Physics

Motivated by the observation of non-exponential run-time distributions of bacterial swimmers, we propose a minimal phenomenological model for taxis of active particles whose motion is controlled by an internal clock. The ticking of the clock depends on an external concentration field, e.g. a chemical substance. We demonstrate that these particles can detect concentration gradients and respond to them by moving up- or down-gradient depending on the clock design, albeit measurements of these fields are purely local in space and instantaneous in time. Altogether, our results open a new route in the study of directional navigation, by showing that the use of a clock to control motility actions represents a generic and versatile toolbox to engineer behavioral responses to external cues, such as light, chemical, or temperature gradients.

We have developed a novel in vitro instrument that can deliver intermediate frequency (100 - 400 kHz), moderate intensity (up to and exceeding 6.5 V/cm pk-pk) electric fields (EFs) to cell and tissue cultures generated using induced electromagnetic fields (EMFs) in a solenoid coil. A major application of these EFs is as an emerging cancer treatment modality. In vitro studies by Novocure Ltd. reported that intermediate frequency (100 - 300 kHz), low amplitude (1 - 3 V/cm) EFs, which they called "Tumor Treating Fields" (TTFields), had an anti-mitotic effect on glioblastoma multiforme (GBM) cells. The effect was found to increase with increasing EF amplitude. Despite continued theoretical, preclinical, and clinical study, the mechanism of action remains incompletely understood. Previous in vitro studies of "TTFields" have used attached, capacitively coupled electrodes to deliver alternating EFs to cell and tissue cultures. This contacting delivery method suffers from a poorly characterized EF profile and conductive heating that limits the duration and amplitude of the applied EFs. In contrast, our device delivers EFs with a well-characterized radial profile in a non-contacting manner, eliminating conductive heating and enabling thermally regulated EF delivery. To test and demonstrate our system, we generated continuous 200 kHz EMF with an EF amplitude profile spanning 0 - 6.5 V/cm pk-pk and applied them to human thyroid cell cultures for 72 hours. We observed moderate reduction in cell density (< 10%) at low EF amplitudes (< 4 V/cm) and a greater reduction in cell density of up to 25% at higher amplitudes (4 - 6.5 V/cm). Our device can be extended to other EF frequency and amplitude regimes. Future studies with this device should contribute to the ongoing debate about the efficacy and mechanism(s) of action of "TTFields" by better isolating the effects of EFs.

An activated process consists of energy activation and barrier crossing; the former is a prerequisite for the latter. Barrier crossing has been studied extensively, but energy activation has been overlooked due to a lack of means to gauge its progress. We define reaction stability as the probability that reactive trajectories pass a vicinity in phase space; it enabled us to analyze energy activation of a biomolecular isomerization. This process follows a mechanism fundamentally different from presumed mechanisms in standard reaction rate theories: it features accumulation of high kinetic energy in reaction coordinates, achieved by precise synergy between them coordinated by momentum space.

Nonlinear dynamics of two biomolecules is studied. These are a microtubule and DNA molecule. Two mathematical procedures are explained, yielding to three kinds of solitary waves moving through the systems. These waves are kinks, modulated solitary waves called breathers and bell-type solitons.

We propose a mathematical model for the onset and progression of Alzheimer's disease based on transport and diffusion equations. We treat brain neurons as a continuous medium and structure them by their degree of malfunctioning. Three different mechanisms are assumed to be relevant for the temporal evolution of the disease: i) diffusion and agglomeration of soluble Amyloid beta, ii) effects of phosphorylated tau protein and iii) neuron-to-neuron prion-like transmission of the disease. We model these processes by a system of Smoluchowski equations for the Amyloid beta concentration, an evolution equation for the dynamics of tau protein and a kinetic-type transport equation for the distribution function of the degree of malfunctioning of neurons. The latter equation contains an integral term describing the random onset of the disease as a jump process localized in particularly sensitive areas of the brain. We are particularly interested in investigating the effects of the synergistic interplay of Amyloid beta and tau on the dynamics of Alzheimer's disease. The output of our numerical simulations, although in 2D with an over-simplified geometry, is in good qualitative agreement with clinical findings concerning both the disease distribution in the brain, which varies from early to advanced stages, and the effects of tau on the dynamics of the disease.

The eye grows during childhood to position the retina at the correct distance behind the lens to enable focused vision, a process called emmetropization. Animal studies have demonstrated that this growth process is dependent upon visual stimuli, while genetic and environmental factors that affect the likelihood of developing myopia have also been identified. The coupling between growth, remodeling and elastic response in the eye is particularly challenging to understand. To analyse this coupling, we develop a simple model of an eye growing under intraocular pressure in response to visual stimuli. Distinct to existing three-dimensional finite-element models of the eye, we treat the sclera as a thin axisymmetric hyperelastic shell which undergoes local growth in response to external stimulus. This simplified analytic model provides a tractable framework in which to evaluate various emmetropization hypotheses and understand different types of growth feedback, which we exemplify by demonstrating that local growth laws are sufficient to tune the global size and shape of the eye for focused vision across a range of parameter values.

The abstract mathematical rules of artificial neural network (ANN) are implemented through computation using electronic computers, photonics and in-vitro DNA computation. Here we demonstrate the physical realization of ANN in living bacterial cells. We created a single layer ANN using engineered bacteria, where a single bacterium works as an artificial neuron and demonstrated a 2-to-4 decoder and a 1-to-2 de-multiplexer for processing chemical signals. The inputs were extracellular chemical signals, which linearly combined and got processed through a non-linear log-sigmoid activation function to produce fluorescent protein outputs. The activation function was generated by synthetic genetic circuits, and for each artificial neuron, the weight and bias values were adjusted manually by engineering the molecular interactions within the bacterial neuron to represent a specific logical function. The artificial bacterial neurons were connected as ANN architectures to implement a 2-to-4 chemical decoder and a 1-to-2 chemical de-multiplexer. To our knowledge, this is the first ANN created by artificial bacterial neurons. Thus, it may open up a new direction in ANN research, where engineered biological cells can be used as ANN enabled hardware.

CRISPR-Cas is an adaptive immune mechanism that has been harnessed for a variety of genetic engineering applications: the Cas9 protein recognises a 2-5nt DNA motif, known as the PAM, and a programmable crRNA binds a target DNA sequence that is then cleaved. While off-target activity is undesirable, it occurs because cross-reactivity was beneficial in the immune system on which the machinery is based. Here, a stochastic model of the target recognition reaction was derived to study the specificity of the innate immune mechanism in bacteria. CRISPR systems with Cas9 proteins that recognised PAMs of varying lengths were tested on self and phage DNA. The model showed that the energy associated with PAM binding impacted mismatch tolerance, cleavage probability, and cleavage time. Small PAMs allowed the CRISPR to balance catching mutant phages, avoiding self-targeting, and quickly dissociating from critically non-matching sequences. Additionally, the results revealed a lower tolerance to mismatches in the PAM and a PAM-proximal region known as the seed, as seen in experiments. This work illustrates the role that the Cas9 protein has in dictating the specificity of DNA cleavage that can aid in preventing off-target activity in biotechnology applications.

The emergence of biomolecular homochirality is a critical open question in the field of origins of life. In order to seek out an answer to this unsettled issue, a number of mechanisms have been offered over time, but it still remains a great challenge to date. In this paper, based on the hydrothermal vent theory for the origins of life, I tentatively put forward a new hypothesis that the prebiotic emergence of the uniform chirality of biomolecules might have been specifically determined by the spin state of electrons during their prebiotic syntheses on the surfaces of greigite, a mineral which has been frequently argued to have played an important role in the evolutionary context of life. An experimental model to test the hypothesis has also been proposed. Taken into consideration the possible widespread existence of greigite in submarine hydrothermal vent systems which have been frequently argued as a potential cradle for the origins of life, the suggested model, if could be experimentally demonstrated, may be suggestive of where and how life originated on early Earth.

Many models established for solving the problem of the prediction of microalgae growth. However, the models are semi-empirical or considerable fitting coefficients exist in the theoretical model. Therefore, the prediction ability of the model is reduced by the fitting coefficients. The growth mechanism of microalgae is not clearly understood until now, and the growth state is related to the microalgae strains. The above reasons conducted the problem of microalgae growth is much difficult in theoretical prediction. Furthermore, the predicted results of the established models are dependent on the size of the photobioreactor (PBR), light intensity, flow field, and concentration field. Therefore, the growth rate of the dependent variable is the function of independent variables including nutrients concentration, light intensity, flow field, PBR size, temperature, pH. The experimental works are 106 for each independent variable selects 10 values of 6 variables which can not be accomplished. The dimensionless method maybe provide a way to solve the problem. In this paper, the analytical solution of the growth rate was obtained for the parallel flow. The dimensionless growth rate expressed as function of Reynolds number and Schmidt number, which can be used for arbitrary parallel flow due to the parameters are expressed as dimensionless quantity. The solution of growth rate was used to predict the experimentally measured data. The results show that the theoretically predicted growth rate is consistent with the experimentally measured growth rate of microalgae on the order of magnitude. These results will be useful in the design and operation of PBRs for biofuel production.