2,784 research outputs found
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
- …