Maintenance and rehabilitation (M&R) is necessary to keep pavement networks in good condition. Due to the capital intensity, M&R funding is always insufficient. The annual budget, determining the ...available funding, is a critical criterion when planning M&R treatments. However, its values are often given, and the determination of the values is seldom discussed. To fill the gap, this paper focuses on both the determination of annual budgets and the budget allocations, and therefore enhances the network-level decision-making on M&R by developing a Multi-Objective Optimization (MOO) method. This method does not only optimize and trade off the annual budgets and their consequences, but also allocates the funding across the entire network through generating the optimized M&R decisions. According to a case study with 50 segments, the developed method successfully and effectively identified non-linear discrete relationship between the minimized annual budgets and the maximized M&R benefits subject to all the constraints, and generated the optimized annual budget allocation for each M&R decision. The achievements of this paper can be used to enhance the efficiency of M&R decisions and contribute to informed pavement management.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Huntington's disease (HD) is a neurodegenerative disorder that manifests with movement dysfunction. The expression of mutant Huntingtin (mHTT) disrupts the functions of brain cells. Galectin-3 (Gal3) ...is a lectin that has not been extensively explored in brain diseases. Herein, we showed that the plasma Gal3 levels of HD patients and mice correlated with disease severity. Moreover, brain Gal3 levels were higher in patients and mice with HD than those in controls. The up-regulation of Gal3 in HD mice occurred before motor impairment, and its level remained high in microglia throughout disease progression. The cell-autonomous up-regulated Gal3 formed puncta in damaged lysosomes and contributed to inflammation through NFκB- and NLRP3 inflammasome-dependent pathways. Knockdown of Gal3 suppressed inflammation, reduced mHTT aggregation, restored neuronal DARPP32 levels, ameliorated motor dysfunction, and increased survival in HD mice. Thus, suppression of Gal3 ameliorates microglia-mediated pathogenesis, which suggests that Gal3 is a novel druggable target for HD.
Geochemical studies of sulfur in coals comprise several major aspects relating to the nature and origin of sulfur in coals, including the abundance and distribution of sulfur in coal seams, abundance ...of sulfur in coal lithotypes and macerals, characteristics and geochemical significance of sulfur-containing organic compounds, sulfur isotopic studies relating to the sources of sulfur in coals, and sedimentary environments controlling the geochemistry of sulfur in coal. A review of the evidence suggests that the variation of sulfur in coals is closely related to the depositional environments of coal seams. For low-sulfur coal (<1% S), sulfur is derived primarily from parent plant material. For medium-sulfur (1 to <3% S) and high-sulfur (≥3% S) coals, there are two major sources of sulfur: 1) parent plant material, and 2) sulfate in seawater that flooded peat swamps. Abundances of sulfur in coal are largely controlled by the degree of seawater influence during peat accumulation and by postdepositional changes (diagenesis). In high-sulfur coals, seawater sulfate diffuses into the peat, which is subsequently reduced by bacteria into hydrogen sulfide, polysulfides, and elemental sulfur. Reaction of hydrogen sulfide with ferrous iron generates fine pyrite crystals and mackinawite FeS0.9. Mackinawite reacts with elemental sulfur to converts to greigite Fe3S4 and then to framboidal pyrite. The reduced sulfur species in the peat (hydrogen sulfide, elemental sulfur and polysulfides) react with the organic matter to form organic sulfur compounds. During coal diagenesis, nodular pyrite forms. Permineralized peat was formed during diagenesis which contains appreciable fraction of pyrite. After coal is solidified, pyrite can deposit in the cleats from circulating groundwater. Epigenetic pyrite veins may be deposited from basinal fluids. Thus, pyrite forms during various stages of coal formation from peat to coal, as well as late epigenetic activity.
The relationships between sulfur abundance in coal seams and depositional environments of coals were reviewed for cases from the U.S., China, U.K., Germany, Hungary, Turkey, Indonesia, and Brazil. In most cases, low-sulfur coals formed in a fluvial environment and high-sulfur coals were deposited in seawater-influenced environments. There are exceptions. For example, Turkish lignites formed in freshwater environments are high-sulfur. Sulfur sources other than seawater are needed for these high-sulfur coals. The superhigh-organic-sulfur (SHOS) coals are highly enriched in organic sulfur but depleted in pyritic sulfur. The SHOS coals were deposited in sulfur-rich, iron-poor environments, such as carbonate platforms or in an iron-poor and clastic-starved environment in which algae accumulate. Speciation of organic sulfur compounds in coal appears to be related to coal rank; thiophenic compounds are more abundant in bituminous coal and anthracite than in low-rank coals.
► Sulfur abundance in coals is controlled primarily by depositional environments. ► Sulfur isotopic evidence indicates a seawater source for sulfur in high-sulfur coal. ► Formation of pyrite and organic sulfur compounds during diagenesis. ► A high-sulfur, iron-poor environment for the superhigh-organic-sulfur coal.
Previous studies have revealed that coronary artery calcium is related to cardiovascular diseases and mortality. However, most studies have been conducted in Western countries and have excluded ...patients with pre-existing heart disease. We investigated the association between coronary artery calcium (CAC) and all-cause mortality in an Asian cohort and in subgroups stratified by age, sex, smoking, obesity, diabetes, cardiovascular disease, blood pressure, and biochemical parameters. We conducted a retrospective cohort study on 4529 health examinees who underwent multidetector computed tomography in a tertiary medical center in Taiwan between 2011 and 2016. The mean follow-up was 3.5 years. Cox regression was used to estimate the relative hazards of death. Stratified analyses were performed. The all-cause mortality rates were 2.94, 4.88, 17.6, and 33.1 per 1000 person-years for CAC scores of 0, 1-100, 101-400, and >400, respectively. The multivariable adjusted hazard ratios (95% confidence intervals CIs) for all-cause mortality were 0.95 (0.53, 1.72), 1.87 (0.89, 3.90), and 3.05 (1.46, 6.39) for CAC scores of 1-100, 101-400, and >400, respectively, relative to a CAC score of 0. Compared with CAC less than or equal to 400, the HRs (95% CIs) for CAC > 400 were 6.46 (2.44, 17.15) and 1.94 (1.00, 3.76) in younger and older adults, respectively, indicating that age was a moderating variable (p = 0.02). High CAC scores were associated with increased all-cause mortality. Although older adult patients had higher risks of death, the relative risk of death for patients with CAC > 400 was more prominent in people younger than 65 years.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Herein, the fabrication of a lead-free cesium germanium halide perovskite produced
a simple solvothermal process is reported for the first time. By tuning the composition of the CsGeX
quantum rods, a ...power conversion efficiency of 4.92% under AM 1.5 G was achieved.
We evaluate the connection between corporate characteristics and the reaction of stock returns to COVID-19 cases using data on more than 6,700 firms across 61 economies. The pandemic-induced drop in ...stock returns was milder among firms with stronger pre-2020 finances (more cash and undrawn credit, less total and short-term debt, and larger profits), less exposure to COVID-19 through global supply chains and customer locations, more corporate social responsibility activities, and less entrenched executives. Furthermore, the stock returns of firms controlled by families (especially through direct holdings and with non-family managers), large corporations, and governments performed better, and those with greater ownership by hedge funds and other asset management companies performed worse. Stock markets positively price small amounts of managerial ownership but negatively price high levels of managerial ownership during the pandemic.
Conventional subsidence analysis methods are generally based on the assumption of instantaneous stretching, which totally ignores the heat loss during continental rifting. For long-duration or ...multi-episodic extensional tectonics, such assumption is no longer valid and could cause significant deviation from real subsidence. Here I extend original finite stretching model to a multi-stage scenario in terms of geothermal and structural successions between two adjacent rifting events. A procedure is designed to estimate stretching factor by fitting the whole tectonic subsidence history in a self-consistent manner on the basis of the extended model. I apply this procedure to the Baiyun Sag in the continent slope of the South China Sea. Subsidence analysis shows that the sag is characterized by two episodes of rifting. The first stage (49 to 23.8Ma) resulted in stretching factors in the range of 1.3 to 4.0 with the greatest stretching at the sag center, while the second one (17.5 to 10.5Ma) yielded minor stretching factors of 1.1 to 1.2. These estimates agree well with that determined from crustal thinning for the northern and central potions of the sag, but significant discrepancy occurs between the southern edge of the sag and the present continent–ocean boundary, where the crustal thickness is less than 20km and potentially extensive magmatic intrusion was well imaged in the seismic profiles. I suggest that the magma-assisted rheologically weakening and possible lower crust ductile flow contributed to the extension discrepancy. The margin north of the Baiyun Sag, having a relatively thick crust and vacant of magmatic activity, was basically stretched in a depth-uniform style. It is inferred that preexisting weakness in the lithosphere and abundant sediment supply were responsible for the extremely thick Cenozoic sediment developed in the Baiyun Sag.
•Procedure is presented to estimate stretching factor for multi-episode extension.•Stretching factors were estimated from subsidence analysis for Baiyun Sag.•Magmatic activity influences the style of continental extension.•Preexisting weakness and rich sediment supply were responsible for thick sediment.
BACKGROUND:The impact of gut microbiota on the regulation of host physiology has recently garnered considerable attention, particularly in key areas such as the immune system and metabolism. These ...areas are also crucial for the pathophysiology of and repair after myocardial infarction (MI). However, the role of the gut microbiota in the context of MI remains to be fully elucidated.
METHODS:To investigate the effects of gut microbiota on cardiac repair after MI, C57BL/6J mice were treated with antibiotics 7 days before MI to deplete mouse gut microbiota. Flow cytometry was applied to examine the changes in immune cell composition in the heart. 16S rDNA sequencing was conducted as a readout for changes in gut microbial composition. Short-chain fatty acid (SCFA) species altered after antibiotic treatment were identified by high-performance liquid chromatography. Fecal reconstitution, transplantation of monocytes, or dietary SCFA or Lactobacillus probiotic supplementation was conducted to evaluate the cardioprotective effects of microbiota on the mice after MI.
RESULTS:Antibiotic-treated mice displayed drastic, dose-dependent mortality after MI. We observed an association between the gut microbiota depletion and significant reductions in the proportion of myeloid cells and SCFAs, more specifically acetate, butyrate, and propionate. Infiltration of CX3CR1+ monocytes to the peri-infarct zone after MI was also reduced, suggesting impairment of repair after MI. Accordingly, the physiological status and survival of mice were significantly improved after fecal reconstitution, transplantation of monocytes, or dietary SCFA supplementation. MI was associated with a reorganization of the gut microbial community such as a reduction in Lactobacillus. Supplementing antibiotic-treated mice with a Lactobacillus probiotic before MI restored myeloid cell proportions, yielded cardioprotective effects, and shifted the balance of SCFAs toward propionate.
CONCLUSIONS:Gut microbiota–derived SCFAs play an important role in maintaining host immune composition and repair capacity after MI. This suggests that manipulation of these elements may provide opportunities to modulate pathological outcome after MI and indeed human health and disease as a whole.
Lithium–sulfur (Li–S) batteries have attracted much attention lately because they have very high theoretical specific energy (2500 Wh kg−1), five times higher than that of the commercial ...LiCoO2/graphite batteries. As a result, they are strong contenders for next-generation energy storage in the areas of portable electronics, electric vehicles, and storage systems for renewable energy such as wind power and solar energy. However, poor cycling life and low capacity retention are main factors limiting their commercialization. To date, a large number of electrode and electrolyte materials to address these challenges have been investigated. In this review, we present the latest fundamental studies and technological development of various nanostructured cathode materials for Li–S batteries, including their preparation approaches, structure, morphology and battery performance. Furthermore, the development of other significant components of Li–S batteries including anodes, electrolytes, additives, binders and separators are also highlighted. Not only does the intention of our review article comprise the summary of recent advances in Li–S cells, but also we cover some of our proposals for engineering of Li–S cell configurations. These systematic discussion and proposed directions can enlighten ideas and offer avenues in the rational design of durable and high performance Li–S batteries in the near future.
•Li–S batteries have great potential as the next generation high capacity batteries.•Nanostructured sulfur electrodes are essential to realize this potential.•Anodes, electrolytes, additives, binders and separators also play critical roles.•Cell configuration with novel components can result in breakthroughs.
The continued threat of emerging, highly lethal infectious pathogens such as Middle East respiratory syndrome coronavirus (MERS‐CoV) calls for the development of novel vaccine technology that offers ...safe and effective prophylactic measures. Here, a novel nanoparticle vaccine is developed to deliver subunit viral antigens and STING agonists in a virus‐like fashion. STING agonists are first encapsulated into capsid‐like hollow polymeric nanoparticles, which show multiple favorable attributes, including a pH‐responsive release profile, prominent local immune activation, and reduced systemic reactogenicity. Upon subsequent antigen conjugation, the nanoparticles carry morphological semblance to native virions and facilitate codelivery of antigens and STING agonists to draining lymph nodes and immune cells for immune potentiation. Nanoparticle vaccine effectiveness is supported by the elicitation of potent neutralization antibody and antigen‐specific T cell responses in mice immunized with a MERS‐CoV nanoparticle vaccine candidate. Using a MERS‐CoV‐permissive transgenic mouse model, it is shown that mice immunized with this nanoparticle‐based MERS‐CoV vaccine are protected against a lethal challenge of MERS‐CoV without triggering undesirable eosinophilic immunopathology. Together, the biocompatible hollow nanoparticle described herein provides an excellent strategy for delivering both subunit vaccine candidates and novel adjuvants, enabling accelerated development of effective and safe vaccines against emerging viral pathogens.
To improve vaccination efforts against Middle East respiratory syndrome coronavirus (MERS‐CoV), a virus‐mimicking vaccine is herein prepared with a capsid‐like hollow polymeric nanoparticle loaded with STING agonists and coated in MERS‐CoV antigens. The viromimetic nanoparticle facilitates safe and effective vaccination against the lethal virus and offers a versatile platform for combatting emerging infectious threats.
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