Subscribe to the gold package and get unlimited access to Shamra Academy
Register a new userCongenital anomalies from a physics perspective. The key role of manufacturing volatility
82
0
0.0
(
0
)
Ask ChatGPT about the research
No Arabic abstract
Genetic and environmental factors are traditionally seen as the sole causes of congenital anomalies. In this paper we introduce a third possible cause, namely random manufacturing discrepancies with respect to ``design values. A clear way to demonstrate the existence of this component is to ``shut the two others and to see whether or not there is remaining variability. Perfect clones raised under well controlled laboratory conditions fulfill the conditions for such a test. Carried out for four different species, the test reveals a variability remainder of the order of 10%-20% in terms of coefficient of variation. As an example, the CV of the volume of E.coli bacteria immediately after binary fission is of the order of 10%. In short, ``manufacturing discrepancies occur randomly, even when no harmful mutation or environmental factors are involved. Not surprisingly, there is a strong connection between congenital defects and infant mortality. In the wake of birth there is a gradual elimination of defective units and this screening accounts for the post-natal fall of infant mortality. Apart from this trend, post-natal death rates also have humps and peaks associated with various inabilities and defects.qL In short, infant mortality rates convert the case-by-case and mostly qualitative problem of congenital malformations into a global quantitative effect which, so to say, summarizes and registers what goes wrong in the embryonic phase. Based on the natural assumption that for simple organisms (e.g. rotifers) the manufacturing processes are shorter than for more complex organisms (e.g. mammals), fewer congenital anomalies are expected. Somehow, this feature should be visible on the infant mortality rate. How this conjecture can be tested is outlined in our conclusion.
rate research
Read More
Six thermo-activated transient receptor potential (TRP) channels are the molecular basis of the thermosensation for mammals. But the molecular source of their gating remains unknown. In the Letter, we suggest a physically based model for the TRP channels and show that the temperature dependence of the internal friction can be a key factor governing the ion channels gating. Results of the computer modeling allowed us to successfully reproduce the experimental data for the open probability Popen of the TRPV1 and TRPM8 channels at different temperatures and voltages.
The liver performs critical physiological functions, including metabolizing and removing substances, such as toxins and drugs, from the bloodstream. Hepatotoxicity itself is intimately linked to abnormal hepatic transport and hepatotoxicity remains the primary reason drugs in development fail and approved drugs are withdrawn from the market. For this reason, we propose to analyze, across liver compartments, the transport kinetics of fluorescein-a fluorescent marker used as a proxy for drug molecules-using intravital microscopy data. To resolve the transport kinetics quantitatively from fluorescence data, we account for the effect that different liver compartments (with different chemical properties) have on fluoresceins emission rate. To do so, we develop ordinary differential equation transport models from the data where the kinetics are related to the observable fluorescence levels by measurement parameters that vary across different liver compartments. On account of the steep non-linearities in the kinetics and stochasticity inherent to the model, we infer kinetic and measurement parameters by generalizing the method of parameter cascades. For this application, the method of parameter cascades ensures fast and precise parameter estimates from noisy time traces.
We analyse high-frequency realised volatility dynamics and spillovers in the bitcoin market, focusing on two pairs: bitcoin against the US dollar (the main fiat-crypto pair) and trading bitcoin against tether (the main crypto-crypto pair). We find that the tether-margined perpetual contract on Binance is clearly the main source of volatility, continuously transmitting strong flows to all other instruments and receiving only a little volatility. Moreover, we find that (i) during US trading hours, traders pay more attention and are more reactive to prevailing market conditions when updating their expectations and (ii) the crypto market exhibits a higher interconnectedness when traditional Western stock markets are open. Our results highlight that regulators should not only consider spot exchanges offering bitcoin-fiat trading but also the tether-margined derivatives products available on most unregulated exchanges, most importantly Binance.
The term In Silico Trial indicates the use of computer modelling and simulation to evaluate the safety and efficacy of a medical product, whether a drug, a medical device, a diagnostic product or an advanced therapy medicinal product. Predictive models are positioned as new methodologies for the development and the regulatory evaluation of medical products. New methodologies are qualified by regulators such as FDA and EMA through formal processes, where a first step is the definition of the Context of Use (CoU), which is a concise description of how the new methodology is intended to be used in the development and regulatory assessment process. As In Silico Trials are a disruptively innovative class of new methodologies, it is important to have a list of possible CoUs highlighting potential applications for the development of the relative regulatory science. This review paper presents the result of a consensus process that took place in the InSilicoWorld Community of Practice, an online forum for experts in in silico medicine. The experts involved identified 46 descriptions of possible CoUs which were organised into a candidate taxonomy of nine CoU categories. Examples of 31 CoUs were identified in the available literature; the remaining 15 should, for now, be considered speculative.
Signal transduction in biological cells is effected by signaling pathways that typically include multiple feedback loops. Here we analyze information transfer through a prototypical signaling module with biochemical feedback. The module switches stochastically between an inactive and active state; the input to the module governs the activation rate while the output (i.e., the product concentration) perturbs the inactivation rate. Using a novel perturbative approach, we compute the rate with which information about the input is gained from observation of the output. We obtain an explicit analytical result valid to first order in feedback strength and to second order in the strength of input. The total information gained during an extended time interval is found to depend on the feedback strength only through the total number of activation/inactivation events.
Log in to be able to interact and post comments
comments
Fetching comments
Sign in to be able to follow your search criteria
