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.

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.

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.

Gold nanoparticles generated through "green route" bind Hg2+ with a concomitant blue shift in plasmon absorption peak.

We discuss here a quick, simple, economic and ecofriendly method through a completely green route for the selective detection of Hg(2+) in aqueous samples. Here we exploited the ability of chitosan to generate gold nanoparticles and subsequently to act as a stabilizer for the formed nanoparticles. When chitosan stabilized gold nanoparticles (CH-Au NPs) are interacted with Hg(2+) a blue shift for its localized surface plasmon resonance absorbance (LSPR) band is observed. The blue shift is reasoned to be due to the formation of a thin layer of mercury over gold. A concentration as low as 0.01 ppm to a maximum of 100 ppm Hg(2+) can be detected based on this blue shift of the CH-Au NPs. While all other reported methods demand complex reaction steps and costly chemicals, the method we reported here is a simple, rapid and selective approach for the detection of Hg(2+). Our results also show that the CH-Au NPs have excellent selectivity to Hg(2+) over common cations namely, Pb(2+), Cd(2+), Mn(2+), Fe(2+), Ag(1+), Ce(4+), Ni(2+), and Cu(2+).

Fluorescent gold clusters as nanosensors for copper ions in live cells.

This paper reports the use of fluorescent gold nanoclusters synthesized using bovine serum albumin (Au-BSA) for the sensing of copper ions in live cells. The fluorescence of the clusters was found to be quenched by Cu(2+) enabling its detection in cells. The selectivity of the nanosensor was demonstrated in the presence of several cations excluding Hg(2+). We did not study the effect of Hg(2+) since it was reported earlier. The present study suggests that Cu(2+) induced fluorescence quenching is due to its binding to BSA rather than the fluorescence quenching by metal-metal interaction as in the case of Hg(2+). The Au-BSA showed excellent selectivity to Cu(2+) at various pH conditions. The 'turn off' of fluorescence can be retrieved by a Cu(2+) chelator glycine. Our results showed that gold clusters can be used as a 'turn off' sensor for copper and a 'turn on' sensor for glycine. Under the experimental conditions, the probe showed a response for Cu(2+) over a range of 100 µM to 5 mM with a detection limit of 50 µM. The role of Cu(2+) in the misfolding and disassembly of Prion Protein (PrP) leading to various maladies is well ascertained. The methodology we reported here seems to be useful in supplementing other techniques in predicting disease conditions involving Cu(2+).

In vitro cytocompatibility evaluation of a thermoresponsive NIPAAm-MMA copolymeric surface using L929 cells.

Scaffold free tissue constructs are preferred in tissue engineering as they overcome all the problems associated with scaffolds. Stimuli responsive polymers enable generation of scaffold free multilayered tissue constructs which would in turn reduce the use of biomaterials in vivo. In this study, we investigated cytocompatibility and thermoresponsiveness of a copolymer of N-Isopropylacrylamide and Methyl Methacrylate. Thermoresponsive surfaces were prepared by coating tissue culture polystyrene with the copolymer solution in isopropanol. Mammalian fibroblast cells (L929 cells) readily adhered on the copolymer. The viability and cellular activity was ensured through Neutral red staining, MTT assay, Tritiated thymidine uptake assay and Immunofluorescent staining for cytoskeletal organisation. Incubation under lower critical solution temperature of copolymer resulted in intact detachment of cells. To conclude, in-house synthesized cytocompatible smart culture substrate intended for tissue engineering was developed using a cost effective and simple technique. Moreover, presence of methyl methacrylate in the copolymer reduced the lower critical solution temperature facilitating extended in vitro manipulation time. As the copolymer is insoluble in water, the copolymer could be polymerised without additional crosslinkers.

A sensitive estimation of residual ethylene glycol in ethylene oxide sterilized medical devices by HPLC with electrospray ionization mass spectrometric detection.

A novel analytical methodology for the estimation of residual ethylene glycol (EG) in ethylene oxide sterilized polymer is reported. The method involves the monitoring of ammonium adduct of EG ions in the presence of 10 mM ammonium acetate buffer and methanol using electrospray ionization liquid chromatography and mass spectrometry (LC-ESI-MS). The method enables the detection and quantification of EG without prior derivatization up to a level of 0.06 microg/ml. The potentiality of the method is demonstrated by estimating EG in ethylene oxide (EtO) sterilized polyethylene terephthalate fabric used in heart valve sewing ring. The method is simple, rapid and can routinely be used for the quantification of residual EG in EtO sterilized medical devices.

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.

Taylor's frozen-flow hypothesis in Burgers turbulence.

By detailed analytical treatment of the shock dynamics in the Burgers turbulence with large scale forcing we calculate the velocity structure functions between pairs of points displaced both in time and space. Our analytical treatment verifies the so-called Taylor's frozen-flow hypothesis without relying on any closure and under very general assumptions. We discuss the limitation of the hypothesis and show that it is valid up to time scales smaller than the correlation time scale of temporal velocity correlation function. We support the analytical calculation by performing numerical simulation of the periodically kicked Burgers equation.

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.

Fluctuations of temperature gradients in turbulent thermal convection.

Broad theoretical arguments are proposed to show, formally, that the magnitude G of the temperature gradients in turbulent thermal convection at high Rayleigh numbers obeys the same advection-diffusion equation that governs the temperature fluctuation T , except that the velocity field in the new equation is substantially smoothed. This smoothed field leads to a -1 scaling of the spectrum of G in the same range of scales for which the spectral exponent of T lies between -7/5 and -5/3 . This result is confirmed by measurements in a confined container with cryogenic helium gas as the working fluid for Rayleigh number Ra=1.5x 10(11) . Also confirmed is the logarithmic form of the autocorrelation function of G . The anomalous scaling of dissipation-like quantities of T and G are identical in the inertial range, showing that the analogy between the two fields is quite deep.

Critical fluctuation of wind reversals in convective turbulence.

The irregular reversals of wind direction in convective turbulence are found to have fluctuating intervals that can be related, under certain circumstances, to critical behavior. In particular, by focusing on its temporal evolution, the net magnetization of a two-dimensional Ising lattice of finite size is observed to fluctuate in the same way. Detrended fluctuation analysis of the wind reversal time series results in a scaling behavior that agrees remarkably well with that of the Ising problem. The specific properties found here, as well as the lack of an external tuning parameter, also suggest that the wind reversal phenomenon exhibits signs of self-organized criticality.

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.

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.

Effect of steam sterilization on polyethylene terephthalate.

Subtle changes on the surface of polymeric materials on autoclaving have been ignored so far. An increase in cyclic trimer content on the surface of polyethylene terephthalate on autoclaving is reported. This increase may affect the biocompatibility of polyethylene terephthalate. Quantification of the cyclic trimer was done by high performance liquid chromatography.

Multiple gamma radiation sterilization of polyester fibres.

Gamma radiation with a dose of 2.5 Mrad has been found to be suitable to sterilize polyethylene terephthalate (PET) bulk materials intended for biomedical applications. The radiation stability of PET bulk materials and fibre may not however be taken as identical due to the changes in the polymer structure during the processing of bulk materials for fibre. The chemical changes occurring in PET fibres during single and multiple (prolonged) sterilization in air were investigated. It was found that single sterilization (2.5 Mrad) itself affected the PET yarn and fibre. This was exhibited by the increase of crystallinity from 30.5 to 37% in the case of yarn and from 40 to 44% in the case of fibre. The breaking load of the yarn also increased from 441 g to 451 g. These changes were attributed to the degradation of PET in the amorphous region and the recombination of degraded aliphatic segments. Sterilization at higher doses affected the crystalline region which decreased the crystallinity, breaking load and molecular weight. For samples irradiated at 2.5 Mrad, the breaking load increased, though the dispersity increased. This was attributed to cross-linking by recombination. The increase in crystallinity also enhanced the breaking load of the samples. Higher doses of sterilization led to drastic microstructural and macrostructural changes as seen from the molecular weight. It was inferred that the changes in crystallinity and microstructure that occurred during multiple sterilization might affect the biocompatibility of the material.