twofold, and increased the number of doses 9.6 fold. CONCLUSION: This study demonstrates that a rabies vaccine for animal vaccination can be produced efficiently in the AGE1.CR.pIX suspension cell line in a scalable process in chemically defined medium.
Keywords	Rabies lyssavirus ; bioreactors ; birds ; cell lines ; culture flasks ; dogs ; heat stress ; rabies ; vaccination ; vaccines ; virus replication ; viruses
Language	English
Dates of publication	2022-12
Size	p. 17.
Publishing place	BioMed Central
Document type	Article ; Online
ZDB-ID	2052746-9
ISSN	1472-6750
ISSN	1472-6750
DOI	10.1186/s12896-022-00747-5
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Article ; Online: Cell-line screening and process development for a fusogenic oncolytic virus in small-scale suspension cultures.

Göbel, Sven / Kortum, Fabian / Chavez, Karim Jaén / Jordan, Ingo / Sandig, Volker / Reichl, Udo / Altomonte, Jennifer / Genzel, Yvonne

Applied microbiology and biotechnology

2022 Volume 106, Issue 13-16, Page(s) 4945–4961

Abstract: Oncolytic viruses (OVs) represent a novel class of immunotherapeutics under development for the treatment of cancers. OVs that express a cognate or transgenic fusion protein is particularly promising as their enhanced intratumoral spread via syncytia ... ...

Abstract	Oncolytic viruses (OVs) represent a novel class of immunotherapeutics under development for the treatment of cancers. OVs that express a cognate or transgenic fusion protein is particularly promising as their enhanced intratumoral spread via syncytia formation can be a potent mechanism for tumor lysis and induction of antitumor immune responses. Rapid and efficient fusion of infected cells results in cell death before high titers are reached. Although this is an attractive safety feature, it also presents unique challenges for large-scale clinical-grade manufacture of OVs. Here we evaluate the use of four different suspension cell lines for the production of a novel fusogenic hybrid of vesicular stomatitis virus and Newcastle disease virus (rVSV-NDV). The candidate cell lines were screened for growth, metabolism, and virus productivity. Permissivity was evaluated based on extracellular infectious virus titers and cell-specific virus yields (CSVYs). For additional process optimizations, virus adaptation and multiplicity of infection (MOI) screenings were performed and confirmed in a 1 L bioreactor. BHK-21 and HEK293SF cells infected at concentrations of 2 × 10
MeSH term(s)	Animals ; Cell Line ; Neoplasms ; Newcastle disease virus/genetics ; Oncolytic Virotherapy ; Oncolytic Viruses/genetics ; Virus Cultivation/methods ; Virus Replication
Language	English
Publishing date	2022-06-29
Publishing country	Germany
Document type	Journal Article
ZDB-ID	392453-1
ISSN	1432-0614 ; 0171-1741 ; 0175-7598
ISSN (online)	1432-0614
ISSN	0171-1741 ; 0175-7598
DOI	10.1007/s00253-022-12027-5
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Article ; Online: mRNA as novel technology for passive immunotherapy.

Schlake, Thomas / Thess, Andreas / Thran, Moritz / Jordan, Ingo

Cellular and molecular life sciences : CMLS

2018 Volume 76, Issue 2, Page(s) 301–328

Abstract: While active immunization elicits a lasting immune response by the body, passive immunotherapy transiently equips the body with exogenously generated immunological effectors in the form of either target-specific antibodies or lymphocytes functionalized ... ...

Abstract	While active immunization elicits a lasting immune response by the body, passive immunotherapy transiently equips the body with exogenously generated immunological effectors in the form of either target-specific antibodies or lymphocytes functionalized with target-specific receptors. In either case, administration or expression of recombinant proteins plays a fundamental role. mRNA prepared by in vitro transcription (IVT) is increasingly appreciated as a drug substance for delivery of recombinant proteins. With its biological role as transient carrier of genetic information translated into protein in the cytoplasm, therapeutic application of mRNA combines several advantages. For example, compared to transfected DNA, mRNA harbors inherent safety features. It is not associated with the risk of inducing genomic changes and potential adverse effects are only temporary due to its transient nature. Compared to the administration of recombinant proteins produced in bioreactors, mRNA allows supplying proteins that are difficult to manufacture and offers extended pharmacokinetics for short-lived proteins. Based on great progress in understanding and manipulating mRNA properties, efficacy data in various models have now demonstrated that IVT mRNA constitutes a potent and flexible platform technology. Starting with an introduction into passive immunotherapy, this review summarizes the current status of IVT mRNA technology and its application to such immunological interventions.
MeSH term(s)	Animals ; Antibodies/genetics ; Antibodies/metabolism ; Genetic Vectors/genetics ; Genetic Vectors/metabolism ; Humans ; Immunization, Passive ; Immunotherapy, Adoptive ; RNA Caps/chemistry ; RNA Caps/genetics ; RNA Caps/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
Chemical Substances	Antibodies ; RNA Caps ; RNA, Messenger
Keywords	covid19
Language	English
Publishing date	2018-10-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-018-2935-4
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Article: Cell-line screening and process development for a fusogenic oncolytic virus in small-scale suspension cultures

Göbel, Sven / Kortum, Fabian / Chavez, Karim Jaén / Jordan, Ingo / Sandig, Volker / Reichl, Udo / Altomonte, Jennifer / Genzel, Yvonne

Applied microbiology and biotechnology. 2022 Aug., v. 106, no. 13-16

2022

Abstract	Oncolytic viruses (OVs) represent a novel class of immunotherapeutics under development for the treatment of cancers. OVs that express a cognate or transgenic fusion protein is particularly promising as their enhanced intratumoral spread via syncytia formation can be a potent mechanism for tumor lysis and induction of antitumor immune responses. Rapid and efficient fusion of infected cells results in cell death before high titers are reached. Although this is an attractive safety feature, it also presents unique challenges for large-scale clinical-grade manufacture of OVs. Here we evaluate the use of four different suspension cell lines for the production of a novel fusogenic hybrid of vesicular stomatitis virus and Newcastle disease virus (rVSV-NDV). The candidate cell lines were screened for growth, metabolism, and virus productivity. Permissivity was evaluated based on extracellular infectious virus titers and cell-specific virus yields (CSVYs). For additional process optimizations, virus adaptation and multiplicity of infection (MOI) screenings were performed and confirmed in a 1 L bioreactor. BHK-21 and HEK293SF cells infected at concentrations of 2 × 10⁶ cells/mL were identified as promising candidates for rVSV-NDV production, leading to infectious titers of 3.0 × 10⁸ TCID₅₀/mL and 7.5 × 10⁷ TCID₅₀/mL, and CSVYs of 153 and 9, respectively. Compared to the AGE1.CR.pIX reference produced in adherent cultures, oncolytic potency was not affected by production in suspension cultures and possibly even increased in cultures of HEK293SF and AGE1.CR.pIX. Our study describes promising suspension cell-based processes for efficient large-scale manufacturing of rVSV-NDV. KEY POINTS: • Cell contact-dependent oncolytic virus (OV) replicates in suspension cells. • Oncolytic potency is not encompassed during suspension cultivation. • Media composition, cell line, and MOI are critical process parameters for OV production. • The designed process is scalable and shows great promise for manufacturing clinical-grade material.
Keywords	Avian orthoavulavirus 1 ; Vesiculovirus ; bioreactors ; cell death ; cell lines ; genetically modified organisms ; giant cells ; hybrids ; immunotherapy ; manufacturing ; metabolism ; neoplasms ; viruses
Language	English
Dates of publication	2022-08
Size	p. 4945-4961.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ZDB-ID	392453-1
ISSN	1432-0614 ; 0171-1741 ; 0175-7598
ISSN (online)	1432-0614
ISSN	0171-1741 ; 0175-7598
DOI	10.1007/s00253-022-12027-5
Database	NAL-Catalogue (AGRICOLA)

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Article: A Deleted Deletion Site in a New Vector Strain and Exceptional Genomic Stability of Plaque-Purified Modified Vaccinia Ankara (MVA)

Jordan, Ingo / Horn, Deborah / Thiele, Kristin / Haag, Lars / Fiddeke, Katharina / Sandig, Volker

Virologica Sinica. 2020 Apr., v. 35, no. 2

2020

Abstract: Vectored vaccines based on highly attenuated modified vaccinia Ankara (MVA) are reported to be immunogenic, tolerant to pre-existing immunity, and able to accommodate and stably maintain very large transgenes. MVA is usually produced on primary chicken ... ...

Abstract	Vectored vaccines based on highly attenuated modified vaccinia Ankara (MVA) are reported to be immunogenic, tolerant to pre-existing immunity, and able to accommodate and stably maintain very large transgenes. MVA is usually produced on primary chicken embryo fibroblasts, but production processes based on continuous cell lines emerge as increasingly robust and cost-effective alternatives. An isolate of a hitherto undescribed genotype was recovered by passage of a non-plaque-purified preparation of MVA in a continuous anatine suspension cell line (CR.pIX) in chemically defined medium. The novel isolate (MVA-CR19) replicated to higher infectious titers in the extracellular volume of suspension cultures and induced fewer syncytia in adherent cultures. We now extend previous studies with the investigation of the point mutations in structural genes of MVA-CR19 and describe an additional point mutation in a regulatory gene. We furthermore map and discuss an extensive rearrangement of the left telomer of MVA-CR19 that appears to have occurred by duplication of the right telomer. This event caused deletions and duplications of genes that may modulate immunologic properties of MVA-CR19 as a vaccine vector. Our characterizations also highlight the exceptional genetic stability of plaque-purified MVA: although the phenotype of MVA-CR19 appears to be advantageous for replication, we found that all genetic markers that differentiate wildtype and MVA-CR19 are stably maintained in passages of recombinant viruses based on either wildtype or MVA-CR.
Keywords	cell lines ; chick embryos ; cost effectiveness ; fibroblasts ; genetic stability ; genomics ; genotype ; giant cells ; immunity ; phenotype ; point mutation ; regulator genes ; transgenes ; vaccines
Language	English
Dates of publication	2020-04
Size	p. 212-226.
Publishing place	Springer Singapore
Document type	Article
ZDB-ID	2425817-9
ISSN	1995-820X ; 1674-0769
ISSN (online)	1995-820X
ISSN	1674-0769
DOI	10.1007/s12250-019-00176-3
Database	NAL-Catalogue (AGRICOLA)

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