Endoglin Targeting: Lessons Learned and Questions That Remain

Approximately 30 years ago, endoglin was identified as a transforming growth factor (TGF)-β coreceptor with a crucial role in developmental biology and tumor angiogenesis. Its selectively high expression on tumor vessels and its correlation with poor survival in cancer patients led to the exploration of endoglin as a therapeutic target for cancer. The endoglin neutralizing antibody TRC105 (Carotuximab^®, Tracon Pharmaceuticals (San Diego, CA, USA) was subsequently tested in a wide variety of preclinical cancer models before being tested in phase I-III clinical studies in cancer patients as both a monotherapy and in combination with other chemotherapeutic and anti-angiogenic therapies. The combined data of these studies have revealed new insights into the role of endoglin in angiogenesis and its expression and functional role on other cells in the tumor microenvironment. In this review, we will summarize the preclinical work, clinical trials and biomarker studies of TRC105 and explore what these studies have enabled us to learn and what questions remain unanswered.     

Matrix Transformation in Boron Containing High-Temperature Co–Re–Cr Alloys

An addition of boron largely increases the ductility in polycrystalline high-temperature Co–Re alloys. Therefore, the effect of boron on the alloy structural characteristics is of high importance for the stability of the matrix at operational temperatures. Volume fractions of ε (hexagonal close-packed—hcp), γ (face-centered cubic—fcc) and σ (Cr₂Re₃ type) phases were measured at ambient and high temperatures (up to 1500 °C) for a boron-containing Co–17Re–23Cr alloy using neutron diffraction. The matrix phase undergoes an allotropic transformation from ε to γ structure at high temperatures, similar to pure cobalt and to the previously investigated, more complex Co–17Re–23Cr–1.2Ta–2.6C alloy. It was determined in this study that the transformation temperature depends on the boron content (0–1000 wt. ppm). Nevertheless, the transformation temperature did not change monotonically with the increase in the boron content but reached a minimum at approximately 200 ppm of boron. A probable reason is the interplay between the amount of boron in the matrix and the amount of σ phase, which binds hcp-stabilizing elements (Cr and Re). Moreover, borides were identified in alloys with high boron content.     

Robust Metallic Actuators Based on Nanoporous Gold Rapidly Dealloyed from Gold–Nickel Precursors

Dealloyed nanoporous gold (np-Au) has applications as oxygen reduction catalysis in Li-air batteries and fuel cells, or as actuators to convert electricity into mechanical energy. However, it faces the challenges of coarsening-induced structure instability, mechanical weakness due to low relative densities, and slow dealloying rates. Here, monolithic np-Au is dealloyed from a single-phase Au₂₅Ni₇₅ solid-solution at a one-order faster dealloying rate, ultra-low residual Ni content, and importantly, one-third more relative density than np-Au dealloyed from conventional Au₂₅Ag₇₅. The small atomic radius and low dealloying potential of the sacrificing element Ni are intrinsically beneficial to fast produce high relative density np-Au, as predicted by a general model for dealloying of binary alloys and validated by experiments. Stable, durable, and reversible actuation of np-Au takes place under cyclic potential triggering in alkaline and acidic electrolytes with negligible coarsening-induced strain-shift. The thermal and mechanical robustness of bulk np-Au is confirmed by two-order slower ligament coarsening rates during annealing at 300 °C and 45 MPa macroscopic yielding strength distinctive from the typical early onset of plastic yielding. This article opens a rich direction to achieve high relative density np-Au which is essential for porous network connectivity, mechanical strength, and nanostructure robustness for electrochemical functionality.     

Diversity of Biogas Plant Realizations

A techno‐economic analysis for four different types of biogas plant realizations was performed, including one biogas biorefinery concept. For each concept detail, a process flow diagram was created. Mass and energy balances were estimated. The net present value and payback were calculated for each concept for a better feasibility understanding. The results showed that with the used expensive substrate, namely, wheat straw, the obtained paybacks appeared to be more than 100 years. Sensitivity analysis was done for the price range of a substrate. Critical factors were defined to improve feasibility.     

Extracellular Vesicles and Asthma—More Than Just a Co-Existence

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.     

Polymer on Top: Current Limits and Future Perspectives of Quantitatively Evaluating Surface Grafting

Well‐defined polymer strands covalently tethered onto solid substrates determine the properties of the resulting functional interface. Herein, the current approaches to determine quantitative grafting densities are assessed. Based on a brief introduction into the key theories describing polymer brush regimes, a user's guide is provided to estimating maximum chain coverage and—importantly—examine the most frequently employed approaches for determining grafting densities, i.e., dry thickness measurements, gravimetric assessment, and swelling experiments. An estimation of the reliability of these determination methods is provided via carefully evaluating their assumptions and assessing the stability of the underpinning equations. A practical access guide for comparatively and quantitatively evaluating the reliability of a given approach is thus provided, enabling the field to critically judge experimentally determined grafting densities and to avoid the reporting of grafting densities that fall outside the physically realistic parameter space. The assessment is concluded with a perspective on the development of advanced approaches for determination of grafting density, in particular, on single‐chain methodologies.     

Innovative focused ultrasound-based sealing method of flexible packaging films—Principles and characteristics

A key process to package goods is the closure procedure. It ensures the good protection against the environment and vice versa. Ultrasonic sealing presents the advantage of converting locally ultrasound into heat, which is optimal for temperature sensitive goods. The disadvantages remain, however, the equipment cost, the noise generation, and the process sensitivity to materials. It is necessary to develop a sealing process to decrease the acquisition cost of the sealing equipment and cover a wide range of polymer films. This paper focuses on a new sealing method based on high-intensity focused ultrasound. The principles and characteristics of this process are discussed and underpinned with experimental results. Both the acoustic and thermal effects of the sealing process are summarized. A study of the process parameter impact on the seam strength in static and dynamic operating is proposed. Low-density polyethylene films with a carrier layer of bi-oriented polypropylene and polyethylene terephthalate are used. A first test bench generates point-shaped seam. The heat generation is recorded with an infrared thermography system. A second test bench, a horizontal form fill and seal machine, produces longitudinal seams. The seam quality is controlled by tensile test and tightness test. A quick heating of the polymer films is found. Point seams and longitudinal seams are successfully generated. The seams behave similarly to the ones generated with ultrasonic sealing process. However, the sealing velocity is limited to 3 m/min. This work provides a summary of the characteristics and principles of the new sealing method in packaging applications.     

Experimentelle und analytische Untersuchung des out‐of‐plane‐Verhaltens von unbewehrten Mauerwerkswänden unter Erdbebenbelastung

Experimental and analytical investigation of the seismic out‐of‐plane behavior of unreinforced masonry walls In addition to the vertical and horizontal load‐bearing in‐plane, masonry must also withstand out‐of‐plane loads that occur in earthquake scenarios. The out‐of‐plane behavior of unreinforced masonry walls depends on a variety of parameters and is very complex due to the strong non‐linearity. Current design methods in German codes and various international codes have not been explicitly developed for out‐of‐plane behavior and contain considerable conservatism. In the present work, shaking‐table experiments with heat‐insulating masonry walls have been conducted to investigate the out‐of‐plane behavior of vertical spanning unreinforced masonry walls. As shown in previous numerical investigations, important parameters are neglected in existing design and analysis models and the out‐of‐plane capacity is underestimated significantly. In the conducted experiments the results of these numerical investigations are verified. Furthermore, the development of an analytical design model to determine the force‐displacement relationship and the out‐of‐plane load‐bearing capacity considering all significant parameters is presented.