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Based on the successful application of the adaptive meshless local maximum-entropy finite element method to solve the convection-diffusion equation, this study extends the same principle to study the 2-dimensional Navier-Stokes equations. Through extensive case studies, this work demonstrates that the present approach is a viable alternative to resolve the high Reynolds number Navier-Stokes equations. The simulation results indicate that by incorporating additional points into the elements without increasing the bandwidth or refinement via the local maximum-entropy procedure, it will enhance the accuracy and efficiency of numerical simulations. A 2-dimensional square lid-driven cavity with various Reynolds numbers will serve as the first example. In the second example, we address a more complex geometry by solving the cavity with a hole inside the cavity center. The numerical results of the model compare favorably with other numerical solutions, including the finite difference method and the finite element method. This paper provides a very powerful tool to study the boundary layer theory with irregular geometry of the Navier-Stokes equations.

Gene therapy approaches using adeno-associated viral vectors have been successfully tested in the equine post-traumatic osteoarthritis (PTOA) model. Owing to differences in the levels of transgene expression and adverse tissue reactions observed in published studies, we sought to identify a safe therapeutic dose of scAAVIL-1ra in an inflamed and injured joint that would result in improved functional outcomes without any adverse events. scAAVIL-1ra was delivered intra-articularly over a 100-fold range, and horses were evaluated throughout and at the end of the 10-week study. A dose-related increase in IL-1ra levels with a decrease in PGE2levels was observed, with the peak IL-1ra concentration being observed 7 days post-treatment in all groups. Perivascular infiltration with mononuclear cells was observed within the synovial membrane of the joint treated with the highest viral dose of 5 × 1012vg, but this was absent in the lower-dosed joints. The second-highest dose of scAAVeqIL-1ra 5 × 1011vg demonstrated elevated IL-1ra levels without any cellular response in the synovium. Taken together, the data suggest that the 10-fold lower dose of 5 × 1011vg scAAVIL-1ra would be a safe therapeutic dose in an equine model of PTOA.

Purpose: Numerous biomarkers of diabetic kidney disease (DKD) are associated with renal prognosis but head-to-head comparisons are lacking. This study aimed to examine the association of soluble tumor necrosis factor receptor type 1 (sTNFR1), fibroblast growth factor 21 (FGF-21), endocan, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and renal outcomes of patients with or without clinical signs of DKD. Methods: A total of 312 patients were enrolled in a prospective observational study that excluded individuals with estimated glomerular filtration rates (eGFR) < 30 mL/min/1.73 m2. Composite renal outcomes included either a > 30% decline in eGFR and worsening albuminuria or both from consecutive tests of blood/urine during a 3.5-year follow-up period. Results: Higher sTNFR1 and FGF-21, rather than endocan and NT-pro-BNP, levels were associated with renal outcomes but the significance was lost after adjusting for confounders. However, sTNFR1 levels ≥ 9.79 pg/dL or FGF-21 levels ≥ 1.40 pg/dL were associated with renal outcomes after adjusting for the confounders (hazard ration [HR] 2.76, 95% confidence interval [CI] 1.36–5.60, p= 0.005 for sTNFR1 level; HR 1.95, 95% CI 1.03–3.69, p= 0.03 for FGF-21 level). The combination of both levels exhibited even better association with renal outcomes than did either one alone (adjusted HR 4.45, 95% CI 1.86–10.65, p= 0.001). The results were consistent among patients with preserved renal function and normoalbuminuria. Conclusion: Both sTNFR1 and FGF-21 levels were associated with renal outcomes of in patients with type 2 diabetes, and the combination of the abovementioned markers exhibits better predictability.

This article will first briefly review the impressive advancements made in high-temperature superconductivity (HTS) before the arrival of room-temperature superconductivity (RTS). Accompanying the advancements made in superconductivity science and technology over the last century, a solid experimental framework concerning the search, development, and even authentication of new discoveries has been established. All these can serve as valuable references in the infancy of RTS research. In this spirit, we will comment on the current status of rare-earth hydride RTS and present our preliminary negative results on Lu-N-H and LK-99, the two most studied materials in the search for RTS in the last few months, although several more reports of negation than affirmation have appeared.

Parasitic fringe drift from unwanted scatterings limits the long-term stability of waveguide-based optical spectrometers. Yet their spectral features provide relevant information that can be used to improve performance of the spectrometer. We show that fringe drift can be extracted and utilized to perform accurate thermal stabilization, especially in the case of integrated waveguide sensors. In this Letter, effective stabilization of a methane silicon photonic sensor is demonstrated, and significant reduction in fringe noise is clearly observed.

We argue that three structural changes to the global trading economy not foreseen by the original WTO rules framers have rendered existing WTO rules outdated, and partially contributed to the US–China trade war. The first change is the prevalence of the Internet. The lack of relevant WTO rules in this field allows authoritarian countries to exercise control over Internet access, create cyberspace trade barriers, and abuse locally collected data. The second change is the emergence of the property of ‘increasing returns’ in the knowledge-based industries. The early front-runner in a hi-tech industry today is most likely to establish an invincible position tomorrow. Governments thus have motives to subsidize not-yet-existing industries to help them compete for the front-runner position. China’s Made in China 2025 project may be one example. WTO existing subsidy rules are incapable of regulating effectively. The third change is the emergence of large previously communist economies, where the distinction between the public and the private sector is blurred. The prevalence of state-owned industries shakes the WTO’s free-market foundations. Current WTO transparency rules cannot reveal the true extent of government intervention or guarantee fair competition. We propose possible directions for rules modifications to deal with these changes.

There is good scientific rationale to support the use of growth factors to promote musculoskeletal tissue regeneration. However, the clinical effectiveness of platelet-rich plasma (PRP) and other blood-derived products has yet to be proven. Characterization and reporting of PRP preparation protocols utilized in clinical trials for the treatment of musculoskeletal disease is highly inconsistent, and the majority of studies do not provide sufficient information to allow the protocols to be reproduced. Furthermore, the reporting of blood-derived products in orthopaedics is limited by the multiple PRP classification systems available, which makes comparison of results between studies challenging. Several attempts have been made to characterize and classify PRP; however, no consensus has been reached, and there is lack of a comprehensive and validated classification. In this annotation, we outline existing systems used to classify preparations of PRP, highlighting their advantages and limitations. There remains a need for standardized universal nomenclature to describe biological therapies, as well as a comprehensive and reproducible classification system for autologous blood-derived products.Cite this article: Bone Joint J2019;101-B:891–896.

Most studies on the nanoscale mainly focus on regular rectangular nanoplates, but according to the synthesis of nanostructures, the dynamic response of non-rectangular nanoplates is noticeable and there are not many works on these complex nanostructures. This work presents energy absorption, and forced and free vibrations of sandwich non-rectangular nanoplates with a single sinusoidal edge resting on a fractional torsional viscoelastic medium. The nanostructure is made from alumina reinforced by graphene platelets (GPLs) as a core covered by the flexoelectric and magnetostrictive materials as top and bottom layers, respectively. The consideration of size effects is derived from the innovative theory of local/nonlocal phenomena in a two-phase context. The Halpin–Tsai micromechanical and Kelvin–Voigt models are applied for the effective characteristics of the material in the nanocomposite layer and structural damping, respectively. Based on Hamilton’s principle and refined zigzag theory (RZT), the coupled electro-magneto-mechanical equations of motion are gained and analyzed by Galerkin’s and Newmark’s procedures. The effects of different components, including factors related to both the nonlocal and local phase fractions, the volume fraction of GPLs, various elastic mediums, electric field, structural damping, magnetic field, piezoelectric and flexoelectric effects on the absorption of energy, and forced and free vibrations of the sandwich nanostructure. Numerical simulations demonstrate that optimal energy absorption occurs when the flexoelectric factor is set to zero and the piezoelectric constant is non-zero but of opposite polarity. Additionally, it is concluded that when the coefficient of the local phase fraction is zero, increasing the nonlocal factor has more influence on the energy absorption and vibration of the nanostructure.

Tumor metastasis depends on the dynamic regulation of cell adhesion through β1-integrin. The Cub-Domain Containing Protein-1, CDCP1, is a transmembrane glycoprotein which regulates cell adhesion. Overexpression and loss of CDCP1 have been observed in the same cancer types to promote metastatic progression. Here, we demonstrate reduced CDCP1 expression in high-grade, primary prostate cancers, circulating tumor cells and tumor metastases of patients with castrate-resistant prostate cancer. CDCP1 is expressed in epithelial and not mesenchymal cells, and its cell surface and mRNA expression declines upon stimulation with TGFβ1 and epithelial-to-mesenchymal transition. Silencing of CDCP1 in DU145 and PC3 cells resulted in 3.4-fold higher proliferation of non-adherent cells and 4.4-fold greater anchorage independent growth. CDCP1-silenced tumors grew in 100% of mice, compared to 30% growth of CDCP1-expressing tumors. After CDCP1 silencing, cell adhesion and migration diminished 2.1-fold, caused by loss of inside-out activation of β1-integrin. We determined that the loss of CDCP1 reduces CDK5 kinase activity due to the phosphorylation of its regulatory subunit, CDK5R1/p35, by c-SRC on Y234. This generates a binding site for the C2 domain of PKCδ, which in turn phosphorylates CDK5 on T77. The resulting dissociation of the CDK5R1/CDK5 complex abolishes the activity of CDK5. Mutations of CDK5-T77 and CDK5R1-Y234 phosphorylation sites re-establish the CDK5/CDKR1 complex and the inside-out activity of β1-integrin. Altogether, we discovered a new mechanism of regulation of CDK5 through loss of CDCP1, which dynamically regulates β1-integrin in non-adherent cells and which may promote vascular dissemination in patients with advanced prostate cancer.

PurposeThe aim of this study was to determine a sequence of structural changes in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) using optical coherence tomography-angiography (OCT-A) and comparing with other imaging modalities.Patients and methodsPatients with a new diagnosis of acute-onset APMPPE referred to a regional specialist centre from October 2015 to October 2016 were included. Multimodal imaging employed on all patients from diagnosis included the following: fundus fluorescein angiography, indocyanine green angiography, fundus autofluorescence, spectral domain-OCT (SD-OCT), and OCT-A. All non-invasive imaging processes were repeated during follow-up.ResultsTen eyes of five patients were included in the study, three males and two females, with a mean age of 26.2 years (range: 21–32) and a mean follow-up of 6.4 months (range: 2.6–13.3). All patients presented with bilateral disease and macular involving lesions. OCT-A imaging of the choriocapillaris was supportive of hypoperfusion at the site of APMPPE lesions during the acute phase of this condition with normalisation of choroidal vasculature during follow-up. Multimodal imaging consistently highlighted four sequential phases from presentation to resolution of active disease.ConclusionsMultimodal imaging in patients with APMPPE in acute and long-term follow-up demonstrates a reversible choroidal hypoperfusion supporting the primary inciting pathology as a choriocapillaritis. The evolution shows resolution of the ischaemia through a defined sequence that results in persistent changes at the level of the retinal pigment epithelium and outer retina. OCT-A was able to detect preclinical changes and chart resolution at the level of the choriocapillaris.

MgZnO/ZnO two-dimensional electron gas (2DEG) structures with ZnO annealed at various temperatures (600–900 °C) and photodetectors (PDs) with and without a 2DEG structure were fabricated using a radio frequency magnetron sputtering system. It was found that the carrier concentration and mobility increase with the annealing temperature owing to the improved crystalline in ZnO; however, high-temperature (800 °C or higher) annealing can degrade the crystalline of the ZnO layer. Hall measurements showed that compared with that of bulk ZnO, the sheet carrier concentration of the 2DEG sample increased from 1.3 × 1013to 1.2 × 1014cm–2, and the mobility was enhanced from 5.1 to 17.5 cm2/V s. This is because the channel layer is the total thickness (300 nm) in bulk ZnO, whereas the carriers are confined to a 45 nm region beneath the MgZO layer in the 2DEG sample, confirming the 2DEG behavior at the MgZnO/ZnO interface. The PDs with 2DEG structures demonstrate a higher ultraviolet (UV) response and a UV/visible rejection ratio that is six times larger than that of the PDs without a 2DEG structure. The 2DEG structure also induces a photocurrent gain, which results in a 240% quantum efficiency for the 310 nm incident wavelength. The related mechanism is elucidated with a band diagram.

The four Magnetospheric Multiscale (MMS) spacecraft observed a ∼1 min burst of energetic ions (50–1000 keV) in the region upstream from the subsolar quasi‐perpendicular bow shock on 6 December 2015. The composition, flux levels, and spectral indices of these energetic protons, helium, and oxygen ions greatly resemble those seen in the outer magnetosphere earlier while MMS crossed the magnetopause and differ significantly from those simultaneously observed far upstream by Advanced Composition Explorer (ACE). However, the event cannot be explained solely in terms of leakage from the magnetosphere. The strongly southward orientation of the interplanetary magnetic field (IMF) lines at the time of the event precludes any connection to the magnetosphere. This point is confirmed by the presence of energetic electrons, known to occur on magnetic field lines that graze the bow shock rather than connect to the magnetosphere. We suggest that the ions gradient drifted out of the nearby quasi‐parallel foreshock and into the quasi‐perpendicular bow shock. Each of the ion species exhibited an inverse energy dispersion. As predicted by models for shock drift acceleration, the energies of the ions increased as θBn, the angle between the IMF and the shock normal, increased. Finally, we note that a similar event was observed a few minutes later in the subsolar magnetosheath, indicating that such events can be swept downstream of the bow shock. The energetic ions observed in the upstream and downstream region of the bow shock originated in the magnetosphereMagnetospheric energetic ions gradient drifted out of the nearby quasi‐parallel foreshock and into the quasi‐perpendicular bow shock regionInverse dispersions can be caused by the IMF orientation changes, from quasi‐perpendicular to (nearly) perpendicular local bow shock