Binding and disruption of phospholipid bilayers by supramolecular RNA complexes

In an RNA world, RNAs would have regulated traffic through normally impermeable bilayer membranes. Using selection-amplification we previously found RNAs that bind stably and increase the ionic conductance of phospholipid membranes at high Mg2+ and Ca2+ concentrations. Now selection in reduced divalents yields RNAs that bind phosphatidylcholine liposomes under conditions closer to physiological. Such affinity for phospholipid membranes requires interactions between RNAs. In fact, we detected no functional monomeric membrane-binding RNAs. A membrane-active end-to-end heterotrimer consisting of 2 RNA 9 and 1 RNA 10 is defined by nucleotide protection, oligonucleotide competition, and mutant analysis. Oligomers of the heterotrimer bind stably, cause release of liposome-encapsulated solutes, and disrupt model black membranes. Individual RNA molecules do not show any of these activities. This novel mechanism of RNA binding to lipid membranes may not only regulate membrane permeability, but suggests that arrays of catalytic or structural RNAs on membranes are plausible. Finally, a selection met only by RNA complexes evokes new possibilities for selection-amplification itself.

Intracellular pH in adipocytes: effects of free fatty acid diffusion across the plasma membrane, lipolytic agonists, and insulin.

The main function of white adipose tissue is to store nutrient energy in the form of triglycerides. The mechanism by which free fatty acids (FFA) move into and out of the adipocyte has not been resolved. We show here that changes in intracellular pH (pH1) in adipocytes correlate with the movement of FFA across cellular membranes as predicted by the Kamp and Hamilton model of passive diffusion of FFA. Exposure of fat cells to lipolytic agents or external FFA results is a rapid intracellular acidification that is reversed by metabolism of the FFA or its removal by albumin. In contrast, insulin causes an alkalinization of the cell, consistent with its main function to promote esterification. Inhibition of Na+/H+ exchange in adipocytes does not prevent the changes in pHi caused by FFA, lipolytic agents, or insulin. A fatty acid dimer, which diffuses into the cell but is not metabolized, causes an irreversible acidification. Taken together, the data suggest that changes in pHi occur in adipocytes in response to the passive diffusion of un-ionized FFA (flip-flop) into and out of the cell and in response to their metabolism and production within the cell. These changes in pHi may, in turn, modulate hormonal signaling and metabolism with significant impact on cell function.

Shared fine specificity between T-cell receptors and an antibody recognizing a peptide/major histocompatibility class I complex.

Cytotoxic T cells recognize mosaic structures consisting of target peptides embedded within self-major histocompatibility complex (MHC) class I molecules. This structure has been described in great detail for several peptide-MHC complexes. In contrast, how T-cell receptors recognize peptide-MHC complexes have been less well characterized. We have used a complete set of singly substituted analogs of a mouse MHC class I, Kk-restricted peptide, influenza hemagglutinin (Ha)255-262, to address the binding specificity of this MHC molecule. Using the same peptide-MHC complexes we determined the fine specificity of two Ha255-262-specific, Kk-restricted T cells, and of a unique antibody, pSAN, specific for the same peptide-MHC complex. Independently, a model of the Ha255-262-Kk complex was generated through homology modeling and molecular mechanics refinement. The functional data and the model corroborated each other showing that peptide residues 1, 3, 4, 6, and 7 were exposed on the MHC surface and recognized by the T cells. Thus, the majority, and perhaps all, of the side chains of the non-primary anchor residues may be available for T-cell recognition, and contribute to the stringent specificity of T cells. A striking similarity between the specificity of the T cells and that of the pSAN antibody was found and most of the peptide residues, which could be recognized by the T cells, could also be recognized by the antibody.

Evolutionarily conserved Galphabetagamma binding surfaces support a model of the G protein-receptor complex.

The pivotal role of G proteins in sensory, hormonal, inflammatory, and proliferative responses has provoked intense interest in understanding how they interact with their receptors and effectors. Nonetheless, the locations of the receptors and effector binding sites remain poorly characterized, although nearly complete structures of the alphabetagamma heterotrimeric complex are available. Here we apply evolutionary trace (ET) analysis [Lichtarge, O., Bourne, H. R. & Cohen, F. E. (1996) J. Mol. Biol. 257, 342-358] to propose plausible locations for these sites. On each subunit, ET identifies evolutionarily selected surfaces composed of residues that do not vary within functional subgroups and that form spatial clusters. Four clusters correctly identify subunit interfaces, and additional clusters on Galpha point to likely receptor or effector binding sites. Our results implicate the conformationally variable region of Galpha in an effector binding role. Furthermore the range of predicted interactions between the receptor and Galphabetagamma, is sufficiently limited that we can build a low resolution and testable model of the receptor-G protein complex.

The kinesin walk: a dynamic model with elastically coupled heads.

Recently individual two-headed kinesin molecules have been studied in in vitro motility assays revealing a number of their peculiar transport properties. In this paper we propose a simple and robust model for the kinesin stepping process with elastically coupled Brownian heads that show all of these properties. The analytic and numerical treatment of our model results in a very good fit to the experimental data and practically has no free parameters. Changing the values of the parameters in the restricted range allowed by the related experimental estimates has almost no effect on the shape of the curves and results mainly in a variation of the zero load velocity that can be directly fitted to the measured data. In addition, the model is consistent with the measured pathway of the kinesin ATPase.

Dynamic friction and the origin of the complexity of earthquake sources.

We study a simple antiplane fault of finite length embedded in a homogeneous isotropic elastic solid to understand the origin of seismic source heterogeneity in the presence of nonlinear rate- and state-dependent friction. All the mechanical properties of the medium and friction are assumed homogeneous. Friction includes a characteristic length that is longer than the grid size so that our models have a well-defined continuum limit. Starting from a heterogeneous initial stress distribution, we apply a slowly increasing uniform stress load far from the fault and we simulate the seismicity for a few 1000 events. The style of seismicity produced by this model is determined by a control parameter associated with the degree of rate dependence of friction. For classical friction models with rate-independent friction, no complexity appears and seismicity is perfectly periodic. For weakly rate-dependent friction, large ruptures are still periodic, but small seismicity becomes increasingly nonstationary. When friction is highly rate-dependent, seismicity becomes nonperiodic and ruptures of all sizes occur inside the fault. Highly rate-dependent friction destabilizes the healing process producing premature healing of slip and partial stress drop. Partial stress drop produces large variations in the state of stress that in turn produce earthquakes of different sizes. Similar results have been found by other authors using the Burridge and Knopoff model. We conjecture that all models in which static stress drop is only a fraction of the dynamic stress drop produce stress heterogeneity.

Variability of the ocean heat content during the last millennium - an assessment with the ECHO-g Model

Studies addressing climate variability during the last millennium generally focus on variables with a direct influence on climate variability, like the fast thermal response to varying radiative forcing, or the large-scale changes in atmospheric dynamics (e. g. North Atlantic Oscillation). The ocean responds to these variations by slowly integrating in depth the upper heat flux changes, thus producing a delayed influence on ocean heat content (OHC) that can later impact low frequency SST (sea surface temperature) variability through reemergence processes. In this study, both the externally and internally driven variations of the OHC during the last millennium are investigated using a set of fully coupled simulations with the ECHO-G (coupled climate model ECHAMA4 and ocean model HOPE-G) atmosphere-ocean general circulation model (AOGCM). When compared to observations for the last 55 yr, the model tends to overestimate the global trends and underestimate the decadal OHC variability. Extending the analysis back to the last one thousand years, the main impact of the radiative forcing is an OHC increase at high latitudes, explained to some extent by a reduction in cloud cover and the subsequent increase of short-wave radiation at the surface. This OHC response is dominated by the effect of volcanism in the preindustrial era, and by the fast increase of GHGs during the last 150 yr. Likewise, salient impacts from internal climate variability are observed at regional scales. For instance, upper temperature in the equatorial Pacific is controlled by ENSO (El Nino Southern Oscillation) variability from interannual to multidecadal timescales. Also, both the Pacific Decadal Oscillation (PDO) and the Atlantic Multidecadal Oscillation (AMO) modulate intermittently the interdecadal OHC variability in the North Pacific and Mid Atlantic, respectively. The NAO, through its influence on North Atlantic surface heat fluxes and convection, also plays an important role on the OHC at multiple timescales, leading first to a cooling in the Labrador and Irminger seas, and later on to a North Atlantic warming, associated with a delayed impact on the AMO.

The Role of Hope in Rehabilitation and Long-term Outcomes among patients with Comorbid Spinal Cord and Traumatic Brain Injuries.

Spinal cord injury (SCI) and traumatic brain injury (TBI) are two potentially devastating conditions alone; when they co-occur in an individual they can be doubly so. The role of hope in rehabilitating oneself and recovering emotionally is examined in this paper. More specifically, Snyder's Model of Hope (1991) is examined as a tool that can aid in the rehabilitative process and help treatment providers, their patients, and the families of patients keep hope alive during a time of physical and emotional upheaval. This paper further examines the roles of hope in a rehabilitation program at Craig Hospital, a private, non-profit hospital dedicated exclusively to the rehabilitation of SCIs and TBIs and designated as a TBI and SCI Model Systems Center.

USLE and WEPP Soil Erosion Models: Their Applicability and Use in Generating Cover Values to Stabilize Soil in the Los Alamos, New Mexico Area

Soil erosion is a naturally occurring process that involves the detachment, transport, and deposition of soil particles. Disturbances such as thinning and wildfire can reduce cover greatly and increase erosion rates. Forest managers may use erosion prediction tools, such as the Universal Soil Loss Equation (USLE) and Water Erosion Prediction Project (WEPP) to estimate erosion rates and develop techniques to manage erosion. However, it is important to understand the differences and the applications of each model. Erosion rates were generated by each model and the model most applicable to the study site, Los Alamos, New Mexico was determined. It was also used to find the amount of cover needed to stabilize soil. The USLE is a simpler model and less complicated than a computer model like WEPP, and thus easier to manipulate to estimate cover values. Predicted cover values were compared to field cover values. Cover is necessary to establish effective erosion control guidelines.

MDWEnet: a practical approach to achieving interoperability of model-driven web engineering methods

Current model-driven Web Engineering approaches (such as OO-H, UWE or WebML) provide a set of methods and supporting tools for a systematic design and development of Web applications. Each method addresses different concerns using separate models (content, navigation, presentation, business logic, etc.), and provide model compilers that produce most of the logic and Web pages of the application from these models. However, these proposals also have some limitations, especially for exchanging models or representing further modeling concerns, such as architectural styles, technology independence, or distribution. A possible solution to these issues is provided by making model-driven Web Engineering proposals interoperate, being able to complement each other, and to exchange models between the different tools. MDWEnet is a recent initiative started by a small group of researchers working on model-driven Web Engineering (MDWE). Its goal is to improve current practices and tools for the model-driven development of Web applications for better interoperability. The proposal is based on the strengths of current model-driven Web Engineering methods, and the existing experience and knowledge in the field. This paper presents the background, motivation, scope, and objectives of MDWEnet. Furthermore, it reports on the MDWEnet results and achievements so far, and its future plan of actions.

Spin dynamics of current-driven single magnetic adatoms and molecules

A scanning tunneling microscope can probe the inelastic spin excitations of a single magnetic atom in a surface via spin-flip assisted tunneling in which transport electrons exchange spin and energy with the atomic spin. If the inelastic transport time, defined as the average time elapsed between two inelastic spin flip events, is shorter than the atom spin-relaxation time, the scanning tunnel microscope (STM) current can drive the spin out of equilibrium. Here we model this process using rate equations and a model Hamiltonian that describes successfully spin-flip-assisted tunneling experiments, including a single Mn atom, a Mn dimer, and Fe Phthalocyanine molecules. When the STM current is not spin polarized, the nonequilibrium spin dynamics of the magnetic atom results in nonmonotonic dI/dV curves. In the case of spin-polarized STM current, the spin orientation of the magnetic atom can be controlled parallel or antiparallel to the magnetic moment of the tip. Thus, spin-polarized STM tips can be used both to probe and to control the magnetic moment of a single atom.

Polarimetric SAR model for soil moisture estimation over vineyards at C-band

In this paper we propose a two-component polarimetric model for soil moisture estimation on vineyards suited for C-band radar data. According to a polarimetric analysis carried out here, this scenario is made up of one dominant direct return from the soil and a multiple scattering component accounting for disturbing and nonmodeled signal fluctuations from soil and short vegetation. We propose a combined X-Bragg/Fresnel approach to characterize the polarized direct response from soil. A validation of this polarimetric model has been performed in terms of its consistency with respect to the available data both from RADARSAT-2 and from indoor measurements. High inversion rates are reported for different phenological stages of vines, and the model gives a consistent interpretation of the data as long as the volume component power remains about or below 50% of the surface contribution power. However, the scarcity of soil moisture measurements in this study prevents the validation of the algorithm in terms of the accuracy of soil moisture retrieval and an extensive campaign is required to fully demonstrate the validity of the model. Different sources of mismatches between the model and the data have been also discussed and analyzed.

Local community perception towards bats (Mammalia: Chiroptera) in Caves in South central Mindanao, Philippines: Threats and Implication for conservation

In the tropics, bats are an essential component of many native ecosystems, through providing various ecological services including pollination and insect pest control, in addition to seed dispersal. Many Philippine bat species roost in caves and underground habitats. However, many caves are disturbed by people, to exploit resources for food, recreation, and mineral and guano extraction. The misunderstanding of the importance of bats to the ecosystem is also considered a threat to many cave roosting species. Understanding the conflicts between humans and ecosystems which provide essential services is important to maintain ecosystem service provision. A total of 100 local respondents from the village of Pisan, Kabacan North Cotabato in south central Mindanao were interviewed through semi-structured interviews and focus group discussions. Respondents were asked about their views, levels of knowledge, use, interaction, and awareness towards both the caves and bats in their locality. Our survey found that most of the respondents are aware of the presence of bats from the caves in their locality. Unfortunately, a large proportion of the respondents noted that bats are hunted in caves for bush meat and trade, and most people perceived bats as pest to fruit crops such as durian. These factors are among the main factors of the execution of many bat colonies in caves of south central Mindanao. In general, cave bats are under appreciated species in caves. The unregulated tourism, hunting for bush meat and trade, and guano extraction are among the alarming threats occurring for both caves and bats in the locality and possibly to other localities in the country. Furthermore, the establishment of strong and effective model conservation education programs and the strengthening the participation of local government, academic, and community are essential steps to preserve the current state of cave bats in the area.

Influence of drill speed and feed rate on bone damage

Implant failures and postoperative complications are often associated to the bone drilling. Estimation and control of drilling parameters are critical to prevent mechanical damage to the bone tissues. For better performance of the drilling procedures, it is essential to understand the mechanical behaviour of bones that leads to their failures and consequently to improve the cutting conditions. This paper investigates the effect of drill speed and feed-rate on mechanical damage during drilling of solid rigid foam materials, with similar mechanical properties to the human bone. Experimental tests were conducted on biomechanical blocks instrumented with strain gauges to assess the drill speed and feed-rate influence. A three-dimensional dynamic finite element model to predict the bone stresses, as a function of drilling conditions, drill geometry and bone model, was developed. These simulations incorporate the dynamic characteristics involved in the drilling process. The element removal scheme is taken into account and allows advanced simulations of tool penetration and material removal. Experimental and numerical results show that generated stresses in the material tend to increase with tool penetration. Higher drill speed leads to an increase of von-Mises stresses and strains in the solid rigid foams. However, when the feed-rate is higher, the stresses and strains are lower. The numerical normal stresses and strains are found to be in good agreement with experimental results. The models could be an accurate analysis tool to simulate the stresses distribution in the bone during the drilling process.

Net Neutrality and Mandatory Network-Sharing: How to disconnect the continent. CEPS Policy Brief No. 309, 18 December 2013

A lively debate emerged on the proposed “Connected Continent” legislative package presented by the European Commission in September 2013. The package contains a proposed rule on the ‘open Internet’, which was heavily discussed in European Parliament hearings in early December. This commentary argues that while the proposed rule is in principle balanced and appealing, it is utterly impractical due to the enormous uncertainty that its application would entail. At the same time, the rule is very far from what neutrality proponents have argued for almost a decade: rather than the place for internet freedom, it would transform the Web into a place requiring constant micro-management and tutoring of user behaviour. Both arguments lead to the conclusion that the current proposal should be at once reformed and analysed under a more holistic lens. On the one hand, Europe should launch an ambitious project for the future, converged infrastructure by mobilising resources and reforming rules to encourage investment into ubiquitous, converged, ‘always on’ connectivity. On the other hand, enhanced legal certainty for broadband investment could justify a more neutrality-oriented approach to traffic management practices on the Internet. The author proposes a new approach to Internet regulation which, altogether, will lead to a more balanced and sustainable model for the future, without jeopardising user freedom.