CHARACTERISTICS OF FIBROUS TISSUE AT HIGH RATES OF TENSILE LOADING

The mechanical behavior of fibrous tissue is generally characterized at very low strain rates. However, many injuries occur at high rates of loading, such as those encountered in sporting events or vehicle accidents. An understanding of injury behavior requires the injury process to be recorded at high strain rates. Even at low rates of loading, the injury/failure within tissues occurs quickly. Furthermore, using conventional imaging systems, the surface of a specimen may be well documented throughout an experiment. However, damage formation does not necessarily begin at the surface of the specimen or even on the surface exposed to a camera. With the integration of a tension Kolsky bar and X-Ray Phase Contrast Imaging (PCI), damage formation within a specimen can be observed without knowledge of when the damage event occurs and without regard for the opaqueness of the specimen. By using these two systems at higher strain rates, the damage event can be correlated with load data, acceleration, and strain rate

Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes

Functional residues in proteins tend to be highly conserved over evolutionary time. However, to what extent functional sites impose evolutionary constraints on nearby or even more distant residues is not known. Here, we report pervasive conservation gradients toward catalytic residues in a dataset of 524 distinct enzymes: evolutionary conservation decreases approximately linearly with increasing distance to the nearest catalytic residue in the protein structure. This trend encompasses, on average, 80% of the residues in any enzyme, and it is independent of known structural constraints on protein evolution such as residue packing or solvent accessibility. Further, the trend exists in both monomeric and multimeric enzymes and irrespective of enzyme size and/or location of the active site in the enzyme structure. By contrast, sites in protein–protein interfaces, unlike catalytic residues, are only weakly conserved and induce only minor rate gradients. In aggregate, these observations show that functional sites, and in particular catalytic residues, induce long-range evolutionary constraints in enzymes.Fil: Jack, Benjamin R.. University of Texas at Austin; Estados UnidosFil: Meyer, Austin G.. University of Texas at Austin; Estados UnidosFil: Echave, Julián. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wilke, Claus O.. University of Texas at Austin; Estados Unido

Collectively canalizing Boolean functions

This paper studies the mathematical properties of collectively canalizing Boolean functions, a class of functions that has arisen from applications in systems biology. Boolean networks are an increasingly popular modeling framework for regulatory networks, and the class of functions studied here captures a key feature of biological network dynamics, namely that a subset of one or more variables, under certain conditions, can dominate the value of a Boolean function, to the exclusion of all others. These functions have rich mathematical properties to be explored. The paper shows how the number and type of such sets influence a function's behavior and define a new measure for the canalizing strength of any Boolean function. We further connect the concept of collective canalization with the well-studied concept of the average sensitivity of a Boolean function. The relationship between Boolean functions and the dynamics of the networks they form is important in a wide range of applications beyond biology, such as computer science, and has been studied with statistical and simulation-based methods. But the rich relationship between structure and dynamics remains largely unexplored, and this paper is intended as a contribution to its mathematical foundation.Comment: 15 pages, 2 figure

Immunomodulatory properties and molecular effects in inflammatory diseases of low-dose X-irradiation

Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice

Strong-field physics with mid-IR fields

Strong-field physics is currently experiencing a shift towards the use of mid-IR driving wavelengths. This is because they permit conducting experiments unambiguously in the quasi-static regime and enable exploiting the effects related to ponderomotive scaling of electron recollisions. Initial measurements taken in the mid-IR immediately led to a deeper understanding of photo-ionization and allowed a discrimination amongst different theoretical models. Ponderomotive scaling of rescattering has enabled new avenues towards time resolved probing of molecular structure. Essential for this paradigm shift was the convergence of two experimental tools: 1) intense mid-IR sources that can create high energy photons and electrons while operating within the quasi-static regime, and 2) detection systems that can detect the generated high energy particles and image the entire momentum space of the interaction in full coincidence. Here we present a unique combination of these two essential ingredients, namely a 160\~kHz mid-IR source and a reaction microscope detection system, to present an experimental methodology that provides an unprecedented three-dimensional view of strong-field interactions. The system is capable of generating and detecting electron energies that span a six order of magnitude dynamic range. We demonstrate the versatility of the system by investigating electron recollisions, the core process that drives strong-field phenomena, at both low (meV) and high (hundreds of eV) energies. The low energy region is used to investigate recently discovered low-energy structures, while the high energy electrons are used to probe atomic structure via laser-induced electron diffraction. Moreover we present, for the first time, the correlated momentum distribution of electrons from non-sequential double-ionization driven by mid-IR pulses.Comment: 17 pages, 11 figure

Hemodynamic behavior of stentless aortic valves in long term follow-up

Objectives Stentless aortic valve replacements show improved hemodynamics due to larger orifice area and lower transvalvular gradients in short and mid-term follow-up. Hemodynamic long-term behavior and the adaptation of the left ventricle as well as valve-durability in patients aged ≤60 years remains unclear. Methods 7 to 16 years after aortic valve replacement, 54 patients (mean age at operation 53.1 ± years) received echocardiography and clinical examination. Mean follow-up time was 10.8 ± 2.2 years. Evaluated were NYHA class, transvalvular gradients, estimated aortic valve orifice area, degree of aortic valve insufficiency, left ventricular mass and function. Results At follow-up only one patient presented with NYHA class III. All other patients were in NYHA class I or II. Maximum and mean pressure gradients of the prostheses were 16.3 ± 7.4 mmHg and 9.1 ± 4.2 mmHg, respectively. Compared to echocardiography at discharge the mean pressure gradients dropped 18.0% (2.0 ± 0.9 mmHg) and stayed stable until 14 years after the operation. Only 5 patients showed relevant regurgitation (at 13–16 years after valve replacement), 49 showed no or trivial regurgitation. Left ventricular mass had decreased 26.5% (107.9 ± 18.5 g). Left ventricular ejection fraction (LVEF) had increased in most patients and decreased in only one. For patients with preoperatively impaired left ventricular function an increase of LVEF of 13.1 ± 3.1% was seen. Conclusion Porcine stentless aortic valves provide excellent hemodynamic long-term results without significant rise of transvalvular pressure gradients or relevant insufficiencies until 14 years after implantation, leading to sustained decrease of left ventricular mass and improvement of left ventricular function

Composition and variability of the Denmark Strait Overflow Water in a high-resolution numerical model hindcast simulation

Author Posting. © American Geophysical Union, 2017. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 122 (2017): 2830–2846, doi:10.1002/2016JC012158.The upstream sources and pathways of the Denmark Strait Overflow Water and their variability have been investigated using a high-resolution model hindcast. This global simulation covers the period from 1948 to 2009 and uses a fine model mesh (1/20°) to resolve mesoscale features and the complex current structure north of Iceland explicitly. The three sources of the Denmark Strait Overflow, the shelfbreak East Greenland Current (EGC), the separated EGC, and the North Icelandic Jet, have been analyzed using Eulerian and Lagrangian diagnostics. The shelfbreak EGC contributes the largest fraction in terms of volume and freshwater transport to the Denmark Strait Overflow and is the main driver of the overflow variability. The North Icelandic Jet contributes the densest water to the Denmark Strait Overflow and shows only small temporal transport variations. During summer, the net volume and freshwater transports to the south are reduced. On interannual time scales, these transports are highly correlated with the large-scale wind stress curl around Iceland and, to some extent, influenced by the North Atlantic Oscillation, with enhanced southward transports during positive phases. The Lagrangian trajectories support the existence of a hypothesized overturning loop along the shelfbreak north of Iceland, where water carried by the North Icelandic Irminger Current is transformed and feeds the North Icelandic Jet. Monitoring these two currents and the region north of the Iceland shelfbreak could provide the potential to track long-term changes in the Denmark Strait Overflow and thus also the AMOC.Norwegian Research Council Grant Number: 2316472017-10-0

Heterogeneity of the cancer cell line metabolic landscape

The unravelling of the complexity of cellular metabolism is in its infancy. Cancer-associated genetic alterations may result in changes to cellular metabolism that aid in understanding phenotypic changes, reveal detectable metabolic signatures, or elucidate vulnerabilities to particular drugs. To understand cancer-associated metabolic transformation, we performed untargeted metabolite analysis of 173 different cancer cell lines from 11 different tissues under constant conditions for 1,099 different species using mass spectrometry (MS). We correlate known cancer-associated mutations and gene expression programs with metabolic signatures, generating novel associations of known metabolic pathways with known cancer drivers. We show that metabolic activity correlates with drug sensitivity and use metabolic activity to predict drug response and synergy. Finally, we study the metabolic heterogeneity of cancer mutations across tissues, and find that genes exhibit a range of context specific, and more general metabolic control