Pulse and Impulse Response in Human Tissues

Mechanical properties of soft human tissues under dynamic loading

The use of tissue cultures as a research tool to investigate the pathophysiological bases of diseases has become essential in the current ag of molecular biomedical research. Although it will always be necessary to translate and validate the observations seen in vitro to the patient or animal, the ability to investigate the role(s) of individual variables free from confounders is paramount toward increasing our understanding of the physiology and their role in disease. Additionally, it is not feasible to conduct certain research in humans because of ethical constraints, yet investigators may still be interested in the physiological response in human tissues; in vitro characterization of human tissue is an acceptable choice. Tissue culture techniques have been utilized extensively to investigate questions pertaining to physiology and disease. The isolation and propagation of human epithelial cells has allowed investigators to begin to characterize the interactions and reactions that occur in response to various stimuli. Moreover, the culture of other human tissue has allowed researchers to investigate pathological cascades as well as other physiological responses. Combining cultured endothelial cells and leukocytes together in vitro under laminar flow conditions has helped elucidate the critical interactions that occur in rolling and emigration of leukocytes during the inflammatory response. Cultured embryonic stem cells that had been subjected to various growth conditions have advanced our understanding of cellular differentiation and growth.

T-cell receptor sequencing (TCRseq) enables tracking of T-cell clonotypes recognizing the same antigen over time and across biological compartments. TCRseq has been used to test if cross-reactive antitumor T cells are responsible for development of immune-related adverse events (irAEs) following immune checkpoint blockade. Prior studies have interpreted T-cell clones shared among the tumor and irAE as evidence supporting this, but interpretations of these findings are challenging, given the constraints of TCRseq. Here we capitalize on a rare opportunity to understand the impact of potential confounders, such as sample size, tissue compartment, and collection batch/timepoint, on the relative proportion of shared T-cell clones between an irAE and tumor specimens. TCRseq was performed on tumor-involved and -uninvolved tissues, including an irAE, that were obtained throughout disease progression and at the time of rapid autopsy from a patient with renal cell carcinoma treated with programmed death-1 (PD-1) blockade. Our analyses show significant effects of these confounders on our ability to understand T-cell receptor overlap, and we present mitigation strategies and study design recommendations to reduce these errors. Implementation of these strategies will enable more rigorous TCRseq-based studies of immune responses in human tissues, particularly as they relate to antitumor T-cell cross-reactivity in irAEs following checkpoint blockade.

The future of personal composite body armor to protect against impacts will inevitably be lighter, stronger, and more flexible to increase comfort for the user. Simulating the performance of the flexible materials requires modeling in finite element analysis using more advanced bio-compatible, bio-inspired composite materials for both the armor and the human soft tissue. These next generation of materials are highly hyper-viscoelastic with extreme hardening under high rate loading which is a current limitation for many numerical simulations. These limitations are addressed starting at the initial assumptions for continuum mechanics and general non-linear assumptions made for the viscoelastic materials. Applying the current built-in finite element code, an Hydrogel is tested via low velocity impacts in both experimental tests and numerical analysis. The results show that there is discrepancy between the two dynamic impact behaviors, whereby the force response of the real test is significantly longer in duration and with slower rise time compared to the numerical results. It is expected that in more extreme impact conditions that will be explored, these differences will diverge more dramatically and invalidate the finite element predictions. This shortcoming can only be prevented by introducing more strong non-linearity in the fundamental material properties and conditions in the impact model approximation.

The antisecretory effects of several Y agonists, including pancreatic polypeptide (PP), indicate the presence of Y(1), Y(2), and Y(4) receptors in mouse and human (h) colon mucosae. Here, we used preparations from human and from wild-type (WT), Y(4), and Y(1) receptor knockout ((-/-)) mice, alongside Y(4) receptor-transfected cells to define the relative functional contribution of the Y(4) receptor. First, rat (r) PP antisecretory responses were lost in murine Y(4)(-/-) preparations, but hPP and Pro(34) peptide YY (PYY) costimulated Y(4) and Y(1) receptors in WT mucosa. The Y(1) antagonist/Y(4) agonist GR231118 [(Ile,Glu,Pro,Dpr,Tyr,Arg,Leu,Arg,Try-NH(2))-2-cyclic(2,4'),(2',4)-diamide] elicited small Y(4)-mediated antisecretory responses in human tissues pretreated with the Y(1) antagonist, BIBO3304 [(R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]methyl]-N(2)-(diphenylacetyl)-argininamide trifluoroacetate)], and attenuated Y(4)-mediated hPP responses in mouse and human mucosa. GR231118 and rPP were also antisecretory in hY(4)-transfected epithelial monolayers but were partial agonists compared with hPP at this receptor. In Y(4)-transfected human embryonic kidney (HEK) 293 cells, Y(4) ligands displaced [(125)I]hPP binding with orders of affinity (pK(i)) at human (hPP = rPP > GR231118 > Pro(34)PYY = PYY) and mouse (rPP = hPP > GR231118 > Pro(34)PYY > PYY) Y(4) receptors. GR231118- and rPP-stimulated guanosine 5'-3-O-(thio)triphosphate binding through hY(4) receptors with significantly lower efficacy than hPP. GR231118 marginally increased basal but abolished further PP-induced hY(4) internalization to recycling (transferrin-labeled) pathways in HEK293 cells. Taken together, these findings show that Y(4) receptors play a definitive role in attenuating colonic anion transport and may be useful targets for novel antidiarrheal agents due to their limited peripheral expression.

Fatty acid ethyl ester (FAEE) associated acute pancreatitis: An ex-vivo study using human pancreatic acini

Conference Article| June 01 1987 Prostacyclin production by cultured human endothelial cells and tissue homogenates in response to fish liver extracts C. EVANS; C. EVANS 1Department of Chemistry and Biochemistry, Liverpool Polytechnic, Byrom Street, Liverpool L3 3AF, U.K. Search for other works by this author on: This Site PubMed Google Scholar D. BILLINGTON; D. BILLINGTON 1Department of Chemistry and Biochemistry, Liverpool Polytechnic, Byrom Street, Liverpool L3 3AF, U.K. Search for other works by this author on: This Site PubMed Google Scholar F. A. McEVOY F. A. McEVOY 1Department of Chemistry and Biochemistry, Liverpool Polytechnic, Byrom Street, Liverpool L3 3AF, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1987) 15 (3): 563–564. https://doi.org/10.1042/bst0150563 Article history Received: December 22 1986 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation C. EVANS, D. BILLINGTON, F. A. McEVOY; Prostacyclin production by cultured human endothelial cells and tissue homogenates in response to fish liver extracts. Biochem Soc Trans 1 June 1987; 15 (3): 563–564. doi: https://doi.org/10.1042/bst0150563 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1987 Biochemical Society1987 Article PDF first page preview Close Modal You do not currently have access to this content.

Objective To investigate influence on dose distribution due to cavity and inhomogeneous structures using thermoluminescence dosimeters (TLD) and Chengdu phantoms.Methods A cavity 4 cm × 4 cm × 3 cm was made by a head and neck phantom and a lung phantom was cut into slices which were got a CT scanning and setup in a digital simulator.The TLD were pasted on edge and in the center of cavity structure and inhomogeneous structures.Treatment plans of different radiotherapy technologies were made generated and delivered on a linear accelerator.Then the TLD were read and analyzed.Results There were remarkable cavity effects of conventional single field,opposite fields and IMRT plans with 7 fields for head and neck phantom.There is similar effect in lung phantom.The more complexity the radiotherapy technology was the less cavity effect.Conclusions It is necessary to consider using more advanced radiotherapy technology or applying more fields to make treatment plans in order to decrease the cavity effect or similar effect when there are inhomogeneous structures. Key words: Chengdudosimetric phantoms ; Cavity; Inhomogeneous tissue; Thermoluminescence

A global review for the hydrodynamic response investigation method of submerged floating tunnels

Исследование взаимодействия электромагнитных волн с неоднородной плазмой позволяет значительно улучшить существующие представления о динамике волн в сильно неоднородных и нестационарных диэлектрических средах, а также имеет большое значение для различных практических приложений, таких как нагрев плазмы, диагностика и интерпретация экспериментальных данных. Представляет интерес анализ возможностей реализации безотражательного прохождения волн через волновые барьеры на основе разработки точно решаемых физикоматематических моделей. В работе проведён анализ такой модели на основе нелинейного уравнения, определяющего профиль эффективной диэлектрической проницаемости плазмы в зависимости от выбора профиля безразмерного волнового вектора с учетом положительности профиля безразмерной плотности плазмы. В работе рассмотрено распространение электромагнитных волн для случая периодических возмущений и для случая локализованных неоднородностей. Показано, что при соответствующем выборе параметров задачи могут получаться достаточно сложные пространственные профили, реализующие безотражательное распространение электромагнитной волны через неоднородную плазму. The study of the interaction of electromagnetic waves with inhomogeneous plasma can significantly improve the existing concepts about the dynamics of waves in highly inhomogeneous and nonstationary dielectric media, and is also of great importance for various practical applications, such as plasma heating, diagnostics and interpretation of experimental data. It is of interest to analyze the possibilities of implementing reflectionless wave passage through wave barriers based on the development of exactly solvable physical and mathematical models. This paper analyzes such a model based on a nonlinear equation that determines the effective dielectric permittivity profile of the plasma depending on the choice of the dimensionless wave vector profile, taking into account the positive profile of the dimensionless plasma density. The propagation of electromagnetic waves for the case of periodic perturbations and for the case of localized inhomogeneities is considered. It is shown that with an appropriate choice of the parameters of the problem, rather complex spatial profiles can be obtained that implement reflectionless propagation of the electromagnetic wave through the inhomogeneous plasma.

This work aims to describe the dielectric behaviors of four main tissues in the human forearm using mathematical modelling, including fat, muscle, blood and bone. Multi-frequency bioimpedance analysis (MF-BIA) was initially performed using the finite element method (FEM) with a 3D forearm model to estimate impedance spectra from 10 kHz to 1 MHz, followed by a pilot study involving two healthy subjects to characterize the response of actual forearm tissues from 1 kHz to 349 kHz. Both the simulation and experimental results were fitted to a single-dispersion Cole model (SDCM) and a multi-dispersion Cole model (MDCM) to determine the Cole parameters for each tissue. Cole-type responses of both simulated and actual human forearms were observed. A paired t-test based on the root mean squared error (RMSE) values indicated that both Cole models performed comparably in fitting both simulated and measured bioimpedance data. However, MDCM exhibited higher accuracy, with a correlation coefficient (R2) of 0.99 and 0.89, RMSE of 0.22 Ω and 0.56 Ω, mean difference (mean ± standard deviation) of 0.00 ± 0.23 Ω and -0.28 ± 0.23 Ω, and mean absolute error (MAE) of 0.0007 Ω and 0.2789 Ω for the real part and imaginary part of impedance, respectively. Determining the electrical response of multi-tissues can be helpful in developing physiological monitoring of an organ or a section of the human body through MF-BIA and hemodynamic monitoring by filtering out the impedance contributions from the surrounding tissues to blood-flow-induced impedance variations.

High-resolution phosphor imaging: validation for use with human brain tissue sections to determine the affinity and density of radioligand binding

Introduction ; Adequate tissue oxygenation is vital for resuscitation. Intravascular O 2 carrying compounds may enhance tissue O 2 delivery under ischemic conditions but use of both hemoglobin and nonhemoglobin O 2 carriers have limitations. Use of compounds capable of producing O 2 at the tissue level may be useful. Solid peroxides such as percarbamide may provide novel means of tissue O 2 delivery since they contain stored O 2 which can be released upon activation with catalase. However, the chemistry is complex and a product must be designed for controlled O 2 production. Objectives : To develop and use a mathematical and physical model to examine the feasibility of creating encapsulated solid peroxides for intravenous O 2 delivery. Methods : An O 2 delivery vehicle combining percarbamide, a non-aqueous liquid carrier, and a biodegradable-compatible polymer coating was developed for controlled O 2 production. Upon contact with plasma, water diffuses across the polymer coating to cause release of H 2 O 2 from percarbamide. The H 2 O 2 then diffuses back across the membrane into plasma reacting with the blood enzyme catalase to form O 2 and water. A permeation cell system was constructed to validate the physical chemistry of this controlled O 2 production approach. A mathematical model incorporating Fickian diffusion and shrinking surface kinetics was derived to model O 2 production. Results : The permeation cell experiments validated the physical chemistry approach of delivering O 2 using encapsulated percarbamide. The mathematical model successfully predicted O 2 release. Experimental and modeling results show that by tuning the coating thickness, coating type, non-aqueous carrier liquid, and solid peroxide size, the rate of O 2 production can be precisely controlled. Percarbamide (150 gms) would produce 250 cc/min of O 2 for 60 minutes to meet whole body metabolic demands. Conclusions : A mathematical and physical model of O 2 production was successfully created allowing manipulation of multiple variables related to releasing O 2 from a solid peroxide delivery system. Experimental results validate the model’s accuracy. This work suggests the feasibility of using encapsulated solid peroxides to produce life sustaining amounts of O 2 for intravenous tissue oxygenation.

Introduction : 3D anthropomorphic models of human tissues have become a requirement for conducting realistic virtual studies. One of the current directions in the research of X-ray imaging is the development of physical models with 3D printing techniques using specific materials aiming to obtain replica of the human body tissues with similar radiological characteristics. Aim : The aim of this study is to create a calibration phantom for establishing the X-ray properties of different cartridge infills and their suitability to represent the X-ray properties of different breast types. Materials and Methods : A physical calibration model consisting of 22 objects was designed and printed by using an inkjet printer. A mixture was obtained from 5 mL printer ink and 3 g of potassium iodide (KI), which was used to fill the printer’s cartridge and to print the model on a set of plain office paper. Experimental X-ray images of the physical model were acquired on radiographic system SEDECAL X PLUS LP+. The obtained attenuation coefficient of the printing mixture was evaluated and compared to the breast tissue coefficients corresponding to the used X-ray energy. Results and Discussion : The physical model was printed on ten office sheets and stacked above one another. The obtained attenuation coefficient of the printing mixture was found very similar to that of the glandular tissue of the breast for the used X-ray energy. Conclusion: The obtained printer ink-KI mixture is suitable for representing the glandular part of breast tissue. The method has the potential to be used for creation of a realistic physical breast model.

1. The ability of fat-free homogenates of human adipose tissue to incorporate [1-14C]palmitate into neutral lipid and long-chain fatty acyl-CoA has been studied. Homogenates readily incorporated [1-14C]palmitate into neutral lipid. Addition of l-glycerol 3-phosphate was required before synthesis of neutral lipid occurred whereas the system contained sufficient endogenous fatty acid for esterification with l-glycerol 3-phosphate. 2. Glucose, glucose 6-phosphate and fructose 1,6-diphosphate could replace l-glycerol 3-phosphate if the system was supplemented with NADH. The order of efficiency of each substrate to support esterification of [1-14C]palmitate was: l-glycerol 3-phosphate, fructose, 1,6-diphosphate, glucose 6-phosphate and glucose. 3. Factors known to alter the activity of phosphofructokinase (E.C.2.7.1.11) also altered the rates of incorporation of [1-14C]palmitate into neutral lipid. Thus citrate (10 mm) inhibited lipogenesis in this system when glucose 6-phosphate was used as initial substrate, but not when fructose 1,6-diphosphate was used. 3′5′-(cyclic)-AMP reversed the inhibition of lipogenesis by citrate. 4. Preparations of lipomata (benign tumours of adipose tissue) were found to be less sensitive to inhibition of lipogenesis by citrate (7 mm) but inhibition was observed at higher concentrations of citrate (21 mm). 3′5′-(cyclic)-AMP had no effect on lipogenesis in fat-free homogenates of lipomata in the presence of citrate (7 mm). 5. AMP (1·2 mm) inhibited the synthesis of long-chain fatty acyl-CoA without altering the rate of synthesis of neutral lipid from l-glycerol 3-phosphate. When the concentration of AMP was increased to 4 mm a concurrent decrease in lipid synthesis was observed.