Influenza virus infections lead to numerous deaths and millions of hospitalizations each year. One challenge facing anti-influenza drug development is the heterogeneity of the circulating influenza ...viruses, which comprise several strains with variable susceptibility to antiviral drugs. For example, the wild-type (WT) influenza A viruses, such as the seasonal H1N1, tend to be sensitive to antiviral drugs, amantadine and rimantadine, while the S31N mutant viruses, such as the pandemic 2009 H1N1 (H1N1pdm09) and seasonal H3N2, are resistant to this class of drugs. Thus, drugs targeting both WT and the S31N mutant are highly desired. We report our design of a novel class of dual inhibitors along with their ion channel blockage and antiviral activities. The potency of the most active compound 11 in inhibiting WT and the S31N mutant influenza viruses is comparable with that of amantadine in inhibiting WT influenza virus. Solution NMR studies and molecular dynamics (MD) simulations of drug-M2 interactions supported our design hypothesis: namely, the dual inhibitor binds in the WT M2 channel with an aromatic group facing down toward the C-terminus, while the same drug binds in the S31N M2 channel with its aromatic group facing up toward the N-terminus. The flip-flop mode of drug binding correlates with the structure–activity relationship (SAR) and has paved the way for the next round of rational design of broad-spectrum antiviral drugs.
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IJS, KILJ, NUK, PNG, UL, UM
Selected results were gathered during investigation of centrifugal pumps used in a sea water cooling system of one of Diesel power stations are presented in the paper. The main goal of research was ...to explain the reason of occurring fractures in pump shafts. The investigation has shown that the fractures were caused mainly by the resonance between pump shaft torsional natural vibrations and those following from the pressure fluctuations related to the frequency of the shaft rotational speed and the number of impeller blades. The resonance occurred as a result of intense erosion of pump impellers derived mainly from cavitation phenomenon that caused about 20% of the impeller mass decrease. The scope of the investigation has covered among others: erosion damage recognition, tests of the investigated pumps operating conditions, spectral analysis of pressure fluctuation generated by the pump blade system as well as strength analysis of the pump shaft and the frequencies of its natural bending and torsional vibrations.
•Failures of centrifugal pumps operated in a cooling system of Diesel power plant were investigated.•The reason of fractures occurring in pump shafts has been detected and explained.•The resonance between pump shaft natural torsional vibrations and pressure fluctuations was found.•The intense cavitation erosion of pump impellers resulted in significant mass imbalance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The adverse effects of proton pump inhibitors (PPIs) have been documented for pneumonia; however, there is no consensus regarding whether the use of PPIs might be harmful regarding the risk of severe ...acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this regard, we aimed to measure the potential associations of the current use of PPIs with the infection rates of COVID-19 among patients who underwent SARS-CoV-2 testing.
Data were derived from a Korean nationwide cohort study with propensity score matching. We included 132 316 patients older than 18 years who tested for SARS-CoV-2 between 1 January and 15 May 2020. Endpoints were SARS-CoV-2 positivity (primary) and severe clinical outcomes of COVID-19 (secondary: admission to intensive care unit, administration of invasive ventilation or death).
In the entire cohort, there were 111 911 non-users, 14 163 current PPI users and 6242 past PPI users. After propensity score matching, the SARS-CoV-2 test positivity rate was not associated with the current or past use of PPIs. Among patients with confirmed COVID-19, the current use of PPIs conferred a 79% greater risk of severe clinical outcomes of COVID-19, while the relationship with the past use of PPIs remained insignificant. Current PPI use starting within the previous 30 days was associated with a 90% increased risk of severe clinical outcomes of COVID-19.
Patients taking PPIs are at increased risk for severe clinical outcomes of COVID-19 but not susceptible to SARS-CoV-2 infection. This suggests that physicians need to assess benefit-risk assessments in the management of acid-related diseases amid the COVID-19 pandemic.
ABSTRACT
Objectives:
Proton‐pump inhibitor‐responsive esophageal eosinophilia is a newly recognized entity with an unclear prevalence in children, as only retrospective data are available. The aim of ...this study was to determine the prevalence and clinical features of proton‐pump inhibitor‐responsive esophageal eosinophilia in children.
Methods:
This prospective study enrolled patients with esophageal symptoms and esophageal eosinophilic counts as 15 or more than 15 eos/hpf (eosinophils per high‐power field). Children received treatment with esomeprazole 1 mg · kg−1 per dose twice daily for 8 weeks and the endoscopy was repeated. Complete response to proton‐pump inhibitor (PPI) was defined as 5 or less than 5 eos/hpf, and a partial response as >5 and <15 eos/hpf in post‐treatment biopsies.
Results:
Fifty‐one children (74.5% boys) were included. Histological response was observed in 35 children (68.6%): 24 children (47%) had a complete response and 11 children (21.6%) had a partial response. Only 16 children (31.4%) were diagnosed with eosinophilic esophagitis (EoE). There were no differences in history of atopy, allergy tests, pH study results, and endoscopic scores. Clinical symptoms were similar, with the exception of food impaction, which was more frequent in children with EoE (56.2% vs 20%, P = 0.01). The mean pretreatment peak eosinophil count was higher in patients with EoE (74.8 ± 36.2 vs 46.3 ± 30.7, P = 0.007). Eleven of the 14 patients (78.6%) on a lower PPI treatment maintenance dose remained in clinicopathologic remission at 1‐year follow‐up.
Conclusions:
A significant proportion of children with esophageal eosinophilia responded to high dose PPI treatment. Clinical, endoscopic, and pH study results were similar, with exception of patients with EoE, who were more likely to experience food impaction and have higher esophageal eosinophil counts.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A large number of ground-coupled heat pump (GCHP) systems have been used in residential and commercial buildings throughout the world due to the attractive advantages of high efficiency and ...environmental friendliness. This paper gives a detailed literature review of the research and developments of the vertical-borehole GCHP technology for applications in air-conditioning. A general introduction on the ground source heat pump system and its development is briefly presented first. Then, the most typical simulation models of the vertical ground heat exchangers currently available are summarized in detail including the heat transfer processes outside and inside the boreholes. The various design/simulation programs for vertical GCHP systems primarily based on the typical simulation models are also reviewed in this paper. Finally, the various hybrid GCHP systems for cooling or heating-dominated buildings are well described. It is found that the GCHP technology can be used both in cold and hot weather areas and the energy saving potential is significant.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Estimates of the ocean biological carbon pump are limited by uncertainties in the magnitude of the physical injection of particulate and dissolved organic carbon to the ocean interior. A major ...challenge is to evaluate the contribution of these physical pumps at small spatial and temporal scales (<100 km and <1 month). Here, we use a submesoscale permitting biophysical model covering a large domain representative of a subpolar and a subtropical gyre to quantify the impact of small‐scale physical carbon pumps.The model successfully simulates intense eddy‐driven subduction hot spots with a magnitude comparable to what has been observed in nature (1,000–6,000 mg C·m−2·day−1). These eddy‐driven subduction events are able to transfer carbon below the mixed‐layer, down to 500‐ to 1,000‐m depth. However, they contribute <5% to the annual flux at the scale of the basin, due to strong compensation between upward and downward fluxes. The model also simulates hot spots of export associated with small‐scale heterogeneity of the mixed layer, which intermittently export large amounts of suspended particulate and dissolved organic carbon. The mixed‐layer pump contributes ∼20% to the annual flux. High‐resolution measurements of export flux are needed to test models such as this one and to improve our mechanistic understanding of the biological pump and how it will respond to climate change.
Key Points
A high‐resolution model simulates realistic hot spots of organic carbon export by physical subduction
Eddy‐driven subduction contributes little to annual export due to compensation between upward and downward fluxes
Eddy‐driven spatiotemporal variations in the mixed‐layer efficiently export dissolved and particulate organic carbon
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The growing worldwide demand for Greenhouse gas (GHG) emission reduction has led to a new age of energy saving. Besides the energy saving extent, the costs of energy saving measures as well as the ...environmental and social impacts are also necessary to be evaluated in order to make sure that the application of these measures can also meet sustainable development requirements. Thus, a sustainability evaluation method based on Life Cycle Theory is innovatively designed in this study. We present its new aspects, describe its working steps in detail and also test this new method by means of a case study on Ground Source Heat Pump (GSHP), which is a renewable technology that is widely applied in the building sector in China. Data for the case study is collected by literature review and site investigation. Results show that the energy consumption of the investigated GSHP cases has an energy saving rate as around 40.2%.The main environmental impacts of GSHP are found to be global warming, acidification and eutrophication in the production process, and soil temperature change in the operation process. The prevention cost of the environmental impacts is around 15.84 RMB/m2 in the production process, and 5 RMB/m2 in the operation process. The payback time of our cases is around 4 years, and it will rise to 4.29 years if accounting the environmental prevention cost. We conclude based on the case study that our assessment method proofs to be useful as it can demonstrate comprehensive characteristics of sustainability for energy saving measures in the whole life cycle.
•A sustainability evaluation method based on Life Cycle Theory is designed.•This new method is tested in a case study on Ground Source Heat Pump in China.•Our innovated method gives a more comprehensive and concise view of the measures assessed.•The evaluation ideas provide reference for assessment of other energy saving measures.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Over the last decade, clinical experiences and research studies raised concerns regarding use of proton pump inhibitors (PPIs) as part of the diagnostic strategy for eosinophilic esophagitis (EoE). ...We aimed to clarify the use of PPIs in the evaluation and treatment of children and adults with suspected EoE to develop updated international consensus criteria for EoE diagnosis.
A consensus conference was convened to address the issue of PPI use for esophageal eosinophilia using a process consistent with standards described in the Appraisal of Guidelines for Research and Evaluation II. Pediatric and adult physicians and researchers from gastroenterology, allergy, and pathology subspecialties representing 14 countries used online communications, teleconferences, and a face-to-face meeting to review the literature and clinical experiences.
Substantial evidence documented that PPIs reduce esophageal eosinophilia in children, adolescents, and adults, with several mechanisms potentially explaining the treatment effect. Based on these findings, an updated diagnostic algorithm for EoE was developed, with removal of the PPI trial requirement.
EoE should be diagnosed when there are symptoms of esophageal dysfunction and at least 15 eosinophils per high-power field (or approximately 60 eosinophils per mm2) on esophageal biopsy and after a comprehensive assessment of non-EoE disorders that could cause or potentially contribute to esophageal eosinophilia. The evidence suggests that PPIs are better classified as a treatment for esophageal eosinophilia that may be due to EoE than as a diagnostic criterion, and we have developed updated consensus criteria for EoE that reflect this change.
•The performance of rotors with different lobe numbers is analyzed by experiments.•Comparing the internal flow of Roots rotors with different lobe numbers.•The pressure signal characteristics of ...different rotor exhausts are analyzed.•Suggestions on the selection of rotors of multi-stage vacuum pump are put forward.
Multi-stage Roots dry vacuum pumps are widely used in the semiconductor industry, metallurgy, pharmaceuticals, solar photovoltaic, thin film equipment, and other such fields. There are many combinations of rotors from the inlet to the exhaust of the multi-stage Roots vacuum pump. Depending on the application process of the multi-stage Roots vacuum pump, different rotation and self-combination designs are required. Currently, the pumping characteristics of different rotor types of the multi-stage Roots dry vacuum pump are not clear, and the combined design of the multi-stage pump rotor cannot be supported. In order to realize the applicability analysis of different rotors in different pressure ranges, a vacuum pump test platform and an adjustable rotor Roots experimental pump were designed. The pumping performance and power consumption of two-lobe Roots rotors, three-lobe Roots rotors and five-lobe Roots rotors in different pressure ranges were tested in experiments, and the internal flow conditions of multi-stage pump exhaust stages were numerically simulated. The results demonstrate that considering the ultimate performance and power consumption, the two-lobe Roots rotors and the three-lobe Roots rotors are more suitable for the exhaust pressure range of 1–10,000 Pa. With the increase of the exhaust pressure, the pumping performance of the three-lobe Roots rotors begins to gradually improve, and the pumping performance has obvious advantages. When the exhaust pressure exceeds 50,000 Pa, the advantages of the five-lobe Roots rotors gradually become obvious. The five-lobe Roots rotors can better handle the process of direct exhaust to atmosphere. The research methods and conclusions adopted in this paper can provide a reference for the design of the rotor combination scheme of the multi-stage Roots dry vacuum pump.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•System drying performance influenced by air flow ratio changing was investigated.•Drying performances of adjusting air temperature and flow ratio was compared.•Drying time decreased 42 min, or ...15.0%, by the strategy of hot air bypassed.•Energy consumption of compressor was shorted from 4.27 kWh to 3.63 kWh.•Contributions of this study can guide low temperature material drying process.
As the quick development of industry drying technology, different heat pump drying systems were proposed in recent decades. Enclosed heat pump drying system was considered as the most widely used system. For an existed enclosed fixed frequency heat pump drying system, drying time could be decreased by increasing air temperature at inlet of drying chamber. However, as a fundamental problem, system drying performance influenced by air flow ratio was not tested and reported in open literatures. Therefore, basing on adding an air bypass duct, drying performance of an enclosed system was experimental investigated in this study, with 15 mm thickness fresh carrot chips used. Furthermore, qualitatively and quantitatively comparisons and discussions on experimental results were conducted. A whole drying process were firstly divided into three stages by different water content ratios, preheating stage at 98–100%, fast drying stage at 20–98%, and later drying stage at 0–20%, respectively. For the inlet air temperature of drying chamber is fixed at 40 °C, material drying time for water content ratio reaching 20% could be effectively decreased as much as 42 min, or 15.0%, by the strategy of hot air bypassed. After the drying time shortened, the calculated energy consumption for compressor was also decreased from 4.27 kWh for AFR at 1.0 to 3.63 kWh for AFR at 0.6. Contributions of this study can guide low temperature material drying process. Clearly, system control optimization and energy saving were both expected.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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