Design Considerations for Embankment Protection During Road Overtopping Events

This report describes the research conducted by the University of Minnesota and project partners on roadway embankment overtopping by flood water. Roadway overtopping is a major safety concern for Minnesota transportation managers because of the potential for rapid soil erosion and mass wasting resulting in partial or complete failure of the roadway embankment. This multi-year research study focused on various aspects of the roadway embankment overtopping. A robust literature survey was performed to identify research, reports and other published knowledge that would inform the project. A field- based research campaign was developed with the goal of collecting data on the hydraulics associated with full-scale overtopping events. Finally, a series of laboratory experiments were conducted at the St. Anthony Falls Laboratory, University of Minnesota to study the hydraulic and erosional processes associated with embankment overtopping and in particular study of three slope protection techniques under overtopping flow. The largest component of the research project was the laboratory hydraulic testing, which focused on bare soil (base case) and three slope protection technologies. A full- scale laboratory facility was constructed to carry out the testing. Three erosion protection techniques were examined including 1) armored sod, 2) turf reinforcement mat, and 3) flexible concrete geogrid mat. Overtopping depths of up to 1-ft were used to determine the failure point of the protection technique and soil on both the 4h:1V and 6V:1H slopes. The full project report details the testing of each protection technique as well as observations and findings made during the testing

High-intensity interval training is safe, feasible and efficacious in nonalcoholic steatohepatitis : a randomized controlled trial

Background: High-Intensity Interval Training (HIIT) involves bursts of high-intensity exercise interspersed with lower-intensity exercise recovery. HIIT may benefit cardiometabolic health in people with nonalcoholic steatohepatitis (NASH). Aims: We aimed to examine the safety, feasibility, and efficacy of 12-weeks of supervised HIIT compared with a sham-exercise control (CON) for improving aerobic fitness and peripheral insulin sensitivity in biopsy-proven NASH. Methods: Participants based in the community [(n = 14, 56 ± 10 years, BMI 39.2 ± 6.7 kg/m2, 64% male), NAFLD Activity Score 5 (range 3–7)] were randomized to 12-weeks of supervised HIIT (n = 8, 4 × 4 min at 85–95% maximal heart rate, interspersed with 3 min active recovery; 3 days/week) or CON (n = 6, stretching; 3 days/week). Safety (adverse events) and feasibility determined a

T cell mediated cerebral hemorrhages and microhemorrhages during passive Aβ immunization in APPPS1 transgenic mice

<p>Abstract</p> <p>Background</p> <p>Immunization against amyloid-β (Aβ), the peptide that accumulates in the form of senile plaques and in the cerebrovasculature in Alzheimer's disease (AD), causes a dramatic immune response that prevents plaque formation and clears accumulated Aβ in transgenic mice. In a clinical trial of Aβ immunization, some patients developed meningoencephalitis and hemorrhages. Neuropathological investigations of patients who died after the trial showed clearance of amyloid pathology, but also a powerful immune response involving activated T cells probably underlying the negative effects of the immunization.</p> <p>Results</p> <p>To define the impact of T cells on this inflammatory response we used passive immunization and adoptive transfer to separate the effect of IgG and T cell mediated effects on microhemorrhage in APPPS1 transgenic mice. Neither anti Aβ IgG nor adoptively transferred T cells, alone, led to increased cerebrovascular damage. However, the combination of adoptively transferred T cells and passive immunization led to massive cerebrovascular bleeding that ranged from multiple microhemorrhages in the parenchyma to large hematomas.</p> <p>Conclusions</p> <p>Our results indicate that vaccination can lead to Aβ and T cell induced cerebral micro-hemorrhages and acute hematomas, which are greatly exacerbated by T cell mediated activity.</p

Numerical evidence for `multi-scalar stars'

We present a class of general relativistic soliton-like solutions composed of multiple minimally coupled, massive, real scalar fields which interact only through the gravitational field. We describe a two-parameter family of solutions we call ``phase-shifted boson stars'' (parameterized by central density rho_0 and phase delta), which are obtained by solving the ordinary differential equations associated with boson stars and then altering the phase between the real and imaginary parts of the field. These solutions are similar to boson stars as well as the oscillating soliton stars found by Seidel and Suen [E. Seidel and W.M. Suen, Phys. Rev. Lett. 66, 1659 (1991)]; in particular, long-time numerical evolutions suggest that phase-shifted boson stars are stable. Our results indicate that scalar soliton-like solutions are perhaps more generic than has been previously thought.Comment: Revtex. 4 pages with 4 figures. Submitted to Phys. Rev.

Increased mRNA Levels of TCF7L2 and MYC of the Wnt Pathway in Tg-ArcSwe Mice and Alzheimer's Disease Brain

Several components in the Wnt pathway, including β-catenin and glycogen synthase kinase 3 beta, have been implied in AD pathogenesis. Here, mRNA brain levels from five-month-old tg-ArcSwe and nontransgenic mice were compared using Affymetrix microarray analysis. With surprisingly small overall changes, Wnt signaling was the most affected pathway with altered expression of nine genes in tg-ArcSwe mice. When analyzing mRNA levels of these genes in human brain, transcription factor 7-like 2 (TCF7L2) and v-myc myelocytomatosis viral oncogene homolog (MYC), were increased in Alzheimer's disease (AD) (P < .05). Furthermore, no clear differences in TCF7L2 and MYC mRNA were found in brains with frontotemporal lobar degeneration, suggesting that altered regulation of these Wnt-related genes could be specific to AD. Finally, mRNA levels of three neurogenesis markers were analyzed. Increased mRNA levels of dihydropyrimidinase-like 3 were observed in AD brain, suggesting that altered Wnt pathway regulation may signify synaptic rearrangement or neurogenesis

Increased mRNA Levels of TCF7L2 and MYC of the Wnt Pathway in Tg-ArcSwe Mice and Alzheimer's Disease Brain

Several components in the Wnt pathway, including β-catenin and glycogen synthase kinase 3 beta, have been implied in AD pathogenesis. Here, mRNA brain levels from five-month-old tg-ArcSwe and nontransgenic mice were compared using Affymetrix microarray analysis. With surprisingly small overall changes, Wnt signaling was the most affected pathway with altered expression of nine genes in tg-ArcSwe mice. When analyzing mRNA levels of these genes in human brain, transcription factor 7-like 2 (TCF7L2) and v-myc myelocytomatosis viral oncogene homolog (MYC), were increased in Alzheimer's disease (AD) (P < .05). Furthermore, no clear differences in TCF7L2 and MYC mRNA were found in brains with frontotemporal lobar degeneration, suggesting that altered regulation of these Wnt-related genes could be specific to AD. Finally, mRNA levels of three neurogenesis markers were analyzed. Increased mRNA levels of dihydropyrimidinase-like 3 were observed in AD brain, suggesting that altered Wnt pathway regulation may signify synaptic rearrangement or neurogenesis

A reporter of local dendritic translocation shows plaque- related loss of neural system function in APP-transgenic mice

Although neuronal communication is thought to be summated within local dendritic segments, no technique is currently available to monitor activity in vivo at this level of resolution. To overcome this challenge, we developed an optical reporter of neuronal activity utilizing the coding sequence of Venus, flanked by short stretches of the 5' and 3' untranslated regions from CAMKIIα. This reporter takes advantage of the fact that CAMKIIα mRNA is transported to the dendrite and locally translated in an activity dependent manner (Aakalu et al., 2001). Using adeno associated virus (AAV), we used this reporter to study neuronal activity in adult mice. Exposure of the mice to an enriched environment led to enhancement of Venus expression in dendritic segments of somatosensory cortex, demonstrating in vivo that dendritic mRNA translocation and local transcription occur in response to physiologically relevant stimuli. We then utilized this system to examine the impact of Alzheimer related local amyloid-β deposits on neural system function, to test the hypothesis that plaques are toxic. In APPswe/PS1d9 (APP/PS1) mice, neurons close to plaques, and dendritic segments close to plaques, both showed diminished fluorescent intensity and therefore neuronal activity. In contrast to wildtype mice, fluorescent intensity in neurons near plaques in transgenic mice did not increase after environmental enrichment. These data indicate that neuronal activity in dendritic segments and neurons in the vicinity of a plaque is decreased compared to wildtype mice, supporting the idea that plaques are a focal lesion leading to impaired neural system function

PARP1 is required for preserving telomeric integrity but is dispensable for A-NHEJ

Poly-ADP ribose polymerase 1 (PARP1) is clinically important because of its synthetic lethality with breast cancer allele 1 and 2 mutations, which are causative for inherited breast and ovarian cancers. Biochemically, PARP1 is a single-stranded DNA break repair protein that is needed for preserving genomic integrity. In addition, PARP1 has been implicated in a veritable plethora of additional cellular pathways and thus its precise contribution(s) to human biology has remained obscure. To help address this deficiency, we utilized gene editing to construct genetically-null PARP1 human cancer cells. We found a minor role for PARP1 in an alternative form of DNA double-strand break (DSB) repair, but only when these cells were deficient for the classical form of DSB repair. Despite being proficient for DSB repair, however, cell cycle progression defects and elevated endogenous DNA damage signaling were observed. These deficiencies were instead linked to telomere defects, where PARP1-/- cells had short telomeres that co-localized with markers of endogenous DNA damage and were compromised in their ability to escape a telomere-driven crisis. Our data suggest that while PARP1 does not participate significantly in DNA DSB repair itself, it does prevent the incidence of telomeric DSBs, which, in turn, can drive genomic instability

Lead exposure in adult males in urban Transvaal Province, South Africa during the apartheid era

Human exposure to lead is a substantial public health hazard worldwide and is particularly problematic in the Republic of South Africa given the country’s late cessation of leaded petrol. Lead exposure is associated with a number of serious health issues and diseases including developmental and cognitive deficiency, hypertension and heart disease. Understanding the distribution of lifetime lead burden within a given population is critical for reducing exposure rates. Femoral bone from 101 deceased adult males living in urban Transvaal Province (now Gauteng Province), South Africa between 1960 and 1998 were analyzed for lead concentration by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Of the 72 black and 29 white individuals sampled, chronic lead exposure was apparent in nearly all individuals. White males showed significantly higher median bone lead concentration (ME = 10.04 µg·g−1), than black males (ME = 3.80 µg·g−1) despite higher socioeconomic status. Bone lead concentration covaries significantly, though weakly, with individual age. There was no significant temporal trend in bone lead concentration. These results indicate that long-term low to moderate lead exposure is the historical norm among South African males. Unexpectedly, this research indicates that white males in the sample population were more highly exposed to lead

Defining imaging biomarker cut points for brain aging and Alzheimer's disease

AbstractIntroductionOur goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro-deoxyglucose (FDG) PET, and MRI cortical thickness.MethodsWe examined five methods for determining cut points.ResultsThe reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of cognitively impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness. Cut points defined using the accuracy of cognitively impaired versus age-matched CN method labeled fewer people abnormal.DiscussionIn the future, we will use a single cut point for amyloid PET (standardized uptake value ratio, 1.42; centiloid, 19) based on the reliable worsening cut point method. We will base lenient cut points for tau PET, FDG PET, and cortical thickness on the accuracy of cognitively impaired versus young CN method and base conservative cut points on the accuracy of cognitively impaired versus age-matched CN method