Abstract
The unstable nature of the material point method (MPM) is widely documented and is a barrier to the method being used for routine engineering analyses of large deformation problems. The vast ...majority of articles concerning this issue are focused on the instabilities that manifest when a material point crosses between background grid cells. However, there are other issues related to the stability of MPMs. This article focuses on the issue of the conditioning of the global system of equations caused by the arbitrary nature of the position of the physical domain relative to the background computational grid. The issue is remedied here via the use of a ghost stabilisation technique that penalises variations in the gradient of the solution field near the boundaries of the physical domain. This technique transforms the stability of the MPM, providing a robust computational framework for large deformation explicit dynamic and implicit
quasi
‐static analysis.
Iron overload causes progressive organ damage and is associated with arthritis, liver damage, and heart failure. Elevated iron levels are present in 1%–5% of individuals; however, iron overload is ...undermonitored and underdiagnosed. Genetic factors affecting iron homeostasis are emerging. Individuals with hereditary xerocytosis, a rare disorder with gain-of-function (GOF) mutations in mechanosensitive PIEZO1 ion channel, develop age-onset iron overload. We show that constitutive or macrophage expression of a GOF Piezo1 allele in mice disrupts levels of the iron regulator hepcidin and causes iron overload. We further show that PIEZO1 is a key regulator of macrophage phagocytic activity and subsequent erythrocyte turnover. Strikingly, we find that E756del, a mild GOF PIEZO1 allele present in one-third of individuals of African descent, is strongly associated with increased plasma iron. Our study links macrophage mechanotransduction to iron metabolism and identifies a genetic risk factor for increased iron levels in African Americans.
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•Expression of gain-of-function PIEZO1 in macrophages induces iron overload in mice•PIEZO1 in macrophages plays an important role in regulating phagocytosis•PIEZO1 contributes to iron overload by increasing red blood cell turnover in vivo•Gain-of-function PIEZO1 is linked to elevated serum iron in American African individuals
Gain-of-function mutations in the mechanosensitive ion channel PIEZO1 result in iron overload and interference with iron metabolism.
Anticancer peptides (ACPs) are cationic amphipathic peptides that bind to and kill cancer cells either by a direct- or indirect-acting mechanism. ACPs provide a novel treatment strategy, and selected ...ACPs are currently in phase I clinical trials to examine their safety and overall benefit in cancer patients. Increasing the selectivity of ACPs is important so that these peptides kill cancer cells without harming normal cells. Peptide sequence modifications may help to improve ACP selectivity. ACPs also have immune-modulatory effects, including the release of danger signals from dying cancer cells, induction of chemokine genes, increasing T-cell immune responses, and inhibiting T regulatory cells. These effects ultimately increase the potential for an effective anticancer immune response that may contribute to long-term benefits and increased patient survival. Packaging ACPs in nanoparticles or fusogenic liposomes may be beneficial for increasing ACP half-life and enhancing the delivery of ACPs to tumor target cells. Additionally, engineering ACP-producing oncolytic viruses may be an effective future treatment strategy. Overall research in this area has been slow to progress, but with ongoing ACP-based clinical trials, the potential for ACPs in cancer treatments is closer to being realized. The integration of basic research with computer modeling of ACPs is predicted to substantially advance this field of research.
Serum starvation is a widely used condition in molecular biology experiments. Opti‐MEM is a serum‐reduced media used during transfection of genetic molecules into mammalian cells. However, the impact ...of such media on cell viability and protein synthesis is unknown. A549 human lung epithelial cell viability and morphology were adversely affected by growing in Opti‐MEM. The cellular protein levels of chloride intracellular channel protein 1, proteasome subunit alpha Type 2, and heat shock 70 kDa protein 5 were dysregulated in A549 cells after growing in serum‐reduced media. Small interfering RNA transfection was done in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum, and knockdown efficacy was determined compared with Opti‐MEM. Similar amounts of knockdown of the target proteins were achieved in DMEM, and cell viability was higher compared with Opti‐MEM after transfection. Careful consideration of the impact of Opti‐MEM media during the culture or transfection is important for experimental design and results interpretation.
Opti‐MEM is a serum‐reduced media used during the transfection of genetic molecules into mammalian cells. The media adversely affects cell morphology, viability, and protein synthesis in the human lung epithelial A549 cell. Complete media with regular amounts of fetal bovine serum show similar transfection efficacy but are less harmful to cell viability.
Liposuction is the second most commonly performed cosmetic surgery in the United States and the most common surgical procedure in patients between the ages of 35 and 64; practitioners of medicine and ...surgery will undoubtedly encounter these patients in their practice. This brief review discusses the role of liposuction and fat transfer in aesthetic and reconstructive surgery, as well as key considerations, indications, and safety concerns.
Material point methods suffer from volumetric locking when modelling near incompressible materials due to the combination of a low-order computational mesh and large numbers of material points per ...element. However, large numbers of material points per element are required to reduce integration errors due to non-optimum placement of integration points. This restricts the ability of current material point methods in modelling realistic material behaviour.
This paper presents for the first time a method to overcome finite deformation volumetric locking in standard and generalised interpolation material point methods for near-incompressible non-linear solid mechanics. The method does not place any restriction on the form of constitutive model used and is straightforward to implement into existing implicit material point method codes. The performance of the method is demonstrated on a number of two and three-dimensional examples and its correct implementation confirmed through convergence studies towards analytical solutions and by obtaining the correct order of convergence within the global Newton–Raphson equilibrium iterations. In particular, the proposed formulation has been shown to remove the over-stiff volumetric behaviour of conventional material point methods and reduce stress oscillations. It is straightforward to extend this approach to other material point methods and the presented formulation can be incorporated into all existing material point methods available in the literature.
•The proposed formulation overcomes finite deformation volumetric locking for near-incompressible non-linear solid mechanics.•The method is applicable to all existing material point methods.•No restriction is placed on the constitutive model.•Quasi-static implicit implementation ensures asymptotic quadratic convergence.•The formulation reduces spurious stress oscillations.
Virus infection induces different cellular responses in infected cells. These include cellular stress responses like autophagy and unfolded protein response (UPR). Both autophagy and UPR are ...connected to programed cell death I (apoptosis) in chronic stress conditions to regulate cellular homeostasis via Bcl2 family proteins, CHOP and Beclin-1. In this review article we first briefly discuss arboviruses, influenza virus, and HIV and then describe the concepts of apoptosis, autophagy, and UPR. Finally, we focus upon how apoptosis, autophagy, and UPR are involved in the regulation of cellular responses to arboviruses, influenza virus and HIV infections.
Abbreviation: AIDS: Acquired Immunodeficiency Syndrome; ATF6: Activating Transcription Factor 6; ATG6: Autophagy-specific Gene 6; BAG3: BCL Associated Athanogene 3; Bak: BCL-2-Anatagonist/Killer1; Bax; BCL-2: Associated X protein; Bcl-2: B cell Lymphoma 2x; BiP: Chaperon immunoglobulin heavy chain binding Protein; CARD: Caspase Recruitment Domain; cART: combination Antiretroviral Therapy; CCR5: C-C Chemokine Receptor type 5; CD4: Cluster of Differentiation 4; CHOP: C/EBP homologous protein; CXCR4: C-X-C Chemokine Receptor Type 4; Cyto c: Cytochrome C; DCs: Dendritic Cells; EDEM1: ER-degradation enhancing-a-mannosidase-like protein 1; ENV: Envelope; ER: Endoplasmic Reticulum; FasR: Fas Receptor;G2: Gap 2; G2/M: Gap2/Mitosis; GFAP: Glial Fibrillary Acidic Protein; GP120: Glycoprotein120; GP41: Glycoprotein41; HAND: HIV Associated Neurodegenerative Disease; HEK: Human Embryonic Kidney; HeLa: Human Cervical Epithelial Carcinoma; HIV: Human Immunodeficiency Virus; IPS-1: IFN-β promoter stimulator 1; IRE-1: Inositol Requiring Enzyme 1; IRGM: Immunity Related GTPase Family M protein; LAMP2A: Lysosome Associated Membrane Protein 2A; LC3: Microtubule Associated Light Chain 3; MDA5: Melanoma Differentiation Associated gene 5; MEF: Mouse Embryonic Fibroblast; MMP: Mitochondrial Membrane Permeabilization; Nef: Negative Regulatory Factor; OASIS: Old Astrocyte Specifically Induced Substrate; PAMP: Pathogen-Associated Molecular Pattern; PERK: Pancreatic Endoplasmic Reticulum Kinase; PRR: Pattern Recognition Receptor; Puma: P53 Upregulated Modulator of Apoptosis; RIG-I: Retinoic acid-Inducible Gene-I; Tat: Transactivator Protein of HIV; TLR: Toll-like receptor; ULK1: Unc51 Like Autophagy Activating Kinase 1; UPR: Unfolded Protein Response; Vpr: Viral Protein Regulatory; XBP1: X-Box Binding Protein 1
(1) Background: Influenza A Virus (IAV) uses host cellular proteins during replication in host cells. IAV infection causes elevated expression of chloride intracellular channel protein 1 (CLIC1) in ...lung epithelial cells, but the importance of this protein in IAV replication is unknown. (2) In this study, we determined the role of CLIC1 in IAV replication by investigating the effects of CLIC1 knockdown (KD) on IAV viral protein translation, genomic RNA transcription, and host cellular proteome dysregulation. (3) Results: CLIC1 KD in A549 human lung epithelial cells resulted in a significant decrease in progeny supernatant IAV, but virus protein expression was unaffected. However, a significantly larger number of viral RNAs accumulated in CLIC1 KD cells. Treatment with a CLIC1 inhibitor also caused a significant reduction in IAV replication, suggesting that CLIC1 is an important host factor in IAV replication. SomaScan
, which measures 1322 proteins, identified IAV-induced dysregulated proteins in wild-type cells and in CLIC1 KD cells. The expression of 116 and 149 proteins was significantly altered in wild-type and in CLIC1 KD cells, respectively. A large number of the dysregulated proteins in CLIC1 KD cells were associated with cellular transcription and predicted to be inhibited during IAV replication. (4) Conclusions: This study suggests that CLIC1 is involved in later stages of IAV replication. Further investigation should clarify mechanism(s) for the development of anti-IAV drugs targeting CLIC1 protein.
Magmatic minerals record the pre-eruptive timescales of magma ascent and mixing in crustal reservoirs and conduits. Investigations of the mineral records of magmatic processes are fundamental to our ...understanding of what controls eruption style, as ascent rates and magma mixing processes are well known to control and/or trigger potentially hazardous explosive eruptions. Thus, amphibole reaction rims are often used to infer pre-eruptive magma dynamics, and in particular to estimate magma ascent rates. However, while several experimental studies have investigated amphibole destabilization during decompression, only two investigated thermal destabilization relevant to magma mixing processes. This study examines amphibole decomposition experimentally through isobaric heating of magnesio-hornblende phenocrysts within a natural high-silica andesite glass. The experiments first equilibrated for 24 h at 870 °C and 140 MPa at H2O-saturated conditions and ƒO2 ∼ Re–ReO prior to rapid heating to 880, 900, or 920 °C and hold times of 3–48 h. At 920 °C, rim thicknesses increased from 17 μm after 3 h, to 55 μm after 12 h, and became pseudomorphs after longer durations. At 900 °C, rim thicknesses increased from 7 μm after 3 h, to 80 μm after 24 h, to pseudomorphs after longer durations. At 880 °C, rim thicknesses increased from 7 μm after 3 h, to 18 μm after 36 h, to pseudomorphs after 48 h. Reaction rim microlites vary from 5–16 μm in size, with no systematic relationship between crystal size and the duration or magnitude of heating. Time-averaged rim microlite growth rates decrease steadily with increasing experimental duration (from 3.97×10−7 mms−1 to 3.1 to 3.5×10−8 mms−1). Time-averaged microlite nucleation rates also decrease with increasing experimental duration (from 1.2×103 mm−3s−1 to 5.3 mm−3 s−1). There is no systematic relationship between time-averaged growth or nucleation rates and the magnitude of the heating step. Ortho- and clinopyroxene together constitute 57–90 modal % mineralogy in each reaction rim. At constant temperature, clinopyroxene abundances decrease with increasing experimental duration, from 72 modal % (3 h at 900 °C) to 0% (48 h at 880 °C, and 36 h at 900 and 920 °C). Fe–Ti oxides increase from 6–12 modal % (after 3–6 h) to 26–34 modal % (after 36–48 h). Plagioclase occurs in relatively minor amounts (<1–11 modal %), with anorthite contents that increase from An56 to An88 from 3 to 36 h of heating. Distal glass compositions (>500 μm from reacted amphibole) are consistent with inter-microlite rim glasses (71.3–77.7 wt.% SiO2) within a given experiment and there is a weakly positive correlation between increasing run duration and inter-microlite melt SiO2 (68.9–78.5 wt.%). Our results indicate that experimental heating-induced amphibole reaction rims have thicknesses, textures, and mineralogies consistent with many of the natural reaction rims seen at arc-andesite volcanoes. They are also texturally consistent with experimental decompression reaction rims. On this basis it may be challenging to distinguish between decompression and heating mechanisms in nature.
•Amphibole reaction rims form rapidly (3–48 h) following 10–50 °C of heating.•Reaction rim growth rates increases with increasing temperature.•Rim microlites formed during heating are fine grained (<20 μm).•Rims microlites formed by heating include plagioclase, oxides, and pyroxene.•Unambiguous differentiation between heating and decompression rims is challenging.
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