While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring ...human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17-16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Display omitted
Approximately 20 kg of dust and sludges are produced per ton of liquid steel produced via the blast furnaces (BF)/basic oxygen furnace (BOF) production route. Many of these dusts are ...recycled through the sinter plant or blast furnace route without issue, but high zinc content dusts are routinely landfilled. Hydrometallurgical techniques, such as alkaline leaching, that are often utilized to remove zinc from electric arc furnace dusts are inappropriate for recovery of material from BOS dust due to the lower zinc concentration present and extra post-processing steps to utilize the separated iron product. Pyrometallurgical treatment through a rotary hearth furnace (RHF), in processes such as FASTMET®, can currently be considered as the most commercially attractive option for the processing and recovery of iron and zinc units when employed as part of an integrated steelworks. The crude zinc oxide produced is suitable for sale to zinc smelters, and the direct reduced iron produced provides process benefits through use, such as reduced blast furnace coking rates and increased productivity. The advantages and disadvantages of variations and alternatives are reviewed with regard to future developments.
RATIONALE:Sympathetic nervous system control of inflammation plays a central role in hypertension. The gut receives significant sympathetic innervation, is densely populated with a diverse microbial ...ecosystem, and contains immune cells that greatly impact overall inflammatory homeostasis. Despite this uniqueness, little is known about the involvement of the gut in hypertension.
OBJECTIVE:Test the hypothesis that increased sympathetic drive to the gut is associated with increased gut wall permeability, increased inflammatory status, and microbial dysbiosis and that these gut pathological changes are linked to hypertension.
METHODS AND RESULTS:Gut epithelial integrity and wall pathology were examined in spontaneously hypertensive rat and chronic angiotensin II infusion rat models. The increase in blood pressure in spontaneously hypertensive rat was associated with gut pathology that included increased intestinal permeability and decreased tight junction proteins. These changes in gut pathology in hypertension were associated with alterations in microbial communities relevant in blood pressure control. We also observed enhanced gut–neuronal communication in hypertension originating from paraventricular nucleus of the hypothalamus and presenting as increased sympathetic drive to the gut. Finally, angiotensin-converting enzyme inhibition (captopril) normalized blood pressure and was associated with reversal of gut pathology.
CONCLUSIONS:A dysfunctional sympathetic–gut communication is associated with gut pathology, dysbiosis, and inflammation and plays a key role in hypertension. Thus, targeting of gut microbiota by innovative probiotics, antibiotics, and fecal transplant, in combination with the current pharmacotherapy, may be a novel strategy for hypertension treatment.
The global pandemic response to COVID-19 has led to the generation of huge volumes of unrecyclable plastic waste from single use disposable face coverings. Rotary hearth furnaces can be used to ...recover Zn and Fe from non-recyclable steelmaking by-product dusts, and waste plastic material such as facemasks could be utilized as a supplementary reductant for the rotary hearth furnace (RHF), but their fibrous form makes milling and processing to appropriate sizing for RHF application extremely challenging. A scalable method of grinding facemasks to powder by melting and mixing with Welsh coal dust reported herein provides a solution to both environmental challenges. The melt-blended PPE/coal dust shows a dramatically improved CO
gasification reactivity (E
= 133-159 kJmol
) when compared to the untreated coal (E
= 183-246 kJmol
), because of improved pore development in the coal during the pyrolysis stage of heating and the catalytic activity of the CaO based ash present in the facemask plastic. The results are promising for the application of waste facemasks in recycling steelmaking by-product dusts in rotary hearth furnaces and may also be suitable for direct injection to the blast furnace subject to further study.
Inflammatory bowel disease (IBD) continues to increase in prevalence in industrialized countries. Major complications of IBD include formation of fibrotic strictures, fistulas, reduced absorptive ...function, cancer risk, and the need for surgery. In other chronic gastrointestinal disease models, stiffness has been shown to precede fibrosis; therefore, stiffness may be a reasonable indicator of progression toward stricture formation in IBD patients. Herein, we seek to quantify tissue stiffness and characterize fibrosis in patients with IBD and to compare mechanical properties of unaffected human tissue to common animal species used for IBD studies. Inflamed and unaffected tissue from IBD patients and unaffected tissue from mice, pigs, and cows were indented using a custom device to determine the effective stiffness. Histology was performed on matched tissues, and total RNA was isolated from IBD tissue samples and used for gene expression analysis of pro-fibrotic genes. We observed an increase in the effective stiffness (steady-state modulus, SSM) (p < 0.0001) and increased expression of the collagen type I gene (COL1A1, p = 0.01) in inflamed tissue compared to unaffected areas in our IBD patient cohort. We also found that increased staining of collagen fibers in submucosa positively correlated with SSM (p = 0.093). We determined that unaffected animal bowel stiffness is significantly greater than similar human tissues, suggesting additional limitations on animal models for translational investigations regarding stiffness-related hypotheses. Taken together, our data support development of tools for evaluation of bowel stiffness in IBD patients for prognostic applications that may enable more accurate prediction of those who will develop fibrosis and more precise prescription of aggressive therapies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The efficient conversion of carbon dioxide (CO2) to high-value chemicals using renewable solar energy is a highly attractive but very challenging process that is used to address ever-growing energy ...demands and environmental issues. In recent years, metal–organic frameworks (MOFs) have received significant research attention owing to their tuneability in terms of their composition, structure, and multifunctional characteristics. The functionalisation of MOFs by metal nanoparticles (NPs) is a promising approach used to enhance their light absorption and photocatalytic activity. The efficient charge separation and strong CO2 binding affinity of hybrid MOF-based photocatalysts facilitate the CO2 conversion process. This review summarises the latest advancements involving noble metal, non-noble-metal, and miscellaneous species functionalised MOF-based hybrid photocatalysts for the reduction of CO2 to carbon monoxide (CO) and other value-added chemicals. The novel synthetic strategies and their corresponding structure–property relationships have also been discussed for solar-to-chemical energy conversion. Furthermore, the current challenges and prospects in practical applications are also highlighted for sustainable energy production.
MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose ...cell death, precisely how it functions to promote survival of normal and malignant cells is poorly understood. Here, we report that different forms of MCL-1 reside in distinct mitochondrial locations and exhibit separable functions. On the outer mitochondrial membrane, an MCL-1 isoform acts like other anti-apoptotic BCL-2 molecules to antagonize apoptosis, whereas an amino-terminally truncated isoform of MCL-1 that is imported into the mitochondrial matrix is necessary to facilitate normal mitochondrial fusion, ATP production, membrane potential, respiration, cristae ultrastructure and maintenance of oligomeric ATP synthase. Our results provide insight into how the surprisingly diverse salutary functions of MCL-1 may control the survival of both normal and cancer cells.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although aspects of Smo signaling are conserved from ...Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and the ability of vertebrate Smo to induce distinct G protein-dependent and independent signals in response to ligand. Whereas the canonical Smo signal to Gli transcriptional effectors occurs in a G protein-independent manner, its non-canonical signal employs Gαi. Whether vertebrate Smo can selectively bias its signal between these routes is not yet known. N-linked glycosylation is a post-translational modification that can influence GPCR trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila and vertebrate systems harbor N-linked glycans, but their role in Smo signaling has not been established. Herein, we present a comprehensive analysis of Drosophila and murine Smo glycosylation that supports a functional divergence in the contribution of N-linked glycans to signaling. Of the seven predicted glycan acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at this site disrupted Smo trafficking and attenuated its signaling capability. In stark contrast, we found that all four predicted N-glycosylation sites on murine Smo were dispensable for proper trafficking, agonist binding and canonical signal induction. However, the under-glycosylated protein was compromised in its ability to induce a non-canonical signal through Gαi, providing for the first time evidence that Smo can bias its signal and that a post-translational modification can impact this process. As such, we postulate a profound shift in N-glycan function from affecting Smo ER exit in flies to influencing its signal output in mice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Zinc contaminated steelmaking by-products such as blast furnace (BF) dust and basic oxygen steelmaking (BOS) dust present a significant recycling challenge at integrated steelmaking plants. Rotary ...Hearth Furnaces (RHFs) provide an attractive route for recovery of Fe and Zn from these materials through carbothermal reduction of the oxides in the material to yield Direct Reduced Iron (DRI) and crude zinc oxide. The next generation of RHF processes such as ITmk3 and e-nugget produce pig iron nuggets from iron ore concentrates and coal, as iron and gangue separate in-situ without an additional melting unit. A computational study of the metal-slag system using FACTSAGE 7.3 suggests that production of pig iron nuggets of good quality (93.75 wt.% Fe, 4.3 wt.% C, 0.116 wt.% S, 0.66 wt.% Mn) can be produced from BF dust and BOS dust in a ratio of 37:63 with addition of 5.4 wt.% SiO2 and 1.51 wt% MgO at 1450 °C. These computational results are in good agreement with experimental studies on similar material and, as such, suggest a practically feasible process.
Display omitted
Despite a fair amount of conjecture regarding the circumstances that lead to the generation of status orders, most of the previous literature in this area typically has studied the effects of social ...cues within a laboratory setting. This article analyzes the evolution of the status hierarchy within a large-scale, natural setting. The results of empirical analyses assessing a large online community of software developers show that in the process of status attainment, community members tend to evaluate a focal actor's reputation according to publicly available social references. Ironically, these same social references also work to constrain an actor's status mobility.
PDF
