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IMPORTANCE: The potential benefit of combining intracranial effective systemic therapy with radiotherapy for patients with breast cancer with brain metastases remains unclear. OBJECTIVE: To assess the activity and safety of combining radiotherapy with pyrotinib and capecitabine in patients with ERBB2-positive breast cancer and brain metastases. DESIGN, SETTING, AND PARTICIPANTS: This was a single-arm, single-center, phase 2 nonrandomized clinical trial with a safety run-in phase. Between January 2020 and August 2022, patients with ERBB2-positive breast cancer and brain metastases were enrolled. The data cutoff date was February 1, 2023. INTERVENTIONS: Patients received either fractionated stereotactic radiotherapy or whole-brain radiotherapy. Treatment with pyrotinib (400 mg, once daily) and capecitabine (1000 mg/m2, twice daily, on days 1-14 of each 21-day cycle) was initiated from the first day of radiotherapy to the seventh day after the completion of radiotherapy and continued until disease progression or unacceptable toxic effects. MAIN OUTCOMES AND MEASURES: The primary end point was 1-year central nervous system (CNS) progression-free survival (PFS) rate. Secondary end points included CNS objective response rate (ORR), PFS, overall survival (OS), safety, and changes in neurocognitive function. RESULTS: A total of 40 female patients (median age, 50.5 years [IQR, 46-59 years]) were enrolled and received treatment, including 3 patients in safety run-in phase. With a median follow-up of 17.3 months (IQR, 10.3-26.9), the 1-year CNS PFS rate was 74.9% (95% CI, 61.9%-90.7%), and the median CNS PFS was 18.0 months (95% CI, 15.5 to not reached). The 1-year PFS rate was 66.9% (95% CI, 53.1%-84.2%), and the median PFS was 17.6 months (95% CI, 12.8-34.1). The CNS objective response rate was 85% (34 of 40). Median overall survival was not reached. The most common grade 3 or 4 treatment-related adverse event was diarrhea (7.5%). Asymptomatic radiation necrosis was identified in 4 of 67 lesions (6.0%) treated with fractionated stereotactic radiotherapy. Most patients maintained neurocognitive function, as evaluated by the Mini-Mental State Examination at different points. CONCLUSIONS AND RELEVANCE: The results of this trial suggest that radiotherapy combined with pyrotinib and capecitabine is associated with long intracranial survival benefit in patients with ERBB2-positive advanced breast cancer and brain metastases with an acceptable safety profile. This combination deserves further validation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04582968

Gastrointestinal surgery using a stapler is usually associated with tissue damage, anastomosis leakage, bleeding, and other complications, which is one of the effective methods for treating digestive tract cancer. The cutting properties of staples and the tissue damage occurring in the process of stapling porcine esophageal and gastric tissues have been evaluated and a new type of stapler has been designed. Since different structural and mechanical properties esophageal and gastric tissues layers, the puncturing force exhibits a fluctuating trend. Compressive stress caused by the bending of the staple legs can lead to the destruction of the vascular network inside the tissue, tissue deforms and tears. Finally, a staple with an internal incision arc (IIA) tip is designed, which meeting the performance requirements.

Pseudoceranoid A (1), a rare merosesquiterpene featuring a rearranged 4,9-friedodrimane-type core with a crotonolactone moiety, two new rearranged 4,9-friedodrimane-type sesquiterpene cyclopentanones (2and 3), and three new rearranged 4,9-friedodrimane-type sesquiterpene hydroquinones (4–6), along with two new drimane-type sesquiterpene derivatives (7and 8), as well as two new 4,9-friedodrimane-type sesquiterpene quinones (9and 10), were isolated from the South China Sea sponge Pseudoceratina purpurea. The structures of compounds were established by analysis of spectroscopic data, as well as by single-crystal X-ray diffraction, DP4+ probability analyses, and calculated electronic circular dichroism. Compound 4showed weak cytotoxicity against K562, H69AR, and MDAMB-231 cell lines with IC50values of 3.01, 7.74, and 9.82 μM, respectively. Compound 5exhibited cytotoxicity against the H69AR cell line with an IC50value of 2.85 μM.

Circadian disorder and high-fat diet (HFD) can disturb lipid metabolism homeostasis and may promote the development of various metabolic diseases. The relationship between them is of great concern. This study aimed to explore the effects of Per1/Per2double knockout (DKO) on hepatic lipid metabolism in mice under HFD and HFD with docosahexaenoic acid (DHA) substitution.

The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions1,2. Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS)3and the transcription regulator Integrator-PP2A (INTAC)4–6. Through SSB1-mediated recognition of single-stranded DNA, SOSS–INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability. SOSS–INTAC-dependent attenuation of R-loops is enhanced by the ability of SSB1 to form liquid-like condensates. Deletion of NABP2(encoding SSB1) or introduction of cancer-associated mutations into its intrinsically disordered region leads to a pervasive accumulation of R-loops, highlighting a genome surveillance function of SOSS–INTAC that enables timely termination of transcription at promoters to constrain R-loop accumulation and ensure genome stability.

Refined energy allocation can avoid energy shortages during peak energy consumption periods. Latent thermal energy storage (LTES) coupled with power-to-heat technology is gaining prominence as a potential solution for meeting residential heating demands. By utilizing energy storage, LTES can address the temporal mismatch between off-peak electricity and peak heat loads, thereby, ensuring a cost-effective heating solution. In order to investigate the performance of the LTES system in the context of domestic hot water supply, this study involved the design of a prototype thermal battery. Two charging modes, namely hot water charging and electric modes are utilized to charge the thermal battery considering the compatibility with existing energy systems and the standalone convenience. Results indicated that increasing the charging temperature and electricity consumption are conducive to elevating the thermal battery's ability to produce hot water. Under the hot water charging mode, the V40is enhanced by 20 % with the charging temperature increased from 65 to 70 °C, further increasing the charging temperature will have limited effects on increasing V40. While the electric charging mode requires higher electricity consumption to achieve V40similar to that of the hot water charging mode. In addition, a techno-economic analysis was also conducted on the use of heat batteries, instantaneous water heaters and storage water heaters in a three-person household heating scenario under the peak and valley tariff. Compared to traditional electric water heaters, the thermal battery not only reduces electricity consumption by 55.2 % but also lowers the cost of producing hot water by 77.3 %. This makes the thermal battery a promising and efficient solution for residential heating.

Compressed air energy storage (CAES) is a promising large-scale energy storage technology to mitigate the fluctuations and intermittence of renewable energies. The application of latent thermal energy storage (LTES) using phase change materials (PCM) to recover compressed waste heat can further improve the energy storage density and round-trip efficiency of CAES. However, there are very few guidelines of PCM selection for a CAES system. In view of the challenge, this study first conducts orthogonal experiments to analyze the effects of the thermophysical properties of PCMs on the performance of the packed-bed LTES and CAES system. Then a PCM selection procedure for CAES is developed based on the orthogonal experiment design and TOPSIS method. The results of range analysis indicate that each thermophysical property of PCM has quite different relative importance to the performance indicators of the CAES system. From the aspect of packed-bed LTES, the density (40.8 %) and latent heat (32.8 %) of PCMs are the top two impact factors for the heat storage rate, while the melting temperature (45.7 %) and thermal conductivity (22.4 %) are the top two impact factors for the residual heat. From the aspect of the CAES system, the density (31.9 %) and melting temperature (24.4 %) are the top two impact factors for the round-trip efficiency, while the density (42.2 %) and latent heat (35.2 %) rank the top two impact factors for the air storage capacity.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a bunyavirus that causes SFTS, with a case fatality rate of up to 30 %. The innate immune system plays a crucial role in the defense against SFTSV; however, the impact of viral propagation of STFSV on the innate immune system remains unclear. Although proteomics analysis revealed that the expression of the downregulator of transcription 1 (DR1) increased after SFTSV infection, the specific change trend and the functional role of DR1 during viral infection remain unelucidated. In this study, we demonstrate that DR1 was highly expressed in response to SFTSV infection in HEK 293T cells using qRT-PCR and Western blot analysis. Furthermore, viral replication significantly increased the expression of various TLRs, especially TLR9. Our data indicated that DR1 positively regulated the expression of TLRs in HEK 293T cells, DR1 overexpression highly increased the expression of numerous TLRs, whereas RNAi-mediated DR1 silencing decreased TLR expression. Additionally, the myeloid differentiation primary response gene 88 (MyD88)-dependent or TIR-domain-containing adaptor inducing interferon-β (TRIF)-dependent signaling pathways were highly up- and downregulated by the overexpression and silencing of DR1, respectively. Finally, we report that DR1 stimulates the expression of TLR7, TLR8, and TLR9, thereby upregulating the TRIF-dependent and MyD88-dependent signaling pathways during the SFTSV infection, attenuating viral replication, and enhancing the production of type I interferon and various inflammatory factors, including IL-1β, IL-6, and IL-8. These results imply that DR1 defends against SFTSV replication by inducing the expression of TLR7, TLR8, and TLR9. Collectively, our findings revealed a novel role and mechanism of DR1 in mediating antiviral responses and innate immunity.

Ion thermodiffusion coefficients are crucial to analyse effects of thermodiffusion in thermocells and these values are difficult to measure experimentally. To determine these coefficients, this paper adopts parameter identification and studies their identifiability. Time dependence of open-circuit voltage is measured in an aqueous potassium ferri/ferrocyanide thermocell as data set. A one-dimensional numerical model is established according to theories of electrochemistry and non-equilibrium thermodynamics. Identification of thermodiffusion coefficients is conducted using genetic algorithm in eight parameter spaces, which are divided according to signs of three parameters. Thermodiffusion is suggested to induce a 9.38% drop in voltage. The best identification results are −8.30 ×10−12, −6.56 ×10−12, −3.48 ×10−12m2/(s K) for ferricyanide, ferrocyanide and potassium ion, respectively. However, five optimal parameters in other parameter spaces have close fitness, implying multimodality of identification. And only one of these parameters is practically identifiable using this method. To improve identification results, more accurate estimation of inner temperature difference and determination of ion mobilities are necessary. Besides, electric current data has the potential to determine the actual combination of thermodiffusion coefficients from these six optimal results.

Dose–response experiments and data analyses are often carried out according to an optimal design under a model assumption. A two-parameter logistic model is often used because of its nice mathematical properties and plausible stochastic response mechanisms. There is an extensive literature on its optimal designs and data analysis strategies. However, a model is at best a good approximation in a real-world application, and researchers must be aware of the risk of model mis-specification. In this paper, we investigate the effectiveness of the sequential ED-design, the D-optimal design, and the up-and-down design under the three-parameter logistic regression model, and we develop a numerical method for the parameter estimation. Simulations show that the combination of the proposed model and the data analysis strategy performs well. When the logistic model is correct, this more complex model has hardly any efficiency loss. The three-parameter logistic model works better than the two-parameter logistic model in the presence of model mis-specification.

A detailed chemical study of the extract from the soft coral Stereonephthya bellissimaresulted in the isolation and identification of seven new sesquiterpenoids, bellissinanes A–G (1–7), along with four new diterpenes (8–11). Bellissinane A (1) is the third reported nardosinane-type sesquiterpene bearing a 6/5/6 tricyclic system. Bellissinanes C and D (3, 4) contain a phenylethylamine fragment, which is relatively unusual in marine organisms. Bellissinanes E–G (5–7) belong to the rare class of nornardosinane sesquiterpenoids. Structurally uncommon octahydro-1H-indenyl-type and prenyleudesmane-type skeletons were characterized for herpetopanone B (8) and bellissimain A (9), respectively. Bellissinane E (5) exhibited in vivo angiogenesis-promoting activity.

Background: We have previously reported that hippocampal long-term potentiation (LTP) was suppressed in temporal lobe epilepsy (TLE) rats. The N-methyl-D-aspartic acid receptors containing 2B subunit (NR2B-NMDARs) are indispensable to induce the LTP of hippocampus. However, it is still unknown whether the NR2B-NMDARs are implied with the cognitive dysfunction in TLE rats. Methods: The TLE model was lithium chloride-pilocarpine (li-pilo) model. Morris water maze test was used to evaluate the cognitive function of epileptic rats. Expression of hippocampal NR2B-NMDAs was evaluated by western blotting. Stereotactic injection of NMDA, an agonist of NR2B-NMDARs, into the hippocampus of TLE rats was used to investigate the role of NR2B-NMDARs on cognitive dysfunction. Results: Cognitive function TLE rats was significantly reduced compared with controls in the Morris water maze test (P< 0.05). Western blotting data showed the down-expression of hippocampal NR2B-NMDARs and p-NR2B in TLE rats compared with the control (P< 0.05). In addition, hippocampal stereolocalization of NMDA injection improved partially the learning and memory in TLE rats (P< 0.05). Conclusions: Down-expression and low activity of hippocampal NR2B-NMDARs may be implied with chronic cognitive dysfunction in TLE rats.

Aiming at identifying the difference between heat and electricity storage in distributed energy systems, this paper tries to explore the potential of cost reduction by using time-of-use electricity prices and a variety of energy storage methods. The current situation is defined as basic situation which is purchasing electricity for all loads in real-time (Scenario 1). For the Scenario 2, battery energy storage to utilize valley electricity is considered (Scenario 2). Besides, considering that the price of the battery is relatively high, heat and cold pumps are also included as well as thermal storage to provide dispatchable heat and cold (Scenario 3). Lastly, as a representation of renewable heat, the solar collector was used to collect solar heat for supplying heat and cold (via absorption refrigeration) to the building (Scenario 4). Using levelized cost of electricity (LCOE) and payback time of scenarios as the main indicators, the influence rules of key parameters is analyzed and the capacity is optimized, aiming to explore the sensitive reaction of scenarios to components and compare the performance of different scenarios on typical days in four seasons. Based on the results, the utilization of valley electricity and storage methods in different scenarios can reduce the LCOEof commercial buildings. When the lifetime is considered as 10 years, Scenarios 2, 3, and 4 can reduce the LCOEfrom 0.9795 CNY/kWh (Scenario 1) to 0.9183, 0.6791 and 0.7748 CNY/kWh, respectively. Scenario 2 is sensitive to the lifetime of the battery. Scenario 4 has great potential for a long lifetime such as 20 years and it is also sensitive to the price of components.

Aim: We aimed to identify new plasma biomarkers for the diagnosis of Pulmonary Tuberculosis (PTB). Background: Tuberculosis is an ancient infectious disease that remains one of the major global health problems. Until now, effective, convenient, and affordable methods for diagnosis of PTB were still lacking. Objective: This study focused on constructing a label-free LC-MS/MS-based comparative proteomics between six tuberculosis patients and six healthy controls to identify Differentially Expressed Proteins (DEPs) in plasma. Methods: To reduce the influences of high-abundant proteins, albumin and globulin were removed from plasma samples using affinity gels. Then DEPs from the plasma samples were identified using a label-free Quadrupole-Orbitrap LC-MS/MS system. The results were analyzed by the protein database search algorithm SEQUEST-HT to identify mass spectra to peptides. The predictive abilities of combinations of host markers were investigated by General Discriminant Analysis (GDA), with Leave-One-Out Cross- Validation (LOOCV). Results: A total of 572 proteins were identified and 549 proteins were quantified. The threshold for DEPs was set as adjusted p-value< 0.05 and fold change ≥1.5 or ≤0.6667, 32 DEPs were found. ClusterVis, TBtools, and STRING were used to find new potential biomarkers of PTB. Six proteins, LY6D, DSC3, CDSN, FABP5, SERPINB12, and SLURP1, which performed well in the LOOCV method validation, were termed as potential biomarkers. The percentage of cross-validated grouped cases correctly classified and original grouped cases correctly classified is greater than or equal to 91.7%. Conclusion: We successfully identified five candidate biomarkers for immunodiagnosis of PTB in plasma, LY6D, DSC3, CDSN, SERPINB12, and SLURP1. Our work supported this group of proteins as potential biomarkers for PTB, and be worthy of further validation.

Submerged plants in wetlands play important roles as ecosystem engineers to improve self-purification and promote elemental cycling. However, their effects on the functional capacity of microbial communities in wetland sediments remain poorly understood. Here, we provide detailed metagenomic insights into the biogeochemical potential of microbial communities in wetland sediments with and without submerged plants (i.e., Vallisneria natans). A large number of functional genes involved in carbon (C), nitrogen (N) and sulfur (S) cycling were detected in the wetland sediments. However, most functional genes showed higher abundance in sediments with submerged plants than in those without plants. Based on the comparison of annotated functional genes in the N and S cycling databases (i.e., NCycDB and SCycDB), we found that genes involved in nitrogen fixation (e.g., nifD/H/K/W), assimilatory nitrate reduction (e.g., nasAand nirA), denitrification (e.g., nirK/Sand nosZ), assimilatory sulfate reduction (e.g., cysD/H/J/N/Qand sir), and sulfur oxidation (e.g., glpE, soeA, sqrand sseA) were significantly higher (corrected p< 0.05) in vegetated vs. unvegetated sediments. This could be mainly driven by environmental factors including total phosphorus, total nitrogen, and C:N ratio. The binning of metagenomes further revealed that some archaeal taxa could have the potential of methane metabolism including hydrogenotrophic, acetoclastic, and methylotrophic methanogenesis, which are crucial to the wetland methane budget and carbon cycling. This study opens a new avenue for linking submerged plants with microbial functions, and has further implications for understanding global carbon, nitrogen and sulfur cycling in wetland ecosystems.

Lithium-ion battery (LIB) nowadays plays a key role as one of the most widely used energy storage technologies such as the application in electric vehicles. Thermal management critically affects the performance of LIB. Phase change cooling using phase change material (PCM) has become a promising method due to its high latent heat and no need to consume extra pump power. In this study, thermal performance of a battery module with 25-parallel 18650 lithium-ion battery has been numerically and experimentally investigated by adopting phase change cooling with PCM. Firstly, the internal resistance of the unit cell has been experimentally tested to build up the heat generation model. Based on the heat generation model and heat transfer model, the effects of PCMs thermophysical parameters including thermal conductivity, latent heat and porosity are investigated when they are applied in the thermal management of designed LIB module. The results indicate that the higher thermal conductivity and latent heat lead to better thermal management performance comprehensively considering the maximum temperature and temperature uniformity of LIB module. Results also illustrate that thermal management performance increases very slightly when the thermal conductivity and latent heat attain a relatively high value. As for the porosity of paraffin/metal foam, an optimal value of 94% exists to achieve the lowest maximum temperature for LIB module.

As a rescue vehicle, damaged-aircraft trailer is used to move damaged aircraft quickly to restore the normal order of the airport. Several damaged-aircraft trailer parameters such as tire stiffness and damping of the suspension hydraulic system influence the dynamic performance significantly. In this article, a simplified 9 degrees of freedom model of damaged-aircraft trailer is established considering the physical parameters of suspension and tires. The relationships among the parameters of the suspension hydraulic components, the elastic force and damping force are established, and then the optimization model of the whole vehicle is obtained. In order to reduce the secondary damage to the aircraft, the multi-island genetic algorithm is used to optimize the suspension system and tire. During the calculation, the maximum vertical acceleration of damaged-aircraft trailer is taken as objective function for variable parameters of the suspension hydraulic system and the tire. As a result, the performance of the vehicle is greatly improved with the maximum acceleration of 0.2 m/s2after optimization.

ABSTRACTSince severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread from the early epicenter, Wuhan, to the rest of China, the virulence of SARS-CoV-2 might have evolved at different phases of the pandemic. We therefore compared the unique features among 62 coronavirus disease 2019 (COVID-19) inpatients who contracted SARS-CoV-2 in Wuhan (15 cases), exposed to the patients from Wuhan (26 cases), or acquired the disease without exposure to Wuhan patients (21 cases). Median incubation periods are 4.5 days (3–5) for Wuhan patients, 8 days (3–11) for those infected by Wuhan patients, and 12 days (7–13) for those without aforementioned experience. The disease onset dates are earliest for Wuhan patients and latest for those without exposure to Wuhan patients. Blood lymphocytes were lowest in Wuhan patients, lower in those affected by Wuhan patients, and modest reduced in remaining ones. Disease severity is worst for Wuhan patients, and modest for those without contact with Wuhan patients. Wuhan patients had longest (27 days, 18–28), those transmitted by Wuhan patients had intermediate (16 days, 8–23), and the rest of the patients had shortest (13 days, 8.5–22.5) hospital stay. Early viral exposure, older age, lymphocytopenia, and underlying conditions are risk factors which warrant aggressive intervention. Even though the virulence of SARS-CoV-2 appears decline over the course of serial transmissions, viral testing, contact tracing, social distancing, and face masking should be imposed on general public to contain viral dissemination from both symptomatic and asymptomatic patients with this highly contagious disease.

•The composite sorbent material SrCl2-ENG under various mixture ratios was developed.•Heat and mass transfer performance of the composite materials were investigated.•The sorption performance for refrigeration application was studied.

A damaged aircraft trailer is an essential piece of airport emergency rescue equipment which is made up of frames and multiple suspensions. As a load–force transferring mechanism, the suspension bears heavy loads which can cause fatigue damage. Therefore, reducing the maximum stress of the suspension is necessary to improve the vehicle performance. Besides, lightweight design should be considered to reduce energy consumption. Thus, lighter suspension which can bear more pressure is the optimization objective of this research. A multi-objective optimization method was carried out to analyze the suspension arm of a damaged aircraft trailer. Firstly, to investigate the dynamic characteristics and the reliability of the damaged aircraft trailer, a detailed three combined damaged aircraft trailers model was built. Based on the flexible-rigid coupled method, dynamic simulation of the damaged aircraft trailer was conducted in MSC.ADAMS. Then a suspension model was established, and the stress under different loads was measured to verify the accuracy of the finite element suspension arm model by experiments. Based on the design of experiment method, the effect of suspension arm parameters were obtained to build the approximate models. Besides, the influences of some effect parameters on optimal objectives were analyzed based on the surface response method. During the optimization process, a non-dominated sorting genetic algorithm II was adopted to optimize the mass and stress of the suspension arm. The results show that the mass of the suspension arm is reduced from 146.81 kg to 126.69 kg, which is a reduction of 14%. The maximum von Mises stress is changed from 325 MPa to 297 MPa, which is a decrease of 8.6%. This optimal method can be extended to the overall vehicle, which has an important significance in the whole damaged aircraft trailer characteristics improvement design.

There is temperature unevenness inside the operating battery, and the internal temperature distribution of the battery has gradually attracted attention. To establish a thermal model of the 21,700 cylindrical battery that can reflect the internal temperature distribution, thermophysical parameters including anisotropic thermal conductivity and specific heat capacity are tested through experiments. The thermal model includes the heat generation part and heat transfer part. Thermophysical parameters are essential for the heat transfer part. Hybrid pulse power characterization (HPPC) tests are carried out to obtain battery internal resistance, and the entropy coefficient of the battery is also obtained by tests. Internal resistance and entropy coefficient data are used as inputs for the battery heat generation part. The core temperature and surface temperature of the operating battery are measured by the thermocouple embedded inside the battery and the thermocouple pasted on the battery surface. The calculated core and surface temperatures from the battery thermal model are both in good agreement with the measured temperature results. The maximum core temperature of 2C discharging battery is about 60 °C and the maximum temperature difference inside the 21,700 battery reaches 3 °C. The established simulation model can be used for extended research work. When heat dissipation is enhanced by increasing the convection heat transfer coefficient, the overall temperature of the battery decreases but the temperature non-uniformity inside the battery is aggravated.

ABSTRACTLncRNA in non-homologous end joining (NHEJ) pathway 1 (LINP1) is an lncRNA which promotes therapeutic resistance in triple-negative breast cancer (TNBC). However, the expression and function of LINP1 in cervical cancer is not yet well-understood. In this study, we evaluated the expression levels of LINP1 in tumor tissues and cell lines of cervical cancer. We found that LINP1 associates with NHEJ proteins (Ku80 and DNA-PKcs). LINP1 translocates from cytosol to nucleus in response to irradiation. In addition, LINP1 knockdown significantly increases the levels of cleaved caspase3 and PARP, leading to enhanced cell apoptosis after ionizing radiation (IR). LINP1-knockdown cells showed delayed repairs of DNA double-strand breaks (DSBs) after IR. Finally, LINP1 knockdown increases radiosensitivity of Hela S3 cells. These results suggest that LINP1 facilitates DSBs repair through NHEJ pathway and may thus serve as a prognostic marker and a potential target for the therapy of cervical cancer.

To study the pressure distribution of the volute casing, front casing and back casing in a prototype centrifugal pump, the pressure experiments and numerical simulations are carried out at six working conditions in this paper. The experimental results shows that the asymmetry of static pressure distribution on volute casing and front cavity is caused by the tongue of the volute and it may result in high radial and axial resultant force which can cause vibration and noise in the centrifugal pump. With the increasing of flow rate, the asymmetry of static pressure distribution and the magnitude of static pressure values reduce. The numerical results indicate that the pressure fluctuation near the tongue is strongest and it becomes slighter at point away from the tongue. With the increasing of flow rate, the local high-pressure region in impeller passage reduces and the flow becomes smoother accordingly, whereas the fluid speed becomes much higher which may cause further flow losses. The results predicted by numerical simulation are in coincident with the experimental ones. It shows that the turbulence model for simulating the flow field in centrifugal pumps is feasible.

Background:Neuroinflammation is ubiquitous in acute stroke and worsens outcome. However, the precise timing of the inflammatory response is unknown, hindering the design of acute anti-inflammatory therapeutic interventions. We used a mobile stroke unit (MSU) to identify the onset of the neuroinflammatory cascade within minutes of symptom onset.Methods:The study is a prospective, cohort investigation of ultra-early blood- and extracellular vesicle (EV)-derived markers of neuroinflammation and outcome in acute stroke. Blood was obtained on the MSU with head CT, and from healthy controls. Plasma biomarkers were analyzed with ELISA, SIMOA and ECL. EVs were isolated with HSP pull down. Confirmed strokes, mimics and healthy controls were compared. Variables included demographics, mRS, NIHSS and discharge disposition.Results:Forty one adults were analyzed, including 15 patients treated on the MSU between August 2021 and April 2022, and 26 controls. For MSU patients, median age was 74 (range 36-97) years, 60% were female, and 80% white. Ten (67%) were diagnosed as stroke, with 8 (53%) confirmed and 2 likely TIA or stroke averted by thrombolysis; 5 were stroke mimics. For strokes, median initial NIHSS score was 11 (range 4-19) and 6 (75%) received tPA. Blood was obtained a median of 58 (range 36-133) minutes after symptom onset. Within 36 minutes after stroke, plasma interleukin-6 (IL-6), neurofilament light chain (NfL), ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were elevated by as much as 10 times normal. In EVs, matrix metalloproteinase-9 (MMP-9), chemokine (C-X-C motif) ligand 4 (CXCL4), C-reactive protein (CRP), IL-6, osteopontin (OPN) and platelet and endothelial cell adhesion molecule 1 (PECAM1) were elevated. Inflammatory markers increased rapidly in the first two hours, and continued rising for 24 hours.Conclusions:This study found the inflammatory cascade is activated as early as 36 minutes after stroke, and progresses rapidly. This is earlier than observed previously in humans, and suggests injury from neuroinflammation may occur faster than had been surmised. The findings may inform development of immunomodulatory therapies for acute stroke, and lead to new diagnostic tools and improved outcomes.

•Performance of liquid cooling plate for high power density IGBT modules is analyzed.•Effects of flow channel numbers, widths and heights comprehensively considered.•Different flow channel shapes are designed and their performance are compared.•There is a trade-off effect between the cooling performance and pressure drop.•Arc-shaped channel has comprehensively better cooling performance and pressure drop.

Heat generation measurements of the lithium-ion battery are crucial for the design of the battery thermal management system. Most previous works use the accelerating rate calorimeter (ARC) to test heat generation of batteries. However, utilizing ARC can only obtain heat generation of the battery operating under the adiabatic condition, deviating from common operation scenarios with heat dissipation. Besides, using ARC is difficult to measure heat generation of the high-rate operating battery because the battery temperature easily exceeds the maximum safety limit. To address these problems, we propose a novel method to obtain heat generation of cylindrical battery based on core and surface temperature measurements and select the 21700 cylindrical battery as the research object. Based on the method, total heat generation at 1 C discharge rate under the natural convection air cooling condition in the environmental chamber is about 3.2 kJ, and the average heat generation rate is about 0.9 W, while these two results measured by ARC are about 2.2 kJ and 0.6 W. This gap also reflects that different battery temperature histories have significant impacts on heat generation. In addition, using our approach, total heat generation at 2 C discharge rate measured in the environmental chamber is about 5.0 kJ, with the average heat generation rate being about 2.8 W. Heat generation results obtained by our method are approximate to the actual battery operation and have advantages in future applications.

In this paper, we propose a new family of block ciphers named DBlock. It consists of three variants which are specified as DBlock-128, DBlock-192, and DBlock-256, respectively. DBlock-nhas the equal n-bit block length and key length. The structure of DBlock successfully combines the advantages of Feistel and Type-2 generalized Feistel structures together. Also, its design of round function employs different linear transforms operating on various word-sizes, which efficiently improve the diffusion effect. For key schedule of DBlock, it basically employs the same module used in encryption, except the choice of different byte permutations, which can improve its suitability for various implementation environments and also enhance its security against many cryptanalytic techniques. Our preliminary evaluation shows that DBlock can achieve enough security margin against known attacks, and it can also obtain excellent performances on various software and hardware platforms.

This paper investigates the feasibility of applying a compressed air powertrain to mine rescue vehicles, which require strict explosion-proof and flame-proof characteristics. Based on both simulation and preliminary tests of a single-cylinder air-powered engine prototype, the concept of compressed air powertrain for a rescue vehicle is proposed. Compared to conventional internal combustion engines, the exhaust emissions of the proposed air-powered engine concept are innoxious and its gas temperature is very low, which guarantees the safety and explosion-proof requirements. Preliminary selection and matching of both a transmission and final gear reduction are carried out, considering vehicle traction and air consumption performance characteristics. Simulation results show that given properly designed drivetrain gear ratios, the air-powered rescue vehicle can reach a speed of 7 km/h with gear 1 on a 30% slope road. Compared to current products, its feasibility in driving mileage and traction performance are further confirmed.

The paper proposes a novel pneumatic-fuel hybrid system, which combines a traditional internal combustion engine (ICE) and a pneumatic engine. One important merit of this concept is that the system can recover waste from cooling water of internal combustion engine to optimize the working process of pneumatic engine, and thus to improve the entire efficiency of the hybrid system. Meanwhile, energy-saving effect due to lower cooling fan power can be achieved on ICE by waste heat recovery of pneumatic engine. Based on thermodynamic analysis, an experimental system is designed and established for verification. The experimental results show that the performance of pneumatic engine is improved when the waste heat recovery concept of the hybrid system is applied. Then an application example on a 4-cylinder engine is analyzed and discussed using numerical simulation. The results show that the fan power of the ICE cooling system can be saved up to 50% by applying the hybrid system. Considering the appreciable improvements on the energy efficiency with only limited system modifications when the concept is applied to traditional ICE based power systems, the proposed hybrid concept has the potential to serve as an alternative technology aiming for energy saving and emission reduction.

In this study, a two-dimensional, depth-averaged computational model (River2DMix) was used to predict the flow pattern and residence time distribution for flow through the Calgary Glenmore Water Treatment Plant northeast clearwell. Results are compared to those from flow visualization and tracer studies in a 1  :  19 scale model of the clearwell, as well as tracer studies conducted at the plant. Tests were carried out for three flow rates that ranged from minimum to maximum operating conditions. A key observation in the physical model was that it was necessary to let the flow fully develop before starting a tracer test to determine the residence time distribution. This flow development time to achieve steady-state results was approximately 10·5  h at the minimum flow rate tested. Results also show that it was unnecessary to model the structural columns either in the simulation or the scale model for developed flow in this clearwell, although for undeveloped or transient flow conditions the columns were important to consider.

•Charging performance of fin-tube LTES is analyzed under fluctuating heat source.•Effects of critical aspects including fin layouts and eccentricity are considered.•Fin height dominates the charging rate and density compared to angle and thickness.•Eccentric layout improves heat storage capacity of LTES under fluctuating heat source.

To expand the application and the added value of rare earth compounds, it was utilized to enhance fire safety of flexible polyurethane foam (FPUF) in furniture field. La2Sn2O7with pyrochlore structure was utilized to wrap ammonium polyphosphate (APP), forming a novel core-shell structure compound(LAPP) and used in FPUF. Compared to pure FPUF, the peak of heat release (PHRR) and peak of smoke production rate (PSPR) of FPUF composites were reduced by 37.5% and 33.3%, respectively. Moreover, the released toxic gases (such as, CO, CO2, NO and NO2) during combustion were dramatically decreased. This is due to the LAPP not only exerted the combustion catalysis toxic gases and smoke reduction effect, but also enhanced the char residue with high quality and quantity. Therefore, to make full use of China's rare earth resources, it provides a facile and effective strategy to fabricate polymer composites with high fire safety for the furniture field.

Tumor bed (TB) change is often seen during the whole breast irradiation (WBI) in early breast cancer patients. The aims of this study were to evaluate change in seroma volume on repeat CTs and to explore whether replanning is necessary in breast conserving radiotherapy (RT) using the intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB). Thirty patients underwent WBI with 84 CT scans (24 with 3 CTs (CT1, CT2 and CT3) and 6 without CT3) during the 6 weeks of RT were reviewed. TB and other target volumes on all CTs were delineated and compared. IMRT-SIB treatment plans with 50.68 Gy to the whole breast and 64.4 Gy to the boost in 28 fractions were constructed in the CT1. Replan and hybrid plan (without replanning) in the CT2 were reproduced. Dosimetric differences between the replans and hybrid plans were also compared. The mean TB volumes for CT1, CT2 and CT3 were 42.1 cm3, 20.1 cm3, 17.0 cm3, respectively. The mean TB volume reduction was 40.5% from the CT1 to CT2 and 4.3% from the CT2 to CT3. The difference of TB volumes between the CT1 and CT2 was statistically significance (p< 0.001), but not significant between the CT2 and CT3 (p= 1.000). For all patients, target coverage remained adequate with either hybrid plans or replans. However, replanning can significantly decrease the whole breast mean dose (35.2 vs. 35.6 Gy, p= 0.026) and breast volume outside the boost receiving 95% of the boost prescribed dose (39.5 vs. 68.2 cm3, p< 0.001). In summary, boost volume could irradiate adequately after the significance shrinkage of tumor bed with the fractionated schedule of IMRT-SIB, but replanning on a second CT could avoid the undesired high dose irradiated breast_tissue outside boost.

Carboxyamidotrizole (CAI) has been reported to suppress the production of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β and be effective in rats with adjuvant arthritis. The aim of this study was to investigate the role of CAI in inflammatory bowel disease (IBD). We assessed the effect of CAI in dextran sodium sulfate-induced colitis. Inflammation was scored histologically, and potential mediators of IBD were assessed by immunohistochemical and molecular biochemical approaches. CAI-treated colitis animals revealed much fewer signs of colitis with significantly decreased macroscopic and microscopic scores than vehicle-treated animals. CAI inhibited the production of TNF-α, IL-1β, and IL-6 in serum, supernatant of peritoneal macrophages, and lamina propria. CAI also decreased the expression of intercellular adhesion molecule-1 in colonic tissues. Furthermore, CAI prevented nuclear factor-κB (NF-κB) activation and inhibitor of nuclear factor-κBα phosphorylation and degradation. In addition, CAI showed a beneficial effect on colonic fibrosis, possibly by reducing the production of the fibrogenic cytokine transforming growth factor-β. The results support that CAI administration is effective in ameliorating experimental colitis and preventing colonic fibrosis. The inhibition of proinflammatory cytokines and adhesion molecules and suppression of NF-κB activation seem to contribute to this effect.

•A SoC estimation method based on a fusion of cubature Kalman filters is proposed.•The accuracy difference between two cubature Kalman filters is explored.•The impact of the filters’ initial weights on the fusion method is analyzed.•The proposed method can improve the SoC estimation accuracy.

Carboxyamidotriazole (CAI) is a calcium influx inhibitor that is undergoing clinical trials for the treatment of various human cancers following the identification of its antiproliferative and antimetastatic activities. The exact mechanism of its action is not clearly understood, and whether it has other functions besides the established antitumor activity has not been reported either. In the present study, we demonstrate for the first time that CAI possesses anti-inflammatory and analgesic activities using a variety of animal models, including croton oil-induced ear edema, cotton-induced granuloma, rat adjuvant-induced arthritis, acetic acid-induced writhing, and the formalin test. We also show that CAI significantly inhibits local vascular permeability stimulated by vascular endothelial growth factor or histamine and decreases tumor necrosis factor-alpha and interleukin-1beta levels at the site of inflammation and in serums, which may contribute to the anti-inflammatory effect. These data suggest that CAI is a promising anti-inflammatory and analgesic agent, and they provide new insight into the biological activity of the drug.

Our group has demonstrated that tangential radiation therapy (RT) to the left breast or chest wall can cause perfusion changes in the anterior myocardium. We assess if RT-induced perfusion changes are associated with the development of symptoms consistent with cardiac dysfunction. Between 1998 and 2001, 114 patients were enrolled into an institutional review board—approved prospective study and had pre-RT and serial post-RT (range, 6-24 months) single photon emission computed tomography (SPECT) scans to assess changes in regional cardiac perfusion. Thirty-one patients were excluded. The incidence of cardiac symptoms in patients with and without RT-induced perfusion defects was compared using a 2-tailed Fisher's exact test. With a median follow-up of 16 months (range, 6-24 months), 10 of 83 evaluable patients had ≥ 1 episode of transient chest pain, occurring 0-14 months after RT (median, 6 months). The rates of chest pain in the patients with and without new perfusion defects were 9 of 31 and 1 of 52, respectively (P= 0.0004). A similar result was found when patients were segregated based on the use of chemotherapy. Two of these 10 cases were diagnosed as pericarditis. No patient had myocardial infarction or congestive heart failure. Cardiac symptoms occur more frequently in patients with perfusion abnormalities by SPECT after RT than in patients with normal SPECT scans, suggesting that such perfusion defects may be clinically significant. One confounding factor is that women who know they have RT-induced perfusion defects may be more likely to report episode of chest pain. Long-term follow-up will be necessary to better assess the clinical significance of RT-induced perfusion defects.

The closer muscle of large-clawed decapod crustaceans undergoes a proecdysial (premolt) atrophy to facilitate withdrawal of the appendage at ecdysis. This atrophy involves the activation of both calcium-dependent (calpains) and ubiquitin (Ub)/proteasome-dependent proteolytic systems that break down proteins to reduce muscle mass. Moreover, the large slow-twitch (S1) fibers undergo a greater atrophy than the small slow-tonic (S2) fibers. Both polyUb mRNA and Ub-protein conjugates increase during claw muscle atrophy. In this study in situ hybridization and RT-PCR were used to determine the temporal and spatial expression of polyUb and α-actin. A cDNA encoding the complete sequence of lobster muscle α-actin was characterized; a probe synthesized from the cDNA provided a positive control for optimizing RT-PCR and in situ hybridization. PolyUb was expressed at low levels in claw closer muscle from anecdysial (intermolt) land crab. By early proecdysis (premolt; stage D0), polyUb mRNA levels increased in medial fibers that insert along the midline of the apodeme, with greater expression in S1 than S2, while levels remained low in peripheral fibers. By late proecdysis, polyUb mRNA decreased in central fibers, while mRNA increased in peripheral S1 fibers. In contrast, α-actin was expressed in lobster claw muscles at relatively constant levels during the intermolt cycle. These results suggest that Ub/proteasome-dependent proteolysis contributes to enhanced turnover of myofibrillar proteins during claw closer muscle atrophy. Furthermore, atrophy is not synchronous within the muscle; it begins in medial fibers and then progresses peripherally. J. Exp. Zool. 292:618–632, 2002. © 2002 Wiley-Liss, Inc.

Emission free compressed air powered energy system can be used as the main power source or as an auxiliary power unit in vehicular transportation with advantages of zero carbon emissions and improved the overall energy efficiency of the integrated energy system. This work presented a detailed technological development of compressed-air energy systems. The studies on compressed-air powered powertrain in transport sector are summarised including the design of new valve technologies, prototype developments, and integration of the system. Furthermore, compressed-air based hybrid technologies using different pneumatic hybridisation methods are comprehensively presented aiming to provide in-depth insight on the advantages and limitations of different pneumatic hybridisation. The opportunities and challenges for the compressed-air based technology in transport application are discussed. It can be expected the transformation of energy systems to a cleaner and more sustainable future would promote the technological development and implementation of Zero-Emission compressed air solutions.

Increased immunoglobulin G (IgG) antibodies and oligoclonal bands (OCB) are the most characteristic features of multiple sclerosis (MS), a neuroinflammatory demyelinating disease with neurodegeneration at chronic stages. OCB are shown to be associated with disease activity and brain atrophy. Despite intensive research over the last several decades, the antigen specificities of the IgG in MS have remained elusive. We present evidence which supports that intrathecal IgG is not driven by antigen-stimulation, therefore provide reasoning for failed MS antigen identification. Further, the presence of co-deposition of IgG and activated complement products in MS lesions suggest that the IgG effector functions may play a critical role in disease pathogenesis.

The study compares the physical and biologically effective doses (BED) received by the heart and cardiac substructures using three-dimensional conformal RT (3D-CRT), intensity-modulated radiotherapy (IMRT), and simple IMRT (s-IMRT) in postoperative radiotherapy for patients with left-sided breast cancer.