40 research outputs found

    On the Mechanical Response in Boundary Resisted Motion

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    In engineering and science literature, there seems to be a lack of consensus on a modeling framework clarifying how resistance to boundary motion affects mechanical performance. By mechanical performance, is implied the action of a force moving an object from one point to another that generates changes in position, velocity, acceleration and jerk. Apart from affecting a whole vehicle, critical power transmission components and subcomponents all rely on the mechanical responses that change due to an applied force. For example, the power needed to move an aircraft, an automobile, a ship, a submarine etc. will be reduced if resistance to their motion diminishes. Of the three laws of friction, the first one stating friction as directly proportional to normal load is well known and almost universally proven. The second law asserting friction as independent of the area of contact has been found not to apply when rough surfaces are considered. Finally, the third law of friction proposing friction as independent of sliding velocity remains paradoxical considering that the dependence of friction on sliding velocity emerges demonstrably from the Stribeck effect and Stokes’ law of aerodynamic drag. To understand the dependence of friction on sliding velocity, this thesis establishes a deterministic framework for identifying boundary resistance effects on mechanical responses such as distance, velocity, acceleration, jerk, frequency, interacting forces, and efficiency. For this study, two cases are considered. The first case is considered to understand the effect of boundary friction and aerodynamic drag on mechanical sliding motion. In the second case, the effects of boundary friction on spring-resisted motion are explored. These two cases are further broken down into two sub cases, where the effects of constant and variable applied forces are separately investigated. The theoretical modeling effort shows that in general boundary resistance like solid friction and aerodynamic drag detrimentally impacts mechanical responses including efficiency during sliding. The deterministic framework created will be important for studying, synthesizing and designing future sustainable energy-efficiency technologies while dramatically improving existing technologies

    The yeast homologue of the microtubule-associated protein Lis1 interacts with the sumoylation machinery and a SUMO-targeted ubiquitin ligase

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    Microtubules and microtubule-associated proteins are fundamental for multiple cellular processes, including mitosis and intracellular motility, but the factors that control microtubule-associated proteins (MAPs) are poorly understood. Here we show that two MAPs - the CLIP-170 homologue Bik1p and the Lis1 homologue Pac1p - interact with several proteins in the sumoylation pathway. Bik1p and Pac1p interact with Smt3p, the yeast SUMO; Ubc9p, an E2; and Nfi1p, an E3. Bik1p interacts directly with SUMO in vitro, and overexpression of Smt3p and Bik1p results in its in vivo sumoylation. Modified Pac1p is observed when the SUMO protease Ulp1p is inactivated. Both ubiquitin and Smt3p copurify with Pac1p. In contrast to ubiquitination, sumoylation does not directly tag the substrate for degradation. However, SUMO-targeted ubiquitin ligases (STUbLs) can recognize a sumoylated substrate and promote its degradation via ubiquitination and the proteasome. Both Pac1p and Bik1p interact with the STUbL Nis1p-Ris1p and the protease Wss1p. Strains deleted for RIS1 or WSS1 accumulate Pac1p conjugates. This suggests a novel model in which the abundance of these MAPs may be regulated via STUbLs. Pac1p modification is also altered by Kar9p and the dynein regulator She1p. This work has implications for the regulation of dynein\u27s interaction with various cargoes, including its off-loading to the cortex. © 2012 Alonso et al

    Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

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    Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

    Elimination of Chromosomal Island SpyCIM1 from Streptococcus pyogenes Strain SF370 Reverses the Mutator Phenotype and Alters Global Transcription

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    This work was made possible by an Oklahoma Center for the Advancement of Science and Technology (OCAST) grant HR11-133 and by NIH Grant Number R15A1072718 to WMM and NIH Grant AI11822 to VAF.Streptococcus pyogenes chromosomal island M1 (SpyCIM1) integrates by site-specific recombination into the 5’ end of DNA mismatch repair (MMR) gene mutL in strain SF370SmR, blocking transcription of it and the downstream operon genes. During exponential growth, SpyCIM1 excises from the chromosome and replicates as an episome, restoring mutL transcription. This process is reversed in stationary phase with SpyCIM1 re-integrating into mutL, returning the cells to a mutator phenotype. Here we show that elimination of SpyCIM1 relieves this mutator phenotype. The downstream MMR operon genes, multidrug efflux pump lmrP, Holliday junction resolution helicase ruvA, and DNA base excision repair glycosylase tag, are also restored to constitutive expression by elimination of SpyCIM1. The presence of SpyCIM1 alters global transcription patterns in SF370SmR. RNA sequencing (RNA-Seq) demonstrated that loss of SpyCIM1 in the SpyCIM1 deletion mutant, CEM1Δ4, impacted the expression of over 100 genes involved in virulence and metabolism both in early exponential phase, when the SpyCIM1 is episomal, as well as at the onset of stationary phase, when SpyCIM1 has reintegrated into mutL. Among these changes, the up-regulation of the genes for the antiphagocytic M protein (emm1), streptolysin O (slo), capsule operon (hasABC), and streptococcal pyrogenic exotoxin (speB), are particularly notable. The expression pattern of the MMR operon confirmed our earlier observations that these genes are transcribed in early exponential phase but silenced as stationary phase is approached. Thus, the direct role of SpyCIM1 in causing the mutator phenotype is confirmed, and further, its influence upon the biology of S. pyogenes was found to impact multiple genes in addition to the MMR operon, which is a novel function for a mobile genetic element. We suggest that such chromosomal islands are a remarkable evolutionary adaptation to promote the survival of its S. pyogenes host cell in changing environments.Yeshttp://www.plosone.org/static/editorial#pee

    Comparative study of different fiber materials based PCF for enhancing medical imaging quality

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    The image's quality is a crucial consideration in medical imaging, therefore selecting a fiber that offers more benefits is important. The primary objective of this work is to explore the imperative applications of Photonic Crystal Fiber (PCF) in medical imaging. Numerical studies utilizing the finite element method and a normal mesh have been performed on the proposed PCF with several different types of fiber materials in the core and background. More broadly in terms of wavelength, from 0.5 μm to 1.6 μm, some of the optical parameters investigated, including confinement loss, nonlinearity, effective area, and numerical aperture (NA). Changing PCF’s background material from BK7, fused silica, or ZBLAN has resulted in a shift in the parameters. Here, BK7 is discovered to be a promising possibility in medical imaging, and a thorough comparative analysis of PCF parameters has been performed. The comparison reveals that at an optical wavelength of 0.5 μm, the proposed PCF with BK7 exhibits strong nonlinearity of 119 W−1Km−1, low confinement loss of 2.97 × 10−12 dB/m, a numerical aperture of 0.15, along with a very low effective area of 4.18 × 10−12 m2. It is therefore anticipated that the suggested PCF with BK7 will be more suitable for the imaging application

    Prognostics of Lithium-Ion batteries using knowledge-constrained machine learning and Kalman filtering

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    Accurately predicting the remaining useful life (RUL) of lithium-ion rechargeable batteries remains challenging as the battery capacity degrades in a stochastic manner given the internal complex electrochemical reactions of the battery and the external operational conditions. In this work, a knowledge-constrained machine learning framework is developed to learn the stochastic degradation of battery performance over working cycles for health prognostics of lithium-ion batteries. An artificial neural network (ANN) model is first trained and synchronized using a Dual Extended Kalman Filter (DEKF) to obtain critical health information of lithium-ion batteries. With the obtained health information, a knowledge-constrained machine learning method (KcML) is then developed to predict the stochastic degradation of the battery capacity in operation. Specifically, prior knowledge on battery capacity fade can be formulated as extra constraints to facilitate the development of machine learning models with improved fidelity level for battery capacity predictions. A dataset published by NASA is utilized to demonstrate the effectiveness of the proposed approach

    Effect of black pepper, turmeric and ajwa date on the endocrine pancreas of the experimentally induced diabetes in wister albino rats: A histological and immunohistochemical study

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    Background: Diabetes is now a global problem and millions of people are suffering all over the world. Reports exist for the allopathic use of turmeric, black pepper, and date palm as an antidiabetic and antioxidant agent. Aim: The current study was designed to assess the antihyperglycemic, antioxidants and antihyperlipidemic consequences of black pepper (BP), turmeric (T), ajwa pulp (AP), and ajwa seeds (AS) in alloxan-induced diabetic rats. Methodology: Diabetes was induced by a single intraperitoneal injection of alloxan (150 mg/kg b.w) in rats. They were randomly divided into 11 groups of 18 male and 18 female rats each. Group-1 normal control, group-2 diabetic control, group-3 was administered with glibenclamide (10 mg/kg), group-4 was administered with aqueous extract of BP (50 mg/kg), group-5, 6, 7 were administered with T, AP and AS (500 mg/kg) and group-8, 9, 10, 11 were administered with different combinations of aqueous extract (500 mg/kg) once in a day for eight weeks. The antihyperglycemic potential was determined through biochemical and histological investigations of the experimental animals at the end of the experiment. Results: The results of the study revealed that treatments improved glucose (229.53 mg/dL), Ghb (7.68%), insulin (13.63 U/L), Tg (95.92 mg/dL), Tc (152.86 mg/dL), HDL (23.22 mg/dL), LDL (110.30 mg/dL), TAC (1.89 mmol/L) and TOS (20.05 μmol/L) in comparison to diabetic control rats after 8 weeks of study period. Histological and immunohistochemical investigation of tissues exhibited severe changes in the pancreas of diabetic rats and treatments modulate these changes; this improvement in cells may explain the antidiabetic effects. Conclusion: It is concluded that aqueous extract of BP+AS; and BP+T+AP+AS could be promising nutraceutical therapy for diabetes management and its associated complications

    Functionalization of surfactant templated magnetite by chitosan and PEGylated/Chitosan – In vitro studies on drug loading, release and anti-proliferative activity

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    Magnetite iron oxide nanoparticles (MNPs) were synthesized using micro emulsion assisted co-precipitation method. The surface functionalization of MNPs was done with chitosan and PEGylated/chitosan and three samples of each were prepared. These materials were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron (SEM), and transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The Methotrexate (MTX) drug was then loaded on each functionalized MNPs as MCT-1–3 (chitosan; 0.1,0.5, and 1%) and MPCT-1–3 (PEGylated/chitosan (1% each with volume ratio 1:1, 3:1, and 1:3). Each composition showed maximum encapsulation efficiency (>95%). The pH dependent drug release studies were done under acidic (pH 5.0) and physiological (pH 7.4) conditions. These studies revealed consistent drug release and no burst release was observed from both functionalized MNPs. A comparatively delayed release from MPCTs than MCTs could be attributed to the formation of more compact sphere due to cross-linking of chitosan with PEG. The drug release was found greater at pH 5.0 for all functionalized MNPs. However, among all functionalized MNPs, maximum drug release was found to be 78.88% by MPCT-1 in acidic medium (pH 5.0). Cyclic voltametric (CV) analysis at slow scan rate (10 mV/s) further indicated controlled drug release and complimented the UV-findings. The MCF-7 (human breast cancer) cell line studies, however, indicated anticancer potential only for MPCT-1–3 with IC50 values ranging from 1.4 to 1.7 μM. Overall results pointed that methotrexate loaded PEGylated/chitosan coated magnetic nanoparticles MPCT-1 is the more compassionate material to be used as vehicle for controlled drug delivery

    Vitamin D3 decreases glycolysis and invasiveness, and increases cellular stiffness in breast cancer cells

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    Breast cancer is one of the major causes of death in the USA. Cancer cells, including breast, have high glycolysis rates to meet their energy demands for survival and growth. Vitamin

    Does Laparoscopic Lens Contamination Effect Operative Time? A Study on the Frequency and Duration of Lens Contamination and Commonly Used Measures to Maintain Clear Vision

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    Objective: To determine factors affecting lens fogging and different methods used for decreasing lens fogging and operation time.Methods: This cross-sectional study was conducted in General surgery department of Gulab Devi Hospital, Lahore from January 2022 to July 2022. A total of 70 patient undergoing laparoscopic surgery were recruited in this study. Operative time, duration of time the lens remained cleaned or dirty, time wasted during cleaning, methods used for cleaning of lens and causes of lens contamination were the variables of this study.Results: Total operative time in all 70 laparoscopic procedures was found to be 53 hours and 13 minutes with a mean of 43.8 ± 8.3 minutes. A total of 288 lens contamination events were observed in all these operations with an average of 4.11 lens contamination events per case. According to study an average, 60.9% of the operational time lens remained clear, 31.2% of the operational time lens remained contaminated and 7.92% of the operative time was spent in cleaning the laparoscope.Conclusion: Our study demonstrates that a significant period of a laparoscopic surgery is performed with foggy display. A lot of time is wasted in lens cleaning
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