696 research outputs found

    A Nation Deceived: How Schools Hold Back America's Brightest Students, Volume II

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    Provides a comprehensive review of research on the academic acceleration of gifted students

    A Nation Deceived: How Schools Hold Back America's Brightest Students, Volume I

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    Identifies twelve main reasons why schools have held back students. Includes examples of effective acceleration practice, attests to the cost effectiveness of acceleration, and provides specific ideas for promoting accelerative practices

    Sudden Acquired Retinal Degeneration in the Dog: Clinical and Morphologic Characterization of the Silent Retina Syndrome

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    Adult dogs occasionally become suddenly, totally and permanently blind. If examined soon after the onset of blindness, the dogs show no ophthalmologic evidence of disease sufficient to account for their problem and are usually in otherwise good health. The hallmark of this sudden, acquired retinal degeneration (SARD), that establishes it as a retinopathy, and distinguishes it from neurological disease, is the extinguished electroretinogram. The syndrome has been termed Silent Retina Syndrome and Metabolic Toxic Retinopathy . Although uncommon, SARD has been diagnosed with increased frequency in recent years. Little retinal tissue has, however, become available for histopathologic characterization of the disease. This report reviews twenty six cases of SARD examined by the authors at the Veterinary Hospital, University of Pennsylvania (VHUP). The histopathology and ultrastructural morphology of four cases are described

    The ion seeps tonight: Assessing ionic transport in multilayered nanocomposites

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    Figure 6 – Schematic of cation (M+) transport through an organized multilayered composite. Controlling ion transport across membranes and interfaces is one of the central themes challenging technological pursuits ranging from corrosion to energy storage and chemical separations. Here, we present several examples in which we have studied the application of multilayer nanocomposites to regulate ion transport. These composites comprise organized layers of functional or structural elements, integrated within composites such that the specific nanostructure and composition of the materials play important roles in defining ionic interactions and mobility. In cases such as corrosion inhibition, thin film composite coatings are intended to block ionic transport, retarding deleterious corrosion reactions. We show that by manipulating the materials chemistry of highly organized polymer clay nanocomposite thin film barriers, it is possible to significantly increase corrosion resistance of steel samples in a simulated sea water environment. In contrast, for energy storage applications such as batteries, composite separators capable of rapid ionic diffusion are desired for high current performance. We explore how layered composite structures may provide effective ion diffusion planes, leading to promising ionic conductivity in new solid state separators. Finally, in chemical separations, the selective transport of ions becomes important. We examine how manipulating the chemical and electrostatic composition of layered polyelectrolyte materials leads to preferential cation transport through these composite structures, a key property for an effective separations membrane. These different technologies exemplify how the principles governing ion transport through multilayered materials can be adapted for widely varied applications, and they illustrate the potential for this materials development strategy to enable new classes of functional composite materials. Please click Additional Files below to see the full abstract

    Methylome-wide Analysis of Chronic HIV Infection Reveals Five-Year Increase in Biological Age and Epigenetic Targeting of HLA

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    HIV-infected individuals are living longer on antiretro-viral therapy, but many patients display signs that in some ways resemble premature aging. To investigate and quantify the impact of chronic HIV infection on aging, we report a global analysis of the whole-blood DNA methylomes of 137 HIV+ individuals under sustained therapy along with 44 matched HIV- individuals. First,we develop and validate epigenetic models of aging that are independent of blood cell composition. Using these models, we find that both chronic and recent HIV infection lead to an average aging advancement of 4.9 years, increasing expected mortality risk by 19%. In addition, sustained infection results in global deregulation of the methylome across \u3e80,000 CpGs and specific hypomethylation of the region encoding the human leukocyte antigen locus (HLA).We find that decreased HLA methylation is predictive of lower CD4/CD8T cell ratio, linking molecular aging, epigenetic regulation, and disease progression

    B-lymphocyte stimulator/a proliferation-inducing ligand heterotrimers are elevated in the sera of patients with autoimmune disease and are neutralized by atacicept and B-cell maturation antigen-immunoglobulin

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    Abstract Introduction B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) are members of the tumor necrosis factor (TNF) family that regulate B-cell maturation, survival, and function. They are overexpressed in a variety of autoimmune diseases and reportedly exist in vivo not only as homotrimers, but also as BLyS/APRIL heterotrimers. Methods A proprietary N-terminal trimerization domain was used to produce recombinant BLyS/APRIL heterotrimers. Heterotrimer biologic activity was compared with that of BLyS and APRIL in a 4-hour signaling assay by using transmembrane activator and CAML interactor (TACI)-transfected Jurkat cells and in a 4-day primary human B-cell proliferation assay. A bead-based immunoassay was developed to quantify native heterotrimers in human sera from healthy donors (n = 89) and patients with systemic lupus erythematosus (SLE; n = 89) or rheumatoid arthritis (RA; n = 30). Heterotrimer levels were compared with BLyS and APRIL homotrimer levels in a subset of these samples. Results The recombinant heterotrimers consisted mostly of one BLyS and two APRIL molecules. Heterotrimer signaling did not show any significant difference compared with APRIL in the TACI-Jurkat assay. Heterotrimers were less-potent inducers of B-cell proliferation than were homotrimeric BLyS or APRIL (EC50, nMol/L: BLyS, 0.02; APRIL, 0.17; heterotrimers, 4.06). The soluble receptor fusion proteins atacicept and B-cell maturation antigen (BCMA)-immunoglobulin (Ig) neutralized the activity of BLyS, APRIL, and heterotrimers in both cellular assays, whereas B-cell activating factor belonging to the TNF family receptor (BAFF-R)-Ig neutralized only the activity of BLyS. In human sera, significantly more patients with SLE had detectable BLyS (67% versus 18%; P < 0.0001), APRIL (38% versus 3%; P < 0.0002), and heterotrimer (27% versus 8%; P = 0.0013) levels compared with healthy donors. Significantly more patients with RA had detectable APRIL, but not BLyS or heterotrimer, levels compared with healthy donors (83% versus 3%; P < 0.0001). Heterotrimer levels weakly correlated with BLyS, but not APRIL, levels. Conclusions Recombinant BLyS/APRIL heterotrimers have biologic activity and are inhibited by atacicept and BCMA-Ig, but not by BAFF-R-Ig. A novel immunoassay demonstrated that native BLyS/APRIL heterotrimers, as well as BLyS and APRIL homotrimers, are elevated in patients with autoimmune diseases

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    Pulmonary function measures predict mortality differently in IPF versus combined pulmonary fibrosis and emphysema

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    The composite physiologic index (CPI) was derived to represent the extent of fibrosis on high-resolution computed tomography (HRCT), adjusting for emphysema in patients with idiopathic pulmonary fibrosis (IPF). We hypothesised that longitudinal change in CPI would better predict mortality than forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) or diffusing capacity of the lung for carbon monoxide (DLCO) in all patients with IPF, and especially in those with combined pulmonary fibrosis and emphysema (CPFE). Cox proportional hazard models were performed on pulmonary function data from IPF patients at baseline (n=321), 6 months (n=211) and 12 months (n=144). Presence of CPFE was determined by HRCT. A five-point increase in CPI over 12 months predicted subsequent mortality (HR 2.1, p=0.004). At 12 months, a 10% relative decline in FVC, a 15% relative decline in DLCO or an absolute increase in CPI of five points all discriminated median survival by 2.1 to 2.2 yrs versus patients with lesser change. Half our cohort had CPFE. In patients with moderate/severe emphysema, only a 10% decline in FEV1 predicted mortality (HR 3.7, p=0.046). In IPF, a five-point increase in CPI over 12 months predicts mortality similarly to relative declines of 10% in FVC or 15% in DLCO. For CPFE patients, change in FEV1 was the best predictor of mortality.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91949/1/2011 ERJ - Pulmonary function measures predict mortality differently in IPF versus combined pulmonary fibrosis and emphysema.pd
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