Fluorescent Probe DCVJ Shows High Sensitivity for Characterization of Amyloid β-Peptide Early in the Lag Phase

The aggregation of intrinsically disordered and misfolded proteins in the form of oligomers and fibrils plays a crucial role in a number of neurological and neurodegenerative diseases. Currently, most probes and biophysical techniques that detect and characterize fibrils at high resolution fail to show sensitivity and binding for oligomers. Here, we show that 9-(dicyano-vinyl)julolidine (DCVJ), a class of molecular rotor, binds amyloid beta (Aβ) early aggregates, and we report the kinetics as well as packing of the oligomer formation. The binding of DCVJ to Aβ40 increased its emission intensity with time at 510 nm and produced a second excimer peak at 575 nm. However, DCVJ did not bind to the prefibrillar aggregates of Aβ42, which indicated that the oligomers formed by Aβ40 and Aβ42 were not the same. The F4C F19W mutant of Aβ40, which did not form fibrils, also bound DCVJ, but the emission spectral profile varied from that of the wild-type (WT). Atomic force microscopy images of WT Aβ40, the F4C F19W mutant, and Aβ42 oligomers displayed differences in size and shape, confirming the difference in their DCVJ spectra. The effect of epigallocatechin-3-gallate (EGCG) on the reduction of Aβ42 fibrils was also observed with finer detail than with other techniques. The results of this study show that DCVJ detects early aggregates and provides valuable information regarding the oligomer kinetics, packing, and mechanism of formation.     

Every team deserves a second chance: an extended study on predicting team performance

Voting among different agents is a powerful tool in problem solving, and it has been widely applied to improve the performance in finding the correct answer to complex problems. We present a novel benefit of voting, that has not been observed before: we can use the voting patterns to assess the performance of a team and predict their final outcome. This prediction can be executed at any moment during problem-solving and it is completely domain independent. Hence, it can be used to identify when a team is failing, allowing an operator to take remedial procedures (such as changing team members, the voting rule, or increasing the allocation of resources). We present three main theoretical results: (1) we show a theoretical explanation of why our prediction method works; (2) contrary to what would be expected based on a simpler explanation using classical voting models, we show that we can make accurate predictions irrespective of the strength (i.e., performance) of the teams, and that in fact, the prediction can work better for diverse teams composed of different agents than uniform teams made of copies of the best agent; (3) we show that the quality of our prediction increases with the size of the action space. We perform extensive experimentation in two different domains: Computer Go and Ensemble Learning. In Computer Go, we obtain high quality predictions about the final outcome of games. We analyze the prediction accuracy for three different teams with different levels of diversity and strength, and show that the prediction works significantly better for a diverse team. Additionally, we show that our method still works well when trained with games against one adversary, but tested with games against another, showing the generality of the learned functions. Moreover, we evaluate four different board sizes, and experimentally confirm better predictions in larger board sizes. We analyze in detail the learned prediction functions, and how they change according to each team and action space size. In order to show that our method is domain independent, we also present results in Ensemble Learning, where we make online predictions about the performance of a team of classifiers, while they are voting to classify sets of items. We study a set of classical classification algorithms from machine learning, in a data-set of hand-written digits, and we are able to make high-quality predictions about the final performance of two different teams. Since our approach is domain independent, it can be easily applied to a variety of other domains.     

Modulation of Cellular Fate of Vinyl Triarylamines through Structural Fine Tuning: To Stay or Not To Stay in the Mitochondria?

Mitochondria are involved in many cellular pathways and dysfunctional mitochondria are linked to various diseases. Hence efforts have been made to design mitochondria-targeted fluorophores for monitoring the mitochondrial status. However, the factors that govern the mitochondria-targeted potential of dyes are not well-understood. In this context, we synthesized analogues of the TP-2Bzim probe belonging to the vinyltriphenylamine (TPA) class and already described for its capacity to bind nuclear DNA in fixed cells and mitochondria in live cells. These analogues ( TP-1Bzim, TPⁿ-2Bzim, TP¹⁺-2Bzim, TN-2Bzim ) differ in the cationic charge, the number of vinylbenzimidazolium branches and the nature of the triaryl core. Using microscopy, we demonstrated that the cationic derivatives accumulate in mitochondria but do not reach mtDNA. Under depolarisation of the mitochondrial membrane, TP-2Bzim and TP¹⁺-2Bzim translocate to the nucleus in direct correlation with their strong DNA affinity. This reversible phenomenon emphasizes that these probes can be used to monitor ΔΨ_m variations.     

Technical note Temporal remote sensing data and GIS application in landslide hazard zonation of part of Western ghat,India

Spatial and temporal multi-layered information is required to assess landslide hazard susceptibility. The manual method of data integration for targeting potential zones susceptible to landslide hazard is time consuming. The present study highlights the utility of temporal remotely-sensed data and knowledgebased Geographical Information Systems for collection, integration and analysis of spatially-oriented data, as well as in finding out the inherent relation between separate entities in parts of West ghat in India.     

Error diffusion in cell-oriented Fourier-transform computer-generated holograms to compensate for printing constraints

Abstract

Error-diffused quantization has been applied to the generation of cell-oriented computer-generated Fourier transform holograms, resulting in reduced reconstruction errors. Improvements are demonstrated when applied to the algorithms of Lohmann, Lee and Burckhardt after invoking realistic constraints on the minimum size of the printable spot for an electrophotographic laser printer.     

Nitrites Derived From Foneiculum Vulgare (Fennel) Seeds Promotes Vascular Functions

Abstract: Recent evidence has demonstrated that nitrites play an important role in the cardiovascular system. Fennel (Foneiculum vulgare) seeds are often used as mouth fresheners after a meal in both the Indian sub‐continent and around the world. The present study aims to quantify the nitrite and nitrates in fennel seeds as well as elucidating the effect of fennel derived‐nitrites on vascular functions. Results from our study show that fennel seeds contain significantly higher amount of nitrites when compared to other commonly used post‐meal seeds. Furthermore our study confirmed the functional effects of fennel derived‐nitrites using in vitro and ex vivo models that describe the promotion of angiogenesis, cell migration, and vasorelaxation. We also showed that chewing fennel seeds enhanced nitrite content of saliva. Thus our study indicates the potential role of fennel derived‐nitrites on the vascular system. Practical Application: This study is focused on determining the effect of fennel‐derived nitrites on angiogenesis (the formation of new blood vessels from pre‐existing ones), cell migration, and vasorelaxation (dilation of blood vessels) thereby preserving cardiovascular health.     

Influence of plastic deformation in flexible pad laser shock forming – experimental and numerical analysis

Flexible Pad Laser Shock Forming (FPLSF) is a new microforming process using laser-induced shock pressure and a hyperelastic flexible pad to induce high strain-rate (~10⁵ s^?1) plastic deformation on metallic foils to produce 3D microcraters. This paper studies the effect of two significant process parameters of FPLSF, flexible pad material and its thickness, on the deformation characteristics of the metal foils using experiments and finite element analysis. A finite element model is developed to simulate the FPLSF process. The stress-strain distribution across the foil and the flexible pad at different process stages of FPLSF are studied using FE analysis. Flexible pad materials including silicone rubber, polyurethane rubber, and natural rubber with thicknesses ranging between 300 μm and 3000 μm have been investigated in detail. Experimental results highlight that both the hardness and thickness of the flexible pad significantly influence the deformed crater geometry, thickness distribution across the formed crater and surface hardness at the crater surfaces. The experimental results are correlated with the stress-strain distributions from finite element analysis to study the underlying behaviors.     

Protective Immunity against Listeria monocytogenes in Rats,Provided by HCl- and NaOH-Induced Listeria monocytogenes Bacterial Ghosts (LMGs) as Vaccine Candidates

Listeria monocytogenes (Lm) bacterial ghosts (LMGs) were produced by the minimum inhibitory concentration (MIC) of HCl, H₂SO₄, and NaOH. Acid and alkali effects on the LMGs were compared by in vitro and in vivo analyses. Scanning electron microscope showed that all chemicals form lysis pores on the Lm cell envelopes. Real-time qPCR revealed a complete absence of genomic DNA in HCl- and H₂SO₄-induced LMGs but not in NaOH-induced LMGs. HCl-, H₂SO₄- and NaOH-induced LMGs showed weaker or missing protein bands on SDS-PAGE gel when compared to wild-type Lm. Murine macrophages exposed to the HCl-induced LMGs showed higher cell viability than those exposed to NaOH-induced LMGs or wild-type Lm. The maximum level of cytokine expression (TNF-α, iNOS, IFN-γ, and IL-10 mRNA) was observed in the macrophages exposed to NaOH-induced LMGs, while that of IL-1β mRNA was observed in the macrophages exposed to HCl-induced LMGs. To investigate LMGs as a vaccine candidate, mice were divided into PBS buffer-injected, HCl- and NaOH-induced LMGs immunized groups. Mice vaccinated with HCl- and NOH-induced LMGs, respectively, significantly increased in specific IgG antibodies, bactericidal activities of serum, and CD4⁺ and CD8⁺ T-cell population. Antigenic Lm proteins reacted with antisera against HCl- and NOH-induced LMGs, respectively. Bacterial loads in HCl- and NaOH-induced LMGs immunized mice were significantly lower than PBS-injected mice after virulent Lm challenges. It suggested that vaccination with LMGs induces both humoral and cell-mediated immune responses and protects against virulent challenges.     

Photostimulated luminescence studies of γ-irradiated KBr1−xIx:TlI mixed crystals

Results on photoluminescence and photostimulated luminescence studies of KBr_1−xI_x:TlI (0.01 and 0.05 mol%) mixed crystals grown in vacuum and air are presented. Photoluminescence spectra of the mixed crystals excited in the A-absorption band of KBr:Tl⁺ exhibited the characteristic emission bands of Tl⁺ ions in KBr:Tl⁺. When excited in the low energy tail of A-band absorption, additional emission bands were observed. Compared with earlier reports, excitation bands observed around 4.8, 4.6 and 4.4 eV are attributed to complex thallium centres of the form TlBr_6−nI_n (n = 0, 1, 2, 3). Photostimulated luminescence of γ-irradiated KBr_1−xI_x:TlI mixed crystals showed the presence of emission bands similar to the characteristic photoluminescence of Tl⁺ ions. The photostimulated luminescence slightly shifted towards the low energy side with increasing iodide composition x. The mechanism of emission in these mixed crystals is discussed. Dose response and storage stability (fading characteristics) in these mixed crystals are reported.