In Dwelling King, Peter
2008, 20160523, 2012, 2008-03-01, 2016-05-26, 20080101
eBook
Using innovative theoretical concepts, this book develops a new approach to looking at dwelling and how we use it. Combining philosophical analysis and literary and film criticism, it puts forward an ...innovative and insightful new approach to looking at housing and explores issues of exclusion, isolation, anxiety, privacy and the relations between parent and child.
Honey taken directly from 59 bee hives on the Hawaiian island of Kaua'i was analyzed for glyphosate residue using ELISA techniques. Glyphosate residue was detected (> LOQ) in 27% of honey samples, at ...concentrations up to 342 ppb, with a mean = 118 ppb, S.E.M. 24 ppb. Of 15 honey samples store-purchased on Kaua'i, glyphosate was detected in 33%, with a mean concentration of 41 ppb, S.E.M. 14. Glyphosate residue was not detected in two samples from the island of Molokai but was in one of four samples from the island of Hawai'i. Presence and concentration of glyphosate residues were geospatially mapped with respect to Hawaiian land divisions. Mapping showed higher occurrence of glyphosate that was over LOQ (48%) and concentrations of glyphosate (mean = 125 ppb, S.E.M. 25 ppb; N = 15) in honey from the western, predominantly agricultural, half of Kaua'i versus the eastern half (4%, mean = 15 ppb; N = 1). Geographic Information System analysis of land use percentage was performed within a circular zone of 1 Km radius around each hive. Various land use types within each circular zone were transcribed into polygons and percent land use calculated. Only agriculture land use showed a strong positive correlation with glyphosate concentration. High glyphosate concentrations were also detected when extensive golf courses and/or highways were nearby. This suggests herbicide migration from the site of use into other areas by bees. Best management practices in use for curtailing pesticide migration are not effective and must be carefully re-assessed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Vertical walls and square corners were made with cold spray and two 6-DoF robots.•CSAM produced a 3D square frame with geometry reasonably close to the CAD file.•Reasonable geometry ...control can be achieved by understanding motion parameters.•Porosity distribution in the 3D volume is influenced by tool path planning.•Overbuilt structures were more porous than underbuilt structures.
Cold spray additive manufacturing (CSAM) is a solid-state deposition process well-suited to titanium that has the potential to make large, near-net-shape parts at high productivity. However, further research is required to truly accomplish the freedom of design expected from CSAM and, in particular, to address how to manufacture a specific 3D object with minimal porosity. Therefore, this paper focuses on understanding how tool path planning strategy and robot kinematics affect the geometry and porosity distribution in a 3D object. Square titanium frames were manufactured layer-by-layer using a continuous tool path planning strategy in which the contour spray angle, traverse speed and corner smoothing radius were varied selectively. The sample geometry was analysed by 3D laser scanning, and the capacity to produce straight, vertical walls and square corners were demonstrated. The total porosity in the manufactured objects was measured using the Archimedes’ principle, further investigated by metallographic cross-section analysis, and then validated by X-ray computed tomography on selected samples. Porosity was distributed layer by layer, creating a fishbone structure in the cross-section with higher porosity between the layers and near the edges of the walls and corners. The influence of robot kinematics and toolpath planning on forming underbuilt and overbuilt structures and how they influenced porosity development are also discussed. The knowledge generated from this research can significantly influence the development of tool path planning strategies in CSAM, providing the means to produce improved near-net-shapes with controlled porosity formation.
Weight loss is a predictor of shorter survival in amyotrophic lateral sclerosis (ALS). We performed serial measures of body composition using Dual-energy X-ray Absorptiometry (DEXA) in ALS patients ...to explore its utility as a biomarker of disease progression.
DEXA data were obtained from participants with ALS (enrollment, at 6- and 12- months follow ups) and Parkinson's disease (enrollment and at 4-month follow up) as a comparator group. Body mass index, total lean mass index, appendicular lean mass index, total fat mass index, and percentage body fat at enrollment were compared between the ALS and PD cohorts and age-matched normative data obtained from the National Health and Nutrition Examination Survey database. Estimated monthly changes of body composition measures in the ALS cohort were compared to those of the PD cohort and were correlated with disease progression measured by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).
The ALS cohort (N = 20) had lower baseline total and appendicular lean mass indices compared to the PD cohort (N = 20) and general population. Loss in total and appendicular lean masses were found to be significantly associated with follow-up time. Low baseline percentage body fat (r = 0.72, p = 0.04), loss of percentage body fat (r = 0.81, p = 0.01), and total fat mass index (r = 0.73, p = 0.04) during follow up correlated significantly with monthly decline of ALSFRS-R scores in ALS cohort who had 2 or more follow-ups (N = 8).
Measurement of body composition with DEXA might serve as a biomarker for rapid disease progression in ALS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target. Although progressive weakness is a hallmark feature of amyotrophic lateral ...sclerosis, there is considerable heterogeneity, including clinical presentation, progression, and the underlying triggers for disease initiation. Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations, it has become apparent that overt disease is preceded by a prodromal phase, possibly in years, where compensatory mechanisms delay symptom onset. Since 85-90% of amyotrophic lateral sclerosis is sporadic, there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration. Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease. Skeletal muscle, including the neuromuscular junction, manifests abnormalities at the earliest stages of the disease, before motor neuron loss, making it a promising source for identifying biomarkers of the prodromal phase. The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time. The advent of "omics" technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle, ranging from coding and non-coding RNAs to proteins and metabolites. This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms. A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease. There are two major goals of this review. The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity, evidence of a similar dysregulation in the SOD1
mouse during presymptomatic stages, and evidence of progressive change during disease progression. The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression, and as such, their potential as therapeutic targets in amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that selectively attacks motor neurons, and leads to progressive muscle weakness and death. A common pathological feature is ...the misfolding, aggregation, and cytoplasmic mislocalization of TAR DNA‐binding protein 43 (TDP‐43) proteins in more than 95% of ALS patients, suggesting a universal role TDP‐43 proteinopathy in ALS. Mutations in SQSTM1/p62 have been identified in familial and sporadic cases of ALS. MicroRNAs (miRNAs) are small non‐coding RNAs that post‐transcriptionally regulate their target genes. Emerging evidence indicates that miRNA dysregulation is associated with neuronal toxicity and mitochondrial dysfunction, and also plays a pivotal role in ALS pathogenesis. Here, we report the first evidence that miR‐183‐5p is aberrantly upregulated in spinal cords of patients with ALS. Using luciferase reporter assays and miR‐183‐5p agomirs, we demonstrate that miR‐183‐5p regulates the SQSTM1/p62 3′‐untranslated region to suppress expression. A miR‐183‐5p agomir attenuated SOSTM1/p62 expression and led to an increase in TDP‐43 protein levels in neuronal and non‐neuronal cells. In contrast, a miR‐183‐5p antagomir decreased TDP‐43 but increased SQSTM1/p62 protein levels. The antagomir repressed formation of stress granules and aggregated TDP43 protein in neuronal cells under stress‐induced conditions and protected against cytotoxicity. Knockdown of SQSTM1/p62 decreased total ubiquitination and increased TDP‐43 protein aggregation, indicating that SQSTM1/p62 may play a protective role in cells. In summary, our study reveals a novel mechanism of TDP‐43 proteinopathy mediated by the miR‐183‐5p and provides a molecular link between aberrant RNA processing and protein degradation, two major pillars in ALS pathogenesis.
MiR‐183‐5p was previously found to be elevated in serum exosomes from ALS patients. Here, we found that miR‐183‐5p is aberrantly upregulated in spinal cord tissues of ALS patients. Using neuronal and non‐neuronal cells, we found that miR‐183‐5p increased TDP‐43 expression, aggregation, and stress‐induced cytotoxicity. SQSTM1/p62, on the other hand, was suppressed posttranscriptionally by miR‐183‐5p via the 3′ untranslated region. We found that silencing of SQSTM1/p62 recapitulates the increase in TDP‐43 expression and aggregation as observed with miR‐183‐5p. These findings suggest that the miR‐183‐5p/ SQSTM1/p62 axis plays a key role in the pathophysiology of ALS by promoting TDP‐43 aggregation and cellular toxicity.
Using targeted exome sequencing, we identified mutations in NNT, an antioxidant defense gene, in individuals with familial glucocorticoid deficiency. In mice with Nnt loss, higher levels of ...adrenocortical cell apoptosis and impaired glucocorticoid production were observed. NNT knockdown in a human adrenocortical cell line resulted in impaired redox potential and increased reactive oxygen species (ROS) levels. Our results suggest that NNT may have a role in ROS detoxification in human adrenal glands.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Investigating hydraulic and petrophysical properties of porous media has been an active area of research. Despite numerous progress in modeling flow and transport over the past decades, we are still ...far from accurately estimating the scale dependence of soil and rock properties. In this study, we propose applying renormalization group theory (RGT) at the pore scale. Using the RGT, we determine the scale dependence of effective pore‐throat radius (rteff) and develop two theoretical models to estimate permeability (k) in pore networks of various sizes. The first theoretical model estimates k(L) from the rteff(L) and simulated formation factor F(L), while the second model uses information at the smallest scale (L = Lmin) in addition to rteff(L) and F(L). By comparing with 25 pore‐network simulations, we show that the RGT estimates the scale‐dependent k reasonably well. The first model estimates k(L) with average relative errors ranged between −53.1% and −3.0%, while the second model between −1.0% and 14.33%. We also conduct fluid flow simulations in 40 other pore networks above the representative elementary volume and compare the results of the RGT with those of the effective‐medium approximation (EMA). Results showed that both RGT and EMA accurately estimate k from pore‐throat radius distribution and formation factor with root mean square log‐transformed error = 0.119 and 0.096, respectively.
Key Points
Scale dependence of permeability at the pore scale is investigated using pore‐network simulations
Renormalization group theory estimates scale‐dependent permeability with good accuracy
Effective‐medium and renormalization group theories similarly estimate permeability in the studied networks
The potential of induced pluripotent stem cells (iPSCs) in disease modeling and regenerative medicine is vast, but current methodologies remain inefficient. Understanding the cellular mechanisms ...underlying iPSC reprogramming, such as the metabolic shift from oxidative to glycolytic energy production, is key to improving its efficiency. We have developed a lentiviral reporter system to assay longitudinal changes in cell signaling and transcription factor activity in living cells throughout iPSC reprogramming of human dermal fibroblasts. We reveal early NF-κB, AP-1, and NRF2 transcription factor activation prior to a temporal peak in hypoxia inducible factor α (HIFα) activity. Mechanistically, we show that an early burst in oxidative phosphorylation and elevated reactive oxygen species generation mediates increased NRF2 activity, which in turn initiates the HIFα-mediated glycolytic shift and may modulate glucose redistribution to the pentose phosphate pathway. Critically, inhibition of NRF2 by KEAP1 overexpression compromises metabolic reprogramming and results in reduced efficiency of iPSC colony formation.
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•Cells increase proliferation, OXPHOS, and ROS production early in reprogramming•The antioxidant response is therefore active at this stage, prior to HIFα activation•NRF2 promotes HIFα activation, the metabolic switch, and colony formation•NRF2 activation is concomitant with glucose redistribution to the PPP
Hawkins et al. examine the metabolic shift during iPSC reprogramming. They propose that increased proliferation of cells driven by transgene expression can lead to increased oxidative phosphorylation resulting in ROS production. Elevated ROS activates NRF2, promoting HIFα activation and the switch to glycolysis.
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