Dynamics of protein-protein encounter: a Langevin equation approach with reaction patches

We study the formation of protein-protein encounter complexes with a Langevin equation approach that considers direct, steric and thermal forces. As three model systems with distinctly different properties we consider the pairs barnase:barstar, cytochrome c:cytochrome c peroxidase and p53:MDM2. In each case, proteins are modeled either as spherical particles, as dipolar spheres or as collection of several small beads with one dipole. Spherical reaction patches are placed on the model proteins according to the known experimental structures of the protein complexes. In the computer simulations, concentration is varied by changing box size. Encounter is defined as overlap of the reaction patches and the corresponding first passage times are recorded together with the number of unsuccessful contacts before encounter. We find that encounter frequency scales linearly with protein concentration, thus proving that our microscopic model results in a well-defined macroscopic encounter rate. The number of unsuccessful contacts before encounter decreases with increasing encounter rate and ranges from 20-9000. For all three models, encounter rates are obtained within one order of magnitude of the experimentally measured association rates. Electrostatic steering enhances association up to 50-fold. If diffusional encounter is dominant (p53:MDM2) or similarly important as electrostatic steering (barnase:barstar), then encounter rate decreases with decreasing patch radius. More detailed modeling of protein shapes decreases encounter rates by 5-95 percent. Our study shows how generic principles of protein-protein association are modulated by molecular features of the systems under consideration. Moreover it allows us to assess different coarse-graining strategies for the future modelling of the dynamics of large protein complexes

Rock Physics Based Velocity-Porosity Correlations Developed For Estimation Of The Elastic Properties Of The Bakken Formations Of The Williston Basin, North Dakota

Rock Physics Based Velocity-Porosity Correlations Developed for Estimation of the Elastic Properties of the Bakken Formations of the Williston Basin, North DakotaABSTRACT Oil production from the Bakken Shale in North Dakota has benefitted from significant technological advancements since its beginning approximately two decades ago. Most of the advancements resulted from better characterization of shales, which are very heterogeneous and their properties vary at different scales. The need for costly operations such as drilling long laterals and multi-stage hydraulic fracturing for production from these unconventional reservoirs, signifies the importance of understanding the physical and mechanical properties of these formations in order to reduce the risk margins and improve project economics at diffetent phases of the life of the field. Rock physics is a relatively new discipline that has been used in shale reservoirs to integrate petrophysical, geomechanical and seismic measurements. Rock physics models are predictive tools used to estimate the velocity, or elastic properties of formations, based on strong theoretical foundations, as opposed to some of the simple empirical correlations that have been developed for specific regional formations. While the basic rock physics models use simplified asumptions and involve less input, more complex models, such as inclusion-based models, estimate velocity-porosity relation as function of different parameters including pore fluid saturation and type, cementation, confining pressure and diagenesis. The downside is that these models require performing tedious calculations and in some cases solving complex differential equations. These models may also differ depending on the type of formation, for example, in the Bakken, separate models may be used for the upper Bakken and lower Bakken shales (UBS, LBS) compared to the clastic or carbonate formations in the Middle Bakken (MB) member. In this research study, we developed velocity-porosity correlations for the Bakken formation. These models were developed based on large volume of data from simulaion of many cases using the differential equivalent medium (DEM) theory, a commonly used rock physics model. DEM models were developed for single mineral rocks, i.e. rocks composed of only one mineral, with different porosities. The pores were then modeled with three phase fluid (water, oil and gas) at different saturation levels and finally, different pore aspect ratios were assumed to simulate crack, interparticle, intergranular and moldic type pore geometries. The correlation constants were extracted for different key minerals in the Bakken, including quartz, calcite, dolomite, anhydrite, illite and kerogen. Having the volume fraction of minerals from lab-based XRD or Elemental Capture Spectroscopy (ECS) logs, linerar averaging was applied to estimate the velocity and elastic properties of the formations. The correlations were applied to several wells in the Bakken and also compared with the existing lab data, which showed a good agreement with the DEM model. The simplicity of using the correlations, that can be developed in an excel spreadsheet and using a single approach for different type of formations, offers a great advangtage for their applications

Improving Self-Care Awareness Among Undergraduate Nursing Students

The purpose of this DNP project was to improve self-care (SC) awareness among undergraduate nursing students by educating on the use of constructive SC activities. Twenty-two senior level nursing students attended an educational seminar, completed the Mindful Self-Care Scale – Clinical (MSCS-C) pre- and post-survey, and reflective journaling. A paired-samples t test was calculated to compare the mean pretest score to the mean posttest score. The mean on the pretest was 77.68 (sd= 9.33), and the mean on the posttest was 75.27 (sd= 31.59). A significant increase from pretest to posttest was found (t (21) = .307, p \u3c .05). Thematical analysis revealed enhanced awareness and incorporation of constructive SC activities. Educational interventions which seek to improve SC awareness will generate practical and sustainable acts of SC, thus improving students’ overall success and further empowering students in their transition from graduate to licensed nurses

Students’ Knowledge of Alzheimer’s Disease

Preparing nursing students to care for the ever-growing aging population with memory impairment is vital. This research study aimed to determine the prevalence of knowledge of Alzheimer’s disease (AD) among Baccalaureate nursing students. A descriptive correlational design was used to determine the prevalence of AD knowledge among juniors in an Adult I course and seniors in a Mental Health nursing course. A cross-sectional design was used to collect data using the Alzheimer’s Disease Knowledge Scale (ADKS). A convenience sample of 63 student cohorts completed the survey. Results indicated that students were aware that AD is a form of dementia; however, students were lacking more comprehensive knowledge of this debilitating brain disease. Based on this study’s findings, students’ knowledge of AD could be expanded. The number of those suffering from various forms of dementia is steadily rising. Taking into consideration the continued rise of patients with dementia-related illnesses, it is imperative for nurse educators to recognize these vicissitudes. Failure to address the delivery of inadequate care has the potential to produce devastating effects in this vulnerable population. It is recommended that nurse educators incorporate nursing curricula which addresses care of the aging adult, specifically those with memory impairments as dementia has already be deemed a public health concern

Exploring barriers in expertise seeking : why don\u27t they ask an expert?

This paper reports findings from a research project that explores reasons why some employees prefer to seek expertise to resolve work-related problems from direct colleagues rather than designated internal experts. Several studies suggest that while an expert generally provides a higher quality solution in a shorter time, workers tend to ask friendly or proximate colleagues to help with knowledge-based problems at work. Prior research provides only fragmented insights into understanding the barriers to asking a designated internal expert for help at work. To address this gap, we asked post-graduate students enrolled in a knowledge management subject at a large Australian university to share their perspectives in an online discussion forum. Content analysis of the collected perspectives enabled identification of twenty-one factors that may limit the seeking of expertise from a designated internal expert. The factors are grouped in four categories: environment, accessibility, communication and personality. In addition one context variable is described, determining the extent to which the barriers are influential in a specific situation. By synthesising the results, we have proposed two models of expertise-seeking barriers. A literature review helps validate the barriers identified by the study. Key theoretical and practical implications are also discussed.<br /

Hemoglobin-Mediated Nitric Oxide Signaling

The rate that hemoglobin reacts with nitric oxide (NO) is limited by how fast NO can diffuse into the heme pocket. The reaction is as fast as any ligand/protein reaction can be and the result, when hemoglobin is in its oxygenated form, is formation of nitrate in what is known as the dioxygenation reaction. As nitrate, at the concentrations made through the deoxygenation reaction, is biologically inert, the only role hemoglobin was once thought to play in NO signaling was to inhibit it. However, there are now several mechanisms that have been discovered by which hemoglobin may preserve, control, and even create NO activity. These mechanisms involve compartmentalization of reacting species and conversion of NO from or into other species such as nitros othiols or nitrite which could transport NO activity. Despite the tremendous amount of work devoted to this field, major questions concerning precise mechanisms of NO activity preservation as well as if and how Hb creates NO activity remain unanswered

Brain tissue properties differentiate between motor and limbic basal ganglia circuits

Despite advances in understanding basic organizational principles of the human basal ganglia, accurate in vivo assessment of their anatomical properties is essential to improve early diagnosis in disorders with corticosubcortical pathology and optimize target planning in deep brain stimulation. Main goal of this study was the detailed topological characterization of limbic, associative, and motor subdivisions of the subthalamic nucleus (STN) in relation to corresponding corticosubcortical circuits. To this aim, we used magnetic resonance imaging and investigated independently anatomical connectivity via white matter tracts next to brain tissue properties. On the basis of probabilistic diffusion tractography we identified STN subregions with predominantly motor, associative, and limbic connectivity. We then computed for each of the nonoverlapping STN subregions the covariance between local brain tissue properties and the rest of the brain using high-resolution maps of magnetization transfer (MT) saturation and longitudinal (R1) and transverse relaxation rate (R2*). The demonstrated spatial distribution pattern of covariance between brain tissue properties linked to myelin (R1 and MT) and iron (R2*) content clearly segregates between motor and limbic basal ganglia circuits. We interpret the demonstrated covariance pattern as evidence for shared tissue properties within a functional circuit, which is closely linked to its function. Our findings open new possibilities for investigation of changes in the established covariance pattern aiming at accurate diagnosis of basal ganglia disorders and prediction of treatment outcom