Статті в журналах: "Biological heterogeneities"

1

Brace, Christopher L., and Sevde Etoz. "An Analysis of Open-Ended Coaxial Probe Sensitivity to Heterogeneous Media." Sensors 20, no. 18 (September 19, 2020): 5372. http://dx.doi.org/10.3390/s20185372.

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Open-ended coaxial probe spectroscopy is commonly used to determine the dielectric permittivity of biological tissues. However, heterogeneities in the probe sensing region can limit measurement precision and reproducibility. This study presents an analysis of the coaxial probe sensing region to elucidate the effects of heterogeneities on measured permittivity. Coaxial probe spectroscopy at 0.5–20 GHz was numerically simulated while a homogenous background was perturbed with a small inclusion of contrasting permittivity. Shifts in the measured effective permittivity provided a three-dimensional assessment of the probe sensitivity field. Sensitivity was well-approximated by the square of the electric field for each analyzed probe. Smaller probes were more sensitive to heterogeneities throughout their sensing region, but were less sensitive to spectral effects compared to larger probes. The probe sensing diameter was less than 0.5 mm in all directions by multiple metrics. Therefore, small heterogeneities may substantially impact permittivity measurement in biological tissues if located near the probe-tissue interface.

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2

Rabanel, Jean-Michel, Vahid Adibnia, Soudeh F. Tehrani, Steven Sanche, Patrice Hildgen, Xavier Banquy, and Charles Ramassamy. "Nanoparticle heterogeneity: an emerging structural parameter influencing particle fate in biological media?" Nanoscale 11, no. 2 (2019): 383–406. http://dx.doi.org/10.1039/c8nr04916e.

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3

Mittal, Divyansh, and Rishikesh Narayanan. "Degeneracy in the robust expression of spectral selectivity, subthreshold oscillations, and intrinsic excitability of entorhinal stellate cells." Journal of Neurophysiology 120, no. 2 (August 1, 2018): 576–600. http://dx.doi.org/10.1152/jn.00136.2018.

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Biological heterogeneities are ubiquitous and play critical roles in the emergence of physiology at multiple scales. Although neurons in layer II (LII) of the medial entorhinal cortex (MEC) express heterogeneities in channel properties, the impact of such heterogeneities on the robustness of their cellular-scale physiology has not been assessed. Here, we performed a 55-parameter stochastic search spanning nine voltage- or calcium-activated channels to assess the impact of channel heterogeneities on the concomitant emergence of 10 in vitro electrophysiological characteristics of LII stellate cells (SCs). We generated 150,000 models and found a heterogeneous subpopulation of 449 valid models to robustly match all electrophysiological signatures. We employed this heterogeneous population to demonstrate the emergence of cellular-scale degeneracy in SCs, whereby disparate parametric combinations expressing weak pairwise correlations resulted in similar models. We then assessed the impact of virtually knocking out each channel from all valid models and demonstrate that the mapping between channels and measurements was many-to-many, a critical requirement for the expression of degeneracy. Finally, we quantitatively predict that the spike-triggered average of SCs should be endowed with theta-frequency spectral selectivity and coincidence detection capabilities in the fast gamma-band. We postulate this fast gamma-band coincidence detection as an instance of cellular-scale-efficient coding, whereby SC response characteristics match the dominant oscillatory signals in LII MEC. The heterogeneous population of valid SC models built here unveils the robust emergence of cellular-scale physiology despite significant channel heterogeneities, and forms an efficacious substrate for evaluating the impact of biological heterogeneities on entorhinal network function. NEW & NOTEWORTHY We assessed the impact of heterogeneities in channel properties on the robustness of cellular-scale physiology of medial entorhinal cortical stellate neurons. We demonstrate that neuronal models with disparate channel combinations were endowed with similar physiological characteristics, as a consequence of the many-to-many mapping between channel properties and the physiological characteristics that they modulate. We predict that the spike-triggered average of stellate cells should be endowed with theta-frequency spectral selectivity and fast gamma-band coincidence detection capabilities.

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4

JACOBSEN, C., T. BEETZ, M. FESER, A. OSANNA, A. STEIN, and S. WIRICK. "SPECTROMICROSCOPY OF BIOLOGICAL AND ENVIRONMENTAL SYSTEMS AT STONY BROOK: INSTRUMENTATION AND ANALYSIS." Surface Review and Letters 09, no. 01 (February 2002): 185–91. http://dx.doi.org/10.1142/s0218625x0200177x.

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Soft X-ray microscopy allows one to study nanoscale heterogeneities in dry and wet environmental science, biological, polymer, and geochemical specimens. Recent advances in instrumentation at the X-1A beamline at the National Synchrotron Light Source at Brookhaven National Laboratory are described. Spectromicroscopy data analysis methods including component mapping and principal component analysis (PCA) are then discussed.

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5

Sindyaeva, A. R., and V. P. Zakharov. "Multi-parametric function of differential backscattering in 3D biological media with heterogeneities." Laser Physics 19, no. 6 (June 2009): 1361–65. http://dx.doi.org/10.1134/s1054660x09060292.

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6

Mohamed, M., K. Hatfield, A. Hassan, and H. Klammler. "Stochastic evaluation of subsurface contaminant discharges under physical, chemical, and biological heterogeneities." Advances in Water Resources 33, no. 7 (July 2010): 801–12. http://dx.doi.org/10.1016/j.advwatres.2010.04.010.

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7

Babychenko, O., and A. Pashchenko. "Kinetics of photoconductivity of c-Si with amorphous heterogeneities." Radiotekhnika, no. 190 (October 16, 2017): 36–43. http://dx.doi.org/10.30837/rt.2017.3.190.05.

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The influence of amorphous inclusions of a cylindrical shape on the photoconductivity of crystalline silicon under the action of radiation from the photosensitivity region of the structure under study was theoretically investigated. The photoconductivity of the structure is analyzed depending on the geometric dimensions of the inclusions, their location in the structure, and the rate of surface recombination of nonequilibrium charge carriers. It is established that when the fraction of inclusions in the structure increases, the processes of generation of nonequilibrium charge carriers are determined mainly by an amorphous matrix. The appearance of the effect of negative photoconductivity under certain conditions has been revealed.

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8

Liu, Zengqian, Marc A. Meyers, Zhefeng Zhang, and Robert O. Ritchie. "Functional gradients and heterogeneities in biological materials: Design principles, functions, and bioinspired applications." Progress in Materials Science 88 (July 2017): 467–98. http://dx.doi.org/10.1016/j.pmatsci.2017.04.013.

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9

Pardini, P. A. "STUDY OF DIFFUSIVE MEDIA WITH LOW SCATTERING HETEROGENEITIES." Anales AFA 32, no. 4 (January 15, 2022): 99–105. http://dx.doi.org/10.31527/analesafa.2021.32.4.99.

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Biological tissues have the particularity of allowing light between 600 and 900 nm, within a range called optical window, to penetrate them a few centimeters. This characteristic arouses interest in the near-infrared light for its use as a diagnosis tool, with the characteristic of being non-invasive, its application in breast diagnosis is of particular interest for this study. These tissues do not allow the propagation of light in this spectral range in a rectilinear manner, but rather appear as diffusive, thus deteriorating the spatial resolution of the images that can be obtained from them. In this way, it is necessary to develop experimental techniques and specific data analysis strategies in order to obtain optical information from them. Breast tissue can suffer different types of lesions, such as tumors or cysts. This work presents the study of phantoms, which reproduce their optical properties with inclusions that represent tumors and/or cysts, analyzing the influence of the latter, which optical characteristics are non-diffusive, on optical images and the transport of light in these media. The main objective of this work is focused on the 3D localization and optical characterization of translucent heterogeneities in turbid media.

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10

Poelzing, Steven, and David S. Rosenbaum. "Nature, significance, and mechanisms of electrical heterogeneities in ventricle." Anatomical Record 280A, no. 2 (2004): 1010–17. http://dx.doi.org/10.1002/ar.a.20103.

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11

Hu, Jinwei, Isabella J. Yuan, Saied Mirshahidi, Alfred Simental, Steve C. Lee, and Xiangpeng Yuan. "Thyroid Carcinoma: Phenotypic Features, Underlying Biology and Potential Relevance for Targeting Therapy." International Journal of Molecular Sciences 22, no. 4 (February 16, 2021): 1950. http://dx.doi.org/10.3390/ijms22041950.

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Thyroid carcinoma consists a group of phenotypically heterogeneous cancers. Recent advances in biological technologies have been advancing the delineation of genetic, epigenetic, and non-genetic factors that contribute to the heterogeneities of these cancers. In this review article, we discuss new findings that are greatly improving the understanding of thyroid cancer biology and facilitating the identification of novel targets for therapeutic intervention. We review the phenotypic features of different subtypes of thyroid cancers and their underlying biology. We discuss recent discoveries in thyroid cancer heterogeneities and the critical mechanisms contributing to the heterogeneity with emphases on genetic and epigenetic factors, cancer stemness traits, and tumor microenvironments. We also discuss the potential relevance of the intratumor heterogeneity in understanding therapeutic resistance and how new findings in tumor biology can facilitate designing novel targeting therapies for thyroid cancer.

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12

Ren, Xiang, Clifford P. Weisel, and Panos G. Georgopoulos. "Modeling Effects of Spatial Heterogeneities and Layered Exposure Interventions on the Spread of COVID-19 across New Jersey." International Journal of Environmental Research and Public Health 18, no. 22 (November 14, 2021): 11950. http://dx.doi.org/10.3390/ijerph182211950.

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COVID-19 created an unprecedented global public health crisis during 2020–2021. The severity of the fast-spreading infection, combined with uncertainties regarding the physical and biological processes affecting transmission of SARS-CoV-2, posed enormous challenges to healthcare systems. Pandemic dynamics exhibited complex spatial heterogeneities across multiple scales, as local demographic, socioeconomic, behavioral and environmental factors were modulating population exposures and susceptibilities. Before effective pharmacological interventions became available, controlling exposures to SARS-CoV-2 was the only public health option for mitigating the disease; therefore, models quantifying the impacts of heterogeneities and alternative exposure interventions on COVID-19 outcomes became essential tools informing policy development. This study used a stochastic SEIR framework, modeling each of the 21 New Jersey counties, to capture important heterogeneities of COVID-19 outcomes across the State. The models were calibrated using confirmed daily deaths and SQMC optimization and subsequently applied in predictive and exploratory modes. The predictions achieved good agreement between modeled and reported death data; counterfactual analysis was performed to assess the effectiveness of layered interventions on reducing exposures to SARS-CoV-2 and thereby fatality of COVID-19. The modeling analysis of the reduction in exposures to SARS-CoV-2 achieved through concurrent social distancing and face-mask wearing estimated that 357 [IQR (290, 429)] deaths per 100,000 people were averted.

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13

Rao Allu, Srinivasa, Thomas Troxler, and Sergei Vinogradov. "Arylphthalimidoporphyrins: New Approaches to Imaging pH and Temperature Simultaneously with Oxygen." ECS Meeting Abstracts MA2022-01, no. 14 (July 7, 2022): 945. http://dx.doi.org/10.1149/ma2022-0114945mtgabs.

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Tetraarylphalimidoporphyrins (TAPIP) and diarylphalimidoporphyrins (DAPIP) possess unique photophysical properties that enable new and superior approaches to optical biological sensing of pH and temperature in parallel with oxygen. The syntheses of TAPIP and DAPIP have been reported by our group recently. We also have reported the photophysical properties of free-base (H2), Zn(II), Pt(II) and Pd(II) DAPIP and TAPIP, including their non-linear spectroscopic properties, such as two- and three-photon absorption spectra. Using a combination of phosphorescent Pt complexes of TAPIP and DAPIP we are designing a phosphorescent sensor for pH and oxygen, termed pHOx, which operates by measuring ratios of phosphorescence lifetimes. Unlike all existing optical pH sensors, measurements by pHOx are not affected by optical heterogeneities of the medium and provide unbiased pH readings in vivo simultaneously with pO2. At the same time, Pd complexes of TAPIP have been shown to emit both phosphorescence and thermally activated E-type delayed fluorescence, providing a functional element for optical sensing of temperature. However, to make the temperature readings unobstructed by optical heterogeneities of biological tissue, a PdTAPIP-based probe is supplemented by another probe system, based on H2DAPIP, which emits prompt fluorescence at the same wavelengths and can serve as a correction standard for unbiased temperature measurements.

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14

Clancy, Damian, and Christopher J. Pearce. "The effect of population heterogeneities upon spread of infection." Journal of Mathematical Biology 67, no. 4 (September 2, 2012): 963–87. http://dx.doi.org/10.1007/s00285-012-0578-x.

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15

Wang, Yanjun, Gang Li, Wenjuan Yan, Guoquan He, and Ling Lin. "Heterogeneity Detection Method for Transmission Multispectral Imaging Based on Contour and Spectral Features." Sensors 19, no. 24 (December 5, 2019): 5369. http://dx.doi.org/10.3390/s19245369.

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Transmission multispectral imaging (TMI) has potential value for medical applications, such as early screening for breast cancer. However, because biological tissue has strong scattering and absorption characteristics, the heterogeneity detection capability of TMI is poor. Many techniques, such as frame accumulation and shape function signal modulation/demodulation techniques, can improve detection accuracy. In this work, we develop a heterogeneity detection method by combining the contour features and spectral features of TMI. Firstly, the acquisition experiment of the phantom multispectral images was designed. Secondly, the signal-to-noise ratio (SNR) and grayscale level were improved by combining frame accumulation with shape function signal modulation and demodulation techniques. Then, an image exponential downsampling pyramid and Laplace operator were used to roughly extract and fuse the contours of all heterogeneities in images produced by a variety of wavelengths. Finally, we used the hypothesis of invariant parameters to do heterogeneity classification. Experimental results show that these invariant parameters can effectively distinguish heterogeneities with various thicknesses. Moreover, this method may provide a reference for heterogeneity detection in TMI.

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16

Bharti, Nita, Yingcun Xia, Ottar N. Bjornstad, and Bryan T. Grenfell. "Measles on the Edge: Coastal Heterogeneities and Infection Dynamics." PLoS ONE 3, no. 4 (April 9, 2008): e1941. http://dx.doi.org/10.1371/journal.pone.0001941.

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17

Zhang, Zhengjun. "Genomic Biomarker Heterogeneities between SARS-CoV-2 and COVID-19." Vaccines 10, no. 10 (October 2, 2022): 1657. http://dx.doi.org/10.3390/vaccines10101657.

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Genes functionally associated with SARS-CoV-2 infection and genes functionally related to the COVID-19 disease can be different, whose distinction will become the first essential step for successfully fighting against the COVID-19 pandemic. Unfortunately, this first step has not been completed in all biological and medical research. Using a newly developed max-competing logistic classifier, two genes, ATP6V1B2 and IFI27, stand out to be critical in the transcriptional response to SARS-CoV-2 infection with differential expressions derived from NP/OP swab PCR. This finding is evidenced by combining these two genes with another gene in predicting disease status to achieve better-indicating accuracy than existing classifiers with the same number of genes. In addition, combining these two genes with three other genes to form a five-gene classifier outperforms existing classifiers with ten or more genes. These two genes can be critical in fighting against the COVID-19 pandemic as a new focus and direction with their exceptional predicting accuracy. Comparing the functional effects of these genes with a five-gene classifier with 100% accuracy identified and tested from blood samples in our earlier work, the genes and their transcriptional response and functional effects on SARS-CoV-2 infection, and the genes and their functional signature patterns on COVID-19 antibodies, are significantly different. We will use a total of fourteen cohort studies (including breakthrough infections and omicron variants) with 1481 samples to justify our results. Such significant findings can help explore the causal and pathological links between SARS-CoV-2 infection and the COVID-19 disease, and fight against the disease with more targeted genes, vaccines, antiviral drugs, and therapies.

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Sart, Sébastien, Raphaël F. X. Tomasi, Antoine Barizien, Gabriel Amselem, Ana Cumano, and Charles N. Baroud. "Mapping the structure and biological functions within mesenchymal bodies using microfluidics." Science Advances 6, no. 10 (March 2020): eaaw7853. http://dx.doi.org/10.1126/sciadv.aaw7853.

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Organoids that recapitulate the functional hallmarks of anatomic structures comprise cell populations able to self-organize cohesively in 3D. However, the rules underlying organoid formation in vitro remain poorly understood because a correlative analysis of individual cell fate and spatial organization has been challenging. Here, we use a novel microfluidics platform to investigate the mechanisms determining the formation of organoids by human mesenchymal stromal cells that recapitulate the early steps of condensation initiating bone repair in vivo. We find that heterogeneous mesenchymal stromal cells self-organize in 3D in a developmentally hierarchical manner. We demonstrate a link between structural organization and local regulation of specific molecular signaling pathways such as NF-κB and actin polymerization, which modulate osteo-endocrine functions. This study emphasizes the importance of resolving spatial heterogeneities within cellular aggregates to link organization and functional properties, enabling a better understanding of the mechanisms controlling organoid formation, relevant to organogenesis and tissue repair.

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Akinwehinmi, Joseph, Taye Amos, and Kolawole Ogundari. "Consumer preferences for organic vegetables in southwestern Nigeria: A choice experiment approach." African Journal of Agricultural and Resource Economics 16, no. 1 (March 30, 2021): 1–13. http://dx.doi.org/10.53936/afjare.2021.16(2).01.

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In sub-Saharan Africa, identifying estimates of consumers’ preferences and willingness to pay (WTP) for safe food continues to receive attention in the literature. Using experimental data from Nigeria, we examined the source of heterogeneities in preference and WTP for organically produced food. The subjective valuation by consumers of certification in relation to third-party certification and the participatory guarantee system (PGS) was also investigated. A sample of 196 households subjected to a discrete choice experiment yielded 1 764 observations that were analysed using the generalised multinomial logit and mixed logit models. The results reveal a strong preference for food safety in terms of reducing chemical residue, which dominated the respondents’ preference and WTP patterns. Concerning certification attributes, consumers were positively disposed to third-party certification, but showed no significant preference for the PGS form of certification. Significant heterogeneities in preference were due mainly to age and awareness of organic products. We suggest that policies should focus on consumers’ understanding of organic food, third-party certification, and organic agriculture

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20

Ramar, Kaladevi, and . "Heterogeneity Management Using OAEI Benchmark Dataset." International Journal of Engineering & Technology 7, no. 3.12 (July 20, 2018): 481. http://dx.doi.org/10.14419/ijet.v7i3.12.16163.

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The evolution of ontologies and itsapplications are in various fields like artificial intelligence, reasoning, philosophy, biological science, and medical field. The components of ontologiesare concepts, instance, relationships, constraints, axioms and inference mechanism. Ontology is a main source for enabling interoperability in the semantic web. In this paper heterogeneities are identified between information systems and the possible rectification are carried out using OAEI benchmark datasets. Proposed method is compared with S-Match algorithm. The evaluation results shows that proposed method is performed better and structure changes of input ontologies not affect the results.

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21

Pigou, Maxime, and Jérôme Morchain. "Investigating the interactions between physical and biological heterogeneities in bioreactors using compartment, population balance and metabolic models." Chemical Engineering Science 126 (April 2015): 267–82. http://dx.doi.org/10.1016/j.ces.2014.11.035.

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Le Verge-Serandour, Mathieu, and Hervé Turlier. "A hydro-osmotic coarsening theory of biological cavity formation." PLOS Computational Biology 17, no. 9 (September 3, 2021): e1009333. http://dx.doi.org/10.1371/journal.pcbi.1009333.

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Fluid-filled biological cavities are ubiquitous, but their collective dynamics has remained largely unexplored from a physical perspective. Based on experimental observations in early embryos, we propose a model where a cavity forms through the coarsening of myriad of pressurized micrometric lumens, that interact by ion and fluid exchanges through the intercellular space. Performing extensive numerical simulations, we find that hydraulic fluxes lead to a self-similar coarsening of lumens in time, characterized by a robust dynamic scaling exponent. The collective dynamics is primarily controlled by hydraulic fluxes, which stem from lumen pressures differences and are dampened by water permeation through the membrane. Passive osmotic heterogeneities play, on the contrary, a minor role on cavity formation but active ion pumping can largely modify the coarsening dynamics: it prevents the lumen network from a collective collapse and gives rise to a novel coalescence-dominated regime exhibiting a distinct scaling law. Interestingly, we prove numerically that spatially biasing ion pumping may be sufficient to position the cavity, suggesting a novel mode of symmetry breaking to control tissue patterning. Providing generic testable predictions, our model forms a comprehensive theoretical basis for hydro-osmotic interaction between biological cavities, that shall find wide applications in embryo and tissue morphogenesis.

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23

Yanagisawa, Kiyoshi, Kosaku Uchida, Masaaki Nagatake, Akira Masuda, Miyabi Sugiyama, Toshiko Saito, Kenichi Yamaki, Takashi Takahashi, and Hirotaka Osada. "Heterogeneities in the biological and biochemical functions of Smad2 and Smad4 mutants naturally occurring in human lung cancers." Oncogene 19, no. 19 (May 2000): 2305–11. http://dx.doi.org/10.1038/sj.onc.1203591.

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Amoddeo, Antonino. "Indirect Contributions to Tumor Dynamics in the First Stage of the Avascular Phase." Symmetry 12, no. 9 (September 18, 2020): 1546. http://dx.doi.org/10.3390/sym12091546.

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A continuum model for tumor invasion in a two-dimensional spatial domain based on the interaction of the urokinase plasminogen activation system with a model for cancer cell dynamics is proposed. The arising system of partial differential equations is numerically solved using the finite element method. We simulated a portion of biological tissue imposing no flux boundary conditions. We monitored the cancer cell dynamics, as well the degradation of an extra cellular matrix representative, vitronectin, and the evolution of a specific degrading enzyme, plasmin, inside the biological tissue. The computations were parameterized as a function of the indirect cell proliferation induced by a plasminogen activator inhibitor binding to vitronectin and of the indirect plasmin deactivation due to the plasminogen activator inhibitor binding to the urokinase plasminogen activator. Their role during the cancer dynamical evolution was identified, together with a possible marker helping the mapping of the cancer invasive front. Our results indicate that indirect cancer cell proliferation biases the speed of the tumor invasive front as well as the heterogeneity of the cancer cell clustering and networking, as it ultimately acts on the proteolytic activity supporting cancer formation. Because of the initial conditions imposed, the numerical solutions of the model show a symmetrical dynamical evolution of heterogeneities inside the simulated domain. Moreover, an increase of up to about 12% in the invasion speed was observed, increasing the rate of indirect cancer cell proliferation, while increasing the plasmin deactivation rate inhibits heterogeneities and networking. As cancer cell proliferation causes vitronectin consumption and plasmin formation, the intensities of the concentration maps of both vitronectin and plasmin are superimposable to the cancer cell concentration maps. The qualitative imprinting that cancer cells leave on the extra cellular matrix during the time evolution as well their activity area is identified, framing the numerical results in the context of a methodology aimed at diagnostic and therapeutic improvement.

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Neves, Marta, and Daniel Martín-Yerga. "Advanced Nanoscale Approaches to Single-(Bio)entity Sensing and Imaging." Biosensors 8, no. 4 (October 26, 2018): 100. http://dx.doi.org/10.3390/bios8040100.

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Individual (bio)chemical entities could show a very heterogeneous behaviour under the same conditions that could be relevant in many biological processes of significance in the life sciences. Conventional detection approaches are only able to detect the average response of an ensemble of entities and assume that all entities are identical. From this perspective, important information about the heterogeneities or rare (stochastic) events happening in individual entities would remain unseen. Some nanoscale tools present interesting physicochemical properties that enable the possibility to detect systems at the single-entity level, acquiring richer information than conventional methods. In this review, we introduce the foundations and the latest advances of several nanoscale approaches to sensing and imaging individual (bio)entities using nanoprobes, nanopores, nanoimpacts, nanoplasmonics and nanomachines. Several (bio)entities such as cells, proteins, nucleic acids, vesicles and viruses are specifically considered. These nanoscale approaches provide a wide and complete toolbox for the study of many biological systems at the single-entity level.

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Richards, Paul, Gelejimah Alfred Mokuwa, Ahmed Vandi, and Susannah Harding Mayhew. "Re-analysing Ebola spread in Sierra Leone: The importance of local social dynamics." PLOS ONE 15, no. 11 (November 5, 2020): e0234823. http://dx.doi.org/10.1371/journal.pone.0234823.

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Background The 2013–15 Ebola epidemic in West Africa was the largest so far recorded, and mainly affected three adjacent countries, Guinea, Liberia and Sierra Leone. The worst affected country (in terms of confirmed cases) was Sierra Leone. The present paper looks at the epidemic in Sierra Leone. The epidemic in this country was a concatenation of local outbreaks. These local outbreaks are not well characterized through analysis using standard numerical techniques. In part, this reflects difficulties in record collection at the height of the epidemic. This paper offers a different approach, based on application of field-based techniques of social investigation that provide a richer understanding of the epidemic. Methods In a post-epidemic study (2016–18) of two districts (Bo and Moyamba) we use ethnographic data to reconstruct local infection pathways from evidence provided by affected communities, cross-referenced to records of the epidemic retained by the National Ebola Response Commission, now lodged in the Ebola Museum and Archive at Njala University. Our study documents and discusses local social and contextual factors largely missing from previously published studies. Results Our major finding is that the epidemic in Sierra Leone was a series of local outbreaks, some of which were better contained than others. In those that were not well contained, a number of contingent factors helps explain loss of control. Several numerical studies have drawn attention to the importance of local heterogeneities in the Sierra Leone Ebola epidemic. Our qualitative study throws specific light on a number of elements that explain these heterogeneities: the role of externalities, health system deficiencies, cultural considerations and local coping capacities. Conclusions Social issues and local contingencies explain the spread of Ebola in Sierra Leone and are key to understanding heterogeneities in epidemiological data. Integrating ethnographic research into epidemic-response is critical to properly understand the patterns of spread and the opportunities to intervene. This conclusion has significant implications for future interdisciplinary research and interpretation of standard numerical data, and consequently for control of epidemic outbreaks.

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Dalton, Helen M., Judith Stein, and Paul E. March. "A biological assay for detection of heterogeneities in the surface hydrophobicity of polymer coatings exposed to the marine environment." Biofouling 15, no. 1-3 (May 2000): 83–94. http://dx.doi.org/10.1080/08927010009386300.

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de Castro, Caio Porto, Gervásio Ferreira dos Santos, Anderson Dias de Freitas, Maria Isabel dos Santos, Roberto Fernandes Silva Andrade, and Maurício Lima Barreto. "Socio-economic urban scaling properties: Influence of regional geographic heterogeneities in Brazil." PLOS ONE 15, no. 12 (December 4, 2020): e0242778. http://dx.doi.org/10.1371/journal.pone.0242778.

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The recent efforts dedicated to understanding important features and consequences of city growth have profited from the scaling approach to urban indicators. This kind of analysis can be conveniently used to investigate the impact of geo-economic transformations, like fast urbanization and industrial development, which occurred in continental size countries (e.g., India, China, and Brazil) during the past half-century. Profiting from high quality data, this work explores how scaling relationships among urban indicators are influenced by strong regional heterogeneities in Brazil. It is based on economic, infrastructure and violence related data sets for the time interval 2002-2016. Results indicate that regional specificities related to infrastructure, economic development, and geography have a larger influence on the absolute value of the urban indexes. Regional scaling similarities and differences among Brazilian regions were also uncovered. Interesting enough, the results indicate that the richest and poorest Brazilian regions share similar scaling behavior, despite all huge different local influences. By contrast, the results for the two richest regions, with similar average values of urban indexes and the same kind of local influences have rather different scaling properties. Thus, scaling analysis suggests that distinct political solutions might be necessary to improve life’s quality, even for two regions with similar average values of urban indicators.

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Jomoui, Wittaya, Goonnapa Fucharoen, Kanokwan Sanchaisuriya, Van Hoa Nguyen, and Supan Fucharoen. "Hemoglobin Constant Spring among Southeast Asian Populations: Haplotypic Heterogeneities and Phylogenetic Analysis." PLOS ONE 10, no. 12 (December 18, 2015): e0145230. http://dx.doi.org/10.1371/journal.pone.0145230.

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Li, Li, Chang Liu, Fang Wang, Wei Miao, Jie Zhang, Zhiqian Kang, Yihan Chen, and Luying Peng. "Unraveling the Hidden Heterogeneities of Breast Cancer Based on Functional miRNA Cluster." PLoS ONE 9, no. 1 (January 30, 2014): e87601. http://dx.doi.org/10.1371/journal.pone.0087601.

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Wiemann, Jasmina, Jason M. Crawford, and Derek E. G. Briggs. "Phylogenetic and physiological signals in metazoan fossil biomolecules." Science Advances 6, no. 28 (July 2020): eaba6883. http://dx.doi.org/10.1126/sciadv.aba6883.

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Proteins, lipids, and sugars establish animal form and function. However, the preservation of biological signals in fossil organic matter is poorly understood. Here, we used high-resolution in situ Raman microspectroscopy to analyze the molecular compositions of 113 Phanerozoic metazoan fossils and sediments. Proteins, lipids, and sugars converge in composition during fossilization through lipoxidation and glycoxidation to form endogenous N-, O-, and S-heterocyclic polymers. Nonetheless, multivariate spectral analysis reveals molecular heterogeneities: The relative abundance of glycoxidation and lipoxidation products distinguishes different tissue types. Preserved chelating ligands are diagnostic of different modes of biomineralization. Amino acid–specific fossilization products retain phylogenetic information and capture higher-rank metazoan relationships. Molecular signals survive in deep time and provide a powerful tool for reconstructing the evolutionary history of animals.

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Sherrod, Laura, William Sauck, Edward Simpson, Dale Werkema, and Jarred Swiontek. "Case Histories of GPR for Animal Burrows Mapping and Geometry." Journal of Environmental and Engineering Geophysics 24, no. 1 (March 2019): 1–17. http://dx.doi.org/10.2113/jeeg24.1.1.

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Ground-penetrating radar (GPR) has a wide range of applications, from geologic mapping to concrete inspection. A recently emerging GPR application is deployment in biological investigations as a non-invasive technique. Geophysical mapping of features such as tree roots and turtle burrows has proved valuable for the understanding of these subsurface systems for ecological, environmental, or engineering purposes. Four case histories of GPR investigations pertaining to animal burrows are described: cutter ants in Brazil, groundhogs in Michigan, and groundhogs, and burrowing bees in Pennsylvania. Cutter ants ( Atta spp.) in Amazonian Brazil are known to construct burrows of nearly the same dimensions as groundhogs as they excavate galleries up to 7 m deep for leaf storage. Cutter ant burrows are hazardous to heavy equipment and may also cause loss of mud circulation during rotary drilling. Groundhogs ( Marmota monax), found throughout the United States, cause unseen hazards, particularly for equestrian facilities where a sudden collapse can cause severe injuries to both horse and rider. Burrowing bees ( Colletes inaequalis) are common in the northeastern United States. The size of the bee burrows is significantly smaller than that of the cutter ants and the groundhogs. The data for these surveys were collected over a twenty-year span, crossing several generations of survey equipment and processing techniques. Together, these four case histories highlight the historic and current capabilities of GPR systems applied to mapping subsurface burrow systems. These examples demonstrate the important impact near surface heterogeneities have in altering ecological, environmental, or engineering systems and the utility of GPR for mapping such heterogeneities.

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Takahashi, Eiji, Tomohiro Takano, Yasutomo Nomura, Satoshi Okano, Osamu Nakajima, and Michihiko Sato. "In vivo oxygen imaging using green fluorescent protein." American Journal of Physiology-Cell Physiology 291, no. 4 (October 2006): C781—C787. http://dx.doi.org/10.1152/ajpcell.00067.2006.

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In vivo oxygen measurement is the key to understanding how biological systems dynamically adapt to reductions in oxygen supply. High spatial resolution oxygen imaging is of particular importance because recent studies address the significance of within-tissue and within-cell heterogeneities in oxygen concentration in health and disease. Here, we report a new technique for in vivo molecular imaging of oxygen in organs using green fluorescent protein (GFP). GFP-expressing COS-7 cells were briefly photoactivated with a strong blue light while lowering the oxygen concentration from 10% to <0.001%. Red fluorescence (excitation 520–550 nm, emission >580 nm) appeared after photoactivation at <2% oxygen (the red shift of GFP fluorescence). The red shift disappeared after reoxygenation of the cell, indicating that the red shift is stable as long as the cell is hypoxic. The red shift of GFP fluorescence was also demonstrated in single cardiomyocytes isolated from the GFP knock-in mouse (green mouse) heart. Then, we tried in vivo molecular imaging of hypoxia in organs. The red shift could be imaged in the ischemic liver and kidney in the green mouse using macroscopic optics provided that oxygen diffusion from the atmospheric air was prevented. In crystalloid-perfused beating heart isolated from the green mouse, significant spatial heterogeneities in the red shift were demonstrated in the epicardium distal to the coronary artery ligation. We conclude that the present technique using GFP as an oxygen indicator may allow in vivo molecular imaging of oxygen in organs.

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Nie, Ming, Qiang Yang, Li-Fen Jiang, Chang-Ming Fang, Jia-Kuan Chen, and Bo Li. "Do plants modulate biomass allocation in response to petroleum pollution?" Biology Letters 6, no. 6 (May 19, 2010): 811–14. http://dx.doi.org/10.1098/rsbl.2010.0261.

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Biomass allocation is an important plant trait that responds plastically to environmental heterogeneities. However, the effects on this trait of pollutants owing to human activities remain largely unknown. In this study, we investigated the response of biomass allocation of Phragmites australis to petroleum pollution by a 13 CO 2 pulse-labelling technique. Our data show that plant biomass significantly decreased under petroleum pollution, but the root–shoot ratio for both plant biomass and 13 C increased with increasing petroleum concentration, suggesting that plants could increase biomass allocation to roots in petroleum-polluted soil. Furthermore, assimilated 13 C was found to be significantly higher in soil, microbial biomass and soil respiration after soils were polluted by petroleum. These results suggested that the carbon released from roots is rapidly turned over by soil microbes under petroleum pollution. This study found that plants can modulate biomass allocation in response to petroleum pollution.

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35

Plavchak, Christine L., William C. Smith, Carmen R. M. Bria, and S. Kim Ratanathanawongs Williams. "New Advances and Applications in Field-Flow Fractionation." Annual Review of Analytical Chemistry 14, no. 1 (June 5, 2021): 257–79. http://dx.doi.org/10.1146/annurev-anchem-091520-052742.

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Field-flow fractionation (FFF) is a family of techniques that was created especially for separating and characterizing macromolecules, nanoparticles, and micrometer-sized analytes. It is coming of age as new nanomaterials, polymers, composites, and biohybrids with remarkable properties are introduced and new analytical challenges arise due to synthesis heterogeneities and the motivation to correlate analyte properties with observed performance. Appreciation of the complexity of biological, pharmaceutical, and food systems and the need to monitor multiple components across many size scales have also contributed to FFF's growth. This review highlights recent advances in FFF capabilities, instrumentation, and applications that feature the unique characteristics of different FFF techniques in determining a variety of information, such as averages and distributions in size, composition, shape, architecture, and microstructure and in investigating transformations and function.

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36

Kawli, Tprupti S., and Sonia Kaushik. "Cell fate choice and social evolution indictyostelium discoideum: interplay of morphogens and heterogeneities." Journal of Biosciences 26, no. 2 (June 2001): 130–33. http://dx.doi.org/10.1007/bf02703636.

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37

Garske, Tini, Anne Cori, Archchun Ariyarajah, Isobel M. Blake, Ilaria Dorigatti, Tim Eckmanns, Christophe Fraser, et al. "Heterogeneities in the case fatality ratio in the West African Ebola outbreak 2013–2016." Philosophical Transactions of the Royal Society B: Biological Sciences 372, no. 1721 (April 10, 2017): 20160308. http://dx.doi.org/10.1098/rstb.2016.0308.

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The 2013–2016 Ebola outbreak in West Africa is the largest on record with 28 616 confirmed, probable and suspected cases and 11 310 deaths officially recorded by 10 June 2016, the true burden probably considerably higher. The case fatality ratio (CFR: proportion of cases that are fatal) is a key indicator of disease severity useful for gauging the appropriate public health response and for evaluating treatment benefits, if estimated accurately. We analysed individual-level clinical outcome data from Guinea, Liberia and Sierra Leone officially reported to the World Health Organization. The overall mean CFR was 62.9% (95% CI: 61.9% to 64.0%) among confirmed cases with recorded clinical outcomes. Age was the most important modifier of survival probabilities, but country, stage of the epidemic and whether patients were hospitalized also played roles. We developed a statistical analysis to detect outliers in CFR between districts of residence and treatment centres (TCs), adjusting for known factors influencing survival and identified eight districts and three TCs with a CFR significantly different from the average. From the current dataset, we cannot determine whether the observed variation in CFR seen by district or treatment centre reflects real differences in survival, related to the quality of care or other factors or was caused by differences in reporting practices or case ascertainment. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.

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Lloyd, Alun L., Uriel Kitron, T. Alex Perkins, Gonzalo M. Vazquez-Prokopec, and Lance A. Waller. "The basic reproductive number for disease systems with multiple coupled heterogeneities." Mathematical Biosciences 321 (March 2020): 108294. http://dx.doi.org/10.1016/j.mbs.2019.108294.

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Schleinkofer, Nicolai, Jacek Raddatz, André Freiwald, David Evans, Lydia Beuck, Andres Rüggeberg, and Volker Liebetrau. "Environmental and biological controls on Na∕Ca ratios in scleractinian cold-water corals." Biogeosciences 16, no. 18 (September 20, 2019): 3565–82. http://dx.doi.org/10.5194/bg-16-3565-2019.

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Abstract. Here we present a comprehensive attempt to correlate aragonitic Na∕Ca ratios from Desmophyllum pertusum (formerly known as Lophelia pertusa), Madrepora oculata and a caryophylliid cold-water coral (CWC) species with different seawater parameters such as temperature, salinity and pH. Living CWC specimens were collected from 16 different locations and analyzed for their Na∕Ca ratios using solution-based inductively coupled plasma-optical emission spectrometry (ICP-OES) measurements. The results reveal no apparent correlation with salinity (30.1–40.57 g kg−1) but a significant inverse correlation with temperature (-0.31±0.04 mmolmol-1∘C-1). Other marine aragonitic organisms such as Mytilus edulis (inner aragonitic shell portion) and Porites sp. exhibit similar results highlighting the consistency of the calculated CWC regressions. Corresponding Na∕Mg ratios show a similar temperature sensitivity to Na∕Ca ratios, but the combination of two ratios appears to reduce the impact of vital effects and domain-dependent geochemical variation. The high degree of scatter and elemental heterogeneities between the different skeletal features in both Na∕Ca and Na∕Mg, however, limit the use of these ratios as a proxy and/or make a high number of samples necessary. Additionally, we explore two models to explain the observed temperature sensitivity of Na∕Ca ratios for an open and semi-enclosed calcifying space based on temperature-sensitive Na- and Ca-pumping enzymes and transport proteins that change the composition of the calcifying fluid and consequently the skeletal Na∕Ca ratio.

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40

Alves, Carlos, Carlos Figueiredo, and Jorge Sanjurjo-Sánchez. "Rock Features and Alteration of Stone Materials Used for the Built Environment: A Review of Recent Publications on Ageing Tests." Geosciences 10, no. 3 (February 28, 2020): 91. http://dx.doi.org/10.3390/geosciences10030091.

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This work presents a review of recent publications, with publication date between 2017 and 2019, with information on the relation between rock characteristics and the effects of diverse agents associated with alteration of stone materials in the built environment. It considers information obtained from ageing tests performed under laboratory conditions and by exposure to outdoor agents. Several lithological groups were considered, with sedimentary carbonate rocks being the most frequently studied lithotypes and silicate metamorphic rocks being the group with scarcer information. In terms of ageing tests, salt weathering was the most frequent one while there was a noticeable lesser amount of information from tests with biological colonization. The collected data showed the influence of diverse features, from specific minerals to whole-rock properties and the presence of heterogeneities. These information are discussed in the context of formulating a general framework for stone decay.

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Mitsunaga, Takayuki, and Koichi Fujii. "The effects of spatial and temporal environmental heterogeneities on persistence in a laboratory experimental community." Researches on Population Ecology 39, no. 2 (December 1997): 249–60. http://dx.doi.org/10.1007/bf02765271.

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42

Heberle, Frederick A., Milka Doktorova, Haden L. Scott, Allison D. Skinkle, M. Neal Waxham, and Ilya Levental. "Direct label-free imaging of nanodomains in biomimetic and biological membranes by cryogenic electron microscopy." Proceedings of the National Academy of Sciences 117, no. 33 (August 5, 2020): 19943–52. http://dx.doi.org/10.1073/pnas.2002200117.

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The nanoscale organization of biological membranes into structurally and compositionally distinct lateral domains is believed to be central to membrane function. The nature of this organization has remained elusive due to a lack of methods to directly probe nanoscopic membrane features. We show here that cryogenic electron microscopy (cryo-EM) can be used to directly image coexisting nanoscopic domains in synthetic and bioderived membranes without extrinsic probes. Analyzing a series of single-component liposomes composed of synthetic lipids of varying chain lengths, we demonstrate that cryo-EM can distinguish bilayer thickness differences as small as 0.5 Å, comparable to the resolution of small-angle scattering methods. Simulated images from computational models reveal that features in cryo-EM images result from a complex interplay between the atomic distribution normal to the plane of the bilayer and imaging parameters. Simulations of phase-separated bilayers were used to predict two sources of contrast between coexisting ordered and disordered phases within a single liposome, namely differences in membrane thickness and molecular density. We observe both sources of contrast in biomimetic membranes composed of saturated lipids, unsaturated lipids, and cholesterol. When extended to isolated mammalian plasma membranes, cryo-EM reveals similar nanoscale lateral heterogeneities. The methods reported here for direct, probe-free imaging of nanodomains in unperturbed membranes open new avenues for investigation of nanoscopic membrane organization.

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Saison, C., P. Cattan, X. Louchart, and M. Voltz. "Effect of Spatial Heterogeneities of Water Fluxes and Application Pattern on Cadusafos Fate on Banana-Cultivated Andosols." Journal of Agricultural and Food Chemistry 56, no. 24 (December 24, 2008): 11947–55. http://dx.doi.org/10.1021/jf802435c.

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Ayibaike, Dilinuer, Mingyang Cui, and Jiaqi Wei. "Single-Cell Patterning Based on Immunocapture and a Surface Modified Substrate." Applied Sciences 8, no. 11 (November 3, 2018): 2152. http://dx.doi.org/10.3390/app8112152.

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Micropatterning technology offers powerful methods for biological analyses at the molecular level, enabling the investigation of cell heterogeneities, as well as high throughput detection. We herein propose an approach for single-cell patterning. The substrate was prepared using micro fabrication and surface modification processes, and the patterning template was prepared using bovine serum albumin and streptavidin, which can be employed for the patterning of any biological molecules containing biotin. Subsequent to photolithography, etching, chemical vapor deposition (CVD), and polyethylene glycol (PEG) treatment, the optimized patterns were obtained with high accuracy, strong contrast, and good repeatability, thus providing good foundations for the subsequent single-cell patterning. The surface passivation method was proven effective, preventing unwanted binding of the antibodies and cells. Based on this streptavidin template, the specific binding between the biotinylated antibodies and the antigens expressed on the surface of the cells was enabled, and we successfully achieved single-cell patterning with a single-cell capture rate of 92%. This single-cell array offers an effective method in the investigation of cell heterogeneity and drug screening. Further, these methods can be used in the final step for the screening and enrichment of certain cells, such as circulating tumor cells.

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Childs, Lauren M., and Caroline O. Buckee. "Dissecting the determinants of malaria chronicity: why within-host models struggle to reproduce infection dynamics." Journal of The Royal Society Interface 12, no. 104 (March 2015): 20141379. http://dx.doi.org/10.1098/rsif.2014.1379.

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The duration of infection is fundamental to the epidemiological behaviour of any infectious disease, but remains one of the most poorly understood aspects of malaria. In endemic areas, the malaria parasite Plasmodium falciparum can cause both acute, severe infections and asymptomatic, chronic infections through its interaction with the host immune system. Frequent superinfection and massive parasite genetic diversity make it extremely difficult to accurately measure the distribution of infection lengths, complicating the estimation of basic epidemiological parameters and the prediction of the impact of interventions. Mathematical models have qualitatively reproduced parasite dynamics early during infection, but reproducing long-lived chronic infections remains much more challenging. Here, we construct a model of infection dynamics to examine the consequences of common biological assumptions for the generation of chronicity and the impact of co-infection. We find that although a combination of host and parasite heterogeneities are capable of generating chronic infections, they do so only under restricted parameter choices. Furthermore, under biologically plausible assumptions, co-infection of parasite genotypes can alter the course of infection of both the resident and co-infecting strain in complex non-intuitive ways. We outline the most important puzzles for within-host models of malaria arising from our analysis, and their implications for malaria epidemiology and control.

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46

Bae, JuneSung, Yun Sik Choi, Gunsik Cho, and Se Jin Jang. "The Patient-Derived Cancer Organoids: Promises and Challenges as Platforms for Cancer Discovery." Cancers 14, no. 9 (April 25, 2022): 2144. http://dx.doi.org/10.3390/cancers14092144.

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The cancer burden is rapidly increasing in most countries, and thus, new anticancer drugs for effective cancer therapy must be developed. Cancer model systems that recapitulate the biological processes of human cancers are one of the cores of the drug development process. PDCO has emerged as a unique model that preserves the genetic, physiological, and histologic characteristics of original cancer, including inter- and intratumoral heterogeneities. Due to these advantages, the PCDO model is increasingly investigated for anticancer drug screening and efficacy testing, preclinical patient stratification, and precision medicine for selecting the most effective anticancer therapy for patients. Here, we review the prospects and limitations of PDCO compared to the conventional cancer models. With advances in culture success rates, co-culture systems with the tumor microenvironment, organoid-on-a-chip technology, and automation technology, PDCO will become the most promising model to develop anticancer drugs and precision medicine.

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Bae, JuneSung, Yun Sik Choi, Gunsik Cho, and Se Jin Jang. "The Patient-Derived Cancer Organoids: Promises and Challenges as Platforms for Cancer Discovery." Cancers 14, no. 9 (April 25, 2022): 2144. http://dx.doi.org/10.3390/cancers14092144.

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Анотація:

The cancer burden is rapidly increasing in most countries, and thus, new anticancer drugs for effective cancer therapy must be developed. Cancer model systems that recapitulate the biological processes of human cancers are one of the cores of the drug development process. PDCO has emerged as a unique model that preserves the genetic, physiological, and histologic characteristics of original cancer, including inter- and intratumoral heterogeneities. Due to these advantages, the PCDO model is increasingly investigated for anticancer drug screening and efficacy testing, preclinical patient stratification, and precision medicine for selecting the most effective anticancer therapy for patients. Here, we review the prospects and limitations of PDCO compared to the conventional cancer models. With advances in culture success rates, co-culture systems with the tumor microenvironment, organoid-on-a-chip technology, and automation technology, PDCO will become the most promising model to develop anticancer drugs and precision medicine.

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Pajtler, Kristian, and Elizabeth Gerstner. "Ependymoma." Seminars in Neurology 38, no. 01 (February 2018): 104–11. http://dx.doi.org/10.1055/s-0038-1636503.

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AbstractEpendymoma can arise throughout the whole neuraxis. In children, tumors predominantly occur intracranially, whereas the spine is the most prevalent location in adults. Significant variance in the grade II versus grade III distinction of ependymomas has led to the acknowledgment that the clinical utility of histopathological classification is limited. Epigenomic profiling efforts have identified molecularly distinct groups of ependymomas that adequately reflect the biological, clinical, and histopathological heterogeneities across anatomical compartments, age groups, and grades. The recent update of the World Health Organization classification of central nervous system tumors has already integrated one of these groups, and molecular classification will be part of future clinical trials to improve risk stratification. Clinical management of this rare disease is challenging, making professional experience and intensified multidisciplinary cooperation pivotal factors for treatment success. Novel research strategies are currently applied for target discovery in ependymomas since for most molecular groups, genetic drivers are unknown.

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Beltran, Chris, H. Wan Chan Tseung, Kurt E. Augustine, Martin Bues, Daniel W. Mundy, Timothy J. Walsh, Michael G. Herman, and Nadia N. Laack. "Clinical Implementation of a Proton Dose Verification System Utilizing a GPU Accelerated Monte Carlo Engine." International Journal of Particle Therapy 3, no. 2 (September 1, 2016): 312–19. http://dx.doi.org/10.14338/ijpt-16-00011.1.

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Abstract Purpose: To develop a clinical infrastructure that allows for routine Monte Carlo dose calculation verification of spot scanning proton treatment plans and includes a simple biological model to aid in normal tissue protection. Materials and Methods: A graphical processing unit accelerated Monte Carlo dose engine was used as the calculation engine for dose verification on spot scanning proton plans. An infrastructure was built around this engine that allows for seamless exporting of treatment plans from the treatment planning system and importing of dose distribution from the Monte Carlo calculation via DICOM (digital imaging and communications in medicine). An easy-to-use Web-based interface was developed so that the application could be run from any computer. In addition to the standard relative biological effectiveness = 1.1 for proton therapy, a simple linear equation dependent on dose-weighted linear energy transfer was included. This was used to help detect possible high biological dose in critical structures. Results: More than 270 patients were treated at our proton center in the first year of operation. Because most plans underwent multiple iterations before final approval, more than 1000 plans have been run through the system from multiple users with minimal downtime. The average time from plan export to importing of the Monte Carlo doses was less than 15 minutes. Treatment plans have been modified based on the nominal Monte Carlo dose or the biological dose. Conclusion: Monte Carlo dose calculation verification of spot scanning proton treatment plans is feasible in a clinical environment. The 3-dimensional dose verification, particularly near heterogeneities, has resulted in plan modifications. The biological dose data provides actionable feedback for end of range effects, especially in pediatric patients.

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Hiebeler, David E. "Competing populations on fragmented landscapes with spatially structured heterogeneities: improved landscape generation and mixed dispersal strategies." Journal of Mathematical Biology 54, no. 3 (December 7, 2006): 337–56. http://dx.doi.org/10.1007/s00285-006-0054-6.

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