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71.
The occurrence of accidents and injuries continues to be a major problem in construction worldwide. Even though accident statistics have been improving in most markets there are significant areas requiring further attention. The extent of integrated working between designers and constructors may be an instrumental factor. A comparison is undertaken of the accident performance of 55 large construction projects in the UK, with varying levels of design/construction integration as represented by procurement path. Although a statistical relationship between high levels of integration and low levels of accidents was weak, a follow‐up interview study provided strong support, suggesting that a lack of significance was related to the unreliability of the statistics available. The interview study also indicated reasons for this link. A key element in improved safety was seen to be better communications and a more positive relationship between designers and constructors. Further research into designing for safety for all procurement paths is recommended.  相似文献   
72.
While contemporary urban theories suggest that individuals have transcended their geographical community, evidence suggests that urban residents still feel ‘attached’ to place. In the literature, several socio-demographic characteristics are associated with place attachment. Scholars suggest physical features, such as community ‘greenspace’, may also influence place attachment. Yet research does not consider the relationship between one's objective proximity to greenspace or the objective availability of community greenspace on residents' place attachment. This study employs multi-level models and draws on police incident data, census data, two spatial data sets and survey data from over 4000 residents living across 148 state suburbs in Australia to assess the relationship between greenspace proximity and greenspace availability on place attachment. Our findings indicate that greater proportions and more accessible greenspace may not improve residents' attachment to their local community.  相似文献   
73.
Large wood (re)introduction can deliver multiple benefits in river restoration, but there is a dearth of the detailed and longer‐term post‐project monitoring and evaluation required for improving best practice. We present findings from an academic partnership approach to post‐project evaluation, based on successive MSc research projects on restored large wood in the Loddon catchment, UK. Field and modelling data reveal: (i) key differences in large wood features between restored and natural reaches; (ii) increased hydraulic retention and changes to mesohabitats associated with large wood; (iii) differences in macroinvertebrate community composition around large wood but a lack of site‐level effects; (iv) interactions between macrophytes and large wood that may be specific to restored reaches; (v) a need for further field and modelling studies to inform the accurate representation of large wood in hydraulic models. Some key challenges in partnership working are identified to aid planning and effectiveness of future collaborations.  相似文献   
74.
Excess dietary fructose is a major public health concern, yet little is known about its influence on offspring development and later-life disease when consumed in excess during pregnancy. To determine whether increased maternal fructose intake could have long-term consequences on offspring health, we investigated the effects of 10% w/v fructose water intake during preconception and pregnancy in guinea pigs. Female Dunkin Hartley guinea pigs were fed a control diet (CD) or fructose diet (FD; providing 16% of total daily caloric intake) ad libitum 60 days prior to mating and throughout gestation. Dietary interventions ceased at day of delivery. Offspring were culled at day 21 (D21) (weaning) and at 4 months (4 M) (young adult). Fetal exposure to excess maternal fructose intake significantly increased male and female triglycerides at D21 and 4 M and circulating palmitoleic acid and total omega-7 through day 0 (D0) to 4 M. Proteomic and functional analysis of significantly differentially expressed proteins revealed that FD offspring (D21 and 4 M) had significantly increased mitochondrial metabolic activities of β-oxidation, electron transport chain (ETC) and oxidative phosphorylation and reactive oxygen species production compared to the CD offspring. Western blotting analysis of both FD offspring validated the increased protein abundances of mitochondrial ETC complex II and IV, SREBP-1c and FAS, whereas VDAC1 expression was higher at D21 but lower at 4 M. We provide evidence demonstrating offspring programmed hepatic mitochondrial metabolism and de novo lipogenesis following excess maternal fructose exposure. These underlying asymptomatic programmed pathways may lead to a predisposition to metabolic dysfunction later in life.  相似文献   
75.
Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein–kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE+ MCs, tryptase+ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient.  相似文献   
76.
Teriflunomide (TFN) limits relapses in relapsing–remitting multiple sclerosis (RRMS) by reducing lymphocytic proliferation through the inhibition of the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) and the subsequent modulation of de novo pyrimidine synthesis. Alterations of mitochondrial function as a consequence of oxidative stress have been reported during neuroinflammation. Previously, we showed that TFN prevents alterations of mitochondrial motility caused by oxidative stress in peripheral axons. Here, we aimed to validate TFN effects on mitochondria and neuronal activity in hippocampal brain slices, in which cellular distribution and synaptic circuits are largely preserved. TFN effects on metabolism and neuronal activity were investigated by assessing oxygen partial pressure and local field potential in acute slices. Additionally, we imaged mitochondria in brain slices from the transgenic Thy1-CFP/COX8A)S2Lich/J (mitoCFP) mice using two-photon microscopy. Although TFN could not prevent oxidative stress-related depletion of ATP, it preserved oxygen consumption and neuronal activity in CNS tissue during oxidative stress. Furthermore, TFN prevented mitochondrial shortening and fragmentation of puncta-shaped and network mitochondria during oxidative stress. Regarding motility, TFN accentuated the decrease in mitochondrial displacement and increase in speed observed during oxidative stress. Importantly, these effects were not associated with neuronal viability and did not lead to axonal damage. In conclusion, during conditions of oxidative stress, TFN preserves the functionality of neurons and prevents morphological and motility alterations of mitochondria.  相似文献   
77.
Monomeric RGD peptides show unspecific fluid-phase uptake in cells, whereas multimeric RGD peptides are thought to be internalized by integrin-mediated endocytosis. However, a potential correlation between uptake mechanism and molecular mass has been neglected so far. A dual derivatization of peptide c(RGDw(7Br)K) was performed to investigate this. A fluorescent probe was installed by chemoselective Suzuki–Miyaura cross-coupling of the 7-bromotryptophan and a poly(ethylene glycol) (PEG) linker was attached to the lysine residue. Flow cytometry and live cell imaging confirmed unspecific uptake of the small, non-PEGylated peptide, whereas the PEG5000 peptide conjugate unveiled a selective internalization by M21 cells overexpressing αvβ3 and no uptake in αv-deficient M21L cells.  相似文献   
78.
Sustainable process design (SPD) problems combine a process design problem with life cycle assessment (LCA) to optimize process economics and life cycle environmental impacts. While SPD makes use of recent advances in process systems engineering and optimization, its use of LCA has stagnated. Currently, only process LCA is utilized in SPD, resulting in designs based on incomplete and potentially inaccurate life cycle information. To address these shortcomings, the multiscale process to planet (P2P) modeling framework is applied to formulate and solve the SPD problem. The P2P framework offers a more comprehensive analysis boundary than conventional SPD and greater modeling detail than advanced LCA methodologies. Benefits of applying this framework to SPD are demonstrated with an ethanol process design case study. Results show that current methods shift emissions outside the analysis boundary, while applying the P2P modeling framework results in environmentally superior process designs. Future extensions of the P2P framework are discussed. © 2015 American Institute of Chemical Engineers AIChE J, 61: 3320–3331, 2015  相似文献   
79.
Cairns-Smith has proposed that life began as structural patterns in clays that self-replicated during cycles of crystal growth and fragmentation. Complex, evolved crystal forms could then have catalyzed the formation of a more advanced genetic material. A crucial weakness of this theory is that it is unclear how complex crystals might arise through Darwinian evolution and selection. Here we investigate whether complex crystal patterns could evolve using a model system for crystal growth, DNA tile crystals, that is amenable to both theoretical and experimental inquiry. It was previously shown that in principle, the evolution of crystals assembled from a set of thousands of DNA tile types under very specific environmental conditions could produce arbitrarily complex patterns. Here we show that evolution driven only by the dearth of one monomer type could produce complex crystals from just 12 monomer types. When a monomer type is rare, crystals that use few of this monomer type are selected for. We use explicit enumeration to show that there are situations in which crystal species that use a particular monomer type less frequently will grow faster, yet to do so requires that the information contained in the crystal become more complex. We show that this feature of crystal organization could allow more complex crystal morphologies to be selected for in the right environment, using both analysis in a simple model of self-assembly and stochastic kinetic simulations of crystal growth. The proposed mechanism of evolution is simple enough to test experimentally and is sufficiently general that it may apply to other DNA tile crystals or even to natural crystals, suggesting that complex crystals could evolve from simple starting materials because of relative differences in concentrations of the materials needed for growth.  相似文献   
80.
Older occupants in motor-vehicle crashes are more likely to experience injury than younger occupants. One possible reason for this is that increasing age is associated with increased prevalence of osteoporosis, which decreases bone strength.Crash-injury data were used with Bayes’ Theorem to estimate the conditional probability of AIS 3+ skeletal injury given that an occupant is osteoporotic for the injury to the head, spine, thorax, lower extremities, and upper extremities. This requires the conditional probabilities of osteoporosis given AIS 3+ injury for each of the body regions, which were determined from analysis of the Crash Injury Research and Engineering Network database. It also requires information on probability of osteoporosis in the crash-involved population and the probabilities of AIS 3+ skeletal injury to different body regions in crashes. The latter probabilities were obtained from the National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) database. The former was obtained by modeling the probability of osteoporosis in the US populations using data from the 2006 National Health Examination Nutrition Survey and applying this model to the estimate of the crash-involved population in NASS-CDS. To attempt to account for the effects of age on injury outcome that are independent of osteoporosis, only data from occupants who were 60 years of age or older were used in all analyses.Results indicate that the only body region that experiences a statistically significant change in fracture injury risk with osteoporosis is the spine, for which osteoporosis increases the risk of AIS 3+ fracture by 3.28 times, or from 0.41% to 1.34% (p < 0.0001). This finding suggests that the increase in AIS 3+ injury risk with age for non-spine injuries is likely influenced by factors other than osteoporosis.  相似文献   
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