Acoustically Induced Flashback in a Staged Swirl-Stabilized Combustor

This paper describes a joint experimental and numerical investigation of the inter- action between thermoacoustics and flashback mechanisms in a swirled turbulent burner. An academic air/propane combustor terminated by a choked nozzle is operated up to 2.5 bars. Experiments show that the flame can stabilize either within the combustion chamber or flashback inside the injection duct, intermittently or permanently. The present study focuses on the mechanisms leading to flashback: this phenomenon can occur naturally, depending on the swirl level which can be adjusted in the experiment by introducing axial flow through the upstream inlet. It can also be triggered by acoustic waves, either through acoustic forc- ing or self-excited thermoacoustic instability. Flashback is difficult to study experimentally, but it can be investigated numerically using LES: in a first configuration, the outlet of the chamber is treated as a non-reflecting surface through which harmonic waves can be intro- duced. In this case, a 20 kPa acoustic forcing is sufficient to trigger permanent flashback after a few cycles. When the LES computational domain includes the choked nozzle used experimentally, no forcing is needed for flashback to occur. Self-excited oscillations reach high levels rapidly, leading to flame flashback, as observed experimentally. These results also suggest a simple method to avoid flashback by using fuel staging, which is then tested successfully in both LES and experiments

The clamping selection method to reduce the vibration of large-size workpieces during the face milling process

The article introduces a method for selecting the best clamping conditions to obtain vibration reduction during the milling of large-size workpieces. It is based on experimental modal analysis performed for a set of assumed, fixing conditions of a considered workpiece to identify frequency response functions (FRFs) for each tightening torque of the mounting screws. Simulated plots of periodically changing nominal cutting forces are then calculated. Subsequently, by multiplying FRF and spectra of cutting forces, a clamping selection function (CSF) is determined, and, thanks to this function, vibration root mean square (RMS) is calculated resulting in the clamping selection indicator (CSI) that indicates the best clamping of the workpiece. The effectiveness of the method was evidenced by assessing the RMS value of the vibration level observed in the time domain during the real-time face milling process of a large-sized exemplary item. The proposed approach may be useful for seeking the best conditions for fixing the workpiece on the table

Successful Transplantation of a Split Crossed Fused Ectopic Kidney into a Patient with End-Stage Renal Disease

Potential donors with congenital renal anomalies but normal renal function are often overlooked because of a possible increase in technical difficulty and complications associated with the surgery. However, as the waiting list for a deceased donor kidney transplant continues to grow, it is important to consider these kidneys for potential transplant. This paper describes the procurement of a crossed fused ectopic kidney, and subsequent parenchymal transection prior to transplantation as part of a combined simultaneous kidney pancreas transplant. The transplant was uncomplicated, and the graft had immediate function. The patient is now two years from transplant with excellent function

Influence of Hydrodynamic Interactions on Mechanical Unfolding of Proteins

We incorporate hydrodynamic interactions in a structure-based model of ubiquitin and demonstrate that the hydrodynamic coupling may reduce the peak force when stretching the protein at constant speed, especially at larger speeds. Hydrodynamic interactions are also shown to facilitate unfolding at constant force and inhibit stretching by fluid flows.Comment: to be published in Journal of Physics: Condensed Matte

1,2,3,4,6 penta-O -galloyl-β-D-glucose modulates perivascular inflammation and prevents vascular dysfunction in angiotensin II-induced hypertension

Background and Purpose: Hypertension is a multifactorial disease, manifested by vascular dysfunction, increased superoxide production and perivascular inflammation. In this study, we have hypothesized that 1,2,3,4,6 Penta‐O‐Galloyl‐β‐D‐Glucose (PGG) would inhibit vascular inflammation and protect from vascular dysfunction in an experimental model of hypertension. Experimental Approach: PGG was administered every two days in a dose of 10 mg·kg‐1 i.p during 14‐days of Ang II infusion and was used in a final concentration of 20 μM for in vitro studies. Key Results: Ang II administration increased leukocyte and T cell content in perivascular adipose tissue (pVAT) and administration of PGG significantly decreased total leukocyte and T cell infiltration in pVAT (1640±150 vs. 1028±57, p<0.01; 321±22 vs 158±18, cells/mg; p<0.01, respectively). This effect was observed in relation to all T cell subsets. PGG also decreased the content of T cells bearing CD25, CCR5 and CD44 receptors and the expression of both MCP‐1 in aorta and RANTES in pVAT. PGG administration decreased the content of TNF+ and IFN‐γ+ CD8 T cells and IL‐17A+ CD4+ and CD3+CD4‐CD8‐ cells. Importantly, these effects of PGG were associated with improved vascular function and decreased ROS production in the aortas of Ang II‐infused animals independently of blood pressure increase. Mechanistically, PGG (20 μM) directly inhibited CD25 and CCR5 expression in cultured T cells. It also decreased the content of IFN‐γ+ by CD8+ and CD3+CD4‐CD8‐ cells and IL‐17A+ by CD3+CD4‐CD8‐ cells. Conclusion and Implication: PGG may constitute an interesting immunomodulating strategy in the regulation of vascular dysfunction and hypertension

Extrema of Mass, First Law of Black Hole Mechanics and Staticity Theorem in Einstein-Maxwell-axion-dilaton Gravity

Using the ADM formulation of the Einstein-Maxwell axion-dilaton gravity we derived the formulas for the variation of mass and other asymptotic conserved quantities in the theory under consideration. Generalizing this kind of reasoning to the initial dota for the manifold with an interior boundary we got the generalized first law of black hole mechanics. We consider an asymptotically flat solution to the Einstein-Maxwell axion-dilaton gravity describing a black hole with a Killing vector field timelike at infinity, the horizon of which comprises a bifurcate Killing horizon with a bifurcate surface. Supposing that the Killing vector field is asymptotically orthogonal to the static hypersurface with boundary S and compact interior, we find that the solution is static in the exterior world, when the timelike vector field is normal to the horizon and has vanishing electric and axion- electric fields on static slices.Comment: 17 pages, Revtex, a few comments (introduction) and references adde

Variations in Suppressor Molecule CTLA-4 Gene Are Related to Susceptibility to Multiple Myeloma in a Polish Population

Various phenotype and functional T-cell abnormalities are observed in multiple myeloma (MM) patients. The aim of this study was to investigate the association between polymorphisms in the gene encoding cytotoxic T-lymphocyte antigen-4 (CTLA-4), a negative regulator of the T-lymphocyte immune response and susceptibility to multiple myeloma in a Polish population. Two hundred MM patients and 380 healthy subjects were genotyped for the following polymorphisms: CTLA-4c.49A>G, CTLA-4g.319C>T, CTLA-4g.*642AT(8_33), CT60 (CTLA-4g.*6230G>A), Jo31 (CTLA-4g.*10223G>T). Our study is the largest and most comprehensive evaluation to date of the association between genetic polymorphisms in the CTLA-4 molecule and multiple myeloma. It was found that CTLA-4c.49A>G[G], CT60[G], and Jo31[G] alleles were more frequently observed in MM patients than in controls (0.50 vs. 0.44, p = 0.03, 0.65 vs. 0.58, p = 0.04, and 0.63 vs. 0.57, p = 0.03, respectively). Moreover, the haplotype CTLA-4c.49A>G[G], CTLA-4g.319C>T[C], CTLA-4g.*642AT(8_33) [8], CT60[G], Jo31[G] including all susceptibility alleles increases the risk of MM about fourfold (OR: 3.79, 95%CI: 2.08–6.89, p = 0.00001). These findings indicate that genetic variations in the CTLA-4 gene play role in susceptibility to multiple myeloma and warrant further investigation through replication studies

Identification of miRSNPs associated with the risk of multiple myeloma

Accepted articleMultiple myeloma (MM) is a malignancy of plasma cells usually infiltrating the bone marrow, associated with the production of a monoclonal immunoglobulin (M protein) which can be detected in the blood and/or urine. Multiple lines of evidence suggest that genetic factors are involved in MM pathogenesis, and several studies have identified single nucleotide polymorphisms (SNPs) associated with the susceptibility to the disease. SNPs within miRNA-binding sites in target genes (miRSNPs) may alter the strength of miRNA-mRNA interactions, thus deregulating protein expression. MiRSNPs are known to be associated with risk of various types of cancer, but they have never been investigated in MM. We performed an in silico genome-wide search for miRSNPs predicted to alter binding of miRNAs to their target sequences. We selected 12 miRSNPs and tested their association with MM risk. Our study population consisted of 1,832 controls and 2,894 MM cases recruited from seven European countries and Israel in the context of the IMMEnSE (International Multiple Myeloma rESEarch) consortium. In this population two SNPs showed an association with p<0.05: rs286595 (located in gene MRLP22) and rs14191881 (located in gene TCF19). Results from IMMEnSE were meta-analyzed with data from a previously published genome-wide association study (GWAS). The SNPs rs13409 (located in the 3UTR of the POU5F1 gene), rs1419881 (TCF19), rs1049633, rs1049623 (both in DDR1) showed significant associations with MM risk. In conclusion, we sought to identify genetic polymorphisms associated with MM risk starting from genome-wide prediction of miRSNPs. For some mirSNPs, we have shown promising associations with MM risk. What's new? Even though deregulation of miRNA expression has been associated with human cancers little information is available regarding their relation with MM susceptibility. We performed an in silico genome-wide search for miRSNPs and selected the most promising ones for an association study. The SNPs with the strongest associations with MM risk are localized in genes which have never been related with MM.This work was partially funded by: intramural funds of German Cancer Research Center (DKFZ), Grant ref. HUS412A1271 from the “Gerencia Regional de Salud de la Junta de Castilla y Léon”. This work was supported by grants from the Instituto de Salud Carlos III (Madrid, Spain; PI12/02688). Catalan Government DURSI grant 2014SGR647 and Instituto de Salud Carlos III, co7funded by FEDER funds –a way to build Europe– grants PI11701439 and PIE13/00022info:eu-repo/semantics/publishedVersio

Polymorphisms within autophagy-related genes as susceptibility biomarkers for multiple myeloma: a meta-analysis of three large cohorts and functional characterization

Functional data used in this project have been meticulously catalogued and archived in the BBMRI-NL data infrastructure (https://hfgp.bbmri.nl/, accessed on 12 February 2020) using the MOLGENIS open-source platform for scientific data.Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10−9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10−4−5.79 × 10−14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10−4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10−4) and circulating serum concentrations of Monocyte hemoattractant Protein (MCP)-2 (p = 3.6 × 10−4). We also found that the CD46rs1142469 SNP corre lated with numbers of CD19+ B cells, CD19+CD3− B cells, CD5+ IgD− cells, IgM− cells, IgD−IgM− cells, and CD4−CD8− PBMCs (p = 4.9 × 10−4−8.6 × 10−4 ) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27− cells (p = 9.3 × 10−4 ). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3−, MCP-2−, and IL20-dependent pathways.This work was supported by the European Union’s Horizon 2020 research and innovation program, N° 856620 and by grants from the Instituto de Salud Carlos III and FEDER (Madrid, Spain; PI17/02256 and PI20/01845), Consejería de Transformación Económica, Industria, Conocimiento y Universidades and FEDER (PY20/01282), from the CRIS foundation against cancer, from the Cancer Network of Excellence (RD12/10 Red de Cáncer), from the Dietmar Hopp Foundation and the German Ministry of Education and Science (BMBF: CLIOMMICS [01ZX1309]), and from National Cancer Institute of the National Institutes of Health under award numbers: R01CA186646, U01CA249955 (EEB).This work was also funded d by Portuguese National funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020 and by the project NORTE-01-0145-FEDER-000055, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)