Nasal Model Experiments Show That a Collimated Fluid Delivers Precise Doses to the Human Olfactory Cavity in the Side-Laying Position.

The nasal administration of therapeutic fluids and vaccines is used to treat allergic rhinitis, sinusitis, congestion, coronaviruses and even Alzheimer's disease. In the latter, the drug must reach the olfactory region, so it finds its way into the central nervous system. Effective administration techniques able to reach the olfactory region are challenging due to the tortuous anatomy of the nasal cavity, and are frequently evaluated in vitro using transparent anatomical models. Here, the liquid distribution inside a 3D printed human nasal cavity is quantified for model fluids resulting from the discharge of a 1-mL syringe with either a spray-generating nozzle, and a straight tip emitting a collimated fluid stream. Experiments using two model fluids with different viscosities suggest that a simple, correctly positioned straight tip attached to a syringe is able to efficiently deliver most of a therapeutic fluid in the human olfactory region in the side-laying position, avoiding the adoption of head-back and head-down positions that can be difficult for patients in the age range typical of Alzheimer's disease. Furthermore, we demonstrate by computer simulations that the conclusion is valid within a wide range of parameters.

Continuous to intermittent flows in growing granular heaps.

If a granular material is poured from above on a horizontal surface between two parallel, vertical plates, a sand heap grows in time. For small piles, the grains flow smoothly downhill, but after a critical pile size X_{c}, the flow becomes intermittent: sudden avalanches slide downhill from the apex to the base, followed by an "uphill front" that slowly climbs up, until a new downhill avalanche interrupts the process. By means of experiments, controlling the distance between the apex of the sandpile and the container feeding it from above, we show that X_{c} grows linearly with the input flux, but scales as the square root of the feeding height. We explain these facts from a phenomenological model based on the experimental observation that the flowing granular phase forms a "wedge" on top of the static one, differently from the case of stationary heaps. Moreover, we demonstrate that our controlled experiments allow to predict the value of X_{c} for the common situation in which the feeding height decreases as the pile increases in size.

Sink versus tilt penetration into shaken dry granular matter: The role of the foundation.

We study the behavior of cylindrical objects as they sink into a dry granular bed fluidized due to lateral oscillations. Somewhat unexpectedly, we have found that, within a large range of lateral shaking powers, cylinders with flat bottoms sink vertically, while those with a "foundation" consisting of a shallow ring attached to their bottom, tilt besides sinking. The latter scenario seems to dominate independently from the nature of the foundation when strong enough lateral vibrations are applied. We are able to explain the observed behavior by quasi-2D numerical simulations, which also demonstrate the influence of the intruder's aspect ratio. The vertical sink dynamics is explained with the help of a Newtonian equation of motion for the intruder. Our findings may shed light on the behavior of buildings and other manmade structures during earthquakes.

Rolling away from the Wall into Granular Matter.

The sedimentation of solid objects into granular matter near boundaries is an almost virgin field of research. Here we describe in detail the penetration dynamics of a cylindrical object into a quasi-2D granular medium. By tracking the trajectory of the cylinder as it penetrates the granular bed, we characterize two distinct kinds of motion: its center of mass moves horizontally away from the lateral wall, and it rotates around its symmetry axis. While the repulsion is caused by the loading of force chains between the intruder and the wall, the rotation can be associated to the frictional forces between the grains and the intruder. Finally, we show the analogies between the sedimentation of twin intruders released far from any boundaries, and that of one intruder released near a vertical wall.

An autonomous robot for continuous tracking of millimetric-sized walkers.

The precise and continuous tracking of millimetric-sized walkers-such as ants-is quite important in behavioral studies. However, due to technical limitations, most studies concentrate on trajectories within areas no more than 100 times bigger than the size of the walker or longer trajectories at the expense of either accuracy or continuity. Our work describes a scientific instrument designed to push the boundaries of precise and continuous motion analysis up to 1000 body lengths or more. It consists of a mobile robotic platform that uses digital image processing techniques to track the targets in real time by calculating their spatial position. During the experiments, all the images are stored and afterwards processed to estimate with higher precision the path traced by the walkers. Some preliminary results achieved using the proposed tracking system are presented.

Note: Planetary gravities made simple: Sample test of a Mars rover wheel.

We introduce an instrument for a wide spectrum of experiments on gravities other than our planet's. It is based on a large Atwood machine where one of the loads is a bucket equipped with a single board computer and different sensors. The computer is able to detect the falling (or rising) and then the stabilization of the effective gravity and to trigger actuators depending on the experiment. Gravities within the range 0.4 g-1.2 g are easily achieved with acceleration noise of the order of 0.01 g. Under Martian gravity, we are able to perform experiments of approximately 1.5 s duration. The system includes features such as WiFi and a web interface with tools for the setup, monitoring, and data analysis of the experiment. We briefly show a case study in testing the performance of a model Mars rover wheel in low gravities.

Exponential velocity profile of granular flows down a confined heap.

Thick granular flows are essential to many natural and industrial phenomena. Experimentally, it has been well established that the grain velocity profile is linear from the free surface to a certain depth, after which it decreases exponentially in the so-called "creep region". In this paper we obtain an exponential velocity profile based on the force balance of a grain near a wall, where the Janssen effect and the non-locality of interactions between grains are considered. When experimental parameters such as flow angles and friction coefficients are introduced in our model, it is able to reproduce experimental creep velocity profiles previously reported in the literature.

Note: "Lock-in accelerometry" to follow sink dynamics in shaken granular matter.

Understanding the penetration dynamics of intruders in granular beds is relevant not only for fundamental physics, but also for geophysical processes and construction on sediments or granular soils in areas potentially affected by earthquakes. While the penetration of intruders in two dimensional (2D) laboratory granular beds can be followed using video recording, this is useless in three dimensional (3D) beds of non-transparent materials such as common sand. Here, we propose a method to quantify the sink dynamics of an intruder into laterally shaken granular beds based on the temporal correlations between the signals from a reference accelerometer fixed to the shaken granular bed, and a probe accelerometer deployed inside the intruder. Due to its analogy with the working principle of a lock-in amplifier, we call this technique lock-in accelerometry.

Foraging at the edge of chaos: internal clock versus external forcing.

Activity rhythms in animal groups arise both from external changes in the environment, as well as from internal group dynamics. These cycles are reminiscent of physical and chemical systems with quasiperiodic and even chaotic behavior resulting from "autocatalytic" mechanisms. We use nonlinear differential equations to model how the coupling between the self-excitatory interactions of individuals and external forcing can produce four different types of activity rhythms: quasiperiodic, chaotic, phase locked, and displaying over or under shooting. At the transition between quasiperiodic and chaotic regimes, activity cycles are asymmetrical, with rapid activity increases and slower decreases and a phase shift between external forcing and activity. We find similar activity patterns in ant colonies in response to varying temperature during the day. Thus foraging ants operate in a region of quasiperiodicity close to a cascade of transitions leading to chaos. The model suggests that a wide range of temporal structures and irregularities seen in the activity of animal and human groups might be accounted for by the coupling between collectively generated internal clocks and external forcings.

Application of recombinant antibody fragments for troponin I measurements.

The cardiac isoform of troponin I is a reliable biomarker of damaged cardiomyocytes that accompanies such severe cardiovascular diseases as myocardial infarction. Monoclonal antibody 19C7 recognizes troponin I in the bloodstream with high affinity and specificity. Recombinant antibodies can be used to improve detection systems based on monoclonal antibodies produced with hybridoma technology. In the present study, we compare the properties of monoclonal antibody 19C7 and its recombinant fragments. It is shown that the recombinant antibody fragments demonstrate similar affinity values as monoclonal antibodies and can be applied for troponin I detection.

Infinite penetration of a projectile into a granular medium.

An object falling in a fluid reaches a terminal velocity when the drag force and its weight are balanced. Contrastingly, an object impacting into a granular medium rapidly dissipates all its energy and comes to rest always at a shallow depth. Here we study, experimentally and theoretically, the penetration dynamics of a projectile in a very long silo filled with expanded polystyrene particles. We discovered that, above a critical mass, the projectile reaches a terminal velocity and, therefore, an endless penetration.

Generation of recombinant antibodies and means for increasing their affinity.

Highly specific interaction with foreign molecules is a unique feature of antibodies. Since 1975, when Keller and Milstein proposed the method of hybridoma technology and prepared mouse monoclonal antibodies, many antibodies specific to various antigens have been obtained. Recent development of methods for preparation of recombinant DNA libraries and in silico bioinformatics approaches for protein structure analysis makes possible antibody preparation using gene engineering approaches. The development of gene engineering methods allowed creating recombinant antibodies and improving characteristics of existing antibodies; this significantly extends the applicability of antibodies. By modifying biochemical and immunochemical properties of antibodies by changing their amino acid sequences it is possible to create antibodies with properties optimal for certain tasks. For example, application of recombinant technologies resulted in antibody preparation of high affinity significantly exceeding the initial affinity of natural antibodies. In this review we summarize information about the structure, modes of preparation, and application of recombinant antibodies and their fragments and also consider the main approaches used to increase antibody affinity.

Avalanche prediction in a self-organized pile of beads.

It is a common belief that power-law distributed avalanches are inherently unpredictable. This idea affects phenomena as diverse as evolution, earthquakes, superconducting vortices, stock markets, etc., from atomic to social scales. It mainly comes from the concept of "self-organized criticality" (SOC), where criticality is interpreted in the way that, at any moment, any small avalanche can eventually cascade into a large event. Nevertheless, this work demonstrates experimentally the possibility of avalanche prediction in the classical paradigm of SOC: a pile of grains. By knowing the position of every grain in a two-dimensional pile, avalanches of moving grains follow a distinct power-law distribution. Large avalanches, although uncorrelated, are on average preceded by continuous, detectable variations in the internal structure of the pile that are monitored in order to achieve prediction.

Revolving rivers in sandpiles: from continuous to intermittent flows.

In a previous paper [E. Altshuler, Phys. Rev. Lett. 91, 014501 (2003)], the mechanism of "revolving rivers" for sandpile formation is reported: As a steady stream of dry sand is poured onto a horizontal surface, a pile forms which has a river of sand on one side flowing from the apex of the pile to the edge of the base. For small piles the river is steady, or continuous. For larger piles, it becomes intermittent. In this paper we establish experimentally the "dynamical phase diagram" of the continuous and intermittent regimes, and give further details of the piles' "topography," improving the previous kinematic model to describe it and shedding further light on the mechanisms of river formation. Based on experiments in Hele-Shaw cells, we also propose that a simple dimensionality reduction argument can explain the transition between the continuous and intermittent dynamics.

Uphill solitary waves in granular flows.

We have experimentally observed uphill solitary waves in the surface flow on a granular material. A heap is constructed by injecting sand between two vertical glass plates separated by a distance much larger than the average grain size, with an open boundary. As the heap reaches the open boundary, solitary fluctuations appear on the flowing layer and move "up the hill" (i.e., against the direction of the flow). We explain the phenomenon in the context of stop-and-go traffic models.

Quasiperiodic events in an earthquake model.

We introduce a modification of the Olami-Feder-Christensen earthquake model [Phys. Rev. Lett. 68, 1244 (1992)10.1103/PhysRevLett.68.1244] in order to improve the resemblence with the Burridge-Knopoff mechanical model and with possible laboratory experiments. A constant and finite force continually drives the system, resulting in instantaneous relaxations. Dynamical disorder is added to the thresholds following a narrow distribution. We find quasiperiodic behavior in the avalanche time series with a period proportional to the degree of dissipation of the system. Periodicity is not as robust as criticality when the threshold force distribution widens, or when an increasing noise is introduced in the values of the dissipation.

Symmetry breaking in escaping ants.

The phenomenon of herding is a very general feature of the collective behavior of many species in panic conditions, including humans. It has been predicted theoretically that panic-induced herding in individuals confined to a room can produce a nonsymmetrical use of two identical exit doors. Here we demonstrate the existence of that phenomenon in experiments, using ants as a model of pedestrians. We show that ants confined to a cell with two symmetrically located exits use both exits in approximately equal proportions to abandon it in normal conditions but prefer one of the exits if panic is created by adding a repellent fluid. In addition, we are able to reproduce the observed escape dynamics in detail using a modification of a previous theoretical model that includes herding associated with a panic parameter as a central ingredient. Our experimental results, combined with theoretical models, suggest that some features of the collective behavior of humans and ants can be quite similar when escaping under panic.

Sandpile formation by revolving rivers.

Experimental observation of a new mechanism of sandpile formation is reported. As a steady stream of dry sand is poured onto a horizontal surface, a pile forms which has a thin river of sand on one side flowing from the apex of the pile to the edge of its base. The river rotates about the pile, depositing a new layer of sand with each revolution, thereby causing the pile to grow. For small piles the river is steady and the pile formed is smooth. For larger piles, the river becomes intermittent and the surface of the pile becomes undulating. The essential features of the system that produce the phenomenon are discussed, and the robustness of the phenomena is demonstrated with experiments using different boundary conditions and sands.

Avalanches in one-dimensional piles with different types of bases.

We perform a systematic experimental study of the influence of the type of base on the avalanche dynamics of slowly driven 1D ball piles. The control of base details allows us to explore a wide spectrum of pile structures and dynamics. The scaling properties of the observed avalanche distributions suggest that self-organized critical behavior is approached as the "base-induced" disorder at the pile profile increases.