Tau PET and multimodal brain imaging in patients at risk for chronic traumatic encephalopathy.

ObjectiveTo characterize individual and group-level neuroimaging findings in patients at risk for Chronic Traumatic Encephalopathy (CTE).MethodsEleven male patients meeting criteria for Traumatic Encephalopathy Syndrome (TES, median age: 64) underwent neurologic evaluation, 3-Tesla MRI, and PET with [18F]-Flortaucipir (FTP, tau-PET) and [11C]-Pittsburgh compound B (PIB, amyloid-PET). Six patients underwent [18F]-Fluorodeoxyglucose-PET (FDG, glucose metabolism). We assessed imaging findings at the individual patient level, and in group-level comparisons with modality-specific groups of cognitively normal older adults (CN). Tau-PET findings in patients with TES were also compared to a matched group of patients with mild cognitive impairment or dementia due to Alzheimer's disease (AD).ResultsAll patients with TES sustained repetitive head injury participating in impact sports, ten in American football. Three patients met criteria for dementia and eight had mild cognitive impairment. Two patients were amyloid-PET positive and harbored the most severe MRI atrophy, FDG hypometabolism, and FTP-tau PET binding. Among the nine amyloid-negative patients, tau-PET showed either mildly elevated frontotemporal binding, a "dot-like" pattern, or no elevated binding. Medial temporal FTP was mildly elevated in a subset of amyloid-negative patients, but values were considerably lower than in AD. Voxelwise analyses revealed a convergence of imaging abnormalities (higher FTP binding, lower FDG, lower gray matter volumes) in frontotemporal areas in TES compared to controls.ConclusionsMildly elevated tau-PET binding was observed in a subset of amyloid-negative patients at risk for CTE, in a distribution consistent with CTE pathology stages III-IV. FTP-PET may be useful as a biomarker of tau pathology in CTE but is unlikely to be sensitive to early disease stages

Constructing a WISE High Resolution Galaxy Atlas

After eight months of continuous observations, the Wide-field Infrared Survey Explorer (WISE) mapped the entire sky at 3.4 {\mu}m, 4.6 {\mu}m, 12 {\mu}m and 22 {\mu}m. We have begun a dedicated WISE High Resolution Galaxy Atlas (WHRGA) project to fully characterize large, nearby galaxies and produce a legacy image atlas and source catalogue. Here we summarize the deconvolution technique used to significantly improve the spatial resolution of WISE imaging, specifically designed to study the internal anatomy of nearby galaxies. As a case study, we present results for the galaxy NGC 1566, comparing the WISE super-resolution image processing to that of Spitzer, GALEX and ground-based imaging. The is the first paper in a two part series; results for a much larger sample of nearby galaxies is presented in the second paper.Comment: Published in the AJ (2012, AJ, 144, 68

Population genomics of domestic and wild yeasts

The natural genetics of an organism is determined by the distribution of sequences of its genome. Here we present one- to four-fold, with some deeper, coverage of the genome sequences of over seventy isolates of the domesticated baker's yeast, _Saccharomyces cerevisiae_, and its closest relative, the wild _S. paradoxus_, which has never been associated with human activity. These were collected from numerous geographic locations and sources (including wild, clinical, baking, wine, laboratory and food spoilage). These sequences provide an unprecedented view of the population structure, natural (and artificial) selection and genome evolution in these species. Variation in gene content, SNPs, indels, copy numbers and transposable elements provide insights into the evolution of different lineages. Phenotypic variation broadly correlates with global genome-wide phylogenetic relationships however there is no correlation with source. _S. paradoxus_ populations are well delineated along geographic boundaries while the variation among worldwide _S. cerevisiae_ isolates show less differentiation and is comparable to a single _S. paradoxus_ population. Rather than one or two domestication events leading to the extant baker's yeasts, the population structure of _S. cerevisiae_ shows a few well defined geographically isolated lineages and many different mosaics of these lineages, supporting the notion that human influence provided the opportunity for outbreeding and production of new combinations of pre-existing variation

Influence of the initial chemical conditions on the rational design of silica particles

The influence of the water content in the initial composition on the size of silica particles produced using the Stöber process is well known. We have shown that there are three morphological regimes defined by compositional boundaries. At low water levels (below stoichiometric ratio of water:tetraethoxysilane), very high surface area and aggregated structures are formed; at high water content (>40 wt%) similar structures are also seen. Between these two boundary conditions, discrete particles are formed whose size are dictated by the water content. Within the compositional regime that enables the classical Stöber silica, the structural evolution shows a more rapid attainment of final particle size than the rate of formation of silica supporting the monomer addition hypothesis. The clearer understanding of the role of the initial composition on the output of this synthesis method will be of considerable use for the establishment of reliable reproducible silica production for future industrial adoption

Changes in the expression of the Alzheimer's disease-associated presenilin gene in drosophila heart leads to cardiac dysfunction

Mutations in the presenilin genes cause the majority of early-onset familial Alzheimer’s disease. Recently, presenilin mutations have been identified in patients with dilated cardiomyopathy (DCM), a common cause of heart failure and the most prevalent diagnosis in cardiac transplantation patients. However, the molecular mechanisms, by which presenilin mutations lead to either AD or DCM, are not yet understood. We have employed transgenic Drosophila models and optical coherence tomography imaging technology to analyze cardiac function in live adult Drosophila. Silencing of Drosophila ortholog of presenilins (dPsn) led to significantly reduced heart rate and remarkably age-dependent increase in end-diastolic vertical dimensions. In contrast, overexpression of dPsn increased heart rate. Either overexpression or silencing of dPsn resulted in irregular heartbeat rhythms accompanied by cardiomyofibril defects and mitochondrial impairment. The calcium channel receptor activities in cardiac cells were quantitatively determined via real-time RT-PCR. Silencing of dPsn elevated dIP[subscript 3]R expression, and reduced dSERCA expression; overexprerssion of dPsn led to reduced dRyR expression. Moreover, overexpression of dPsn in wing disc resulted in loss of wing phenotype and reduced expression of wingless. Our data provide novel evidence that changes in presenilin level leads to cardiac dysfunction, owing to aberrant calcium channel receptor activities and disrupted Wnt signaling transduction, indicating a pathogenic role for presenilin mutations in DCM pathogenesis.Cure Alzheimer’s FundNational Institutes of Health (U.S.) (Grant R01AG014713)National Institutes of Health (U.S.) (Grant R01MH60009)National Institutes of Health (U.S.) (Grant R01CA75289)National Institutes of Health (U.S.) (Grant R01HL095717)National Institutes of Health (U.S.) (Grant FA9550-07-1-0014

Shale Oil Value Enhancement Research. Quarterly Report, June 1 - August 31, 1996

The overall objective is to develop a new technology for manufacturing valuable marketable products from shale oil. The quarter`s efforts were concentrated on (a) THDA and reaction of alkylpyridines at elevated conditions, (b) compound type analysis of kerogen oil and its derived products, (b) thermal hydrodealkylation of the > 290{degrees}C polar fraction, (c) secondary reactions of pyridinic type compounds to form marketable products, and (d) preparation of presentation to the Dawnbreaker Commercial Assistance Program. Excellent progress is being made in all cases. Our market analysis and industrial feedback indicate that the low molecular weight pyridines are the main market driving force. We are concentrating our effort toward increasing the yield of ``light`` pyridines before the end of Phase II(a). Our current laboratory set-up can only produce analytical quantity of samples, which is not sufficient for marketing purpose. However, the completion of a secondary flow THDA unit for a pilot-scale production depends on the availability of the Phase-II(b) and Phase-III funding

A behavioral comparison of male and female adults with high functioning autism spectrum conditions

Autism spectrum conditions (ASC) affect more males than females in the general population. However, within ASC it is unclear if there are phenotypic sex differences. Testing for similarities and differences between the sexes is important not only for clinical assessment but also has implications for theories of typical sex differences and of autism. Using cognitive and behavioral measures, we investigated similarities and differences between the sexes in age- and IQ-matched adults with ASC (high-functioning autism or Asperger syndrome). Of the 83 (45 males and 38 females) participants, 62 (33 males and 29 females) met Autism Diagnostic Interview-Revised (ADI-R) cut-off criteria for autism in childhood and were included in all subsequent analyses. The severity of childhood core autism symptoms did not differ between the sexes. Males and females also did not differ in self-reported empathy, systemizing, anxiety, depression, and obsessive-compulsive traits/symptoms or mentalizing performance. However, adult females with ASC showed more lifetime sensory symptoms (p = 0.036), fewer current socio-communication difficulties (p = 0.001), and more self-reported autistic traits (p = 0.012) than males. In addition, females with ASC who also had developmental language delay had lower current performance IQ than those without developmental language delay (p<0.001), a pattern not seen in males. The absence of typical sex differences in empathizing-systemizing profiles within the autism spectrum confirms a prediction from the extreme male brain theory. Behavioral sex differences within ASC may also reflect different developmental mechanisms between males and females with ASC. We discuss the importance of the superficially better socio-communication ability in adult females with ASC in terms of why females with ASC may more often go under-recognized, and receive their diagnosis later, than males

Role of apamin sensitive small conductance calcium-activated potassium currents in long term cardiac memory in rabbits

Background Apamin-sensitive small conductance calcium-activated K current (IKAS) is upregulated during ventricular pacing and masks short-term cardiac memory (CM). Objective – To determine the role of IKAS in long-term CM. Methods – CM was created with 3-5 weeks of ventricular pacing and defined by a flat or inverted T-wave off pacing. Epicardial optical mapping was performed in both paced and normal ventricles. Action potential duration (APD80) was determined during RA pacing. Ventricular stability was tested before and after IKAS blockade. Four paced hearts and 4 normal hearts were used for western blotting and histology. Results – There were no significant differences in either the echocardiographic parameters or in fibrosis levels between groups. Apamin induced more APD80 prolongation in CM than in normal ventricles (9.6% [8.8%-10.5%] vs 3.1% [1.9%-4.3%], p<0.001). Apamin significantly lengthend the APD80 in the CM model at late activation sites, indicating significant IKAS upregulation at those sites. The CM model also had altered Ca2+ handling as the 50% Ca2+ transient duration and amplitude were increased at distal sites compared to a proximal site (near the pacing site). After apamin, the CM model had increased VF inducibility (paced vs control, 33/40 (82.5%) vs 7/20 (35%) P<0.001), and longer VF durations (124 vs 26 seconds, P<0.001). Conclusions Chronic ventricular pacing increases Ca2+ transients at late activation sites which activates IKAS to maintain repolarization reserve. IKAS blockade increases VF vulnerability in chronically paced rabbit ventricles

Simulations of extensional flow in microrheometric devices

We present a detailed numerical study of the flow of a Newtonian fluid through microrheometric devices featuring a sudden contraction–expansion. This flow configuration is typically used to generate extensional deformations and high strain rates. The excess pressure drop resulting from the converging and diverging flow is an important dynamic measure to quantify if the device is intended to be used as a microfluidic extensional rheometer. To explore this idea, we examine the effect of the contraction length, aspect ratio and Reynolds number on the flow kinematics and resulting pressure field. Analysis of the computed velocity and pressure fields show that, for typical experimental conditions used in microfluidic devices, the steady flow is highly three-dimensional with open spiraling vortical structures in the stagnant corner regions. The numerical simulations of the local kinematics and global pressure drop are in good agreement with experimental results. The device aspect ratio is shown to have a strong impact on the flow and consequently on the excess pressure drop, which is quantified in terms of the dimensionless Couette and Bagley correction factors. We suggest an approach for calculating the Bagley correction which may be especially appropriate for planar microchannels