Molecular-level understanding of protein adsorption at the interface between water and a strongly interacting uncharged solid surface

Although protein adsorption on solids is of immense relevance, experimental limitations mean there is still a remarkable lack of understanding of the adsorption mechanism, particularly at a molecular level. By subjecting 240+ molecular dynamics simulations of two peptide/water/solid surface systems to statistical analysis, a generalized molecular level mechanism for peptide adsorption has been identified for uncharged surfaces that interact strongly with the solution phase. This mechanism is composed of three phases: (1) biased diffusion of the peptide from the bulk phase toward the surface; (2) anchoring of the peptide to the water/solid interface via interaction of a hydrophilic group with the water adjacent to the surface or a strongly interacting hydrophobic group with the surface; and (3) lockdown of the peptide on the surface via a slow, stepwise and largely sequential adsorption of its residues, which we term 'statistical zippering'. The adsorption mechanism is dictated by the existence of water layers adjacent to the solid and orientational ordering therein. By extending the solid into the solution by ∼8 Å and endowing it with a charged character, the water layers ensure the peptide feels the effect of the solid at a range well beyond the dispersion force that arises from it, thus inducing biased diffusion from afar. The charging of the interface also facilitates anchoring of the peptide near the surface via one of its hydrophilic groups, allowing it time it would otherwise not have to rearrange and lockdown. Finally, the slowness of the lockdown process is dictated by the need for the peptide groups to replace adjacent tightly bound interfacial water. © 2014 American Chemical Society

Untersuchungen über die Strahlungsempfindlichkeit von Rebenknospen

Die Bestrahlung der Winterknospen der Sorte Gamay schwarz mit Strahlungsdosen von 200-1000 rad 0°Co übt einen stimulativen Einfluß auf den Austrieb und auf das Anfangswachstum der Triebe aus. Während eine Dosis von 5000 rad für die Rebenknospen letal ist, hängt die Letalität der Strnhlungsdosen von 2000-4000 rad im wesentlichen von den Anzuchtbedingungen ab: je günstiger diese sind, umso geringer ist die Strahlungsempfindlichkeit der Knospen. Die Winterknospen können im Ruhestadium zur Auslösung somatischer Mutationen mit Dosen bis zu 4000 rad bestrahlt werden, wenn anschließend günstige Bedingungen für die Anzucht und das Wachstum der Stecklinge geboten werden.Die Untersuchungen haben gezeigt, daß die Verwendung bestrahlter Pfropfreiser für den Weinbau keine praktische Bedeutung hat, da nur ein schwacher Anwuchs und ein geringes Wachstum der Pfropfreben erzielt werden

Fine tuning of dwelling time in friction stir welding for preventing material overheating, weld tensile strength increase and weld nugget size decrease

After successful welding, destructive testing into test samples from Al 2024-T351 friction stir butt welds showed that tensile strength of the weld improve along the joint line, while dimensions of the weld nugget decrease. For those welds, both the base material and the welding tool constantly cool down during the welding phase. Obviously, the base material became overheated during the long dwelling phase what made conditions for creation of joints with the reduced mechanical properties. Preserving all process parameters but varying the dwelling time from 5-27 seconds a new set of welding is done to reach maximal achievable tensile strength. An analytical-numerical-experimental model is used for optimising the duration of the dwelling time while searching for the maximal tensile strength of the welds

Energy landscapes of a pair of adsorbed peptides

The wide relevance of peptide adsorption in natural and synthetic contexts means it has attracted much attention. Molecular dynamics (MD) simulation has been widely used in these endeavors. Much of this has focused on single peptides due to the computational effort required to capture the rare events that characterize their adsorption. This focus is, however, of limited practical relevance as in reality, most systems of interest operate in the nondilute regime where peptides will interact with other adsorbed peptides. As an alternative to MD simulation, we have used energy landscape mapping (ELM) to investigate two met-enkephalin molecules adsorbed at a gas/graphite interface. Major conformations of the adsorbed peptides and the connecting transition states are elucidated along with the associated energy barriers and rates of exchange. The last of these makes clear that MD simulations are currently of limited use in probing the co-adsorption of two peptides, let alone more. The constant volume heat capacity as a function of temperature is also presented. Overall, this study represents a significant step toward characterizing peptide adsorption beyond the dilute limit

Energy landscape mapping and replica exchange molecular dynamics of an adsorbed peptide

Adsorption of peptides at the interface between a fluid and a solid occurs widely in both nature and applications. Knowing the dominant conformations of adsorbed peptides and the energy barriers between them is of interest for a variety of reasons. Molecular dynamics (MD) simulation is a widely used technique that can yield such understanding. However, the complexity of the energy landscapes of adsorbed peptides means that comprehensive exploration of the energy landscape by MD simulation is challenging. An alternative approach is energy landscape mapping (ELM), which involves the location of stationary points on the potential energy surface, and its analysis to determine, for example, the pathways and energy barriers between them. In the study reported here, a comparison is made between this technique and replica exchange molecular dynamics (REMD) for met-enkephalin adsorbed at the interface between graphite and the gas phase: the first ever direct comparison of these techniques for adsorbed peptides. Both methods yield the dominant adsorbed peptide conformations. Unlike REMD, however, ELM readily allows the identification of the connectivity and energy barriers between the favored conformations, transition paths, and structures between these conformations and the impact of entropy. It also permits the calculation of the constant volume heat capacity although the accuracy of this is limited by the sampling of high-energy minima. Overall, compared to REMD, ELM provides additional insights into the adsorbed peptide system provided sufficient care is taken to ensure that key parts of the landscape are adequately sampled

Characterizing the switching transitions of an adsorbed peptide by mapping the potential energy surface

Peptide adsorption occurs across technology, medicine, and nature. The functions of adsorbed peptides are related to their conformation. In the past, molecular simulation methods such as molecular dynamics have been used to determine key conformations of adsorbed peptides. However, the transitions between these conformations often occur too slowly to be modeled reliably by such methods. This means such transitions are less well understood. In the study reported here, discrete path sampling is used for the first time to study the potential energy surface of an adsorbed peptide (polyalanine) and the transition pathways between various stable adsorbed conformations that have been identified in prior work by two of the authors [Mijajlovic, M.; Biggs, M. J. J. Phys. Chem. C 2007, 111, 15839−15847]. Mechanisms for the switching of adsorbed polyalanine between the stable conformations are elucidated along with the energetics of these switches

Effective Temperature Based Algorithm for Achieving Constant Quality Resistance Seam Weld

The resistance seam welding is a welding technique that is often used for the creation of the leak-tight welds. It is a technique where the weld is created as a set of overlapping weld nuggets between the cylindrical welding electrodes. The creation of the weld nuggets is depending on many external and internal parameters. Some of the external parameters are pressing force, welding electrodes, electrical current and time, while the internal parameters are electrical resistance, resistivity, and temperature. The main issue with the resistance seam welding is to properly set up internal and external parameters, create a weld nugget of a certain quality, reconfigure the parameters, relocate, and create another weld nugget of the same quality. The modern welding machines must have monitoring systems capable to make decisions and recalibration of the parameters. These systems are very complex and expensive, and as such, non-affordable for many small enterprises. This paper is presenting an effective, temperature-based algorithm for selecting the optimal welding parameters before the welding begins. The algorithm bases on the data from the experimental welding and numeric simulation of the welding process. The verification of the algorithm is done after testing the quality of the welds

Temperature dependent effective friction coefficient estimation in friction stir welding with the bobbin tool

The friction coefficient in many friction stir welding researches is generally used as an effective, constant value without concern on the adaptable and changeable nature of the friction during welding sequence. This is understandable because the main problem in analyzing friction in friction stir welding are complex nature of the friction processes, case-dependent and time dependent contact between the bodies, influence of the temperature, sliding velocity, etc. This paper is presenting a complex experimental-numerical-analytical model for estimating the effective friction coefficient on contact of the bobbin tool and welding plates during welding, considering the temperature at the contact as the most influencing parameter on friction. The estimation criterion is the correspondence of the experimental temperature and temperature from the numerical model. The estimation procedure is iterative and parametric - the heat transport parameters and friction coefficient are adapted during the estimation procedure in a realistic manner to achieve relative difference between experimental and model's temperature lower than 3%. The results show that friction coefficient varies from 0.01 to 0.21 for steel-aluminium alloy contact and temperature range from 406 degrees C to 22 degrees C

Microfluidic hydrodynamic focusing based synthesis of POPC liposomes for model biological systems

Lipid vesicles have received significant attention in areas ranging from pharmaceutical and biomedical engineering to novel materials and nanotechnology. Microfluidic-based synthesis of liposomes offers a number of advantages over the more traditional synthesis methods such as extrusion and sonication. One such microfluidic approach is microfluidic hydrodynamic focusing (MHF), which has been used to synthesize nanoparticles and vesicles of various lipids. We show here that this method can be utilized in synthesis of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) vesicles with controllable size. Since POPC is among the primary constituents of cellular membranes, this work is of direct applicability to modelling of biological systems and development of nano-containers with higher biologic compatibility for pharmaceutical and medical applications.M. Mijajlovic, D. Wright, V. Zivkovic, J.X. Bi, M.J. Bigg

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

Background There is a link between high on-treatment platelet reactivity (HPR) and adverse vascular events in stroke. This study aimed to compare multiple electrode platelet aggregometry (MEA), in healthy subjects and ischaemic stroke patients, and between patients naive to antiplatelet drugs (AP) and those on regular low dose AP. We also aimed to determine prevalence of HPR at baseline and at 3–5 days after loading doses of aspirin. Methods Patients with first ever ischaemic stroke were age and sex-matched to a healthy control group. Three venous blood samples were collected: on admission before any treatment given (baseline); at 24 h and 3–5 days after standard treatment. MEA was determined using a Mutliplate® analyser and agonists tested were arachidonic acid (ASPI), adenosine diphosphate (ADP) and collagen (COL). Results Seventy patients (mean age 73 years [SD 13]; 42 men, 28 women) were age and sex-matched to 72 healthy subjects. Thirty-three patients were on antiplatelet drugs (AP) prior to stroke onset and 37 were AP-naive. MEA results for all agonists were significantly increased in AP-naive patients compared to healthy subjects: ADP 98 ± 31 vs 81 ± 24, p < 0.005; ASPI 117 ± 31 vs 98 ± 27, p < 0.005; COL 100 ± 25 vs 82 ± 20, p < 0.005. For patients on long term AP, 33% (10/30) of patients were considered aspirin-resistant. At 3–5 days following loading doses of aspirin, only 11.1% were aspirin resistant based on an ASPI cut-off value of 40 AU*min. Conclusions Many patients receiving low dose aspirin met the criteria of aspirin resistance but this was much lower at 3–5 days following loading doses of aspirin. Future studies are needed to establish the causes of HPR and potential benefits of individualizing AP treatment based on platelet function testing