Volume and surface effects on two-photonic and three-photonic processes in dry co-doped upconversion nanocrystals

Despite considerable advances in synthesizing high-quality core/shell upconversion(UC)nanocrystals(NC;UCNC)and UCNC photophysics,the application of near-infrare...     

Spin-Wave Optics in YIG Realized by Ion-Beam Irradiation

Direct focused-ion-beam writing is presented as an enabling technology for realizing functional spin-wave devices of high complexity, and demonstrate its potential by optically-inspired designs. It is shown that ion-beam irradiation changes the characteristics of yttrium iron garnet films on a submicron scale in a highly controlled way, allowing one to engineer the magnonic index of refraction adapted to desired applications. This technique does not physically remove material, and allows rapid fabrication of high-quality architectures of modified magnetization in magnonic media with minimal edge damage (compared to more common removal techniques such as etching or milling). By experimentally showing magnonic versions of a number of optical devices (lenses, gratings, Fourier-domain processors) this technology is envisioned as the gateway to building magnonic computing devices that rival their optical counterparts in their complexity and computational power.     

Implicit Contact Handling for Deformable Objects

We present an algorithm for robust and efficient contact handling of deformable objects. By being aware of the internal dynamics of the colliding objects, our algorithm provides smooth rolling and sliding, stable stacking, robust impact handling, and seamless coupling of heterogeneous objects, all in a unified manner. We achieve dynamicsawareness through a constrained dynamics formulation with implicit complementarity constraints, and we present two major contributions that enable an efficient solution of the constrained dynamics problem: a time stepping algorithm that robustly ensures non-penetration and progressively refines the formulation of constrained dynamics, and a new solver for large mixed linear complementarity problems, based on iterative constraint anticipation. We show the application of our algorithm in challenging scenarios such as multi-layered cloth moving at high velocities, or colliding deformable solids simulated with large time steps.     

A New Access to Piperidino-cyclopiperidinecarboxamides – constrained analogues of a pharmaceutical used diaminic building block

6-Piperidino-3-azabicyclo[3.1.0]hexane-6-carboxamide diastereomers 1a and 2a represent conformationally rigid analogues of 3a which is a building block in some pharmaceutical compounds. A new access to these compounds 1a and 2a was found via the cleavage of bicyclic N,N-acetal 6 with hydrocyanic acid as the stereodetermining step. Reaction of derivatives 1a and 2a with bromodiphenyl-butyronitrile 14 gave cyclopiritramide isomers 1c and 2c , respectively. Qualitative preliminary investigations showed different affinities of 1c and 2c to the opiate-μ receptor. These results were discussed on the basis of an X-ray structural analysis of cyclopiritramide isomer 2c . 1-Benzylcyclopiperidine derivatives 1d and 2d were used as model systems for studying the conformation of cyclopiritramide isomer 1c and 2c , respectively.     

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.     

Biosynthetic Plasticity Enables Production of Fluorinated Aurachins

Enzyme promiscuity has important implications in the field of biocatalysis. In some cases, structural analogues of simple metabolic building blocks can be processed through entire pathways to give natural product derivatives that are not readily accessible by chemical means. In this study, we explored the plasticity of the aurachin biosynthesis pathway with regard to using fluoro- and chloroanthranilic acids, which are not abundant in the bacterial producers of these quinolone antibiotics. The incorporation rates of the tested precursor molecules disclosed a regiopreference for halogen substitution as well as steric limitations of enzymatic substrate tolerance. Three previously undescribed fluorinated aurachin derivatives were produced in preparative amounts by fermentation and structurally characterized. Furthermore, their antibacterial activities were evaluated in comparison to their natural congener aurachin D.     

Site-Directed Immobilization of an Engineered Bone Morphogenetic Protein 2 (BMP2) Variant to Collagen-Based Microspheres Induces Bone Formation In Vivo

For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone-inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here, we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group, allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2′s bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induces the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild-type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs.