Immunotherapeutic approaches to Alzheimer's disease

Although neurodegenerative diseases such as Alzheimer's disease are not classically considered mediated by inflammation or the immune system, in some instances the immune system may play an important role in the degenerative process. Furthermore, it has become clear that the immune system itself may have beneficial effects in nervous system diseases considered neurodegenerative. Immunotherapeutic approaches designed to induce a humoral immune response have recently been developed for the treatment of Alzheimer's disease. These studies have led to human trials that resulted in both beneficial and adverse effects. In animal models, it has also been shown that immunotherapy designed to induce a cellular immune response may be of benefit in central nervous system injury, although T cells may have either a beneficial or detrimental effect depending on the type of T cell response induced. These areas provide a new avenue for exploring immune system-based therapy of neurodegenerative diseases and will be discussed here with a primary focus on Alzheimer's disease. We will also discuss how these approaches affect microglia activation, which plays a key role in therapy of such diseases.     

Earthquake prediction: modeling the anomalous vp/vs source region

Soviet observations of anomalously low values of the ratio of the compressional wave velocity to the shear wave velocity (V(p)/ V(s)) in a restricted volume around the locus of a future earthquake are duplicated by models based on the dilatancy hypothesis. In nature the cracks that cause the dilation may be oriented, leading to anisotropic seismic wave propagation in the anomalous region. The models show that vertical cracks are most effective in producing the observed effects, but that a slightly higher density of randomly oriented cracks will yield similar effects. The premonitory observations at Blue Mountain Lake, New York, are also duplicated by the models. These models demonstrate that V(p)/V(s) measured at the surface is not that of the anomalous zone, but is related to it by a transfer function, involving the shape and velocity gradient of the zone boundary.     

Biologically based computational models of high-level cognition

Computer models based on the detailed biology of the brain can help us understand the myriad complexities of human cognition and intelligence. Here, we review models of the higher level aspects of human intelligence, which depend critically on the prefrontal cortex and associated subcortical areas. The picture emerging from a convergence of detailed mechanistic models and more abstract functional models represents a synthesis between analog and digital forms of computation. Specifically, the need for robust active maintenance and rapid updating of information in the prefrontal cortex appears to be satisfied by bistable activation states and dynamic gating mechanisms. These mechanisms are fundamental to digital computers and may be critical for the distinctive aspects of human intelligence.     

Stability of Perovskite (MgSiO3) in the Earth's Mantle

Available thermodynamic data and seismic models favor perovskite (MgSiO3) as the stable phase in the mantle. MgSiO3 was heated at temperatures from 1900 to 3200 kelvin with a Nd-YAG laser in diamond-anvil cells to study the phase relations at pressures from 45 to 100 gigapascals. The quenched products were studied with synchrotron x-ray radiation. The results show that MgSiO3 broke down to a mixture of MgO (periclase) and SiO2 (stishovite or an unquenchable polymorph) at pressures from 58 to 85 gigapascals. These results imply that perovskite may not be stable in the lower mantle and that it might be necessary to reconsider the compositional and density models of the mantle.     

Amazon forests green-up during 2005 drought

Coupled climate-carbon cycle models suggest that Amazon forests are vulnerable to both long- and short-term droughts, but satellite observations showed a large-scale photosynthetic green-up in intact evergreen forests of the Amazon in response to a short, intense drought in 2005. These findings suggest that Amazon forests, although threatened by human-caused deforestation and fire and possibly by more severe long-term droughts, may be more resilient to climate changes than ecosystem models assume.     

Violently active galaxies: the search for the energy machine

The energy source in these galaxies will be shown to be a black hole, I think, even though it may take 100 years before we have proven it.-MARTIN REES, at the Institute of Astronomy in Cambridge, England I think it will take 1000 years and we may very well be on the wrong track. These [black hole] models are getting into the textbooks now, but there is never anything testable and people are working on smaller and smaller pieces of the problem.- GEOFFREY BURBIDGE, at the Univeristy of California, San Diego, and soon to assume the post of head of the Kitt Peak National Observatory in Tucson, Arizona REES: I agree, but I would argue that the way we are going about it is the most productive approach, even though the modelers may be getting the illusory satisfaction of a Ptolomean theorist who adds another epicycle. BURBRIDGE: I'm glad to hear you say that, Martin. The trouble is that so many people take these things more seriously than you do.     

The ecological context of life history evolution

There is now a good theoretical understanding of life history evolution, and detailed explicit optimality models have been constructed. These present a challenge for empirical work examining some of the assumptions, such as the extent and mechanisms of the costs of growth and reproduction. In addition, there is an obvious need for comparative tests of the models. These tests, properly applied, may be particularly informative because they can deal with multiple independent variables, including ecological variables, and can reveal broad trends against a background of constraints on optima and the rate of evolutionary approach to them. Life histories are the probabilities of survival and the rates of reproduction at each age in the life-span. Reproduction is costly, so that fertility at all ages cannot simultaneously be maximized by natural selection. Allocation of reproductive effort has evolved in response to the demographic impact of different environments but is constrained by genetic variance and evolutionary history.     

Microbiology. Simple hosts may help reveal how bacteria infect cells

Important human pathogens invade and harm simple organisms. What's more, these infections require many of the same bacterial genes needed to make mammals sick. These observations suggest that even though simple organisms aren't perfect models for complex hosts such as mammals, the basic mechanisms by which bacteria establish infections in the various organisms may be similar. As a result, the work may help microbiologists identify the host proteins involved in infections, thereby providing potential new targets for antibacterial drugs.     

Applications of open geospatial web services in precision agriculture: a review

Precision agriculture requires the collection, storage, sharing and analysis of large quantities of spatially referenced data. For this data to be effectively used, it must be transferred between different hardware, software and organisations. These data flows currently present a hurdle to uptake of precision agriculture as the multitude of data models, formats, interfaces and reference systems in use result in incompatibilities. This paper presents work on applying standards from the Open Geospatial Consortium and related initiatives to automate agricultural data processing. The selected use-cases demonstrate how such standards may be used to improve the inter-operability of data and software in precision agriculture.     

The politics of agricultural abundance

Agriculture should be viewed not as an industry but rather as a set of sectors organized around region, commodity, and institution. As such, agriculture adjusts well to a situation of “abundance” (excess supplies of major commodities). Although these sector interests are often referred to as “special interests,” they have effectively used public policy to generate agricultural development, and will continue to have a developmental impulse. Sector interests will, therefore, resist most proposals based on macrosystem perspectives which would reduce government support for agricultural development. These sectors will continue to be quite influential in deciding agricultural policy, though they will find it possible to adjust not only to “abundance” in the market place, but also to such political constraints as may be imposed in pursuit of such goals as consumer health, soil conservation, and environmental preservation.     

An experimental study of homophily in the adoption of health behavior

How does the composition of a population affect the adoption of health behaviors and innovations? Homophily--similarity of social contacts--can increase dyadic-level influence, but it can also force less healthy individuals to interact primarily with one another, thereby excluding them from interactions with healthier, more influential, early adopters. As a result, an important network-level effect of homophily is that the people who are most in need of a health innovation may be among the least likely to adopt it. Despite the importance of this thesis, confounding factors in observational data have made it difficult to test empirically. We report results from a controlled experimental study on the spread of a health innovation through fixed social networks in which the level of homophily was independently varied. We found that homophily significantly increased overall adoption of a new health behavior, especially among those most in need of it.     

Molecular models for DNA damaged by photoreaction

Structural models of a DNA molecule containing a radiation-induced psoralen cross-link and of a DNA containing a thymine photodimer were constructed by applying energy-minimization techniques and model-building procedures to data from x-ray crystallographic studies. The helical axes of the models show substantial kinking and unwinding at the sites of the damage, which may have long-range as well as local effects arising from the concomitant changes in the supercoiling and overall structure of the DNA. The damaged areas may also serve as recognition sites for repair enzymes. These results should help in understanding the biologic effects of radiation-induced damage on cells.     

果品主要真菌毒素污染检测、风险评估与控制研究进展

果品在生产、贮运过程中易发生真菌性病害,不但可引起腐烂或腐败,带来严重的经济损失,部分霉菌还可能产生真菌毒素对人体健康造成潜在危害。真菌毒素是一类由丝状真菌在适宜条件下产生的有毒次级代谢产物,是继农药残留、重金属污染后,影响果品质量安全的又一类关键风险因子,具有强毒性。大量研究表明,真菌毒素可致DNA损伤,低浓度下即可对人和动物健康造成危害,使肝脏、肾脏和胃肠道发生病变,并且可致癌、致畸、致突变等,研究真菌毒素的污染状况,进行精准检测、风险评估和控制,对于果品质量安全研究具有重要意义。展青霉素(Patulin,PAT)、黄曲霉毒素(Aflatoxins,AF)、链格孢毒素(Alternaria toxins)和赭曲霉毒素A(Ochratoxin A,OTA)是存在于果品中的主要真菌毒素种类,国际癌症研究机构(IARC)分别将PAT、AFB1、AFM1和OTA列为第3类、1类、2B类和2B类致癌物质。通常果品中检出的真菌毒素含量极低,因此对检测方法的要求较高,目前主要的分析方法有薄层色谱法、高效液相色谱(含质谱联用)技术、气相色谱(含质谱联用)技术、毛细管电泳技术等,但往往由于化学结构和性质各异,无法采用一种标准方法完成对所有真菌毒素的定量测定。因此,筛选准确、高效、快速的检测方法也是该领域当今的研究热点。迄今为止,已有80个国家和地区制定了果品中真菌毒素的限量标准来保护消费者健康,但均未涉及链格孢霉毒素。许多国家均不同程度地开展了真菌毒素风险评估研究,基于毒理学数据的评估结果表明,大多情形下通过果品摄入的真菌毒素水平极低,不会对居民健康产生危害。果品中的真菌毒素可采用化学、物理、生物等方法进行防治、降解和控制,但无法将被真菌毒素污染后产品中的毒素完全脱除,果品中真菌毒素污染重在"防"而非"除"。本文从果品中主要真菌毒素的种类、污染状况、毒性、检测方法、限量标准、风险评估及控制技术等方面进行概述,同时,对果品中真菌毒素的重点研究方向进行了展望,以期为该领域研究者提供参考。     

Three-dimensional instabilities of mantle convection with multiple phase transitions

The effects of multiple phase transitions on mantle convection are investigated by numerical simulations that are based on three-dimensional models. These simulations show that cold sheets of mantle material collide at junctions, merge, and form a strong downflow that is stopped temporarily by the transition zone. The accumulated cold material gives rise to a strong gravitational instability that causes the cold mass to sink rapidly into the lower mantle. This process promotes a massive exchange between the lower and upper mantles and triggers a global instability in the adjacent plume system. This mechanism may be cyclic in nature and may be linked to the generation of superplumes.     

乳头溢液及诊断方法

乳头溢液是乳腺外科常见的就诊原因,既可以发生于乳腺病变,也可能来源于乳腺外因素,甚至是正常的生理现象.随着人们对乳腺健康重视程度的提高,乳头溢液的诊查手段也逐渐丰富进步,了解各种方法的原理和特点,并加以扬长避短的应用是正确诊治的前提,会使我们的工作事半功倍,十分必要.     

Severely impaired adipsin expression in genetic and acquired obesity

Adipsin, a serine protease homolog, is synthesized and secreted by adipose cells and is found in the bloodstream. The expression of adipsin messenger RNA (mRNA) and protein was analyzed in rodents during metabolic perturbations and in several experimental models of obesity. Adipsin mRNA abundance is increased in adipose tissue during fasting in normal rats and in diabetes due to streptozotocin-induced insulin deficiency. Adipsin mRNA abundance decreased during the continuous infusion of glucose, which induces a hyperglycemic, hyperinsulinemic state that is accompanied by an increased adipose mass; it is suppressed (greater than 100-fold) in two strains of genetically obese mice (db/db and ob/ob), compared to their congenic counterparts, and is also reduced when obesity is induced chemically by injection of monosodium glutamate into newborn mice. Circulating adipsin protein is decreased in these animal models of obesity, as determined by immunoblotting with antisera to adipsin. Little change in adipsin expression is observed in a model of obesity obtained by pure overfeeding of normal rats (cafeteria model). These data suggest a possible role for adipsin in the above-mentioned disordered metabolic states, and raise the possibility that adipsin expression may be used to distinguish obesities that arise from certain genetic or metabolic defects from those that result from pure overfeeding.     

Atmospheric warming and the amplification of precipitation extremes

Climate models suggest that extreme precipitation events will become more common in an anthropogenically warmed climate. However, observational limitations have hindered a direct evaluation of model-projected changes in extreme precipitation. We used satellite observations and model simulations to examine the response of tropical precipitation events to naturally driven changes in surface temperature and atmospheric moisture content. These observations reveal a distinct link between rainfall extremes and temperature, with heavy rain events increasing during warm periods and decreasing during cold periods. Furthermore, the observed amplification of rainfall extremes is found to be larger than that predicted by models, implying that projections of future changes in rainfall extremes in response to anthropogenic global warming may be underestimated.     

昆虫种群生命系统研究的状态方程

应用状态空间法研究系统的控制,不仅有利于把系统划分为若干组分或子系统对各种因子分别进行动态描述,同时更好地解决多输入和多输出的研究技术,因而有可能成为种群生命系统控制研究的重要手段。本文拟通过网络模型着重讨论适应于昆虫种群研究的状态空间方程的建立问题。     

Atmospheric halocarbons, hydrocarbons, and sulfur hexafluoride: global distributions, sources, and sinks

The global distribution of fluorocarbon-12 and fluorocarbon-11 is used to establish a relatively fast interhemispheric exchange rate of 1 to 1.2 years. Atmospheric residence times of 65 to 70 years for fluorocarbon-12 and 40 to 45 years for fluorocarbon-l1 best fit the observational data. These residence times rule out the possibility of any significant missing sinks that may prevent these fluorocarbons from entering the stratosphere. Atmospheric measurements of methyl chloroform support an 8-to 10-year residence time and suggest global average hydroxyl radical (HO) concentrations of 3 x 10(5) to 4 x 10(5) molecules per cubic centimeter. These are a factor of 5 lower than predicted by models. Additionally, methyl chloroform global distribution supports Southern Hemispheric HO levels that are a factor of 1.5 or more larger than the Northern Hemispheric values. The long residence time and the rapid growth of methyl chloroform cause it to be a potentially significant depleter of stratospheric ozone. The oceanic sink for atmospheric carbon tetrachloride is about half as important as the stratospheric sink. A major source of methyl chloride (3 x 10(12)grams per year), sufficient to account for nearly all the atmospheric methyl chloride, has been identified in the ocean.     

Persistence of transients in spatially structured ecological models

Simple discrete-time ecological models for a species with alternating reproduction and dispersal are shown to have complex transient dynamics. If the density dependence (nonlinearity) is strong enough, then the time required to reach the final dynamics is usually very long, approaching thousands of generations, and there are typically very sudden changes in the form of the dynamics. Apparent chaos can change to cycles or vice versa. These results are consistent with observed sudden changes in the form of the dynamics of a single species and imply that transient dynamics of ecological models may be more relevant than long-term behavior.