Improvement of the Fairbanks Atmospheric Carbon Monoxide Transport Model -- A Program for Calibration, Verification and Implementation

Completion Report Prepared for the Research Section, Alaska Department of Transportation and Public FacilitiesIn the early 70s, state, local and federal officials in Fairbanks, Alaska, became concerned with the rising incidence of high carbon monoxide episodes. Because of that concern, the Alaska Department of Highways (forerunner of the Department of Transportation and Public Facilities) and the Fairbanks North Star Borough requested that the Institute of Water Resources undertake a study to develop a computer model capability for understanding the transport of carbon monoxide and other pollutants within the Fairbanks airshed. The work was completed in June of 1976. Two publications (Carlson and Fox, 1976; Norton and Carlson, 1976) describe the initial development, documentation and implementation of the computer model. The model, ACOSP (Atmospheric Carbon monOxide Simulation Program), describes the two-dimensional behavior of pollutants in the atmosphere via solution of the convection-diffusion equation using the finite element method of numerical analysis

Effects of Thermal Discharge Upon a Subarctic Stream: Completion Report

The work upon which this report is based was supported in part by funds provided by the United States Department of Interior, Office of Water Research and Technology (Project B-020-ALAS), as authorized by the Water Resources Research Act of 1964, Public Law 88-279, as amended; in part by funds provided by the Municipal Utility System of the City of Fairbanks, Alaska; and in part by funds provided by the University of Alaska, Fairbanks

Arsenic in the Water, Soil Bedrock, and Plants of the Ester Dome Area of Alaska

Concentrations of arsenic as large as 10 ppm (200 times the safe limit for drinking water) occur in the groundwater of a mineralized residential area near Fairbanks. Bedrock of the area contains 750 ppm As, primarily as arsenopyrite and scorodite. The oxygen-poor groundwater is enriched in As(III) and ferrous iron while the surface waters are iron free and contain less than 50 ppb As(V). Arsenic is removed from the water by coprecipitation with ferric hydroxide. Some iron-rich stream sediments contain as much as 1,400 ppm arsenic. The distribution of arsenic in the groundwater is controlled by the distribution of arsenic in the bedrock. The arsenic content of the B soil horizon over mineralized veins is about 150 ppm, while that over barren rock is 30 ppm. The vegetation over the veins is not significantly enriched in arsenic. Lettuce, radishes and tomatoes grown with arsenic-rich water (5 ppm) contain 16, 8 and 1 ppm As, respectively; these amounts are significantly greater than plants not treated with arsenic. Preliminary studies by state and federal health agencies show no detrimental effects on the health of persons drinking these arsenic-rich waters.The work upon which this publication is based was supported in part by funds provided by the Office of Water Research and Technology (Project B-037-ALAS, Agreement No. 14-34-0001-8056), U.S. Department of the Interior, Washington, D.C., as authorized by the Water Research and Development Act of 1978

Circular 64

Treatment of Alaska-produced food products by ionizing radiation may benefit the seafood and agricultural industries and the Alaskan consumer. A feasibility study to evaluate the potential social and economic benefits and risks as well as the costs of using the process in Alaska on Alaskan products is being coordinated by the Institute of Northern Engineering. A research and development project to determine effects on the quality o f Alaskan products could be the next phase in the introduction o f a new food-preservation technique to Alaska

CSF proteomics in autosomal dominant Alzheimer's disease highlights parallels with sporadic disease

Autosomal dominant Alzheimer's disease (ADAD) offers a unique opportunity to study pathophysiological changes in a relatively young population with few comorbidities. A comprehensive investigation of proteome changes occurring in ADAD could provide valuable insights into AD-related biological mechanisms and uncover novel biomarkers and therapeutic targets. Furthermore, ADAD might serve as a model for sporadic AD, but in-depth proteome comparisons are lacking. We aimed to identify dysregulated CSF proteins in ADAD and determine the degree of overlap with sporadic AD. We measured 1472 proteins in CSF of PSEN1 or APP mutation carriers (n = 22) and age- and sex-matched controls (n = 20) from the Amsterdam Dementia Cohort using proximity extension-based immunoassays (PEA). We compared protein abundance between groups with two-sided t-tests and identified enriched biological pathways. Using the same protein panels in paired plasma samples, we investigated correlations between CSF proteins and their plasma counterparts. Finally, we compared our results with recently published PEA data from an international cohort of sporadic AD (n = 230) and non-AD dementias (n = 301). All statistical analyses were false discovery rate-corrected. We detected 66 differentially abundant CSF proteins (65 increased, 1 decreased) in ADAD compared to controls (q &lt; 0.05). The most strongly upregulated proteins (fold change &gt;1.8) were related to immunity (CHIT1, ITGB2, SMOC2), cytoskeletal structure (MAPT, NEFL) and tissue remodelling (TMSB10, MMP-10). Significant CSF-plasma correlations were found for the upregulated proteins SMOC2 and LILR1B. Of the 66 differentially expressed proteins, 36 had been measured previously in the sporadic dementias cohort, 34 of which (94%) were also significantly upregulated in sporadic AD, with a strong correlation between the fold changes of these proteins in both cohorts (rs = 0.730, P &lt; 0.001). Twenty-nine of the 36 proteins (81%) were also upregulated among non-AD patients with suspected AD co-pathology. This CSF proteomics study demonstrates substantial biochemical similarities between ADAD and sporadic AD, suggesting involvement of the same biological processes. Besides known AD-related proteins, we identified several relatively novel proteins, such as TMSB10, MMP-10 and SMOC2, which have potential as novel biomarkers. With shared pathophysiological CSF changes, ADAD study findings might be translatable to sporadic AD, which could greatly expedite therapy development.</p

Age-related declines in delayed non-match-to-sample performance (DNMS) are reversed by the novel 5HT6 receptor antagonist SB742457

International audienc

Age-related declines in delayed non-match-to-sample performance (DNMS) are reversed by the novel 5HT6 receptor antagonist SB742457

International audienc

Rosiglitazone enhances learning, place cell activity, and synaptic plasticity in middle-aged rats

International audienc

Neuroinflammatory CSF biomarkers MIF, sTREM1, and sTREM2 show dynamic expression profiles in Alzheimer’s disease

Abstract Background There is a need for novel fluid biomarkers tracking neuroinflammatory responses in Alzheimer’s disease (AD). Our recent cerebrospinal fluid (CSF) proteomics study revealed that migration inhibitory factor (MIF) and soluble triggering receptor expressed on myeloid cells 1 (sTREM1) increased along the AD continuum. We aimed to assess the potential use of these proteins, in addition to sTREM2, as CSF biomarkers to monitor inflammatory processes in AD. Methods We included cognitively unimpaired controls (n = 67, 63 ± 9 years, 24% females, all amyloid negative), patients with mild cognitive impairment (MCI; n = 92, 65 ± 7 years, 47% females, 65% amyloid positive), AD (n = 38, 67 ± 6 years, 8% females, all amyloid positive), and DLB (n = 50, 67 ± 6 years, 5% females, 54% amyloid positive). MIF, sTREM1, and sTREM2 levels were measured by validated immunoassays. Differences in protein levels between groups were tested with analysis of covariance (corrected for age and sex). Spearman correlation analysis was performed to evaluate the association between these neuroinflammatory markers with AD-CSF biomarkers (Aβ42, tTau, pTau) and mini-mental state examination (MMSE) scores. Results MIF levels were increased in MCI (p  0.05) compared to controls. Levels of sTREM1 were specifically increased in AD compared to controls (p  0.05), while sTREM2 levels were increased specifically in MCI compared to all other groups (all p < 0.001). Neuroinflammatory proteins were highly correlated with CSF pTau levels (MIF: all groups; sTREM1: MCI, AD and DLB; sTREM2: controls, MCI and DLB). Correlations with MMSE scores were observed in specific clinical groups (MIF in controls, sTREM1 in AD, and sTREM2 in DLB). Conclusion Inflammatory-related proteins show diverse expression profiles along different AD stages, with increased protein levels in the MCI stage (MIF and sTREM2) and AD stage (MIF and sTREM1). The associations of these inflammatory markers primarily with CSF pTau levels indicate an intertwined relationship between tau pathology and inflammation. These neuroinflammatory markers might be useful in clinical trials to capture dynamics in inflammatory responses or monitor drug–target engagement of inflammatory modulators

Thimet oligopeptidase as a potential CSF biomarker for Alzheimer's disease: A cross‐platform validation study

Abstract INTRODUCTION Our previous antibody‐based cerebrospinal fluid (CSF) proteomics study showed that Thimet oligopeptidase (THOP1), an amyloid beta (Aβ) neuropeptidase, was increased in mild cognitive impairment with amyloid pathology (MCI‐Aβ+) and Alzheimer's disease (AD) dementia compared with controls and dementia with Lewy bodies (DLB), highlighting the potential of CSF THOP1 as an early specific biomarker for AD. We aimed to develop THOP1 immunoassays for large‐scale analysis and validate our proteomics findings in two independent cohorts. METHODS We developed in‐house CSF THOP1 immunoassays on automated Ella and Simoa platforms. The performance of the different assays were compared using Passing–Bablok regression analysis in a subset of CSF samples from the discovery cohort (n = 72). Clinical validation was performed in two independent cohorts (cohort 1: n = 200; cohort 2: n = 165) using the Ella platform. RESULTS THOP1 concentrations moderately correlated between proteomics analysis and our novel assays (Rho > 0.580). In both validation cohorts, CSF THOP1 was increased in MCI‐Aβ+ (>1.3‐fold) and AD (>1.2‐fold) compared with controls; and between MCI‐Aβ+ and DLB (>1.2‐fold). Higher THOP1 concentrations were detected in AD compared with DLB only when both cohorts were analyzed together. In both cohorts, THOP1 correlated with CSF total tau (t‐tau), phosphorylated tau (p‐tau), and Aβ40 (Rho > 0.540) but not Aβ42. DISCUSSION Validation of our proteomics findings underpins the potential of CSF THOP1 as an early specific biomarker associated with AD pathology. The use of antibody‐based platforms in both the discovery and validation phases facilitated the translation of proteomics findings, providing an additional workflow that may accelerate the development of biofluid‐based biomarkers