23 research outputs found
Acoustic energy isotherms: An emergent approach for textural characterization of activated carbons
No full textAcoustic Emission Analysis (AEA) for textural characterization of granular activated carbons (GACs) is an interesting alternative for assessing the GAC volume of pores in a rapid, sensitive and reliable way. Correlations between AEA and conventional methods have demonstrated its potentialities for textural characterization of high-porosity materials. In this study, commercial GACs with different porous characteristics were compared and correlated by applying volumetric gas sorption (N-2 at 77 K, CO2 at 273 K), Hg porosimetry and AEA. The energy, amplitude and power of the acoustic signal produced during GAC immersion in water are used as parameters to correlate with textural characteristics of the carbons. The found relationship between conventional porosity assessment techniques and acoustic parameters demonstrated the potentialities of the acoustic method as complementary technique of exploring textural properties of high-porosity materials.The authors would like to thank VLIR-UOS (Flemish Interuniversity Council for University Development Cooperation) project between Belgium and Cuba for providing funding and granting the support of the current and future studies.Yperman, J (reprint author), Hasselt Univ, Res Grp Appl & Analyt Chem, Agoralaan Bldg D, B-3590 Diepenbeek, Belgium.
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Numerical simulation of in-pipe particle transportation in CO2 foam
No full textProppant-carrying foam fracturing fluids have complex rheological and transportation properties. Current studies on these fluids often focus on experimental phenomena. However, due to the limitation of experimental research, only macroscopic properties, such as the critical settling velocity, can be obtained. Transportation mechanisms and volume fraction distributions are poorly understood as well. In our study, the liquid-solid drag coefficient is corrected, and the mathematical physical model of non-Newtonian fluids of the particle-foam multiple phase is established by using a two-phase model. Proppant settling and transport properties in foam fracturing fluids are numerically studied, particle distribution on pipe cross section is obtained at various conditions, and a criterion for full development of fluid flow in pipe is set. We also find that when the Reynolds number (Re) is less than 190, the critical point of full development of flow increases with Re, whereas when Re is greater than 190, the critical point of full development decreases exponentially with the increasing of Re before stabilizing at approximately 45.SCI(E)ARTICLE2SF243-SF249
Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study
No full textBACKGROUND: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). METHODS: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. RESULTS: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). CONCLUSIONS: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
Towards the optimization of tumor targeting radiolabeled peptides for molecular imaging and therapy
No full textRadiopharmaceuticals based on regulatory peptides have become an indispensable tool in nuclear medicine for the diagnosis (molecular imaging) and radionuclide therapy of cancer. The specificity of these radiopeptides towards G-protein-coupled receptors (GPCR), which are overexpressed by various cancer cells and their favorable pharmacological properties make them ideal vectors for the targeted delivery of radioactivity to tumors and metastases. However, there are still challenges to be met in order to develop peptide-based radiopharmaceuticals with ideal properties in terms of imaging quality and therapeutic efficacy where therapeutic radionuclides are employed.
A potential drawback of several radiolabeled peptides under investigation is represented by a rapid washout of radioactivity after receptor-mediated internalization into tumor cells. In certain cases, the washout of radioactivity from cells occurs at a rate comparable to that required for accumulation in cancerous tissues. This not only renders the initial efforts of targeted delivery in part futile but also results in an imaging quality and therapeutic efficiency lower than achievable. To address this issue, novel strategies are needed to improve the cellular retention of the radioactivity. A possible approach may include the employment of multi-targeting radioconjugates made of different moieties specific for extra- and intracellular targets. Towards this goal, we investigated the combination of tumor targeting peptides with an additional moiety specific for an intracellular target and radiolabeled the conjugate with the 99mTc-tricarbonyl core as a reporter probe for single-photon emission computed tomography (SPECT). We envisioned that enabling interactions of radioconjugates with intracellular targets after receptor-mediated uptake by endocytosis would result in the trapping of radioactivity in tumors.
Specifically, we combined a modified binding sequence of the peptide bombesin, [Nle14]BBS(7-14), for extracellular targeting of the tumor-associated gastrin releasing peptide receptor (GRP-r) with a triphenylphosphonium group for intracellular targeting of the organelle mitochondria or with the peptide shepherdin, an inhibitor of the cytosolic chaperon heat-shock protein 90 (Hsp90). The conjugates were assembled by the "Click-to-Chelate" approach, an efficient synthetic strategy for the preparation of bifunctional 99mTc-labeled radiopharmaceuticals. The radioconjugates were evaluated in vitro using GRP-r-overexpressing PC-3 cells. Our investigations revealed that the additional moiety for intracellular targeting did not impact the tumor-targeting capability of the bombesin-derived conjugates but neither did it result in an improved cellular retention of the radioactivity. Drawing from our experience and considering recent literature data, we conclude that endosomal entrapment or lysosomal degradation of the bifunctional radiopeptide conjugates is likely to impede with intracellular interactions and thus, responsible for the observed unaltered cellular efflux of radioactivity. Future studies will be directed towards the combination of bifunctional radiopeptide conjugates with drug delivery systems designed to facilitate endosomal escape.
A different approach for the optimization of peptidic radiotracers includes the improvement of their metabolic stability since most of them exhibit a very short biological half-life due to rapid degradation by endogenous peptidases. Enhancement of the stability of radiopeptides results in a prolonged circulation time in the blood and, as a consequence, an improved tumor uptake in vivo. A number of different strategies have been reported for the stabilization of regulatory peptides, however, with varying degree of success in providing peptidomimetics with retained affinity to the corresponding GPCR. In an effort to probe a novel peptide backbone modification methodology, the use of 1,4-disubstituted 1,2,3-triazoles as metabolically stable trans amide bond isosters was investigated. The systematic replacement of amide bonds within the binding sequence of the tumor-affine peptide bombesin, [Nle14]BBS(7-14), by triazoles provided a series of 177Lu-labeled peptidomimetics with both retained affinity towards GRP-r and an increased stability in blood serum. In vivo evaluation of a lead compound in xenografted mice showed that the enhanced stability of the radiopeptidomimetic resulted in a doubling of the uptake of radioactivity in tumors. The described amide-to-triazole substitution methodology is currently being applied to other tumor targeting peptides of medicinal interest.
The specificity and affinity of radiopeptides towards different receptor subtypes is another aspect to consider for optimizations. Inhomogeneous expression of receptor subtypes by tumors may influence the efficiency of a radiotracer. For example, intratumoral administration of radiolabeled substance P (SP) led to significant differences in the clinical response of patients suffering from gliomas despite proven expression of its target, the neurokinin-1 receptor (NK1R). In an effort to identify factors that may be responsible for the varying therapeutic outcome observed, several SP conjugates were evaluated in vitro using four established glioma cell lines differing in their level of RNA expression of the full length and truncated receptor isoforms. Cell binding and internalization of SP-conjugates were only observed with cell lines exhibiting high expression of RNA of the full-length NK1R. Pre-therapeutic screening for NK1R isoforms may therefore be advisable for the selection of glioma patients for NK1R-targeted radionuclide therapy
Characterization and attenuation mechanism of CMOS-compatible micromachined edge-suspended coplanar waveguides on low-resistivity silicon substrate
No full textThis paper presents detailed characterization of a category of edge-suspended coplanar waveguides that were fabricated on low-resistivity silicon substrates using improved CMOS-compatible micromachining techniques. The edge-suspended structure is proposed to provide reduced substrate loss and strong mechanical support at the same time. It is revealed that, at radio or microwave frequencies, the electromagnetic waves are highly concentrated along the edges of the signal line. Removing the silicon underneath the edges of the signal line, along with the silicon between the signal and ground lines, can effectively reduce the substrate coupling and loss. The edge-suspended structure has been implemented by a combination of deep reactive ion etching and anisotropic wet etching. Compared to the conventional silicon-based coplanar waveguides, which show an insertion loss of 2.5dB/mm, the loss of edge- suspended coplanar waveguides with the same dimensions is reduced to as low as 0.5 dB/mm, and a much reduced attenuation per wavelength (dB/lambda(g)) at 39 GHz. Most importantly, the edge-suspended coplanar waveguides feature strong mechanical support provided by the silicon remaining underneath the center of the signal line. The performance of the coplanar waveguides is evaluated by high-frequency measurement and full-wave electromagnetic (EM) simulation. In addition, the resistance, inductance, conductance, capacitance (RLGC) line parameters and the propagation constant of the coplanar waveguides (CPWs) were extracted and analyzed.Engineering, ManufacturingEngineering, Electrical & ElectronicMaterials Science, MultidisciplinarySCI(E)EI5ARTICLE3496-5032
A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms
No full textWe describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms (SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds (a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines--in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases
Folivory elicits a strong defense reaction in Catharanthus roseus: metabolomic and transcriptomic analyses reveal distinct local and systemic responses
No full textPlants deploy distinct secondary metabolisms to cope with environment pressure and to face bio-aggressors notably through the production of biologically active alkaloids. This metabolism-type is particularly elaborated in Catharanthus roseus that synthesizes more than a hundred different monoterpene indole alkaloids (MIAs). While the characterization of their biosynthetic pathway now reaches completion, still little is known about the role of MIAs during biotic attacks. As a consequence, we developed a new plant/herbivore interaction system by challenging C. roseus leaves with Manduca sexta larvae. Transcriptomic and metabolic analyses demonstrated that C. roseus respond to folivory by both local and systemic processes relying on the activation of specific gene sets and biosynthesis of distinct MIAs following jasmonate production. While a huge local accumulation of strictosidine was monitored in attacked leaves that could repel caterpillars through its protein reticulation properties, newly developed leaves displayed an increased biosynthesis of the toxic strictosidine-derived MIAs, vindoline and catharanthine, produced by up-regulation of MIA biosynthetic genes. In this context, leaf consumption resulted in a rapid death of caterpillars that could be linked to the MIA dimerization observed in intestinal tracts. Furthermore, this study also highlights the overall transcriptomic control of the plant defense processes occurring during herbivory.We gratefully acknowledge the financial support from the “Région Centre” (France, ABISAL grant) and from the University of Tours
Efficiency evaluation of thermally and chemically regenerated activated carbons used in a water cleaning system by acoustic emission analysis
No full textAcoustic emission analysis (AEA) results for textural characterization of granular activated carbons (GAC) can be related with its porosity. GACs were evaluated using this AEA technique by band-pass filtering from 3.5 to 50 kHz of the sound produced by flooding GAC with water. Used acoustic parameters for evaluation were: area under the signal envelope curve, acoustic energy and power. An exhausted GAC used in a water filter system of engine-based power plant was subjected to thermal and chemical regeneration under different conditions. Acoustic measurement results have been correlated with TGA, XRF, gas adsorption (N-2 at 77 K), GAC stability and elemental analysis for assessing the AEA. Based on all these techniques, it was found that mainly metal ions were adsorbed on the GAC. It was found that chemical regeneration using a 2.4 N HCl solution was the most successful approach in removing the adsorbed metal ions: Ca, Mn and Ba. Using this HCl solution did have the additional benefit in keeping the amount of elemental and fixed carbon almost intact compared to the more diluted HCl solution of 0.6 N and 1.2 N.The authors would like to thanks the VLIR-UOS project between Belgium and Cuba for providing funding and granting the support of the current and future studies.Yperman, J (corresponding author), Hasselt Univ, Res Grp Appl & Analyt Chem, Agoralaan Bldg D, B-3590 Diepenbeek, Belgium.
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X-ray Absorption (XRA): A New Technique for the Characterization of Granular Activated Carbons
No full textThe X-ray absorption (XRA) method using digital image processing techniques is a reliable technique to determine the exhaustion degree of granular activated carbons (GACs). Using an innovative digital image processing technique, the identification of individual adsorbed molecules or ions in a GAC was possible. Adsorption isotherm models (Langmuir and Freundlich) were used to simulate the adsorption equilibrium data of Methylene Blue (MB), nickel, cobalt and iodine. Freundlich equation was found to have the highest value of R-2 compared with Langmuir. The identification of distinctive patterns applying XRA for different adsorbed ions and molecules onto GAC was explored. It is demonstrated that unique XRA configurations for each adsorbed ion or molecule are found, as well as a proportional relationship between its incident energy (needed to achieve maximum photon attenuation) and the (effective) atomic number, the adsorbate mass and the molar or atomic mass of adsorbed molecule or ion. XRA method in combination with image histogram modifications was used to obtain a digital signature of adsorbed ions/molecules, giving distinct GSI values for each one in the used energy range. Probabilistic models prove that XRA results are within relationships between effective atomic number and photonic interaction probability, reinforcing the potentialities of XRA for monitoring (multi-)ion and/or molecule combinations on GAC using advanced digital image processing techniques. It was proved that the proposed approach could assess different adsorbed ions/molecules onto GACs in water purification systems.The authors thank VLIR-UOS (Flemish Interuniversity Council for University Development Cooperation) project between Belgium and Cuba for the support of the current and future studies. The raw/processed data required to reproduce these findings cannot be shared at this time as the data also form part of an ongoing study.Yperman, J (corresponding author), Hasselt Univ, Res Grp Appl & Analyt Chem, Fac Sci, B-3590 Diepenbeek, Belgium.
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Characterization of MUC1 complexes in human oral epithelial cells
No full textPLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please log in with a valid BU account to access and click Download. If you are the author of this work and would like to make it publicly available, please contact [email protected] (D.Sc.)--Boston University, Henry M. Goldman School of Dental Medicine, 2007 (Dept. of Periodontology and Oral Biology).Includes bibliography: leaves 148-183.Mucins are a famiIy of heavy glycosylated high molecular weight glycoproteins which are invoIved in the protection and lubrication of luminal epithelial surfaces. At least 19 human mucin genes have been distinguished by cDNA cloning—MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6-MUC9, MUC11-MUC13, and MUC15-MUC20. They have been classified into three distinct families: gel forming (MUC2, MUC5AC, MUC5B, MUC6 and MUC19), soluble (MUC7), and membrane-associated (MUC1, MUC3, MUC4 and MUC12, MUC13, MUC15, MUC16, MUC17, MUC18 and MUC20). MUC8, MUC9 and MUC11 remain unclassified.
MUC1 is a large, heavily O-glycosylated, transmembrane protein expressed on the apical membrane of many epithelial tissues, including oral epithelium. It is expressed as a heterodimer after translation of a single polypeptide and cleavage into two subunits in the endoplasmic reticulum. The extracellular domain of MUC1 can interact with other molecules which can alter the adhesive/anti-adhesive properties of cells. The MUC1-CT (intracellular domain) interacts with a variety of kinases and other proteins and is involved in signal transduction pathways. Therefore, our hypothesis is that MUC1 might serve as an outside-to-inside signal that alters the proliferation, differentiation or cell-adhesion status of the epithelial cell.
In the first part of this project, we concentrated our study on the interaction of MUC1-CT with other proteins in human oral epithelial cells using Tandem Affinity purification and Mass Spectrometry. We identified GRP-78, the78-kDa glucose-regulated protein as a protein which interacts with the cytoplasmic tail of MUC1. GRP78 is thought to be crucial in protein folding, proper glycosylation, protein-protein interactions in oligomeric structures, and elimination of misfolded polipeptides. Recently, MUC1 has been reported to be able to translocate to mitochontria and nucleus, but the mechanism remains unclear. Considering our results and the function of GRP78, we suggest that GRP78 (glucose-regulated protein 78) may be involved in either the posttranslational cleavage of MUC1 or may regulate intracellular trafficking of the MUC1-CT.
In the second part of this project, in order to study the function and interaction properties of intact MUC1, we cloned a full length MUC1 containing the Tandem Affinity tags and expressed it in oral epithelial cells. MU1 was found to interact with IQGAP1 (IQ motif containing GTPase activating protein 1). IQGAP1 is considered as a scaffold which participates in multiple fundamental cellular activities, including transcription, cell-cell attachment, and regulation of the cytoskeleton, and it has the ability to turn off activated Ras, which consequently interferes with the activation of several kinases in the Ras/Ref/MEK/ERK signaling pathway. However, MUC1 has been reported to activate the Grb2-Sos-Ras-MEK-ERK pathway. The interaction between these two proteins may contribute to a very important signaling event, by balancing activation and inactivation of this pathway. Further studies are likely to yield additional targets and functions for MUC1 and its interacting proteins
