Critical behaviour in the nonlinear elastic response of hydrogels.

In this paper we study the elastic response of synthetic hydrogels to an applied shear stress. The hydrogels studied here have previously been shown to mimic the behaviour of biopolymer networks when they are sufficiently far above the gel point. We show that near the gel point they exhibit an elastic response that is consistent with the predicted critical behaviour of networks near or below the isostatic point of marginal stability. This point separates rigid and floppy states, distinguished by the presence or absence of finite linear elastic moduli. Recent theoretical work has also focused on the response of such networks to finite or large deformations, both near and below the isostatic point. Despite this interest, experimental evidence for the existence of criticality in such networks has been lacking. Using computer simulations, we identify critical signatures in the mechanical response of sub-isostatic networks as a function of applied shear stress. We also present experimental evidence consistent with these predictions. Furthermore, our results show the existence of two distinct critical regimes, one of which arises from the nonlinear stretch response of semi-flexible polymers.

Fluctuation-stabilized marginal networks and anomalous entropic elasticity.

We study the elastic properties of thermal networks of Hookean springs. In the purely mechanical limit, such systems are known to have a vanishing rigidity when their connectivity falls below a critical, isostatic value. In this work, we show that thermal networks exhibit a nonzero shear modulus G well below the isostatic point and that this modulus exhibits an anomalous, sublinear dependence on temperature T. At the isostatic point, G increases as the square root of T, while we find G∝Tα below the isostatic point, where α≃0.8. We show that this anomalous T dependence is entropic in origin.

Analytical expressions for the shape of axisymmetric membranes with multiple domains.

Based on the Canham-Helfrich free energy, we derive analytical expressions for the shapes of axisymmetric membranes consisting of multiple domains. We give explicit equations for both closed vesicles and almost cylindrical tubes. Using these expressions, we also find the shape of a tube attached to a spherical vesicle. The resulting shapes compare well to numerical data, and our expressions can be used to easily determine membrane parameters from experimentally obtained shapes.

Tympanic temperature during therapeutic hypothermia.

OBJECTIVE: Prehospital induction of therapeutic hypothermia after cardiac arrest may require temperature monitoring in the field. Tympanic temperature is non-invasive and frequently used in clinical practice. Nevertheless, it has not yet been evaluated in patients undergoing mild therapeutic hypothermia (MTH). Therefore, a prospective observational study was conducted comparing three different sites of temperature monitoring during therapeutic hypothermia. METHODS: Ten consecutive patients admitted to our medical intensive care unit after out-of-hospital cardiac arrest were included in this study. During MTH, tympanic temperature was measured using a digital thermometer. Simultaneously, oesophageal and bladder temperatures were recorded in a total of 558 single measurements. RESULTS: Compared with oesophageal temperature, bladder temperature had a bias of 0.019°C (limits of agreement ± 0.61°C (2SD)), and tympanic measurement had a bias of 0.021°C (± 0.80°C). Correlation analysis revealed a high relationship for tympanic versus oesophageal temperature (r = 0.95, p < 0.0001) and also for tympanic versus bladder temperature (r = 0.96, p < 0.0001). CONCLUSIONS: That tympanic temperature accurately indicates both oesophageal and bladder temperatures with a very small discrepancy in patients undergoing MTH after cardiac arrest is demonstrated in this study. Although our results were obtained in the hospital setting, these findings may be relevant for the prehospital application of therapeutic hypothermia as well. In this case, tympanic temperature may provide an easy and non-invasive method for temperature monitoring.

The phase diagram of Ti-6Al-4V at high-pressures and high-temperatures.

We report results from a series of diamond-anvil-cell synchrotron x-ray diffraction and large-volume-press experiments, and calculations, to investigate the phase diagram of commercial polycrystalline high-strength Ti-6Al-4V alloy in pressure-temperature space. Up to ∼30 GPa and 886 K, Ti-6Al-4V is found to be stable in the hexagonal-close-packed, orαphase. The effect of temperature on the volume expansion and compressibility ofα-Ti-6Al-4V is modest. The martensiticα→ω(hexagonal) transition occurs at ∼30 GPa, with both phases coexisting until at ∼38-40 GPa the transition to theωphase is completed. Between 300 K and 844 K theα→ωtransition appears to be independent of temperature.ω-Ti-6Al-4V is stable to ∼91 GPa and 844 K, the highest combined pressure and temperature reached in these experiments. Pressure-volume-temperature equations-of-state for theαandωphases of Ti-6Al-4V are generated and found to be similar to pure Ti. A pronounced hysteresis is observed in theω-Ti-6Al-4V on decompression, with the hexagonal structure reverting back to theαphase at pressures below ∼9 GPa at room temperature, and at a higher pressure at elevated temperatures. Based on our data, we estimate the Ti-6Al-4Vα-ß-ωtriple point to occur at ∼900 K and 30 GPa, in good agreement with our calculations.

Off-lattice Monte Carlo simulation of supramolecular polymer architectures.

We introduce an efficient, scalable Monte Carlo algorithm to simulate cross-linked architectures of freely jointed and discrete wormlike chains. Bond movement is based on the discrete tractrix construction, which effects conformational changes that exactly preserve fixed-length constraints of all bonds. The algorithm reproduces known end-to-end distance distributions for simple, analytically tractable systems of cross-linked stiff and freely jointed polymers flawlessly, and is used to determine the effective persistence length of short bundles of semiflexible wormlike chains, cross-linked to each other. It reveals a possible regulatory mechanism in bundled networks: the effective persistence of bundles is controlled by the linker density.

Semiflexible filamentous composites.

Inspired by the ubiquity of composite filamentous networks in nature, we investigate models of biopolymer networks that consist of interconnected floppy and stiff filaments. Numerical simulations carried out in three dimensions allow us to explore the microscopic partitioning of stresses and strains between the stiff and floppy fractions cs and cf and reveal a nontrivial relationship between the mechanical behavior and the relative fraction of stiff polymer: when there are few stiff polymers, nonpercolated stiff "inclusions" are protected from large deformations by an encompassing floppy matrix, while at higher fractions of stiff material the stiff network is independently percolated and dominates the mechanical response.

[Postcardiac arrest treatment guide]. / Praxisleitfaden für die Postreanimationsbehandlung.

BACKGROUND: Treatment after cardiac arrest has become more complex and interdisciplinary over the last few years. Thus, the clinically active intensive and emergency care physician not only has to carry out the immediate care and acute diagnostics, but also has to prognosticate the neurological outcome. AIM: The different, most important steps are presented by leading experts in the area, taking into account the interdisciplinarity and the currently valid guidelines. MATERIALS AND METHODS: Attention was paid to a concise, practice-oriented presentation. RESULTS AND DISCUSSION: The practical guide contains all important steps from the acute care to the neurological prognosis generation that are relevant for the clinically active intensive care physician.

Anabaseine: venom alkaloid of aphaenogaster ants.

Anabaseine, a tobacco alkaloid, is identified as a poison gland product in Aphaenogaster ants, in which it functions as an attractant.

The structure of abelsonite.

Abelsonite, a C(31) nickel-porphyrin of the deoxophylloerythroetioporphyrin type, is shown to have methyl groups in the 2, 3, 7, 12, and 18 positions and ethyl groups in the 8 and 17 positions by high-resolution, high-field (1)H nuclear magnetic resonance and nuclear Overhauser effect studies. Removal of the nickel by treatment with methanesulfonic acid permitted confirmation of the structure on the free base porphyrin and demonstrated structural integrity under the conditions required for demetallation. The structure is best accounted for geochemically by the hypothesis that abelsonite is derived from a chlorophyll.

Effective-medium approach for stiff polymer networks with flexible cross-links.

Recent experiments have demonstrated that the nonlinear elasticity of in vitro networks of the biopolymer actin is dramatically altered in the presence of a flexible cross-linker such as the abundant cytoskeletal protein filamin. The basic principles of such networks remain poorly understood. Here we describe an effective-medium theory of flexibly cross-linked stiff polymer networks. We argue that the response of the cross-links can be fully attributed to entropic stiffening, while softening due to domain unfolding can be ignored. The network is modeled as a collection of randomly oriented rods connected by flexible cross-links to an elastic continuum. This effective medium is treated in a linear elastic limit as well as in a more general framework, in which the medium self-consistently represents the nonlinear network behavior. This model predicts that the nonlinear elastic response sets in at strains proportional to cross-linker length and inversely proportional to filament length. Furthermore, we find that the differential modulus scales linearly with the stress in the stiffening regime. These results are in excellent agreement with bulk rheology data.

[Biomarkers after resuscitation : Relevance in daily clinical practice for prognosis estimation and definition of therapeutic goals]. / Biomarker nach Reanimation : Relevanz im klinischen Alltag für Prognoseeinschätzung und Therapiezieldefinition.

BACKGROUND: The assessment of the neurological prognosis after cardiac arrest should be made using a multimodal approach involving clinical, physical and laboratory findings. Here, biomarkers are of high importance. The reliable prognostication has far-reaching consequences for the patient on the further course of therapy and rehabilitation. OBJECTIVES: Which biomarkers help in prognosis estimation and therapy target definition and are currently used in daily clinical practice? MATERIALS AND METHODS: Presentation of the multimodal approach for prognosis generation in patients after resuscitation with hypoxic-ischemic encephalopathy with special consideration and discussion of various biomarkers. RESULTS AND CONCLUSION: Neuron-specific enolase (NSE) is the best-established predictive biomarker in patients with hypoxic-ischemic encephalopathy after cardiac arrest. In combination with other methods (clinical examination, physical testing) and considering possible interfering factors (hemolysis, tumor diseases), NSE is used after 48-72 h with a cutoff value of 90 ng/ml. Most other biomarkers have so far only been studied in smaller groups or individual studies and thus cannot currently be routinely used outside of studies.

Geometric localization in supported elastic struts.

Localized deformation patterns are a common motif in morphogenesis and are increasingly finding applications in materials science and engineering, in such instances as mechanical memories. Here, we describe the emergence of spatially localized deformations in a minimal mechanical system by exploring the impact of growth and shear on the conformation of a semi-flexible filament connected to a pliable shearable substrate. We combine numerical simulations of a discrete rod model with theoretical analysis of the differential equations recovered in the continuum limit to quantify (in the form of scaling laws) how geometry, mechanics and growth act together to give rise to such localized structures in this system. We find that spatially localized deformations along the filament emerge for intermediate shear modulus and increasing growth. Finally, we use experiments on a 3D-printed multi-material model system to demonstrate that external control of the amount of shear and growth may be used to regulate the spatial extent of the localized strain texture.

Monte Carlo study of multiply crosslinked semiflexible polymer networks.

We present a method to generate realistic, three-dimensional networks of crosslinked semiflexible polymers. The free energy of these networks is obtained from the force-extension characteristics of the individual polymers and their persistent directionality through the crosslinks. A Monte Carlo scheme is employed to obtain isotropic, homogeneous networks that minimize the free energy and for which all of the relevant parameters can be varied: the persistence length and the contour length as well as the crosslinking length may be chosen at will. We also provide an initial survey of the mechanical properties of our networks subjected to shear strains, showing them to display the expected nonlinear stiffening behavior. Also, a key role for nonaffinity and its relation to order in the network is uncovered.

Improvement of lay rescuer chest compressions with a novel audiovisual feedback device : A randomized trial.

BACKGROUND: Bystander actions and skills determine among others the outcome of out-of-hospital cardiac arrest. However, the depth and rate of chest compressions (CC) are difficult to estimate for laypeople and poor CC quality may result. Our study aimed to evaluate the impact of a new feedback device on CC performance by laypeople. The percentage of CC with both correct rate and correct depth of all CC served as primary endpoint. METHODS: Forty-eight subjects with no medical background performed 2 min of CC on a manikin with and without a novel feedback device (TrueCPR™, Physio-Control, Redmond, Wash.). The device uses a novel, non-accelerometer-based technology. Participants were randomized into two groups. Group 1 performed a 2-min CC trial first with audiovisual feedback followed by a trial with no feedback information, while group 2 performed the task in reverse order. RESULTS: The absolute percentage of CC with correct rate and depth was significantly higher with the use of the device (59 ± 34% vs. 15 ± 21%, p < 0.0001). The longest interval without correct CC was significantly decreased (76.5 s vs. 27.5 s, p < 0.0001). CONCLUSION: The quality of CC carried out by laypeople is significantly improved with the use of a new feedback device. The device may be useful for cardiopulmonary resuscitation (CPR) by laypeople and for educational purposes.

Impact of acute kidney injury on neurological outcome and long-term survival after cardiac arrest - A 10 year observational follow up.

BACKGROUND: Acute kidney injury (AKI) may be associated with short- and long-term patient morbidity and mortality. Therefore, the impact of AKI after cardiac arrest on survival and neurological outcome was evaluated. METHODS: An observational single center study was conducted and consecutively included all out and in hospital cardiac arrest (OHCA/IHCA) patients treated with therapeutic temperature management between 2006 and 2013. Patient morbidity, mortality and neurological outcome according to the widely used Pittsburgh Cerebral Performance Category (CPC) were assessed. A good neurological outcome was defined as a CPC of 1-2 versus a poor neurological outcome with a CPC of 3-5. AKI was defined by using the KDIGO Guidelines 2012. RESULTS: 503 patients were observed in total. 29.4% (n = 148) developed AKI during their intensive care unit (ICU) stay. 70.6% (n = 355) did not experience AKI. The mean age at admission was 62 years, of those 72.8% were male and 77% experienced an out-of-hospital cardiac arrest (OHCA). AKI occurred with 41.2% more often in the group with poor neurological outcome compared to 17.1% in the group with good neurological outcome. The median survival for patients after cardiac arrest with AKI was 0.07 years compared to 6.5 years for patients without AKI. CONCLUSION: Our data suggest that AKI is a major risk factor for a poor neurological outcome and a higher mortality after cardiac arrest. Further important risk factors were age, time to ROSC and high NSE.

Immediate recovery of renal function after orthotopic liver transplantation in a patient with hepatorenal syndrome requiring hemodialysis for more than 8 months.

Severe liver dysfunction may lead to impairment of renal function without an underlying renal pathology. This phenomenon is called hepatorenal syndrome (HRS), which is associated with a poor prognosis showing a median survival of less than 2 months if renal replacement therapy is necessary. Liver transplantation is the best therapeutic option to regain renal function, but because of poor survival, these patients often die before transplantation. Herein we report a 37-year-old patient with ethyl-toxic liver cirrhosis who underwent hemodialysis due to HRS type I for more than 8 months. After living donor liver transplantation, diuresis immediately resumed, renal function soon recovered, and intermittent hemodialysis was stopped at 18 days after transplantation. Renal function was stable with a serum creatinine <2 mg/dL during the last 5 years posttransplantation. As far as we know, only a few cases of an anuric patient suffering from HRS have been reported with a survival beyond 8 months and full recovery of renal function after liver transplantation. This underlined that renal replacement therapy in HRS should be considered as a possible bridging method to liver transplantation even for longer periods.

Biophysical model of the role of actin remodeling on dendritic spine morphology.

Dendritic spines are small membranous structures that protrude from the neuronal dendrite. Each spine contains a synaptic contact site that may connect its parent dendrite to the axons of neighboring neurons. Dendritic spines are markedly distinct in shape and size, and certain types of stimulation prompt spines to evolve, in fairly predictable fashion, from thin nascent morphologies to the mushroom-like shapes associated with mature spines. It is well established that the remodeling of spines is strongly dependent upon the actin cytoskeleton inside the spine. A general framework that details the precise role of actin in directing the transitions between the various spine shapes is lacking. We address this issue, and present a quantitative, model-based scenario for spine plasticity validated using realistic and physiologically relevant parameters. Our model points to a crucial role for the actin cytoskeleton. In the early stages of spine formation, the interplay between the elastic properties of the spine membrane and the protrusive forces generated in the actin cytoskeleton propels the incipient spine. In the maturation stage, actin remodeling in the form of the combined dynamics of branched and bundled actin is required to form mature, mushroom-like spines. Importantly, our model shows that constricting the spine-neck aids in the stabilization of mature spines, thus pointing to a role in stabilization and maintenance for additional factors such as ring-like F-actin structures. Taken together, our model provides unique insights into the fundamental role of actin remodeling and polymerization forces during spine formation and maturation.

Automatic clustering of orthologs and in-paralogs from pairwise species comparisons.

Orthologs are genes in different species that originate from a single gene in the last common ancestor of these species. Such genes have often retained identical biological roles in the present-day organisms. It is hence important to identify orthologs for transferring functional information between genes in different organisms with a high degree of reliability. For example, orthologs of human proteins are often functionally characterized in model organisms. Unfortunately, orthology analysis between human and e.g. invertebrates is often complex because of large numbers of paralogs within protein families. Paralogs that predate the species split, which we call out-paralogs, can easily be confused with true orthologs. Paralogs that arose after the species split, which we call in-paralogs, however, are bona fide orthologs by definition. Orthologs and in-paralogs are typically detected with phylogenetic methods, but these are slow and difficult to automate. Automatic clustering methods based on two-way best genome-wide matches on the other hand, have so far not separated in-paralogs from out-paralogs effectively. We present a fully automatic method for finding orthologs and in-paralogs from two species. Ortholog clusters are seeded with a two-way best pairwise match, after which an algorithm for adding in-paralogs is applied. The method bypasses multiple alignments and phylogenetic trees, which can be slow and error-prone steps in classical ortholog detection. Still, it robustly detects complex orthologous relationships and assigns confidence values for both orthologs and in-paralogs. The program, called INPARANOID, was tested on all completely sequenced eukaryotic genomes. To assess the quality of INPARANOID results, ortholog clusters were generated from a dataset of worm and mammalian transmembrane proteins, and were compared to clusters derived by manual tree-based ortholog detection methods. This study led to the identification with a high degree of confidence of over a dozen novel worm-mammalian ortholog assignments that were previously undetected because of shortcomings of phylogenetic methods.A WWW server that allows searching for orthologs between human and several fully sequenced genomes is installed at http://www.cgb.ki.se/inparanoid/. This is the first comprehensive resource with orthologs of all fully sequenced eukaryotic genomes. Programs and tables of orthology assignments are available from the same location.