Laboratory Modelling of the Various Components of Backward Erosion Piping Behavior Due to Converging Flow With Different Constricted Outlets

Backward Erosion Piping (BEP) is an internal erosion mechanism which occurs at the down stream of dams or levees. Two conditions needed for this failure to occur: 1) head of water in the upstream of the dam or the levee to drive the seepage forces, and 2) crack in the roof or the blanket layer of the cohesionless material in the downstream of the dam or a levee. Numerous researches were performed in the past in an attempt to predict the critical gradient for BEP to initiate. Some researches are too conservative and other researches are under predicting the critical gradient. In general, the physical models were used in these researches are either one or two dimensional modelling. Due to complexity of this phenomenon and the three dimensional aspect of it as the water flowing from all directions toward the exit. Therefore, this problem needed to be simulated in a three dimensional model. The objectives of the research are to predict the critical gradient in the sand boil throat due the suspended material which lifted in the crack. Also, calculate the local critical horizontal gradient at channels tips. A circular physical model was designed by the army corps of engineering and modified at Utah State University. This model consists of two chambers, the outer chamber is where the water applied. The inner chamber is where the soil is placed. Mariotte tube to connected to the outer chamber and used to control the differential head applied to the soil sample. Four risers with different diameters are used to simulate the sand boil throat and placed individually at the center of the model. Three different soils representing a range of grain size with different hydraulic conductivities are in the research and some one soil used for two hydraulic regimes applied to the sample. Eight differential pressure transducers are installed around the exit and in the bottom of the riser. Results of the differential transducers are used to understand the backward erosion process and to measure the head loss in the riser due to the suspension of eroded soil in the riser. Three dimensional finite element software is used to mimic the erosion occurs for each test and calibrated using the results of the experimental data. Results were used to calculate the local horizontal critical gradients at different locations from the pipe tips

Early results of total arterial off-pump coronary artery bypass grafting using bilateral internal mammary arteries

Background: The optimal coronary artery bypass grafting (CABG) technique is still evolving. This study aimed to evaluate the early results of the total arterial off-pump technique using bilateral internal mammary arteries. Methods: This study was performed from May 2018 to May 2019 at a cardiac surgery center in India. It included 200 patients with coronary artery disease who had off-pump CABG using bilateral internal mammary arteries. The patients had follow-ups for three months. There were 50 females, and the mean age was 50±10 years. Results: Conversion to on-pump was required in one case (0.5%). The use of complete vein grafts was needed in three cases (1.5%), and vein graft extension was done for two cases (1%). Intra-aortic balloon pump was used in one case (0.5%). Postoperative re-exploration for bleeding was done in two cases (1%), and sternal dehiscence or deep infection occurred in two cases (1%). A pacemaker was used in one case (0.5%), and postoperative need for dialysis occurred in three patients (1.5%). No operative mortality or postoperative stroke was reported. Redo surgery was required in one patient (0.5%). Conclusions: Off-pump total arterial revascularization technique using bilateral internal mammary arteries could have an acceptable early outcome

Therapeutic targeting of cathepsin C::from pathophysiology to treatment

Cathepsin C (CatC) is a highly conserved tetrameric lysosomal cysteine dipeptidyl aminopeptidase. The best characterized physiological function of CatC is the activation of pro-inflammatory granule-associated serine proteases. These proteases are synthesized as inactive zymogens containing an N-terminal pro-dipeptide, which maintains the zymogen in its inactive conformation and prevents premature activation, which is potentially toxic to the cell. The activation of serine protease zymogens occurs through cleavage of the N-terminal dipeptide by CatC during cell maturation in the bone marrow. In vivo data suggest that pharmacological inhibition of pro-inflammatory serine proteases would suppress or attenuate deleterious effects of inflammatory/auto-immune disorders mediated by these proteases. The pathological deficiency in CatC is associated with Papillon-Lefèvre syndrome. The patients however do not present marked immunodeficiency despite the absence of active serine proteases in immune defense cells. Hence, the transitory pharmacological blockade of CatC activity in the precursor cells of the bone marrow may represent an attractive therapeutic strategy to regulate activity of serine proteases in inflammatory and immunologic conditions. A variety of CatC inhibitors have been developed both by pharmaceutical companies and academic investigators, some of which are currently being employed and evaluated in preclinical/clinical trials

Gründernes arbeidssituasjon i arbeidslivet. En kvalitativ studie om helse, mestring og motivasjon i arbeidslivet.

Bakgrunn for / hensikten med oppgaven: Det å være gründer krever motivasjon og mestring i arbeidslivet. Gründerne bærer et stort ansvar for eget foretak, da det å eie et foretak, samt å drive dette har både fordeler og ulemper i arbeidslivet. Formålet for de fleste gründere er å holde i gang foretaket gjennom mange år. Dette krever et stort engasjement, samt at det kan innebære mange år med økonomiske usikkerhet og risiko. På bakgrunn av dette, ønsket jeg i denne studien å studere på gründeres motivasjon, mestring og helse i arbeidslivet i et helsefremmende perspektiv. Hensikt med studien var derfor å utforske gründeres motivasjon opp mot helsefremmende arbeid. Samtidig prøve å finne ut hvordan gründere kan bevare motivasjon og mestring i arbeidslivet. Tema og problemstilling(er): Temaet handler om kvinnelige gründere som driver i skjønnhetsbransjen i et enkeltmannsforetak. Derfor lyder problemstillingen slik: «Hvordan opprettholder kvinnelige gründere motivasjon og mestring i møte med arbeidslivet?» Teorigrunnlaget: Sentrale teori i denne studien er salutogenese teorien av Aaron Antonvsky. Samtidig tar denne studien i bruk sentrale begreper som også er aktuelt innenfor helsefremmende arbeid. Sentrale begreper som er blitt brukt er motivasjon, mestring og helse. Metode: Studien er bygget på kvalitativ metode, med individuelle intervjuer med fem gründere, som arbeider innen skjønnhetsbransjen inkludert. Data/kilder: Undersøkelsen studerte kvinnelige gründere som drev sitt eget foretak. Innsamling av data ble gjennomført gjennom dybdeintervju. Intervjuene ble gjennomført ansikt til ansikt og også gjennom en digital plattform. Hovedfunn: Å være gründer og å drive sitt eget foretaket kan by på utfordringer og glede i arbeidslivet. Å være en del av arbeidsplassen som en har skapt selv, var med på å bidra til å øke mestringsfølelse og motivasjon i arbeidslivet. Kundene var viktig for foretakets fremdrift, men også viktig for deltakernes motivasjon i arbeidslivet. At deltakernes arbeid ga mening for kundene var av stor betydning for deltakerne. Kontroll, selvbestemmelse og fleksibilitet var de sentrale grunnene til at gründerne trivdes svært godt med arbeidet sitt. Dette bidro til at de opprettholdte motivasjonen i arbeidslivet

Laboratory Modeling of Piping Initiation Behavior Through Constricted Outlet

Internal erosion often occurs when seepage flow is concentrated into a small, unprotected opening. One such example is where sandy soil is eroded through a defect in an overlying clay layer, resulting in a sand boil in the process. The erosion initiates through the heave and backward piping mechanisms and continues beneath the clay layer through the piping process, forming a pipe that progresses toward the source of the seepage. The initiation of erosion at the seepage flow concentration is a complex mechanism involving a number of hydraulic and soil mechanics principles, including: flow concentration, soil arching, heave, detachment of soil grains, and transportation of soil grains. A laboratory testing program is being performed to investigate the mechanisms of erosion into a concentrated, unprotected exit. The study builds upon previous research on the mechanisms of piping initiation performed at Utah State University and uses a similar apparatus. A number of different soils representing a range of grain size, grain shape, and gradations are being forced to erode into a range of constricted seepage exits. The exit is fixed with a riser pipe to model the upward transport of eroding soils. The results are compared with axisymmetric finite element analyses in order to develop a better understanding of the initiation process for backward erosion piping

The roles of beta and alpha tryptases in asthma: genetic and immunopharmacological studies

Tryptases, the dominant secretory granular proteins from human mast cells, are emerging as important mediators in asthma and allergy. The β- and α- tryptases have highly similar nucleotide sequences and located on the same locus. While the entire population expresses β-tryptase, the α-tryptase gene exhibits copy number variation (CNV). We have studied the association of expression of these allelic variants with asthma or allergic diseases. We have investigated also the potential actions of β- and α-tryptases in vitro and in vivo. We have found that the one alpha tryptase copy allele was significantly associated with lower total serum IgE levels (Z= -2.39, p=0.01) and a tri-allelic architecture with alleles carrying no, one or two copies of the α-tryptase gene was postulated. The addition of βtryptase to epithelial cells induced upregulation of mRNA for IL-8, IL-6 and TNF-α, while α-tryptase on the other hand was without effect in this model. Injection of β-tryptase into the mouse peritoneum induced great accumulation of neutrophils but accumulation of other cell types was less marked. Under the same conditions, injection of α- tryptase induced less neutrophilia but eosinophils, macrophages and mast cells numbers were significantly increased. The actions of β-tryptase seemed be independent of PAR-2 receptors but not the case for α-tryptase, where PAR-2 pathway might take the leads. In conclusion, recombinant α-tryptase may be a stimulus for the recruitment of inflammatory cells and altered cytokine gene expression with effects distinct from those of β-tryptase

Vasoactive intestinal peptide (VIP) induces proliferation of human hepatocytes

Background: VIP is a gastrointestinal peptide hormone which regulates cell proliferation and differentiation in many cell types. In vitro, hepatocytes have limited viability and proliferative capacity. Although several growth factors such as epidermal growth factor (EGF) have been studied, role of VIP is still unclear. We have investigated the effect of VIP on proliferation of human hepatocytes.METHODS: Human hepatocytes were isolated by two-steps collagenase protocol from liver specimens obtained from patients undergoing liver surgery. Cells were grown in Williams’ E media on collagen coated culture plate. Following 4 to 6 hours of cell plating, treatment with VIP or EGF was started and continued for 3 or 5 days. DNA replication was investigated by measuring Bromodeoxyuridine, BrdU incorporation using immunoflorescent staining. In parallel experiments; 1, 3 or 5 days total RNA was isolated and RT–PCR was performed. In the cell culture supernatant, urea and albumin concentrations were detected.RESULTS: VIP was able to increase total number of hepatocytes and number of proliferating cells in a dose dependent manner markedly at day 3 of treatment. Treatment with VIP was associated with an increase in mRNA expression of ki-67 and H3 genes in a dose dependent process. Although mRNA expression of albumin gene was increased significantly with EGF, no marked alteration was found with VIP treatment. With increasing time, addition of VIP was associated with a decrease in albumin and urea secretion from liver cells.CONCLUSIONS: VIP was able to induce proliferation of human hepatocytes but with little effects on hepatocytes differentiation.<br/

Alpha tryptase: Potential roles in inflammation distinct from those of b-tryptase

RATIONALE: Tryptases are among the most abundant products of the humanmast cell. Beta-tryptase has emerged as an important mediator of allergicinflammation. The copy number of a-tryptase has recently beenfound to be associated with the asthma phenotype, but the function ofthis allelic variant to b-tryptase is unknown.We have investigated potentialactions of a-tryptase.METHODS: C57BL/6 mice were injected intra-peritoneally with recombinanta or b-tryptases (0.005 or 0.5 ug/mouse; 12 mice per group). After6, 12 or 24 h, mice were killed and peritoneal lavage performed.Inflammatory cells were enumerated and levels of albumin and total proteindetermined. Gelatine zymography was applied to examine the activityof matrix metalloprotease (MMP)-2 and MMP-9. In separate experiments,cells of the human bronchial epithelial line 16HBE were incubated withtryptases and expression of mRNA for IL-8, IL-6 and TNF-a examinedby quantitative PCR.RESULTS: Injection of a-tryptase induced the accumulation of neutrophils,eosinophils, macrophages and mast cells (p&lt;0.01) but not lymphocytes.Under the same conditions, b-tryptase stimulated greaterneutrophil recruitment, but the accumulation of other cell types was lessmarked. MMP-9 activity in lavage fluid was unaffected in a-tryptase injectedmice, but it was increased in those injected with b-tryptase.Following addition of a-tryptase to epithelial cells, there was down-regulationof mRNA for IL-6 and TNF-a (p&lt;0.05) whereas b-tryptase inducedstrong up-regulation of the cytokines investigated.CONCLUSION: Recombinant a-tryptase may be a stimulus for the recruitmentof inflammatory cells and altered cytokine gene expressionwith effects different from those of b-tryptase

Mast cell tryptase as a stimulus for up-regulation of adhesion molecule expression and cytokine release from endothelial cells

RationaleMast cell tryptase can be released in substantial quantities at sites of allergic inflammation. Pro-inflammatory actions mediated through protease activated receptor 2 (PAR-2) have been proposed, but the precise contribution of tryptase to disease processes remains unclear. We have investigated alterations in the whole genome expression profile of endothelial cells in response to tryptase.MethodsHuman umbilical vein endothelial cells (HUVECs) were isolated from umbilical vein tissue and grown to confluence. Following addition of tryptase or other agents, quantitative polymerase chain reactions (qPCR) followed by whole genome microarray analysis were performed. Translation of certain genes was investigated by immunocytochemistry or specific ELISA. In parallel studies, calcium flux was measured using a fluorescence based microplate procedure.ResultsMicroarray analysis indicated that the genes whose expression was most up-regulated following tryptase treatment of endothelial cells were those for the adhesion molecules ICAM-1, VCAM-1, EPCAM and ITGAL, and the cytokines IL-2, IL-3, IL-6 and CXCL10. Increased expression was seen also for genes for the cell signalling molecules TNFAIP3, TLL1 and SMAD2. None of these were up-regulated in response to a peptide agonist (SLIGKV-NH2) of PAR-2. Microarray data was confirmed by separate qPCR experiments, immunocytochemistry and by the measurement of cytokines in cell supernatants. The actions of tryptase were inhibited using selective protease inhibitors indicating a requirement for an intact catalytic site. Addition of tryptase to endothelial cells stimulated concentration-dependent increases in intracellular calcium.ConclusionsThe pro-inflammatory actions of tryptase may be mediated through increased expression of adhesion molecules and production of inflammatory cytokines in endothelial cells

Pro-inflammatory actions of the exodomain shed from Protease Activated Receptor 2 (PAR-2)

Rationale:Activation of PAR-2 by proteases has been implicated as a key mechanism in allergic and other inflammatory conditions. Proteolytic cleavage can lead to exposure of a tethered ligand whose binding to the receptor stimulates cell signalling, and the release from PAR-2 of an exodomain fragment (PAR-2E). Potential functions of PAR-2E have been little studied.Methods:PAR-2E was synthesised and its stability investigated in human biological fluids, cell supernatants and with selected proteases. The ability of PAR-2E to stimulate calcium flux in cultures of human umbilical vein endothelial cells was examined using a fluorescence based microplate procedure, and altered RNA expression by whole genome microarray analysis and quantitative PCR (qPCR) for selected genes. Adhesion molecule expression was investigated by flow cytometry. In parallel studies, nucleated cells were enumerated and levels of matrix metalloproteases (MMP) determined by gelatin zymography in peritoneal lavage fluid from C57BL/6 mice injected intraperitoneally with PAR-2E.Results:PAR-2E was highly susceptible to degradation by proteases, but its addition to cells resulted in calcium flux, and increased expression of genes for various adhesion molecules (including ICAM1, EPCAM and ITGAL), and cytokines (TNFAIP3 and IL1B). PAR-2E-induced upregulation of ICAM1, VCAM-1, EPCAM and ITGAL was observed on flow cytometry. Injection of PAR-2E into mice was associated with eosinophilia and raised levels of MMP2 in peritoneal lavage fluid.Conclusions:PAR-2E may act as a stimulus for increased expression of adhesion molecules, cytokine release and eosinophilia, and deserves consideration as a mediator of inflammation following PAR-2 activation