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Eiamsa-ard, S., and P. Promthaisong. "Counter-rotation vortex flows and heat transfer mechanisms in a V-spirally-corrugated tube." Proceedings of the Institution of Mechanical Engineers, Part A: Journal of Power and Energy 233, no. 7 (February 13, 2019): 928–52. http://dx.doi.org/10.1177/0957650919829367.
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The flow and heat transfer behavior of newly designed V-corrugated tubes with various numbers of starts ( N = 2, 3, 4, and 5), depth ratios ( DR = 0.02–0.14), and pitch ratios ( PR = 1.0–2.0) were studied in the turbulent flow region (5000 ≤ Re ≤ 20,000). The friction factor ( f), friction factor ratio ( f/ f0), Nusselt number ( Nu), Nusselt number ratio ( Nu/ Nu0), and thermal enhancement factor ( TEF) values are reported. The computational results indicate that the conventional spirally-corrugated tube create swirl flows while V-corrugated tubes generate a counter-rotating vortex flow that impinges upon the lower zone of the tubes and enhances fluid transfer between tube core and near-wall regions. The results also show that the f, Nu, f/ f0, Nu/ Nu0 monotonically increase with decreasing PR, increasing DR and N, while the TEF is dependent on a tradeoff between f/ f0 and Nu/ Nu0. Over the studied range, the f/ f0, Nu/ Nu0, and TEF were in the ranges of 1.36–43.82, 1.00–5.35, and 0.80–2.11, respectively. The maximum TEF, 2.11, was achieved with a V-corrugated tube with an N of 4, DR of 0.06, and PR of 2.0 at Re = 5000.
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Liu, Jing, and Jie Li. "Numerical Prediction of Flow Structure and Heat Enhancement with Different Dimple Depth." Applied Mechanics and Materials 574 (July 2014): 147–53. http://dx.doi.org/10.4028/www.scientific.net/amm.574.147.
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Aim at finding the relation between flow structure and heat enhancement, this paper change the dimple depth to print diameter from 0.06 to 0.3, with an interval of 0.02, and keep the print diameter constant. Through vortex structure analysis and Nu number integration, find out that: Vortex structure varies with dimple depth. Shallow depth dimple induces horseshoe vortex; middle depth dimple induces symmetric tornado-like vortex; deep depth dimple induces tornado-like vortex. Heat enhancement is closely related to vortex structure. Where spiral separation focus point exists, there the lowest Nu/Nu0 exists. Flow impingement at the windward side of dimple and new viscous layer generation at immediate plane after the dimple enhance heat transfer. The highest Nu/Nu0 exists in the sharp rearward dimple edge. From Fig 6, the deeper the dimple is, the higher the average Nu/Nu0 is, so does the pressure drop. But from 0.06 to 0.2 dimple, heat enhancement increased because of vortex structure changed. From 0.2 to 0.3 heat enhancement increased because of the increased area.
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PLIVA, J. "The difference bands nu11-nu4 and nu10-nu18 of benzene at high resolution." Molecular Physics 87, no. 4 (March 1, 1996): 859–63. http://dx.doi.org/10.1080/00268979650027216.
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Yang, De Zhi, Meng Long Dong, Xin Wei Lu, and Zhao Yao Zhou. "Numerical Investigation of Convection Heat Transfer in Pipes with Sintered Porous Metal Rings." Applied Mechanics and Materials 556-562 (May 2014): 4275–79. http://dx.doi.org/10.4028/www.scientific.net/amm.556-562.4275.
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Fully developed turbulence single phase convection heat transfer of water in pipes filled with sintered porous metal inner rings or solid inner rings was investigated numerically respectively. Numerical calculations were conducted with the Fluent 6.3 code, using the SST k-ω turbulence model. Comparing to solid-ring turbulator pipes, porous-ring turbulator pipes have better comprehensive heat transfer effect. The maximum PEC for porous-ring turbulator pipes is 4.4 and the PEC of solid-ring turbulator pipes is less than 1. It was also analyzed effect of geometric structures on porous-ring turbulator pipe performance. f/f0 for porous-ring turbulator pipes increases with the increasing of Re while Nu/Nu0 decreases with the increasing of Re ,and PEC decreases with the increasing of Re. With the same Re, if the width of the porous ring is equal to the width of groove, f/f0, Nu/Nu0 increases and PEC decreases with the increasing height of porous ring. When the height of porous ring is constant, the f/f0, Nu/Nu0 and PEC decreases with the increasing height of porous ring under the same Re.
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Yang, Yang, Siddharth Koushik Mohanakrishnan, David S.-K. Ting, and Steve Ray. "DELTA WINGLETS FOR ENHANCING SOLAR ENERGY: TURBULENT STRAIN RATE-HEAT CONVECTION RELATIONSHIP." Journal of Green Building 16, no. 2 (March 1, 2021): 97–114. http://dx.doi.org/10.3992/jgb.16.2.97.
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ABSTRACT Delta winglets are an effective means for enhancing heat exchange and thus the performance of renewable energy technologies, including solar energy. A pair of 0.1 mm thick, 15 mm high (h) and 30 mm long aluminum winglets separated with transversal spacing, s, of 2h, h and 0 were scrutinized in a closed-loop wind tunnel at a Reynolds number based on h of 6300. The turbulent flow was characterized using a 3D hotwire probe, and the heat convection augmentation was quantified in terms of the normalized Nusselt number (Nu/Nu0), indicating the heat transfer improvement compared to the reference case without the winglets. The interaction of the organized counter-rotational vortices intensifies and they become indiscernible at s = 0. The peak strain rate at 10h downstream increased from 390 s–1, to 478 s–1, to 514 s–1, when the spacing decreased from 2h to h to 0, respectively. The zero-spaced winglet pair provided the largest Nu/Nu0, of around 1.21, at X/h = 10 and Y/h = 0, approximately 21% higher than that of 2h-spaced winglet pair, due to the strongest strain rate and the absence of upwash flow. On the other hand, the 2h-spaced winglet pair provided the largest span-averaged Nu/Nu0, which is of practical significance.
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Xu, Tao, Dongbo Shi, Di Zhang, and Yonghui Xie. "Flow and Heat Transfer Characteristics of the Turbine Blade Variable Cross-Section Internal Cooling Channel with Turning Vane." Applied Sciences 13, no. 3 (January 21, 2023): 1446. http://dx.doi.org/10.3390/app13031446.
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The gas turbine blades are scoured by high temperature gas sustainedly and long-term in harsh environment. It is of great significance to explore effective cooling methods to lower the turbine blade temperature so as to ensure safe and stable operation of the gas turbine. However, there are few studies on the cooling channel considering the turning vane, variable cross-section characteristics, and rotation effect. In this paper, five kinds of serpentine cooling channel models with variable cross-section properties and different thickness guide vanes are constructed. The effects of different thickness guide vanes on the overall performance of the channel under stationary and rotating conditions are discussed and compared by numerical method. The result shows that when stationary (Re = 10,000-50,000), the turning vane with suitable thickness can increase the Nu/Nu0 by 56.5%. The f/f0 is decreased by 14.2%, and the comprehensive thermal performance is increased by 4.5%. When rotating (Re = 10,000, Ro = 0-0.5), the turning vane with suitable thickness can increase the Nuup/Nu0 and Nuall/Nu0 by 33.0% and 4.0%, respectively. The comprehensive performance of the variable cross-section serpentine channel can be greatly improved by arranging the turning vane structure with appropriate thickness.
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Machida, Shinichi, David Depierre, Heng-Chang Chen, Suzie Thenin-Houssier, Gaël Petitjean, Cecile M. Doyen, Motoki Takaku, Olivier Cuvier, and Monsef Benkirane. "Exploring histone loading on HIV DNA reveals a dynamic nucleosome positioning between unintegrated and integrated viral genome." Proceedings of the National Academy of Sciences 117, no. 12 (March 11, 2020): 6822–30. http://dx.doi.org/10.1073/pnas.1913754117.
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The aim of the present study was to understand the biology of unintegrated HIV-1 DNA and reveal the mechanisms involved in its transcriptional silencing. We found that histones are loaded on HIV-1 DNA after its nuclear import and before its integration in the host genome. Nucleosome positioning analysis along the unintegrated and integrated viral genomes revealed major differences in nucleosome density and position. Indeed, in addition to the well-known nucleosomes Nuc0, Nuc1, and Nuc2 loaded on integrated HIV-1 DNA, we also found NucDHS, a nucleosome that covers the DNase hypersensitive site, in unintegrated viral DNA. In addition, unintegrated viral DNA-associated Nuc0 and Nuc2 were positioned slightly more to the 5′ end relative to their position in integrated DNA. The presence of NucDHS in the proximal region of the long terminal repeat (LTR) promoter was associated with the absence of RNAPII and of the active histone marks H3K4me3 and H3ac at the LTR. Conversely, analysis of integrated HIV-1 DNA showed a loss of NucDHS, loading of RNAPII, and enrichment in active histone marks within the LTR. We propose that unintegrated HIV-1 DNA adopts a repressive chromatin structure that competes with the transcription machinery, leading to its silencing.
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Lau, S. C., J. C. Han, and Y. S. Kim. "Turbulent Heat Transfer and Friction in Pin Fin Channels With Lateral Flow Ejection." Journal of Heat Transfer 111, no. 1 (February 1, 1989): 51–58. http://dx.doi.org/10.1115/1.3250657.
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Experiments were conducted to study the effects of lateral flow ejection on the overall heat transfer and pressure drops for turbulent flow through pin fin channels. The two test sections of the investigation were rectangular channels with staggered arrays of six and eight streamwise rows of pins, respectively. The pin length-to-diameter ratio was one and both the streamwise and spanwise pin spacings were 2.5 times the pin diameter. Heat transfer and friction data were obtained for various ejection exit geometries, for ejection ratios between 0 and 1, and for Reynolds numbers between 6000 and 60,000. The results of the study show that, for any given ejection ratio, the overall Nusselt number increases with increasing Reynolds number. However, the overall Nusselt number is reduced by as much as 25 percent as the ejection ratio is increased from 0 to 1 over the range of Reynolds number studied. The Nu–Re–ε relationship, which is insensitive to varying the ejection exit geometry, can be correlated by the equation (Nu/Nu0) = (Nu1/Nu0)ε, where Nu0 = c0Rem and Nu1 = c1Ren are the overall Nusselt numbers in the 0 and 100 percent lateral flow ejection cases, respectively. The results also show that the overall friction factor is independent of the flow Reynolds number over the range of Reynolds number studied. However, the friction factor is strongly dependent on the ejection ratio as well as the geometries of the straight flow exit and lateral ejection flow exit.
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Takashima, M. "Article." Canadian Journal of Physics 76, no. 12 (December 1, 1998): 937–47. http://dx.doi.org/10.1139/p98-062.
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The stability of combined plane Poiseuille and Couette flow of an electricallyconducting fluid under a transverse magnetic field is investigated using linear stability theory.In deriving the equations governing the stability, the so-called magnetic Stokes approximationis made using the fact that the magnetic Prandtl number Prm for most electrically conductingfluids is extremely small. The Chebyshev collocation method is adopted to obtain theeigenvalue equation, which is then solved numerically. The critical Reynolds number Rec,the critical wave number αc, and the critical wave speed cc are obtained for wide ranges ofthe Hartmann number Ha and the parameter k = U0 / (U0 + nu0), where U0 is the maximumvelocity of pure Couette flow and nu0 is the maximum velocity of pure Poiseuille flow. It isfound that a transverse magnetic field has both stabilizing and destabilizing effects on theflow depending on the value of k.PACS Nos. 47.20
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Zhao, Zhen, Liang Xu, Jianmin Gao, Lei Xi, Qicheng Ruan, and Yunlong Li. "Multi-Objective Optimization of Parameters of Channels with Staggered Frustum of a Cone Based on Response Surface Methodology." Energies 15, no. 3 (February 8, 2022): 1240. http://dx.doi.org/10.3390/en15031240.
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In this study, Response Surface Methodology (RSM) and multi-objective genetic algorithm were used to obtain optimum parameters of the channels with frustum of a cone with better flow and heat transfer performance. Central composite face-centered design (CCF) was applied to the experimental design of the channel parameters, and on this basis, the response surface models were constructed. The sensitivity of the channel parameters was analyzed by Sobol’s method. The multi-objective optimization of the channel parameters was carried out with the goal of achieving maximum Nusselt number ratio (Nu/Nu0) and minimum friction coefficient ratio (f/f0). The results show that the root mean square errors (RSME) of the fitted response surface models are less than 0.25 and the determination coefficients (R2) are greater than 0.93; the models have high accuracy. Sobol’s method can quantitatively analyze the influence of the channel parameters on flow and heat transfer performance of the channels. When the response is Nu/Nu0, from high to low, the total sensitivity indexes of the channel parameters are frustum of a cone angle (α), Reynolds number (Re), spanwise spacing ratio (Z2/D), and streamwise spacing ratio (Z1/D). When the response is f/f0, the total sensitivity indexes of the channel parameters from high to low are Re, Z1/D, α and Z2/D. Four optimization channels are selected from the Pareto solution set obtained by multi-objective optimization. Compared with the reference channel, the Nu/Nu0 of the optimized channels is increased by 21.36% on average, and the f/f0 is reduced by 9.16% on average.
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Ekman, Sirkka-Liisa, Tarja-Brita Robins Wahlin, Astrid Norberg, and Bengt Winblad. "Relationship between Bilingual Demented Immigrants and Bilingual/Monolingual Caregivers." International Journal of Aging and Human Development 37, no. 1 (July 1993): 37–54. http://dx.doi.org/10.2190/nu87-fgp0-cneu-dch5.
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This study illuminates the relationship between bilingual demented patients and bilingual/monolingual caregivers during morning care sessions regarding the promotion of integrity in demented persons. Seven demented Finnish immigrants were videotaped during morning care together with bilingual and monolingual Swedish-speaking caregivers. A phenomenological-hermeneutic analysis of the videotapes was performed based on Ricoeur's philosophy. The structural analysis was made by means of the Erikson theory of “eight stages of man.” Comparisons were made regarding demented immigrants' relationships with Swedish-Finnish speaking and Swedish speaking caregivers respectively. Three different patterns of relationship were seen: positive, negative, and mixed relationship. The study showed that bilingual caregivers' relationships with bilingual patients was positive or mainly positive (mixed), while the monolingual Swedish speaking caregivers had severe problems communicating with the same patients and therefore had more difficulties creating a positive relationship with them. It seems important that bilingual caregivers engage in the care of demented bilingual patients in order to help them use their latent competence and show themselves more clearly in the communication with their caregivers.
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White, John R. "The Kern Effigy: Evidence for a Prehistoric fort Ancient Summer Solstice Marker." North American Archaeologist 7, no. 2 (October 1986): 137–65. http://dx.doi.org/10.2190/wlf7-5drf-nu10-dqll.
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Recent excavations in Warren County, Ohio, within the shadow of monumental Fort Ancient have brought to light a large prehistoric alignment of limestone flagstones forming an effigy of a serpent. Radiocarbon dates indicate that this effigy was constructed in 1200 A.D. presumably by local peoples archaeologically designated as being of the Anderson focus (or phase) of the Fort Ancient aspect. Strong evidence indicates that this large “artifact” may have seen use as an astronomical ground marker for determining the summer solstice and important dates related thereto. A set of general and site specific hypotheses is presented to support this contention and to briefly discuss its cultural setting.
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Martinez, M. T., J. Favrel, and P. Ghodous. "Product Family Manufacturing Plan Generation and Classification." Concurrent Engineering: Research and Applications 8, no. 1 (March 1, 2000): 12–23. http://dx.doi.org/10.1106/7p7h-5ejt-glct-nu8d.
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Bobker, Michael. "Technology Strategy as Rosetta Stone." Cogeneration and Competitive Power Journal 15, no. 3 (July 1, 2000): 26–27. http://dx.doi.org/10.1092/fxvp-nu8f-2ufy-bfpv.
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Munzenberger, Paul J., and Miriam Jan Hill. "Impact of an asthma-specific questionnaire on problem identification and clinical and economic outcomes in ambulatory patients with persistent asthma." Journal of the American Pharmacists Association 47, no. 2 (March 2007): 147–55. http://dx.doi.org/10.1331/w240-7582-210u-nu82.
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Barbour, Abdelahhad, Koshy Philip, and Sekaran Muniandy. "Enhanced Production, Purification, Characterization and Mechanism of Action of Salivaricin 9 Lantibiotic Produced by Streptococcus salivarius NU10." PLoS ONE 8, no. 10 (October 16, 2013): e77751. http://dx.doi.org/10.1371/journal.pone.0077751.
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Abbaslou, Yousef, Davood Zahmatkesh, Ehsan Mahjoubi, Mehdi Hossein Yazdi, Hamed Beiranvand, and Morteza Gorjidooz. "Nucleotide Supplementation to Whole Milk Has Beneficial Effects on Post-Weaning Holstein Calf Performance." Animals 11, no. 1 (January 18, 2021): 218. http://dx.doi.org/10.3390/ani11010218.
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The positive effects of nucleotide (NU) supplementation in milk replacer have been elucidated in infants and in dairy calves; however, NU addition to whole milk has not been evaluated previously. This study aimed to assess NU supplementation in the whole milk on calf growth and health. Thirty Holstein calves (body weight: 39.1 ± 1.0 kg; 3 d after birth) were randomly assigned to the following treatments: whole milk without any supplementation (NU0), whole milk + 0.5 g/d added a NU-containing supplement to whole milk (NUCS0.5), and whole milk + 1 g/d added a NU-containing supplement to whole milk (NUCS1). Calves were weaned at d 55 and stayed on study until d 75. Calves had free access to feed and water throughout the study. Dry matter intakes (DMI) were similar among treatments (p > 0.05) during the pre-weaning period; however, increasing NU resulted in a linear (p < 0.05) increase in DMI during the post weaning period (2158, 2432, and 2518 g/d for NU0, NUCS0.5, and NUCS1, respectively). Treatments did not affect body weight (BW) at the first and second month of study, but final BW linearly increased as NU was added (87.1, 90.6, and 95.4 kg for NU0, NUCS0.5, and NUCS1, respectively). Neither pre-weaning average daily gain nor post-weaning average daily gain was affected by treatments; accordingly, feed efficiency was similar among treatment groups. Days with loose fecal score were linearly decreased as NU was added to whole milk during the first month of life, while the fecal score did not differ among treatments until the end of the study. No difference was observed in the skeletal growth of calves in the current study. Therefore, it can be concluded that NU supplementation in the whole milk has some beneficial effects on calf performance in terms of final BW, post-weaning DMI, and less days with loose feces.
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Getman, Pavel, Alexey Shchelchkov, Igor Popov, Nikolai Zubkov, and Valeriya Getman. "Intensification of heat exchange in the developed surfaces in flat channels." E3S Web of Conferences 459 (2023): 03009. http://dx.doi.org/10.1051/e3sconf/202345903009.
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The paper presents the results of an experimental study of heat transfer during forced water flow from microstructured surfaces in a slotted channel. The investigated micro-structured surfaces were obtained by a resource-saving (waste-free) method of deforming cutting with various constructive shapes and sizes. A description of the experimental setup, methods for conducting and processing experimental data are presented. The maximum increase in heat transfer coefficients in comparison with a smooth surface reaches Nu/Nu0 = 16.2.
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Wang, T., Masahiro Kawakami, Kazuya Mori, and S. H. Shahidan. "Analysis of Waste Heat Recovery to Steel Scrap Preheating in an Enclosure Vessel." Materials Science Forum 449-452 (March 2004): 329–32. http://dx.doi.org/10.4028/www.scientific.net/msf.449-452.329.
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A method for preheating steel scraps using waste heat in a continuous casting process was proposed. Experiment and numerical analysis were carried out to examine the ability of scrap preheating and to determine the factors affecting the rise in scrap temperature. Coupled natural convection-radiation heat transfer was solved by three-dimensional FEM. The distance and the constant were found to influence the sample's temperature rise greatly. The overall Nusset number can be obtained as Nu0=(-0.33α*D*0.8+7.08)Ra0.15t*-1- 32.4D*-0.99α*-1.98 *-1.98
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Li, Keqiang, and Shangjiu Wang. "Symmetry of positive solutions of a $ p $-Laplace equation with convex nonlinearites." AIMS Mathematics 8, no. 6 (2023): 13425–31. http://dx.doi.org/10.3934/math.2023680.
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<abstract><p>In this paper, we consider the symmetry properties of the positive solutions of a $ p $-Laplacian problem of the form</p> <p><disp-formula> <label/> <tex-math id="FE1"> \begin{document}$ \begin{eqnarray*} \begin{cases} -{{\Delta}}_p u = f(x,u),\ \ \ \ \ \ \ \mathrm{in}\ \ \ \ \ {{\Omega}},\\ \ \ \ \ \ \ \ u = g(x), \ \ \ \ \ \ \ \ \ \ \mathrm{on}\ \ \ \ \partial{{\Omega}}, \end{cases} \end{eqnarray*} $\end{document} </tex-math></disp-formula></p> <p>where $ {{\Omega}} $ is an open smooth bounded domain in $ R^N, N\geq2 $, and symmetric w.r.t. the hyperplane $ T_0^\nu (\nu $ is a direction vector in $ R^N, |\nu| = 1 $$) $, $ f $: $ {{\Omega}}\times R^+\rightarrow R^+ $ is a continuous function of class $ C^1 $ w.r.t. the second variable, $ g\geq 0 $ is continuous, and both $ f $ and $ g $ are symmetric w.r.t. $ T^\nu_0 $, respectively. Introducing some assumptions on nonlinearities, we get that the positive solutions of the problem above are symmetric w.r.t. the direction $ \nu $ by a new simple idea even if $ {{\Omega}} $ is not convex in the direction $ \nu $.</p></abstract>
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Xiong, Jiajuan, and Chu-Ren Huang. "Plurality and definiteness in Chengdu Chinese." Language and Linguistics / 語言暨語言學 21, no. 4 (September 18, 2020): 652–84. http://dx.doi.org/10.1075/lali.00074.xio.
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Abstract The authors identify a plural marker -ɕiɛ in Chengdu Chinese that can apply to both count and mass nouns, encoding plurality as well as definiteness. This post-nominal -ɕiɛ differs from the pre-nominal ɕiɛ, as the latter is purely plural but not inherently definite. Our analysis shows that the pre-nominal ɕiɛ functions as a quantifier, which occupies the [Spec, NumP] position, whereas the suffixal -ɕiɛ, by virtue of being a plural marker, is base-generated in the Num0 position and move to D0 to encode both plurality and definiteness. Moreover, the two ɕiɛs can co-occur in one and the same nominal phrase, exhibiting the double definiteness effect. The syntactic analysis of ɕiɛ in Chengdu Chinese, coupled with the study of di in Cantonese, has theoretical impacts on nominal phrase structures, in particular, on “plurality” and “definiteness”. First, plural markers in classifier languages contrast with those in number languages, as the former, but not the latter, defies numerical modification. Second, definiteness can be expressed by a non-D element, which may check its [+def] feature either by undergoing an upward movement to D (or [Spec, DP]) or by agreeing with the [+def] feature of a demonstrative. Third, the DP-NP distinction is strongly supported by our account of Chengdu Chinese.
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Zhu, Qifeng, Feiyue Zhu, Dianwei Fu, Anchao Zhang, and Sen Zhang. "Effects of geometric parameters on fluid flow and heat transfer in microchannel heat sink with trapezoidal grooves in sidewalls." Thermal Science, no. 00 (2022): 49. http://dx.doi.org/10.2298/tsci220129049z.
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Trapezoidal grooves were arranged in channel sidewalls of the proposed microchannel heat sinks to enhance heat transfer for cooling microelectronic systems. Three-dimensional numerical simulations were carried out to investigate the characteristics of fluid flow and heat transfer in the proposed microchannels. Field structures of thermal fluid flow, Nusselt number (Nu) and friction factor (f) were employed to study the effects of the relative groove depth (?) and relative grooves spacing length (?) of trapezoidal grooves on the thermal and hydraulic performance of the proposed microchannels. The results showed that the proposed microchannel presented better flow and thermal performance than the smooth straight one for Re <597.74 with f/f0<1 and for Re >149.44 with Nu/Nu0>1, respectively. The thermal enhancement factor (?) was achieved up to 1.197 with ?=0.4 and ?=1 for Re=714.18. Furthermore, the relative groove depth had much more significant influence on the overall performance than the relative groove spacing length.
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LI, Haofan, and Xue YUN. "Numerical simulation and experimental investigation of heat transfer performance of turbine blade with ribbed channel." Xibei Gongye Daxue Xuebao/Journal of Northwestern Polytechnical University 41, no. 4 (August 2023): 750–56. http://dx.doi.org/10.1051/jnwpu/20234140750.
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A combination of numerical simulation and experimental test is carried out, and the vortex core visualization technology is adopted to visualize vortex in the flow field and study the heat transfer mechanism. The heat transfer characteristics of air flow in 45° ribbed straight channel with aspect ratio of 1 and the other 6 new ribbed channels are studied. The results show that the average heat transfer performance of the new ribbed channel with all the fins 3.8 mm cut at the far end of fins along the flow direction is the best by comparing with the original ribbed straight channel under the same conditions. The average Nu, the average Nu/Nu0 and the average heat transfer enhancement factor FT of the ribbed wall is increased respectively by 25.1%, 24.8%, 22.7% on the average by comparing with the original ribbed channel. The experimental results show that the error between the experimental value and the simulated is about 10% for the outer wall temperature of ribbed channel.
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Iachachene, Farida, Amina Mataoui, and Yacine Halouane. "Steady interaction of a turbulent plane jet with a rectangular heated cavity." Thermal Science 20, no. 5 (2016): 1485–98. http://dx.doi.org/10.2298/tsci131106060i.
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Turbulent heat transfer between a confined jet flowing in a hot rectangular cavity is studied numerically by finite volume method using the k-w SST one point closure turbulence model. The location of the jet inside the cavity is chosen so that the flow is in the non-oscillation regime. The flow structure is described for different jet-to-bottom-wall distances. A parametrical study was conducted to identify the influence of the jet exit location and the Reynolds number on the heat transfer coefficient. The parameters of this study are: the jet exit Reynolds number (Re, 1560< Re <33333), the temperature difference between the cavity heated wall and the jet exit (DT=60?C) and the jet location inside the cavity (Lf, 2? Lf? 10 and Lh 2.5<Lh?10). The Nusselt number increased and attained its maximum value at the stagnation points and then decreased. The flow structure is found in good agreement with the available experimental data. The maximum local heat transfer between the cavity walls and the flow occurs at the potential core end. The ratio between the stagnation point Nusselt numbers of the cavity bottom (NuB0) to the maximum Nusselt number on the lateral cavity wall (NuLmax) decreased with the Reynolds number for all considered impinging distances. For a given lateral confinement, the stagnation Nusselt number of the asymmetrical interaction Lh?10 is almost equal to that of the symmetrical interaction Lh=10.
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STOPPA, S. GIORGIANNI, R. VISINONI,, P. "Infrared laser spectrum of cis-CHCl=CHF near 1060 cm-1: rovibrational analysis of the perturbed nu6 fundamental and determination of the constants of the dark vibrational state nu9 + nu10." Molecular Physics 97, no. 3 (August 10, 1999): 329–38. http://dx.doi.org/10.1080/002689799163721.
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Darzi, A. A. R., M. Farhadi, and K. Sedighi. "Numerical study of the fin effect on mixed convection heat transfer in a lid-driven cavity." Proceedings of the Institution of Mechanical Engineers, Part C: Journal of Mechanical Engineering Science 225, no. 2 (July 19, 2010): 397–406. http://dx.doi.org/10.1243/09544062jmes2307.
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In this study, the mixed convective heat transfer in a lid-driven cavity was investigated numerically. The finite volume discritization method was used to solve the momentum and energy equations by using the classic Boussinesq incompressible approximation. The cavity vertical walls are insulated whereas the bottom (hot wall) and top (cold wall) surface are maintained at a uniform temperature and fins are located on bottom wall. The effect of fin numbers over the flow field and heat transfer was investigated at various Richardson numbers. Study was carried out for Richardson numbers ranging from 0.01 to 10, fin numbers between 1 and 7, fin height ratio change from 0.05 to 0.3, and thermal conductivity ratio (fin to fluid) from 10 to 104, respectively. The results are presented in the form of streamlines, temperature contours, and Nusselt number distributions. The results show that the Nusselt number increases when the number of fin and fin height decrease. In addition, in all cases an increasing Richardson number caused increasing the relative Nusselt number ( Nu / Nu0). The heat transfer enhancement was observed at low fin numbers (1 and 3) and high Richardson number in comparison with the cavity without fins.
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Boonloi, Amnart. "The Influence of the Punched Delta Wings on Flow Pattern and Heat Transfer Characteristic in a Fin-and-Oval-Tube Heat Exchanger." Journal of Thermodynamics 2015 (October 26, 2015): 1–18. http://dx.doi.org/10.1155/2015/368960.
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3D numerical investigations are performed to study the heat transfer, friction factor, and thermal performance of a fin-and-oval heat exchanger with punched delta wings for a range of 500 ≤ Re ≤ 2500 (based on the hydraulic diameter). The influences of the punched angles, 20°, 30°, and 45°, flow directions, wing tips pointing downstream and upstream, and pitch ratios, 2, 3, 4, 5, and 6, are investigated. The results show that the use of the punched delta wings in the fin-and-oval-tube heat exchanger leads to an enhancement in the heat transfer and friction loss as compared to the plain fin for all cases (Nu/Nu0 and f/f0 higher than 1). The enhancements of the heat transfer and friction factor are around 1.01–1.22 and 1.37–2.65 times higher than the base case, respectively. The punched delta wings create the vortex flows through the test section that helps enhance the strength of the impinging flow on the tube walls. The impingement of the fluid flow is an important key to augment the heat transfer rate and thermal performance in the heat exchanger.
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Boonloi, Amnart, and Withada Jedsadaratanachai. "Effect of Flow Attack Angle for V-Wavy Plate on Flow and Heat Transfer in a Square Channel Heat Exchanger." Journal of Engineering 2018 (2018): 1–10. http://dx.doi.org/10.1155/2018/9487070.
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Effects of flow attack angles of the V-wavy plate on flow and heat transfer in a square channel heat exchanger are investigated numerically. The V-wavy plates with V-tips pointing downstream and upstream called V-Downstream and V-Upstream, respectively, are examined for the Reynolds number in the range of 3000–10,000. The finite volume method with SIMPLE algorithm is selected to solve the present problem. The numerical results are presented in terms of flow and heat transfer visualization. The thermal performance analysis is also concluded in the form of Nusselt number ratio (Nu/Nu0), friction factor ratio (f/f0), and thermal enhancement factor (TEF). The numerical result shows that the wavy plate can induce the swirling flow through the test section for all cases. The swirling flow disturbs the thermal boundary layer on the channel wall which is the reason for heat transfer enhancement. In range studies, the heat transfer rate increases around 3–6.5 and 2.8–6 times above the smooth channel for V-Downstream and V-Upstream, respectively. The optimum TEF is found at α = 20° and Re = 3000 to be around 2.09 for V-Upstream case.
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Hwang, G. J., and C. R. Kuo. "Experimental Studies and Correlations of Convective Heat Transfer in a Radially Rotating Serpentine Passage." Journal of Heat Transfer 119, no. 3 (August 1, 1997): 460–66. http://dx.doi.org/10.1115/1.2824119.
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The present paper investigates experimentally the effects of rotation on the convective heat transfer of air flow in a radially rotating three-passage serpentine square channel. Due to rotation, the cross-stream and radial secondary flows are induced by the Coriolis force and the centrifugal-buoyancy force, respectively. The channel walls were made of low thermal conductivity material for suppressing wall heat conduction. The wall surfaces were heated individually by four separate stainless-steel film heaters to distinguish the local heat transfer rates. The hydraulic diameter and the mean rotational radius of the flow passages were 4 and 180 mm, respectively. The governing parameters are the through-flow Reynolds number Re, the rotation number Ro, the buoyancy parameter Gr* and the main flow direction. The results show that the local heat transfer rate was enhanced by rotation on the trailing side for outward flow and on the leading side for inward flow. In the first and third passages, the effect of rotation on heat transfer is relatively prominent. The buoyancy effect is favorable to the heat transfer enhancement on four sides of these passages. The data of NuΩ/Nu0 are correlated on the leading and trailing sides of these passages.
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Boonloi, Amnart, and Withada Jedsadaratanachai. "Thermo-hydraulic performance improvement, heat transfer, and pressure loss in a channel with sinusoidal-wavy surface." Advances in Mechanical Engineering 11, no. 9 (September 2019): 168781401987257. http://dx.doi.org/10.1177/1687814019872573.
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Thermal efficiency development in a square channel heat exchanger attached with sinusoidal wavy surface is presented numerically. The affectation of flow attack angles ( α = 30°, 45°, and 60°), flow directions or sinusoidal wavy surface arrangements (V-apex directing downstream named “V-Downstream” and V-apex indicating upstream named “V-Upstream”), and amplitude ratios (blockage ratios = 0.10, 0.15, 0.20, and 0.25) for heat transfer and flow structure are examined for laminar flow regime ( Re = 100–1000). The physical model for the present investigation is validated with the correlation data. The current problem is resolved with the finite volume approach (semi-implicit method for pressure-linked equations algorithm). The computational information is illustrated in forms of flow topology and heat transfer mechanism in the square channel heat exchanger. The understanding of flow topology and heat transfer mechanism in the square channel heat exchanger is important knowledge to develop the heat transfer coefficient in the heat exchanger. The present of the sinusoidal wavy surface in the square channel heat exchanger can expand the heat transfer coefficient greater than the plain channel in all examples ( Nu/ Nu0 > 1). The maximal heat transfer rate is around 5.58 times above the plain square unit with the optimal performance around 1.98.
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Manukyan, G., J. Gallo, Z. Mikulkova, M. Trajerova, J. Savara, Z. Slobodova, and E. Kriegova. "SYNOVIAL FLUID NEUTROPHILS PLAY A ROLE IN THE PATHOPHYSIOLOGY OF KNEE OSTEOARTHRITIS: A PHENOTYPIC AND FUNCTIONAL STUDY." Orthopaedic Proceedings 105-B, SUPP_7 (April 4, 2023): 19. http://dx.doi.org/10.1302/1358-992x.2023.7.019.
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An increased number of neutrophils (NEUs) has long been associated with infections in the knee joints; their contribution to knee osteoarthritis (KOA) pathophysiology remains largely unexplored. This study aimed to compare the phenotypic and functional characteristics of synovial fluid (SF)-derived NEUs in KOA and knee infection (INF).Flow cytometric analysis, protein level measurements (ELISA), NEU oxidative burst assays, detection of NEU phagocytosis (pHrodoTM Green Zymosan BiparticlesTM Conjugate for Phagocytosis), morphological analysis of the SF-derived/synovial tissue NEUs, and cultivation of human umbilical vein endothelial cells (HUVECs) using SF supernatant were used to characterise NEUs functionally/morphologically.Results: Compared with INF NEUs, KOA NEUs were characterised by a lower expression of CD11b, CD54 and CD64, a higher expression of CD62L, TLR2 and TLR4, and lower production of inflammatory mediators and proteases, except CCL2.Functionally, KOA NEUs displayed an increased production of radical oxygen species and phagocytic activity compared with INF NEUs. Morphologically, KOA and INF cells displayed different cell sizes and morphology, histological characteristics of the surrounding synovial tissues and influence on endothelial cells. KOA NEUs were further subdivided into two groups: SF containing <10% and SF with 10%–60% of NEUs. Analyses of two KOA NEU subgroups revealed that NEUs with SF <10% were characterised by 1) higher CD54, CD64, TLR2 and TLR4 expression on their surface; 2) higher concentrations of TNF-α, sTREM-1, VILIP-1, IL-1RA and MMP-9 in SFs.Our findings reveal a key role for NEUs in the pathophysiology of KOA, indicating that these cells are morphologically and functionally different from INF NEUs. Further studies should explore the mechanisms that contribute to the increased number of NEUs and their crosstalk with other immune cells in KOA.This study was supported by the Ministry of Health of the Czech Republic (NU20-06-00269; NU21-06-00370).
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Prokešová, Radka, Martin Červený, Valérie Tóthová, Iva Brabcová, and Jiří Vlček. "The influence of selected work characteristics on missed and unfinished nursing care in hospitals: Evidence from the Czech Republic." Problems and Perspectives in Management 22, no. 1 (March 4, 2024): 491–99. http://dx.doi.org/10.21511/ppm.22(1).2024.39.
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Missed and unfinished nursing care in hospitals depends on the quality of human resources. This paper aims to analyze the influence of selected work characteristics on missing and incomplete nursing care in inpatient wards of Czech hospitals. The relationship between the rate of missed and unfinished nursing care and selected work characteristics was studied using the Czech version of the standardized questionnaire, the MISSCARE Survey. The study was conducted from September 26, 2021, to October 15, 2021. Controlled interviews with 1,205 nurses working in ward blocks in Czech hospitals were used. The research results showed statistically significant connections between selected work characteristics and missed and unfinished nursing care. Nurses with the highest level of education (Master, Ph.D.), nurses with specialized education, nurses with the lowest number of working hours (less than 30 hours per week), and nurses with the highest number of years of work experience (21 years and over) show a significantly lower rate of missed nursing care. Nurses from surgical departments, specialist nurses, and nurses with the highest education (Master, Ph.D.) report statistically significantly lower unfinished care levels. In contrast, nurses from regional/district hospitals, practical nurses/nursing assistants, and nurses with the lowest education (secondary school of nursing) report significantly higher unfinished nursing care levels. The information obtained can be used to improve nursing processes in the identified weak parts, strategic planning of nursing care, and sufficient personnel. AcknowledgmentsI would like to express my gratitude to co-authors and other members of the research team – Hana Hajduchová, Chloubová Ivana, Hana Kubešová, Josef Malý, Martin Doseděl, Ondřej Tesař, and Kateřina Malá-Ládová, without whose support the article could not have been published.Supported by the Ministry of Health of the Czech Republic, grant no. NU20-09-00257. All rights reserved.
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Youk, Hyun, Roland List, and Theophilus Ola. "The Growth of Ice Crystals by Molecular Diffusion." Journal of the Atmospheric Sciences 63, no. 6 (June 1, 2006): 1650–57. http://dx.doi.org/10.1175/jas3712.1.
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Abstract The mass transfer of water molecules by diffusion onto ice particles is best described by their Sherwood number (Sh), a dimensionless quantity, which combines molecular and convective effects and depends on the airflow as represented by the Reynolds number (Re). While Sh (Re > 0) has been previously measured in experiments for typical crystal shapes, the limiting case of pure molecular diffusion (Sh0) for zero flow with Re = 0 is not known well and needs independent determination. The direct numerical solution of the controlling Laplace equation links diffusion with electric fields through the electrostatic analogy. It will be solved for the electrostatic potential V around a crystal-shaped conductor of capacitance C. The results will then be converted by similarity theory. This led to the first numerical determination of Sh0 for hexagonal plates, hexagonal columns, stellar crystals, capped columns, and broad-branched crystals. The new data represent another necessary step in the formulation of an experiment-based theory of the growth of freely falling ice crystals in the atmosphere. A discrete version of Gauss's flux law is developed to compute the flux generated by a crystal-shaped conductor in a finite Cartesian grid box, using a Gauss–Seidel iterative scheme. This method is general and can be applied to compute Sh0 for any rectilinear shapes to any degree of accuracy. The dimensionless mass transfer by molecular diffusion, Sh0, is identical to the diffusion of heat characterized by the Nusselt number Nu0.
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Brahimi, Amine, Redha Rebhi, and Mounir Alliche. "Numerical Study of the Effects of Roughness Coupled with Inclination on a Turbulent Flow around an Obstacle." Processes 11, no. 7 (June 30, 2023): 1979. http://dx.doi.org/10.3390/pr11071979.
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In this study, we simulate the cooling of a microprocessor by thermal convection in three different shapes: a square, a trapezoidal, and a triangular shape. The latter is improved by a variety of types of roughness, including square roughness, triangular roughness Type 1, triangular roughness Type 2, and triangular roughness Type 3. The microprocessors are kept at a constant temperature, the air flow is constant, and the geometry is fixed. The physical phenomenon is simulated by the ANSYS software. The numerical results reported in this study cover the ranges of the obstacle’s angle of inclination, 0°≤θ≤45°, (square obstacles, θ=0°, trapezoidal obstacles, 0°<θ<45°, triangular obstacles, θ=45°) and Reynolds number, 2500≤Re≤10,000. The findings relate to streamlines, dynamic pressure (max), mean velocity, temperature field, mean Nusselt number (Nu/Nu0) profiles, local coefficient of friction (Cf/f0), mean coefficient of friction (f/f0) profiles, mean velocity field with roughness, and fluid temperature field with roughness. The aim of the study is to show the interaction between the roughness parameter and the obstacle geometry. In the case of a triangular obstacle, the contact between the cold air and the obstacle is significant downstream of the obstacle, which gives us good cooling, and the Nusselt number has an important value because the agitation of the flow increases convective heat transfer, and the coefficient of friction is low because the air flow is uniform.
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Kaplan, Mahmut. "Enhancement of the Thermohydraulic Performance in a Double Passage Square Duct with the Use of Inclined Ribs of 45°: A Comparative Computational Study." International Journal of Energy Research 2024 (January 16, 2024): 1–13. http://dx.doi.org/10.1155/2024/9935818.
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The modern gas turbines need to run at very high inlet temperature to promote their power output. Thus, improvements in cooling technologies play a significant role for enhancing the gas turbine blade life. In this paper, thermohydraulic performance (THP) of a two-pass square channel with inclined ribs at 45° was scrutinized employing the k–ε realizable model with enhanced wall treatment in ANSYS Fluent. The calculations were performed for the rib pitch to height ratio (p/e) of 5-10, rib height to hydraulic diameter ratio (e/Dh) of 0.1-0.2, and Reynolds number (Re) of 20,000-40,000. Detailed analysis of the flow structure in a double passage square duct was carried out to understand the interaction of the rib and bend-induced secondary flows and its contribution to heat transfer enhancement for the rib configurations with distinct p/e and e/Dh, which was not available in any other existing numerical or experimental investigations. The results revealed that the ribs with higher e/Dh generated the stronger stream-wise secondary flows which led to the augmentation of the cooling performance with the disadvantage of pressure loss increment. The maximum THP of 26.55% was achieved with the ribbed configuration having p/e=5 and e/Dh=0.1 at Re=20,000. The new correlations were developed from the computational data to predict the normalized Nusselt number and friction factor (Nu/Nu0 and f/f0, where 0 is the correlation), taking the e/Dh and flow Re into consideration.
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Svaton, Michael, Aneta Skotnicova, Leona Reznickova, Andrea Rennerova, Tatana Valova, Michaela Kotrova, Vincent H. J. van der Velden, et al. "NGS-Based MRD Quantitation: An Alternative to qPCR Validated on a Large Consecutive Cohort of Children with ALL." Blood 138, Supplement 1 (November 5, 2021): 1314. http://dx.doi.org/10.1182/blood-2021-152971.
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Abstract Together with multicolor flow cytometry, quantitation of clonal immunoglobulin (IG) and T-cell receptor (TR) gene rearrangements represents the current standard for the detection of minimal / measurable residual disease (MRD) in treatment protocols for pediatric acute lymphoblastic leukemia (ALL) patients. Despite the adoption of next generation sequencing (NGS) in the routine identification of clonal IG/TR gene rearrangements as markers for MRD detection, real-time quantitative (q)PCR is still the standard for MRD quantitation in follow-up samples. So far, no large-scale direct comparison of qPCR- and NGS-based MRD quantitation has been performed. We compared qPCR- and NGS-MRD evaluation in a cohort of children with B-cell precursor (BCP) ALL treated on the AIEOP-BFM ALL 2009 protocol and assessed the feasibility and relevance of this method for the stratification at day 33 (EOI). In total, 459 patients were diagnosed with BCP-ALL from 2010 to 2018, and 437 of them were included in our study based on the availability of residual DNA material isolated from day 33 bone marrow aspirates and having at least one IG/TR MRD marker detectable by standard qPCR with protocol-required sensitivity of 10 -4. Sequencing libraries were prepared according to the EuroClonality-NGS group SOP (Brüggemann et al, Leukemia 2019) with the total DNA input normalized to the equivalent of 150,000 nucleated cells to reach MRD sensitivity of 10 -5 and sequenced on Illumina NovaSeq and MiSeq instruments. In total of 780 IG/TR markers evaluated by both NGS and qPCR. Sequencing data were analyzed using the ARResT/Interrogate (Bystry et at, Bioinformatics 2017) pipeline and a custom bioinformatic analysis process and the NGS-MRD results were normalized to the EuroClonality-NGS central in-tube quality/quantification control (cIT-QC; Knecht et al, Leukemia 2019). From the total 780 IG/TR MRD markers evaluated by both methods, 629 (80.6%) were concordant with 242 markers being MRD positive and 387 negative. From 82 markers that were only positive by qPCR and not by NGS, 76 were positive below the quantitative range (positive non-quantifiable). Specificity analysis was performed for each marker by searching for the junction sequence across the dataset of all patients' NGS results. Based on these results, 22 out of 82 markers positive only by qPCR were classified as potentially unspecific (false positive) and similarly 32 unspecific markers were identified among the 69 positive only by NGS. This was also supported by unspecific amplification of the polyclonal control in 27 out of these 32 corresponding qPCR systems, in some cases leading to qPCR negative classification determined by the EuroMRD guidelines. Overall stratification of patients based only on day 33 MRD by qPCR or NGS was concordant in 76% of patients by both methods, while in 19% of patients, NGS-MRD quantitation led to the assignment to a lower-risk group, mainly due to the elimination of false-positive results. Furthermore, analysis of all positive markers across all patients' NGS libraries showed, that one out of 10 markers (mainly in the IGK, TRG and TRD loci) used for qPCR-MRD stratification did not provide satisfactory specificity, although they fully met EuroMRD criteria during the optimization of qPCR patient-specific assays. Our results show that NGS-MRD is highly concordant with traditional qPCR-based strategy and has comparable sensitivity and clinical value in the setting of a BFM-based clinical protocol, while being less laborious and providing significantly more specific results and additional information on the IG/TR repertoire (Kotrova et al, Blood 2016). Our study also emphasizes the importance of selecting MRD markers of adequate specificity at diagnosis. Currently, this selection can be assisted by these broad sequencing data on IG/TR repertoire of large number of patients. Based on these results, we propose that frontline NGS-MRD evaluation developed by the EuroClonality-NGS working group can be used as an alternative to traditional qPCR-based MRD quantitation in future MRD-based treatment protocols. Supported by grants NU20-03-00284 and NU20-07-00322 from the Czech Health Research Council and 534120 from Charles University. All methods were established through collaboration within the EuroClonality-NGS and EuroMRD groups. Disclosures van der Velden: Agilent: Research Funding; Navigate: Other: Service Level Agreement; Janssen: Other: Service Level Agreement; EuroFlow: Other: Service Level Agreement, Patents & Royalties: for network, not personally; BD Biosciences: Other: Service Level Agreement. Brüggemann: Incyte: Other: Advisory Board; Janssen: Speakers Bureau; Amgen: Other: Advisory Board, Travel support, Research Funding, Speakers Bureau. Langerak: Erasmus MS, University Medical Center: Current Employment; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Research Funding; Gilead: Research Funding; Janssen: Speakers Bureau.
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Kazda, T., R. Lakomy, I. Selingerova, P. Pospisil, L. Hynkova, R. Belanova, and P. Slampa. "P14.59 Rapid early progression of glioblastoma is not related to cortical/neural stem cells regions." Neuro-Oncology 23, Supplement_2 (September 1, 2021): ii49. http://dx.doi.org/10.1093/neuonc/noab180.170.
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Abstract BACKGROUND Rapid early progression (REP) of glioblastoma after surgery observed on pre-radiotherapy MRI scan is common. Subventricular zone (SVZ) and hippocampal regions are supposed to harbor astrocyte-like neural stem cells (NSC) with tumors arising from these transformed stem cells threatening of higher risk of REP. REP is defined as a new enhancing tumor or >25% increase in enhancement before radiotherapy. Lim′s classification of initial glioblastoma location related to these NSC regions predicts invasive and multifocal tumor phenotype. Glioblastomas are classified preoperatively into four groups by the spatial relationship of the contrast-enhancing lesion with the SVZ and cortex. The aim of this retrospective single-institutional study is to evaluate the relations of this Lim classification on REP in unselected cohort of glioblastoma patients. MATERIAL AND METHODS Patients receiving radiotherapy between 2014–2017 were analyzed, 95 were evaluable. 47 patients (30.5%) were treated with the Stupp regimen. Lim1 classification (contact with cortex as well as SVZ) was presented in 74(48%) patients, Lim2 (contact with SVZ only) in 22(14.3%), Lim3 (contact with cortex only) in 50(32.5%) and Lim4 in 8(5.2%) patients. A total of 52% of patients developed REP. RESULTS Significantly better overall survival was with Stupp regimen (23.3 vs. 8.6 months, p<0.001) and without REP (18.5 vs. 10.2 months, p=0.001). There was no significant impact of time to start of radiotherapy. No significant relation between REP and Lim classification was observed. CONCLUSION The initial location is not predictive for REP. Patients experiencing REP have significantly worse overall survival and modification of their management represents an urgent unmet clinical need. Molecular and clinical biomarkers indicating an increased risk of REP are needed.Presented will also be an already published analysis of clinical factors associated with REP in glioblastoma and the effect of REP and treatment on survival outcomes. Newly, we will introduce the investigator-initiated prospective academic clinical trial (GlioMET) focused on optimization of glioblastoma radiotherapy by 11C-Methionine PET scan in patients with REP. Supported by Ministry of Health of the Czech Republic AZV, No.18-03-00469 and AZV NU20-03-00148.
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Slaby, Ondrej, Petra Pokorna, Hana Pálová, Michal Kyr, Peter Múdry, and Jaroslav Sterba. "Comprehensive genomic profiling and individual therapeutic planning in high-risk/refractory pediatric solid tumors: A single-center real-world study." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): 10035. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.10035.
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10035 Background: Despite major improvements in the survival of pediatric cancer patients that were achieved through the intensification of chemotherapy and the perfection of supportive care in the past decades, treatment outcomes for high-risk, relapsed, and refractory solid cancers remain unsatisfactory. Accelerating the progress of pediatric oncology requires both therapeutic advances and attention to reducing the long-term cytotoxic treatment-related side effects. This could be achieved by targeting specific molecular changes that drive pediatric malignancies. Methods: From September 2016 to August 2020, a total of 192 patients with pediatric high-risk solid tumors successfully underwent comprehensive genomic profiling. Since more than thirty patients had two or more biopsies from recurrent relapses, the total number of samples examined was 295. In the cohort, there were 78 cases of central nervous system tumors, 68 sarcomas, 14 neuroblastomas, 10 lymphomas, and 22 tumors of other histology. Whole-exome sequencing was performed in all patients, fusion gene analysis in 96% of patients, whole-transcriptome profiling in 84% of patients, and CNV analysis in 63% of patients. Results: The diagnostic yield of therapeutically actionable findings was 40%, with single-nucleotide variants and small insertions/deletions being the most common actionable alteration types. In 23% of patients, a clinically relevant gene fusion was identified. The majority of the identified fusions were of diagnostic significance, and 18% of those were therapeutically targetable gene fusions involving BRAF, RAF1, ALK, FGFR1, or NTRK2. Four patients were eligible for immunotherapy based on high tumor mutational burden ( > 10 mut/Mb). Lymphomas and CNS tumors showed the highest rate of patients with therapeutically actionable findings (60% and 56%, respectively), followed by neuroblastomas (36%), sarcomas (25%), and other solid tumors (23%). All results and individual treatment plans were discussed and approved at multidisciplinary molecular tumor boards. Conclusions: Precision medicine in pediatric oncology has rapidly developed over the last decade and resulted in new therapeutic options based on molecular biomarkers and increased our understanding of the complexity of pediatric malignancies. Supported by the Ministry of Health of the Czech Republic, grant nr. NU20-03-00240 and the project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU.
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Saha, A. K., and Sumanta Acharya. "Flow and Heat Transfer in an Internally Ribbed Duct With Rotation: An Assessment of Large Eddy Simulations and Unsteady Reynolds-Averaged Navier-Stokes Simulations." Journal of Turbomachinery 127, no. 2 (December 7, 2004): 306–20. http://dx.doi.org/10.1115/1.1861917.
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Large eddy simulations (LES) and unsteady Reynolds averaged Navier-Stokes (URANS) simulations have been performed for flow and heat transfer in a rotating ribbed duct. The ribs are oriented normal to the flow and arranged in a staggered configuration on the leading and trailing surfaces. The LES results are based on a higher-order accurate finite difference scheme with a dynamic Smagorinsky model for the subgrid stresses. The URANS procedure utilizes a two equation k-ε model for the turbulent stresses. Both Coriolis and centrifugal buoyancy effects are included in the simulations. The URANS computations have been carried out for a wide range of Reynolds number (Re=12,500-100,000), rotation number (Ro=0-0.5) and density ratio (Δρ∕ρ=0-0.5), while LES results are reported for a single Reynolds number of 12,500 without and with rotation (Ro=0.12,Δρ∕ρ=0.13). Comparison is made between the LES and URANS results, and the effects of various parameters on the flow field and surface heat transfer are explored. The LES results clearly reflect the importance of coherent structures in the flow, and the unsteady dynamics associated with these structures. The heat transfer results from both LES and URANS are found to be in reasonable agreement with measurements. LES is found to give higher heat transfer predictions (5–10% higher) than URANS. The Nusselt number ratio (Nu∕Nu0) is found to decrease with increasing Reynolds number on all walls, while they increase with the density ratio along the leading and trailing walls. The Nusselt number ratio on the trailing and sidewalls also increases with rotation. However, the leading wall Nusselt number ratio shows an initial decrease with rotation (till Ro=0.12) due to the stabilizing effect of rotation on the leading wall. However, beyond Ro=0.12, the Nusselt number ratio increases with rotation due to the importance of centrifugal-buoyancy at high rotation.
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Menni, Younes, Ahmed Azzi, Ali J. Chamkha, and Souad Harmand. "Effect of wall-mounted V-baffle position in a turbulent flow through a channel." International Journal of Numerical Methods for Heat & Fluid Flow 29, no. 10 (October 7, 2019): 3908–37. http://dx.doi.org/10.1108/hff-06-2018-0270.
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Purpose The purpose of this paper is to carry out a numerical study on the dynamic and thermal behavior of a fluid with a constant property and flowing turbulently through a two-dimensional horizontal rectangular channel. The upper surface was put in a constant temperature condition, while the lower one was thermally insulated. Two transverse, solid-type obstacles, having different shapes, i.e. flat rectangular and V-shaped, were inserted into the channel and fixed to the top and bottom walls of the channel, in a periodically staggered manner to force vortices to improve the mixing, and consequently the heat transfer. The flat rectangular obstacle was put in the first position and was placed on the hot top wall of the channel. However, the second V-shaped obstacle was placed on the insulated bottom wall, at an attack angle of 45°; its position was varied to find the optimum configuration for optimal heat transfer. Design/methodology/approach The fluid is considered Newtonian, incompressible with constant properties. The Reynolds averaged Navier–Stokes equations, along with the standard k-epsilon turbulence model and the energy equation, are used to control the channel flow model. The finite volume method is used to integrate all the equations in two-dimensions; the commercial CFD software FLUENT along with the SIMPLE-algorithm is used for pressure-velocity coupling. Various values of the Reynolds number and obstacle spacing were selected to perform the numerical runs, using air as the working medium. Findings The channel containing the flat fin and the 45° V-shaped baffle with a large Reynolds number gave higher heat transfer and friction loss than the one with a smaller Reynolds number. Also, short separation distances between obstacles provided higher values of the ratios Nu/Nu0 and f/f0 and a larger thermal enhancement factor (TEF) than do larger distances. Originality/value This is an original work, as it uses a novel method for the improvement of heat transfer in completely new flow geometry.
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Kalita, O., T. Kazda, S. Reguli, R. Jancalek, P. Fadrus, M. Slachta, P. Pospisil, et al. "P11.59.B HIGH GRADE GLIOMAS IN PATIENTS WITH HISTORY OF EXTRACRANIAL CANCERS, A RETROSPECTIVE MULTICENTRIC STUDY." Neuro-Oncology 25, Supplement_2 (September 1, 2023): ii88. http://dx.doi.org/10.1093/neuonc/noad137.293.
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Abstract BACKGROUND Metastases are most frequent brain cancer, involving 50-60% of all intracranial neoplasm. Dominated origins are lung, breast, colorectal cancers. A progress in diagnostic and treatment strategies significantly improved the life expectancy of patients with extracranial cancers. Patients with neurological symptoms should be recommended to the brain MRI. Rarely silent primary brain cancers are revealed. Metastases are considered as a first option, but brain lesions with contrast enhancement could be misdiagnosed. We more and more often meet with high grade glioma (HGG) in patients experienced with other primary cancer. Aim of our study is evaluated an incidence of concurrent cancers, relations between former cancer staging and malignant primary brain tumor evaluation, and also appreciation of treatment efficiency. MATERIAL AND METHODS Data of all glioma patients treated at the three Czech neuro-oncology centers are collected regularly and prospectively during routine maintenance of a database. This work focuses on adult patients with concurrent history both of extracranial cancers and HGGs who underwent resection and oncotherapy between January 2008 and December 2020. Information on the patients’ clinical condition (Karnofsky score (KS)) was collected along with imaging and histological data on each patient’s tumor and details of their cytogenic alterations. Also regarding former extracranial cancers they have been followed up by oncologic center. We excluded the patients with prostate cancer. RESULTS The analysis included 48 patients aged between 44 and 79 years. The median age was 65.3 years. The group contained more women (35/48) than men (13/48). Thirty one patients had a history of breast carcinoma, nine of renal carcinomas and eight of colorectal carcinomas. Following the diagnosis of carcinoma, forty four patients received oncotherapy and four had no adjuvant therapy. Surgery of brain tumors has always revealed HGGs, IDH wild-type. Following the diagnosis HGG thirty patients underwent chemoradiotherapy, thirteen had palliative radiotherapy and five had no oncotherapy. The average time from the diagnosis of extracranial cancer to that of GBM was 4 years. The OS was 11.4 months (range 3-29 months). All the patients succumbed to GBM progression. CONCLUSION Limited number of these patients has been selected. Prognosis was depended on staging of extracranial cancer and performance status. If these patients would be able to pass standard oncologic treatment of primary HGG, they did not find survival distinctions to compare with no extracranial cancer history patients. For right treatment strategy it is mandatory to eliminate misdiagnose of brain metastases and primary malignant brain tumors. This research was funded and supported by Ministry of Health of the Czech Republic (grant NU21-03-00195, NU20-03-00148)
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Ivkovic, Tina Catela, Marie Mądrzyk, Karolina Trachtova, Petra Faltejskova-Vychytilova, Tana Machackova, Petra Pokorna, Jaroslav Juracek, Jiri Sana, and Ondrej Slaby. "Abstract 2802: Molecular and functional characterization of colorectal cancer derived-exosomes and exosomal coding and long non-coding RNA." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2802. http://dx.doi.org/10.1158/1538-7445.am2022-2802.
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Abstract Colorectal cancer (CRC) accounts for 9.7% of all cancers which makes it one of the three most commonly diagnosed cancer types worldwide. Prognosis of the patients with CRC depends mainly on the extent of the disease at the time of diagnosis. Therefore, the early detection of CRC and precancerous lesions is one of the main requirements of successful treatment. In recent years exosomes emerged as potential reservoirs of clinically useful biomarkers. Exosomes are 30-150 nm sized membranous vesicles that are endogenously produced by almost all cell types. They participate in intercellular communication by delivering proteins, microRNAs (miRNAs), mRNAs or long non-coding RNAs (lncRNAs) to recipient cells. In the context of cancer, intercellular communication allows cancer cells to create a favorable microenvironment for their growth. It has been shown that cancer-derived exosomes promote pathways contributing to hallmarks of cancer.To investigate diagnostic potential of exosomal RNA in CRC, blood serum samples were collected from patients with CRC and age- and sex-matched controls. Exosome isolation protocol was optimized, and the presence of vesicles in the exosome size range was confirmed using both dynamic light scattering (DLS) analysis as well as electron microscopy (TEM). Downstream analysis of serum exosomal RNA using next-generation sequencing (Illumina NextSeq 550) from exploratory cohort of CRC samples (N=50) and healthy controls (N=20) revealed both coding and non-coding RNAs to be differentially expressed (FC>1.5, p-value < 0.01). Among these were genes already reported to be dysregulated in CRC such as GAS5, but also lncRNAs previously unreported in CRC exosomes (AC103760.1, LINC02709 or PGBP) were identified. Gene set enrichment analysis (GSEA) was used to link RNAs identified within exosomes to their molecular functions. Using the Hallmark gene sets (MsigDB) as a reference, we discovered high enrichment of genes related to MYC targets, E2F targets and G2M checkpoint in healthy controls compared to CRC samples. All three hallmarks comprise genes crucial for cell proliferation. The first results indicated that the exosomal RNAs could be promising candidates as new diagnostic biomarkers in CRC, although further in vitro and in vivo exploration of identified differentially expressed lncRNAs is necessary. This work was supported by Ministry of Health of the Czech Republic grant nr. NU20-03-00127, NV19-03-00501 and NV19-03-00559. All rights reserved. Citation Format: Tina Catela Ivkovic, Marie Mądrzyk, Karolina Trachtova, Petra Faltejskova-Vychytilova, Tana Machackova, Petra Pokorna, Jaroslav Juracek, Jiri Sana, Ondrej Slaby. Molecular and functional characterization of colorectal cancer derived-exosomes and exosomal coding and long non-coding RNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2802.
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Pokorna, Petra, Renata Faberova, Olga Koskova, Martin Sterba, Hana Palova, Katerina Kozelkova, Robin Jugas, et al. "Abstract 1063: Precision medicine and cancer drug repurposing in the management of vascular anomalies." Cancer Research 83, no. 7_Supplement (April 4, 2023): 1063. http://dx.doi.org/10.1158/1538-7445.am2023-1063.
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Abstract Vascular anomalies are a heterogeneous group of rare diseases caused by defects in the early stages of vascular development that result in abnormal growth and development of vessels. The treatment typically consists of surgical approaches; unfortunately, many anomalies cannot be cured. Therefore, the goal of the treatment is to control the lesion, and progression or recurrence after an intervention is no exception. In the last 15 years, tremendous progress in understanding the molecular basis of the disease has been made, with alterations in more than 40 genes proven to be causal in the disease pathogenesis. Interestingly, such alterations are also found in many human cancers, which recently raised the question of whether repurposing anti-cancer drugs could be utilized in this setting. Tissue biopsies from 38 patients with vascular anomalies have been analyzed using different approaches ranging from Sanger sequencing to NGS-based detection. In 31 patients, known causal alterations of either germline or somatic origin were found. For the remaining seven patients, sampling issues were considered a cause of the negative result. Given that most patients suffered from a venous type of malformation, most alterations were found in TEK and PIK3CA genes, which are commonly altered in this subgroup. Other findings included alterations of KRAS, GLMN, PTEN, or IDH2 genes. TEK gene mutations were predominantly located in exon 17, which encodes for a part of the tyrosine kinase domain of the protein, with frequent L914F substitution being found in 12 cases. Identified PIK3CA gene mutations were all well-characterized activating alterations described in cancer-related context. Based on an identification of either TEK or PIK3CA mutation, 13 patients were administered targeted treatment using selective PI3K alpha subunit inhibitor alpelisib. For all patients, improvement in quality of life, lesion reduction and normalization of coagulation parameters was achieved. A deeper understanding of the pathophysiology of vascular anomalies can significantly contribute to patient stratification, identification of potential therapeutic targets, and overall better clinical management. At the same time, identifying potential therapeutic targets could lead to the administration of novel anti-cancer drugs within the concept of drug repurposing and better overall disease control compared to routinely used approaches. Supported by the Ministry of Health of the Czech Republic, grant nr. NU20-03-00240 and by the project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU. Citation Format: Petra Pokorna, Renata Faberova, Olga Koskova, Martin Sterba, Hana Palova, Katerina Kozelkova, Robin Jugas, Dagmar Al Tukmachi, Tana Machackova, Jiri Sana, Peter Mudry, Jaroslav Sterba, Ondrej Slaby. Precision medicine and cancer drug repurposing in the management of vascular anomalies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1063.
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Pokorna, Petra, Hana Palova, Sona Adamcova, Vojtech Bystry, Michal Kyr, Dagmar Al Tukmachi, Sona Mejstrikova, Peter Mudry, Jaroslav Sterba, and Ondrej Slaby. "Abstract 4511: Impact of the comprehensive genomic profiling on the individual therapeutic planning in high-risk/refractory tumors: real-world precision medicine in pediatric oncology." Cancer Research 83, no. 7_Supplement (April 4, 2023): 4511. http://dx.doi.org/10.1158/1538-7445.am2023-4511.
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Abstract Background: Despite major improvements in the survival of pediatric cancer patients that were achieved through the intensification of chemotherapy and the perfection of supportive care in the past decades, treatment outcomes for high-risk, relapsed, and refractory solid cancers remain unsatisfactory. Accelerating the progress of pediatric oncology requires both therapeutic advances and attention to reducing the long-term cytotoxic treatment-related side effects. This could be achieved by targeting specific molecular changes that drive pediatric malignancies. Material and Methods: From September 2016 to August 2020, a total of 192 patients with pediatric high-risk solid tumors successfully underwent comprehensive genomic profiling. Since more than thirty patients had two or more biopsies from recurrent relapses, the total number of samples examined was 295. In the cohort, there were 78 cases of central nervous system tumors, 68 sarcomas, 14 neuroblastomas, 10 lymphomas, and 22 tumors of other histology. Whole-exome sequencing was performed in all patients, fusion gene analysis in 96% of patients, whole-transcriptome profiling in 84% of patients, and CNV analysis in 63% of patients. Results: The diagnostic yield of therapeutically actionable findings was 40%, with single-nucleotide variants and small insertions/deletions being the most common actionable alteration types. In 23% of patients, a clinically relevant gene fusion was identified. The majority of the identified fusions were of diagnostic significance, and 18% of those were therapeutically targetable gene fusions involving BRAF, RAF1, ALK, FGFR1, or NTRK2. Four patients were eligible for immunotherapy based on high tumor mutational burden (>10 mut/Mb). Lymphomas and CNS tumors showed the highest rate of patients with therapeutically actionable findings (60% and 56%, respectively), followed by neuroblastomas (36%), sarcomas (25%), and other solid tumors (23%). All results and individual treatment plans were discussed at multidisciplinary molecular tumor boards. Conclusion: Precision medicine in pediatric oncology has rapidly developed over the last decade and resulted in new therapeutic options based on molecular biomarkers and increased our understanding of the complexity of pediatric malignancies. Supported by the Ministry of Health of the Czech Republic, grant nr. NU20-03-00240 and the project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU. Citation Format: Petra Pokorna, Hana Palova, Sona Adamcova, Vojtech Bystry, Michal Kyr, Dagmar Al Tukmachi, Sona Mejstrikova, Peter Mudry, Jaroslav Sterba, Ondrej Slaby. Impact of the comprehensive genomic profiling on the individual therapeutic planning in high-risk/refractory tumors: real-world precision medicine in pediatric oncology. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4511.
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Pokorna, Petra, Hana Palova, Tina Catela Ivkovic, Sona Adamcova, Michal Kyr, Vojtech Bystry, Robin Jugas, et al. "Abstract 76: Comprehensive genomic profiling as an approach to guide therapeutic planning in pediatric patients with high-risk solid tumors." Cancer Research 82, no. 12_Supplement (June 15, 2022): 76. http://dx.doi.org/10.1158/1538-7445.am2022-76.
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Abstract Despite the great achievements in treating pediatric cancer patients in the last several decades, approximately one fifth of patients remains uncurable using standard therapeutic modalities and require search for innovative therapeutic approaches. Advances in sequencing techniques and bioinformatic data processing enabled identification of wide spectrum of molecular alterations including single nucleotide variants, copy number aberrations, fusion genes or changes in expression and methylation patterns, which could serve as therapeutic targets. Translation of comprehensive molecular profiling into clinical practice is still limited, however, multiple precision oncology initiatives have already explored feasibility of this approach. From September 2016 to December 2020, a total of 160 patients with high-risk solid tumors that were treated or consulted at Department of Pediatric Oncology of University Hospital Brno were subjected to molecular analysis of tumor tissue using whole-exome sequencing, targeted RNA sequencing, whole-transcriptome profiling and array-CGH. In 18 patients, 2 or more biopsies were analyzed due to relapse or progression of the disease. In the cohort, CNS tumors were the most prevalent (41%), followed by sarcomas (33%) and neuroblastoma (9%). All patients were presented at multidisciplinary molecular tumor board, where treatment recommendations were discussed. In 37% of patients (n = 59), therapeutic targets were identified. Most commonly identified targets included BRAF (n = 9), FGFR1 (n = 7), NF1 (n = 6), NRAS (n = 5) and PIK3CA (n = 4), making RAS/MAPK signaling most frequently altered pathway in the subgroup. Single nucleotide variants or small indels accounted for 65% of actionable findings, followed by fusion genes (12%), copy number aberrations (9%), CD274 expression (7%, confirmed by IHC staining for PD-L1 protein), and high tumor mutational burden (7%). Clinically relevant fusions were found in 25% of patients and 20% of identified fusions were targetable. 8 patients were eligible for immunotherapy based on either PD-L1 expression, or high tumor mutational burden (>10 mut/Mb). Using molecular-based approach in treating high-risk patients represents a promising strategy and helps to understand the complexity of pediatric malignancies though examining tumor biology at multiple levels. Implementing the concept of precision oncology into clinical practice could not only be beneficial in the context of chances for improved survival of high-risk patients, but might also be convenient for other patients, whose successful treatment comes at cost of various secondary complications due to intensive chemotherapy/radiotherapy approaches. Supported by Ministry of Health of the Czech Republic, grant nr. NV19-03-00562, NV19-03-00501, NV19-03-00559 and NU20-03-00240. All rights reserved. Citation Format: Petra Pokorna, Hana Palova, Tina Catela Ivkovic, Sona Adamcova, Michal Kyr, Vojtech Bystry, Robin Jugas, Karolina Trachtova, Dagmar Al Tukmachi, Tomas Merta, Jaroslav Juracek, Jiri Sana, Sona Mejstrikova, Marta Jezova, Peter Mudry, Zdenek Pavelka, Jaroslav Sterba, Ondrej Slaby. Comprehensive genomic profiling as an approach to guide therapeutic planning in pediatric patients with high-risk solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 76.
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Kazda, T., R. Lakomy, L. Hynkova, P. Pospisil, J. Vasina, R. Belanova, T. Prochazka, et al. "P15.16.A 11C-METHIONIN PET FOR RADIOTHERAPY TREATMENT PLANNING IN PATIENTS WITH RAPID EARLY PROGRESSION AFTER GLIOBLASTOMA SURGERY: PROSPECTIVE PHASE II TRIAL." Neuro-Oncology 25, Supplement_2 (September 1, 2023): ii113. http://dx.doi.org/10.1093/neuonc/noad137.380.
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Abstract BACKGROUND Treatment of glioblastoma, the most aggressive primary brain tumor in adults, is multimodal with radiotherapy (RT) involved in almost of patients after the initial surgery. According to rare retrospective studies, progression is unfortunately seen on planning MR (called Rapid Early Progression, REP), performed usually up to 1 week before RT initiation, in a few tens of percent of patients, with no proven effect of waiting time to RT. REP was proved to be an independent negative prognostic factor. The optimal treatment of patients with REP is unknown and has not yet been studied in detail. The aim of this ongoing prospective phase II clinical trial (Eudra CT number 2020-000640-64) is to evaluate the effect of 11C-Methionin PET scan used for RT planning of glioblastoma patients with REP in order to prolong progression-free survival (PFS, primary outcome). Here we present the initial experience after the enrollment of first 26 patients out of the 67 planned. MATERIAL AND METHODS We included patients with Glioblastoma, IDHwt or Astrocytoma, IDHmt, WHO gr. IV, who developed REP and are fit for concurrent chemoradiotherapy. REP is evaluated by comparison of planning MRI and early postoperative MRI and is defined as 1) increase in postoperative residuum by ≥ 25% in any direction, 2) appearance of a new contras enhancing lesion (T1w MRI), 3) unequivocal progression of the enhancing lesion (e.g., in the case of multifocal glioblastoma where only the main tumor has been removed and the retained satellite has progressed). Patients were treated according to the Stupp or Perry protocol based on their age, and respective overall condition. Treatment response was evaluated using RANO criteria. Target volumes for RT were constructed as follows: Gross tumor volume: tumor cavity + enhancing lesion on T1w MRI + 11C-MET PET with 1.3 tumor-to- BACKGROUND ratio. Clinical target volume: GTV plus modified 2cm. The study is powered to prove increase of PFS from 4.9 months (historical cohort of patients with REP who had median overall survival of 10.7 months) to PFS 8 months. RESULTS A total of 26 patients were evaluated so far, 14 were treated according to Stupp protocol, the rest with an abbreviated course of RT in 15 fractions. The median follow up is 9.7 months. The median volume of GTV-MR was 22.2ccm (range 1.7-110.6ccm), the median volume of GTV-MET was 8.4ccm (range 0.3-46.3ccm). Median PFS was 5.6 months (6months-PFS of 46%) with a difference between those who underwent Perry protocol (8.5 months) and Stupp protocol (4.2 months). Median OS was 14 months (12months OS of 51%). CONCLUSION 11C-MET PET may be valuable in target definitions for RT of glioblastoma patients with REP. Volumetric studies, patterns of failure and quality of life will be important secondary outcomes.Supported by the Ministry of Health of the Czech Republic, grant NU20-03-00148.
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Machackova, Tana, Petra Vychytilova-Faltejskova, Marie Madrzyk, Karolina Trachtova, Marketa Pavlikova, Jan Kotoucek, Jana Halamkova, et al. "Abstract 6709: Utility of RNA sequencing for transcriptome analysis of small extracellular vesicles derived from blood sera of colorectal cancer patients." Cancer Research 83, no. 7_Supplement (April 4, 2023): 6709. http://dx.doi.org/10.1158/1538-7445.am2023-6709.
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Abstract Introduction: Currently used molecular diagnostic tests for colorectal cancer (CRC) are underperforming and more sensitive, non-invasive biomarkers are needed. Long non-coding RNAs (lncRNA) and microRNA (miRNA) have shown potential as diagnostic biomarkers. Unfortunately, the identification of non-coding RNA circulating biomarkers in blood serum is significantly burdened by abundant RNA specimens from disrupted blood cells. Recently, small extracellular vesicles (sEVs) emerged as potential reservoirs of clinically relevant biomarkers, including lncRNAs and miRNAs. In theory, sEVs protect RNAs from degradation and might serve as a source of intact RNA for further analyses. However, there is a lack of evidence supporting the superior quality of RNA extracted from sEVs over RNA from whole blood serum. This study aimed to analyze the RNA content of blood serum and the sEVs derived from the blood serum of CRC patients and healthy controls using RNA sequencing. Moreover, small RNA sequencing was used to evaluate the difference in miRNA profiles of sEVs and corresponding blood sera of CRC patients and healthy controls. Methods: Spin-column chromatography (Exiqon), precipitation-based method (Norgen), and size-exclusion chromatography (iZON) were used to extract sEVs from blood sera. The concentration of sEVs was measured by dynamic light scattering (DLS), the size was evaluated by electron microscopy (EM), and sEV-specific content was analyzed by western blot and qRT-PCR. RNA was extracted using the column-based method. Next-generation sequencing (NGS) analyses of blood serum and sEVs extracted from blood serum included samples from 10 CRC patients and 10 healthy controls for RNAseq, and 5 CRC patients and 5 healthy controls for small RNAseq. Differential expression analysis was carried out in R using DESeq2 package. Results: DLS and EM showed that size-exclusion chromatography yielded the purest population of sEVs characterized according to ISEV recommendations. Extraction of sEVs and subsequent RNA extraction and sequencing library preparation from ultra-low input samples were optimized. Over 30k different RNAs were identified in the sEVs derived from blood sera of CRC patients and healthy controls, including lncRNAs, miRNAs, and protein-coding RNAs. A detailed comparison of the transcriptome of blood sera and corresponding sEVs is a part of the poster. Conclusion: sEVs could serve as a source of RNA biomarkers; however, proper characterization and optimal methodology are necessary. This work was supported by the Ministry of Health of the Czech Republic grant No. NU20-03-00127, by The project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU, by the project BBMRI-CZ, nr. LM2018125, and in co-operation with CEMCOF, CEITEC MU (CIISB) supported by MEYS CR, LM2018127. Citation Format: Tana Machackova, Petra Vychytilova-Faltejskova, Marie Madrzyk, Karolina Trachtova, Marketa Pavlikova, Jan Kotoucek, Jana Halamkova, Dagmar Al Tukmachi, Jiri Sana, Petra Pokorna, Milana Sachlova, Ondrej Slaby. Utility of RNA sequencing for transcriptome analysis of small extracellular vesicles derived from blood sera of colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6709.
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Zavada, J., Z. Forejtová, L. Nováková, and T. Serranová. "AB0258 PREPULSE INHIBITION OF THE BLINK REFLEX -A PUTATIVE MARKER OF “FIBROMYALGIANESS” - IS ALTERED IN PTS WITH RHEUMATOID ARTHRITIS COMPARED TO HEALTHY CONTROLS, BUT NOT PREDICTIVE FOR PAIN LEVEL OR THERAPEUTIC RESPONSE TO BDMARDS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1312.1–1312. http://dx.doi.org/10.1136/annrheumdis-2023-eular.1177.
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BackgroundConcomitant fibromyalgia (FM) is highly prevalent in pts with RA. In FM patients, altered abnormalities in processing of sensory stimuli including abnormal subcortical sensorimotor integration measured using prepulse inhibition (PPI) have been described [1]. PPI is a robust neurophysiological phenomenon in which a weak sensory event leads to reduction in magnitude of the reflex response that would be otherwise elicited by a reflex-eliciting stimulus presented 30-500 ms later. Its physiological purpose is to protect salient from irrelevant information at the subcortical level, thereby preventing undesired motor reactions. In RA patients, abnormal processing of sensory information may affect subjective aspects of disease activity indices, and thus influence treatment decisions.ObjectivesWe aimed to investigate, whether PPI may serve as a predictive marker of FM in pts with RA starting their first targeted therapy.MethodsPPI was measured in 15 patients with RA before initiation of treatment with bDMARDs, and 50 healthy controls (HC). We examined the effect of a weak electrical stimulus to the index finger (prepulse) on the blink reflex magnitude induced by electrical stimuli delivered to the supraorbital nerve at interstimulus interval 100 ms. To analyze the degree to which PPI affects baseline actual pain (VAS-NRS), patient global assessment PGA, discordance between PGA and EGA (expert global assessment) calculated as PGA minus EGA we performed univariate linear regression analyses using VAS-NRS, PGA, and PGA minus EGA as dependent variables. We selected the following predictive variables: age; sex; BMI; disease duration; erosive disease; SJC; TJC; pain VAS, ESR; mHAQ; ACPA. We used standardised β to compare the strengths of the relationships. We also analyzed the contribution of PPI to therapeutic response in month 3 and 6.ResultsAs compared to HC, patients with RA were older, reported higher pain levels, and their mean PPI scores were significantly lower (Table 1). In RA pts PPI was neither predictive for baseline VAS-NRS, PGA, PGA-EGA, nor for ΔDAS28, ΔHAQ or ΔVAS in month 3 or 6. The trajectory of mean DAS28 according to ordinal level of PPI is shown in Figure 1.ConclusionLower PPI in RA patients may reflect abnormal filtering of afferent information flow to the brain. Together with previous findings in FM, our results suggest abnormal subcortical sensory information may be involved in nociplastic pain in RA patients. However, PPI was neither predictive for baseline level of pain, PGA, or EGA-PGA, nor for therapeutic response in pts with RA.Reference[1] Kofler M, Halder W. Clin Neurophysiol. 2014 Mar;125(3):593-601Table 1.Comparison of PPI, age and gender between RA patients (n=15) and controls (n=50)PredictorRA patients (n=15)Controls (n=50)p-valueAge, median (IQR)47 (43–69)44 (35–49)0.023Women, n (%)11 (73.3%)34 (68.0%)0.761PPI, mean (SD)0.53 (0.12)0.65 (0.17)0.020Actual pain (0–10), median (IQR)6.0 (4.0–7.0)1.6 (0.3–2.3)<0.001IQR – inter-quartile range; SD – standard deviationFigure 1.The average trajectory of disease activity after start of targeted therapy in pts with RA according to their baseline PPI. PPI results are stratified as follows: normal, borderline and abnormal inhibition >60%, 40-60%, and <40% resp.AcknowledgementsThis work was supported by the project (Ministry of Health, Czech Republic) for consensual development of research organization 023728 and by grant Nr. NU20-04-00332 and Cooperatio Program in Neuroscience.Disclosure of InterestsJakub Zavada Speakers bureau: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Sanofi, Astra Zeneca, Sobi, Zuzana Forejtová: None declared, Lucia Nováková: None declared, Tereza Serranová: None declared.
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Trsová, Iva, Andrea Hrustincova, Monika Belickova, Monika Kaisrlikova, Zuzana Lenertová, David Kundrat, Zdenek Krejcik, et al. "Different Mutations in SF3B1 Gene Have Specific Transcriptomic Characteristics in Myelodysplastic Neoplasms." Blood 142, Supplement 1 (November 28, 2023): 3218. http://dx.doi.org/10.1182/blood-2023-179068.
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Myelodysplastic neoplasms (MDS) are hematopoietic stem cell (HSC) disorders characterized by ineffective hematopoiesis, peripheral cytopenia, and increased tendency to leukemic transformation. Somatic mutations in spliceosome machinery occur in approx. 50% of MDS patients. Among these, up to 30% of MDS patients carry a mutation in SF3B1. According to the 2022 classification system, MDS-SF3B1 is now considered as separate MDS subtype. Mutated SF3B1 perturbs mitochondrial function, resulting in apoptosis and ineffective erythropoiesis. The most common mutation of SF3B1, K700E, accounts for 50% of the variants, with additional codons (such as 666 and 662) acting as hotspot sites. Different mutations seem to be associated with distinct clinicopathological features. However, the prognostic implication of different SF3B1 mutations in MDS remains controversial and needs further clarification. This study investigated differences in clinical and molecular features of MDS-SF3B1 with different types of SF3B1 mutations. To investigate a direct impact of different point mutations in SF3B1, the study was based on four isogenic NALM6 cell lines, the wildtype (wt) and three cell lines, each with different SF3B1 mutation (CRISPR/Cas9-edited K700E, K666N, and H662Q). To understand phenotypic manifestations of the mutations in the disease, we also analyzed clinical and transcriptional characteristics of 146 lower-risk MDS patients. Using RNA-seq in the cell lines and CD34+ BM patient cells (17 patients with no mutation, 11 patients with K700E SF3B1 mutation, 5 patients with K666N/E SF3B1 mutation), we investigated effects of different SF3B1 mutations on RNA splicing events and gene expression levels. Initially, outcome analysis confirmed the previously described observation that patients with a SF3B1 mutation have favorable outcomes compared to those with other splicing factor mutations. Further, the analysis showed that specific mutations in SF3B1 tend to lead to different prognoses; patients with K700E had longer survival compared to those with other SF3B1 mutations (mean progression-free survival was 64.8 vs. 29.1 months). Analysis of RNA splicing in NALM6 showed that K666N and H662Q mutations share similar characteristics whereas K700E mutation is more similar to wt-cells. Most significant changes were found in retained introns (RI); increased RI inclusion levels were detected in K666N/H662Q cells compared to K700E/wt cells. In patients, RI events were also strongly increased in K666N/E compared to K700E samples (Fig. 1). A significant overlap was identified between cell line and patient data; out of 173 genes with higher RI inclusion level in K666N-NALM6 cells, 77 genes had higher RI inclusion also in patients. Interestingly, 12 out of these 77 genes were related to mitochondrial functions (e.g., CREBZF, DDX1, MRPL23, MUTYH, and RAF1). RNA-seq data further showed significant alternations in gene expression levels in the four isogenic cell lines and also in patient samples with different mutations. Surprisingly, a more pronounced difference was detected in gene expression between patients with different SF3B1 mutations than between patients with no mutation and with any SF3B1 mutation (irrespective of its type), suggesting that specific SF3B1 mutations result in different phenotypes. Pathway analyses showed that deregulated genes in samples with K700E vs. other hotspot mutations were significantly enriched in electron transport, cell cycle, proliferation, quiescence, and HSC differentiation. Importantly, expression of multiple mitochondria-related genes was altered between K700E and K666N/H662Q NALM6 cells (334 genes, FDR < 0.01; Fig. 2), indicating different metabolic characteristics of the cells with non-K700E mutations. For example, several subunits of mitochondrial respiratory complexes I and IV were upregulated in K700E cells, pointing to differences in energetic metabolism. Altogether, our data support the hypothesis that only K700E mutation of SF3B1 may have a positive prognostic value and that other SF3B1 mutations may influence cells differently, specifically affecting their mitochondrial functions. Based on our results, we conclude that prognostic implication of different SF3B1 mutations in MDS will need additional refinements in future. Supported by AZV CR (NU20-03-00412), GA CR (20-19162S), and MH CZ-DRO (00023736).
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Zaliova, Marketa, Jan Zuna, Lucie Winkowska, Iveta Janotova, Justina Skorepova, Julius Lukes, Claus Meyer, et al. "Independent Prognostic Value of DNA-Based Minimal Residual Disease Assessment in Unselected Population-Based Cohort of Pediatric Acute Myeloid Leukemia." Blood 142, Supplement 1 (November 28, 2023): 4327. http://dx.doi.org/10.1182/blood-2023-179723.
Full textAbstract:
Monitoring of minimal residual disease (MRD) in childhood acute myeloid leukemia (AML) can assess response to treatment and predict relapse. Current MRD monitoring methods in childhood AML - flow cytometry and quantitation of fusion transcripts - have significant shortcomings and do not cover the entire spectrum of patients. We demonstrated (Lukes et al, Hemasphere 2020) the feasibility of MRD monitoring using DNA-based primary targets in selected subgroups of AML. Now we extended this approach to the unselected consecutive population of pediatric AML. We included 133 children (0-18) out of 135 consecutively diagnosed with AML in Czechia (2012-2022), all treated on non-MRD-based protocols. For genetic characterization, we used algorithm consisting of screening for recurrent gene fusions and mutations by PCR and targeted-NGS followed by transcriptome sequencing (WTS). Targeted-NGS (or PCR) was performed to identify genomic fusion sequences. 130 patients were eligible for MRD monitoring (3 patients died early). MRD was preferentially monitored by DNA-based qPCR (alternatively by amplicon NGS or qRT-PCR). MRD levels were expressed relative to diagnosis. Primary genetic aberration was found by targeted screening in 102 children; remaining 31 were further investigated using WTS. In 27 children, WTS identified rare, novel or atypical primary genetic aberrations not covered by the targeted screening. Primary genetic aberration was found in 97% of cases (129/133). Majority of AMLs (81%) were classified into common subtypes: AML with KMT2Ar, PML::RARA, RUNX1::RUNX1T1, CBFB::MYH11, mutation (m) of GATA1 , CEBPA or NPM1. Recurrent but rare aberrations in pediatric AML were found in 16 patients: UBTFm, RUNX1m, HOXA10 translocation, KAT6A::CREBBP, KAT6A::LEUTX, DEK::NUP214, BCR::ABL1, NUP98::NSD1 and CBFA2T3::GLIS2. In 5 patients, fusion genes were found, previously described sporadically (SPFQ::ZFP36L216, XPO1::TNRC1817) or not at all in AML (ETV6::CTNNB1, FUS::FEV, ZEB2::RUNX1). Only secondary aberrations were identified in remaining 4 patients. In 82 patients (of 84 examined), genomic fusion sequence was found and qPCR designed and used. Of 41 children carrying genetic aberrations other than fusions, in 29 quantification system was successfully implemented. Altogether, quantification system for MRD monitoring was established in 122 patients, with primary aberrations as DNA targets in 116 patients, reaching sensitivity of 10 -4 in 112 and 5x10 -4 in 4 patients. Four and two children were monitored with sensitivity of 10 -4 using secondary aberrations as DNA targets or by qRT-PCR-based quantification of fusion transcripts, respectively. MRD clearance significantly differed among genetic subtypes: while GATA1m AML had the fastest response, in contrast to patients with prognostically favorable genetic subtypes - CBFB::MYH11, RUNX1::RUNX1T1, CEBPAm and NPM1m - who were treated predominantly on the standard risk (SR) arm of the AML-BFM 2012 Registry Protocol and none achieved molecular remission (mREM) at D28 (70% vs 0%, p < 0.0001). Significant proportion of patients (25-89% within individual subtypes) did not achieve mREM even after the last block of chemotherapy. The response of patients with KMT2Ar AML and AML classified into remaining subtypes (predominantly intermediate- and high-risk) was overall faster compared to prognostically favorable subtypes on SR arm (KMT2Ar D28 mREM 33% vs 0% at D28, p < 0.0001). KMT2A::MLLT10/3 had faster clearance then other KMT2Ar (mREM D28 44% vs. 0% in other KMT2Ar, p = 0.02). In a multivariate analysis including (cyto)genetic risk and treatment, D28 MRD was the only significant predictor of outcome using both the 10 -3 (p = 0.006 for EFS and 0.012 for OS) and 10 -2 levels (p = 0.004 for EFS and 0.01 for OS) for stratification. Similarly, in an alternative multivariate analysis model, D56 MRD (positive at any level versus negative) was also the only significant predictor of outcome independent of risk and treatment (p = 0.005 for EFS and 0.01 for OS) In summary, we present a strategy for MRD monitoring in pediatric AML that is technologically feasible, real-life applicable to vast majority of all patients, and has clear prognostic significance. Supported by National Institute of Cancer Research No. LX22NPO5102 funded by the European Union-Next Generation EU, and AZV grant NU20-07-00322.