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  1. Article ; Online: Resource allocation in a PDE ecosystem model.

    Valega-Mackenzie, Wencel / Bintz, Jason / Lenhart, Suzanne

    Journal of mathematical biology

    2023  Volume 86, Issue 6, Page(s) 96

    Abstract: The effects of habitat heterogeneity on a diffusing population are investigated here. We formulate a reaction-diffusion system of partial differential equations to analyze the effect of resource allocation in an ecosystem with resource having its own ... ...

    Abstract The effects of habitat heterogeneity on a diffusing population are investigated here. We formulate a reaction-diffusion system of partial differential equations to analyze the effect of resource allocation in an ecosystem with resource having its own dynamics in space and time. We show a priori estimates to prove the existence of state solutions given a control. We formulate an optimal control problem of our ecosystem model such that the abundance of a single species is maximized while minimizing the cost of inflow resource allocation. In addition, we show the existence and uniqueness of the optimal control as well as the optimal control characterization. We also establish the existence of an optimal intermediate diffusion rate. Moreover, we illustrate several numerical simulations with Dirichlet and Neumann boundary conditions with the space domain in 1D and 2D.
    MeSH term(s) Ecosystem ; Population Dynamics ; Models, Biological ; Diffusion
    Language English
    Publishing date 2023-05-22
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 187101-8
    ISSN 1432-1416 ; 0303-6812
    ISSN (online) 1432-1416
    ISSN 0303-6812
    DOI 10.1007/s00285-023-01932-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1495: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Dose optimization of an adjuvanted peptide-based personalized neoantigen melanoma vaccine.

    Valega-Mackenzie, Wencel / Rodriguez Messan, Marisabel / Yogurtcu, Osman N / Nukala, Ujwani / Sauna, Zuben E / Yang, Hong

    PLoS computational biology

    2024  Volume 20, Issue 3, Page(s) e1011247

    Abstract: The advancements in next-generation sequencing have made it possible to effectively detect somatic mutations, which has led to the development of personalized neoantigen cancer vaccines that are tailored to the unique variants found in a patient's cancer. ...

    Abstract The advancements in next-generation sequencing have made it possible to effectively detect somatic mutations, which has led to the development of personalized neoantigen cancer vaccines that are tailored to the unique variants found in a patient's cancer. These vaccines can provide significant clinical benefit by leveraging the patient's immune response to eliminate malignant cells. However, determining the optimal vaccine dose for each patient is a challenge due to the heterogeneity of tumors. To address this challenge, we formulate a mathematical dose optimization problem based on a previous mathematical model that encompasses the immune response cascade produced by the vaccine in a patient. We propose an optimization approach to identify the optimal personalized vaccine doses, considering a fixed vaccination schedule, while simultaneously minimizing the overall number of tumor and activated T cells. To validate our approach, we perform in silico experiments on six real-world clinical trial patients with advanced melanoma. We compare the results of applying an optimal vaccine dose to those of a suboptimal dose (the dose used in the clinical trial and its deviations). Our simulations reveal that an optimal vaccine regimen of higher initial doses and lower final doses may lead to a reduction in tumor size for certain patients. Our mathematical dose optimization offers a promising approach to determining an optimal vaccine dose for each patient and improving clinical outcomes.
    MeSH term(s) Humans ; Melanoma/genetics ; Cancer Vaccines/genetics ; Antigens, Neoplasm/genetics ; Adjuvants, Immunologic ; Peptides
    Chemical Substances Cancer Vaccines ; Antigens, Neoplasm ; Adjuvants, Immunologic ; Peptides
    Language English
    Publishing date 2024-03-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1011247
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Dosage optimization for reducing tumor burden using a phenotype-structured population model with a drug-resistance continuum.

    Han, Lifeng / Yogurtcu, Osman N / Rodriguez Messan, Marisabel / Valega-Mackenzie, Wencel / Nukala, Ujwani / Yang, Hong

    Mathematical medicine and biology : a journal of the IMA

    2024  Volume 41, Issue 1, Page(s) 35–52

    Abstract: Drug resistance is a significant obstacle to effective cancer treatment. To gain insights into how drug resistance develops, we adopted a concept called fitness landscape and employed a phenotype-structured population model by fitting to a set of ... ...

    Abstract Drug resistance is a significant obstacle to effective cancer treatment. To gain insights into how drug resistance develops, we adopted a concept called fitness landscape and employed a phenotype-structured population model by fitting to a set of experimental data on a drug used for ovarian cancer, olaparib. Our modeling approach allowed us to understand how a drug affects the fitness landscape and track the evolution of a population of cancer cells structured with a spectrum of drug resistance. We also incorporated pharmacokinetic (PK) modeling to identify the optimal dosages of the drug that could lead to long-term tumor reduction. We derived a formula that indicates that maximizing variation in plasma drug concentration over a dosing interval could be important in reducing drug resistance. Our findings suggest that it may be possible to achieve better treatment outcomes with a drug dose lower than the levels recommended by the drug label. Acknowledging the current limitations of our work, we believe that our approach, which combines modeling of both PK and drug resistance evolution, could contribute to a new direction for better designing drug treatment regimens to improve cancer treatment.
    MeSH term(s) Tumor Burden
    Language English
    Publishing date 2024-02-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2119786-6
    ISSN 1477-8602 ; 0265-0746 ; 1477-8599
    ISSN (online) 1477-8602
    ISSN 0265-0746 ; 1477-8599
    DOI 10.1093/imammb/dqae003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 2790: Show issues Location:
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  4. Article ; Online: Can Vaccination Save a Zika Virus Epidemic?

    Valega-Mackenzie, Wencel / Ríos-Soto, Karen R

    Bulletin of mathematical biology

    2018  Volume 80, Issue 3, Page(s) 598–625

    Abstract: Zika virus (ZIKV) is a vector-borne disease that has rapidly spread during the year 2016 in more than 50 countries around the world. If a woman is infected during pregnancy, the virus can cause severe birth defects and brain damage in their babies. The ... ...

    Abstract Zika virus (ZIKV) is a vector-borne disease that has rapidly spread during the year 2016 in more than 50 countries around the world. If a woman is infected during pregnancy, the virus can cause severe birth defects and brain damage in their babies. The virus can be transmitted through the bites of infected mosquitoes as well as through direct contact from human to human (e.g., sexual contact and blood transfusions). As an intervention for controlling the spread of the disease, we study a vaccination model for preventing Zika infections. Although there is no formal vaccine for ZIKV, The National Institute of Allergy and Infectious Diseases (part of the National Institutes of Health) has launched a vaccine trial at the beginning of August 2016 to control ZIKV transmission, patients who received the vaccine are expected to return within 44 weeks to determine if the vaccine is safe. Since it is important to understand ZIKV dynamics under vaccination, we formulate a vaccination model for ZIKV spread that includes mosquito as well as sexual transmission. We calculate the basic reproduction number of the model to analyze the impact of relatively, perfect and imperfect vaccination rates. We illustrate several numerical examples of the vaccination model proposed as well as the impact of the basic reproduction numbers of vector and sexual transmission and the effect of vaccination effort on ZIKV spread. Results show that high levels of sexual transmission create larger cases of infection associated with the peak of infected humans arising in a shorter period of time, even when a vaccine is available in the population. However, a high level of transmission of Zika from vectors to humans compared with sexual transmission represents that ZIKV will take longer to invade the population providing a window of opportunities to control its spread, for instance, through vaccination.
    MeSH term(s) Animals ; Basic Reproduction Number ; Computer Simulation ; Epidemics/prevention & control ; Female ; Humans ; Male ; Mathematical Concepts ; Models, Biological ; Mosquito Vectors ; Pregnancy ; Vaccination ; Viral Vaccines/pharmacology ; Zika Virus/immunology ; Zika Virus Infection/epidemiology ; Zika Virus Infection/prevention & control ; Zika Virus Infection/transmission
    Chemical Substances Viral Vaccines
    Language English
    Publishing date 2018-01-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 184905-0
    ISSN 1522-9602 ; 0007-4985 ; 0092-8240
    ISSN (online) 1522-9602
    ISSN 0007-4985 ; 0092-8240
    DOI 10.1007/s11538-018-0393-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 754: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  5. Article ; Online: The optimal controlling strategy on a dispersing population in a two-patch system: Experimental and theoretical perspectives.

    Zhang, Bo / Zhai, Lu / Bintz, Jason / Lenhart, Suzanne M / Valega-Mackenzie, Wencel / David Van Dyken, J

    Journal of theoretical biology

    2021  Volume 528, Page(s) 110835

    Abstract: Invasive species, disease vectors, and pathogens are significant threats to biodiversity, ecosystem function and services, and human health. Understanding the optimal management strategy, which maximizes the effectiveness is crucial. Despite an abundance ...

    Abstract Invasive species, disease vectors, and pathogens are significant threats to biodiversity, ecosystem function and services, and human health. Understanding the optimal management strategy, which maximizes the effectiveness is crucial. Despite an abundance of theoretical work has conducted on projecting the optimal allocation strategy, almost no empirical work has been performed to validate the theory. We first used a consumer-resource model to simulate a series of allocation fractions of controlling treatment to determine the optimal controlling strategy. Further, we conducted rigorous laboratory experiments using spatially diffusing laboratory populations of yeast to verify our mathematical results. We found consistent results that: (1) When population growth is limited by the local resource, the controlling priority should be given to the areas with higher concentration of resource; (2) When population growth is not limited by the resource concentration, the best strategy is to allocate equal amount of controlling efforts among the regions; (3) With restricted budget, it is more efficient to prioritize the controlling effects to the areas with high population abundance, otherwise, it is better to control equally among the regions. The new theory, which was tested by laboratory experiments, will reveal new opportunities for future field interventions, thereby informing subsequent biological decision-making.
    MeSH term(s) Biodiversity ; Ecosystem ; Humans ; Introduced Species
    Language English
    Publishing date 2021-07-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2972-5
    ISSN 1095-8541 ; 0022-5193
    ISSN (online) 1095-8541
    ISSN 0022-5193
    DOI 10.1016/j.jtbi.2021.110835
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 923: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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