Undisturbed clear day diurnal wind and temperature pattern in northeastern Colorado

Bibliography: pages [68]-69.Sponsored by the National Oceanic and Atmospheric Administration through the Cooperative Institute for Research in the Atmosphere (CIRA) NA80-RAC-0021

Effect of age and cytoskeletal elements on the indentation-dependent mechanical properties of chondrocytes.

Articular cartilage chondrocytes are responsible for the synthesis, maintenance, and turnover of the extracellular matrix, metabolic processes that contribute to the mechanical properties of these cells. Here, we systematically evaluated the effect of age and cytoskeletal disruptors on the mechanical properties of chondrocytes as a function of deformation. We quantified the indentation-dependent mechanical properties of chondrocytes isolated from neonatal (1-day), adult (5-year) and geriatric (12-year) bovine knees using atomic force microscopy (AFM). We also measured the contribution of the actin and intermediate filaments to the indentation-dependent mechanical properties of chondrocytes. By integrating AFM with confocal fluorescent microscopy, we monitored cytoskeletal and biomechanical deformation in transgenic cells (GFP-vimentin and mCherry-actin) under compression. We found that the elastic modulus of chondrocytes in all age groups decreased with increased indentation (15-2000 nm). The elastic modulus of adult chondrocytes was significantly greater than neonatal cells at indentations greater than 500 nm. Viscoelastic moduli (instantaneous and equilibrium) were comparable in all age groups examined; however, the intrinsic viscosity was lower in geriatric chondrocytes than neonatal. Disrupting the actin or the intermediate filament structures altered the mechanical properties of chondrocytes by decreasing the elastic modulus and viscoelastic properties, resulting in a dramatic loss of indentation-dependent response with treatment. Actin and vimentin cytoskeletal structures were monitored using confocal fluorescent microscopy in transgenic cells treated with disruptors, and both treatments had a profound disruptive effect on the actin filaments. Here we show that disrupting the structure of intermediate filaments indirectly altered the configuration of the actin cytoskeleton. These findings underscore the importance of the cytoskeletal elements in the overall mechanical response of chondrocytes, indicating that intermediate filament integrity is key to the non-linear elastic properties of chondrocytes. This study improves our understanding of the mechanical properties of articular cartilage at the single cell level

The Health Status of Southern Children: A Neglected Regional Disparity

Purpose: Great variations exist in child health outcomes among states in the United States, with southern states consistently ranked among the lowest in the country. Investigation of the geographical distribution of children’s health status and the regional factors contributing to these outcomes has been neglected. We attempted to identify the degree to which region of residence may be linked to health outcomes for children with the specific aim of determining whether living in the southern region of the United States is adversely associated with children’s health status. Methods: A child health index (CHI) that ranked each state in the United States was computed by using statespecific composite scores generated from outcome measures for a number of indicators of child health. Five indicators for physical health were chosen (percent low birth weight infants, infant mortality rate, child death rate, teen death rate, and teen birth rates) based on their historic and routine use to define health outcomes in children. Indicators were calculated as rates or percentages. Standard scores were calculated for each state for each health indicator by subtracting the mean of the measures for all states from the observed measure for each state. Indicators related to social and economic status were considered to be variables that impact physical health, as opposed to indicators of physical health, and therefore were not used to generate the composite child health score. These variables were subsequently examined in this study as potential confounding variables. Mapping was used to redefine regional groupings of states, and parametric tests (2-sample t test, analysis of means, and analysis-of-variance F tests) were used to compare the means of the CHI scores for the regional groupings and test for statistical significance. Multiple regression analysis computed the relationship of region, social and economic indicators, and race to the CHI. Simple linear-regression analyses were used to assess the individual effect of each indicator. Results: A geographic region of contiguous states, characterized by their poor child health outcomes relative to other states and regions of the United States, exists within the “Deep South” (Mississippi, Louisiana, Arkansas, Tennessee, Alabama, Georgia, North Carolina, South Carolina, and Florida). This Deep-South region is statistically different in CHI scores from the US Census Bureau– defined grouping of states in the South. The mean of CHI scores for the Deep-South region was \u3e1 SD below the mean of CHI scores for all states. In contrast, the CHI score means for each of the other 3 regions were all above the overall mean of CHI scores for all states. Regression analysis showed that living in the Deep- South region is a stronger predictor of poor child health outcomes than other consistently collected and reported variables commonly used to predict children’s health. Conclusions: The findings of this study indicate that region of residence in the United States is statistically related to important measures of children’s health and may be among the most powerful predictors of child health outcomes and disparities. This clarification of the poorer health status of children living in the Deep South through spatial analysis is an essential first step for developing a better understanding of variations in the health of children. Similar to early epidemiology work linking geographic boundaries to disease, discovering the mechanisms/pathways/causes by which region influences health outcomes is a critical step in addressing disparities and inequities in child health and one that is an important and fertile area for future research. The reasons for these disparities may be complex and synergistically related to various economic, political, social, cultural, and perhaps even environmental (physical) factors in the region. This research will require the use and development of new approaches and applications of spatial analysis to develop insights into the societal, environmental, and historical determinants of child health that have been neglected in previous child health outcomes and policy research. The public policy implications of the findings in this study are substantial. Few, if any, policies identify these children as a high-risk group on the basis of their region of residence. A better understanding of the depth and breadth of disparities in health, education, and other social outcomes among and within regions of the United States is necessary for the generation of policies that enable policy makers to address and mitigate the factors that influence these disparities. Defining and clarifying the regional boundaries is also necessary to better inform public policy decisions related to resource allocation and the prevention and/or mitigation of the effects of region on child health. The identification of the Deep South as a clearly defined sub-region of the Census Bureau’s regional definition of the South suggests the need to use more culturally and socially relevant boundaries than the Census Bureau regions when analyzing regional data for policy development

Apparatus and Method for Remote Assessment and Therapy Management in Medical Devices via Interface Systems

A remote medical assessment and therapy management apparatus comprising a center user interface, a center computer coupleable with the center user interface. The center computer displays information via the center user interface for use in developing a therapeutic prescription and receives therapeutic control inputs from a user. A remote device includes a medical diagnostic instrument for acquiring biophysical data from a patient, a medical therapeutic instrument that provides a therapy to the patient, and a remote computer that receives diagnostic signals from the diagnostic instrument and transmits therapeutic control signals to the therapeutic instrument. A network interface is connected between the first center computer and the remote computer and transmits diagnostic signals from the remote computer to the center computer and control signals from the center computer to the therapeutic instrument via the remote computer

Nod1 signaling overcomes resistance of S. pneumoniae to opsonophagocytic killing

Airway infection by the Gram-positive pathogen Streptococcus pneumoniae (Sp) leads to recruitment of neutrophils but limited bacterial killing by these cells. Co-colonization by Sp and a Gram-negative species, Haemophilus influenzae (Hi), provides sufficient stimulus to induce neutrophil and complement-mediated clearance of Sp from the mucosal surface in a murine model. Products from Hi, but not Sp, also promote killing of Sp by ex vivo neutrophil-enriched peritoneal exudate cells. Here we identify the stimulus from Hi as its peptidoglycan. Enhancement of opsonophagocytic killing was facilitated by signaling through nucleotide-binding oligomerization domain-1 (Nod1), which is involved in recognition of γ-D-glutamyl-meso-diaminopimelic acid (meso-DAP) contained in cell walls of Hi but not Sp. Neutrophils from mice treated with Hi or compounds containing meso-DAP, including synthetic peptidoglycan fragments, showed increased Sp killing in a Nod1-dependent manner. Moreover, Nod1-/- mice showed reduced Hi-induced clearance of Sp during co-colonization. These observations offer insight into mechanisms of microbial competition and demonstrate the importance of Nod1 in neutrophil-mediated clearance of bacteria in vivo

Bioresorbable Polylactide Interbody Implants in an Ovine Anterior Cervical Discectomy and Fusion Model: Three-Year Results

Study Design. In vivo study of anterior discectomy and fusion using a bioresorbable 70:30 poly(l-lactide-co-d,l-lactide) interbody implant in an ovine model. Objective. To evaluate the efficacy of the polylactide implant to function as an interbody fusion device, and to assess the tissue reaction to the material during the resorption process. Summary of Background Data. The use of polylactide as a cervical interbody implant has several potential advantages when compared with traditional materials. Having an elastic modulus very similar to bone minimizes the potential for stress shielding, and as the material resorbs additional loading is transferred to the developing fusion mass. Although preclinical and clinical studies have demonstrated the suitability of polylactide implants for lumbar interbody fusion, detailed information on cervical anterior cervical discectomy and fusion (ACDF) with polylactide devices is desirable. Methods. Single level ACDF was performed in 8 skeletally mature ewes. Bioresorbable 70:30 poly (l-lactide-co-d,l-lactide) interbody implants packed with autograft were used with single-level metallic plates. Radiographs were made every 3 months up to 1 year, and yearly thereafter. The animals were killed at 6 months (3 animals), 12 months (3 animals), and 36 months (2 animals). In addition to the serial plain radiographs, the specimens were evaluated by nondestructive biomechanical testing and undecalcified histologic analysis. Results. The bioresorbable polylactide implants were effective in achieving interbody fusion. The 6-month animals appeared fused radiographically and biomechanically, whereas histologic sections demonstrated partial fusion (in 3 of 3 animals). Radiographic fusion was confirmed histologically and biomechanically at 12 months (3 of 3 animals) and 36 months (2 of 2 animals). A mild chronic inflammatory response to the resorbing polylactide implant was observed at both 6 months and 12 months. At 36 months, the operative levels were solidly fused and the implants were completely resorbed. No adverse tissue response was observed in any animal at any time period. Conclusion. Interbody fusion was achieved using bioresorbable polylactide implants, with no evidence of implant collapse, extrusion, or adverse tissue response to the material. The use of polylactide as a cervical interbody device appears both safe and effective based on these ACDF animal model results

Age and Prostate-Specific Antigen Level Prior to Diagnosis Predict Risk of Death from Prostate Cancer.

A single early prostate-specific antigen (PSA) level has been correlated with a higher likelihood of prostate cancer diagnosis and death in younger men. PSA testing in older men has been considered of limited utility. We evaluated prostate cancer death in relation to age and PSA level immediately prior to prostate cancer diagnosis. Using the Veterans Affairs database, we identified 230,081 men aged 50-89 years diagnosed with prostate cancer and at least one prior PSA test between 1999 and 2009. Prostate cancer-specific death over time was calculated for patients stratified by age group (e.g., 50-59 years, through 80-89 years) and PSA range at diagnosis (10 ranges) using Kaplan-Meier methods. Risk of 10-year prostate cancer mortality across age and PSA was compared using log-rank tests with a Bonferroni adjustment for multiple testing. 10.5% of men diagnosed with prostate cancer died of cancer during the 10-year study period (mean follow-up = 3.7 years). Higher PSA values prior to diagnosis predict a higher risk of death in all age groups (p < 0.0001). Within the same PSA range, older age groups are at increased risk for death from prostate cancer (p < 0.0001). For PSA of 7-10 ng/mL, cancer-specific death, 10 years after diagnosis, increased from 7% for age 50-59 years to 51% for age 80-89 years. Men older than 70 years are more likely to die of prostate cancer at any PSA level than younger men, suggesting prostate cancer remains a significant problem among older men (even those aged 80+) and deserves additional study

Chronic rejection of mouse kidney allografts

Chronic rejection of mouse kidney allografts.BackgroundChronic renal allograft rejection is the leading cause of late graft failure. However, its pathogenesis has not been defined.MethodsTo explore the pathogenesis of chronic rejection, we studied a mouse model of kidney transplantation and examined the effects of altering the expression of donor major histocompatibility complex (MHC) antigens on the development of chronic rejection.ResultsWe found that long-surviving mouse kidney allografts develop pathological abnormalities that resemble chronic rejection in humans. Furthermore, the absence of MHC class I or class II antigens did not prevent the loss of graft function nor alter the pathological characteristics of chronic rejection. Expression of transforming growth factor-β (TGF-β), a pleiotropic cytokine suggested to play a role in chronic rejection, was markedly enhanced in control allografts compared with isografts. However, TGF-β up-regulation was significantly blunted in MHC-deficient grafts. Nonetheless, these differences in TGF-β expression did not affect the character of chronic rejection, including intrarenal accumulation of collagens.ConclusionsReduced expression of either class I or II direct allorecognition pathways is insufficient to prevent the development of chronic rejection, despite a reduction in the levels of TGF-β expressed in the allograft. This suggests that the severity of chronic rejection is independent of the level of MHC disparity between donor and recipient and the level of TGF-β expression within the allograft

Turbulent Concentration of MM-Size Particles in the Protoplanetary Nebula: Scaled-Dependent Multiplier Functions

The initial accretion of primitive bodies (asteroids and TNOs) from freely-floating nebula particles remains problematic. Here we focus on the asteroids where constituent particle (read "chondrule") sizes are observationally known; similar arguments will hold for TNOs, but the constituent particles in those regions will be smaller, or will be fluffy aggregates, and are unobserved. Traditional growth-bysticking models encounter a formidable "meter-size barrier" [1] (or even a mm-cm-size barrier [2]) in turbulent nebulae, while nonturbulent nebulae form large asteroids too quickly to explain long spreads in formation times, or the dearth of melted asteroids [3]. Even if growth by sticking could somehow breach the meter size barrier, other obstacles are encountered through the 1-10km size range [4]. Another clue regarding planetesimal formation is an apparent 100km diameter peak in the pre-depletion, pre-erosion mass distribution of asteroids [5]; scenarios leading directly from independent nebula particulates to this size, which avoid the problematic m-km size range, could be called "leapfrog" scenarios [6-8]. The leapfrog scenario we have studied in detail involves formation of dense clumps of aerodynamically selected, typically mm-size particles in turbulence, which can under certain conditions shrink inexorably on 100-1000 orbit timescales and form 10-100km diameter sandpile planetesimals. The typical sizes of planetesimals and the rate of their formation [7,8] are determined by a statistical model with properties inferred from large numerical simulations of turbulence [9]. Nebula turbulence can be described by its Reynolds number Re = L/eta sup(4/3), where L = ETA alpha sup (1/2) the largest eddy scale, H is the nebula gas vertical scale height, and the nebula turbulent viscosity parameter, and is the Kolmogorov or smallest scale in turbulence (typically about 1km), with eddy turnover time t. In the nebula, Re is far larger than any numerical simulation can handle, so some physical model is needed to extend the results of numerical simulations to nebula conditions

Requirement for PCNA in DNA Mismatch Repair at a Step Preceding DNA Resynthesis

Abstractid system was used to screen yeast and human expression libraries for proteins that interact with mismatch repair proteins. PCNA was recovered from both libraries and shown in the case of yeast to interact with both MLH1 and MSH2. A yeast strain containing a mutation in the PCNA gene had a strongly elevated mutation rate in a dinucleotide repeat, and the rate was not further elevated in a strain also containing a mutation in MLH1. Mismatch repair activity was examined in human cell extracts using an assay that does not require DNA repair synthesis. Activity was inhibited by p21 WAF1 or a p21 peptide, both of which bind to PCNA, and activity was restored to inhibited reactions by addition of PCNA. The data suggest a PCNA requirement in mismatch repair at a step preceding DNA resynthesis. The ability of PCNA to bind to MLH1 and MSH2 may reflect linkage between mismatch repair and replication and may be relevant to the roles of mismatch repair proteins in other DNA transactions