Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse.

Amyloid-beta peptide (Abeta) seems to have a central role in the neuropathology of Alzheimer's disease (AD). Familial forms of the disease have been linked to mutations in the amyloid precursor protein (APP) and the presenilin genes. Disease-linked mutations in these genes result in increased production of the 42-amino-acid form of the peptide (Abeta42), which is the predominant form found in the amyloid plaques of Alzheimer's disease. The PDAPP transgenic mouse, which overexpresses mutant human APP (in which the amino acid at position 717 is phenylalanine instead of the normal valine), progressively develops many of the neuropathological hallmarks of Alzheimer's disease in an age- and brain-region-dependent manner. In the present study, transgenic animals were immunized with Abeta42, either before the onset of AD-type neuropathologies (at 6 weeks of age) or at an older age (11 months), when amyloid-beta deposition and several of the subsequent neuropathological changes were well established. We report that immunization of the young animals essentially prevented the development of beta-amyloid-plaque formation, neuritic dystrophy and astrogliosis. Treatment of the older animals also markedly reduced the extent and progression of these AD-like neuropathologies. Our results raise the possibility that immunization with amyloid-beta may be effective in preventing and treating Alzheimer's disease.     

Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population

The functional heart is comprised of distinct mesoderm-derived lineages including cardiomyocytes, endothelial cells and vascular smooth muscle cells. Studies in the mouse embryo and the mouse embryonic stem cell differentiation model have provided evidence indicating that these three lineages develop from a common Flk-1(+) (kinase insert domain protein receptor, also known as Kdr) cardiovascular progenitor that represents one of the earliest stages in mesoderm specification to the cardiovascular lineages. To determine whether a comparable progenitor is present during human cardiogenesis, we analysed the development of the cardiovascular lineages in human embryonic stem cell differentiation cultures. Here we show that after induction with combinations of activin A, bone morphogenetic protein 4 (BMP4), basic fibroblast growth factor (bFGF, also known as FGF2), vascular endothelial growth factor (VEGF, also known as VEGFA) and dickkopf homolog 1 (DKK1) in serum-free media, human embryonic-stem-cell-derived embryoid bodies generate a KDR(low)/C-KIT(CD117)(neg) population that displays cardiac, endothelial and vascular smooth muscle potential in vitro and, after transplantation, in vivo. When plated in monolayer cultures, these KDR(low)/C-KIT(neg) cells differentiate to generate populations consisting of greater than 50% contracting cardiomyocytes. Populations derived from the KDR(low)/C-KIT(neg) fraction give rise to colonies that contain all three lineages when plated in methylcellulose cultures. Results from limiting dilution studies and cell-mixing experiments support the interpretation that these colonies are clones, indicating that they develop from a cardiovascular colony-forming cell. Together, these findings identify a human cardiovascular progenitor that defines one of the earliest stages of human cardiac development.     

旅游城市的不确定性多目标环境规划优化模型框架研究

简要分析了旅游城市环境规划的特点,针对性地提出了一套不确定性模糊多目标旅游环境系统规划优化方法,这是首次将不确定性多目标规划方法应用于以旅游业发展为重点的城市环境规划领域。并相应地建立了旅游城市环境不确定性模糊多目标系统规划优化模型（ＩＦＭＯＰＯＭＴＵＥ）,既把各种环境要素和经济要素有机地整合入模型中,又充分考虑了旅游城市环境发展的不确定性,通过人机交互式方法,将专家和决策者的意见落实在模型参数上     

Testing for unreliable estimators and insignificant forecasts in combined forecasts

The reliability and precision of the weights used in combining individual forecasts, irrespective of the method of combination, is important in evaluating a combined forecast. The objective of this study is not to suggest the ‘best’ method of combining individual forecasts, but rather to propose exploratory procedures, that make use of all available sample information contained in the covariance matrix of individual forecast errors, to (1) detect if the weights used in combining forecasts are ‘reliable’ (and ‘stable’ if it is known that the covariance matrix of forecast errors is stationary over time) and (2) test for ‘insignificant’ individual forecasts used in forming a combined forecast. We present empirical applications using two-year sales and individual forecast data provided by a major consumer durables manufacturer to illustrate the feasibility of our proposed procedures.     

Obtaining common pruned trees

Given two or more dendrograms (rooted tree diagrams) based on the same set of objects, ways are presented of defining and obtaining common pruned trees. Bounds on the size of a largest common pruned tree are introduced, as is a categorization of objects according to whether they belong to all, some, or no largest common pruned trees. Also described is a procedure for regrafting pruned branches, yielding trees for which one can assess the reliability of the depicted relationships. The tree obtained by regrafting branches on to a largest common pruned tree is shown to contain all the classes present in the strict consensus tree. The theory is illustrated by application to two classifications of a set of forty-nine stratigraphical pollen spectra.This work was supported by the Science and Engineering Research Council. The authors are grateful to the referees for constructive criticisms of an earlier version of the paper, and to Dr. J.T. Henderson for advice on PASCAL.     

Am i using a systems approach?

Collaboration and cooperation within the systems community require a facility to aid recognition and appreciation of how individual contributions fit into the totality of systems practice. A framework to help in this is suggested, linked to characteristic concepts and techniques of three identified generations of systems approaches-two derived from a management-linked systems practice in the 1970s and late 1980s, the third from new attempts to design a better future.     

Early research on the biological effects of microwave radiation: 1940–1960

Two overriding considerations shaped the development of early research on the biological effects of microwave radiation—possible medical application (diathermy) and uncertainty about the hazards of exposure to radar. Reports in the late 1940s and early 1950s of hazards resulting from microwave exposure led to the near abandonment of medical research related to microwave diathermy at the same time that military and industrial concern over hazards grew, culminating in the massive research effort known as ‘the Tri-Service program’ (1957–1960). Both the early focus on medical application and the later search for hazards played important roles in dictating how this field of research developed as a science.