41 research outputs found
A hamis „Ortega-hipotézis"
No full textThe well-known anti-elitist „Ortega Hypothesis" came into being in 1972 in Science, the work of two American science sociologists: J. R. Colé and S- Colé who supported its validity with a quantita-tive author citation analysis conducted in the phys-ics literature. This „hypothesis" has since had a brilliant career in the literature of many widely dif-fering disciplines. This sociometrologic „hypothesis" - which has had a very big indexed influence -is anti-elitist and therefore anti-ORTEGA in mean-ing. The two sociometrologists created it by falsify-ing the quoted text of the eminent elitist Spanish philosopher J. ORTEGA Y GASSET and by misin-terpreting his reál doctrine. The fact of the falsifica-tion of the text serving as the basis of the „hypothesis" has not even arisen in the decades of debates conducted in connection with the falsé „hypothesis" and under its name, mainly on the subject of quantitative citation analysis. The scientific literature showing the indexed influence of the falsé „hypothesis" has stil! not recognized the phi-lological-mental crime committed: none of the much more than one hundred indexed referencing authors has checked the ideological correctness of the reál subject/source of his or her reference. Analysis of the literature case of the falsé „Ortega Hypothesis" throws a sharp light on the current depressing state of referencing practice of publish-ing researches. Scientific Communications shown to be of doubtful authenticity and later even found to be falsé have continued to appear and in today's eiectronic flow of information there has been a leap in the speed and breadth of their world-wide dis-semination. For this reason there has alsó been a great increase in the need for and importance of self-healing by science: the work of controlling and correcting itself.A közismert, antielitista értelmű ún. „Ortega-hipotézis" 1972-ben született meg a Science-ben, két amerikai tudományszociológus: J. R. Colé és S. Colé tollából, akik annak érvényességét a fizikai irodalomban végzett kvantitatív szerzői hivatkozatszámláló elemzéssel támasztották alá. Ez a „hipotézis" azóta fényes életutat járt be a tudomány nagyszámú és egymástól nagyon távol eső diszciplínájának irodalmában. Ezt az antielitista, és ezért anti¬ORTEGA értelmű, igen nagy indexelt hatású szociometrológiai „hipotézist" az eminens elitista spanyol filozófus: J. ORTEGA Y GASSET általuk idézett szövegének meghamisításával és valódi tanításának félremagyarázásával hozta létre a két szociometrológus. A hamis „hipotézissel" kapcsolatban és a neve alatt főleg a kvantitatív hivatkozatelemzésről folyó évtizedes vitákban még a „hipotézist" megalapozó szöveghamisítás ténye sem merült fel. A hamis „hipotézis" hatását indexelten mutató tudományos irodalom mindeddig nem ismerte fel az elkövetett filológiai-mentális bűntettet: a jóval több mint száz indexelten hivatkozó szerző egyike sem ellenőrizte hivatkozása valódi tárgyának/forrásának eszmei helyességét. A hamis „Ortega-hipotézis" szakirodalmi esetének elemzése éles fényt vet a publikáló kutatók hivatkozási gyakorlatának mai lehangoló állapotára. A kétségessé vált hitelességű, sőt a hamisnak bizonyuló közlemények azóta is sorra felbukkannak; elterjesztésük sebessége és hatóköre viszont ugrásszerűen megnőtt az elektronikus ismeretáramlás jelenkorában. Nagyon megnövekedett ezért a tudomány öngyógyító: önmagát ellenőr-ző-kijavító munkájának a szükségessége és fontossága is
A numerical approach to model the dynamics in a mammalian cell exposed to a carcinogenic compound
No full textWhen a mammalian cell is exposed to a carcinogen, the carcinogen gives rise to new compounds. In this paper a numerical approach is taken to find the amount of these compounds overtime. The concentration of the compounds are assumed to satisfy the reaction and/or the diffusion equation, techniques used for solving these equations include the one-dimensional finite element method (FEM) and the lumped parameter approach. The mathematically derived results are compared to in-vitro measurements. The mathematical model set up in this paper will prove insufficient
Multiscale Modelling and Analysis of Tumour Growth and Treatment Strategies
No full textA multiscale, agent-based mathematical framework is here used to capture the multiscale nature of solid tumours. Tumour dynamics and treatment responses are modelled and simulated in silico. Details regarding cell cy-cle progression, tumour growth and oxygen distribution are included in the mathematical framework. Treatment responses to conventional anti-cancer therapies, such as chemotherapy and radiotherapy, as well as to more novel drugs, such as hypoxia-activated prodrugs and DNA-damage repair inhibit-ing drugs, are studied. Uncertainty and sensitivity analyses techniques are discussed in order to mitigate model uncertainty and interpret model sen-sitivity to parameter perturbations. This thesis furthermore discusses the role of mathematical modelling in current cancer research
Targeting cellular DNA damage responses in cancer : an in vitro-calibrated agent-based model simulating monolayer and spheroid treatment responses to ATR-inhibiting drugs
No full textFunding: Medical Research Council (MR/R017506/1).We combine a systems pharmacology approach with an agent-based modelling approach to simulate LoVo cells subjected to AZD6738, an ATR (ataxia–telangiectasia-mutated and rad3-related kinase) inhibiting anti-cancer drug that can hinder tumour proliferation by targeting cellular DNA damage responses. The agent-based model used in this study is governed by a set of empirically observable rules. By adjusting only the rules when moving between monolayer and multi-cellular tumour spheroid simulations, whilst keeping the fundamental mathematical model and parameters intact, the agent-based model is first parameterised by monolayer in vitro data and is thereafter used to simulate treatment responses in in vitro tumour spheroids subjected to dynamic drug delivery. Spheroid simulations are subsequently compared to in vivo data from xenografts in mice. The spheroid simulations are able to capture the dynamics of in vivo tumour growth and regression for approximately 8 days post-tumour injection. Translating quantitative information between in vitro and in vivo research remains a scientifically and financially challenging step in preclinical drug development processes. However, well-developed in silico tools can be used to facilitate this in vitro to in vivo translation, and in this article, we exemplify how data-driven, agent-based models can be used to bridge the gap between in vitro and in vivo research. We further highlight how agent-based models, that are currently underutilised in pharmaceutical contexts, can be used in preclinical drug development.Peer reviewe
Uncertainty and Sensitivity Analyses Methods for Agent-Based Mathematical Models: An Introductory Review
No full textMultiscale, agent-based mathematical models of biological systems are often associated with model uncertainty and sensitivity to parameter perturbations. Here, three uncertainty and sensitivity analyses methods, that are suitable to use when working with agent-based models, are discussed. These methods are namely Consistency Analysis, Robustness Analysis and Latin Hypercube Analysis. This introductory review discusses origins, conventions, implementation and result interpretation of the aforementioned methods. Information on how to implement the discussed methods in MATLAB is included
A single-cell mathematical model of SARS-CoV-2 induced pyroptosis and the effects of anti-inflammatory intervention
No full textSJH is supported by the Medical Research Council grant MR/R017506/1. The authors would like to thank the SARS-CoV-2 Tissue Simulation Coalition for ongoing collaboration and feedback on model development. Further, this work is part of the RAMP (Rapid Assistance in Modelling the Pandemic) initiative, coordinated by the Royal Society, UK. The authors would like to thank Prof. Mark A.J. Chaplain (University of St Andrews) for coordinating our RAMP Task Team modelling within-host dynamics. SARS-CoV-2 Tissue Simulation Coalition: http://physicell.org/covid19/. RAMP: https://royalsociety.org/topics-policy/health-and-wellbeing/ramp/.Pyroptosis is an inflammatory mode of cell death that can contribute to the cytokine storm associated with severe cases of coronavirus disease 2019 (COVID-19). The formation of the NLRP3 inflammasome is central to pyroptosis, which may be induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Inflammasome formation, and by extension pyroptosis, may be inhibited by certain anti-inflammatory drugs. In this study, we present a single-cell mathematical model that captures the formation of the NLRP3 inflammasome, pyroptotic cell death and responses to anti-inflammatory intervention that hinder the formation of the NLRP3 inflammasome. The model is formulated in terms of a system of ordinary differential equations (ODEs) that describe the dynamics of the key biological components involved in pyroptosis. Our results demonstrate that an anti-inflammatory drug can delay the formation of the NLRP3 inflammasome, and thus may alter the mode of cell death from inflammatory (pyroptosis) to non-inflammatory (e.g., apoptosis). The single-cell model is implemented within a SARS-CoV-2 tissue simulator, in collaboration with a multidisciplinary coalition investigating within host-dynamics of COVID-19. In this paper, we additionally provide an overview of the SARS-CoV-2 tissue simulator and highlight the effects of pyroptosis on a cellular level.Peer reviewe
Susainability of savings and credit co-operative societies (SACCOS) : a case of Monduli District-Arusha
No full textSaving and Credit Cooperative Societies (SACCOS) are Community Economic Development Projects which are based on three nexes: Participation, Empowerment and sustainability of the economic ventures carried out by community members. The main objective of this survey is to assess the sustainability of these Peoples' Based Organization (PBOs) by analyzing both their activity and financial performance.The survey was carried out in Monduli District in Arusha Region between October 2005 and August 2006 in collaboration with the CBO-Arusha Community Initiatives Support Trust (ACIST) situated in Arusha City Council (ACC). It involved 105 respondents 100 were SACCOS members and 5 were staff from ACIST (Arusha) Community Development and Cooperatives Departments in Monduli District.The principal methodology used in this survey includes structured interviews, Questionnaires, Focus Group Discuss, Key Informants Interviews and Observation.The general observation from the findings reveled that most SACCOS are not performing well due to lack of adequate capital, low level of education, poor extension services, inaccessibility to credit facilities and services. Only workers based SACCOS had stable source of their income.However, its is a naked fact SACCOS do need a comprehensive and concerted effort by both the Government, NGOs and Civil Society Organization (CSOs) to uplift their status and make them sustainable and be fuelling tool for Community Economic Development. (Author abstract)Kingu, H. A. (2007). Susainability of savings and credit co-operative societies (SACCOS): a case of Monduli District-Arusha. Retrieved from http://academicarchive.snhu.eduMaster of Science (M.S.)School of Community Economic Developmen
What does not kill a tumour may make it stronger: In silico insights into chemotherapeutic drug resistance
No full textWhat does not kill a tumour may make it stronger:<i>in silico</i>Insights into Chemotherapeutic Drug Resistance
No full textAbstractTumour recurrence post chemotherapy is an established clinical problem and many cancer types are often observed to be increasingly drug resistant subsequent to chemotherapy treatments. Drug resistance in cancer is a multipart phenomenon which can be derived from several origins and in many cases it has been observed that cancer cells have the ability to possess, acquire and communicate drug resistant traits.Here, anin silicoframework is developed in order to study drug resistance and drug response in cancer cell populations exhibiting various drug resistant features. The framework is based on an on-lattice hybrid multiscale mathematical model and is equipped to simulate multiple mechanisms on different scales that contribute towards chemotherapeutic drug resistance in cancer. This study demonstrates how drug resistant tumour features may depend on the interplay amongst intracellular, extracelluar and intercellular factors. On a cellular level, drug resistant cell phenotypes are here derived from inheritance or mutations that are spontaneous, drug-induced or communicated via exosomes. Furthermore intratumoural heterogeneity and spatio-temporal drug dynamics heavily influences drug delivery and the development of drug resistant cancer cell subpopulations. Chemotherapy treatment strategies are here optimised for variousin silicotumour scenarios and treatment objectives. We demonstrate that optimal chemotherapy treatment strategies drastically depend on which drug resistant mechanisms are activated, and that furthermore suboptimal chemotherapy administration may promote drug resistance.</jats:p
