529 research outputs found

    Collateral Estoppel

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    The doctrine of collateral estoppel involves the use of an old judgment in a new action to prevent the relitigation of issues resolved by that old judgment. At common law, use of the doctrine required that the party using collateral estoppel and the party against whom it was used be the same as the parties to the prior judgment. This common law requirement of mutuality has been relaxed and since the United States Supreme Court\u27s 1979 decision in ParklaneHoisery Co. v. Shore, the strict common law requirement of mutuality has all but completely vanished. In Parklane the Court sanctioned the use of collateral estoppel by a plaintiff who was a stranger to the original suit against a defendant who was party to that suit. The courts\u27 search for fair results and judicial economy in the application of the doctrine led to this application of the doctrine in circumstances in which the parties were not mutual. This note traces the un- steady course which the doctrine of collateral estoppel traveled before Parklane. The significance of the Court\u27s decision in Parklane is then analyzed. Finally, post-Parklane applications of collateral estoppel are discussed, including the effect of the use of collateral estoppel on the seventh amendment right to jury trial and its impact on substantive areas of law

    Thermoregulatory Adaptations following Sprint Interval Training

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    Traditional endurance training typically involves weeks of long-duration (60–90 min) exercise performed at a moderate to vigorous intensity. An alternative paradigm, sprint interval training, is characterized by multiple bouts of short-duration, high-intensity exercise. Similar fitness benefits from the two paradigms have been demonstrated, but whether sprint interval training—like traditional endurance training—induces heat acclimation remains unclear. Purpose To test the hypothesis that sprint interval training performed over six sessions results in measureable thermoregulatory and cardiovascular adaptations consistent with heat acclimation. Methods Seven untrained men [mean ± SD, 13 ± 5% body fat, 22 ± 3 y, 3.1 ± 0.3 L/min peak oxygen uptake (V̇O2peak)] performed 6 sprint interval training sessions over 12 days with 48­–72 h between sessions. Sessions consisted of 4–6 thirty-second Wingate Anaerobic Tests separated by ~4 min. Before and after the two-week training protocol, participants cycled for 30 min at 65% V̇O2peak in 25 °C to assess the effects of sprint interval training on heat acclimation. Results Main outcome variables (onset of sweating, sweat sensitivity, heart rate at end of exercise, percent change in plasma volume, and core temperature change from pre- to post-exercise) were not different from pre- to post-training (all p \u3e 0.05). Conclusion Two weeks of sprint interval training performed under the conditions specified does not result in heat acclimation

    Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age

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    In advanced age, some individuals maintain a stable cognitive trajectory while others experience a rapid decline. Such variation in cognitive trajectory is only partially explained by traditional neurodegenerative pathologies. Hence, to identify new processes underlying variation in cognitive trajectory, we perform an unbiased proteome-wide association study of cognitive trajectory in a discovery (n = 104) and replication cohort (n = 39) of initially cognitively unimpaired, longitudinally assessed older-adult brain donors. We find 579 proteins associated with cognitive trajectory after meta-analysis. Notably, we present evidence for increased neuronal mitochondrial activities in cognitive stability regardless of the burden of traditional neuropathologies. Furthermore, we provide additional evidence for increased synaptic abundance and decreased inflammation and apoptosis in cognitive stability. Importantly, we nominate proteins associated with cognitive trajectory, particularly the 38 proteins that act independently of neuropathologies and are also hub proteins of protein co-expression networks, as promising targets for future mechanistic studies of cognitive trajectory.Accelerating Medicine Partnership for AD [U01AG046161, U01 AG061357]; Emory Alzheimer's Disease Research Center [P50 AG025688]; NINDS Emory Neuroscience Core [P30 NS055077]; intramural program of the National Institute on Aging (NIA); Alzheimer's Association; Alzheimer's Research UK; Michael J. Fox Foundation for Parkinson's Research; Weston Brain Institute Biomarkers Across Neurodegenerative Diseases Grant [11060]; National Institute of Neurological Disorders and Stroke [U24 NS072026]; National Institute on Aging [P30 AG19610]; Arizona Department of Health Services [211002]; Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001]; [R01 AG056533]; [R01 AG053960]; [U01 MH115484]; [I01 BX003853]; [IK2 BX001820]; [R01 AG061800]; [R01 AG057911]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

    High Resolution Observations of Drop Size Distribution for GPM Ground Validation

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    During the Mid-latitude Continental Convective Cloud Experiment (MC3E), NASA's GPM GV Disdrometer and Radar Observations of Precipitation (DROP) Facility deployed an array of disdrometers and rain gauges in northern Oklahoma to sample, with high resolution, the drop size distribution for use in development of precipitation retrieval algorithms for the GPM core satellites. The DROP Facility instruments deployed during MC3E consisted of 16 autonomous Parsivel units, 5 two-dimensional video disdrometers (2dvds), a vertically pointing K band radar, and 32 tipping bucket rain gauges. There were several rainfall events during MC3E in which rain drops exceeding 6 mm in diameter were recorded. The disdrometer array revealed large rain drops with diameters exceeding 6 mm and 8 mm during two separate stratiform and convective rainfall events, respectively. The NPOL radar, which was scanning in high resolution RHI mode (every 40 sec) over the disdrometer array during the stratiform event, indicated a 1 km thick bright band with a differential reflectivity column of 2-3 dB extending below the melting layer to the surface where the large drops were recorded by the 2dvds. These large drops are important for GPM since they can have a great impact upon satellite precipitation retrieval, especially near the ground and below heavy convective rainfall cores where satellites have had problems depicting the rainfall

    Effects of APOE Genotype on Brain Proteomic Network and Cell Type Changes in Alzheimer's Disease

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    Polymorphic alleles in the apolipoprotein E (APOE) gene are the main genetic determinants of late-onset Alzheimer's disease (AD) risk. Individuals carrying the APOE E4 allele are at increased risk to develop AD compared to those carrying the more common E3 allele, whereas those carrying the E2 allele are at decreased risk for developing AD. How ApoE isoforms influence risk for AD remains unclear. To help fill this gap in knowledge, we performed a comparative unbiased mass spectrometry-based proteomic analysis of post-mortem brain cortical tissues from pathologically-defined AD or control cases of different APOE genotypes. Control cases (n = 10) were homozygous for the common E3 allele, whereas AD cases (n = 24) were equally distributed among E2/3, E3/3, and E4/4 genotypes. We used differential protein expression and co-expression analytical approaches to assess how changes in the brain proteome are related to APOE genotype. We observed similar levels of amyloid-β, but reduced levels of neurofibrillary tau, in E2/3 brains compared to E3/3 and E4/4 AD brains. Weighted co-expression network analysis revealed 33 modules of co-expressed proteins, 12 of which were significantly different by APOE genotype in AD. The modules that were significantly different by APOE genotype were associated with synaptic transmission and inflammation, among other biological processes. Deconvolution and analysis of brain cell type changes revealed that the E2 allele suppressed homeostatic and disease-associated cell type changes in astrocytes, microglia, oligodendroglia, and endothelia. The E2 allele-specific effect on brain cell type changes was validated in a separate cohort of 130 brains. Our systems-level proteomic analyses of AD brain reveal alterations in the brain proteome and brain cell types associated with allelic variants in APOE, and suggest further areas for investigation into the upstream mechanisms that drive ApoE-associated risk for AD

    Structural basis of transposon end recognition explains central features of Tn7 transposition systems

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    Tn7 is a bacterial transposon with relatives containing element-encoded CRISPR-Cas systems mediating RNA-guided transposon insertion. Here, we present the 2.7 Ă… cryoelectron microscopy structure of prototypic Tn7 transposase TnsB interacting with the transposon end DNA. When TnsB interacts across repeating binding sites, it adopts a beads-on-a-string architecture, where the DNA-binding and catalytic domains are arranged in a tiled and intertwined fashion. The DNA-binding domains form few base-specific contacts leading to a binding preference that requires multiple weakly conserved sites at the appropriate spacing to achieve DNA sequence specificity. TnsB binding imparts differences in the global structure of the protein-bound DNA ends dictated by the spacing or overlap of binding sites explaining functional differences in the left and right ends of the element. We propose a model of the strand-transfer complex in which the terminal TnsB molecule is rearranged so that its catalytic domain is in a position conducive to transposition

    Quantitative measurement of thyroglobulin mRNA in peripheral blood of patients after total thyroidectomy

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    Previous studies have reported the clinical usefulness of reverse transcription-polymerase chain reaction (RT-PCR) detection of thyroglobulin (TG) mRNA in the peripheral blood of patients with differentiated thyroid carcinoma. To evaluate this usefulness, we measured TG mRNA in the peripheral blood of patients diagnosed with thyroid carcinoma after total thyroidectomy by real-time quantitative RT-PCR using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA as an internal control. Surprisingly, we detected TG mRNA in all samples obtained after total thyroidectomy, including those from 4 medullary carcinomas. Further, there was no statistical difference in expression levels of TG mRNA in the patients with or without metastasis, and no significant correlation was found between serum TG concentrations and the expression levels of TG mRNA. These results give rise to a question regarding the clinical applications of not only RT-PCR detection but also quantitative measurement of TG mRNA in peripheral blood. © 2001 Cancer Research Campaign http://www.bjcancer.co

    Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma

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    Napsin A is an aspartic proteinase expressed in lung and kidney. We have reported that napsin A is expressed in type II pneumocytes and in adenocarcinomas of the lung. The expression of napsin was examined in 118 lung tissues including 16 metastases by in situ hybridisation. Napsin was expressed in the tumour cell compartment in 33 of 39 adenocarcinomas (84.6%), in two of 11 large cell carcinomas and in one lung metastasis of a renal cell carcinoma. Expression of napsin was found to be associated with a high degree of differentiation in adenocarcinoma. Immunohistochemistry was performed for three proteins currently used as markers for lung adenocarcinoma : surfactant protein-A, surfactant protein-B and thyroid transcription factor-1. Thyroid transcription factor-1 showed the same sensitivity (84.6%) as napsin for adenocarcinoma, whereas surfactant protein-A and surfactant protein-B showed lower sensitivities. Among these markers, napsin showed the highest specificity (94.3%) for adenocarcinoma in nonsmall cell lung carcinoma. We conclude that napsin is a promising marker for the diagnosis of primary lung adenocarcinoma
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