Microfluidic Templated Multicompartment Microgels for 3D Encapsulation and Pairing of Single Cells

Controlled encapsulation and pairing of single cells within a confined 3D matrix can enable the replication of the highly ordered cellular structure of human tissues. Microgels with independently controlled compartments that can encapsulate cells within separately confined hydrogel matrices would provide precise control over the route of pairing single cells. Here, a one‐step microfluidic method is presented to generate monodisperse multicompartment microgels that can be used as a 3D matrix to pair single cells in a highly biocompatible manner. A method is presented to induce microgels formation on chip, followed by direct extraction of the microgels from oil phase, thereby avoiding prolonged exposure of the microgels to the oil. It is further demonstrated that by entrapping stem cells with niche cells within separate but adjacent compartments of the microgels, it can create complex stem cell niche microenvironments in a controlled manner, which can serve as a useful tool for the study of cell–cell interactions. This microfluidic technique represents a significant step toward high‐throughput single cells encapsulation and pairing for the study of intercellular communications at single cell level, which is of significant importance for cell biology, stem cell therapy, and tissue engineering.     

Autonomous Ultrafast Self‐Healing Hydrogels by pH‐Responsive Functional Nanofiber Gelators as Cell Matrices

The synthesis of hybrid hydrogels by pH‐controlled structural transition with exceptional rheological properties as cellular matrix is reported. “Depsi” peptide sequences are grafted onto a polypeptide backbone that undergo a pH‐induced intramolecular O–N–acyl migration at physiological conditions affording peptide nanofibers (PNFs) as supramolecular gelators. The polypeptide–PNF hydrogels are mechanically remarkably robust. They reveal exciting thixotropic behavior with immediate in situ recovery after exposure to various high strains over long periods and self‐repair of defects by instantaneous reassembly. High cytocompatibility, convenient functionalization by coassembly, and controlled enzymatic degradation but stability in 2D and 3D cell culture as demonstrated by the encapsulation of primary human umbilical vein endothelial cells and neuronal cells open many attractive opportunities for 3D tissue engineering and other biomedical applications.     

Federal reserved rights and California's Groundwater Management Act: resolving groundwater rights tensions in California and the western United States

California introduced its first comprehensive groundwater legislation (the Sustainable Groundwater Management Act) in 2014 to address the overuse of the state’s groundwater resources and to establish a pathway for sustainable groundwater use. However, a recent decision by the US Court of Appeals for the Ninth Circuit declaring the existence of federal reserved rights to groundwater could complicate the future implementation of California’s new groundwater legislation. This article explores the impact of the case and offers recommendations on how the tensions between the court’s decision and the existing legal framework for groundwater management in California could be reduced.     

景观设计展望:国际性和中国特色

中国的当代景观设计仍然在传统的范例和国际的范例之间探寻其自己的风格。北京土人景观规划设计研究院所做的项目展示了当代的、同时又是自己的设计语言,彰显了全球化背景下当代中国人的身份。     

慕尼黑理工大学建筑博物馆

收藏慕尼黑理工大学建筑博物馆于1868年随着该大学一同建成。以前收集的大量建筑收藏品最初是作为教学资料,并可以在陈列室里供人查阅。第二次世界大战以后,不断地收购使这里成为了德国最大的建筑档案馆, 如今,这里有500位重要建筑师的近40万张图纸、近 10万幅摄影作品和800个模型。最早的图纸来自16世纪,最早的模型则出自1659年,藏品中的大部分是19 世纪和20世纪的德国建筑资料,是建筑摄影以及建筑发展文档编制的开端时期的资料。     

An optimal radial profile order based on the Golden Ratio for time-resolved MRI

In dynamic magnetic resonance imaging (MRI) studies, the motion kinetics or the contrast variability are often hard to predict, hampering an appropriate choice of the image update rate or the temporal resolution. A constant azimuthal profile spacing (111.246 degrees), based on the Golden Ratio, is investigated as optimal for image reconstruction from an arbitrary number of profiles in radial MRI. The profile order is evaluated and compared with a uniform profile distribution in terms of signal-to-noise ratio (SNR) and artifact level. The favorable characteristics of such a profile order are exemplified in two applications on healthy volunteers. First, an advanced sliding window reconstruction scheme is applied to dynamic cardiac imaging, with a reconstruction window that can be flexibly adjusted according to the extent of cardiac motion that is acceptable. Second, a contrast-enhancing k-space filter is presented that permits reconstructing an arbitrary number of images at arbitrary time points from one raw data set. The filter was utilized to depict the T1-relaxation in the brain after a single inversion prepulse. While a uniform profile distribution with a constant angle increment is optimal for a fixed and predetermined number of profiles, a profile distribution based on the Golden Ratio proved to be an appropriate solution for an arbitrary number of profiles.     

Predicting and tuning physicochemical properties in lead optimization: amine basicities

This review describes simple and useful concepts for predicting and tuning the pK(a) values of basic amine centers, a crucial step in the optimization of physical and ADME properties of many lead structures in drug-discovery research. The article starts with a case study of tricyclic thrombin inhibitors featuring a tertiary amine center with pK(a) values that can be tuned over a wide range, from the usual value of around 10 to below 2 by (remote) neighboring functionalities commonly encountered in medicinal chemistry. Next, the changes in pK(a) of acyclic and cyclic amines upon substitution by fluorine, oxygen, nitrogen, and sulfur functionalities, as well as carbonyl and carboxyl derivatives are systematically analyzed, leading to the derivation of simple rules for pK(a) prediction. Electronic and stereoelectronic effects in cyclic amines are discussed, and the emerging computational methods for pK(a) predictions are briefly surveyed. The rules for tuning amine basicities should not only be of interest in drug-discovery research, but also to the development of new crop-protection agents, new amine ligands for organometallic complexes, and in particular, to the growing field of amine-based organocatalysis.     

Cadmium accumulation in Scenedesmus vacuolatus under freshwater conditions

Cd accumulation in cultures of Scenedesmus vacuolatus, a freshwater alga, was investigated in water samples from freshwater systems (two hard- and one softwater system) and compared to accumulation from synthetic culture medium. The Cd accumulation in S. vacuolatus was compared to total, labile, and free Cd measured by various analytical methods. In the hardwater samples, Cd accumulation was similar to accumulation from the culture medium and approximately followed the free ion activity model. In the softwater system, Cd accumulation increased with increasing free and total Cd concentrations, but was lower than expected from the free Cd2+ concentrations compared to the other freshwaters and culture media. Cd accumulation in the various freshwaters was not simply related to labile and free Cd concentrations measured by several methods. From experiments using fulvic acid as a ligand in the culture medium, no influence on Cd accumulation other than by modifying the Cd speciation was detected. Modeling of the Cd uptake revealed that besides cation and proton competition, other factors such as dissolved organic carbon composition and the presence of colloids might reduce Cd accumulation in softwater systems.     

Strength properties and density of SO2 polluted spruce wood

2 pollution during approximately 1935 and 1992 respectively, was studied as to its mechanical properties (fracture toughness, acoustic emission (AE)) as well as its density and annual ring width changes. Earlywood and latewood width and density were measured with X-ray densitometry equipment. The mechanical tests were performed with specimens taken from the same trees using the wedge splitting technique. Using notched, rectangularly shaped specimens, the experiments allowed to determine the notch-tensile strength σ_NTS of each yearring in RL orientation separately by differentiating earlywood and latewood. The results show clear correlations between earlywood density and notch-tensile strength, good, inverse correlation to some extent between ring width and σ_NTS and also between AE emission activity and earlywood width for the less polluted trees. Data scattering with resulting less pronounced trends was found for all parameters measured for the more severely polluted trees. The results and correlations allow assuming that σ_NTS is influenced by the SO₂ pollution to some extent via treering growth (ring width) and density. The results point to a more pronounced influence of SO₂ pollution between approximately 1970 and 1985 than before that time, and a subsequent recovery of the tested wood properties in the trees that had survived this period.

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2 -belastet war, wurde auf seine mechanischen Eigenschaften und auf seine Dichte und Jahrringbreite hin untersucht. Früh- und Sp?tholzbreite und Dichte wurden mittels R?ntgendensitometrie, die mechanischen Eigenschaften mittels Keilspaltverfahren bestimmt. Durch die Verwendung von rechteckigen, gekerbten Proben lie? sich die Kerbzugfestigkeit σ_NTS jedes Jahrrings in RL-Orientierung bestimmen. Die Resultate zeigen einen klaren Zusammenhang zwischen Frühholzdichte und Kerbzugfestigkeit sowie einen gewissen inversen Zusammenhang zwischen Jahrringbreite und Kerbzugfestigkeit bzw. Schallemissionsaktivit?t und Frühholzbreite für die wenig gesch?digten B?ume. Bei den st?rker gesch?digten B?umen war die Streuung der Me?werte deutlich h?her und die Abh?ngigkeiten schw?cher ausgepr?gt. Die Resultate und Zusammenh?nge deuten darauf hin, da? die Kerbzugfestigkeit durch die SO₂ Belastung über den Jahrringwuchs (Jahrringbreite) und die Dichte beeinflu?t wird. Die Resultate zeigen einen st?rkeren Einflu? der SO₂ Belastung zwischen 1970 und 1985 und deuten auf eine Erholung in den Holzeigenschaften bei jenen B?umen, die diese Periode überlebt haben, hin.

     

Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells

The aim of this study was to analyze the expression of peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RxRα), a binding heterodimer playing a pivotal role in the successful trophoblast invasion, in the placental tissue of preeclamptic patients. Furthermore, we aimed to characterize a possible interaction between PPARγ and H3K4me3 (trimethylated lysine 4 of the histone H3), respectively H3K9ac (acetylated lysine 9 of the histone H3), to illuminate the role of histone modifications in a defective trophoblast invasion in preeclampsia (PE). Therefore, the expression of PPARγ and RxRα was analyzed in 26 PE and 25 control placentas by immunohistochemical peroxidase staining, as well as the co-expression with H3K4me3 and H3K9ac by double immunofluorescence staining. Further, the effect of a specific PPARγ-agonist (Ciglitazone) and PPARγ-antagonist (T0070907) on the histone modifications H3K9ac and H3K4me3 was analyzed in vitro. In PE placentas, we found a reduced expression of PPARγ and RxRα and a reduced co-expression with H3K4me3 and H3K9ac in the extravillous trophoblast (EVT). Furthermore, with the PPARγ-antagonist treated human villous trophoblast (HVT) cells and primary isolated EVT cells showed higher levels of the histone modification proteins whereas treatment with the PPARγ-agonist reduced respective histone modifications. Our results show that the stimulation of PPARγ-activity leads to a reduction of H3K4me3 and H3K9ac in trophoblast cells, but paradoxically decreases the nuclear PPARγ expression. As the importance of PPARγ, being involved in a successful trophoblast invasion has already been investigated, our results reveal a pathophysiologic connection between PPARγ and the epigenetic modulation via H3K4me3 and H3K9ac in PE.