Immune Checkpoint Blockade in Advanced Cutaneous Squamous Cell Carcinoma: What Do We Currently Know in 2020?

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer that predominantly arises in chronically sun-damaged skin. Immunosuppression, genetic disorders such as xeroderma pigmentosum (XP), exposure to certain drugs and environmental noxae have been identified as major risk factors. Surgical removal of cSCC is the therapy of choice and mostly curative in early stages. However, a minority of patients develop locally advanced tumors or distant metastases that are still challenging to treat. Immune checkpoint blockade (ICB) targeting CTLA-4, PD-L1 and PD-1 has tremendously changed the field of oncological therapy and especially the treatment of skin cancers as tumors with a high mutational burden. In this review, we focus on the differences between cSCC and cutaneous melanoma (CM) and their implications on therapy, summarize the current evidence on ICB for the treatment of advanced cSCC and discuss the chances and pitfalls of this therapy option for this cancer entity. Furthermore, we focus on special subgroups of interest such as organ transplant recipients, patients with hematologic malignancies, XP and field cancerization.     

Technical and economic analysis of solvent-based lithium-ion electrode drying with water and NMP

Processing lithium-ion battery (LIB) electrode dispersions with water as the solvent during primary drying offers many advantages over N-methylpyrrolidone (NMP). An in-depth analysis of the comparative drying costs of LIB electrodes is discussed for both NMP- and water-based dispersion processing in terms of battery pack $/kWh. Electrode coating manufacturing and capital equipment cost savings are compared for water vs. conventional NMP organic solvent processing. A major finding of this work is that the total electrode manufacturing costs, whether water- or NMP-based, contribute about 8–9% of the total pack cost. However, it was found that up to a 2?×?reduction in electrode processing (drying and solvent recovery) cost can be expected along with a $3–6?M savings in associated plant capital equipment (for a plant producing 100,000 10-kWh Plug-in Hybrid Electric Vehicle (PHEV) batteries) using water as the electrode solvent. This paper shows a different perspective in that the most important benefits of aqueous electrode processing actually revolve around capital equipment savings and environmental stewardship and not processing cost savings.     

SMART-Reactors: Tailoring Gas Holdup Distribution by Additively Manufactured Lattice Structures

In chemical process engineering, fast gas-liquid reactions often suffer from an inefficient distribution of gas and therefore mixing and mass transfer performance. This study deals with the possibility of influencing the local gas holdup and bubble size distribution in a gas-liquid process using additively manufactured lattice structures (AMLS). The used measuring technique to study bubble size, velocity, and the local gas holdup is a photo-optical needle probe. By using AMLS, a significant radial homogenization of the local gas holdup and the mean bubble size is achieved. Furthermore, it can be demonstrated that the bubble size can be tailored by the geometry of the inserted structure. It is illustrated that the mean bubble velocities are lowered within the lattice resulting in a higher residence time of the dispersed phase with an impact on the mass transfer performance within the AMLS.     

Bestandsaufnahme Grundwasser nach der EU-Wasserrahmenrichtlinie im Koordinierungsraum Mulde-Elbe-Schwarze Elster

Die Wasserrahmenrichtlinie regelt den Schutz von Grund- und Oberflächengewässern und fordert eine nachhaltige Wassernutzung. Sie legt einen Zeitplan fest, um bis zum Jahr 2015 für alle Gewässer einen guten Zustand zu erreichen. Der erste Schritt ist eine Bestandsaufnahme der Gewässer. Für das Grundwasser besteht diese aus einer erstmaligen Beschreibung, einer weitergehenden Beschreibung und der Prüfung der Auswirkungen menschlicher Tätigkeit auf das Grundwasser. Die Wasserrahmenrichtlinie wird unabhängig von administrativen Grenzen innerhalb von hydrologischen Einzugsgebieten umgesetzt. Im deutschen Teil des Flusseinzugsgebietes der Elbe wurden 5 Koordinierungsräume gegründet. Der Koordinierungsraum Mulde-Elbe-Schwarze Elster (MES) wird vorgestellt. Beispielhaft für die angewandten Methoden wird die Beurteilung diffuser Stoffeinträge in das Grundwasser bei der erstmaligen Beschreibung erläutert. Die Ergebnisse der Bestandsaufnahme Grundwasser im Koordinierungsraum MES werden präsentiert. Von 54 Grundwasserkörpern ist für 25 Körper aufgrund der Belastungen durch Punktquellen und diffuse Quellen, wegen des mengenmäßigen Zustands oder sonstiger anthropogener Einwirkungen die Zielerreichung nach der Wasserrahmenrichtlinie unklar/unwahrscheinlich.     

Degradation of microcystin in sediments at oxic and anoxic, denitrifying conditions

The potent toxin microcystin is frequently released during cyanobacterial blooms in eutrophic waters and may impose a risk to human health, when surface water is used for drinking water. For removal of microcystin in surface waters, infiltration through sediment is commonly used. In the present study, mineralization of 14C-labelled microcystin (accumulation of 14CO(2)) and concentration changes (protein phosphatase inhibition assay) demonstrated that indigenous microorganisms in the sediment of a water recharge facility were capable of degrading microcystin. At oxic or microaerophilic (<2% O(2)) conditions, microcystin added to sediment slurries at 70 microg l(-1) was reduced to <20 microg l(-1) in 1-2 weeks, and less than 3 microg l(-1) after 7 weeks. At anoxic conditions (<0.3% O(2)) and with addition of nitrate, the degradation was significantly stimulated, reducing microcystin from 100 to <20 microg l(-1) within 1 day. The simultaneous production of N(2)O in the samples suggests that the microcystin degradation was coupled to dissimilative nitrate reduction (denitrification). Since aquifers and sediments beneath drinking water reservoirs often are anoxic, nitrate respiration may be an important process in removal and detoxification of microcystin.     

A Novel Approach to Detect Faults Occurring During Power Swings by Abrupt Change of Impedance Trajectory

The main purpose of power swing blocking is to distinguish faults from power swings. However, faults occurred during a power swing should still be detected and cleared promptly. This paper proposes an index based on detecting abrupt jump of impedance trajectory by utilization of the predicting capability of the Kalman Filter. The proposed index is calculated by assessing the difference between predicted and actual samples of impedance. The predicted impedance samples are obtained using the Kalman filter and Taylor expansion, which are used in this paper to track the phasor precisely. Second order of Taylor expansion is used to decrease the corrugation effect of impedance estimation and increase the reliability of the proposed method. Furthermore, in order to increase the selectivity of the proposed method, the proposed index is armed with phase comparison logic to detect internal faults. The instantaneous estimation and prediction capability of the Kalman filter are two reasons for proposing the use of Kalman filter. Intensive studies have been performed and the merit of the method is demonstrated by test simulations.     

基于无谐波检测和选择性谐波补偿原理的组合式同相供电系统控制策略

针对组合式同相供电系统同相补偿装置(CCD)的常规控制方法受负载电流检测精度影响严重,且不能良好跟踪高速铁路负载高次谐波电流的缺陷,提出一种选择性谐波电流控制策略。该控制策略仅需要保留CCD的两单相变流器输出电压、电流的检测部分,不需要检测负载电流;并通过矢量比例积分控制器对连接负载的单相变流器输出电流误差中的各次谐波单独跟踪。该设计方法不受负载电流检测精度的影响,对牵引负荷各个频段谐波都具有良好的跟踪性能。利用MATLAB/Simulink搭建组合式同相供电的常规控制模型、改进控制模型和基于改进控制策略的半桥四臂模块化多电平电路模型,对交-直型、交-直-交型、混跑3种负载分别进行控制,仿真验证了改进电流控制方法的正确性以及在实际工程实现中的有效性。     

Deoxycholate‐Based Glycosides (DCGs) for Membrane Protein Stabilisation

Detergents are an absolute requirement for studying the structure of membrane proteins. However, many conventional detergents fail to stabilise denaturation‐sensitive membrane proteins, such as eukaryotic proteins and membrane protein complexes. New amphipathic agents with enhanced efficacy in stabilising membrane proteins will be helpful in overcoming the barriers to studying membrane protein structures. We have prepared a number of deoxycholate‐based amphiphiles with carbohydrate head groups, designated deoxycholate‐based glycosides (DCGs). These DCGs are the hydrophilic variants of previously reported deoxycholate‐based N‐oxides (DCAOs). Membrane proteins in these agents, particularly the branched diglucoside‐bearing amphiphiles DCG‐1 and DCG‐2, displayed favourable behaviour compared to previously reported parent compounds (DCAOs) and conventional detergents (LDAO and DDM). Given their excellent properties, these agents should have significant potential for membrane protein studies.