In machining, heat concentration is generated at the surface contact between the tool and workpiece. This is the effect of hard frictions at the shear cutting plane to remove hard and brittle ...materials. The highly adhesive behavior of aluminum alloy 6061-T6 is more severe in higher cutting temperature, which may affect tool failures such as flank wear, tool chip and built-up edge, particularly on the edge of cutting inserts during the process. As a result, this may lead to the rough surface and low-dimensional accuracy of the machined parts. Realizing that metal-cutting industry players are demanding high-quality products with better surface finish and dimensional accuracy led to this study. Aluminum alloy 6061-T6 is a standard alloy used in automotive, aerospace and food packaging due to good hardness, high strength-to-weight ratio, resistance to corrosion and weldability. In order to address this problem, a newly developed metal working fluid which is SiO
2
-Al
2
O
3
-ZrO
2
tri-hybrid nanofluid is applied in the cutting zone to achieve a good surface finish of the machined parts and lowering the cutting temperature. This study is the first attempt to enhance machining performance, particularly at high-speed machining, by employing a combination of tri-hybrid nanofluids and a minimum quantity lubricant technique. Industrial standards include uncoated tungsten carbide and CVD TiCN-Al
2
O
3
carbide used during machining of aluminum alloy 6061-T6. The minimum quantity lubricant method is an alternative in supplying the lubricant into the machining zone due to flood machining and conventional fluid possess safety, health, economic and environmental effects. In this study, the experimental data were analyzed statistically using analysis of variance and response surface methodology. The responses studied were reduced significantly when tri-hybrid nanoparticles present at the cutting interface with higher MQL flow rate and concentration. There are two-factor interactions which are significant to the responses studied. Therefore, the combinations of MQL and excellent tri-hybrid nanofluids characteristics have enhanced between 16 and 76% of surface roughness and the cutting temperature, respectively, which is very promising in the future.
Abstract
The wide-area XMM-XXL X-ray survey is used to explore the fraction of obscured active galactic nuclei (AGNs) at high accretion luminosities, L
X(2-10 keV) ≳ 1044 erg s − 1, and out to ...redshift z ≈ 1.5. The sample covers an area of about 14 deg2 and provides constraints on the space density of powerful AGNs over a wide range of neutral hydrogen column densities extending beyond the Compton-thick limit, N
H ≈ 1024 cm − 2. The fraction of obscured Compton-thin (N
H = 1022-1024 cm − 2) AGNs is estimated to be ≈0.35 for luminosities L
X(2-10 keV) > 1044 erg s − 1, independent of redshift. For less luminous sources, the fraction of obscured Compton-thin AGNs increases from 0.45 ± 0.10 at z = 0.25 to 0.75 ± 0.05 at z = 1.25. Studies that select AGNs in the infrared via template fits to the observed spectral energy distribution of extragalactic sources estimate space densities at high accretion luminosities consistent with the XMM-XXL constraints. There is no evidence for a large population of AGNs (e.g. heavily obscured) identified in the infrared and missed at X-ray wavelengths. We further explore the mid-infrared colours of XMM-XXL AGNs as a function of accretion luminosity, column density and redshift. The fraction of XMM-XXL sources that lie within the mid-infrared colour wedges defined in the literature to select AGNs is primarily a function of redshift. This fraction increases from about 20–30 per cent at z = 0.25 to about 50–70 per cent at z = 1.5.
Introduction
Pembrolizumab has been on the market for several years, but most of the safety data is based on clinical trials with limited literature evaluating post-marketing immune-related adverse ...events (irAEs) associated with its use. This study aimed to evaluate the characteristics of irAEs associated with pembrolizumab.
Methods
We included adult patients who had received pembrolizumab between January 2016 and December 2020. The patient electronic profiles and the pharmacy adverse event reporting system were reviewed to identify adverse events. Patients were followed from the start of treatment until 12 months after the last dose, end of the study, or death. The characteristics of the patients and the irAEs were recorded. Univariate and multivariate logistic regression analyses were performed to identify variables associated with the development of irAE.
Results
During the study period, 223 patients and 1601 cycles of pembrolizumab were evaluated. A total of 67 irAEs were reported in 58 patients. The median age was 53 years (range 18–84), and most patients were males (75%) with metastatic lung cancer (62%). The most common irAEs were respiratory (30%), followed by gastrointestinal (25%), endocrine (24%), and dermatologic (21%). Among the reported irAEs, 28 were associated with hospital admission, 15 required long-term treatment, and 9 resulted in pembrolizumab discontinuation. In logistic regression, there were no significant predictors associated with irAE.
Conclusions
Respiratory irAEs were the most common in our population. We were unable to identify predictors of irAE in this cohort. Further studies are necessary to identify predictors of adverse events.
Community resilience planning is challenging as it involves several large-scale systems with interdependency, populations with diverse socio-economic characteristics, and numerous stakeholders. This ...study introduces a new optimization model to decrease a community's burden in developing viable alternative sets of decisions while considering costs and risks associated with uncertain hazard events. The model captures the essential features of a community, and its scope extends beyond infrastructure and buildings to include social goals. Structural engineering and social science approaches are adapted and incorporated into the model formulation to facilitate the identification of engineering decisions meeting the social goals of minimizing population dislocation and time for recovery. A risk-averse approach frames the optimization problem as a two-stage mean-risk stochastic programming model, which enables effective planning for low-probability, high-consequence hazard events. A case study simulating flood hazards in Lumberton, North Carolina, is developed, and the model is run with the generated data set to showcase the model's capability in developing risk-informed mitigation and recovery plans to achieve resilience goals. The insights drawn from the numerical experiments show the effect of changing risk preference on community resilience metrics.
•We propose a novel decision-making framework for community resilience planning considering uncertain hazards.•We incorporate structural engineering and social science approaches to quantify the hazard impact on buildings and the population.•We adopt a risk-averse approach to capture hazard uncertainty and account for rare but high-consequence events.•We present a case study illustrating the applicability of the proposed framework in community resilience planning.•The framework can identify the optimal allocation of resources to improve community resilience, prioritizing the vulnerable population.
This paper presents an experimental study on the thermophysical properties of 40% ethylene glycol-based TiO2-Al2O3 hybrid nanofluids. The hybrid nanofluids were prepared for concentrations of 0.02 to ...0.1% and temperature of 30 to 80 °C. Nanofluid stability is studied using visual observation, spectral UV–Vis, zeta potential, and results obtained excellent stability. The rheological test was conducted to determine the Newtonian behaviour. The viscosity and thermal conductivity were investigated. Viscosity and thermal conductivity of hybrid nanofluids boost as opposed to the base fluid. The thermal conductivity is improved by 40.86% at 0.1% volume concentration and 80 °C. The hybrid nanofluids have higher thermal conductivity than single TiO2 and Al2O3 and better heat transfer efficiency with a concentration greater than 0.04%. The newly developed models of viscosity and thermal conductivity are defined with good accuracy from the experimental data. The performance enhancement ratio shows that hybrid nanofluids with a concentration greater than 0.04% are advantageous due to having better efficiency in heat transfer. The combined effects of TiO2 and Al2O3 nanoparticles on thermal behaviour, compared to viscosity, are more significant. Therefore, the practical application of hybrid nanofluids in heat transfer systems could have a potential influence for its increased thermal conductivity and low viscosity.
•Thermophysical properties of the TiO2-Al2O3 hybrid nanofluids improved with temperature and concentration.•Newtonian behaviour of hybrid nanofluids was analyzed with temperatures and concentrations.•Overall thermal conductivity increase of 40.86% with concentration of 0.1% at 80°C.•Thermal conductivity of hybrid nanofluids are superior to single nanofluids.•Hybrid nanofluids are beneficial due to their increased heat transfer performance at concentrations above 0.04%.
We investigated the predictive capability of various configurations of the Weather Research and Forecasting (WRF) model version 4.4, to predict hub height offshore wind speed and wind power density ...in the Northeast US wind farm lease areas. The selected atmospheric conditions were high-pressure systems (anticyclones) coinciding with wind speed below the cut-in wind turbine threshold. There are many factors affecting the potential of offshore wind power generation, one of them being low winds, namely wind droughts, that have been present in future climate change scenarios. The efficiency of high-resolution hub height wind prediction for such events has not been extensively investigated, even though the anticipation of such events will be important in our increased reliance on wind and solar power resources in the near future. We used offshore wind observations from the Woods Hole Oceanographic Institution’s (WHOI) Air–Sea Interaction Tower (ASIT) located south of Martha’s Vineyard to assess the impact of the initial and boundary conditions, number of model vertical levels, and inclusion of high-resolution sea surface temperature (SST) fields. Our focus has been on the influence of the initial and boundary conditions (ICBCs), SST, and model vertical layers. Our findings showed that the ICBCs exhibited the strongest influence on hub height wind predictions above all other factors. The NAM/WRF and HRRR/WRF were able to capture the decreased wind speed, and there was no single configuration that systematically produced better results. However, when using the predicted wind speed to estimate the wind power density, the HRRR/WRF had statistically improved results, with lower errors than the NAM/WRF. Our work underscored that for predicting offshore wind resources, it is important to evaluate not only the WRF predictive wind speed, but also the connection of wind speed to wind power.
Summary Background Influenza causes substantial morbidity and mortality worldwide. Few data exist for the efficacy of neuraminidase inhibitors, which are the only readily available influenza ...treatment options, especially in low-income settings. We assessed the efficacy of treatment with the neuraminidase inhibitor oseltamivir to reduce patient illness and viral shedding in people with influenza, in whom treatment was started within 5 days of symptom onset, in an urban setting in Bangladesh. Methods We undertook a double-blind, randomised, controlled trial between May, 2008, and December, 2010. Patients with a positive rapid influenza test identified by surveillance of households in Kamalapur, Bangladesh were randomly allocated on a 1:1 basis to receive oseltamivir or placebo twice daily for 5 days. Randomisation lists for individuals enrolled less than 48 h and 48 h or longer since illness onset were generated with permuted blocks of variable length between two and eight. Participants and study staff were masked to treatment group. Participants provided nasal wash specimens at enrolment and 2, 4, and 7 days later, and were visited daily to record symptoms. All specimens were tested for influenza with reverse-transcriptase PCR, and if the result was positive, we isolated the virus. The primary endpoints were duration of clinical illness and viral shedding in patients treated less than and more than 48 h since illness onset and the frequency of oseltamivir resistance during treatment. Analyses were intention to treat unless otherwise specified. This trial is registered with ClinicalTrials.gov , number NCT00707941. Findings Overall, 1190 people with a median age of 5 years (IQR 2–9) were enrolled: 794 (67%) less than 48 h since symptom onset and 396 (33%) 48 h or longer since symptom onset. 592 participants were assigned to placebo and 598 to oseltamivir. The median duration of symptoms was shorter in the oseltamivir group (3 days, IQR 1–5) than in the placebo group (4 days, 1–6; p=0·01). When stratified by timing of treatment initiation, in participants enrolled 48 h or longer since illness onset, the median duration of symptoms was similar in both groups (oseltamivir 3 days IQR 2–5, placebo 3 days 1–5; p=0·04). The median duration of symptoms was reduced by 1 day in the group given oseltamivir who were enrolled less than 48 h since symptom onset compared with those given placebo, but this difference was not significant. In those with all swab specimens (n=1134), oseltamivir significantly reduced virus isolation on days 2 (placebo 374 66% vs oseltamivir 321 56%; difference 15·2%, 95% CI 9·5–20·8, p=0·0004), 4 (241 43% vs 174 30%; difference 30·2%, 95% CI 24·6–35·8, p<0·0001), and 7 (68 12% vs 36 6%; difference 47·5%, 95% CI 44·2–50·8, p=0·0009). In participants enrolled 48 h or longer since illness onset, oseltamivir treatment significantly reduced virus isolation on days 2 and 4, but not day 7. In participants enrolled less than 48 h since illness onset, oseltamivir treatment significantly reduced virus isolation on days 2, 4, and 7. The emergency of resistance to oseltamivir during treatment was rare overall (<1%) and in influenza A H1N1pdm09 viruses (3·9%). Interpretation Oseltamivir treatment resulted in a modest reduction in the duration of symptoms and virus shedding in people with uncomplicated influenza infections, even when treatment was started 48 h or longer after illness onset. Funding Centers for Disease Control and Prevention (in agreement with the International Centre for Diarrhoeal Disease Research, Bangladesh).
Cryo-induced hydrogel from cellulose is a new class of biomaterials for drug delivery, cell delivery, bone and skin tissue engineering for cell proliferation and regeneration applications. This ...research aimed to synthesize cryo-induced hydrogel from cellulose and carboxymethyl cellulose (CMC) produced from empty bunch's cell wall of
. First, the experiment was to produce cellulose-rich material using hot-compressed water extraction followed by alkaline delignification and bleaching with H
O
. The obtained bleached EFB cellulose was used as the substrate for CMC, and the optimal condition with the highest degree of carboxyl substitution (DS) of 0.75 was achieved when varying NaOH and monochloroacetic acid concentration as well as etherification temperature using fractional factorial design. For cryogelation study, hydrogels were synthesized from cellulose, CMC and beta-cyclodextrin (β-CD) by dissolving cellulose-based matrix in a NaOH/urea system, and the cellulose (CEL) solution was frozen spontaneously at -40 °C followed by high speed mixing to loosen cellulose fibrils. Epichlorohydrin (ECH) and Polyethylene glycol diglycidyl ether (PEGDE) were used as a cross-linker. First, the ratio of cellulose and CMC with different amounts of ECH was investigated, and subsequently the proper ratio was further studied by adding different crosslinkers and matrices, i.e., CMC and β-CD. From the result, the ECH crosslinked CMC-CEL (E-CMC-CEL) gel had the highest swelling properties of 5105% with the average pore size of lyophilized hydrogel of 300 µm. In addition, E-CMC-CEL gel had the highest loading and release capability of tetracycline in buffer solution at pH 7.4 and 3.2. At pH 7.4, tetracycline loading and release properties of E-CMC-CEL gel were 65.85 mg g
dry hydrogel and 46.48 mg g
dry hydrogel (70.6% cumulative release), respectively. However, at pH 3.2, the loading and release capabilities of Tetracycline were moderately lower at 16.25 mg g
dry hydrogel and 5.06 mg g
dry hydrogel, respectively. The findings presented that E-CMC-CEL hydrogel was a suitable material for antibiotic tetracycline drug carrying platform providing successful inhibitory effect on
,
and
, respectively.
Rheumatic heart disease (RHD), degenerative aortic stenosis (AS), and congenital valve diseases are prevalent in sub-Saharan Africa. Many knowledge gaps remain in understanding disease mechanisms, ...stratifying phenotypes, and prognostication. Therefore, we aimed to characterise patients through clinical profiling, imaging, histology, and molecular biomarkers to improve our understanding of the pathophysiology, diagnosis, and prognosis of RHD and AS.
In this cross-sectional, case-controlled study, we plan to recruit RHD and AS patients and compare them to matched controls. Living participants will undergo clinical assessment, echocardiography, CMR and blood sampling for circulatory biomarker analyses. Tissue samples will be obtained from patients undergoing valve replacement, while healthy tissues will be obtained from cadavers. Immunohistology, proteomics, metabolomics, and transcriptome analyses will be used to analyse circulatory- and tissue-specific biomarkers. Univariate and multivariate statistical analyses will be used for hypothesis testing and identification of important biomarkers. In summary, this study aims to delineate the pathophysiology of RHD and degenerative AS using multiparametric CMR imaging. In addition to discover novel biomarkers and explore the pathomechanisms associated with RHD and AS through high-throughput profiling of the tissue and blood proteome and metabolome and provide a proof of concept of the suitability of using cadaveric tissues as controls for cardiovascular disease studies.
Accumulation of pathological α-synuclein aggregates plays a major role in Parkinson's disease. Macroautophagy is a mechanism to degrade intracellular protein aggregates by wrapping them into ...autophagosomes, followed by fusion with lysosomes. We had previously shown that pharmacological activation of macroautophagy protects against α-synuclein-induced toxicity in human neurons. Here, we hypothesized that inhibition of macroautophagy would aggravate α-synuclein-induced cell death.Unexpectedly, inhibition of autophagosome formation by silencing of ATG5 protected from α-synuclein-induced toxicity. Therefore, we studied alternative cellular mechanisms to compensate for the loss of macroautophagy. ATG5 silencing did not affect the ubiquitin-proteasome system, chaperone systems, chaperone-mediated autophagy, or the unfolded protein response. However, ATG5 silencing increased the secretion of α-synuclein via exosomes. Blocking exosomal secretion exacerbated α-synuclein-induced cell death.We conclude that exosomal secretion of α-synuclein is increased after impaired formation of autophagosomes to reduce the intracellular α-synuclein burden. This compensatory mechanism prevents α-synuclein-induced neuronal cell death.
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