Biflavonoid-Induced Disruption of Hydrogen Bonds Leads to Amyloid-β Disaggregation

Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC₅₀ values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease.     

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

Neurodegenerative diseases (NDs) including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. In this review, we provide an introduction to CADD and examine the progress in applying CADD and other molecular docking studies to NDs. We provide an updated overview of potential therapeutic targets for various NDs and discuss some of the advantages and disadvantages of these tools.     

A Quantitative Analysis of Current Practices in Optical Flow Estimation and the Principles Behind Them

The accuracy of optical flow estimation algorithms has been improving steadily as evidenced by results on the Middlebury optical flow benchmark. The typical formulation, however, has changed little since the work of Horn and Schunck. We attempt to uncover what has made recent advances possible through a thorough analysis of how the objective function, the optimization method, and modern implementation practices influence accuracy. We discover that “classical” flow formulations perform surprisingly well when combined with modern optimization and implementation techniques. One key implementation detail is the median filtering of intermediate flow fields during optimization. While this improves the robustness of classical methods it actually leads to higher energy solutions, meaning that these methods are not optimizing the original objective function. To understand the principles behind this phenomenon, we derive a new objective function that formalizes the median filtering heuristic. This objective function includes a non-local smoothness term that robustly integrates flow estimates over large spatial neighborhoods. By modifying this new term to include information about flow and image boundaries we develop a method that can better preserve motion details. To take advantage of the trend towards video in wide-screen format, we further introduce an asymmetric pyramid downsampling scheme that enables the estimation of longer range horizontal motions. The methods are evaluated on the Middlebury, MPI Sintel, and KITTI datasets using the same parameter settings.     

Obesity: Prevalence,Theories, Medical Consequences,Management, and Research Directions

Obesity and its associated disorders are a growing epidemic across the world. Many genetic, physiological, and behavioral factors play a role in the etiology of obesity. Diet and exercise are known to play a valuable role in the treatment and prevention of obesity and associated disorders such as hypertension, heart disease, and diabetes. Therefore, the purpose of this review is to examine the prevalence, etiology, consequences, and treatment of obesity.     

Pheromone specificity inEriocrania semipurpurella (Stephens) andE. sangii (Wood) (Lepidoptera: Eriocraniidae) based on chirality of semiochemicals

The fifth abdominal segment of femaleEriocrania semipurpurella (Stephens) andE. sangii (Wood) contains a pair of exocrine glands. Hexane extracts of this segment were prepared from both species and analyzed by gas chromatography with simultaneous flame ionization and electroantennographic detection (EAD). For both species, the EAD active peaks were identified as nonan-2-one, (Z)-6-nonen-2-one, and (Z)-6-nonen-2-ol by means of mass spectrometry and comparison of retention indices with those of synthetic standards. Enantiomeric separation of chiral alcohols from the female extracts was achieved by gas chromatographic analysis on a cyclodextrin column. InE. semipurpurella, a mixture of (2S,6Z)-nonen-2-ol and (2R,6Z)-nonen-2-ol (2: I) was found, whereas inE. sangii (2S,6Z)-nonen-2-ol was the predominant enantiomer and only traces of theR enantiomer were indicated by the antennal response. In field tests, a blend of the three compounds was not attractive to conspecific males. A subtractive assay showed that the alcohol in various enantiomeric mixtures was the only attractive compound, whereas addition of (Z)-6-nonen-2-one to the alcohol completely inhibited the attraction of both species. A trapping experiment including a wide range of ratios between theR andS enantiomers showed that baits containing 95–100% of theS enantiomer were attractive to maleE. sangii, whereas males ofE. semipurpurella were attracted to all tested ratios of the enantiomers. However, the response profiles of maleE. semipurpurella differed between populations from southern Sweden, south Finland, and the Kola Peninsula in Russia. In south Sweden males were maximally attracted to a racemic mixture of the alcohols. At the Kola PeninsulaE. semipurpurella was attracted to baits containing 95–100% of theR enantiomer. In south Finland all tested ratios between 0 and 100%R enantiomer trappedE. semipurpurella, but the trap catches appeared to be bimodally distributed with peaks around 15 and 70%R enantiomer. The trapping results suggest the existence of pheromone races or sibling species among the specimens identified asE. semipurpurella.Dedicated to Prof. H. J. Bestmann on the occasion of his 70th birthday.     

Micro-computed tomography scanning approaches to quantify,parameterize and visualize bioturbation activity in clogged streambeds: A proof of concept

Fine particle clogging and faunal bioturbation are two key processes co-occurring in the hyporheic zone that potentially affect hyporheic exchange through modifications in the sediment structure of streambeds. Clogging results from excessive fine sediment infiltration and deposition in rivers, and it is known to decrease matrix porosity and potentially reduce permeability. Faunal bioturbation activity may compensate for the negative effect of clogging by reworking the sediment, increasing porosity, and preventing further infiltration of fines. Although both processes of clogging and bioturbation have received significant attention in the literature separately, their combined effects on streambed sediment structure are not well understood, mostly due to the lack of a standard methodology for their assessment. Here, we illustrate a novel methodology using X-ray computed tomography (CT), as proof of concept, to investigate how, together, clogging and bioturbation affect streambed porosity in a controlled flow-through flume. By visualising gallery formations of an upward conveyor macroinvertebrate; Lumbriculus variegatus as a model species, we quantified bioturbation activity in a clogged streambed, focusing on orientation, depth, and volume at downwelling and upwelling areas of the flume. Gallery creation increased the porosity of the streambed sediment, suggesting a potential improvement in permeability and a possible offset of clogging effects. We illustrate the promising use of X-ray CT as a tool to assess bioturbation in clogged streambeds, and the potential role of bioturbation activity supporting hyporheic exchange processes in streambeds, warranting further studies to understand the extent of bioturbation impacts in natural systems.     

Quantum commitments from complexity assumptions

Bit commitment schemes are at the basis of modern cryptography. Since information-theoretic security is impossible both in the classical and in the quantum regime, we examine computationally secure commitment schemes. In this paper we study worst-case complexity assumptions that imply quantum bit commitment schemes. First, we show that QSZK \({\not\subseteq}\) QMA implies a computationally hiding and statistically binding auxiliary-input quantum commitment scheme. We then extend our result to show that the much weaker assumption QIP \({\not\subseteq}\) QMA (which is weaker than PSPACE \({\not\subseteq}\) PP) implies the existence of auxiliary-input commitment schemes with quantum advice. Finally, to strengthen the plausibility of the separation QSZK \({\not\subseteq}\) QMA, we find a quantum oracle relative to which honest-verifier QSZK is not contained in QCMA, the class of languages that can be verified using a classical proof in quantum polynomial time.     

An EM approach to mineral analysis using natural gamma rays

We describe here a method for the analysis of materials on a conveyor belt using the natural gamma spectra collected with a BGO (Bismuth Germanate) gamma ray detector. This detector collects gamma ray emissions from the Potassium (K), Uranium (U), and Thorium (Th) atoms in the materials. Based on these data, and using a Poisson model for the data generation, a statistical model is proposed and an approximate maximum likelihood (ML) technique based on the expectation-maximization (EM) algorithm is then used to estimate the amount of each of the three elements in the material. The statistical model is further refined to incorporate parameters of drift in the detector and an estimation technique for this is developed and tested against real data. The Cramér–Rao lower bounds for the estimators are calculated.     

Scala上的Twitter

Twitter将部分应用从Ruby迁移到了Scala。三位开发者详谈决策背后的因素、Scala在现实应用中遇到的困难以及Scala对编程风格的影响。     

Windows 7中的Windows XP模式支持USB设备吗？

Windows XP模式可用在Windows 7的Professiona Enterprise和Ultimate版本中。它实质上由两部分构成版的Virtual PC,名为Windows Virtual PC：通过Windows Firewall进行配置并能自动更新的Windows XP Professiona SP3虚拟机（VM）。如果OEM选择安装Windows XP模式,可以预先在新计算机上安装它,也可以通过微软站点下载它。