Imaging of Extracellular pH Using Hyperpolarized Molecules

Many diseases can overrule natural pH regulatory mechanisms and alter the extracellular pH (pH_e). A non-invasive method that resolves pH_e in vivo with high spatial and temporal resolution could therefore improve diagnosis and monitoring of diseases, contributing to the concept of precision medicine. During the last decades, several techniques have been proposed to image pH_e non-invasively. The majority of these methods rely on magnetic resonance because of its good spatial resolution, high penetration depth, non-ionizing radiation and excellent complimentary soft tissue contrast. Dissolution dynamic nuclear polarization (DNP) is an emerging concept to enhance nuclear magnetic resonance (NMR) signals by more than four orders of magnitude, making it possible to observe in vivo metabolic processes in real-time. Here, we summarize and review recent developments in pH_e imaging techniques based on hyperpolarization methods and give an overview of recently discovered hyperpolarized pH sensor molecules that have been applied in vitro and in vivo.     

Process and performance optimization by selective assembly of battery electrodes

The increasing demand for electric vehicles and thus lithium-ion batteries results in a multitude of challenges in production technology. The reproducibility and performance of large scale batteries for automotive applications are very high. At the same time the production processes are complex and involve many uncertainties. Two essential process steps are the electrode coating and electrode package assembly. The mass loading of anodes and cathodes are determined by the coating process, where deviations can be caused by different reasons. The selective assembly of the electrodes is a reasonable way to balance the production variances. The contribution shows extended algorithms and their benefits and drawbacks of matching electrodes in order to improve the subsequent electrode packaging process. Here, the aim is to reach higher cell capacities and optimized performance values by “optimally” balanced electrodes regarding the mass loading ratio, which is also related to the specific material capacity.     

德国迪林根ROGESA钢铁公司2号烧结机EFA(R)烟气处理系统及其运转情况

多年来,环境保护一直是烧结行业的一个重要课题.由于政府部门提出了更加严格的要求,烧结厂废气的进一步净化已经变得很有必要.一套新开发的、工业化的EFA(曳流吸收塔)烟气处理系统于2006年年中在ROGESA钢铁公司投入运行.本文就该系统的工艺流程、特点及运行情况作一介绍.     

Potent and Selective Non‐hydroxamate Histone Deacetylase 8 Inhibitors

Specific inhibition of histone deacetylase 8 (HDAC8) has been suggested as a promising option for the treatment of neuroblastoma and T‐cell malignancies. A novel class of highly potent and selective HDAC8 inhibitors with a pyrimido[1,2‐c][1,3]benzothiazin‐6‐imine scaffold was studied that is completely different from the traditional concept of HDAC inhibitors comprising a zinc binding group (ZBG), in most cases a hydroxamate group, a spacer, and a capping group that may interact with the surface of the target protein. Although lacking a ZBG, some of the new compounds were shown to have outstanding potency against HDAC8 in the single‐digit nanomolar range. The pyrimido[1,2‐c][1,3]benzothiazin‐6‐imines also inhibited the growth of solid and hematological tumor cells. The small size and beneficial physicochemical properties of the novel HDAC inhibitor class underline the high degree of drug likeness. This and the broad structure–activity relationship suggest great potential for the further development of compounds with the pyrimido[1,2‐c][1,3]benzothiazin‐6‐imine scaffold into innovative and highly effective therapeutic drugs against cancer.     

4‐Biphenylalanine‐ and 3‐Phenyltyrosine‐Derived Hydroxamic Acids as Inhibitors of the JumonjiC‐Domain‐Containing Histone Demethylase KDM4A

Overexpression of the histone lysine demethylase KDM4A, which regulates H3K9 and H3K36 methylation states, has been related to the pathology of several human cancers. We found that a previously reported hydroxamate‐based histone deacetylase (HDAC) inhibitor (SW55) was also able to weakly inhibit this demethylase with an IC₅₀ value of 25.4 μm . Herein we report the synthesis and biochemical evaluations, with two orthogonal in vitro assays, of a series of derivatives of this lead structure. With extensive chemical modifications on the lead structure, also by exploiting the versatility of the radical arylation with aryldiazonium salts, we were able to increase the potency of the derivatives against KDM4A to the low‐micromolar range and, more importantly, to obtain demethylase selectivity with respect to HDACs. Cell‐permeable derivatives clearly showed a demethylase‐inhibition‐dependent antiproliferative effect against HL‐60 human promyelocytic leukemia cells.     

Differential Impact of Hyperglycemia in Critically Ill Patients: Significance in Acute Myocardial Infarction but Not in Sepsis?

Hyperglycemia is a common condition in critically ill patients admitted to an intensive care unit (ICU). These patients represent an inhomogeneous collective and hyperglycemia might need different evaluation depending on the underlying disorder. To elucidate this, we investigated and compared associations of severe hyperglycemia (>200 mg/dL) and mortality in patients admitted to an ICU for acute myocardial infarction (AMI) or sepsis as the two most frequent admission diagnoses. From 2006 to 2009, 2551 patients 69 (58–77) years; 1544 male; 337 patients suffering from type 2 diabetes (T2DM)) who were admitted because of either AMI or sepsis to an ICU in a tertiary care hospital were investigated retrospectively. Follow-up of patients was performed between May 2013 and November 2013. In a Cox regression analysis, maximum glucose concentration at the day of admission was associated with mortality in the overall cohort (HR = 1.006, 95% CI: 1.004–1.009; p < 0.001) and in patients suffering from myocardial infarction (HR = 1.101, 95% CI: 1.075–1.127; p < 0.001) but only in trend in patients admitted to an ICU for sepsis (HR = 1.030, 95% CI: 0.998–1.062; p = 0.07). Severe hyperglycemia was associated with adverse intra-ICU mortality in the overall cohort (23% vs. 13%; p < 0.001) and patients admitted for AMI (15% vs. 5%; p < 0.001) but not for septic patients (39% vs. 40%; p = 0.48). A medical history of type 2 diabetes (n = 337; 13%) was not associated with increased intra-ICU mortality (15% vs. 15%; p = 0.93) but in patients with severe hyperglycemia and/or a known medical history of type 2 diabetes considered in combination, an increased mortality in AMI patients (intra-ICU 5% vs. 13%; p < 0.001) but not in septic patients (intra-ICU 38% vs. 41%; p = 0.53) could be evidenced. The presence of hyperglycemia in critically ill patients has differential impact within the different etiological groups. Hyperglycemia in AMI patients might identify a sicker patient collective suffering from pre-diabetes or undiagnosed diabetes with its’ known adverse consequences, especially in the long-term. Hyperglycemia in sepsis might be considered as adaptive survival mechanism to hypo-perfusion and consecutive lack of glucose in peripheral cells. AMI patients with hyperglycemic derailment during an ICU-stay should be closely followed-up and extensively screened for diabetes to improve patients’ outcome.     

Silver versus white sheet as a back reflector for microcrystalline silicon solar cells deposited on LPCVD‐ZnO electrodes of various textures

We compare the performance of two back reflector designs on the optoelectrical properties of microcrystalline silicon solar cells. The first one consists of a 5‐µm‐thick low‐pressure chemical vapor deposition (LPCVD)‐ZnO electrode combined with a white sheet; the second one incorporates an Ag reflector deposited on a thin LPCVD‐ZnO layer (with thickness below 200 nm). For this latter design, the optical loss in the nano‐rough Ag reflector can be strongly reduced by smoothing the surface of the thin underlying ZnO layer, by means of an Ar‐plasma treatment. Because of its superior lateral conductivity, the thin‐ZnO/Ag back reflector design provides a higher fill factor than the dielectric back reflector design. When decreasing the roughness of the front electrode with respect to our standard front LPCVD‐ZnO layer, the electrical cell performance is improved; in addition, the implementation of the thin‐ZnO/Ag back reflector leads to a significant relative gain in light trapping. Applying this newly optimized combination of front and back electrodes, the conversion efficiency is improved from 8.9% up to 9.4%, for cells with an active‐layer thickness of only 1.1 µm. We thereby highlight the necessity to optimize simultaneously the front and back electrodes. Copyright © 2014 John Wiley & Sons, Ltd.     

New printing inks with barrier performance for packaging applications: Design and investigation

Barrier properties of packaging materials against moisture and oxygen penetration are of high relevance. Enhanced protection of existing materials against weather conditions can be achieved by application of printed coatings. To improve barrier performance of packaging materials, new inks for obtaining printed coatings with a layered structure were developed and investigated. The proposed ink compositions for flexographic printing on paper substrates are based on an environmentally friendly acrylic binder and contain inorganic fillers with platelet particles incorporated in the polymer matrix. Coatings based on the developed printing inks demonstrate significantly decreased water vapour permeability compared to traditional polymer inks. The effect of decreased permeability was investigated considering inks rheological behaviour, the coating structure, mechanical properties, surface energy and water uptake for different ink formulations. The developed inks provide variable optical properties including coatings with a relatively high transparency. The development of the functional barrier inks contributes to saving natural resources by prolonging life performance of packaging materials and goods.