26 research outputs found

    Differential Transcriptional Regulation of meis1 by Gfi1b and Its Co-Factors LSD1 and CoREST

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    Gfi1b (growth factor independence 1b) is a zinc finger transcription factor essential for development of the erythroid and megakaryocytic lineages. To elucidate the mechanism underlying Gfi1b function, potential downstream transcriptional targets were identified by chromatin immunoprecipitation and expression profiling approaches. The combination of these approaches revealed the oncogene meis1, which encodes a homeobox protein, as a direct and prominent target of Gfi1b. Examination of the meis1 promoter sequence revealed multiple Gfi1/1b consensus binding motifs. Distinct regions of the promoter were occupied by Gfi1b and its cofactors LSD1 and CoREST/Rcor1, in erythroid cells but not in the closely related megakaryocyte lineage. Accordingly, Meis1 was significantly upregulated in LSD1 inhibited erythroid cells, but not in megakaryocytes. This lineage specific upregulation in Meis1 expression was accompanied by a parallel increase in di-methyl histone3 lysine4 levels in the Meis1 promoter in LSD1 inhibited, erythroid cells. Meis1 was also substantially upregulated in gfi1b2/2 fetal liver cells along with its transcriptional partners Pbx1 and several Hox messages. Elevated Meis1 message levels persisted in gfi1b mutant fetal liver cells differentiated along the erythroid lineage, relative to wild type. However, cells differentiated along the megakaryocytic lineage, exhibited no difference in Meis1 levels between controls and mutants. Transfection experiments further demonstrated specific repression of meis1 promoter driven reporters by wild type Gfi1b but neither by a SNAG domain mutant nor by a DNA binding deficient one, thus confirming direct functional regulation of this promoter by the Gfi1b transcriptional complex. Overall, our results demonstrate direct yet differential regulation of meis1 transcription by Gfi1b in distinct hematopoietic lineages thus revealing it to be a common, albeit lineage specific, target of both Gfi1b and its paralog Gfi1

    Genetic Burden of TNNI3K in Diagnostic Testing of Patients With Dilated Cardiomyopathy and Supraventricular Arrhythmias

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    BACKGROUND: Genetic variants in TNNI3K (troponin-I interacting kinase) have previously been associated with dilated cardiomyopathy (DCM), cardiac conduction disease, and supraventricular tachycardias. However, the link between TNNI3K variants and these cardiac phenotypes shows a lack of consensus concerning phenotype and protein function. METHODS: We describe a systematic retrospective study of a cohort of patients undergoing genetic testing for cardiac arrhythmias and cardiomyopathy including TNNI3K. We further performed burden testing of TNNI3K in the UK Biobank. For 2 novel TNNI3K variants, we tested cosegregation. TNNI3K kinase function was estimated by TNNI3K autophosphorylation assays.RESULTS: We demonstrate enrichment of rare coding TNNI3K variants in DCM patients in the Amsterdam cohort. In the UK Biobank, we observed an association between TNNI3K missense (but not loss-of-function) variants and DCM and atrial fibrillation. Furthermore, we demonstrate genetic segregation for 2 rare variants, TNNI3K-p.Ile512Thr and TNNI3K-p.His592Tyr, with phenotypes consisting of DCM, cardiac conduction disease, and supraventricular tachycardia, together with increased autophosphorylation. In contrast, TNNI3K-p.Arg556_Asn590del, a likely benign variant, demonstrated depleted autophosphorylation. CONCLUSIONS: Our findings demonstrate an increased burden of rare coding TNNI3K variants in cardiac patients with DCM. Furthermore, we present 2 novel likely pathogenic TNNI3K variants with increased autophosphorylation, suggesting that enhanced autophosphorylation is likely to drive pathogenicity.</p

    Experimental Investigations on the Influence of Coil Arrangement on Melting/Solidification Processes

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    The latent heat thermal energy storage units are very popular because of their high energy density and almost close to constant temperature during the charging/discharging. In the present study has been proposed new shell-and-coil geometry with a shifted coil position to enhance the performance of phase change thermal magazine. The experimental investigations have been performed both for the melting and solidification process of coconut oil for constant wall temperature conditions. The experiments have been carried out for cylindrical as well as coil shape geometry of the TES unit. In the case of annular TES, the copper tube with outer diameter d = 10 mm and total length equal to 165 mm were used (4). In the case of shell-and-coil TES the coil has been also made of a copper tube but with an outer diameter d = 6 mm. The total length of the tube was 460 mm. However, the length of the tube element that has been used in the process of bending the coil had a total length equal to 360 mm. The rest of the tube was straight. The coil pitch was 15 mm and the outer coil diameter was 26 mm. The experiments have been conducted for the coil position at the top and the bottom of the tank. The results showed the influence of heat transfer geometry for phase change efficiency. The article presents the thermal characteristic of melting and solidification phenomena as well as their visual analysis. A significant impact of heat transfer geometry at the shape of the melting and solidification profile. The optimal performance has been achieved for shell-and-coil TES with a coil arranged at the top of the tank

    Performance analyses of helical coil heat exchangers. The effect of external coil surface modification on heat exchanger effectiveness

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    The shell and coil heat exchangers are commonly used in heating, ventilation, nuclear industry, process plant, heat recovery and air conditioning systems. This type of recuperators benefits from simple construction, the low value of pressure drops and high heat transfer. In helical coil, centrifugal force is acting on the moving fluid due to the curvature of the tube results in the development. It has been long recognized that the heat transfer in the helical tube is much better than in the straight ones because of the occurrence of secondary flow in planes normal to the main flow nside the helical structure. Helical tubes show good performance in heat transfer enhancement, while the uniform curvature of spiral structure is inconvenient in pipe installation in heat exchangers. Authors have presented their own construction of shell and tube heat exchanger with intensified heat transfer. The purpose of this article is to assess the influence of the surface modification over the performance coefficient and effectiveness. The experiments have been performed for the steady-state heat transfer. Experimental data points were gathered for both laminar and turbulent flow, both for co current- and countercurrent flow arrangement. To find optimal heat transfer intensification on the shell-side authors applied the number of transfer units analysis

    Comparative study of flow condensation in conventional and small diameter tubes

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    Flow boiling and flow condensation are often regarded as two opposite or symmetrical phenomena. Their description however with a single correlation has yet to be suggested. In the case of flow boiling in minichannels there is mostly encountered the annular flow structure, where the bubble generation is not present. Similar picture holds for the case of inside tube condensation, where annular flow structure predominates. In such case the heat transfer coefficient is primarily dependent on the convective mechanism. In the paper a method developed earlier by the first author is applied to calculations of heat transfer coefficient for inside tube condensation. The method has been verified using experimental data from literature on several fluids in different microchannels and compared to three well established correlations for calculations of heat transfer coefficient in flow condensation. It clearly stems from the results presented here that the flow condensation can be modeled in terms of appropriately devised pressure drop

    Applicability of correlations of heat transfer in arrays of microjets to design compact heat exchangers: part 1. Model heat exchanger design and its characteristics

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    W artykule przedstawiono konstrukcję prototypowego, modułowego mikrostrugowego wymiennika ciepła. Przeprowadzone badania cieplno przepływowe w układzie woda-woda, umożliwiają określenie efektywności wymiany ciepła, charakterystyk cieplno przepływowych, oraz wielkości współczynnika przejmowania ciepła. Eksperymenty w dalszej części publikacji posłużą do weryfikacji stosowalności istniejących korelacji opisujących wymianę ciepła w obszarze uderzającej mikrostrugi.The article presents experimental studies on a compact heat exchanger with heat transfer intensification by means of impinging microjets. The pursuit to provide high performance of heat exchangers is a response to the demand both in economics and in the universal tendency to miniaturization of industrial equipment. This paper presents the design of a prototype, modular microjet heat exchanger. The modular design of the heat exchanger allows to change its geometrical dimensions, as well as changing the heat exchange membrane material. Schematics, view of test section and design of the heat exchanger are shown in Figures 1 to 4. The study of heat transfer in water-water flow, allows to determine the heat transfer efficiency, the characteristics of heat transfer, and the heat transfer coefficient values. Data were collected for the pressure drops in heat exchanger not exceeding 15 kPa, i.e. such as in conventional heat exchangers. Hydraulic characteristics of a model heat exchanger are shown in Figures 5 and 6. Additionally for the two experimental series, comparison of the performance of tested heat exchanger with standard pipe in the pipe heat exchanger has been made, as shown in Figure 9. Conducted experimental research, in the following part of publication will be used to verify the applicability of the existing correlations of heat transfer in microjet impingement area

    Investigations on mixture preparation for two phase adiabatic pressure drop of R134a flowing in 5 mm diameter channel

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    The article presents detailed two-phase adiabatic pressure drops data for refrigerant R134a. Study cases have been set for a mass flux varying from 200 to 400 kg/m2s, at the saturation temperature of 19.4°C. Obtained experimental data was compared with the available correlations from the literature for the frictional pressure drop during adiabatic flow. Influence of mixture preparation on pressure drop was investigated, for varying inlet subcooling temperature in the heated section. The flow patterns have also been obtained by means of a high-speed camera placed in the visualization section and compared with literature observations

    Comparative study of heat transfer and pressure drop during flow boiling and flow condensation in minichannels

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    In the paper a method developed earlier by authors is applied to calculations of pressure drop and heat transfer coefficient for flow boiling and also flow condensation for some recent data collected from literature for such fluids as R404a, R600a, R290, R32,R134a, R1234yf and other. The modification of interface shear stresses between flow boiling and flow condensation in annular flow structure are considered through incorporation of the so called blowing parameter. The shear stress between vapor phase and liquid phase is generally a function of nonisothermal effects. The mechanism of modification of shear stresses at the vapor-liquid interface has been presented in detail. In case of annular flow it contributes to thickening and thinning of the liquid film, which corresponds to condensation and boiling respectively. There is also a different influence of heat flux on the modification of shear stress in the bubbly flow structure, where it affects bubble nucleation. In that case the effect of applied heat flux is considered. As a result a modified form of the two-phase flow multiplier is obtained, in which the nonadiabatic effect is clearly pronounced
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