Flow characteristics of gaseous flow through a microtube discharged into the atmosphere

Flow characteristics for a wide range of Reynolds number up to turbulent gas flow regime, including flow choking were numerically investigated with a microtube discharged into the atmosphere. The numerical methodology is based on the Arbitrary-Lagrangian-Eulerian (ALE) method. The LB1 turbulence model was used in the turbulent flow case. Axis-symmetric compressible momentum and energy equations of an ideal gas are solved to obtain the flow characteristics. In order to calculate the underexpanded (choked) flow at the microtube outlet, the computational domain is extended to the downstream region of the hemisphere from the microtube outlet. The back pressure was given to the outside of the downstream region. The computations were performed for adiabatic microtubes whose diameter ranges from 10 to 500 µm and whose aspect ratio is 100 or 200. The stagnation pressure range is chosen in such a way that the flow becomes a fully underexpanded flow at the microtube outlet. The results in the wide range of Reynolds number and Mach number were obtained including the choked flow. With increasing the stagnation pressure, the flow at the microtube outlet is underexpanded and choked. Although the velocity is limited, the mass flow rate (Reynolds number) increases. In order to further validate the present numerical model, an experiment was also performed for nitrogen gas through a glass microtube with 397 µm in diameter and 120 mm in length. Three pressure tap holes were drilled on the glass microtube wall. The local pressures were measured to determine local values of Mach numbers and friction factors. Local friction factors were numerically and experimentally obtained and were compared with empirical correlations in the literature on Moody's chart. The numerical results are also in excellent agreement with the experimental ones

Predicting Functional and Regulatory Divergence of a Drug Resistance Transporter Gene in the Human Malaria Parasite

Background: The paradigm of resistance evolution to chemotherapeutic agents is that a key coding mutation in a specific gene drives resistance to a particular drug. In the case of resistance to the anti-malarial drug chloroquine (CQ), a specific mutation in the transporter pfcrt is associated with resistance. Here, we apply a series of analytical steps to gene expression data from our lab and leverage 3 independent datasets to identify pfcrt-interacting genes. Resulting networks provide insights into pfcrt’s biological functions and regulation, as well as the divergent phenotypic effects of its allelic variants in different genetic backgrounds. Results: To identify pfcrt-interacting genes, we analyze pfcrt co-expression networks in 2 phenotypic states - CQ-resistant (CQR) and CQ-sensitive (CQS) recombinant progeny clones - using a computational approach that prioritizes gene interactions into functional and regulatory relationships. For both phenotypic states, pfcrt co-expressed gene sets are associated with hemoglobin metabolism, consistent with CQ’s expected mode of action. To predict the drivers of co-expression divergence, we integrate topological relationships in the co-expression networks with available high confidence protein-protein interaction data. This analysis identifies 3 transcriptional regulators from the ApiAP2 family and histone acetylation as potential mediators of these divergences. We validate the predicted divergences in DNA mismatch repair and histone acetylation by measuring the effects of small molecule inhibitors in recombinant progeny clones combined with quantitative trait locus (QTL) mapping. Conclusions: This work demonstrates the utility of differential co-expression viewed in a network framework to uncover functional and regulatory divergence in phenotypically distinct parasites. pfcrt-associated co-expression in the CQ resistant progeny highlights CQR-specific gene relationships and possible targeted intervention strategies. The approaches outlined here can be readily generalized to other parasite populations and drug resistances

An optimized microarray platform for assaying genomic variation in Plasmodium falciparum field populations

We present an optimized probe design for copy number variation (CNV) and SNP genotyping in the Plasmodium falciparum genome. We demonstrate that variable length and isothermal probes are superior to static length probes. We show that sample preparation and hybridization conditions mitigate the effects of host DNA contamination in field samples. The microarray and workflow presented can be used to identify CNVs and SNPs with 95% accuracy in a single hybridization, in field samples containing up to 92% human DNA contamination

Population Structure Shapes Copy Number Variation in Malaria Parasites.

If copy number variants (CNVs) are predominantly deleterious, we would expect them to be more efficiently purged from populations with a large effective population size (Ne) than from populations with a small Ne. Malaria parasites (Plasmodium falciparum) provide an excellent organism to examine this prediction, because this protozoan shows a broad spectrum of population structures within a single species, with large, stable, outbred populations in Africa, small unstable inbred populations in South America and with intermediate population characteristics in South East Asia. We characterized 122 single-clone parasites, without prior laboratory culture, from malaria-infected patients in seven countries in Africa, South East Asia and South America using a high-density single-nucleotide polymorphism/CNV microarray. We scored 134 high-confidence CNVs across the parasite exome, including 33 deletions and 102 amplifications, which ranged in size from <500 bp to 59 kb, as well as 10,107 flanking, biallelic single-nucleotide polymorphisms. Overall, CNVs were rare, small, and skewed toward low frequency variants, consistent with the deleterious model. Relative to African and South East Asian populations, CNVs were significantly more common in South America, showed significantly less skew in allele frequencies, and were significantly larger. On this background of low frequency CNV, we also identified several high-frequency CNVs under putative positive selection using an FST outlier analysis. These included known adaptive CNVs containing rh2b and pfmdr1, and several other CNVs (e.g., DNA helicase and three conserved proteins) that require further investigation. Our data are consistent with a significant impact of genetic structure on CNV burden in an important human pathogen

The N⁶-methyladenosine methyltransferase METTL16 enables erythropoiesis through safeguarding genome integrity

RNA修飾による赤血球造血制御機構を解明 --RNAのメチル化がDNA修復に必要--. 京都大学プレスリリース. 2022-11-10.Mice show METTL in DNA blood repair: RNA methylation shows important role in erythropoiesis. 京都大学プレスリリース. 2022-11-25.During erythroid differentiation, the maintenance of genome integrity is key for the success of multiple rounds of cell division. However, molecular mechanisms coordinating the expression of DNA repair machinery in erythroid progenitors are poorly understood. Here, we discover that an RNA N⁶-methyladenosine (m⁶A) methyltransferase, METTL16, plays an essential role in proper erythropoiesis by safeguarding genome integrity via the control of DNA-repair-related genes. METTL16-deficient erythroblasts exhibit defective differentiation capacity, DNA damage and activation of the apoptotic program. Mechanistically, METTL16 controls m⁶A deposition at the structured motifs in DNA-repair-related transcripts including Brca2 and Fancm mRNAs, thereby upregulating their expression. Furthermore, a pairwise CRISPRi screen revealed that the MTR4-nuclear RNA exosome complex is involved in the regulation of METTL16 substrate mRNAs in erythroblasts. Collectively, our study uncovers that METTL16 and the MTR4-nuclear RNA exosome act as essential regulatory machinery to maintain genome integrity and erythropoiesis

Induction of insulin-like growth factor 2 expression in a mesenchymal cell line co-cultured with an ameloblast cell line

Various growth factors have been implicated in the regulation of cell proliferation and differentiation during tooth development. It has been unclear if insulin-like growth factors (IGFs) participate in the epithelium–mesenchyme interactions of tooth development. We previously produced three-dimensional sandwich co-culture systems (SW) containing a collagen membrane that induce the differentiation of epithelial cells. In the present study, we used the SW system to analyze the expression of IGFs and IGFRs. We demonstrate that IGF2 expression in mesenchymal cells was increased by SW. IGF1R transduces a signal; however, IGF2R does not transduce a signal. Recombinant IGF2 induces IGF1R and IGF2R expression in epithelial cells. IGF1R expression is increased by SW; however, IGF2R expression did not increase by SW. Thus, IGF2 signaling works effectively in SW. These results suggest that IGF signaling acts through the collagen membrane on the interaction between the epithelium and mesenchyme. In SW, other cytokines may be suppressed to induce IGF2R induction. Our results suggest that IGF2 may play a role in tooth differentiation

Spillover Effects of Studying with Immigrant Students; A Quantile Regression Approach

Abstract: We analyze how the share of immigrant children in the classroom aects the educational attainment of native Dutch children in terms of their language and math performance at the end of primary school. Our paper studies the spill-over effects at different parts of the test score distribution of native Dutch students using a quantile regression approach. We fi nd no evidence of negative spillover effects of the classroom presence of immigrant children at the median of the test score distribution. In addition, there is no indication that these spill-over effects are present at other parts of the distribution.

Effect of corrugated minichannel variable width on entropy generation for convective heat transfer of alpha-Alumina-water nanofluid

Energy management and sustainability in thermal systems require maximum utilization of resources with minimal losses. However, it is rarely unattainable due to the ever-increasing need for a high-performance system combined with device size reduction. The numerical study examined convective heat transfer of an alpha-Alumina-water nanofluid in variable-width corrugated minichannel heat sinks. The objective is to study the impact of nanoparticle volume fractions and flow area variation on the entropy generation rate. The determining variables are 0.005 – 0.02 volume fractions, the fluid velocity 3 – 5.5 m/s and heat flux of 85 W/cm2. The numerical results show an acceptable correlation with the experiment results. The results indicate the thermal entropy production drop with an increase in nanoparticles volume fraction. Contrastingly, the frictional resistance entropy suggests the opposite trend due to the turbulence effect on the fluid viscosity. The induction of Alumina-Water nanofluid with enhanced thermal conductivity declined the entropy generation rate compared to water alone. The increase in width ratio by 16% between the cases translates to at least a 9% increase in thermal entropy production. The outcome of this study can provide designers and operators of thermal systems more insight into entropy management in corrugated heatsinks