Cancellation exponents in isotropic turbulence and magnetohydrodynamic turbulence.

Small-scale characteristics of turbulence such as velocity gradients and vorticity fluctuate rapidly in magnitude and oscillate in sign. Much work exists on the characterization of magnitude variations, but far less on sign oscillations. While in homogeneous turbulence averages performed on large scales tend to zero because of the oscillatory character, those performed on increasingly smaller scales will vary with the averaging scale in some characteristic way. This characteristic variation at high Reynolds numbers is captured by the so-called cancellation exponent, which measures how local averages tend to cancel out as the averaging scale increases, in space or time. Past experimental work suggests that the exponents in turbulence depend on whether one considers quantities in full three-dimensional (3D) space or uses their one- or two-dimensional cuts. We compute cancellation exponents of vorticity and longitudinal as well as transverse velocity gradients in isotropic turbulence at Taylor-scale Reynolds numbers up to 1300 on 8192^{3} grids. The 2D cuts yield the same exponents as those for full 3D, while the 1D cuts yield smaller numbers, suggesting that the results in higher dimensions are more reliable. We make the case that the presence of vortical filaments in isotropic turbulence leads to this conclusion. This effect is particularly conspicuous in magnetohydrodynamic turbulence, where an increased degree of spatial coherence develops along the direction of an imposed magnetic field.

Turbulent convection and large scale circulation in a cube with rough horizontal surfaces.

Large-eddy simulations of thermal convection are presented and discussed for a cube with rough horizontal surfaces. Two types of roughness are considered: uniformly placed pyramids, and grooves aligned parallel to one set of sidewalls. The Rayleigh number is 10^{8}, the Prandtl number 0.7, and the aspect ratio 1, as in a previous study [N. Foroozani, J. J. Niemela, V. Armenio, and K. R. Sreenivasan, Phys. Rev. E 95, 033107 (2017)10.1103/PhysRevE.95.033107], except that the meshes here are finer. When the thermal boundary layers are sufficiently large relative to the characteristic roughness height, i.e., for hydrodynamically smooth conditions, the mean properties of the large scale circulation (LSC) are qualitatively similar to the case of smooth surfaces. In particular, the LSC is always aligned along one of the diagonals of the cube. When the boundaries are hydrodynamically rough, the same result holds true only for the case of pyramidal structures; for grooved surfaces, the LSC is forced to be parallel to the sidewalls on average, alternating rapidly between the two diagonals of the cube with a mean period of the order 10 turnover times. Our analysis suggests that the difference from the pyramidal case is due to the breaking of the horizontal x-z symmetry under conditions of hydrodynamical roughness, and the corresponding directional concentration of plume emission along the grooves, from which the LSC is generated, providing a strong restoring force. Furthermore, in this study we observed a small reduction in heat transport for both roughness configurations which is in good agreement with past studies.

Histidine and arginine conjugated starch-PEI and its corresponding gold nanoparticles for gene delivery.

The high surface energy of gold nanoparticles (GNPs) along with its unique physical and chemical properties delivers it as an effective nonviral gene delivery platform for anticancer treatments. GNPs were synthesized by using starch-PEI in which PEI act as reducing agent and starch as a stabilizer. Cytocompatibility studies carried out in C6 cells revealed that gold modification significantly improved the percentage cell viability even at higher polymer concentration. Irrespective of excellent cellular internalization, the transfection efficiency studied with p53 plasmid was found to be compromised with gold modification. For better transfection efficiency, we further modified starch-PEI with amino acids (l-Arginine, l-Histidine) and synthesized the corresponding GNPs. Though starch-PEI gold nanoparticles exhibited low transfection, its amino acid modified counterparts were found to have good transfection efficiency along with low cytotoxicity. It was found that the GNPs containing l-Arginine showed improved transfection efficiency. Hence, it can be inferred that selective amino acid modification is beneficial for improving the transfection efficiency.

Asteroseismic detection of latitudinal differential rotation in 13 Sun-like stars.

The differentially rotating outer layers of stars are thought to play a role in driving their magnetic activity, but the underlying mechanisms that generate and sustain differential rotation are poorly understood. We report the measurement using asteroseismology of latitudinal differential rotation in the convection zones of 40 Sun-like stars. For the most significant detections, the stars' equators rotate approximately twice as fast as their midlatitudes. The latitudinal shear inferred from asteroseismology is much larger than predictions from numerical simulations.

Reorientations of the large-scale flow in turbulent convection in a cube.

Large-eddy simulations of turbulent Rayleigh-Bénard convection were conducted for a fluid of Prandtl number Pr=0.7 confined in a cube, for Rayleigh numbers of 10^{6} and 10^{8}. The model solves the unsteady Navier-Stokes equations under the Boussinesq approximation, using a dynamic Smagorinsky model with a Lagrangian averaging technique for the subgrid terms. Under fully developed conditions the flow topology is characterized by a large-scale circulation (LSC) developing in a plane containing one of the diagonals of the cell, while two counter-rotating vortices consequently develop in the other diagonal plane, resulting in a strong inflow at the horizontal midplane. This flow structure is not static, with the LSC undergoing nonperiodic reorientations, or switching, between the two diagonal planes; hence, we supplement the observations of the three-dimensional time-averaged flow structures with single point measurements (time series) to shed light on the dynamics of the reorientations. For all observations, this switching results from a lateral rotation of the LSC in which some finite time spent in a transient state where the large-scale circulation is parallel to one set of side walls; there are, importantly, no observations consistent with so-called cessations of the LSC, in which it decays and then reforms in another plane without such a rotation. The average switching rate for the LSC is in excellent agreement with the results of Bai et al. [K. Bai, D. Ji, and E. Brown, Phys. Rev. E 93, 023117 (2016)PLEEE81539-375510.1103/PhysRevE.93.023117].

Alginate stabilized gold nanoparticle as multidrug carrier: Evaluation of cellular interactions and hemolytic potential.

This work delineates the synthesis of curcumin (Ccm) and methotrexate (MTX) conjugated biopolymer stabilized AuNPs (MP@Alg-Ccm AuNPs). The dual drug conjugated nano-vector was characterized by FTIR, (1)H NMR and UV-vis spectroscopic techniques. Hydrodynamic diameter and surface charge of the AuNPs were determined by DLS analysis and the spherical particles were visualized by TEM. MP@Alg-Ccm AuNPs exhibited improved cytotoxic potential against C6 glioma and MCF-7 cancer cell lines and was found to be highly hemocompatible. MP@Alg-Ccm AuNPs also exhibited active targeting efficiency against MCF-7 cancer cells due to the presence of "antifolate" drug MTX. Thus MP@Alg-Ccm AuNPs may find potential application in targeted combination chemotherapy for the treatment of cancer. The study is also interesting from the synthetic point of view because, here generation of AuNPs was done using "green chemical" alginate and dual drug conjugated AuNPs were created in two simple reaction steps using "green solvent" water.

Management of Bile Duct Injury at Various Stages of Presentation: Experience from a Tertiary Care Centre.

The clinical presentation, management and outcome of all patients with bile duct injury who presented to our tertiary care centre at various stages after cholecystectomy were analyzed. The patients were categorized into three groups: group A-patients in whom the injury was detected during cholecystectomy, group B-patients who presented within 2 weeks of cholecystectomy and group C-patients who presented after 2 weeks of cholecystectomy. Our team acted as rescue surgeons and performed 'on-table' repair for injuries occurring in another unit or in another hospital. Strasberg classification of bile duct injury was followed. In group A, partial and complete transections were managed by repair over T-tube and high hepaticojejunostomy, respectively. Patients in group B underwent endoscopic retrograde cholangiogram and/or magnetic resonance cholangiogram to evaluate the biliary tree. Those with intact common bile duct underwent endoscopic papillotomy and stenting in addition to drainage of intra-abdominal collection when present. For those with complete transection, early repair was considered if there was no sepsis. In presence of intra-abdominal sepsis an attempt was made to create controlled external biliary fistula. This was followed by hepatico jejunostomy at least after 3 months. Group C patients underwent hepaticojejunostomy at least 6 weeks after the injury. The outcome was graded into three categories: grade A-no clinical symptoms, normal LFT; grade B-no clinical symptoms, mild derangement of LFT or occasional episodes of pain or fever; grade C-pain, cholangitis and abnormal LFT; grade D-surgical revision or dilatation required. Fifty nine patients were included in the study and the distribution was group A-six patients, group B-33 patients and group C-20 patients. In group A, one patient with complete transection of the right hepatic duct (type C) and partial injury to left hepatic duct (LHD) underwent right hepaticojejunostomy and repair of the LHD over stent. Two patients with type D and three patients with type E 2 injury underwent repair over T-tube and hepaticojejunostomy, respectively. In group B, all except one of the 18 patients with type A injury underwent endoscopic papillotomy and stenting. The bile leak subsided at a mean interval of 8 days in all, except one patient who died of fulminant sepsis. Of the 15 patients with type E injury, five underwent hepaticojejunostomy after a minimum gap of 3 months. Early repair was considered in 10 patients. Twenty patients in group C underwent hepaticojejunostomy. In a mean follow-up of 40 months, the outcome was grade A in 54 patients, grade B in three patients (one from each of the three groups) and grade D in one patient (group C). The latter patient with a type E3 injury developed recurrent stricture and cholangitis necessitating percutaneous transhepatic dilatation. The high success rate of bile duct repair in the present study can be attributed to the appropriate timing, meticulous technique and the tertiary care experience.

Conjugating curcumin to water soluble polymer stabilized gold nanoparticles via pH responsive succinate linker.

Curcumin is a natural product with immense medicinal assets. The low aqueous solubility and consequent poor bioavailability of curcumin are the most serious limitations to its utilization as a potential therapeutic agent. In order to enhance the aqueous solubility and bioavailability of the drug, we covalently conjugated curcumin onto the surface of gold nanoparticles (AuNPs) aided by a water soluble polymer via a succinate linker. Conjugation of curcumin was confirmed by fluorescence, FTIR, 1H NMR and UV-Visible spectroscopy and XRD studies. The size and surface charge of the AuNPs were determined by DLS, and the morphology was visualized by TEM. Aqueous solubility of curcumin was augmented upon conjugation with the polymer stabilized AuNPs. The pH responsive release of curcumin from the nano-vehicle ensures safer delivery of the drug at physiological pH. Cytotoxic potential and cellular uptake of curcumin conjugated AuNPs were assessed by MTT assay and fluorescence microscopy, respectively, using C6 glioma cancer cells. Thus, the curcumin conjugated polymer stabilized AuNPs circumvent limitations of curcumin and can find applications in pH responsive drug delivery.

Threat-related learning relies on distinct dorsal prefrontal cortex network connectivity.

Conditioned changes in the emotional response to threat (e.g. aversive unconditioned stimulus; UCS) are mediated in part by the prefrontal cortex (PFC). Unpredictable threats elicit large emotional responses, while the response is diminished when the threat is predictable. A better understanding of how PFC connectivity to other brain regions varies with threat predictability would provide important insights into the neural processes that mediate conditioned diminution of the emotional response to threat. The present study examined brain connectivity during predictable and unpredictable threat exposure using a fear conditioning paradigm (previously published in Wood et al., 2012) in which unconditioned functional magnetic resonance imaging data were reanalyzed to assess effective connectivity. Granger causality analysis was performed using the time series data from 15 activated regions of interest after hemodynamic deconvolution, to determine regional effective connectivity. In addition, connectivity path weights were correlated with trait anxiety measures to assess the relationship between negative affect and brain connectivity. Results indicate the dorsomedial PFC (dmPFC) serves as a neural hub that influences activity in other brain regions when threats are unpredictable. In contrast, the dorsolateral PFC (dlPFC) serves as a neural hub that influences the activity of other brain regions when threats are predictable. These findings are consistent with the view that the dmPFC coordinates brain activity to take action, perhaps in a reactive manner, when an unpredicted threat is encountered, while the dlPFC coordinates brain regions to take action, in what may be a more proactive manner, to respond to predictable threats. Further, dlPFC connectivity to other brain regions (e.g. ventromedial PFC, amygdala, and insula) varied with negative affect (i.e. trait anxiety) when the UCS was predictable, suggesting that stronger connectivity may be required for emotion regulation in individuals with higher levels of negative affect.

Conjugation of curcumin onto alginate enhances aqueous solubility and stability of curcumin.

Curcumin is a potential drug for various diseases including cancer. Prime limitations associated with curcumin are low water solubility, rapid hydrolytic degradation and poor bioavailability. In order to redress these issues we developed Alginate-Curcumin (Alg-Ccm) conjugate which was characterized by FTIR and (1)H NMR spectroscopy. The conjugate self-assembled in aqueous solution forming micelles with an average hydrodynamic diameter of 459 ± 0.32 nm and negative zeta potential. The spherical micelles were visualized by TEM. The critical micelle concentration (CMC) of Alg-Ccm conjugate was determined. A significant enhancement in the aqueous solubility of curcumin was observed upon conjugation with alginate. Formation of micelles improved the stability of curcumin in water at physiological pH. The cytotoxic activity of Alg-Ccm was quantified by MTT assay using L-929 fibroblast cells and it was found to be potentially cytotoxic. Hence, Alg-Ccm could be a promising drug conjugate as well as a nanosized delivery vehicle.

Influence of container shape on scaling of turbulent fluctuations in convection.

We perform large-eddy simulations of turbulent convection in a cubic cell for Rayleigh numbers, Ra, between 10(6) and 10(10) and the molecular Prandtl number, Pr=0.7. The simulations were carried out using a second-order-accurate finite-difference method in which subgrid-scale fluxes of momentum and heat were both parametrized using a Lagrangian and dynamic Smagorinsky model. The scaling of the root-mean-square fluctuations of density (temperature) and velocity measured in the cell center are in excellent agreement with the scaling measured in the laboratory experiments of Daya and Ecke [Phys. Rev. Lett. 87, 184501 (2001)] and differ substantially from that observed in cylindrical cells. We also observe the time-averaged spatial distributions of the local heat flux and density fluctuations, and find that they are strongly inhomogeneous in the horizontal midplane, with the largest density gradients occurring at the corners at the midheight, where hot and cold plumes mix in the form of strong counter-rotating eddies.

Functionalized carbon dots enable simultaneous bone crack detection and drug deposition.

Recently, carbon dots (CDs) have become one of the most sought nanomaterials for biological applications owing to their excellent fluorescence, chemical inertness and biocompatibility. This article depicts the generation of a fluorescent nano probe using CDs for viewing bone cracks and simultaneous drug delivery to the cracked or infected sites. Water soluble polyethylene glycol diamine capped CDs were conjugated with glutamic acid (GA), a calcium targeting ligand, and ciprofloxacin as an antibacterial model drug. Physicochemical characterizations, cytotoxicity evaluation, haemolysis and antibacterial activity studies of the synthesized probe and its ability to target onto bone are demonstrated. Our results indicate that there is significant scope in developing functionalized CDs as theranostic agents.

Turbulent mixing and beyond: non-equilibrium processes from atomistic to astrophysical scales II.

This Introduction summarizes and provides a perspective on the papers representing one of the key themes of the 'Turbulent mixing and beyond' programme--the hydrodynamic instabilities of the Rayleigh-Taylor (RT) and Richtmyer-Meshkov (RM) type and their applications in nature and technology. The collection is intended to present the reader a balanced overview of the theoretical, experimental and numerical studies of the subject and to assess what is firm in our knowledge of the RT and RM turbulent mixing.

In vitro detection of calcium in bone by modified carbon dots.

This article depicts a simple and novel approach to locate calcium deposits in bone using modified carbon dots (CDs) through fluorescence imaging. Amino-functionalized CDs along with glutamic acid, a naturally-occurring ligand for calcium ions, were conjugated onto hyaluronic acid using EDC chemistry. The ability of the probe to recognise Ca ions was demonstrated using polymer strips doped with Ca ions and freshly collected bones. The probe was found to bind more at bone cracks, reflecting its potential to locate micro-cracks in bone as well as to map Ca deposits. The bound portions can be visualized through a fluorescence microscope or by illumination by a UV source (365 nm). The components used to generate the probes, namely CD, glutamic acid and hyaluronic acid, are well known for their non-toxicity and biocompatibility. It appears, therefore, that the probe could be used for in vivo applications.

Simultaneous determination of homocysteine and asymmetric dimethylarginine in human urine by liquid chromatography-tandem mass spectrometry.

Increased circulating concentrations of homocysteine (HCY) and asymmetric dimethylarginine (ADMA) are associated with vascular disease and vascular risk factors. HCY has been shown to inhibit the activity of endothelial dimethylaminohydrolase (DDAH), causing the accumulation of ADMA and the inhibition of nitric oxide synthesis. The concentrations of HCY and ADMA in biological fluids are used in the clinical diagnosis of cardiovascular diseases and this necessitates the development of a rapid and sensitive method for simultaneous determination of HCY and ADMA. A rapid, simple and sensitive method for simultaneous determination of HCY and ADMA by liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with electro spray ionization (ESI) in human urine was reported here. The methodology designed here was used to estimate these molecules in urine samples collected from patients reported to Cardiology Department of our hospital. Chromatographic separation was performed on Atlantis HILIC silica (100mm×2.1mm, 5µm, Waters). Positive multiple reactions monitoring (MRM) mode was chosen for quantification of each analyte and cystamine dihydrochloride (CYA) was used as the internal standard (IS) for the assay. The intra-assay precision and accuracy were in the range of 2.4-4.8 and -1.8% to 3.1%, respectively. The inter-assay precision and accuracy were in the range of 3.0-4.2% and -1.2% to 3.2%, respectively. The recoveries were between 94.9% and 101.4%. Our approach is simple, rapid and could be extended to routine urine assay.

Turbulent mixing and beyond: non-equilibrium processes from atomistic to astrophysical scales.

Turbulent mixing is a source of paradigm problems in physics, engineering and mathematics. Beyond this important interdisciplinary role, it has immense consequences for a broad range of applications in astrophysics, geophysics, climate and large-scale energy systems. In two volumes, we summarize and provide a perspective on the topic through some 20 articles focusing on turbulent mixing and beyond. The volumes are grouped, somewhat loosely, into those associated with fundamental aspects of turbulence and those specific to Rayleigh-Taylor turbulent mixing.

Turbulent mixing and beyond: non-equilibrium processes from atomistic to astrophysical scales I.

In this Introduction, we summarize and provide a perspective on 11 articles on 'Turbulent mixing and beyond'. The papers represent the broad variety of themes of the subject, and are concerned with fundamental aspects of turbulence, mixing and non-equilibrium dynamics. While each paper deals with a specific problem, the collection gives a panoramic overview of the subject at its present state of understanding.

Gold nanoparticles generated and stabilized by water soluble curcumin-polymer conjugate: blood compatibility evaluation and targeted drug delivery onto cancer cells.

Curcumin (Cur) shows low anticancer activity in vivo due to its reduced systemic bioavailability stemmed from its poor aqueous solubility and instability. Suitably functionalized nanocarriers designed to empty the drug specifically at tumor sites can potentially enhance the antitumor activity of Cur. We devised a simple method for the fabrication of water soluble Cur conjugated gold nanoparticles to target various cancer cell lines. Cur was conjugated to hyaluronic acid (HA) to get a water soluble conjugate (HA-Cur). We generated gold nanoparticles (AuNPs) by reducing chloroauric acid using HA-Cur, which played the dual role of a reducing and stabilizing agent and subsequently anchored folate conjugated PEG. These entities were probed using different analytical techniques, assayed the blood compatibility and cytotoxicity. Their interaction with cancer cell lines (HeLa cells, glyoma cells and Caco 2 cells) was followed by flow cytometry and confocal microscopy. Blood-materials interactions studies showed that the nanoparticles are highly hemocompatible. Flow cytometry and confocal microscopy results showed significant cellular uptake and internalization of the particles by cells. HA-Cur@AuNPs exhibited more cytotoxicity comparing to free Cur. The strategy, we adopted here, resulted the formation blood compatible Cur conjugated AuNPs with enhanced targeting and improved efficacy.

Enhanced drug loading on magnetic nanoparticles by layer-by-layer assembly using drug conjugates: blood compatibility evaluation and targeted drug delivery in cancer cells.

Drug targeting using magnetic nanoparticles (MNPs) under the action of an external magnetic field constitutes an important mode of drug delivery. Low cargo capacity, particularly in hydrophobic drugs, is one limitation shown by MNPs. This article describes a simple strategy to enhance the drug-loading capacity of MNPs. The approach was to use polymer-drug conjugates to modify MNPs by layer-by-layer assembly (LbL). Curcumin (CUR) has shown remarkably high cytotoxicity toward various cancer cell lines. However, the drug shows low anticancer activity in vivo because of its reduced systemic bioavailability acquired from its poor aqueous solubility and instability. To address this issue, we synthesized cationic and anionic CUR conjugates by anchoring CUR onto poly(vinylpyrroidone) (PVP-Cur) and onto hyaluronic acid (HA-Cur). We used these oppositely charged conjugates to modify MNPs by layer-by-layer (LbL) assembly. Six double layers of curcumin conjugates were constructed on positively charged amino-terminated magnetic nanoparticles, TMSPEDA@MNPs. Finally, HA was coated onto the outer surface to form HA (HA-Cur/PVP-Cur)(6)@MNPs. Cellular viability studies showed the dose-dependent antiproliferative effect of HA (HA-Cur/PVP-Cur)(6)@MNPs in two cancer cell lines (glioma cells and Caco-2 cells). HA (HA-Cur/PVP-Cur)(6)@MNPs exhibited more cytotoxicity than did free curcumin, which was attributed to the enhanced solubility along with better absorption via hyaluronic acid receptor-mediated endocytosis. Flow cytometry showed enhanced intake of the modified MNPs by cells. Confocal microscope images also confirmed the uptake of HA (HA-Cur/PVP-Cur)(6)@MNPs with greater efficacy. Thus, the strategy that we adopted here appears to have substantial potential in carrying enhanced payloads of hydrophobic drugs to specified targets.

Detection of glucose in synthetic tear fluid using dually functionalized gold nanoparticles.

A simple fluorescent sensing of glucose in aqueous fluids (e.g. tear fluid) using dually functionalized gold nanoparticles is presented. As a first step gold nanoparticles (AuNPs) were synthesized using oxidised dextran which acted both as reducing and stabilizing agent. Aminophenyl boronic acid was conjugated onto AuNPs by Schiff's base formation and the formed Schiff's base was stabilized by sodium borohydride reduction. Rhodamine B isothiocyanate (RBITC) was then assembled onto the modified AuNPs. The fluorescence of RBITC was nearly quenched and found to be revived when glucose was added. It is reasoned that the glucose binding induces restructuring of the surface assembly resulting in an overall increase in the size and thereby enhancing the distance between the gold core and fluorophore. TEM image and size measurements using dynamic light scattering (DLS) in fact, reflected this possibility. The increase in fluorescence was proportional with the concentration of glucose enabling quantitative detection. A good linearity was observed between the fluorescence intensity and glucose concentration in a range of 0.025-0.125 µM with detection limit of 0.005 ± 0.002 µM. The potential of the method was demonstrated by measuring glucose in real tear fluids collected from volunteers. The method is extremely sensitive and can be employed to measure low concentration of glucose in aqueous fluids such as tear.