Antitumor effects of an engineered and energized fusion protein consisting of an anti-CD20 scFv fragment and lidamycin

Antibody-based fusion proteins are the next generation of antibody therapies for cancer and other diseases.CD20 antigen,which is overexpressed on cell membranes in nearly 95% of cases of B-cell Non-Hodgkin's Lymphoma,is an attractive target for the therapy of B-lymphoid malignancies.Lidamycin (LDM) is a potent enediyne-containing antitumor antibiotic that now has entered phase II clinical trials.In this study,we prepared an engineered fusion protein,scFv-LDP,consisting of an anti-CD20 scFv fragment and the apoprotein LDP of LDM using DNA recombination.After purification and refolding,scFv-LDP was found to bind specifically to CD20-positive lymphoma cells using ELISA and indirect immunofluorescent cytochemical staining assays.The energized fusion protein scFv-LDP-AE was obtained using molecular reconstitution of the active chromophore AE of LDM and scFv-LDP.MTT assay revealed potent cytotoxicity of scFv-LDP-AE to CD20-positive Raji and Daudi cells,with IC 50 values of 1.21×10-11 and 6.24×10-11 mol L-1,respectively.An in vivo subcutaneous xenograft model of CD20-positive B cell lymphoma in BALB/c (nu/nu) mice was also utilized.Drugs were given intravenously on day 14 and 21 after tumor transplantation.In terms of maximal tolerated doses,scFv-LDP-AE at 0.3 mg kg-1 suppressed tumor growth by 79.3%,and LDM at 0.05 mg kg-1 by 68.6% (P<0.05).Results suggested scFv-LDP-AE could be a potential candidate for tumor-targeting therapy.

Numerical and experimental analysis of the reusability of spring energized metal C rings

It is well known that static seals are usually designed to be used once. In this paper, we discuss the reusability of a type of static seal called the spring energized metal C ring, which is required to be reused 4-5 times without maintenance during the lifetime of the pump. A theoretical analysis based on the nonlinear finite element method and an experimental investigation of the reusability of the C ring are carried out. The effects of the elastic modulus of the ring material, the ring wall thickness, the amount of assembly interference between the spring and the C ring, the operating temperature and the compression ratio are discussed. The parameter S, which denotes the reaction force difference percentage, is determined to measure the reusability of the C ring. The results show that the ring wall thickness plays an important role in the reusability. Although the normal force of a thick wall decreases after the ring is reused eight times, the value is still higher than the first normal force of a thin wall. In contrast, the elastic modulus of the material has the lowest impact. Here, a pre-compression ratio of 18.2% not only produces a larger first normal force but also leads to a smaller reduction in the normal force when the ring is reused. A simulated experiment is carried out to investigate the influence of the coating of the C ring on its reusability. The results show that when plastic deformation occurs on the contact surface, the contact state of the C ring coating becomes a major factor that affects the seal performance. Aging treatment at high temperatures （250℃） reduces gized metal C ring, which leads to the deterioration in the reusability the binding force of the silver coating on the spring ener of the ring.

The influence of boundary conditions on the distribution of energetic electrons during collisionless magnetic reconnection

We conducted 2-D particle-in-cell simulations to investigate the impact of boundary conditions on the evolution of magnetic reconnection. The results demonstrate that the boundary conditions are crucial to this evolution. Specifically, in the cases of traditional periodic boundary(PB) and fully-opened boundary(OB) conditions, the evolutions are quite similar before the system achieves the fastest reconnection rate. However, differences emerge between the two cases afterward. In the PB case, the reconnection electric field experiences a rapid decline and even becomes negative, indicating a reversal of the reconnection process. In contrast, the system maintains a fast reconnection stage in the OB case. Suprathermal electrons are generated near the separatrix and in the exhaust region of both simulation cases. In the electron density depletion layer and the dipolarization front region, a larger proportion of suprathermal electrons are produced in the OB case. Medium-energy electrons are mainly located in the vicinity of the X-line and downstream of the reconnection site in both cases. However, in the OB case, they can also be generated in the electron holes along the separatrix. Before the reverse reconnection stage, no high-energy electrons are present in the PB case. In contrast, about 20% of the electrons in the thin and elongated electron current layer are high-energy in the OB case.

An Energized Alliance

China and its Central Asian neighbors forge crossborder partnerships in energy, culture, education and security The China-Central Asia natural gas pipeline, inaugurated during President Hu Jintao’s recent visit to Turkmenistan,

片状气体放电电子束强度与能量分布的实验研究

片状气体放电电子束强度与能量分布的实验研究罗宗南，崔一平，陈松生，杨正名（东南大学电子工程系．南京２１００１８）气体放电电子束强度高，能量大，在微电子、光电子、加工、材料科学、等离子化学以及表面处理等方面有着广泛的应用前景，加以成本低廉、操作方便，是...

Study on Electrokinetic Remediation of Cadmium-contaminated Soil

[Objectives] This study was conducted to explore the effect of electrokinetic remediation of Cd-contaminated soil.[Methods] By preparing Cd-contaminated soil and constructing an electrokinetic remediation experimental device,the effects of changing remediation time,voltage gradient,electrolyte type and power-on method on the removal rate of Cd were studied.[Results]When the voltage gradient was increased from 0.5 to 1.0 V/cm,the total Cd removal rate increased by 13%;and when the voltage gradient was increased from 1.0 to 1.5 V/cm,the total Cd removal rate only increased by 3%.Compared with 72 h of electrokinetic remediation,96 h of remediation increased the remediation rate by 4%,and the total energy consumption increased by 13%,while 120 h of remediation increased the remediation rate by 6.5%,and the total energy consumption increased by 67%.Compared with citric acid as electrolyte,the remediation rate of the acetic acid group increased by 12%,and the total energy consumption increased by 42%,while the remediation rate of the hydrochloric acid group increased by18%,and the total energy consumption increased by 70.5%.Compared with the conventional remediation method,the total Cd removal rates achieved by the different power-on methods increased by 9% and 31%,respectively,and the total energy consumption decreased by 58% and 45%,respectively.[Conclusions]The electrokinetic remediation technology has certain advantage in remediating Cd-contaminated soil.

Effects of Malonaldehyde Contents in Eschar Extract on Mitochondric Respiratory Function and Energization of the Inner Membrane

Extract of the eschar tissue taken from the rat which had been given full-thickness burn of20% TBSA was found to be inhibitory to the respiratory function of the mitochondria and theenergization of the inner membrane. The inhibition was also demonstrated by the 1: 2 and 1: 4and 1: 8 dilutions of the eschar extract. The extract of normal skin only showed weak inhibitory cf-fect. The 1: 4 dilution of normal skin had no (?) on mitochondrial functions. There is a widegap between the malonaldehyde (MDA) contents of these two kinds of extracts. An apparent posi-tive correlation was found between MDA content and degree of inhibition. However, on close ex-amination, it was found that the MDA content is not the direct cause of the decrease of therespiratory control ratio (RCR). The increase of MDA content is probably related to the destruc-tion of the lipid bilayer of the mitochondria. Data from the energization experiment show that theenergization process is compromised when the destruction of the membrane has proceeded to a cer-tain degrce. The inhibition of mitochondrial respiratory function becomes evident when encrgizationfunction is still normal. Therefore at least two mechanisms are operating in the inhibition process.Further work is needed to elucidate the problem.

Observation and Modeling of Geostationary Orbit Electron Energization Induced by Enhanced Dayside Whistler-Mode Waves

We provide correlated observations of enhanced dayside whistler-mode waves and energetic electron acceleration collected by the CLUSTER and GOES satellites during the 23～24 September 2001 storm. Energetic （〉0.6 MeV） electron fluxes are found to increase significantly during the recovery phase and the main phase, by a factor of～50 higher than the prestorm level. These high electron fluxes occur when strong dayside whistler-mode waves are present. Two-dimensional （2D） numerical simulations are carried out and the results demonstrate that the dayside whistler-mode wave can contribute to such enhancements in electron flux within 24 h, consistent with the observation.

Observations of kinetic Alfvén waves and associated electron acceleration in the plasma sheet boundary layer

Kinetic Alfvén waves(KAWs),with a strong parallel disturbed electric field,play an important role in energy transport and particle acceleration in the magnetotail.On the basis of high-resolution observations of the Magnetospheric Multiscale(MMS)Mission,we present a detailed description of the acceleration process of electrons by KAWs in the plasma sheet boundary layer(PSBL).The MMS observed strong electromagnetic disturbances carrying a parallel disturbed electric field with an amplitude of up to 8 mV/m.The measured ratio of the electric to magnetic field perturbations was larger than the local Alfvén speed and was enhanced as the frequency increased,consistent with the theoretical predictions for KAWs.This evidence indicates that the electromagnetic disturbances should be identified as KAWs.During the KAWs,the energy flux of electrons at energies above 1 keV in the parallel and anti-parallel directions are significantly enhanced,implying occurrences of electron beams at higher energies.Additionally,the KAWs became more electrostaticlike and filled with high-frequency ion acoustic waves.The energy enhancement of electron beams is in accordance with the derived work done with the observed parallel disturbed electric field of KAWs,indicating electron acceleration caused by KAWs.Therefore,these results provide direct evidence of electron acceleration by KAWs embodying electrostatic ion acoustic waves in the PSBL.

Investigation and Mitigation of Transformer Inrush Current during Black Start of an Independent Power Producer Plant

The energizing of large power transformers has long been considered a critical event in the operation of an electric power system. When a transformer is energized by the utility, a typical inrush current could be as high as ten times its rated current. This could cause many problems from mechanical stress on transformer windings to harmonics injection, and system protection malfunction. There have been numerous researches focusing on calculation and mitigation of the transformer inrush current. With the development of smart grid, distributed generation from independent power producers (IPPs) is growing rapidly. This paper investigates the inrush current due to black start of an IPP system with several parallel transformers, through a simulation model in DIgSILENT Power Factory software. The study demonstrates that a single genset is capable of energizing a group of transformers since the overall inrush current is slightly above the inrush of the transformer directly connected to the generator. In addition, a simple method is proposed to mitigate the inrush current of the transformers using an auxiliary transformer.

Intelligent Control of SIRES Using Neural Networks and Fuzzy Logic

Development of energy-resources-poor remote rural areas of the world has been discussed by many in the past. Harnessing locally available renewable energy resources as an environmentally friendly option is gaining momentum. Smart Integrated Renewable Energy Systems (SIRES) offer a resilient and economic path to “energize” the area and reach this goal. This paper discusses its intelligent control using neural networks and fuzzy logic.

Clinical Study on the Retention Enema with Modified Dahuang Mudan Decoction in Treating Lower-Jiao Obstruction Syndrome Caused by Severe Pneumonia Complicated with Heart Failure

[Objectives]To treat patients with Lower-Jiao Obstruction Syndrome caused by severe pneumonia complicated with heart failure using the retention enema with Modified Dahuang Mudan Decoction,and to observe the effect and safety of this treatment on inflammatory indicators,cardiac function,gastrointestinal function and multiple organ failure in patients with Lower-Jiao(lower energizer)Obstruction Syndrome caused by severe pneumonia complicated with heart failure.[Methods]54 patients with Lower-Jiao Obstruction Syndrome caused by severe pneumonia complicated with heart failure diagnosed in Nanchong Chinese Medicine Hospital from January 2020 to December 2021 were randomly divided into experimental group(n=27)and control group(n=27).The control group was given conventional treatment combined with 0.9%sodium chloride injection(100 mL)+glycerine enema(40 mL).The treatment group was treated with Modified Dahuang Mudan Decoction on the basis of conventional treatment for 7 d.The efficacy indicators and adverse events such as white blood count(WBC),C-reactive protein(CRP),procalcitonin(PCT),N-terminal pro-brain natriuretic peptide(NT-proBNP),Lausanne Intestinal Failure Estimation(LIFE)and multiple organ dysfunction score(MODS)were observed.[Results](i)There was no significant difference in WBC,PCT,CRP and NT-proBNP between the two groups before treatment.All indicators after treatment were significantly lower than those before treatment in both groups(P<0.05).The levels of WBC,PCT and CRP in the treatment group were lower than those in the control group after treatment(P<0.05),and there was no significant difference in NT-proBNP between the two groups after treatment(P>0.05),but the difference in NT-proBNP before and after treatment in the treatment group was higher than that in the control group.(ii)The LIFE of the two groups decreased significantly after treatment,and the improvement of LIFE of the treatment group was better than that of the control group(P<0.05).(iii)The MODS of the two groups decreased significantly after treatment(P<0.05),and the degree of decrease after treatment in the treatment group was higher than that in the control group(P<0.05).(iv)There was no significant difference in all-cause mortality between the two groups(P>0.05).(v)No serious adverse events were found in both groups during the treatment period.[Conclusions]The conventional treatment,combined with the retention enema with Modified Dahuang Mudan Decoction could further reduce the inflammatory indicators,improve cardiac function,improve intestinal function and organ function,and the safety was good.

Discussion on Maxing Ganshi Decoction in the Treatment of COVID-19 Based on Triple Energizer Transmission Theory

COVID-19 is caused by novel coronavirus(2019-nCoV),which has the characteristics of strong infectivity,rapid onset and rapid spread.It is popular in China and other parts of the world,and there are no special drugs at present.This disease belongs to the category of plague in traditional Chinese medicine.Combined with the theory of triple energizer transmission in Yang Lishan's"Identification of Warm Disease",the confirmed case in our hospital was analyzed,and it was found that pathogenic qi entered from nose and mouth,injected into middle energizer,and then distributed in upper and lower energizer.The pathogenic qi is mainly diffused in the middle and upper energizer.Modified Maxing Ganshi decoction has a good effect.

Energization of a Half-Wavelength Transmission Line-Pre-Operational Transients Studies

In the present paper the main results of the pre-operational studies related to the energization maneuver of a Half-Wavelength Transmission Line (AC-Link), are presented. The simulations were performed in PSCAD with actual Brazilian system data. Specifically the following studies were performed: electromagnetic transient studies of energization maneuver considering no fault and the occurrence of fault along the trunk;dynamic analysis of generator units that will energize the AC-Link;TRV on the circuit-breaker that will energize the trunk. The main conclusion is that the AC-Link energization experiment can be implemented without jeopardizing or causing time-life reduction of the equipment involved in the experiment, which comprises the generator unit that will energize the trunk, the step-up transformer, the arresters that will be kept during the experiments, as well as the circuit-breaker that will energize and then trip the AC-Link.

Discussion on the Characteristics and Symptom Classification of COVID-19 in Chinese Medicine

Covid-19(Novel coronavirus pneumonia,NCP)was characterized by fever,dry cough,fatigue,greasy tongue coating and pulsating pulse.According to the literature,with those four symptoms,examination and identification,it is believed that NCP belongs to the category of "pandemic" in Chinese medicine.The main infection is dampness,infection location in triple energizer,the basic pathogenesis is characterized by "dampness,phlegm,blood stasis heat,toxin and deficiency."According to the law of blood transfer of symptom differentiation of triple energizer and weiqi-yingxue the treatment is divided into stages,such as early stage,middle stage,severe stage and recovery stage.Most of the patients were early stage and middle stage,which were the direct transmission of the disease.A small number of patients had the reverse transmission of pericardium and the internal and external detachment.The main method of treatment is to remove infection,remove dampness and detoxify.In addition,to grasp the treatment of early stage and middle stage patients,helps to stop the disease from developing,and it is the key to reduce the criticality of the disease,as well as reduce the mortality.

华为：规模商用全球的EnerG BTS解决方案

华为EnerG解决方案已经规模应用于全球80多个国家的150多个运营商,服务于全球2亿GSM用户,是全球TOP 50移动运营商中的26个全球领先运营商的合作伙伴,包括TELEFONICA、ORANGE、MTN、MTS、STC、ETISALAT、MIC、TM、MAXIS、OT、中国移动、中国联通等。GSM BTS全球部署超过10075载频。

Energizing Waste

THE 36-hectare Reppie Sanitary Landfill, also known as Qoshe. dirt in local slanG, has been Ethiopia＇s bisgest rubbish site for more than half a century. The landfill, located on the outskirts of Addis Ababa,

Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

Solute carriers(SLCs) constitute the largest superfamily of membrane transporter proteins.These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions.They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake(e.g., SLC2A4/GLUT4), glucose reabsorption(e.g., SLC5A2/SGLT2), thermogenesis(e.g., SLC25A7/UCP-1), and ATP production(e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus(T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone(SLCO1B1/OATP1B1) and metformin(SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

Asymptotic Behavior of Least Energy Solutions for a Fractional Laplacian Eigenvalue Problem on R^(N)

We are interested in the existence and asymptotic behavior for the least energy solutions of the following fractional eigenvalue problem (P)(-△)^(s)u+V(x)u=μu+am(x)|u|^(4s/N)u,∫_(R^(N))|u|^(2)dx=1,u∈H^(s)(R^(N)),where s∈(0,1),μ∈R,a>0,V(x)and m(x)are L^(∞)(R^(N))functions with N≥2.We prove that there is a threshold a^(*)_(s)>0 such that problem(P)has a least energy solution u_(a)(x)for each a∈(0,a^(*)_(s))and u_(a)blows up,as a↗a^(*)_(s),at some point x_(0)∈R^(N),which makes V(x_(0))be the minimum and m(x_(0))be the maximum.Moreover,the precise blowup rates for u_(a)are obtained under suitable conditions on V(x)and m(x).

Discussion on the mechanisms of BO's abdominal acupuncture therapy

This article discussed the mechanisms and precautions of abdominal acupuncture from three different perspectives. First, the relationship between Shénquè （神阙 CV 8） and zang-fu and eight extra meridians stated in the ancient literature explained that the theory of CV 8 as the theoretical core of abdominal acupuncture therapy had literature support and theoretical evidence; second, with emphasis on the diagnosis and treatment based on differentiation of syndromes, four methods for selecting the points, including the ones according to hologram, meridians and collaterals, the Ba-kuo （八 廓） and three energizer, meanwhile, the origin of method selecting the points according to Three Energizer and clinical experience was also addressed; third, some problems about the manipulation of abdominal acupuncture therapy were put forward, such as selection of depth, direction, needle tool, as well as personal ideas and precautions, in order to ensure the clinical effect.