63 research outputs found
I M Avatar: Implicit Morphable Head Avatars from Videos
Traditional morphable face models provide fine-grained control over
expression but cannot easily capture geometric and appearance details. Neural
volumetric representations approach photo-realism but are hard to animate and
do not generalize well to unseen expressions. To tackle this problem, we
propose IMavatar (Implicit Morphable avatar), a novel method for learning
implicit head avatars from monocular videos. Inspired by the fine-grained
control mechanisms afforded by conventional 3DMMs, we represent the expression-
and pose-related deformations via learned blendshapes and skinning fields.
These attributes are pose-independent and can be used to morph the canonical
geometry and texture fields given novel expression and pose parameters. We
employ ray tracing and iterative root-finding to locate the canonical surface
intersection for each pixel. A key contribution is our novel analytical
gradient formulation that enables end-to-end training of IMavatars from videos.
We show quantitatively and qualitatively that our method improves geometry and
covers a more complete expression space compared to state-of-the-art methods
A six-week hand exercise programme improves strength and hand function in patients with rheumatoid arthritis
Modeling and Simulation of Multi-Lane Traffic Flow
A most important aspect in the field of traffic modeling is the simulation of
bottleneck situations. For their realistic description a macroscopic multi-lane
model for uni-directional freeways including acceleration, deceleration,
velocity fluctuations, overtaking and lane-changing maneuvers is systematically
deduced from a gas-kinetic (Boltzmann-like) approach. The resulting equations
contain corrections with respect to previous models. For efficient computer
simulations, a reduced model delineating the coarse-grained temporal behavior
is derived and applied to bottleneck situations.Comment: For related work see
http://www.theo2.physik.uni-stuttgart.de/helbing.htm
Modeling Supply Networks and Business Cycles as Unstable Transport Phenomena
Physical concepts developed to describe instabilities in traffic flows can be
generalized in a way that allows one to understand the well-known instability
of supply chains (the so-called ``bullwhip effect''). That is, small variations
in the consumption rate can cause large variations in the production rate of
companies generating the requested product. Interestingly, the resulting
oscillations have characteristic frequencies which are considerably lower than
the variations in the consumption rate. This suggests that instabilities of
supply chains may be the reason for the existence of business cycles. At the
same time, we establish some link to queuing theory and between micro- and
macroeconomics.Comment: For related work see http://www.helbing.or
Action of MK‐7264 (Gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation
Background & Purpose The P2X3 receptor is an ATP‐gated ion channel expressed by sensory afferent neurons, and is as a target to treat chronic sensitisation conditions. The first‐in‐class, selective P2X3 and P2X2/3 receptor antagonist, the diaminopyrimidine MK‐7264 (Gefapixant), has progressed to Phase III trials for refractory or unexplained chronic cough. We have used patch‐clamp to elucidate the pharmacology and kinetics of MK‐7264 and rat models of hypersensitivity and hyperalgesia to test efficacy in these conditions. Experimental Approach Whole‐cell patch‐clamp of 1321N1 cells expressing human P2X3 and P2X2/3 receptors was used to determine mode of MK‐7264 action, potency and kinetics. The analgesic efficacy was assessed using paw withdrawal threshold and limb weight distribution in rat models of inflammatory, osteoarthritic and neuropathic sensitisation. Key Results MK‐7264 is a reversible allosteric antagonist at human P2X3 and P2X2/3 receptors with IC50 values of 153 and 220nM, respectively. Experiments with the slowly desensitising P2X2/3 heteromer revealed concentration and state‐dependency to wash‐on, with faster rates and greater inhibition when applied before agonist compared to during agonist application. Wash‐on rate (τ value) for MK‐7264 at maximal concentrations was 19s and 146s when applied before and during agonist application, respectively. In vivo, MK‐7264 (30 mg/kg) displayed efficacy comparable to naproxen (20 mg/kg) in inflammatory and osteoarthritic sensitisation models, and gabapentin (100 mg/kg) in neuropathic sensitisation models, increasing paw withdrawal threshold and decreasing weight bearing discomfort. Conclusions and Implications MK‐7264 is a reversible and selective P2X3 and P2X2/3 antagonist, exerting allosteric antagonism via preferential activity at closed channels. Efficacy in rat models supports clinical investigation of chronic sensitisation conditions
Gas-kinetic derivation of Navier-Stokes-like traffic equations
Macroscopic traffic models have recently been severely criticized to base on
lax analogies only and to have a number of deficiencies. Therefore, this paper
shows how to construct a logically consistent fluid-dynamic traffic model from
basic laws for the acceleration and interaction of vehicles. These
considerations lead to the gas-kinetic traffic equation of Paveri-Fontana. Its
stationary and spatially homogeneous solution implies equilibrium relations for
the `fundamental diagram', the variance-density relation, and other quantities
which are partly difficult to determine empirically.
Paveri-Fontana's traffic equation allows the derivation of macroscopic moment
equations which build a system of non-closed equations. This system can be
closed by the well proved method of Chapman and Enskog which leads to
Euler-like traffic equations in zeroth-order approximation and to
Navier-Stokes-like traffic equations in first-order approximation. The latter
are finally corrected for the finite space requirements of vehicles. It is
shown that the resulting model is able to withstand the above mentioned
criticism.Comment: For related work see
http://www.theo2.physik.uni-stuttgart.de/helbing.htm
Modeling and Analysis of the Molecular Basis of Pain in Sensory Neurons
Intracellular calcium dynamics are critical to cellular functions like pain transmission. Extracellular ATP plays an important role in modulating intracellular calcium levels by interacting with the P2 family of surface receptors. In this study, we developed a mechanistic mathematical model of ATP-induced P2 mediated calcium signaling in archetype sensory neurons. The model architecture, which described 90 species connected by 162 interactions, was formulated by aggregating disparate molecular modules from literature. Unlike previous models, only mass action kinetics were used to describe the rate of molecular interactions. Thus, the majority of the 252 unknown model parameters were either association, dissociation or catalytic rate constants. Model parameters were estimated from nine independent data sets taken from multiple laboratories. The training data consisted of both dynamic and steady-state measurements. However, because of the complexity of the calcium network, we were unable to estimate unique model parameters. Instead, we estimated a family or ensemble of probable parameter sets using a multi-objective thermal ensemble method. Each member of the ensemble met an error criterion and was located along or near the optimal trade-off surface between the individual training data sets. The model quantitatively reproduced experimental measurements from dorsal root ganglion neurons as a function of extracellular ATP forcing. Hypothesized architecture linking phosphoinositide regulation with P2X receptor activity explained the inhibition of P2X-mediated current flow by activated metabotropic P2Y receptors. Sensitivity analysis using individual and the whole system outputs suggested which molecular subsystems were most important following P2 activation. Taken together, modeling and analysis of ATP-induced P2 mediated calcium signaling generated qualitative insight into the critical interactions controlling ATP induced calcium dynamics. Understanding these critical interactions may prove useful for the design of the next generation of molecular pain management strategies
Traffic and Related Self-Driven Many-Particle Systems
Since the subject of traffic dynamics has captured the interest of
physicists, many astonishing effects have been revealed and explained. Some of
the questions now understood are the following: Why are vehicles sometimes
stopped by so-called ``phantom traffic jams'', although they all like to drive
fast? What are the mechanisms behind stop-and-go traffic? Why are there several
different kinds of congestion, and how are they related? Why do most traffic
jams occur considerably before the road capacity is reached? Can a temporary
reduction of the traffic volume cause a lasting traffic jam? Under which
conditions can speed limits speed up traffic? Why do pedestrians moving in
opposite directions normally organize in lanes, while similar systems are
``freezing by heating''? Why do self-organizing systems tend to reach an
optimal state? Why do panicking pedestrians produce dangerous deadlocks? All
these questions have been answered by applying and extending methods from
statistical physics and non-linear dynamics to self-driven many-particle
systems. This review article on traffic introduces (i) empirically data, facts,
and observations, (ii) the main approaches to pedestrian, highway, and city
traffic, (iii) microscopic (particle-based), mesoscopic (gas-kinetic), and
macroscopic (fluid-dynamic) models. Attention is also paid to the formulation
of a micro-macro link, to aspects of universality, and to other unifying
concepts like a general modelling framework for self-driven many-particle
systems, including spin systems. Subjects such as the optimization of traffic
flows and relations to biological or socio-economic systems such as bacterial
colonies, flocks of birds, panics, and stock market dynamics are discussed as
well.Comment: A shortened version of this article will appear in Reviews of Modern
Physics, an extended one as a book. The 63 figures were omitted because of
storage capacity. For related work see http://www.helbing.org
In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization
Treating pain by inhibiting ATP activation of P2X3-containing receptors heralds an exciting new approach to pain management, and Afferent's program marks the vanguard in a new class of drugs poised to explore this approach to meet the significant unmet needs in pain management. P2X3 receptor subunits are expressed predominately and selectively in so-called C- and Aδ-fiber primary afferent neurons in most tissues and organ systems, including skin, joints, and hollow organs, suggesting a high degree of specificity to the pain sensing system in the human body. P2X3 antagonists block the activation of these fibers by ATP and stand to offer an alternative approach to the management of pain and discomfort. In addition, P2X3 is expressed pre-synaptically at central terminals of C-fiber afferent neurons, where ATP further sensitizes transmission of painful signals. As a result of the selectivity of the expression of P2X3, there is a lower likelihood of adverse effects in the brain, gastrointestinal, or cardiovascular tissues, effects which remain limiting factors for many existing pain therapeutics. In the periphery, ATP (the factor that triggers P2X3 receptor activation) can be released from various cells as a result of tissue inflammation, injury or stress, as well as visceral organ distension, and stimulate these local nociceptors. The P2X3 receptor rationale has aroused a formidable level of investigation producing many reports that clarify the potential role of ATP as a pain mediator, in chronic sensitized states in particular, and has piqued the interest of pharmaceutical companies. P2X receptor-mediated afferent activation has been implicated in inflammatory, visceral, and neuropathic pain states, as well as in airways hyperreactivity, migraine, itch, and cancer pain. It is well appreciated that oftentimes new mechanisms translate poorly from models into clinical efficacy and effectiveness; however, the breadth of activity seen from P2X3 inhibition in models offers a realistic chance that this novel mechanism to inhibit afferent nerve sensitization may find its place in the sun and bring some merciful relief to the torment of persistent discomfort and pain. The development philosophy at Afferent is to conduct proof of concept patient studies and best identify target patient groups that may benefit from this new intervention
Hot topics and application trends of the anammox biotechnology: a review by bibliometric analysis
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