The objective of this study is to numerically investigate the thermal performance of cutting fluids dispersed with nanoparticles for effective heat removal during turning operations. The simulations ...are performed using Ansys Fluent software, and the problem is modelled as a three-dimensional turbulent incompressible single-phase flow. The computational domain consists of a heated cutting tool and work piece, and nanocoolants are sprayed from a nozzle located above the machining zone. The nanocoolants are prepared by mixing mineral oil with nanoparticles of Al2O3 (Aluminium Oxide), Al (Aluminium) and SWCNT (Single Walled Carbon Nanotube). The heat transfer performances of different nanocoolants are compared by varying the nanoparticle volume fraction (φ) and coolant velocity (Uc) in the range of 2% ≤ φ ≤ 8% and 1 m/s ≤ Uc ≤ 15 m/s, respectively. The results indicated a drastic drop in the cutting tool temperature with an increase in the volume fraction of dispersed nanoparticles and coolant velocity. The increase in volume fraction decreases the average cutting tool temperature by 25.65% and also enhances the average heat transfer rate by 25.43%. It is additionally observed that SWCNT nanocoolants exhibited a superior thermal performance and heat removal rate compared with Al and Al2O3 nanocoolants. The analysed numerical results are validated and are in good accordance with the benchmark results validated from literature.
Abstract
The biggest challenge that is faced by the human race after World war 2 is the Covid-19, which has affected more than 27.8 million people. The Covid 19 pandemic has entirely changed the ...livelihood of the people. It is not only seen as a global health crisis but also a Socio-economic issue that has disrupted the Governments worldwide. There is situation where normality is being questioned in the post pandemic era. Many regulations such as Quarantine, self-isolation, social-distancing, and travel restrictions have been advised to prevent the spread of covid-19. After several months of quarantine, the world is now slowly pacing its way back to normality as the vaccine has been invented and brought into use. It is expected that the educational institutions, work places and other public arenas will be opened for the use. However, the regulation of wearing mask and following social distancing are mandatory in public places. Considering the above situation as a need of the hour, this article mainly focuses on the Computational study of the Corona Virus diffusion for a confined space such that it can be applied to places with high population mass. The numerical model was simulated using ANSYS fluent and the results obtained are in excellent accordance with the literature.
Two-dimensional conjugate heat transfer performance of stepped lid-driven cavity was numerically investigated in the present study under forced and mixed convection in laminar regime. Pure water and ...Aluminium oxide (Al
2
O
3
)/water nanofluid with three different nanoparticle volume concentrations were considered. All the numerical simulations were performed in ANSYS FLUENT using homogeneous heat transfer model for Reynolds number, Re = 100 to 500 and Grashof number, Gr = 5000, 13,000 and 20,000. Effective thermal conductivity of the Al
2
O
3
/water nanofluid was evaluated by considering the Brownian motion of nanoparticles which results in 20.56% higher value for 3 vol.% Al
2
O
3
/water nanofluid in comparison with the lowest thermal conductivity value obtained in the present study. A solid region made up of silicon is present underneath the fluid region of the cavity in three geometrical configurations (forward step, backward step and no step) which results in conjugate heat transfer. For higher Re values (Re = 500), no much difference in the average Nusselt number (Nu
avg
) is observed between forced and mixed convection. Whereas, for Re = 100 and Gr = 20,000, Nu
avg
value of mixed convection is 24% higher than that of forced convection. Out of all the three configurations, at Re = 100, forward step with mixed convection results in higher heat transfer performance as the obtained interface temperature is lower than all other cases. Moreover, at Re = 500, 3 vol.% Al
2
O
3
/water nanofluid enhances the heat transfer performance by 23.63% in comparison with pure water for mixed convection with Gr = 20,000 in forward step.
Retinal oximetry is an important screening tool for early detection of retinal pathologies due to changes in the vasculature and also serves as a useful indicator of human-body-wide vascular ...abnormalities. We present an automatic technique for the measurement of oxygen saturation in retinal arterioles and venules using dual-wavelength retinal oximetry images. The technique is based on segmenting an optic-disc-centered ring-shaped region of interest and subsequent analysis of the oxygen saturation levels. We show that the two dominant peaks in the histogram of the oxygen saturation levels correspond to arteriolar and venular oxygen saturations from which the arterio-venous saturation difference (AVSD) can be calculated. For evaluation, we use a normative database of Asian Indian eyes containing 44 dual-wavelength retinal oximetry images. Validations against expert manual annotations of arterioles and venules show that the proposed technique results in an average arteriolar oxygen saturation (SatO2) of 87.48%, venular SatO2 of 57.41%, and AVSD of 30.07% in comparison with the expert ground-truth average arteriolar SatO2 of 89.41%, venular SatO2 of 56.32%, and AVSD of 33.09%, respectively. The results exhibit high consistency across the dataset indicating that the automated technique is an accurate alternative to the manual procedure.
Alcohol use disorder (AUD) is highly comorbid with depression. Withdrawal from chronic alcohol drinking results in depression and understanding brain molecular mechanisms that drive ...withdrawal-related depression is important for finding new drug targets to treat these comorbid conditions. Here, we performed RNA sequencing of the rat hippocampus during withdrawal from chronic alcohol drinking to discover key signaling pathways involved in alcohol withdrawal-related depressive-like behavior. Data were analyzed by weighted gene co-expression network analysis to identify several modules of co-expressed genes that could have a common underlying regulatory mechanism. One of the hub, or highly interconnected, genes in module 1 that increased during alcohol withdrawal was the transcription factor, signal transducer and activator of transcription 3 (Stat3), a known regulator of immune gene expression. Total and phosphorylated (p)STAT3 protein levels were also increased in the hippocampus during withdrawal after chronic alcohol exposure. Further, pSTAT3 binding was enriched at the module 1 genes Gfap, Tnfrsf1a, and Socs3 during alcohol withdrawal. Notably, pSTAT3 and its target genes were elevated in the postmortem hippocampus of human subjects with AUD when compared with control subjects. To determine the behavioral relevance of STAT3 activation during alcohol withdrawal, we treated rats with the STAT3 inhibitor stattic and tested for sucrose preference as a measure of anhedonia. STAT3 inhibition alleviated alcohol withdrawal-induced anhedonia. These results demonstrate activation of STAT3 signaling in the hippocampus during alcohol withdrawal in rats and in human AUD subjects, and suggest that STAT3 could be a therapeutic target for reducing comorbid AUD and depression.
We report on the effects of ethanol (EtOH) and Poly (ADP-ribose) polymerase (PARP) inhibition on RNA ribosomal engagement, as a proxy for protein translation, in prefrontal cortical (PFC) pyramidal ...neurons. We hypothesized that EtOH induces a shift in RNA ribosomal-engagement (RE) in PFC pyramidal neurons, and that many of these changes can be reversed using a PARP inhibitor. We utilized the translating ribosome affinity purification (TRAP) technique to isolate cell type-specific RNA. Transgenic mice with EGFP-tagged Rpl10a ribosomal protein expressed only in CaMKIIα-expressing pyramidal cells were administered EtOH or normal saline (CTL) i.p. twice a day, for four consecutive days. On the fourth day, a sub-group of mice that received EtOH in the previous three days received a combination of EtOH and the PARP inhibitor ABT-888 (EtOH + ABT-888). PFC tissue was processed to isolate both, CaMKIIα pyramidal cell-type specific ribosomal-engaged RNA (TRAP-RNA), as well as genomically expressed total-RNA from whole tissue, which were submitted for RNA-seq. We observed EtOH effects on RE transcripts in pyramidal cells and furthermore treatment with a PARP inhibitor "reversed" these effects. The PARP inhibitor ABT-888 reversed 82% of the EtOH-induced changes in RE (TRAP-RNA), and similarly 83% in the total-RNA transcripts. We identified Insulin Receptor Signaling as highly enriched in the ethanol-regulated and PARP-reverted RE pool and validated five participating genes from this pathway. To our knowledge, this is the first description of the effects of EtOH on excitatory neuron RE transcripts from total-RNA and provides insights into PARP-mediated regulation of EtOH effects.
Alcohol consumption is mediated by several important neuromodulatory systems, including the endocannabinoid and neuropeptide Y (NPY) systems in the limbic brain circuitry. However, molecular ...mechanisms through which cannabinoid-1 (CB1) receptors regulate alcohol consumption are still unclear. Here, we investigated the role of the CB1 receptor-mediated downstream regulation of NPY via epigenetic mechanisms in the amygdala. Alcohol drinking behavior was measured in adult male C57BL/6J mice treated with a CB1 receptor neutral antagonist AM4113 using a two-bottle choice paradigm while anxiety-like behavior was assessed in the light-dark box (LDB) test. The CB1 receptor-mediated changes in the protein levels of phosphorylated cAMP-responsive element binding protein (pCREB), CREB binding protein (CBP), H3K9ac, H3K14ac and NPY, and the mRNA levels of Creb1, Cbp, and Npy were measured in amygdaloid brain structures. Npy-specific changes in the levels of acetylated histone (H3K9/14ac) and CBP in the amygdala were also measured. We found that the pharmacological blockade of CB1 receptors with AM4113 reduced alcohol consumption and, in an ethanol-naïve cohort, reduced anxiety-like behavior in the LDB test. Treatment with AM4113 also increased the mRNA levels of Creb1 and Cbp in the amygdala as well as the protein levels of pCREB, CBP, H3K9ac and H3K14ac in the central and medial nucleus of amygdala, but not in the basolateral amygdala. Additionally, AM4113 treatment increased occupancy of CBP and H3K9/14ac at the Npy gene promoter, leading to an increase in both mRNA and protein levels of NPY in the amygdala. These novel findings suggest that CB1 receptor-mediated CREB signaling plays an important role in the modulation of NPY function through an epigenetic mechanism and further support the potential use of CB1 receptor neutral antagonists for the treatment of alcohol use disorder.
•CB1 receptor neutral antagonist decreases alcohol drinking and anxiety-like behavior.•CB1 receptor blockade increases CREB and CBP mRNA and protein levels in the amygdala.•CB1 receptor blockade causes chromatin remodeling by increasing histone H3K9 and H3K14 acetylation in the amygdala.•Increased CBP and histone acetylation at Npy promoter following CB1 receptor blockade is associated with increases in NPY.
We introduce Chákṣu-a retinal fundus image database for the evaluation of computer-assisted glaucoma prescreening techniques. The database contains 1345 color fundus images acquired using three ...brands of commercially available fundus cameras. Each image is provided with the outlines for the optic disc (OD) and optic cup (OC) using smooth closed contours and a decision of normal versus glaucomatous by five expert ophthalmologists. In addition, segmentation ground-truths of the OD and OC are provided by fusing the expert annotations using the mean, median, majority, and Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm. The performance indices show that the ground-truth agreement with the experts is the best with STAPLE algorithm, followed by majority, median, and mean. The vertical, horizontal, and area cup-to-disc ratios are provided based on the expert annotations. Image-wise glaucoma decisions are also provided based on majority voting among the experts. Chákṣu is the largest Indian-ethnicity-specific fundus image database with expert annotations and would aid in the development of artificial intelligence based glaucoma diagnostics.
Alcohol use disorder (AUD) has a complex pathogenesis, making it a difficult disorder to treat. Identifying relevant signaling pathways in the brain may be useful for finding new pharmacological ...targets to treat AUD. The receptor tyrosine kinase anaplastic lymphoma kinase (ALK) activates the transcription factor STAT3 in response to ethanol in cell lines. Here, we show ALK activation and upregulation of known STAT3 target genes (Socs3, Gfap and Tnfrsf1a) in the prefrontal cortex (PFC) and ventral hippocampus (HPC) of mice after 4 days of binge-like ethanol drinking. Mice treated with the STAT3 inhibitor stattic drank less ethanol than vehicle-treated mice, demonstrating the behavioral importance of STAT3. To identify novel ethanol-induced target genes downstream of the ALK and STAT3 pathway, we analyzed the NIH LINCS L1000 database for gene signature overlap between ALK inhibitor (alectinib and NVP-TAE684) and STAT3 inhibitor (niclosamide) treatments on cell lines. These genes were then compared with differentially expressed genes in the PFC of mice after binge-like drinking. We found 95 unique gene candidates, out of which 57 had STAT3 binding motifs in their promoters. We further showed by qPCR that expression of the putative STAT3 genes Nr1h2, Smarcc1, Smarca4 and Gpnmb were increased in either the PFC or HPC after binge-like drinking. Together, these results indicate activation of the ALK-STAT3 signaling pathway in the brain after binge-like ethanol consumption, identify putative novel ethanol-responsive STAT3 target genes, and suggest that STAT3 inhibition may be a potential method to reduce binge drinking in humans.
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