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  1. Article ; Online: Thunder-DDA-PASEF enables high-coverage immunopeptidomics and is boosted by MS

    Gomez-Zepeda, David / Arnold-Schild, Danielle / Beyrle, Julian / Declercq, Arthur / Gabriels, Ralf / Kumm, Elena / Preikschat, Annica / Łącki, Mateusz Krzysztof / Hirschler, Aurélie / Rijal, Jeewan Babu / Carapito, Christine / Martens, Lennart / Distler, Ute / Schild, Hansjörg / Tenzer, Stefan

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2288

    Abstract: Human leukocyte antigen (HLA) class I peptide ligands (HLAIps) are key targets for developing vaccines and immunotherapies against infectious pathogens or cancer cells. Identifying HLAIps is challenging due to their high diversity, low abundance, and ... ...

    Abstract Human leukocyte antigen (HLA) class I peptide ligands (HLAIps) are key targets for developing vaccines and immunotherapies against infectious pathogens or cancer cells. Identifying HLAIps is challenging due to their high diversity, low abundance, and patient individuality. Here, we develop a highly sensitive method for identifying HLAIps using liquid chromatography-ion mobility-tandem mass spectrometry (LC-IMS-MS/MS). In addition, we train a timsTOF-specific peak intensity MS
    MeSH term(s) Humans ; Tandem Mass Spectrometry/methods ; Peptides/chemistry ; Spike Glycoprotein, Coronavirus ; Chromatography, Liquid ; Histocompatibility Antigens Class I/genetics
    Chemical Substances spike protein, SARS-CoV-2 ; Peptides ; Spike Glycoprotein, Coronavirus ; Histocompatibility Antigens Class I
    Language English
    Publishing date 2024-03-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-46380-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Book ; Online: Network Flow Problems with Electric Vehicles

    Pulyassary, Haripriya / Kollias, Kostas / Schild, Aaron / Shmoys, David / Wu, Manxi

    2023  

    Abstract: Electric vehicle (EV) adoption in long-distance logistics faces challenges such as range anxiety and uneven distribution of charging stations. Two pivotal questions emerge: How can EVs be efficiently routed in a charging network considering range limits, ...

    Abstract Electric vehicle (EV) adoption in long-distance logistics faces challenges such as range anxiety and uneven distribution of charging stations. Two pivotal questions emerge: How can EVs be efficiently routed in a charging network considering range limits, charging speeds and prices? And, can the existing charging infrastructure sustain the increasing demand for EVs in long-distance logistics? This paper addresses these questions by introducing a novel theoretical and computational framework to study the EV network flow problems. We present an EV network flow model that incorporates range constraints and nonlinear charging rates, and identify conditions under which polynomial-time solutions can be obtained for optimal single EV routing, maximum flow, and minimum-cost flow problems. Our findings provide insights for optimizing EV routing in logistics, ensuring an efficient and sustainable future.
    Keywords Computer Science - Data Structures and Algorithms
    Subject code 000
    Publishing date 2023-11-08
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Noncanonical functions of Ku may underlie essentiality in human cells.

    Kelly, Rachel D / Parmar, Gursimran / Bayat, Laila / Maitland, Matthew E R / Lajoie, Gilles A / Edgell, David R / Schild-Poulter, Caroline

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 12162

    Abstract: The Ku70/80 heterodimer is a key player in non-homologous end-joining DNA repair but is involved in other cellular functions like telomere regulation and maintenance, in which Ku's role is not fully characterized. It was previously reported that knockout ...

    Abstract The Ku70/80 heterodimer is a key player in non-homologous end-joining DNA repair but is involved in other cellular functions like telomere regulation and maintenance, in which Ku's role is not fully characterized. It was previously reported that knockout of Ku80 in a human cell line results in lethality, but the underlying cause of Ku essentiality in human cells has yet to be fully explored. Here, we established conditional Ku70 knockout cells using CRISPR/Cas9 editing to study the essentiality of Ku70 function. While we observed loss of cell viability upon Ku depletion, we did not detect significant changes in telomere length, nor did we record lethal levels of DNA damage upon loss of Ku. Analysis of global proteome changes following Ku70 depletion revealed dysregulations of several cellular pathways including cell cycle/mitosis, RNA related processes, and translation/ribosome biogenesis. Our study suggests that the driving cause of loss of cell viability in Ku70 knockouts is not linked to the functions of Ku in DNA repair or at telomeres. Moreover, our data shows that loss of Ku affects multiple cellular processes and pathways and suggests that Ku plays critical roles in cellular processes beyond DNA repair and telomere maintenance to maintain cell viability.
    MeSH term(s) Humans ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Antigens, Nuclear/genetics ; Antigens, Nuclear/metabolism ; Ku Autoantigen/genetics ; Ku Autoantigen/metabolism ; DNA Repair/genetics ; DNA End-Joining Repair ; DNA Damage ; Telomere/genetics ; Telomere/metabolism
    Chemical Substances DNA-Binding Proteins ; Antigens, Nuclear ; Ku Autoantigen (EC 4.2.99.-)
    Language English
    Publishing date 2023-07-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-39166-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Author Correction: Linking human male vocal parameters to perceptions, body morphology, strength and hormonal profiles in contexts of sexual selection.

    Schild, Christoph / Aung, Toe / Kordsmeyer, Tobias L / Cardenas, Rodrigo A / Puts, David A / Penke, Lars

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 9780

    Language English
    Publishing date 2021-05-03
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-89157-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Crystal Structure and Stability in Aqueous Solutions of Na

    Fellhauer, David / Lee, Jun-Yeop / DiBlasi, Nicole A / Walter, Olaf / Gaona, Xavier / Schild, Dieter / Altmaier, Marcus

    Journal of the American Chemical Society

    2022  Volume 144, Issue 21, Page(s) 9217–9221

    Abstract: The ternary neptunium(V) (Np(V)) hydroxides ... ...

    Abstract The ternary neptunium(V) (Np(V)) hydroxides Na
    Language English
    Publishing date 2022-05-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3155-0
    ISSN 1520-5126 ; 0002-7863
    ISSN (online) 1520-5126
    ISSN 0002-7863
    DOI 10.1021/jacs.2c03479
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: High Rates of Anxiety Among Adolescents in a Partial Hospitalization Program.

    Pelcovitz, Michelle / Bennett, Shannon / Desai, Payal / Schild, Jennifer / Beaumont, Renae / Walkup, John / Shaffer, David / Chiu, Angela

    Child & youth care forum

    2022  Volume 52, Issue 1, Page(s) 105–122

    Abstract: Background: Anxiety disorders are garnering increasing attention for their contribution to high-risk issues and functional impairment. Adolescents are typically admitted to partial hospitalization programs (PHPs) due to high-risk presentations. However, ...

    Abstract Background: Anxiety disorders are garnering increasing attention for their contribution to high-risk issues and functional impairment. Adolescents are typically admitted to partial hospitalization programs (PHPs) due to high-risk presentations. However, the frequency of anxiety disorders in PHPs is not well-established, in part because anxiety can be overlooked in acute settings due to limited lengths of stay and focus on stabilization.
    Objective: This study aims to evaluate the frequency and severity of anxiety disorders among a sample of adolescent PHP patients to assess the need for anxiety-specific assessment and interventions in higher acuity settings.
    Methods: Participants were 158 youths ages 13 to 19 years old (
    Results: 75% of participants were diagnosed with an anxiety disorder (n = 118). On average, participants with anxiety disorders had elevated SCARED-C scores. Youths with depressive disorders had elevated SCARED-C scores even when they did not carry anxiety disorder diagnoses. Caregiver ratings of the youth's anxiety symptoms on the SCARED-P were elevated when youths had anxiety disorders.
    Conclusions: These findings suggest that anxiety is common in an adolescent PHP setting and support investing in evidence-based assessment and treatment of anxiety in high-acuity settings.
    Language English
    Publishing date 2022-02-24
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1070355-x
    ISSN 1573-3319 ; 1053-1890
    ISSN (online) 1573-3319
    ISSN 1053-1890
    DOI 10.1007/s10566-022-09680-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: RAD51C-XRCC3 structure and cancer patient mutations define DNA replication roles.

    Longo, Michael A / Roy, Sunetra / Chen, Yue / Tomaszowski, Karl-Heinz / Arvai, Andrew S / Pepper, Jordan T / Boisvert, Rebecca A / Kunnimalaiyaan, Selvi / Keshvani, Caezanne / Schild, David / Bacolla, Albino / Williams, Gareth J / Tainer, John A / Schlacher, Katharina

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 4445

    Abstract: RAD51C is an enigmatic predisposition gene for breast, ovarian, and prostate cancer. Currently, missing structural and related functional understanding limits patient mutation interpretation to homology-directed repair (HDR) function analysis. Here we ... ...

    Abstract RAD51C is an enigmatic predisposition gene for breast, ovarian, and prostate cancer. Currently, missing structural and related functional understanding limits patient mutation interpretation to homology-directed repair (HDR) function analysis. Here we report the RAD51C-XRCC3 (CX3) X-ray co-crystal structure with bound ATP analog and define separable RAD51C replication stability roles informed by its three-dimensional structure, assembly, and unappreciated polymerization motif. Mapping of cancer patient mutations as a functional guide confirms ATP-binding matching RAD51 recombinase, yet highlights distinct CX3 interfaces. Analyses of CRISPR/Cas9-edited human cells with RAD51C mutations combined with single-molecule, single-cell and biophysics measurements uncover discrete CX3 regions for DNA replication fork protection, restart and reversal, accomplished by separable functions in DNA binding and implied 5' RAD51 filament capping. Collective findings establish CX3 as a cancer-relevant replication stress response complex, show how HDR-proficient variants could contribute to tumor development, and identify regions to aid functional testing and classification of cancer mutations.
    MeSH term(s) Male ; Humans ; Prostatic Neoplasms ; Rad51 Recombinase ; Mutation ; DNA Replication ; Adenosine Triphosphate ; DNA-Binding Proteins
    Chemical Substances Rad51 Recombinase (EC 2.7.7.-) ; Adenosine Triphosphate (8L70Q75FXE) ; RAD51C protein, human ; DNA-Binding Proteins
    Language English
    Publishing date 2023-07-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-40096-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Severo Sales de Barros

    Ana Lucia Schild / Claudio S.L. Barros / David Driemeier / Franklin Riet-Correa / Paulo V. Peixoto / Ricardo A.A. Lemos

    Pesquisa Veterinária Brasileira, Vol

    obituary

    2022  Volume 42

    Keywords Veterinary medicine ; SF600-1100
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher Colégio Brasileiro de Patologia Animal (CBPA)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Deep-Learning-based Fast and Accurate 3D CT Deformable Image Registration in Lung Cancer.

    Ding, Yuzhen / Feng, Hongying / Yang, Yunze / Holmes, Jason / Liu, Zhengliang / Liu, David / Wong, William W / Yu, Nathan Y / Sio, Terence T / Schild, Steven E / Li, Baoxin / Liu, Wei

    ArXiv

    2023  

    Abstract: Purpose: In some proton therapy facilities, patient alignment relies on two 2D orthogonal kV images, taken at fixed, oblique angles, as no 3D on-the-bed imaging is available. The visibility of the tumor in kV images is limited since the patient's 3D ... ...

    Abstract Purpose: In some proton therapy facilities, patient alignment relies on two 2D orthogonal kV images, taken at fixed, oblique angles, as no 3D on-the-bed imaging is available. The visibility of the tumor in kV images is limited since the patient's 3D anatomy is projected onto a 2D plane, especially when the tumor is behind high-density structures such as bones. This can lead to large patient setup errors. A solution is to reconstruct the 3D CT image from the kV images obtained at the treatment isocenter in the treatment position.
    Methods: An asymmetric autoencoder-like network built with vision-transformer blocks was developed. The data was collected from 1 head and neck patient: 2 orthogonal kV images (1024x1024 voxels), 1 3D CT with padding (512x512x512) acquired from the in-room CT-on-rails before kVs were taken and 2 digitally-reconstructed-radiograph (DRR) images (512x512) based on the CT. We resampled kV images every 8 voxels and DRR and CT every 4 voxels, thus formed a dataset consisting of 262,144 samples, in which the images have a dimension of 128 for each direction. In training, both kV and DRR images were utilized, and the encoder was encouraged to learn the jointed feature map from both kV and DRR images. In testing, only independent kV images were used. The full-size synthetic CT (sCT) was achieved by concatenating the sCTs generated by the model according to their spatial information. The image quality of the synthetic CT (sCT) was evaluated using mean absolute error (MAE) and per-voxel-absolute-CT-number-difference volume histogram (CDVH).
    Results: The model achieved a speed of 2.1s and a MAE of <40HU. The CDVH showed that <5% of the voxels had a per-voxel-absolute-CT-number-difference larger than 185 HU.
    Conclusion: A patient-specific vision-transformer-based network was developed and shown to be accurate and efficient to reconstruct 3D CT images from kV images.
    Language English
    Publishing date 2023-04-21
    Publishing country United States
    Document type Preprint
    ISSN 2331-8422
    ISSN (online) 2331-8422
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Deep-learning based fast and accurate 3D CT deformable image registration in lung cancer.

    Ding, Yuzhen / Feng, Hongying / Yang, Yunze / Holmes, Jason / Liu, Zhengliang / Liu, David / Wong, William W / Yu, Nathan Y / Sio, Terence T / Schild, Steven E / Li, Baoxin / Liu, Wei

    Medical physics

    2023  Volume 50, Issue 11, Page(s) 6864–6880

    Abstract: Background: Deformable Image Registration (DIR) is an essential technique required in many applications of radiation oncology. However, conventional DIR approaches typically take several minutes to register one pair of 3D CT images and the resulting ... ...

    Abstract Background: Deformable Image Registration (DIR) is an essential technique required in many applications of radiation oncology. However, conventional DIR approaches typically take several minutes to register one pair of 3D CT images and the resulting deformable vector fields (DVFs) are only specific to the pair of images used, making it less appealing for clinical application.
    Purpose: A deep-learning-based DIR method using CT images is proposed for lung cancer patients to address the common drawbacks of the conventional DIR approaches and in turn can accelerate the speed of related applications, such as contour propagation, dose deformation, adaptive radiotherapy (ART), etc. METHODS: A deep neural network based on VoxelMorph was developed to generate DVFs using CT images collected from 114 lung cancer patients. Two models were trained with the weighted mean absolute error (wMAE) loss and structural similarity index matrix (SSIM) loss (optional) (i.e., the MAE model and the M+S model). In total, 192 pairs of initial CT (iCT) and verification CT (vCT) were included as a training dataset and the other independent 10 pairs of CTs were included as a testing dataset. The vCTs usually were taken 2 weeks after the iCTs. The synthetic CTs (sCTs) were generated by warping the vCTs according to the DVFs generated by the pre-trained model. The image quality of the synthetic CTs was evaluated by measuring the similarity between the iCTs and the sCTs generated by the proposed methods and the conventional DIR approaches, respectively. Per-voxel absolute CT-number-difference volume histogram (CDVH) and MAE were used as the evaluation metrics. The time to generate the sCTs was also recorded and compared quantitatively. Contours were propagated using the derived DVFs and evaluated with SSIM. Forward dose calculations were done on the sCTs and the corresponding iCTs. Dose volume histograms (DVHs) were generated based on dose distributions on both iCTs and sCTs generated by two models, respectively. The clinically relevant DVH indices were derived for comparison. The resulted dose distributions were also compared using 3D Gamma analysis with thresholds of 3 mm/3%/10% and 2 mm/2%/10%, respectively.
    Results: The two models (wMAE and M+S) achieved a speed of 263.7±163 / 265.8±190 ms and a MAE of 13.15±3.8 / 17.52±5.8 HU for the testing dataset, respectively. The average SSIM scores of 0.987±0.006 and 0.988±0.004 were achieved by the two proposed models, respectively. For both models, CDVH of a typical patient showed that less than 5% of the voxels had a per-voxel absolute CT-number-difference larger than 55 HU. The dose distribution calculated based on a typical sCT showed differences of ≤2cGy[RBE] for clinical target volume (CTV) D
    Conclusion: A deep neural network-based DIR approach was proposed and has been shown to be reasonably accurate and efficient to register the initial CTs and verification CTs in lung cancer.
    MeSH term(s) Humans ; Deep Learning ; Lung Neoplasms/diagnostic imaging ; Lung Neoplasms/radiotherapy ; Image Processing, Computer-Assisted/methods ; Imaging, Three-Dimensional ; Radiotherapy Planning, Computer-Assisted/methods ; Tomography, X-Ray Computed
    Language English
    Publishing date 2023-06-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 188780-4
    ISSN 2473-4209 ; 0094-2405
    ISSN (online) 2473-4209
    ISSN 0094-2405
    DOI 10.1002/mp.16548
    Database MEDical Literature Analysis and Retrieval System OnLINE

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