scholarly journals A LANGUAGE-BASED APPROACH FOR COMPREHENSIVELY SUPPORTING THE IN SILICO EXPERIMENTAL PROCESS

2005 ◽  
Vol 15 (03) ◽  
pp. 487-509
Author(s):  
ANE TRÖGER ◽  
ALVARO A. A. FERNANDES
Keyword(s):  
In Silico ◽  
Research Method ◽  
Formal Semantics ◽  
In Vitro Experiments ◽  
Validation Criteria ◽  
Experimental Process ◽  
Evidence Gathering ◽  
Alternative Approaches ◽  
Over Time

One of the challenges for bioinformaticians is to approximate, in silico, tried and tested research methods used in vitro. One of the problems standing in their way is the lack of a concrete framework for designing and expressing in silico experiments that aim at being isomorphic to in vitro experiments. This paper introduces such a framework in the form of a specification language called ISXL. ISXL projects to biologists a model of in silico experiments that approximates the research method they are most familiar with, as follows. An ISXL-specified experiment (1) conforms to a conceptual model that explicitly captures the basic constituents of experiments in the empirical sciences; (2) may be defined in relation to explicit hypothesis formulation and validation rather than simply taking the form of an evidence gathering process as in alternative approaches; (3) may be long-lived and evolve over time, in the sense that there is built-in support for denoting past versions of specifications, past results, past hypotheses, past validation criteria; (4) may denote other experiments and their constituent parts, thereby reflecting the interrelatedness of scientific processes. Features (1)-(4) above are made possible by endowing ISXL with certain characteristics of a persistent workflow environment. This allows ISXL experiments to be rich in metadata without imposing too great a burden on the biologist. The metadata in turn open the way for ISXL experiments to be capable of introspection and reflection. This paper focuses on describing of ISXL conceptually and syntactically, and indicates how ISXL experiments are given a formal semantics.

scholarly journals The Molecular Basis of Conformational Instability of the Ecdysone Receptor DNA Binding Domain Studied by In Silico and In Vitro Experiments

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e86052 ◽  
Author(s):  
Agnieszka Szamborska-Gbur ◽  
Grzegorz Rymarczyk ◽  
Marek Orłowski ◽  
Tomasz Kuzynowski ◽  
Michał Jakób ◽  
...  
Keyword(s):  
Dna Binding ◽  
In Silico ◽  
Molecular Basis ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
In Vitro Experiments ◽  
Ecdysone Receptor

scholarly journals Tetrodotoxin/Saxitoxins Selectivity of the Euryhaline Freshwater Pufferfish Dichotomyctere fluviatilis

Toxins ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 731
Author(s):  
Hongchen Zhu ◽  
Towa Sakai ◽  
Yuji Nagashima ◽  
Hiroyuki Doi ◽  
Tomohiro Takatani ◽  
...  
Keyword(s):  
The Body ◽  
Skin Tissue ◽  
Takifugu Rubripes ◽  
In Vitro Experiments ◽  
Long Period ◽  
In Vivo Experiment ◽  
The Given ◽  
Over Time

The present study evaluated differences in the tetrodotoxin (TTX)/saxitoxins (STXs) selectivity between marine and freshwater pufferfish by performing in vivo and in vitro experiments. In the in vivo experiment, artificially reared nontoxic euryhaline freshwater pufferfish Dichotomyctere fluviatilis were intrarectally administered a mixture of TTX (24 nmol/fish) and STX (20 nmol/fish). The amount of toxin in the intestine, liver, muscle, gonads, and skin was quantified at 24, 48, and 72 h. STX was detected in the intestine over a long period of time, with some (2.7–6.1% of the given dose) being absorbed into the body and temporarily located in the liver. Very little TTX was retained in the body. In the in vitro experiments, slices of the intestine, liver, and skin tissue prepared from artificially reared nontoxic D. fluviatilis and the marine pufferfish Takifugu rubripes were incubated in buffer containing TTX and STXs (20 nmol/mL each) for up to 24 or 72 h, and the amount of toxin taken up in the tissue was quantified over time. In contrast to T. rubripes, the intestine, liver, and skin tissues of D. fluviatilis selectively took up only STXs. These findings indicate that the TTX/STXs selectivity differs between freshwater and marine pufferfish.

Cereblon Enhancer Methylation and IMiD Resistance in Multiple Myeloma

Blood ◽  
2021 ◽  
Author(s):  
Larissa Haertle ◽  
Santiago Barrio ◽  
Umair Munawar ◽  
Seungbin Han ◽  
Xiang Zhou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Hematologic Malignancy ◽  
In Vitro Experiments ◽  
Immunomodulatory Drugs ◽  
Dna Hypermethylation ◽  
Direct Binding ◽  
Underlying Mechanisms ◽  
Over Time

Cereblon is the direct binding target of the immunomodulatory drugs that are commonly used to treat Multiple Myeloma, the second most frequent hematologic malignancy. Patients respond well to initial IMiD treatment but virtually all develop drug resistance over time with the underlying mechanisms poorly understood. We identified a yet undescribed DNA hypermethylation in an active intronic CRBN enhancer. Differential hypermethylation in this region was found increased in healthy plasma cells, but more pronounced in IMiD refractory MM. Methylation significantly correlated with decreased CRBN expression levels. DNTMi in vitro experiments induced CRBN enhancer demethylation and sensitizing effects on Lenalidomide treatment were observed in two MM cell lines. Thus, we provide first evidence that aberrant CRBN DNA methylation is a novel mechanism of IMiD resistance in Multiple Myeloma and may predict IMiD response prior treatment.

In Silico and In Vitro Experiments on Chevron Nozzles with Enhanced Momentum Thrust using Streamtube Expansion Waves

2021 ◽  
Author(s):  
Surya Balusamy ◽  
Vigneshwaran Rajendran ◽  
Merrish Aloy A ◽  
Vigneshwaran Sankar ◽  
VR Sanal Kumar
Keyword(s):  
In Silico ◽  
In Vitro Experiments ◽  
Expansion Waves ◽  
Chevron Nozzles

scholarly journals In Silico Experiments in Scientific Papers on Molecular Biology

2011 ◽  
Vol 24 (2) ◽  
pp. 23-42
Author(s):  
Sabrina Moretti
Keyword(s):  
Molecular Biology ◽  
In Silico ◽  
In Vitro Experiments ◽  
Technical Object ◽  
Experimental Conditions ◽  
Biological Phenomena ◽  
Scientific Papers

This article explores the role of the so-called in silico experiments used in molecular biology. It is based on the analysis of some papers that present scientific applications which rely on in silico experiments. By means of this study I found two basic ways of viewing them. According to the first view, the in silico experiment is a computer program that realizes some specific operations: it constitutes some particular experimental conditions, which allow us to investigate biological phenomena, and which complement those present in in vivo and in vitro experiments. According to the second view, in silico experimentation has a different meaning, which corresponds more closely to the meaning of “simulation”: its identity is linked to that of the “model” used to construct such simulation. The authors of the analysed papers never express an intention to standardize a model, so its meaning remains contingent, and cannot be turned into a technical object.

scholarly journals Modelling the impact of clot fragmentation on the microcirculation after thrombectomy

2020 ◽  
Author(s):  
Wahbi K. El-Bouri ◽  
Andrew MacGowan ◽  
Tamás I. Józsa ◽  
Matthew J. Gounis ◽  
Stephen J. Payne
Keyword(s):  
Blood Flow ◽  
Ischaemic Stroke ◽  
Computational Model ◽  
In Silico ◽  
Large Scale ◽  
In Vitro Experiments ◽  
Mechanical Removal ◽  
The Impact ◽  
The Brain

1AbstractMany ischaemic stroke patients who have a mechanical removal of their clot (thrombectomy) do not get reperfusion of tissue despite the thrombus being removed. One hypothesis for this ‘no-reperfusion’ phenomenon is micro-emboli fragmenting off the large clot during thrombectomy and occluding smaller blood vessels downstream of the clot location. This is impossible to observe in-vivo and so we here develop an in-silico model based on in-vitro experiments to model the effect of micro-emboli on brain tissue. Through in-vitro experiments we obtain, under a variety of clot consistencies and thrombectomy techniques, micro-emboli distributions post-thrombectomy. Blood flow through the microcirculation is modelled for statistically accurate voxels of brain microvasculature including penetrating arterioles and capillary beds. A novel micro-emboli algorithm, informed by the experimental data, is used to simulate the impact of micro-emboli successively entering the penetrating arterioles and the capillary bed. Scaled-up blood flow parameters – permeability and coupling coefficients – are calculated under various conditions. We find that capillary beds are more susceptible to occlusions than the penetrating arterioles with a 4x greater drop in permeability per volume of vessel occluded. Individual microvascular geometries determine robustness to micro-emboli. Hard clot fragmentation leads to larger micro-emboli and larger drops in blood flow for a given number of micro-emboli. Thrombectomy technique has a large impact on clot fragmentation and hence occlusions in the microvasculature. As such, in-silico modelling of mechanical thrombectomy predicts that clot specific factors, interventional technique, and microvascular geometry strongly influence reperfusion of the brain. Micro-emboli are likely contributory to the phenomenon of no-reperfusion following successful removal of a major clot.2Author summaryAfter an ischaemic stroke - one where a clot blocks a major artery in the brain - patients can undergo a procedure where the clot is removed mechanically with a stent - a thrombectomy. This reopens the blocked vessel, yet some patients don’t achieve blood flow returning to their tissue downstream. One hypothesis for this phenomenon is that the clot fragments into smaller clots (called micro-emboli) which block smaller vessels downstream. However, this can’t be measured in patients due to the inability of clinical imaging resolving the micro-scale. We therefore develop a computational model here, based on experimental thrombectomy data, to quantify the impact of micro-emboli on blood flow in the brain after the removal of a clot. With this model, we found that micro-emboli are a likely contributor to the no-reflow phenomenon after a thrombectomy. Individual blood vessel geometries, clot composition, and thrombectomy technique all impacted the effect of micro-emboli on blood flow and should be taken into consideration to minimise the impact of micro-emboli in the brain. Furthermore, the computational model developed here allows us to now build large-scale models of blood flow in the brain, and hence simulate stroke and the impact of micro-emboli on the entire brain.

scholarly journals Modelling the impact of clot fragmentation on the microcirculation after thrombectomy

2021 ◽  
Vol 17 (3) ◽  
pp. e1008515
Author(s):  
Wahbi K. El-Bouri ◽  
Andrew MacGowan ◽  
Tamás I. Józsa ◽  
Matthew J. Gounis ◽  
Stephen J. Payne
Keyword(s):  
Blood Flow ◽  
In Silico ◽  
In Vitro Experiments ◽  
Coupling Coefficients ◽  
Flow Parameters ◽  
Mechanical Removal ◽  
Brain Microvasculature ◽  
The Impact

Many ischaemic stroke patients who have a mechanical removal of their clot (thrombectomy) do not get reperfusion of tissue despite the thrombus being removed. One hypothesis for this ‘no-reperfusion’ phenomenon is micro-emboli fragmenting off the large clot during thrombectomy and occluding smaller blood vessels downstream of the clot location. This is impossible to observe in-vivo and so we here develop an in-silico model based on in-vitro experiments to model the effect of micro-emboli on brain tissue. Through in-vitro experiments we obtain, under a variety of clot consistencies and thrombectomy techniques, micro-emboli distributions post-thrombectomy. Blood flow through the microcirculation is modelled for statistically accurate voxels of brain microvasculature including penetrating arterioles and capillary beds. A novel micro-emboli algorithm, informed by the experimental data, is used to simulate the impact of micro-emboli successively entering the penetrating arterioles and the capillary bed. Scaled-up blood flow parameters–permeability and coupling coefficients–are calculated under various conditions. We find that capillary beds are more susceptible to occlusions than the penetrating arterioles with a 4x greater drop in permeability per volume of vessel occluded. Individual microvascular geometries determine robustness to micro-emboli. Hard clot fragmentation leads to larger micro-emboli and larger drops in blood flow for a given number of micro-emboli. Thrombectomy technique has a large impact on clot fragmentation and hence occlusions in the microvasculature. As such, in-silico modelling of mechanical thrombectomy predicts that clot specific factors, interventional technique, and microvascular geometry strongly influence reperfusion of the brain. Micro-emboli are likely contributory to the phenomenon of no-reperfusion following successful removal of a major clot.

scholarly journals Pharmacology and similia principle: indirect secondary counter-regulation. Confirmation from in vitro experiments and classical provings

2021 ◽  
Vol 10 (35) ◽  
pp. 69-69
Author(s):  
Andrea Signorini
Keyword(s):  
Healthy Volunteers ◽  
Dose Response ◽  
Response Curve ◽  
Cell Communication ◽  
Dose Response Curve ◽  
Allopathic Medicine ◽  
In Vitro Experiments ◽  
Scientific Medicine ◽  
Over Time

Homeopathy is universally known as an opponent of allopathic Medicine, namely scientific medicine based on ponderal drugs and recognised mechanisms of receptor agonism and antagonism following the dose-response curve. Over time the difficulty to explain with arguments the action of homeopathic ultra-diluted remedies has led many homeopaths to distance themselves from any pharmacological knowledges. Nevertheless this position fortgets not only the modalities in which homeopathy was born and has grown, but a lot of modern changes of view in body-mind communication, cell communication, neuro-immune-endocrinology and bioelectromagnetism, that could give new reasons to treat as clinical homeopathic practice is teaching and to recognize the principle of similars as a modern pharmacological principle. These arguments, receptorial cell communication, bioelectromagnetism and body-mind unity are the bases of Homeopathy and of the Similia Principle and are all included in embryonic but sufficiently clear considerations in the fundamental book of Hahnemann, the Organon (parr. 11, 13, 15-18, 21, 22, 29-32, 63-70). Two kind of evidences confirm the pharmacological bases of SimiliaPriniciple, in vitro experiments and homeopathic pathogenetic trials on healthy volunteers, best known as provings. Even clinical homeopathic phenomena like initial aggravation and return of old symptoms confirm this pharmacological view of the Simila Principle.

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