Interplay of Periodontal Bacterial Metabolites in the Progression of Coronary Artery Disease: A System Biological Approach

Purpose: The purpose of this study is to investigate the intricate relationship between periodontal disease (PD) and coronary artery disease (CAD), as evidenced by epidemiological associations. Metalloproteinase inhibitor (TIMP1) plays a pivotal role in cellular signaling, differentiation, cell death, and migration by binding to target metalloproteinases, forming complexes with other molecules (collagenases) to inactivate them. However, the expression of TIMP1 is reduced in both PD and CAD, leading to an upregulation of other metalloproteinases. This research explores the hypothesis that metabolites released from (Porphyromonas gingivalis), a prevalent bacterium in atherosclerotic patients, may inhibit TIMP1, thereby influencing CAD progression. Methods: This research utilized a series of computational techniques, encompassing data mining, protein network analysis, molecular modeling, molecular docking, and molecular dynamics simulation. In the initial phase, metabolites from Porphyromonas gingivalis were retrieved from the Virtual Metabolic Human (VMH) database. The proteins associated with the TIMP1 were identified through the construction of a protein interaction network in Cytoscape. Subsequently, the TIMP1 underwent modeling using the Swiss-Model web server and was docked with bacterial metabolites. Furthermore, the structural stability of both the protein and metabolite was evaluated over a 100 ns simulation period. Results: In total, 370 metabolites from Porphyromonas gingivalis were obtained from the database. Notably, the network analysis revealed that MMP1, MMP9, and MMP14 were closely associated with TIMP1. Molecular docking outcomes demonstrated that Malonyl CoA displayed a binding affinity of -8.82 kcal/mol at the active sites of TIMP1. Additionally, a stable complex between TIMP1 and Malonyl CoA was observed throughout the simulation period, potentially influencing the activity of TIMP1. Conclusion: This investigation underscores the potential implications of Porphyromonas gingivalis metabolites as a risk factor in the development of CAD. The computational analysis suggests that these metabolites may disrupt the function of TIMP1, thereby contributing to the elevated levels of metalloproteinases observed in CAD patients. This emphasizes the critical need for further research to delve into the intricate mechanisms and exploring potential therapeutic interventions

Isozyme Analysis on Different Varieties of Sugarcane

Isozymic and protein diversity among five sugarcane varieties viz., Co 6304, Co 85019, Co 8371, Co 89003 and Co 91010 were studied to understand the varietal interrelationship and to identify the biochemical marker for the disease resistance and stress tolerance. The standard technique of vertical gel electrophoresis PAGE was employed for size separation of isozymes. The gel was stained with different staining solutions for different isozyme systems viz. peroxidase, esterase, acid phosphatase, alkaline phosphatase and proteins. Rf values of the banding profiles, similarity index and variation between the varieties were analysed. Among the four enzyme systems, peroxidase profile reveals the difference between the disease resistant / susceptible and abiotic stress tolerant / non tolerant varieties. The two isoperoxidase bands with Rf values 0.62 and 0.66 showed their presence in disease resistant and abiotic tolerant varieties. The presence of two marker bands (0.62, 0.66) of resistant and stress tolerant varieties suggest that the variety Co 6304 may also be resistant to smut, wilt and moderately resistant to red rot and tolerant to drought

ADEPOS: Anomaly Detection based Power Saving for Predictive Maintenance using Edge Computing

In industry 4.0, predictive maintenance(PM) is one of the most important applications pertaining to the Internet of Things(IoT). Machine learning is used to predict the possible failure of a machine before the actual event occurs. However, the main challenges in PM are (a) lack of enough data from failing machines, and (b) paucity of power and bandwidth to transmit sensor data to cloud throughout the lifetime of the machine. Alternatively, edge computing approaches reduce data transmission and consume low energy. In this paper, we propose Anomaly Detection based Power Saving(ADEPOS) scheme using approximate computing through the lifetime of the machine. In the beginning of the machines life, low accuracy computations are used when the machine is healthy. However, on the detection of anomalies, as time progresses, the system is switched to higher accuracy modes. We show using the NASA bearing dataset that using ADEPOS, we need 8.8X less neurons on average and based on post-layout results, the resultant energy savings are 6.4 to 6.65XComment: Submitted to ASP-DAC 2019, Japa

Cells exhibiting strong p16INK4a promoter activation in vivo display features of senescence

The activation of cellular senescence throughout the lifespan promotes tumor suppression, whereas the persistence of senescent cells contributes to aspects of aging. This theory has been limited, however, by an inability to identify and isolate individual senescent cells within an intact organism. Toward that end, we generated a murine reporter strain by “knocking-in” a fluorochrome, tandem-dimer Tomato (tdTom), into exon 1α of the p16 INK4a locus. We used this allele (p16 tdTom ) for the enumeration, isolation, and characterization of individual p16 INK4a -expressing cells (tdTom + ). The half-life of the knocked-in transcript was shorter than that of the endogenous p16 INK4a mRNA, and therefore reporter expression better correlated with p16 INK4a promoter activation than p16 INK4a transcript abundance. The frequency of tdTom + cells increased with serial passage in cultured murine embryo fibroblasts from p16 tdTom/+ mice. In adult mice, tdTom + cells could be readily detected at low frequency in many tissues, and the frequency of these cells increased with aging. Using an in vivo model of peritoneal inflammation, we compared the phenotype of cells with or without activation of p16 INK4a and found that tdTom + macrophages exhibited some features of senescence, including reduced proliferation, senescence-associated β-galactosidase (SA-β-gal) activation, and increased mRNA expression of a subset of transcripts encoding factors involved in SA-secretory phenotype (SASP). These results indicate that cells harboring activation of the p16 INK4a promoter accumulate with aging and inflammation in vivo, and display characteristics of senescence

Effect of water vapor on the spallation of thermal barrier coating systems during laboratory cyclic oxidation testing.

The effect of water and water vapor on the lifetime of Ni-based superalloy samples coated with a typical thermal barrier coating system—b-(Ni,Pt)Al bond coat and yttria stabilized zirconia (YSZ) top coat deposited by electron beam physical vapor deposition (EB-PVD) was studied. Samples were thermally cycled to 1,150 C and subjected to a water-drop test in order to elucidate the effect of water vapor on thermal barrier coating (TBC) spallation. It was shown that the addition of water promotes spallation of TBC samples after a given number of cycles at 1,150 C. This threshold was found to be equal to 170 cycles for the present system. Systems based on b-NiAl bond coat or on Pt-rich c/c0 bond coat were also sensitive to the water-drop test. Moreover, it was shown that water vapor in ambient air after minutes or hours at room temperature, promotes also TBC spallation once the critical number of cycles has been reached. This desktop spalling (DTS) can be prevented by locking up the cycled samples in a dry atmosphere box. These results for TBC systems confirm and document Smialek’s theory about DTS and moisture induced delayed spalling (MIDS) being the same phenomenon. Finally, the mechanisms implying hydrogen embrittlement or surface tension modifications are discussed

MALIGNANT SOMATOSTATINOMA PRESENTING WITH DIABETIC KETOACIDOSIS

High circulating levels of somatostatin (SRIF) were detected in a patient with a metastatic tumour after development of diabetic ketoacidosis (DKA). Fasting insulin and C-peptide levels were markedly suppressed, but plasma glucagon was not suppressed below normal. Progressive cachexia ensued; at autopsy a poorly differentiated non-small cell neuroendocrine carcinoma metastatic to liver was found. Small gallstones were noted. Electron microscopy of tumour tissue showed neurosecretory granules and tonofilament bundles. Immunohis-tochemical staining of tumour cells was diffusely positive for carcinoembryonic antigen, bombesin-like immunoreactivity, and calcitonin with focal immuno-reactivity for SRIF, serotonin, neuron-specific enolase, chromogranin, and epithelial membrane antigen. Column chromatography of plasma and tumour extract revealed five or more peaks of material with SRIF-like immunoreactivity (SRIF-LI): predominantly SRIF-28 and intermediates in tumour extract, and SRIF-14 and an intermediate between SRIF-28 and SRIF-14 in plasma. DKA in this case of somatostatinoma syndrome may reflect differential effects of tumour production of larger molecular weight SRIF forms on insulin and glucagon secretion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75579/1/j.1365-2265.1987.tb00817.x.pd

Rhiniodon typus landed at Kovalam fish landing centre

A 21.1 ft dead female whale shark was stranded at Kovalam in a multifilament polypropylene net cast on 18th of July 2005 and was drifted ashore in the early morning hours

Managing Product Returns Within the Customer Value Framework

Customers can create value to the firm by purchasing products, not returning these products, recommending products to other potential customers, influencing other customers, and providing feedback to the company. In this chapter, we first discuss how product returns and engagement behaviors can be included in the customer value framework. Second, we discuss the antecedents of a customer’s product return decision, namely, return policies, information at the moment of purchase, and customer and product characteristics. Third, we focus on the consequences of product returns: the effects on future purchase and product return behavior, as well as on customer engagement behaviors. Thus, this chapter provides a comprehensive synthesis of current knowledge on antecedents and consequences of product returns and how this relates to measuring and managing customer value

Enteral lactoferrin supplementation for very preterm infants: a randomised placebo-controlled trial

Background Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow's milk, prevents infections and associated complications. The aim of this large randomised controlled trial was to collect data to enhance the validity and applicability of the evidence from previous trials to inform practice. Methods In this randomised placebo-controlled trial, we recruited very preterm infants born before 32 weeks' gestation in 37 UK hospitals and younger than 72 h at randomisation. Exclusion criteria were presence of a severe congenital anomaly, anticipated enteral fasting for longer than 14 days, or no realistic prospect of survival. Eligible infants were randomly assigned (1:1) to receive either enteral bovine lactoferrin (150 mg/kg per day; maximum 300 mg/day; lactoferrin group) or sucrose (same dose; control group) once daily until 34 weeks' postmenstrual age. Web-based randomisation minimised for recruitment site, gestation (completed weeks), sex, and single versus multifetal pregnancy. Parents, caregivers, and outcome assessors were unaware of group assignment. The primary outcome was microbiologically confirmed or clinically suspected late-onset infection (occurring >72 h after birth), which was assessed in all participants for whom primary outcome data was available by calculating the relative risk ratio with 95% CI between the two groups. The trial is registered with the International Standard Randomised Controlled Trial Number 88261002. Findings We recruited 2203 participants between May 7, 2014, and Sept 28, 2017, of whom 1099 were assigned to the lactoferrin group and 1104 to the control group. Four infants had consent withdrawn or unconfirmed, leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group. Primary outcome data for 2182 infants (1093 [99·5%] of 1098 in the lactoferrin group and 1089 [99·0] of 1101 in the control group) were available for inclusion in the modified intention-to-treat analyses. 316 (29%) of 1093 infants in the intervention group acquired a late-onset infection versus 334 (31%) of 1089 in the control group. The risk ratio adjusted for minimisation factors was 0·95 (95% CI 0·86–1·04; p=0·233). During the trial there were 16 serious adverse events for infants in the lactoferrin group and 10 for infants in the control group. Two events in the lactoferrin group (one case of blood in stool and one death after intestinal perforation) were assessed as being possibly related to the trial intervention. Interpretation Enteral supplementation with bovine lactoferrin does not reduce the risk of late-onset infection in very preterm infants. These data do not support its routine use to prevent late-onset infection and associated morbidity or mortality in very preterm infants. Funding UK National Institute for Health Research Health Technology Assessment programme (10/57/49)