Outer Domain Research Articles

Evaluation of multi-level barriers and facilitators in a large diabetic retinopathy screening program in federally qualified health centers: a qualitative study

BackgroundRecommended annual diabetic retinopathy (DR) screening for people with diabetes has low rates in the USA, especially in underserved populations. Telemedicine DR screening (TDRS) in primary care clinics could expand access and increase adherence. Despite this potential, studies have observed high variability in TDRS rates among clinics and over time, highlighting the need for implementation supports. Previous studies of determinants of TDRS focus on patients’ perspectives, with few studies targeting upstream multi-level barriers and facilitators. Addressing this gap, this qualitative study aimed to identify and evaluate multi-level perceived determinants of TDRS in Federally Qualified Health Centers (FQHCs), to inform the development of targeted implementation strategies.MethodsWe developed a theory-based semi-structured interview tool based on the Consolidated Framework for Implementation Research (CFIR). We conducted 22 key informant interviews with professionals involved in TDRS (administrators, clinicians, staff). The interviews were audio-recorded and transcribed verbatim. Reported barriers and facilitators were organized into emergent themes and classified according to CFIR constructs. Constructs influencing TDRS implementation were rated for each study site and compared across sites by the investigators.ResultsProfessionals identified 21 main barriers and facilitators under twelve constructs of the five CFIR domains. Several identified themes were novel, whereas others corroborated previous findings in the literature (e.g., lack of time and human resources, presence of a champion). Of the 21 identified themes, 13 were classified under the CFIR’s Inner Setting domain, specifically under the constructs Compatibility and Available Resources. Themes under the Outer Setting domain (constructs External Incentives and Cost) were primarily perceived by administrators, whereas themes in other domains were perceived across all professional categories. Two Inner Setting (Leadership Engagement, Goals and Feedback) and two Process (Champion, Engaging) constructs were found to strongly distinguish sites with high versus low TDRS performance.ConclusionsThis study classified barriers and facilitators to TDRS as perceived by administrators, clinicians, and staff in FQHCs, then identified CFIR constructs that distinguished high- and low-performance clinics. Implementation strategies such as academic detailing and collection and communication of program data and successes to leadership; engaging of stakeholders through involvement in implementation planning; and appointment of intervention champions may therefore improve TDRS implementation and sustainment in resource-constrained settings.

Factors influencing the implementation of mental health recovery into services: a systematic mixed studies review

BackgroundCountries around the world have committed in policy to transforming their mental health services towards a recovery orientation. How has mental health recovery been implemented into services for adults, and what factors influence the implementation of recovery-oriented services?MethodsThis systematic mixed studies review followed a convergent qualitative synthesis design and used the best-fit framework synthesis method. Librarians ran searches in Ovid- MEDLINE, Ovid-EMBASE, Ovid-PsycInfo, EBSCO-CINAHL Plus with Full Text, ProQuest Dissertations and Theses, Cochrane Library, and Scopus. Two reviewers independently screened studies for inclusion or exclusion using DistillerSR. Qualitative, quantitative, and mixed methods peer-reviewed studies published since 1998 were included if they reported a new effort to transform adult mental health services towards a recovery orientation, and reported findings related to implementation experience, process, or factors. Data was extracted in NVivo12 to the 38 constructs of the Consolidated Framework for Implementation Research (CFIR). The synthesis included a within-case and a cross-case thematic analysis of data coded to each CFIR construct. Cases were types of recovery-oriented innovations.ResultsSeventy studies met our inclusion criteria. These were grouped into seven types of recovery-oriented innovations (cases) for within-case and cross-case synthesis. Themes illustrating common implementation factors across innovations are presented by CFIR domain: Intervention Characteristics (flexibility, relationship building, lived experience); Inner Setting (traditional biomedical vs. recovery-oriented approach, the importance of organizational and policy commitment to recovery-transformation, staff turnover, lack of resources to support personal recovery goals, information gaps about new roles and procedures, interpersonal relationships), Characteristics of Individuals (variability in knowledge about recovery, characteristics of recovery-oriented service providers); Process (the importance of planning, early and continuous engagement with stakeholders). Very little data from included studies was extracted to the outer setting domain, and therefore, we present only some initial observations and note that further research on outer setting implementation factors is needed.ConclusionThe CFIR required some adaptation for use as an implementation framework in this review. The common implementation factors presented are an important starting point for stakeholders to consider when implementing recovery-oriented services.

SARS‐CoV‐2 Spike Proteins: A Key Target for COVID‐19 Therapeutics Development

The spike proteins that crown SARS‐CoV‐2, the novel coronavirus behind the nearly 2 million COVID‐19 deaths this year, may be the key to stopping the infectious disease firmly in its tracks. By recognizing and attaching to human cells, these spike proteins spearhead the process of SARS‐CoV‐2 infection in the body. Thus, understanding their architecture and mechanics is critical to pinpointing the vulnerabilities of this coronavirus and guiding therapeutic development. To that end, here we present a review of the latest discoveries in the spike proteins’ structure and function alongside a physical model of the spike protein, highlighting features of clinical interest in antibody, small‐molecule drug, and vaccine development.The spike protein is comprised of two functional domains. The outer S1 domain includes the receptor binding domain, which recognizes and binds to an angiotensin‐converting enzyme 2 (ACE2) receptor on the surface of a lung, heart, kidney, or intestinal cell. Then, facilitated by the highly flexible inner S2 domain, the spike protein folds in on itself and fuses the viral envelope with the plasma membrane of the human cell. In doing so, the spike protein opens the doors for SARS‐CoV‐2 to release its viral genome inside the cell. Because spike proteins are glycoproteins, meaning their ectodomain is covered with sugar chains, the virus can evade the detection of the immune system and spread quickly throughout vital organsThe spike protein's position on the outer surface of SARS‐CoV‐2 and its critical role in the virus's function makes it one of the most promising targets for a coronavirus therapeutic. One novel approach to targeting spike proteins is the design of Anti‐S1 antibodies, which disarm the virus's ability to bind to the cell by attaching to the S1 subunit. The current challenge to antibody development is the flexibility of the S1 domain, which makes fusion highly effective. Further research is needed to stabilize the spike protein and maximize the efficacy of antibodies in inhibiting the virus's function. Another intriguing approach to coronavirus therapeutics is small‐molecule drug development. When linoleic acid (LA), an essential fatty acid molecule that maintains lung cell membranes, nestles into a newly discovered druggable pocket of the spike protein, the spike protein is locked into a less flexible, less infectious form. This new pocket is a putative binding site for even more potent small‐molecule inhibitors, which may be able to trap the spike protein in a completely non‐infectious form. With each new discovery surrounding the structure of the spike proteins at the heart of the COVID‐19 pandemic, we advance one step closer to developing novel therapeutics that trap SARS‐CoV‐2 in a virtually non‐infectious state.

Polyunsaturated fatty acids inhibit a pentameric ligand‐gated ion channel through one of two specific binding sites

Polyunsaturated fatty acids (PUFAs) inhibit pentameric ligand-gated ion channels (pLGICs), including the GABAAreceptor (GABAAR) and nicotinic acetylcholine receptor (nAchR). PUFA inhibition of pLGICs is thought to occur through an allosteric mechanism mediated by direct binding to specific sites. However, the sites of PUFA binding, and those sites that mediate channel inhibition are not fully elucidated. We investigated fatty acid binding sites in the prototypic pLGIC, Erwinia ligand-gated ion channel (ELIC), using a novel fatty acid photolabeling reagent, KK-242. The PUFA, docosahexaenoic acid (DHA), inhibited ELIC channel responses, similar to the effect reported in the GABAAR and nAchR. KK-242 also produced an inhibitory effect in ELIC, and photolabeled two binding sites in the outer transmembrane domain (TMD). In contrast, the commercially-available fatty acid photolabeling reagent, pacFA, did not photolabel ELIC. Fatty acid binding to these photolabeled sites was specific for DHA over palmitic acid (PA), and DHA preferentially bound to these sites in the agonist-bound state. Coarse-grained simulations corroborated the selectivity of polyunsaturated fatty acid binding to these sites. Cysteines introduced in the fatty acid binding sites of the outer TMD were efficiently modified by hexadecyl-methanethiosulfonate (hMTS), while inner TMD sites were not accessible to hMTS, possibly due to the presence of tightly bound phospholipids. hMTS modification of only one of these binding sites recapitulated the inhibitory effect of fatty acids on ELIC function. The results demonstrate that PUFAs occupy multiple sites in the outer TMD of ELIC, but that a single intrasubunit binding site mediates PUFA inhibition of ELIC. Additionally, KK-242 is a useful photolabeling reagent for the identification of fatty acid binding sites in other membrane proteins with advantages over currently available reagents.

Performance characteristics and parametric analysis of a novel multi-purpose platform combining a moonpool-type floating breakwater and an array of wave energy converters

Integration of Wave Energy Converters (WECs) with floating breakwater system provides a multi-function solution to wave energy extraction and offshore infrastructural protection. The contribution of this work is to guide the optimal size and configuration of a multi-purpose platform including a moonpool-type floating breakwater and an array of heaving oscillating-buoy (OB) WECs. The investigation is performed using a developed time-domain numerical wave tank (NWT) based on the three-dimensional (3D) potential flow theory with fully nonlinear boundary conditions on transient wetted body surfaces and free surfaces. The comparison of the hydrodynamic performance among the multi-purpose platform, the isolated array WECs, and the isolated floating breakwater are examined. The internal fluid motion in the moonpools has a positive effect on the wave energy absorption of WECs, which in turn enhances the wave attenuation capacity of the floating breakwater. WECs with larger diameter have a larger water-plane area, which leads to more extracted wave energy. The wave nonlinearity reduces the optimal PTO damping value and has an adverse effect on the wave energy extraction. However, when wave nonlinearity becomes prominent, the wave attenuation capacity is improved with increasing PTO damping. For an unequal layout of moonpools, the thinner moonpools are the major contributor to wave energy extraction, especially in the short wave region. As a result of mass exchange of fluid from the moonpool to the outer domain, the multi-purpose platform indicates favorable performance of wave energy absorption. The novel floating system makes the utilization of wave energy over a wider frequency range.

Time domain TEBEM method of ship motion in waves with forward speed by using impulse response function formulation

A numerical method for solving 3D unsteady potential flow problem of ship advancing in waves is proposed. The flow field is divided into inner and outer domain by an artificial matching surface. The inner domain includes ship-wetted surface, matching surface and free surface inside. The free-surface condition is formulated by perturbation about the double-body flow (DB model) or uniform incoming flow assumption (NK model). The outer domain contains matching surface, free surface outside and infinite far-field boundary, where only NK model is applied. The simple Green function and transient free surface Green function are used to form the boundary integral equation (BIE) by the impulse response function method for the inner and outer domain. Taylor Expansion Boundary Element Method (TEBEM) is utilized to solve the BIEs. Matching conditions for the inner-domain and outer-domain flow are enforced by the continuity of velocity potential and normal velocity on the matching surface. In this paper, several ships are selected to predict the hydrodynamic coefficients and displacement at different forward speed. The experiment measurements in physical tank is also used to validate the accuracy of numerical results. Good agreement of 6DOF ship motions in various wave headings can be obtained using TEBEM method.

Size-Controlled Polarization Retention and Wall Current in Lithium Niobate Single-Crystal Memories.

Highly conductive domain walls in insulating ferroelectric LiNbO3 (LNO) single-crystal thin films with atomic smoothness are attractive for use in high-density integration of the ferroelectric domain wall random access memory (DWRAM) because of their excellent reliability and high read currents. However, downscaling of the memory size to the nanoscale could cause poor polarization retention. Understanding the size-dependent electrical performance of a memory cell is therefore crucial. In this work, highly insulating X-cut LNO thin films were bonded to SiO2/Si wafers and lateral mesa-like cells were fabricated on the film surfaces, where contact occurred with two-sided electrodes along the polar z-axis. Under application of an in-plane electric field above a coercive field (Ec), the domain within each memory cell was switched to be antiparallel to the unswitched referencing domain at the bottom; this resulted in the formation of a conducting domain wall, which enables the nondestructive readout strategy of the DWRAM. The cell, which has a lateral length (l) above a critical size (l0) of 105 nm, is found to be a mixture of two phases across the cell area. The inner area of the cell suffers from poor polarization retention because Ec = 150 kV/cm, as demonstrated by in-plane piezoresponse force microscopy imaging. In comparison, the outer periphery domains, which have lengths of 70 nm (∼l0/2), show good retention but require a much higher Ec of 785 kV/cm. The relevant physics is discussed as phase reconstruction occurs after release of the in-plane compressive strain near the outer regions; the results show good agreement with those of one-dimensional thermodynamic calculations and phase-field simulations. The measured current-voltage curves demonstrated a sudden enhancement of the wall current across the cell when l < l0, thus implying higher readout wall currents and better retention for the DWRAM at higher storage densities.

Simulation of wake bimodality behind squareback bluff-bodies using LES

A large eddy simulation (LES) study of the flow around a 1/4 scale squareback Ahmed body at ReH=33,333 is presented. The study consists of both wall-resolved (WRLES) and wall-modelled (WMLES) simulations, and investigates the bimodal switching of the wake between different horizontal positions. Within a non-dimensional time-window of 1050 convective flow units, both WRLES and WMLES simulations, for which only the near-wall region of the turbulent boundary layer is treated in a Reynolds-averaged sense, are able to capture horizontal (spanwise) shifts in the wake’s cross-stream orientation. Equilibrium wall-models in the form of Spalding’s law and the log-law of the wall are successfully used. Once these wall-models are, however, applied to a very coarse near-wall WMLES mesh, in which a portion of the turbulent boundary layer’s outer region dynamics is treated in a Reynolds-averaged manner as well, large-scale horizontal shifts in the wake’s orientation are no longer detected. This suggests larger-scale flow structures found within the turbulent boundary layer’s outer domain are responsible for generating the critical amount of flow intermittency needed to trigger a bimodal switching event. By looking at mean flow structures, instantaneous flow features and their associated turbulent kinetic energy (TKE) production, it becomes clear that the front separation bubbles just aft of the Ahmed body nose generate high levels of TKE through the shedding of large hairpin vortices. Only in the reference WRLES and (relatively) fine near-wall mesh WMLES simulations are these features present, exemplifying their importance in triggering a bimodal event. This motivates studies on the suppression of wake bimodality by acting upon the front separation bubbles.

Modelling the response of a double‐barred sandy beach system to time‐varying wave angles

SummarySandy beaches typically have one or more shore‐parallel bars with superimposed smaller‐scale three‐dimensional (3D) bars. Knowledge of their morphodynamic behaviour under more realistic wave conditions is limited. This study investigates the response of beaches with two shore‐parallel bars to sinusoidally time‐varying angles of incidence, using a non‐linear morphodynamic model. Different periods and amplitudes of this sinusoidal variation are considered, as well as different time‐mean wave angles. For time‐invariant and normally incident waves, results show that alongshore rhythmic 3D bars form in the domains of inner and outer shore‐parallel bars. The 3D bars in the inner domain are coupled at half the outer‐bars wavelength. This phase coupling breaks up when the wave angle varies in time. Initially, regular 3D bars form in the inner domain (free behaviour), which become irregular when 3D bars develop in the outer domain (forced behaviour). The heights of the 3D bars oscillate with time, reaching maximum values when the forcing period is comparable to the system adjustment time scale (∼ 10–20 days). For a time‐varying wave angle around an oblique mean, alongshore migrating 3D bars emerge in both inner and outer domains. In contrast, for an oblique (constant) wave angle, 3D bars only form in the inner domain and they hardly migrate alongshore. For any forcing period, the dominant response period of the oscillating bar heights is at half the forcing period when waves are (on average) normally incident, and it equals the forcing period when waves are on average obliquely incident. Compared with time‐invariant angles, heights of inner and outer 3D bars are (on average) smaller and larger, respectively, when the angle varies with time, particularly for forcing periods in the order of the system adjustment time scale. Increasing the amplitude of the time‐varying wave angle weakens bar growth. Explanations of these results are also provided.

A novel numerical method for the hydrodynamic analysis of floating bodies over a sloping bottom

A novel numerical method combining Eigenfunction matching method (EMM) and 3D Rankine source method is developed to investigate wave-body interaction over a sloping bottom. The extended EMM is proposed to create an incident wave model over the sloping bottom, thereby obtaining the Froude-Krylov force and Neumann data on wet surfaces of the floating body for the diffraction problem. A 3D Rankine source method concerning the sloping bottom is developed, in which the free surface and seabed are both divided into the inner domain and outer domain. Source panels are placed in an exponential manner in the latter domain, by which the far field radiation condition is well satisfied. To verify the proposed method, comparisons with other mathematical models involving added mass and damping coefficients, wave exciting forces and motion RAOs by a floating hemisphere and a LNG carrier are carried out.

A concurrent multiscale framework based on self-consistent clustering analysis for cylinder structure under uniaxial loading condition

Accurate and efficient multiscale simulation of multifilament composite remains challenges due to expensive computation cost of solving the nonlinear representative volume element (RVE) responses in microscale. An effective reduced-order method called self-consistent clustering analysis (SCA) has been proposed recently to solve the dilemma. This paper extends the application of traditional multilevel finite element (FE2) to cylinder structure with domain division, where the inner domain is computed by finite element method (FEM) with SCA instead of direct FE2 method and outer domain is calculated by conventional FEM. The presented framework is named as concurrent modified FEM-SCA. To validate the accuracy and efficiency of presented method, the computation results of SCA, Fast Fourier Transform (FFT) and FEM are compared in microscale at first. Then, under the presented framework, the cylinder structures with diverse RVEs in uniaxial loading are studied, and the results are compared with full-scale direct numerical simulation (DNS) by FEM. Besides, the effects of different element positions, inclusion variations and loading phases on the RVE responses are also studied.

Mineralogical and geochemical investigation of megaspherulites from Argentina, Germany, and the USA

Textures and whole-rock chemistry, as well as mineral composition, were analyzed in megaspherulites (high-temperature crystallization domains [HTCDs]) that formed in different geographical and geotectonic contexts and during different geological periods (Silver Cliff, CO, USA—Paleogene; El Quevar, Argentina—Miocene; Meissen Volcanic Complex, Germany—Late Carboniferous). All of these megaspherulites have formed exclusively in rhyolitic lava, and their mineral composition is dominated by K-feldspar (sanidine) and SiO2 phases (quartz, cristobalite, tridymite). All megaspherulites represent composite HTCDs, comprising three zones: inner domain (ID), outer domain (OD), and a marginal domain (MD). Early evolution of megaspherulites is characterized by either central cavities and sector- to full-sphere spherulites or dendritic quartz-sanidine domains. The latter consist of bundles of fibrils each radiating from a single point reflecting relatively high growth rates. A common feature of OD and MD of all three megaspherulite occurrences is autocyclic banding. It mainly comprises fibrous (≤ 100 μm length), radially oriented sanidine and quartz, which formed at a temperature close to glass transition temperature (Tg). The termination of megaspherulite growth is marked by centimeter-sized sector-sphere spherulites on the surface. Megaspherulite formation requires limited nucleation, which is probably related to the low phenocryst content of the hosting lava. Latent heat from overlying crystallizing lithoidal rhyolite maintained low undercooling conditions keeping nucleation density low and facilitating high diffusion and growth rates. Late megaspherulite growth and its termination under low diffusion conditions is controlled by cooling close to Tg. Calculations based on literature data suggest that the megaspherulite growth presumably lasted less than 60 years, perhaps 30 to 40 years.

Effect of overlayer–substrate interaction on the coalescence behaviors of in-plane graphene/hexagonal boron nitride heterostructures

In-plane graphene/hexagonal boron nitride (h-BN) heterostructures show promising applications in novel two-dimensional electronic and optoelectronic devices. The quality of graphene/h-BN (G-BN) domain boundaries, which plays a critical role in device performances, depends on their coalescence. Here, the coalescing mechanism determined by the overlayer–substrate interaction and the growth dynamics during the heterostructure synthesis were studied by in situ surface imaging measurements. In-plane G-BN heterostructures were grown (h-BN first and graphene then) on Pt(111) and Ru(0001) surfaces by chemical vapor deposition. Oxygen intercalation acted as a probe reaction to investigate the coalescing behaviors of the G-BN domain boundaries. Oxygen atoms can intercalate from the outer graphene edges and cross the G-BN domain boundaries into the interior h-BN zone on Pt(111) surfaces. On Ru(0001) surfaces, only interior h-BN domains could be intercalated from G-BN domain boundaries, while no intercalation occurred on outer graphene domains. This shows that graphene can seamlessly stitch with h-BN on Pt(111) but not on Ru(0001), because the weaker overlayer–substrate interaction on Pt(111) compared to that on Ru(0001) makes the G-BN coalescing interface flatter and allows stitching at an identical height. High-quality in-plane G-BN heterostructures are expected to grow on weakly interacting surfaces rather than on strong ones.

Barriers impacting the POINT pragmatic trial: the unavoidable overlap between research and intervention procedures in \u201creal-world\u201d research

BackgroundThis manuscript provides a research update to the ongoing pragmatic trial of Project POINT (Planned Outreach, Intervention, Naloxone, and Treatment), an emergency department-based peer recovery coaching intervention for linking patients with opioid use disorder to evidence-based treatment. The research team has encountered a number of challenges related to the “real-world” study setting since the trial began. Using an implementation science lens, we sought to identify and describe barriers impacting both the intervention and research protocols of the POINT study, which are often intertwined in pragmatic trials due to the focus on external validity.MethodQualitative data were collected from 3 peer recovery coaches, 2 peer recovery coach supervisors, and 3 members of the research team. Questions and deductive qualitative analysis were guided by the Consolidated Framework for Implementation Research (CFIR).ResultsNine unique barriers were noted, with 5 of these barriers impacting intervention and research protocol implementation simultaneously. These simultaneous barriers were timing of intervention delivery, ineffective communication with emergency department staff, lack of privacy in the emergency department, the fast-paced emergency department setting, and patient’s limited resources. Together, these barriers represent the intervention characteristics, inner setting, and outer setting domains of the CFIR.ConclusionResults highlight the utility of employing an implementation science framework to assess implementation issues in pragmatic trials and how this approach might be used as a quality assurance mechanism given the considerable overlap that exists between research and intervention protocols in real-world trial settings. Previously undocumented changes to the trial design that have been made as a result of the identified barriers are discussed.

Structural Studies of Straight and Supercoiled Flagellar Filaments from Campylobacter jejuni

Thousands of angstroms long, the flagellar filament serves as the propeller of the bacterial flagellum. In the two-state switching model, protofilaments of the flagella switch between one of two states which allows for changing between different flagellar waveforms, associated with different modes of motility. Many pathogenic bacteria have flagellar-based motility and thus produce thousands of copies of the flagellar filament subunit, the flagellin. A small region of about 10 amino acids in domain D1 in most bacterial flagellins such as those from Salmonella typhimurium and Bacillus subtilis are recognized by toll-like receptor 5 (TLR5) which then activates innate immune response. ε Proteobacteria such as Campylobacter jejuni and H. pylori escape detection by TLR5 due to sequence changes in this 10 AA region of their flagellin sequence. When mutated onto the S. typhimurium flagellin the H. pylori sequence impairs flagellar filament formation, thus motility. The similar C. jejuni sequence is thought to have the same destabilizing interactions. This leads to the question “How do ε Proteobacteria compensate for these destabilizing mutations in their D1 domains?”. With a 3.5 Å resolution cryoEM structure of straight C. jejuni G508A flagellar filaments we are able to show a unique and extensive network of interactions between the outer domains of adjacent flagellins which compensates for weakened interactions in D1. These interactions are further stabilized by glycosylation of specific residues with pseudaminic acid. Lastly, recent high-resolution structures of the wild type flagellar filament and flagellar hook have called into question the validity of the two-state switching model for flagella. Using single particle and helical cryoEM reconstruction techniques, as well as cryo-electron tomography and fluorescence light microscopy we investigate the structure of wildtype supercoiled C. jejuni flagellar filaments.

Time-domain TEBEM method for mean drift force and moment of ships with forward speed under the oblique seas

A numerical method for solving 3D unsteady potential flow problem of ship advancing in waves is put forward. The flow field is divided into an inner and an outer domain by introducing an artificial matching surface. The inner domain is surrounded by ship wetted surface and matching surface as well as part of the free surface. The free surface condition for the inner domain is formulated by perturbation about the double-body flow or uniform incoming flow assumption. The outer domain is surrounded by matching surface and the rest free surface as well as infinite far-field radiation boundary. The free surface condition for the outer domain is formulated by perturbation about uniform incoming flow. The simple Green function and transient free surface Green function are used to form the boundary integral equation (BIE) for the inner and outer domains, respectively. Taylor Expansion Boundary Element Method (TEBEM) is utilized to solve the double-body flow and inner domain and outer domain unsteady flow BIE. Matching conditions for the inner domain flow and outer domain flow are enforced by the continuity of velocity potential and normal velocity on the matching surface. Direct pressure integration on ship wetted surface is used to obtain the first-order and second-order wave forces (moments). The numerical predictions on the displacement, added resistance, sway mean drift force and yaw mean drift moment of the modified KVLCC2 ship at different forward speeds are investigated by the proposed TEBEM method. It is also compared with the other numerical results. The physical tank experiment results are also developed to validate the accuracy of numerical tank results. Compared with the experiment solutions, a good agreement can be obtained by TEBEM method.

SPACE SECURITY DIPLOMACY IN INTERNATIONAL ORGANIZATIONS: SOME LEGAL ASPECTS

Space security is an important area in international diplomacy and is undertaken by international organizations, such as the UN or NATO. This is why diplomatic law is concentrated on space. The outer space domain has become more and more challenging recently. Some challenges are threats, such as cyber or nuclear tests and weapons. In many ways, diplomacy is the only way to negotiate and make progress in ensuring peace and security–which, according to the UN Charter, are key priorities for states. This article shows how international diplomacy is connected to international relations and policies relating to space and how important diplomacy is as a tool to maintain international peace. Law is also one of the tools that help prevent space conflicts and wars among the states. This article outlines some tools of space diplomacy used by states and international organizations, namely, conferences, bilateral dialogues, and other forms of negotiations. It seems that professional diplomatic teams are necessary to achieve diplomatic goals in space. Today, space is connected to politics, trade, and especially the security of states. Thus, the role of space diplomacy is more significant than ever.

Retroviral prototype foamy virus intasome binding to a nucleosome target does not determine integration efficiency

Retroviral integrases must navigate host DNA packaged as chromatin during integration of the viral genome. Prototype foamy virus (PFV) integrase (IN) forms a tetramer bound to two viral DNA (vDNA) ends in a complex termed an intasome. PFV IN consists of four domains: the amino terminal extension domain (NED), amino terminal domain (NTD), catalytic core domain (CCD), and carboxyl terminal domain (CTD). The domains of the two inner IN protomers have been visualized, as well as the CCDs of the two outer IN protomers. However, the roles of the amino and carboxyl terminal domains of the PFV intasome outer subunits during integration to a nucleosome target substrate are not clear. We used the well-characterized 601 nucleosome to assay integration activity as well as intasome binding. PFV intasome integration to 601 nucleosomes occurs in clusters at four independent sites. We find that the outer protomer NED and NTD domains have no significant effects on integration efficiency, site selection, or binding. The CTDs of the outer PFV intasome subunits dramatically affect nucleosome binding but have little effect on total integration efficiency. The outer PFV IN CTDs did significantly alter the integration efficiency at one site. Histone tails also significantly affect intasome binding, but have little impact on PFV integration efficiency or site selection. These results indicate that binding to nucleosomes does not correlate with integration efficiency and suggests most intasome-binding events are unproductive.

Nonlinear ship motion with forward speed in waves based on 3D time domain hybrid Green function method

In this research, based on three-dimensional (3D) time domain hybrid Green function method, the time-domain nonlinear initial boundary value problem of a ship motion in waves with forward speed is solved. The 3D Rankine source and 3D time domain free surface Green function are adopted to solve flow fields of the inner and the outer domains respectively. Meantime, the instantaneous wet surface during ship motion is divided into boundary elements in every time step, to calculate nonlinear incident wave and static restoring forces. Combining with the linear solution of radiation and diffraction problems, the nonlinear time domain numerical method based on 3D hybrid Green function method for ship motion in waves with forward speed is established. Numerical simulation and analysis are carried out for Wigley and S175 ships with different forward speeds and wave angles respectively by developed numerical solver. The comparison with the experimental results show that the proposed nonlinear numerical method has an obvious improvement in predicting accuracy under complicated conditions such as with higher forward speed and large flare, which proves it has good prospect in engineering applications.

Review of Domain Wall Dynamics Engineering in Magnetic Microwires.

The influence of magnetic anisotropy, post-processing conditions, and defects on the domain wall (DW) dynamics of amorphous and nanocrystalline Fe-, Ni-, and Co-rich microwires with spontaneous and annealing-induced magnetic bistability has been thoroughly analyzed, with an emphasis placed on the influence of magnetoelastic, induced and magnetocrystalline anisotropies. Minimizing magnetoelastic anisotropy, either by the selection of a chemical composition with a low magnetostriction coefficient or by heat treatment, is an appropriate route for DW dynamics optimization in magnetic microwires. Stress-annealing allows further improvement of DW velocity and hence is a promising method for optimization of DW dynamics in magnetic microwires. The origin of current-driven DW propagation in annealing-induced magnetic bistability is attributed to magnetostatic interaction of outer domain shell with transverse magnetization orientation and inner axially magnetized core. The beneficial influence of the stress-annealing on DW dynamics has been explained considering that it allows increasing of the volume of outer domain shell with transverse magnetization orientation at the expense of decreasing the radius of inner axially magnetized core. Such transverse magnetic anisotropy can similarly affect the DW dynamics as the applied transverse magnetic field and hence is beneficial for DW dynamics optimization. Stress-annealing allows designing the magnetic anisotropy distribution more favorable for the DW dynamics improvement. Results on DW dynamics in various families of nanocrystalline microwires are provided. The role of saturation magnetization on DW mobility improvement is discussed. The DW shape, its correlation with the magnetic anisotropy constant and the microwire diameter, as well as manipulation of the DW shape by induced magnetic anisotropy are discussed. The engineering of DW propagation through local stress-annealing and DW collision is demonstrated.