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Because it lacks a lymphatic circulation, the brain must clear extracellular proteins by an alternative mechanism. The cerebrospinal fluid (CSF) functions as a sink for brain extracellular solutes, but it is not clear how solutes from the brain interstitium move from the parenchyma to the CSF. We demonstrate that a substantial portion of subarachnoid CSF cycles through the brain interstitial space. On the basis of in vivo two-photon imaging of small fluorescent tracers, we showed that CSF enters the parenchyma along paravascular spaces that surround penetrating arteries and that brain interstitial fluid is cleared along paravenous drainage pathways. Animals lacking the water channel aquaporin-4 (AQP4) in astrocytes exhibit slowed CSF influx through this system and a ~70% reduction in interstitial solute clearance, suggesting that the bulk fluid flow between these anatomical influx and efflux routes is supported by astrocytic water transport. Fluorescent-tagged amyloid β, a peptide thought to be pathogenic in Alzheimer's disease, was transported along this route, and deletion of the Aqp4 gene suppressed the clearance of soluble amyloid β, suggesting that this pathway may remove amyloid β from the central nervous system. Clearance through paravenous flow may also regulate extracellular levels of proteins involved with neurodegenerative conditions, its impairment perhaps contributing to the mis-accumulation of soluble proteins.

GROMACS is one of the most widely used open-source and free software codes in chemistry, used primarily for dynamical simulations of biomolecules. It provides a rich set of calculation types, preparation and analysis tools. Several advanced techniques for free-energy calculations are supported. In version 5, it reaches new performance heights, through several new and enhanced parallelization algorithms. These work on every level; SIMD registers inside cores, multithreading, heterogeneous CPU–GPU acceleration, state-of-the-art 3D domain decomposition, and ensemble-level parallelization through built-in replica exchange and the separate Copernicus framework. The latest best-in-class compressed trajectory storage format is supported.

Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.

Emerging adulthood is proposed as a new conception of development for the period from the late teens through the twenties, with a focus on ages 18-25. A theoretical background is presented. Then evidence is provided to support the idea that emerging adulthood is a distinct period demographically, subjectively, and in terms of identity explorations. How emerging adulthood differs from adolescence and young adulthood is explained. Finally, a cultural context for the idea of emerging adulthood is outlined, and it is specified that emerging adulthood exists only in cultures that allow young people a prolonged period of independent role exploration during the late teens and twenties.

Economic history is about the performance of economies through time. The objective of research in the field is not only to shed new light on the economic past but also to contribute to economic theory by providing an analytical framework that will enable us to understand economic change. A theory of economic dynamics comparable in precision to general equilibrium theory would be the ideal tool of analysis. In the absence of such a theory we can describe the characteristics of past economies, examine the performance of economies at various times, and engage in comparative static analysis; but missing is an analytical understanding of the way economies evolve through time.

The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved for the alignment of divergent protein sequences. Firstly, individual weights are assigned to each sequence in a partial alignment in order to down-weight near-duplicate sequences and up-weight the most divergent ones. Secondly, amino acid substitution matrices are varied at different alignment stages according to the divergence of the sequences to be aligned. Thirdly, residue-specific gap penalties and locally reduced gap penalties in hydrophilic regions encourage new gaps in potential loop regions rather than regular secondary structure. Fourthly, positions in early alignments where gaps have been opened receive locally reduced gap penalties to encourage the opening up of new gaps at these positions. These modifications are incorporated into a new program, CLUSTAL W which is freely available.

การวิจัยเชิงคุณภาพ เป็นเครื่องมือสำคัญอย่างหนึ่งสำหรับทำความเข้าใจสังคมและพฤติกรรมมนุษย์ การวิจัยแบบการสร้างทฤษฎีจากข้อมูล ก็เป็นหนึ่งในหลายระเบียบวิธีการวิจัยเชิงคุณภาพที่กำลังได้รับความสนใจ และเป็นที่นิยมเพิ่มสูงขึ้นเรื่อยๆ จากนักวิชาการ และนักวิจัยในสาขาสังคมศาสตร์ และศาสตร์อื่นๆ เช่น พฤติกรรมศาสตร์ สังคมวิทยา สาธารณสุขศาสตร์ พยาบาลศาสตร์ จิตวิทยาสังคม ศึกษาศาสตร์ รัฐศาสตร์ และสารสนเทศศึกษา ดังนั้น หนังสือเรื่อง “ConstructingGrounded Theory: A Practical Guide through Qualitative Analysis” หรือ “การสร้างทฤษฎีจากข้อมูล:แนวทางการปฏิบัติผ่านการวิเคราะห์เชิงคุณภาพ” จะช่วยให้ผู้อ่านมีความรู้ความเข้าใจถึงพัฒนาการของปฏิบัติการวิจัยแบบสร้างทฤษฎีจากข้อมูล ตลอดจนแนวทาง และกระบวนการปฏิบัติการวิจัยอย่างเป็นระบบ จึงเป็นหนังสือที่ควรค่าแก่การอ่านโดยเฉพาะนักวิจัยรุ่นใหม่ เพื่อเป็นแนวทางในการนำความรู้ความเข้าใจไประยุกต์ในงานวิจัยของตน อีกทั้งนักวิจัยผู้เชี่ยวชาญสามารถอ่านเพื่อขยายมโนทัศน์ด้านวิจัยให้กว้างขวางขึ้น

Models for the processes by which ideas and influence propagate through a social network have been studied in a number of domains, including the diffusion of medical and technological innovations, the sudden and widespread adoption of various strategies in game-theoretic settings, and the effects of "word of mouth" in the promotion of new products. Recently, motivated by the design of viral marketing strategies, Domingos and Richardson posed a fundamental algorithmic problem for such social network processes: if we can try to convince a subset of individuals to adopt a new product or innovation, and the goal is to trigger a large cascade of further adoptions, which set of individuals should we target?We consider this problem in several of the most widely studied models in social network analysis. The optimization problem of selecting the most influential nodes is NP-hard here, and we provide the first provable approximation guarantees for efficient algorithms. Using an analysis framework based on submodular functions, we show that a natural greedy strategy obtains a solution that is provably within 63% of optimal for several classes of models; our framework suggests a general approach for reasoning about the performance guarantees of algorithms for these types of influence problems in social networks.We also provide computational experiments on large collaboration networks, showing that in addition to their provable guarantees, our approximation algorithms significantly out-perform node-selection heuristics based on the well-studied notions of degree centrality and distance centrality from the field of social networks.

The flow of liquids in unsaturated porous mediums follows the ordinary laws of hydrodynamics, the motion being produced by gravity and the pressure gradient force acting in the liquid. By making use of Darcey's law, that flow is proportional to the forces producing flow, the equation K∇2ψ+∇K·∇ψ+g∂K/∂z=−ρsA∂ψ/∂t may be derived for the capillary conduction of liquids in porous mediums. It is possible experimentally to determine the capillary potential ψ=∫dp/ρ, the capillary conductivity K, which is defined by the flow equation q=K(g−▿ψ), and the capillary capacity A, which is the rate of change of the liquid content of the medium with respect to ψ. These variables are analogous, respectively, to the temperature, thermal conductivity, and thermal capacity in the case of heat flow. Data are presented and application of the equations is made for the capillary conduction of water through soil and clay but the mathematical formulations and the experimental methods developed may be used to express capillary flow for other liquids and mediums. The possible existance of a hysteresis effect between the capillary potential and moisture content of a porous medium is considered.

Food's environmental impacts are created by millions of diverse producers. To identify solutions that are effective under this heterogeneity, we consolidated data covering five environmental indicators; 38,700 farms; and 1600 processors, packaging types, and retailers. Impact can vary 50-fold among producers of the same product, creating substantial mitigation opportunities. However, mitigation is complicated by trade-offs, multiple ways for producers to achieve low impacts, and interactions throughout the supply chain. Producers have limits on how far they can reduce impacts. Most strikingly, impacts of the lowest-impact animal products typically exceed those of vegetable substitutes, providing new evidence for the importance of dietary change. Cumulatively, our findings support an approach where producers monitor their own impacts, flexibly meet environmental targets by choosing from multiple practices, and communicate their impacts to consumers.

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PURPOSE: Myopia is a common cause of vision loss, with uncorrected myopia the leading cause of distance vision impairment globally. Individual studies show variations in the prevalence of myopia and high myopia between regions and ethnic groups, and there continues to be uncertainty regarding increasing prevalence of myopia. DESIGN: Systematic review and meta-analysis. METHODS: We performed a systematic review and meta-analysis of the prevalence of myopia and high myopia and estimated temporal trends from 2000 to 2050 using data published since 1995. The primary data were gathered into 5-year age groups from 0 to ≥100, in urban or rural populations in each country, standardized to definitions of myopia of -0.50 diopter (D) or less and of high myopia of -5.00 D or less, projected to the year 2010, then meta-analyzed within Global Burden of Disease (GBD) regions. Any urban or rural age group that lacked data in a GBD region took data from the most similar region. The prevalence data were combined with urbanization data and population data from United Nations Population Department (UNPD) to estimate the prevalence of myopia and high myopia in each country of the world. These estimates were combined with myopia change estimates over time derived from regression analysis of published evidence to project to each decade from 2000 through 2050. RESULTS: We included data from 145 studies covering 2.1 million participants. We estimated 1406 million people with myopia (22.9% of the world population; 95% confidence interval [CI], 932-1932 million [15.2%-31.5%]) and 163 million people with high myopia (2.7% of the world population; 95% CI, 86-387 million [1.4%-6.3%]) in 2000. We predict by 2050 there will be 4758 million people with myopia (49.8% of the world population; 3620-6056 million [95% CI, 43.4%-55.7%]) and 938 million people with high myopia (9.8% of the world population; 479-2104 million [95% CI, 5.7%-19.4%]). CONCLUSIONS: Myopia and high myopia estimates from 2000 to 2050 suggest significant increases in prevalences globally, with implications for planning services, including managing and preventing myopia-related ocular complications and vision loss among almost 1 billion people with high myopia.

Abstract When a soluble substance is introduced into a fluid flowing slowly through a small-bore tube it spreads out under the combined action of molecular diffusion and the variation of velocity over the cross-section. It is shown analytically that the distribution of concentration produced in this way is centred on a point which moves with the mean speed of flow and is symmetrical about it in spite of the asymmetry of the flow. The dispersion along the tube is governed by a virtual coefficient of diffusivity which can be calculated from observed distributions of concentration. Since the analysis relates the longitudinal diffusivity to the coefficient of molecular diffusion, observations of concentration along a tube provide a new method for measuring diffusion coefficients. The coefficient so obtained was found, with potassium permanganate, to agree with that measured in other ways. The results may be useful to physiologists who may wish to know how a soluble salt is dispersed in blood streams.

Basic backpropagation, which is a simple method now being widely used in areas like pattern recognition and fault diagnosis, is reviewed. The basic equations for backpropagation through time, and applications to areas like pattern recognition involving dynamic systems, systems identification, and control are discussed. Further extensions of this method, to deal with systems other than neural networks, systems involving simultaneous equations, or true recurrent networks, and other practical issues arising with the method are described. Pseudocode is provided to clarify the algorithms. The chain rule for ordered derivatives-the theorem which underlies backpropagation-is briefly discussed. The focus is on designing a simpler version of backpropagation which can be translated into computer code and applied directly by neutral network users.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Both the magnitude and the urgency of the task of assessing global biodiversity require that we make the most of what we know through the use of estimation and extrapolation. Likewise, future biodiversity inventories need to be designed around the use of effective sampling and estimation procedures, especially for 'hyperdiverse' groups of terrestrial organisms, such as arthropods, nematodes, fungi, and microorganisms. The challenge of estimating patterns of species richness from samples can be separated into (i) the problem of estimating local species richness, and (ii) the problem of estimating the distinctness, or complementarity, of species assemblages. These concepts apply on a wide range of spatial, temporal, and functional scales. Local richness can be estimated by extrapolating species accumulation curves, fitting parametric distributions of relative abundance, or using non-parametric techniques based on the distribution of individuals among species or of species among samples. We present several of these methods and examine their effectiveness for an example data set. We present a simple measure of complementarity, with some biogeographic examples, and outline the difficult problem of estimating complementarity from samples. Finally, we discuss the importance of using 'reference' sites (or sub-sites) to assess the true richness and composition of species assemblages, to measure ecologically significant ratios between unrelated taxa, to measure taxon/sub-taxon (hierarchical) ratios, and to 'calibrate' standardized sampling methods. This information can then be applied to the rapid, approximate assessment of species richness and faunal or floral composition at 'comparative' sites.

Since publication of the first edition of this text in 1998, there have been several new, important developments in the theory of beam wave propagation through a random medium, which have been incorporated into this second edition. Also new to this edition are models for the scintillation index under moderate-to-strong irradiance fluctuations; models for aperture averaging based on ABCD ray matrices; beam wander and its effects on scintillation; theory of partial coherence of the source; models of rough targets for ladar applications; phase fluctuations; analysis of other beam shapes; plus expanded analysis of free-space optical communication systems and imaging systems.

An Invitation to Grounded Theory Gathering Rich Data Coding in Grounded Theory Practice Memo-Writing Theoretical Sampling, Saturation and Sorting Reconstructing Theory in Grounded Theory Studies Writing the Draft Reflecting on the Research Process

The authors present a new molecular dynamics algorithm for sampling the canonical distribution. In this approach the velocities of all the particles are rescaled by a properly chosen random factor. The algorithm is formally justified and it is shown that, in spite of its stochastic nature, a quantity can still be defined that remains constant during the evolution. In numerical applications this quantity can be used to measure the accuracy of the sampling. The authors illustrate the properties of this new method on Lennard-Jones and TIP4P water models in the solid and liquid phases. Its performance is excellent and largely independent of the thermostat parameter also with regard to the dynamic properties.

Hollow nanocrystals can be synthesized through a mechanism analogous to the Kirkendall Effect, in which pores form because of the difference in diffusion rates between two components in a diffusion couple. Starting with cobalt nanocrystals, we show that their reaction in solution with oxygen and either sulfur or selenium leads to the formation of hollow nanocrystals of the resulting oxide and chalcogenides. This process provides a general route to the synthesis of hollow nanostructures of a large number of compounds. A simple extension of the process yielded platinum-cobalt oxide yolk-shell nanostructures, which may serve as nanoscale reactors in catalytic applications.