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Article ; Online: Simulating the relative influence of tire, vehicle and driver factors on forward collision accident rates.

Christ, Daniel

2020 Volume 73, Page(s) 253–262

Abstract: Introduction: There is currently a strong focus within the automotive industry centered on traffic safety, with topics such as distracted driving, accident avoidance technologies, and autonomous vehicles. These papers tend to focus on the possible ... ...

Abstract	Introduction: There is currently a strong focus within the automotive industry centered on traffic safety, with topics such as distracted driving, accident avoidance technologies, and autonomous vehicles. These papers tend to focus on the possible improvements from a single factor. However, there are many factors that are present in each accident, and it is important to understand the influence of each factor on the relative accident risk in order to identify the most effective approaches for improving driver safety. Rear-end accidents tend to be the most common accident type with approximately 1.8 M cases, or 31% of all accidents, in 2012, according to NHTSA. Of the rear-end accident scenarios, approximately 18-23% occur on wet surfaces. Method: A Monte Carlo Forward Collision Simulation models the conditions of a wet rear-end accident and estimates the relative impact of various vehicle collision parameters. The model takes distributions of these parameters as inputs, and outputs a risk of collision relative to a known reference case. The parameters that can be studied include: tire grip level, road grip level, vehicle velocity, following distances, and the presence of vehicle technologies (ABS, FCW & AEB). Distributions of some of these parameters have been improved thanks to Naturalistic Driving Study data from SHRP2. Results: This study shows that these vehicle systems have a large impact on safety and can change the amount of influence attributed to other parameters such as tire grip levels. As the use of automated vehicle systems expands, so will the influence of tire grip performance levels on collision risks. Practical Applications: It is more important than ever for consumers and auto manufacturers to consider tire performance levels. Therefore, the tire industry should continue to focus on wet grip as a key performance related to safety and should strive to continue to improve tire performance.
MeSH term(s)	Accidents, Traffic/classification ; Accidents, Traffic/statistics & numerical data ; Automobiles/statistics & numerical data ; Distracted Driving/psychology ; Distracted Driving/statistics & numerical data ; Humans ; Models, Theoretical ; Risk
Language	English
Publishing date	2020-04-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2015321-1
ISSN	1879-1247 ; 0022-4375
ISSN (online)	1879-1247
ISSN	0022-4375
DOI	10.1016/j.jsr.2020.03.009
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Article ; Online: Antibody-mediated delivery of CRISPR-Cas9 ribonucleoproteins in human cells.

Ubiparipovic, Stephanie / Christ, Daniel / Rouet, Romain

Protein engineering, design & selection : PEDS

2022 Volume 35

Abstract: The CRISPR genome editing technology holds great clinical potential for the treatment of monogenetic disorders such as sickle cell disease. The therapeutic in vivo application of the technology relies on targeted delivery methods of the Cas9 and gRNA ... ...

Abstract	The CRISPR genome editing technology holds great clinical potential for the treatment of monogenetic disorders such as sickle cell disease. The therapeutic in vivo application of the technology relies on targeted delivery methods of the Cas9 and gRNA complex to specific cells or tissues. However, such methods are currently limited to direct organ delivery, preventing clinical application. Here, we show that monoclonal antibodies can be employed to deliver the Cas9/gRNA complex directly into human cells via cell-surface receptors. Using the SpyCatcher/SpyTag system, we conjugated the Fab fragment of the therapeutic antibodies Trastuzumab and Pertuzumab directly to the Cas9 enzyme and observed HER2-specific uptake of the ribonucleoprotein in a human HER2 expressing cell line. Following cellular uptake in the presence of an endosomolytic peptide, modest gene editing was also observed. This finding provides a blueprint for the targeted delivery of the CRISPR technology into specific cells using monoclonal antibodies.
MeSH term(s)	Humans ; CRISPR-Cas Systems ; RNA, Guide, CRISPR-Cas Systems/genetics ; RNA, Guide, CRISPR-Cas Systems/metabolism ; Ribonucleoproteins/genetics ; Ribonucleoproteins/metabolism ; Gene Editing ; Antibodies, Monoclonal/genetics ; Antibodies, Monoclonal/metabolism
Chemical Substances	RNA, Guide, CRISPR-Cas Systems ; Ribonucleoproteins ; Antibodies, Monoclonal
Language	English
Publishing date	2022-10-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1466729-0
ISSN	1741-0134 ; 1741-0126
ISSN (online)	1741-0134
ISSN	1741-0126
DOI	10.1093/protein/gzac011
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Book ; Thesis: Untersuchungen an Streptococcus uberis unter besonderer Berücksichtigung mutmasslicher Pathogenitätsfaktoren

Christ, Diana

1989

Size	155 S. : Ill., graph. Darst.
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Gießen, Univ., Diss., 1989
HBZ-ID	HT003618412
Database	Catalogue ZB MED Nutrition, Environment, Agriculture

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Article ; Online: Efficient Intracellular Delivery of CRISPR-Cas Ribonucleoproteins through Receptor Mediated Endocytosis.

Rouet, Romain / Christ, Daniel

ACS chemical biology

2019 Volume 14, Issue 3, Page(s) 554–561

Abstract: We recently reported a new delivery system harnessing surface receptors for targeted uptake of CRISPR-Cas9 ribonucleoprotein into mammalian cells (Rouet et al., JACS 2018). For this purpose, Cas9 protein was labeled with the small molecule ligand ASGRL, ... ...

Abstract	We recently reported a new delivery system harnessing surface receptors for targeted uptake of CRISPR-Cas9 ribonucleoprotein into mammalian cells (Rouet et al., JACS 2018). For this purpose, Cas9 protein was labeled with the small molecule ligand ASGRL, specific for the asialoglycoprotein receptor, enabling endosomal uptake of the ribonucleoprotein into human cells expressing the receptor. However, detailed mechanistic insights had remained unknown and editing efficiency low. Here we investigate the mechanism of endosomal escape as mediated by the ppTG21 endosomolytic peptide and outline the development of novel Cas9 or Cas12a ribonucleoprotein complexes with increased editing efficiency.
MeSH term(s)	Asialoglycoprotein Receptor/chemistry ; Asialoglycoprotein Receptor/metabolism ; Biological Transport ; CRISPR-Associated Proteins/genetics ; CRISPR-Associated Proteins/metabolism ; CRISPR-Cas Systems/physiology ; Cell Line ; Endocytosis/physiology ; Gene Editing/methods ; Humans ; Oligopeptides/metabolism ; Ribonucleoproteins/metabolism ; Signal Transduction
Chemical Substances	Asialoglycoprotein Receptor ; CRISPR-Associated Proteins ; Oligopeptides ; Ribonucleoproteins
Language	English
Publishing date	2019-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.9b00116
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Article ; Online: Advances in antibody-based therapy in oncology.

Zinn, Sacha / Vazquez-Lombardi, Rodrigo / Zimmermann, Carsten / Sapra, Puja / Jermutus, Lutz / Christ, Daniel

Nature cancer

2023 Volume 4, Issue 2, Page(s) 165–180

Abstract: Monoclonal antibodies are a growing class of targeted cancer therapeutics, characterized by exquisite specificity, long serum half-life, high affinity and immune effector functions. In this review, we outline key advances in the field with a particular ... ...

Abstract	Monoclonal antibodies are a growing class of targeted cancer therapeutics, characterized by exquisite specificity, long serum half-life, high affinity and immune effector functions. In this review, we outline key advances in the field with a particular focus on recent and emerging classes of engineered antibody therapeutic candidates, discuss molecular structure and mechanisms of action and provide updates on clinical development and practice.
MeSH term(s)	Humans ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal/pharmacology ; Neoplasms/drug therapy ; Radioimmunotherapy
Chemical Substances	Antibodies, Monoclonal
Language	English
Publishing date	2023-02-20
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ISSN	2662-1347
ISSN (online)	2662-1347
DOI	10.1038/s43018-023-00516-z
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Article ; Online: Systematic Implementation of Effective Quality Assurance Processes for the Assessment of Radiation Target Volumes in Head and Neck Cancer.

Gogineni, E / Schaefer, D / Ewing, A / Andraos, T / DiCostanzo, D / Weldon, M / Christ, D / Baliga, S / Jhawar, S / Mitchell, D / Grecula, J / Konieczkowski, D J / Palmer, J / Jahraus, T / Dibs, K / Chakravarti, A / Martin, D / Gamez, M E / Blakaj, D

Practical radiation oncology

2024 Volume 14, Issue 3, Page(s) e205–e213

Abstract: Purpose: Significant heterogeneity exists in clinical quality assurance (QA) practices within radiation oncology departments, with most chart rounds lacking prospective peer-reviewed contour evaluation. This has the potential to significantly affect ... ...

Abstract	Purpose: Significant heterogeneity exists in clinical quality assurance (QA) practices within radiation oncology departments, with most chart rounds lacking prospective peer-reviewed contour evaluation. This has the potential to significantly affect patient outcomes, particularly for head and neck cancers (HNC) given the large variance in target volume delineation. With this understanding, we incorporated a prospective systematic peer contour-review process into our workflow for all patients with HNC. This study aims to assess the effectiveness of implementing prospective peer review into practice for our National Cancer Institute Designated Cancer Center and to report factors associated with contour modifications. Methods and materials: Starting in November 2020, our department adopted a systematic QA process with real-time metrics, in which contours for all patients with HNC treated with radiation therapy were prospectively peer reviewed and graded. Contours were graded with green (unnecessary), yellow (minor), or red (major) colors based on the degree of peer-recommended modifications. Contours from November 2020 through September 2021 were included for analysis. Results: Three hundred sixty contours were included. Contour grades were made up of 89.7% green, 8.9% yellow, and 1.4% red grades. Physicians with >12 months of clinical experience were less likely to have contour changes requested than those with <12 months (8.3% vs 40.9%; P < .001). Contour grades were significantly associated with physician case load, with physicians presenting more than the median number of 50 cases having significantly less modifications requested than those presenting <50 (6.7% vs 13.3%; P = .013). Physicians working with a resident or fellow were less likely to have contour changes requested than those without a trainee (5.2% vs 12.6%; P = .039). Frequency of major modification requests significantly decreased over time after adoption of prospective peer contour review, with no red grades occurring >6 months after adoption. Conclusions: This study highlights the importance of prospective peer contour-review implementation into systematic clinical QA processes for HNC. Physician experience proved to be the highest predictor of approved contours. A growth curve was demonstrated, with major modifications declining after prospective contour review implementation. Even within a high-volume academic practice with subspecialist attendings, >10% of patients had contour changes made as a direct result of prospective peer review.
MeSH term(s)	Humans ; Head and Neck Neoplasms/radiotherapy ; Quality Assurance, Health Care/standards ; Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy Planning, Computer-Assisted/standards ; Prospective Studies ; Female ; Radiation Oncology/standards ; Radiation Oncology/methods ; Male
Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2655748-4
ISSN	1879-8519 ; 1879-8500
ISSN (online)	1879-8519
ISSN	1879-8500
DOI	10.1016/j.prro.2023.12.012
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Article ; Online: Crystal structure of duck egg lysozyme isoform II (DEL-II).

Langley, David B / Christ, Daniel

BMC structural biology

2018 Volume 18, Issue 1, Page(s) 10

Abstract: Background: Lysozyme purified from duck eggs (DEL) has long been used as a model antigen as a counterpoint to the enzyme purified from hen eggs (HEL). However, unlike the single C-type variant found in hen eggs, duck eggs contain multiple isoforms: I, ... ...

Abstract	Background: Lysozyme purified from duck eggs (DEL) has long been used as a model antigen as a counterpoint to the enzyme purified from hen eggs (HEL). However, unlike the single C-type variant found in hen eggs, duck eggs contain multiple isoforms: I, II and III. We recently reported the structures of isoforms I and III from Pekin duck (Anas platyrhynchos) and unequivocally determined the sequences of all three isoforms by mass spectrometry. Here we present the crystal structure of isoform II (DEL-II). Results: Lysozyme isoform II was purified from isoforms I and III using ion-exchange and gel-filtration chromatography, then crystallized. X-ray diffraction data were collected to 1.15 Å resolution and the structure of DEL-II was solved by molecular replacement using the structure of DEL-I as the search model. It contains two molecules in the crystallographic asymmetric unit: both molecules display a canonical C-type lysozyme fold and electron density consistent with the expected sequence. The most significant difference between the two molecules concerns different conformations of a surface loop containing one of the expected amino acid differences between the isoforms. Conclusions: The structure of DEL-II supports the primary sequence as elucidated by a combination of amino acid sequencing, DNA sequencing and mass spectrometry, with strong electron density confirming it to be an S37G G71R variant of DEL I, and differing from hen egg lysozyme at a total of 21 amino acid positions.
MeSH term(s)	Animals ; Avian Proteins/chemistry ; Catalytic Domain ; Crystallography, X-Ray ; Ducks/metabolism ; Egg Proteins/chemistry ; Models, Molecular ; Muramidase/chemistry ; Protein Conformation ; Protein Isoforms/chemistry ; X-Ray Diffraction
Chemical Substances	Avian Proteins ; Egg Proteins ; Protein Isoforms ; Muramidase (EC 3.2.1.17)
Language	English
Publishing date	2018-08-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2050440-8
ISSN	1472-6807 ; 1472-6807
ISSN (online)	1472-6807
ISSN	1472-6807
DOI	10.1186/s12900-018-0090-7
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Article ; Online: Crystal structures of human neuropeptide Y (NPY) and peptide YY (PYY).

Langley, David B / Schofield, Peter / Jackson, Jenny / Herzog, Herbert / Christ, Daniel

Neuropeptides

2022 Volume 92, Page(s) 102231

Abstract: Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) form the evolutionarily conserved pancreatic polypeptide family. While the fold is widely utilized in nature, crystal structures remain elusive, particularly for the human forms, with ...

Abstract	Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) form the evolutionarily conserved pancreatic polypeptide family. While the fold is widely utilized in nature, crystal structures remain elusive, particularly for the human forms, with only the structure of a distant avian form of PP reported. Here we utilize a crystallization chaperone (antibody Fab fragment), specifically recognizing the amidated peptide termini, to solve the structures of human NPY and human PYY. Intriguingly, and despite limited sequence identity (~50%), the structure of human PYY closely resembles that of avian PP, highlighting the broad structural conservation of the fold throughout evolution. Specifically, the PYY structure is characterized by a C-terminal amidated α-helix, preceded by a backfolded poly-proline N-terminus, with the termini in close proximity to each other. In contrast, in the structure of human NPY the N-terminal component is disordered, while the helical component of the peptide is observed in a four-helix bundle type arrangement, consistent with a propensity for multimerization suggested by NMR studies.
MeSH term(s)	Humans ; Neuropeptide Y ; Pancreatic Polypeptide ; Peptide YY ; Receptors, Neuropeptide Y
Chemical Substances	Neuropeptide Y ; Receptors, Neuropeptide Y ; Peptide YY (106388-42-5) ; Pancreatic Polypeptide (59763-91-6)
Language	English
Publishing date	2022-02-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	9048-7
ISSN	1532-2785 ; 0143-4179
ISSN (online)	1532-2785
ISSN	0143-4179
DOI	10.1016/j.npep.2022.102231
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Article: A potential role of nitric oxide in postharvest pest control: A review

Granella, S.J. / Bechlin, T.R. / Christ, D. / Coelho, S.R.M.

Journal of the Saudi Society of Agricultural Sciences. 2021 Dec. 19,

2021

Abstract: Novel methods of stored-product pest control are essential to greater success against a wide variety of pest species worldwide, especially in tropical regions. Modern methods such as ozonation and organic pesticides have ensured grain preservation ... ...

Abstract	Novel methods of stored-product pest control are essential to greater success against a wide variety of pest species worldwide, especially in tropical regions. Modern methods such as ozonation and organic pesticides have ensured grain preservation without loss of quality and without the accumulation of residues; these properties are considered fundamental to food safety. Thereby, nitric oxide (NO) is a newly discovered fumigant that has shown the potential to control stored product pests. It has also been described as a substitute for phosphine and sulfuryl fluoride. In this regard, NO has the potential to become an alternative method of postharvest pest control, primarily due to its high pest mortality rate from a broader range of pests and products. However, research is needed to reduce the impact of NO on food quality due to the high reactive power of NO. Potentially toxic residues, such as the primary forms of NO oxidation, NO₂⁻ and NO₃⁻, can accumulate in treated products and damage consumers' health. Further research is needed into the possible use of NO fumigation as an alternative practice in controlling stored grain pests.
Keywords	food quality ; food safety ; fumigation ; mortality ; nitric oxide ; oxidation ; ozonation ; phosphine ; stored grain ; stored product protection ; sulfuryl fluoride ; toxicity
Language	English
Dates of publication	2021-1219
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	2635379-9
ISSN	1658-077X
ISSN	1658-077X
DOI	10.1016/j.jssas.2021.12.002
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Expression of Human VH Single Domains as Fc Fusions in Mammalian Cells.

Abdelatti, Mahmoud / Schofield, Peter / Christ, Daniel

Methods in molecular biology (Clifton, N.J.)

2019 Volume 1953, Page(s) 121–136

Abstract: Single-domain antibodies represent an emerging class of antibody fragments with promising therapeutic and diagnostic potential. As a result, multiple strategies have been developed in order to improve their biophysical and/or biological properties. In ... ...

Abstract	Single-domain antibodies represent an emerging class of antibody fragments with promising therapeutic and diagnostic potential. As a result, multiple strategies have been developed in order to improve their biophysical and/or biological properties. In particular, the fusion of single-domain antibodies to the Fc part of an IgG molecule has become a common protein engineering approach toward this aim. Here, we describe a detailed protocol for a streamlined laboratory-scale production of VH single-domain antibodies as Fc fusions in mammalian cells. Firstly, DNA sequence encoding VH domain of interest fused to an IgG Fc is synthesized as a double-stranded gene fragment. Secondly, the DNA fragment is directly assembled into a restriction enzyme-digested vector in an assembly reaction. Finally, vector carrying the VH-Fc-fusion construct is introduced into suspension-adapted mammalian cells for transient expression of the Fc chimeric fusion. One-week post-transfection, the expressed Fc-fusion protein is purified using protein A/G affinity chromatography. Using this protocol, we were able to clone, express, and purify milligrams of isolated anti-HER2 VH domain as a mouse IgG2c Fc fusion in less than 2 weeks. This protocol can be readily modified to express proteins of interest other than VH domains as Fc fusions.
MeSH term(s)	Animals ; Biotinylation ; Cell Line ; Chromatography, Affinity/methods ; Cloning, Molecular/methods ; Humans ; Immunoglobulin Fc Fragments/genetics ; Immunoglobulin Fc Fragments/immunology ; Immunoglobulin Fc Fragments/isolation & purification ; Immunoglobulin G/genetics ; Immunoglobulin G/immunology ; Immunoglobulin G/isolation & purification ; Mice ; Plasmids/genetics ; Receptor, ErbB-2/immunology ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/immunology ; Recombinant Fusion Proteins/isolation & purification ; Single-Domain Antibodies/genetics ; Single-Domain Antibodies/immunology ; Single-Domain Antibodies/isolation & purification ; Transfection/methods
Chemical Substances	Immunoglobulin Fc Fragments ; Immunoglobulin G ; Recombinant Fusion Proteins ; Single-Domain Antibodies ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2019-03-25
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-9145-7_8
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