650 research outputs found

    Effects of spray angle variation on mixing in a cold supersonic combustor with kerosene fuel

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    Abstract: Effective fuel injection and mixing is of particular importance for scramjet engines to be operated reliably because the fuel must be injected into high-speed crossflow and mixed with the supersonic air at an extremely short time-scale. This study numerically characterizes an injection jet under different spray angles in a cold kerosene-fueled supersonic flow and thus assesses the effects of the spray angle on the mixing between incident shock wave and transverse cavity injection. A detailed computational fluid dynamics model is developed in accordance with the real scramjet combustor. Next, the spray angles are designated as 45º, 90º, and 135º respectively with the other constant operational conditions (such as the injection diameter, velocity and pressure). Next, a combination of a three dimensional Couple Level Set & Volume of Fluids with an improved Kelvin-Helmholtz & Rayleigh-Taylor model is used to investigate the interaction between kerosene and supersonic air. The numerical predictions are focused on penetration depth, span expansion area, angle of shock wave and sauter mean diameter distribution of the kerosene droplets with or without evaporation. Finally, validation has been implemented by comparing the calculated to the measured in literature with good qualitative agreement. Results show that no matter whether the evaporation is considered, the penetration depth, span-wise angle and expansion area of the kerosene droplets are all increased with the spray angle, and most especially, that the size of the kerosene droplets is surely reduced with the spray angle increase. These calculations are beneficial to better understand the underlying atomization mechanism in the cold kerosene-fueled supersonic flow and hence provide insights into scramjet design improvement

    IL-22–producing neutrophils contribute to antimicrobial defense and restitution of colonic epithelial integrity during colitis

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    IL-22 plays an important role in mucosal epithelial cell homeostasis. Using a dextran sodium sulfate-induced mouse model of acute colitis, we observed an IL-23–dependent up-regulation of IL-22 in the middle and distal colon at the onset of epithelial cell damage. This heightened IL-22 correlated with an influx of innate immune cells, suggesting an important role in colonic epithelial protection. Freshly isolated colon-infiltrating neutrophils produced IL-22 contingent upon IL-23 signaling, and IL-22 production was augmented by TNF-α. Importantly, the depletion of neutrophils resulted in diminished IL-22 levels in the colon, and the transfer of IL-22–competent neutrophils to Il22a-deficient mice protected the colonic epithelium from dextran sodium sulfate-induced damage. In addition, IL-22–producing neutrophils targeted colonic epithelial cells to up-regulate the antimicrobial peptides, RegIIIβ and S100A8. This study establishes a role for neutrophils in providing IL-22–dependent mucosal epithelial support that contributes to the resolution of colitis

    The nucleolar protein NIFK promotes cancer progression via CK1α/β-catenin in metastasis and Ki-67-dependent cell proliferation.

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    Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis and metastasis. Furthermore, NIFK enhances Ki-67-dependent proliferation, and promotes migration, invasion in vitro and metastasis in vivo via downregulation of casein kinase 1α (CK1α), a suppressor of pro-metastatic TCF4/β-catenin signaling. Inversely, CK1α is upregulated upon NIFK knockdown. The silencing of CK1α expression in NIFK-silenced cells restores TCF4/β-catenin transcriptional activity, cell migration, and metastasis. Furthermore, RUNX1 is identified as a transcription factor of CSNK1A1 (CK1α) that is negatively regulated by NIFK. Our results demonstrate the prognostic value of NIFK, and suggest that NIFK is required for lung cancer progression via the RUNX1-dependent CK1α repression, which activates TCF4/β-catenin signaling in metastasis and the Ki-67-dependent regulation in cell proliferation

    Genomic diversity of citrate fermentation in Klebsiella pneumoniae

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    <p>Abstract</p> <p>Background</p> <p>It has long been recognized that <it>Klebsiella pneumoniae </it>can grow anaerobically on citrate. Genes responsible for citrate fermentation of <it>K. pneumoniae </it>were known to be located in a 13-kb gene cluster on the chromosome. By whole genome comparison of the available <it>K. pneumoniae </it>sequences (MGH 78578, 342, and NTUH-K2044), however, we discovered that the fermentation gene cluster was present in MGH 78578 and 342, but absent in NTUH-K2044. In the present study, the previously unknown genome diversity of citrate fermentation among <it>K. pneumoniae </it>clinical isolates was investigated.</p> <p>Results</p> <p>Using a genomic microarray containing probe sequences from multiple <it>K. pneumoniae </it>strains, we investigated genetic diversity among <it>K. pneumoniae </it>clinical isolates and found that a genomic region containing the citrate fermentation genes was not universally present in all strains. We confirmed by PCR analysis that the gene cluster was detectable in about half of the strains tested. To demonstrate the metabolic function of the genomic region, anaerobic growth of <it>K. pneumoniae </it>in artificial urine medium (AUM) was examined for ten strains with different clinical histories and genomic backgrounds, and the citrate fermentation potential was found correlated with the genomic region. PCR detection of the genomic region yielded high positive rates among a variety of clinical isolates collected from urine, blood, wound infection, and pneumonia. Conserved genetic organizations in the vicinity of the citrate fermentation gene clusters among <it>K. pneumoniae</it>, <it>Salmonella enterica</it>, and <it>Escherichia coli </it>suggest that the13-kb genomic region were not independently acquired.</p> <p>Conclusion</p> <p>Not all, but nearly half of the <it>K. pneumoniae </it>clinical isolates carry the genes responsible for anaerobic growth on citrate. Genomic variation of citrate fermentation genes in <it>K. pneumoniae </it>may contribute to metabolic diversity and adaptation to variable nutrient conditions in different environments.</p

    Effects of injection pressure variation on mixing in a cold supersonic combustor with kerosene fuel

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    Abstract: Spray jet in cold kerosene-fueled supersonic flow has been characterized under different injection pressures to assess the effects of the pressure variation on the mixing between incident shock wave and transverse cavity injection. Based on the real scramjet combustor, a detailed computational fluid dynamics model is developed. The injection pressures are specified as 0.5, 1.0, 2.0, 3.0 and 4.0 MPa, respectively, with the other constant operation parameters (such as the injection diameter, angle and velocity). A three dimensional Couple Level Set & Volume of Fluids approach incorporating an improved Kelvin-Helmholtz & Rayleigh-Taylor model is used to investigate the interaction between kerosene and supersonic air. The numerical simulations primarily concentrate on penetration depth, span expansion area, angle of shock wave and sauter mean diameter distribution of the kerosene droplets with/without evaporation. Validation has been implemented by comparing the calculated against the measured in literature with good qualitative agreement. Results show that the penetration depth, span-wise angle and expansion area of the transverse cavity jet are all increased with the injection pressure. However, when the injection pressure is further increased, the value in either penetration depth or expansion area increases appreciably. This study demonstrates the feasibility and effectiveness of the combination of Couple Level Set & Volume of Fluids approach and an improved Kelvin-Helmholtz & Rayleigh-Taylor model, in turn providing insights into scramjet design improvement

    Prevalence of PIK3CA mutations in Taiwanese patients with breast cancer: a retrospective next-generation sequencing database analysis

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    BackgroundBreast cancer is the most common cancer type that affects women. In hormone receptor–positive (HR+), human epidermal growth factor receptor 2−negative (HER2–) advanced breast cancer (ABC), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the most frequently mutated gene associated with poor prognosis. This study evaluated the frequency of PIK3CA mutations in the Taiwanese breast cancer population.MethodologyThis is a retrospective study; patient data were collected for 2 years from a next-generation sequencing database linked to electronic health records (EHRs). The primary endpoint was the regional prevalence of PIK3CA mutation. The secondary endpoints were to decipher the mutation types across breast cancer subtype, menopausal status, and time to treatment failure after everolimus (an mTOR inhibitor) or cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment.ResultsPIK3CA mutations were identified in 278 of 728 patients (38%). PIK3CA mutations were reported in 43% of patients with HR−/HER2+ subtype and 42% of patients with HR+/HER2– postmenopausal status. A lower prevalence of PIK3CA mutations was observed in triple-negative (27%) and HR+/HER2– premenopausal patients (29%). The most common mutation was at exon 20 (H1047R mutation, 41.6%), followed by exon 9 (E545K mutation, 18.9% and E542K mutation, 10.3%). Among patients treated with CDK4/6 inhibitors, the median time to treatment failure was 12 months (95% CI: 7-21 months) in the PIK3CA mutation cohort and 16 months (95% CI: 11-23 months) in the PIK3CA wild-type cohort, whereas patients receiving an mTOR inhibitor reported a median time to treatment failure of 20.5 months (95% CI: 8-33 months) in the PIK3CA mutation cohort and 6 months (95% CI: 2-9 months) in the PIK3CA wild-type cohort.ConclusionA high frequency of PIK3CA mutations was detected in Taiwanese patients with breast cancer, which was consistent with previous studies. Early detection of PIK3CA mutations might influence therapeutic decisions, leading to better treatment outcomes

    Results of Fabry Disease Screening in Male Pre-End Stage Renal Disease Patients with Unknown Etiology Found Through the Platform of a Chronic Kidney Disease Education Program in a Northern Taiwan Medical Center

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    Background/Aims: Fabry disease (FD), a rare x-lined genetic disorder is a cause of renal deterioration. The phenotype of FD is highly variable and nonspecific, and correct diagnosis has always been delayed. We aimed to explore the prevalence and clinical presentation of FD in this high-risk male population in a Northern Taiwan medical center. Methods: This is the first study to survey the incidence of FD in this high-risk population through the platform of a chronic kidney disease (CKD) education program in Asia. A total of 1,012 male patients with unknown CKD causes were screened using an assay of alpha-galactosidase A activity (α-Gal A) by dried blood spots (DBS). A final GLA gene analysis was also done for those with low enzyme activity. Results: We identified two new patients with classic FD and four patients with late-onset FD. One novel GLA mutation with c.413 G&#x3e;A was found in one classic FD patient (index 5). The prevalence of FD is about 0.59 % (6 in 1,012) in the high-risk population group with CKD. The clinical symptoms of FD patients are nonspecific except in those with various degrees of renal failure. Those patients’ correct diagnosis was delayed, taking years and even decades. Three patients received enzyme replacement therapy and one started regular hemodialysis due to persistent renal function deterioration. Another two patients were found from family screening through a new index. In addition, a false negative result occurred in one patient who was proved to have FD by his kidney pathology as determined by this screening. Conclusion: FD is not such as rare a disease and its prevalence is greater in this high-risk male population. Clinicians need to be aware that FD should be included in the differential diagnosis in CKD with unknown etiology

    AV-SUPERB: A Multi-Task Evaluation Benchmark for Audio-Visual Representation Models

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    Audio-visual representation learning aims to develop systems with human-like perception by utilizing correlation between auditory and visual information. However, current models often focus on a limited set of tasks, and generalization abilities of learned representations are unclear. To this end, we propose the AV-SUPERB benchmark that enables general-purpose evaluation of unimodal audio/visual and bimodal fusion representations on 7 datasets covering 5 audio-visual tasks in speech and audio processing. We evaluate 5 recent self-supervised models and show that none of these models generalize to all tasks, emphasizing the need for future study on improving universal model performance. In addition, we show that representations may be improved with intermediate-task fine-tuning and audio event classification with AudioSet serves as a strong intermediate task. We release our benchmark with evaluation code and a model submission platform to encourage further research in audio-visual learning.Comment: Submitted to ICASSP 2024; Evaluation Code: https://github.com/roger-tseng/av-superb Submission Platform: https://av.superbbenchmark.or

    Zeranol Down-Regulates p53 Expression in Primary Cultured Human Breast Cancer Epithelial Cells through Epigenetic Modification

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    Epidemiological studies have suggested that there are many risk factors associated with breast cancer. Silencing tumor suppressor genes through epigenetic alterations play critical roles in breast cancer initiation, promotion and progression. As a growth promoter, Zeranol (Z) has been approved by the FDA and is widely used to enhance the growth of beef cattle in the United States. However, the safety of Z use as a growth promoter is still under debate. In order to provide more evidence to clarify this critical health issue, the current study investigated the effect of Z on the proliferation of primary cultured human normal and cancerous breast epithelial cells (PCHNBECs and PCHBCECs, respectively) isolated from the same patient using MTS assay, RT-PCR and Western blot analysis. We also conducted an investigation regarding the mechanisms that might be involved. Our results show that Z is more potent to stimulate PCHBCEC growth than PCHNBEC growth. The stimulatory effects of Z on PCHBCECs and PCHBCECs may be mediated by its down-regulating expression of the tumor suppressor gene p53 at the mRNA and protein levels. Further investigation showed that the expression of DNA methylatransferase 1 mRNA and protein levels is up-regulated by treatment with Z in PCHBCECs as compared to PCHNBECs, which suggests a role of Z in epigenetic modification involved in the regulation of p53 gene expression in PCHBCECs. Our experimental results imply the potentially adverse health effect of Z in breast cancer development. Further study is continuing in our laboratory
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