scholarly journals Towards a unified theory for morphomechanics

2009 ◽  
Vol 367 (1902) ◽  
pp. 3555-3583 ◽  
Author(s):  
Larry A. Taber
Keyword(s):  
Computational Models ◽  
Evolution Equations ◽  
Pressure Vessels ◽  
Mechanical Forces ◽  
Unified Theory ◽  
Wide Range ◽  
Stress Changes ◽  
The Difference ◽  
New Strategies

Mechanical forces are closely involved in the construction of an embryo. Experiments have suggested that mechanical feedback plays a role in regulating these forces, but the nature of this feedback is poorly understood. Here, we propose a general principle for the mechanics of morphogenesis, as governed by a pair of evolution equations based on feedback from tissue stress. In one equation, the rate of growth (or contraction) depends on the difference between the current tissue stress and a target (homeostatic) stress. In the other equation, the target stress changes at a rate that depends on the same stress difference. The parameters in these morphomechanical laws are assumed to depend on stress rate. Computational models are used to illustrate how these equations can capture a relatively wide range of behaviours observed in developing embryos, as well as show the limitations of this theory. Specific applications include growth of pressure vessels (e.g. the heart, arteries and brain), wound healing and sea urchin gastrulation. Understanding the fundamental principles of tissue construction can help engineers design new strategies for creating replacement tissues and organs in vitro .

scholarly journals The making of a muscle

2012 ◽  
Vol 34 (3) ◽  
pp. 4-11 ◽  
Author(s):  
Marta Fiorotto
Keyword(s):  
High Performance ◽  
Rubber Tree ◽  
In Vitro Study ◽  
Cell Types ◽  
Experimental Manipulation ◽  
Point Of Use ◽  
Wide Range ◽  
The Difference ◽  
Environmental Causes

The skeletal musculature is usually thought of as the primary organ of locomotion, and, like the tyres of a high-performance racing car, their composition, design, preparation and plasticity can make the difference between winner and ‘wannabe’. The similarities do not end there, however. Their primary components (cells of the mesodermal layer in the embryo and latex from the rubber tree) begin their existence in locations that can be quite distant from their final point of use and in forms that bear no resemblance to the final product. Their differentiation from primary material to final product entails extensive processing, and the integration of other materials and structures are essential to ensure their function. A fundamental difference, however, is that, in the case of muscle, once the embryo is formed, the progression from relatively undifferentiated mesodermal cells to the final structures is on autopilot, provided there are no contextual aberrations either from genetic or environmental causes. Our current understanding of how muscles develop is a synthesis of observations made on a wide array of organisms, including nematode worms, fruitflies, fish, frogs, birds and various mammals, as well as from the in vitro study of cells isolated from these species. The study of myogenesis in mammals, although less amenable to experimental manipulation, has been facilitated by the recent advances in mouse genetic engineering which has enabled the function of individual genes and cell types to be investigated, as well as the lineage of cells to be traced back to their origin. In this rapid trek through the life of a muscle, how the production of a mature functional muscle from its early inception is orchestrated will be outlined in exceedingly broad strokes so as to convey the wide range of processes that must be engaged in order to generate a functional muscle. Hopefully, enough information will be provided to encourage those interested to explore further.

scholarly journals Homologue of Macrophage-Activating Lipoprotein in Mycoplasmagallisepticum Is Not Essential for Growth and Pathogenicity in Tracheal Organ Cultures

2003 ◽  
Vol 185 (8) ◽  
pp. 2538-2547 ◽  
Author(s):  
Philip F. Markham ◽  
Anna Kanci ◽  
György Czifra ◽  
Bo Sundquist ◽  
Peter Hains ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Tetracycline Resistance ◽  
Surface Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Homologous Gene ◽  
Organ Cultures ◽  
Western Blots ◽  
Wide Range ◽  
The Difference

ABSTRACT While the genomes of a number of Mycoplasma species have been fully determined, there has been limited characterization of which genes are essential. The surface protein (p47) identified by monoclonal antibody B3 is the basis for an enzyme-linked immunosorbent assay for serological detection of Mycoplasma gallisepticum infection and appears to be constitutively expressed. Its gene was cloned, and the DNA sequence was determined. Subsequent analysis of the p47 amino acid sequence and searches of DNA databases found homologous gene sequences in the genomes of M. pneumoniae and M. genitalium and identity with a gene family in Ureaplasma urealyticum and genes in M. agalactiae and M. fermentans. The proteins encoded by these genes were found to belong to a family of basic membrane proteins (BMP) that are found in a wide range of bacteria, including a number of pathogens. Several of the BMP family members, including p47, contain selective lipoprotein-associated motifs that are found in macrophage-activating lipoprotein 404 of M. fermentans and lipoprotein P48 of M. agalactiae. The p47 gene was predicted to encode a 59-kDa peptide, but affinity-purified p47 had a molecular mass of approximately 47 kDa, as determined by polyacrylamide gel analysis. Analysis of native and recombinant p47 by mass peptide fingerprinting revealed the absence of the carboxyl end of the protein encoded by the p47 gene in native p47, which would account for the difference seen in the predicted and measured molecular weights and indicated posttranslational cleavage of the lipoprotein at its carboxyl end. A DNA construct containing the p47 gene interrupted by the gene encoding tetracycline resistance was used to transform M. gallisepticum cells. A tetracycline-resistant mycoplasma clone, P2, contained the construct inserted within the genomic p47 gene, with crossovers occurring between 73 bp upstream and 304 bp downstream of the inserted tetracycline resistance gene. The absence of p47 protein in clone P2 was determined by the lack of reactivity with rabbit anti-p47 sera or monoclonal antibody B3 in Western blots of whole-cell proteins. There was no difference between the p47− mutant and wild-type M. gallisepticum in pathogenicity in chicken tracheal organ cultures. Thus, p47, although homologous to genes that occur in many prokaryotes, is not essential for growth in vitro or for attachment and the initial stages of pathogenesis in chickens.

scholarly journals Nanoscale patterning of in vitro neuronal circuits

2021 ◽  
Author(s):  
János Vörös ◽  
Sean Weaver ◽  
Jose C. Mateus ◽  
Paulo Aguiar ◽  
Dirk van Swaay ◽  
...  
Keyword(s):  
Computational Models ◽  
Synapse Formation ◽  
Ex Vivo ◽  
Axon Growth ◽  
Neuronal Circuits ◽  
Calcium Indicator ◽  
The Difference ◽  
Pass Through

Methods for patterning neurons in vitro have gradually improved and are used to investigate questions difficult to address in or ex vivo. Though these techniques guide axons between groups of neurons, multiscale control of neuronal connectivity, from circuits to synapses, is yet to be achieved in vitro. As studying neuronal circuits with synaptic resolution in vivo poses significant challenges, an in vitro alternative could serve as a testbed for in vivo experiments or as a platform for validating biophysical and computational models. In this work we use a combination of electron beam and photolithography to create polydimethylsiloxane (PDMS) structures with features ranging from 150 nanometers to a few millimeters. Leveraging the difference between average axon and dendritic spine diameters, we restrict axon growth while allowing spines to pass through nanochannels to guide synapse formation between small groups of neurons (i.e. nodes). We show this technique can be used to generate large numbers of isolated feed-forward circuits where connections between nodes are restricted to regions connected by nanochannels. Using a genetically encoded calcium indicator in combination with fluorescently tagged post synaptic protein, PSD-95, we demonstrate functional synapses can form in this region. Although more work needs to be done to control connectivity in vitro, we believe this is a significant step in that direction.

scholarly journals Critical evaluation of kinetic schemes for coagulation

2021 ◽  
Author(s):  
Alexandre Ranc ◽  
Salome Bru ◽  
Simon Mendez ◽  
Muriel Giansily-Blaizot ◽  
Franck Nicoud ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Computational Models ◽  
Initial Conditions ◽  
Numerical Models ◽  
Critical Evaluation ◽  
Reaction Rates ◽  
Coagulation Cascade ◽  
Pathological Conditions ◽  
Wide Range

AbstractComputational models of the coagulation cascade are used for a wide range of applications in bio-medical engineering such as drug and bio-medical device developments. However, a lack of robustness of numerical models has been highlighted when studying clinically relevant scenarios. In order to develop more robust models, numerical simulations need to be confronted with realistic situations relevant to clinical practice. In this work, two well-established numerical representations of the coagulation cascade initiated by the intrinsic and extrinsic systems, respectively, were compared with thrombin generation assays considering realistic pathological conditions. Proper modifications were needed to align the in vitro and in silico data, namely; adapting initial conditions to the thrombin assay system, omitting reactions irrelevant to our case study, and improving the fitting of some reaction rates. The modified models were able to capture the experimental trends of thrombin generation for a range of concentrations of factors XII, XI, and VIII for cases in which the coagulation cascade is triggered through the extrinsic and intrinsic systems. Our work emphasizes that when existing coagulation cascade models are extrapolated to experimental settings for which they were not calibrated, careful adjustments must be made. We show that the two coagulation models used in this work can predict physiological conditions, but when studying pathological conditions, proper modifications are needed to improve the numerical results.

Measurement of erythrocyte velocity by use of a periodic differential detector

1985 ◽  
Vol 249 (4) ◽  
pp. H899-H905 ◽  
Author(s):  
B. P. Fleming ◽  
B. Klitzman ◽  
W. O. Johnson
Keyword(s):  
Linear Array ◽  
Mass Conservation ◽  
Differential Amplifier ◽  
Center Frequency ◽  
Voltage Converter ◽  
One Dimensional ◽  
Wide Range ◽  
The Difference

An optical velocimeter employing a linear array of photodiodes has been developed and utilized for measuring erythrocyte velocities in the microcirculation. A magnified image of a microvessel is projected and aligned on a one-dimensional array of photodiodes. Photocurrent from odd-ordered diodes is summed, photocurrent from even-ordered diodes is summed, and a signal proportional to the difference between these two currents is produced by a differential amplifier. The center frequency of the output signal of the differential amplifier is proportional to the erythrocyte velocity. After lowpass filtering the output of the differential amplifier, a signal proportional to its frequency and therefore velocity is produced by a frequency-voltage converter. In vitro calibration with a moving dried smear of erythrocytes illustrated a linear relation between the output of the frequency-voltage converter and erythrocyte velocity for a wide range of velocities and magnifications. The system produces a stable zero output at zero velocity and had an estimated frequency response of greater than 40 Hz in vivo. Volumetric flow rates computed from velocity and diameter measurements at arteriolar bifurcations in the rat cremaster muscle were consistent with mass conservation.

scholarly journals The logic of containing tumors

2020 ◽  
Author(s):  
Yannick Viossat ◽  
Robert Noble
Keyword(s):  
Cancer Therapy ◽  
Computational Models ◽  
Maximum Tolerated Dose ◽  
Tumor Burden ◽  
Wide Range ◽  
Clinical Benefits ◽  
Control Tumor ◽  
Cost Of Resistance ◽  
Cell Subpopulations

AbstractChallenging the paradigm of the maximum tolerated dose, recent studies have shown that a strategy aiming for containment, not elimination, can control tumor burden more effectively in vitro, in mouse models, and in the clinic. These outcomes are consistent with the hypothesis that emergence of resistance to cancer therapy may be prevented or delayed by exploiting competitive ecological interactions between drug-sensitive and resistant tumor cell subpopulations. However, although various mathematical and computational models have been proposed to explain the superiority of particular containment strategies, this evolutionary approach to cancer therapy lacks a rigorous theoretical foundation. Here we combine extensive mathematical analysis and numerical simulations to establish general conditions under which a containment strategy is expected to control tumor burden more effectively than applying the maximum tolerated dose. We show that when resistant cells are present, an idealized strategy of containing a tumor at a maximum tolerable size maximizes time to treatment failure (that is, the time at which tumor burden becomes intolerable). These results are very general and do not depend on any fitness cost of resistance. We further provide formulas for predicting the clinical benefits attributable to containment strategies in a wide range of scenarios, and we compare outcomes of theoretically optimal treatments with those of more practical protocols. Our results strengthen the rationale for clinical trials of evolutionarily-informed cancer therapy.

Comparative Effects of High-Tech Visual Scene Displays and Low-Tech Isolated Picture Symbols on Engagement From Students With Multiple Disabilities

2019 ◽  
Vol 50 (4) ◽  
pp. 693-702 ◽  
Author(s):  
Christine Holyfield ◽  
Sydney Brooks ◽  
Allison Schluterman
Keyword(s):  
Language Learning ◽  
Augmentative And Alternative Communication ◽  
Visual Analysis ◽  
Multiple Disabilities ◽  
Visual Scene ◽  
Future Research ◽  
High Tech ◽  
Single Subject ◽  
Wide Range ◽  
The Difference

Purpose Augmentative and alternative communication (AAC) is an intervention approach that can promote communication and language in children with multiple disabilities who are beginning communicators. While a wide range of AAC technologies are available, little is known about the comparative effects of specific technology options. Given that engagement can be low for beginning communicators with multiple disabilities, the current study provides initial information about the comparative effects of 2 AAC technology options—high-tech visual scene displays (VSDs) and low-tech isolated picture symbols—on engagement. Method Three elementary-age beginning communicators with multiple disabilities participated. The study used a single-subject, alternating treatment design with each technology serving as a condition. Participants interacted with their school speech-language pathologists using each of the 2 technologies across 5 sessions in a block randomized order. Results According to visual analysis and nonoverlap of all pairs calculations, all 3 participants demonstrated more engagement with the high-tech VSDs than the low-tech isolated picture symbols as measured by their seconds of gaze toward each technology option. Despite the difference in engagement observed, there was no clear difference across the 2 conditions in engagement toward the communication partner or use of the AAC. Conclusions Clinicians can consider measuring engagement when evaluating AAC technology options for children with multiple disabilities and should consider evaluating high-tech VSDs as 1 technology option for them. Future research must explore the extent to which differences in engagement to particular AAC technologies result in differences in communication and language learning over time as might be expected.

Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan
Keyword(s):  
Soft Tissue ◽  
Room Temperature ◽  
Normal Subjects ◽  
Left Testis ◽  
Wide Range ◽  
Activity Ratios ◽  
The Right ◽  
Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

On the Role of Transferrin in 67Ga Uptake by Tumor Cells

1988 ◽  
Vol 27 (04) ◽  
pp. 151-153
Author(s):  
P. Thouvenot ◽  
F. Brunotte ◽  
J. Robert ◽  
L. J. Anghileri
Keyword(s):  
Specific Binding ◽  
Subcellular Fractionation ◽  
Animal Blood ◽  
Tumor Bearing ◽  
Cell Structures ◽  
The Difference ◽  
Sarcoma Cells ◽  
In Vitro Uptake

In vitro uptake of 67Ga-citrate and 59Fe-citrate by DS sarcoma cells in the presence of tumor-bearing animal blood plasma showed a dramatic inhibition of both 67Ga and 59Fe uptakes: about ii/io of 67Ga and 1/5o of the 59Fe are taken up by the cells. Subcellular fractionation appears to indicate no specific binding to cell structures, and the difference of binding seems to be related to the transferrin chelation and transmembrane transport differences

Enhancement of ADP-induced Platelet Aggregation by Adrenaline in Vivo and Its Prevention

1973 ◽  
Vol 29 (02) ◽  
pp. 490-498 ◽  
Author(s):  
Hiroh Yamazaki ◽  
Itsuro Kobayashi ◽  
Tadahiro Sano ◽  
Takio Shimamoto
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
The Other ◽  
Endothelial Surface ◽  
Important Interaction ◽  
Blood Coagulability ◽  
The Difference

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P<0.01-0.05). The above change was not observed in each group of rabbits injected with saline, 1 µg per Kg of 1-noradrenaline or 0.1 and 10 µg per Kg of adrenaline. Also, it was prevented by oral administration of 10 mg per Kg of phenoxybenzamine or propranolol or aspirin or pyridinolcarbamate 3 hours before the challenge. On the other hand, the enhancement of ADP-induced platelet aggregation was not observed in vitro, when 10-5 or 3 × 10-6 molar and 129.4 ± 12.8% of the value before 10∼6 molar ADP was added to citrated platelet rich plasma (CPRP) of rabbit after incubation at 37°C for 30 second with 0.01, 0.1, 1, 10 or 100 µg per ml of adrenaline or noradrenaline. These results suggest an important interaction between endothelial surface and platelets in connection with the enhancement of ADP-induced platelet aggregation by adrenaline in vivo.

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