Thermal-cracking system has been adopted to produce cracked selenium and the influence of cracked selenium flux on the structure and reaction pathway during the first-step selenization is ...investigated. High Cracked-Selenium (HC-Se) may facilitate the Cu–Se and In–Se reaction at lower temperatures. The “Polygon grains” observed in the HC-Se samples play a key role in further selenium diffusion into the film since they make the film more incompact. In addition, activation energy analysis indicates that Cu2−xSe and β-In2Se3 formed in the samples prepared in HC-Se atmosphere may result in different growth pathway of Cu(In1−xGax)Se2 (CIGS) thin film compared with that prepared in Low Cracked-Selenium (LC-Se) atmosphere during the first-step selenization, which restrains lamination in CIGS films effectively so that the distribution of Ga is more uniform throughout CIGS films and no small grains of CuGaSe2 (CGS) accumulate near the Mo back-contact. As a result, the shunt conductance in this CIGS thin film device prepared in HC-Se is reduced, and the fill factor, open-circuit voltage, as well as the cell efficiency are improved.
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•HC-Se facilitates the Cu–Se and In–Se reaction at lower temperatures.•“Polygon grains” in HC-Se samples are necessary for selenium diffusion since they make the film incompact.•HC-Se atmosphere delays compact CIS formation at the first heating.•Ga is more uniform throughout CIGS films in HC-Se atmosphere.•Cell performance is improved in HC-Se samples due to shunt conductance reduction.
HER2 is a validated target in breast cancer therapy. Two drugs are currently approved for HER2-positive breast cancer: trastuzumab (Herceptin), introduced in 1998, and lapatinib (Tykerb), in 2007. ...Despite these advances, some patients progress through therapy and succumb to their disease. A variation on antibody-targeted therapy is utilization of antibodies to deliver cytotoxic agents specifically to antigen-expressing tumors. We determined in vitro and in vivo efficacy, pharmacokinetics, and toxicity of trastuzumab-maytansinoid (microtubule-depolymerizing agents) conjugates using disulfide and thioether linkers. Antiproliferative effects of trastuzumab-maytansinoid conjugates were evaluated on cultured normal and tumor cells. In vivo activity was determined in mouse breast cancer models, and toxicity was assessed in rats as measured by body weight loss. Surprisingly, trastuzumab linked to DM1 through a nonreducible thioether linkage (SMCC), displayed superior activity compared with unconjugated trastuzumab or trastuzumab linked to other maytansinoids through disulfide linkers. Serum concentrations of trastuzumab-MCC-DM1 remained elevated compared with other conjugates, and toxicity in rats was negligible compared with free DM1 or trastuzumab linked to DM1 through a reducible linker. Potent activity was observed on all HER2-overexpressing tumor cells, whereas nontransformed cells and tumor cell lines with normal HER2 expression were unaffected. In addition, trastuzumab-DM1 was active on HER2-overexpressing, trastuzumab-refractory tumors. In summary, trastuzumab-DM1 shows greater activity compared with nonconjugated trastuzumab while maintaining selectivity for HER2-overexpressing tumor cells. Because trastuzumab linked to DM1 through a nonreducible linker offers improved efficacy and pharmacokinetics and reduced toxicity over the reducible disulfide linkers evaluated, trastuzumab-MCC-DM1 was selected for clinical development.
Contrary to the general connection style, the vibration characteristics of the ship foundation vibration is researched under the arrangement style of isolators acted on it. And the influence of the ...parameters of rigidity and damp to the excitation force characteristic is studied too. Based on the real ship data and the finite element method, the study is shown that the excitation force from the device to the foundation is not only related to the rigidity, damp of isolators and the natural frequency of device-isolator-foundation system but also the related to arrangement style of isolator. When the excited frequency is lower it had little effect on the vibration characteristics relatively. However that the frequency is higher, it had significant effect on the vibration.
Antibody-drug conjugates (ADCs) for the treatment of cancer aim to achieve selective delivery of a cytotoxic payload to tumor cells while sparing normal tissue. In vivo, multiple tumor-dependent and ...-independent processes act on ADCs and their released payloads to impact tumor-versus-normal delivery, often resulting in a poor therapeutic window. An ADC with a labeled payload would make synchronous correlations between distribution and tissue-specific pharmacological effects possible, empowering preclinical and clinical efforts to improve tumor-selective delivery; however, few methods to label small molecules without destroying their pharmacological activity exist. Herein, we present a bioorthogonal switch approach that allows a radiolabel attached to an ADC payload to be removed tracelessly at will. We exemplify this approach with a potent DNA-damaging agent, the pyrrolobenzodiazepine (PBD) dimer, delivered as an antibody conjugate targeted to lung tumor cells. The radiometal chelating group, DOTA, was attached via a novel trans-cyclooctene (TCO)-caged self-immolative para-aminobenzyl (PAB) linker to the PBD, stably attenuating payload activity and allowing tracking of biodistribution in tumor-bearing mice via SPECT-CT imaging (live) or gamma counting (post-mortem). Following TCO-PAB-DOTA reaction with tetrazines optimized for extra- and intracellular reactivity, the label was removed to reveal the unmodified PBD dimer capable of inducing potent tumor cell killing in vitro and in mouse xenografts. The switchable antibody radio-drug conjugate (ArDC) we describe integrates, but decouples, the two functions of a theranostic given that it can serve as a diagnostic for payload delivery in the labeled state, but can be switched on demand to a therapeutic agent (an ADC).Antibody-drug conjugates (ADCs) for the treatment of cancer aim to achieve selective delivery of a cytotoxic payload to tumor cells while sparing normal tissue. In vivo, multiple tumor-dependent and -independent processes act on ADCs and their released payloads to impact tumor-versus-normal delivery, often resulting in a poor therapeutic window. An ADC with a labeled payload would make synchronous correlations between distribution and tissue-specific pharmacological effects possible, empowering preclinical and clinical efforts to improve tumor-selective delivery; however, few methods to label small molecules without destroying their pharmacological activity exist. Herein, we present a bioorthogonal switch approach that allows a radiolabel attached to an ADC payload to be removed tracelessly at will. We exemplify this approach with a potent DNA-damaging agent, the pyrrolobenzodiazepine (PBD) dimer, delivered as an antibody conjugate targeted to lung tumor cells. The radiometal chelating group, DOTA, was attached via a novel trans-cyclooctene (TCO)-caged self-immolative para-aminobenzyl (PAB) linker to the PBD, stably attenuating payload activity and allowing tracking of biodistribution in tumor-bearing mice via SPECT-CT imaging (live) or gamma counting (post-mortem). Following TCO-PAB-DOTA reaction with tetrazines optimized for extra- and intracellular reactivity, the label was removed to reveal the unmodified PBD dimer capable of inducing potent tumor cell killing in vitro and in mouse xenografts. The switchable antibody radio-drug conjugate (ArDC) we describe integrates, but decouples, the two functions of a theranostic given that it can serve as a diagnostic for payload delivery in the labeled state, but can be switched on demand to a therapeutic agent (an ADC).
Asymmetric supercapacitors (ASCs) with free-standing electrodes have attracted extensive attention due to enhanced power density, high energy density, long-term stability, and low inner resistance. ...Herein, a three-dimensional (3D) hierarchical nanosheet array electrode (CC@NiCo2O4@PPy), consisting of a polypyrrole (PPy) thin film shell and spinel NiCo2O4 as the core, was prepared on carbon cloth (CC) via a simple two-step electrodeposition. Since the protection of the highly conductive pseudocapacitive PPy shell, the integrated electrode delivers an enhanced specific capacitance (1687.2 F g–1 or 257.8 mAh g–1 at 1 A g–1) and a high cycling stability (91.9% capacitance retention after 10,000 cycles at 10 A g–1). We further demonstrate the ASC based on CC@NiCo2O4@PPy/6 M KOH/active carbon, which can be cycled over 10,000 times with 80% retention at 4 A g–1. Moreover, the prepared ASCs present a favorable rate capability with high energy densities of 46.5 and 31 Wh kg–1 at power densities of 725 and 7246 W kg–1, respectively. Our work provides a viable approach to construct a hierarchical 3D structure under ambient conditions and opens possibilities for adopting it in hybrid supercapacitors.
Background and Objective: Elderly people are at high prevalence of atherosclerotic cerebral infarction. Cerebral white matter lesions (WMLs) increase the risk of bleeding after intravenous ...thrombolysis (IVT) although they may also require the IVT. The aim of this study is to develop a clinical nomogram model for post-IVT symptomatic intracranial hemorrhage (sICH), with the aim to prevent sICH in elderly patients with severe WMLs when IVT is being considered.
Methods: This is a large single-center retrospective analysis study of elderly patients with severe WMLs receiving IVT from January 2018 to December 2022. Univariate and multi-factor logistic regression analysis were used to construct nomogram model, and a series of validations were performed on the model.
Results: More than 2,000 patients with IVT were screened for inclusion in this study after cranial magnetic resonance imaging evaluation. Out of these, 163 elderly patients had cerebral WMLs, and 25 had sICH. In univariate analysis, history of hypertension (p=0.037), hyperlipidemia (p<0.001), NIHSS score before IVT (p<0.001), low-density lipoprotein levels (p=0.016), cholesterol levels (p=0.020), platelet count (p=0.006), systolic blood pressure (p<0.001), diastolic blood pressure (p<0.001) were significantly associated with sICH. In a multifactorial analysis, the NIHSS score before IVT (OR 42.056 CI 7.308-242.012, p<0.001), and diastolic blood pressure (OR 1.050 CI 1.002-1.100, p=0.040) were found to be significantly associated with sICH after IVT. The four most significant risk factors from logistic regression are subsequently fitted to create a predictive model. The accuracy was verified using calibration curves, decision curves, and clinical impact curves, and the model was considered to have strong stability.
Conclusions: The NHISS score before IVT and diastolic blood pressure are independent risk factors for sICH after IVT in elderly patients with severe WMLs. The models are highly accurate and can be applied clinically to provide a reliable predictive basis for IVT in elderly patients with severe WMLs.
Abstract
This study aims to investigate the dynamic and static characteristics of a Differential Relay Valve (DRV). The fact that DRV has a complex physical structure leads to more nonlinear coupling ...property. Thus, theoretical analysis and simulation are not enough when studying its characteristics. In this article, the static and dynamic performance of a DRV is studied based on a novel test bench with NI Labview platform, and both the input and output gas pressure are detected in real time. The outcomes of the experiment show that both the service brake pressure and the parking brake pressure affect the output gas pressure of the DRV, and determined by the larger one. Moreover, the valve has good dynamical follow-up response performance.
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•The control of microcapsule size was realized by a designed agitator paddle system.•Effects of stirring speed and reactor dimension on prepared microcapsule size were studied.•Flow ...field in different agitator paddle systems was investigated by CFD.•Average fluid velocity was negatively-linearly correlated with average microcapsule size.
Controlling the size of fragrance microcapsules using designed agitator paddles was investigated and studied by CFD simulation. First, different fluid flows were established by varying stirring speeds, reactor scales, and agitator paddle design, and the effects of each on particle size and distribution of prepared microcapsules were determined. The experimental results showed that the pattern design of orifices in the plate paddles control the flow field well. Narrow particle-size distributions of the microcapsules were obtained. The fluid flow characteristics including fluid velocity field, turbulent kinetic energy field, and shear stress distribution for the different agitator paddle types in different reaction kettles were simulated using CFD technology. The correlations between simulated data and experimental results were analyzed. Significantly, the simulated average flow velocity was found to show good negative linear correlation with the average particle size of prepared microcapsules, with a correlation of y=–2.166x+42.626.
Antibody–drug conjugates (ADCs) have a significant impact toward the treatment of cancer, as evidenced by the clinical activity of the recently approved ADCs, brentuximab vedotin for Hodgkin lymphoma ...and ado-trastuzumab emtansine (trastuzumab-MCC-DM1) for metastatic HER2+ breast cancer. DM1 is an analog of the natural product maytansine, a microtubule inhibitor that by itself has limited clinical activity and high systemic toxicity. However, by conjugation of DM1 to trastuzumab, the safety was improved and clinical activity was demonstrated. Here, we report that through chemical modification of the linker–drug and antibody engineering, the therapeutic activity of trastuzumab maytansinoid ADCs can be further improved. These improvements include eliminating DM1 release in the plasma and increasing the drug load by engineering four cysteine residues into the antibody. The chemical synthesis of highly stable linker–drugs and the modification of cysteine residues of engineered site-specific antibodies resulted in a homogeneous ADC with increased therapeutic activity compared to the clinically approved ADC, trastuzumab-MCC-DM1.
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