One‐Step Formulation of Protein Microparticles with Tailored Properties: Hard Templating at Soft Conditions

Formulation of therapeutic proteins into particulate forms is a main strategy for site‐specific and prolonged protein delivery as well as for protection against degradation. Precise control over protein particle size, dispersity, purity, as well as mild preparation conditions and minimal processing steps are highly desirable. It is, however, hard to fit all these criteria with conventional preparation techniques. Here a one‐step hard‐templating synthesis of microparticles composed of functional, non‐denatured protein is reported. The method is based on filling porous CaCO₃ microtemplates with the protein near to its isoelectric point (pI) followed by pH‐ or EDTA‐mediated dissolution of the tempplates. In principle, a wide variety of proteins can be converted into microparticles using this approach. The main requirement is an overlap of the protein insolubility and a template solubility for a certain parameter (here pH or EDTA). Here the formulation of insulin particles is studied in detail and it is shown that particles consisting of high molecular weight protein (catalase) can also be prepared. In this context, the synthesis of CaCO₃ templates with controlled size, the mechanism of the protein microparticle formation and mechanical properties of the microparticles are discussed. For the first time, the fabrication of mesoporous monodispersed CaCO₃ microtemplates with identical porocity but tuned diameter from 3 to 20 μm is demonstrated. The protein particle diameter can be adjusted by choosing the appropriate template size that is critical for successful pulmonary delivery of insulin. As a first step towards insulin delivery, the in vitro release of insulin at physiological conditions is studied.     

Constellation Rearrangement: Enhancement for Multilevel Modulation Formats and Transmit Diversity

Radio link adaptivity will be a key feature of the air interfaces of future mobile communication systems. This adaptivity includes techniques such as fast scheduling, hybrid ARQ, transmit diversity and adaptive modulation and coding. The performance of adaptive modulation generally suffers from the power inefficiencies of multilevel modulation formats. This is due to the variations in bit reliabilities caused by the bit-mapping onto the signal constellation. This article presents a concept, called constellation rearrangement (CoRe), which improves the multilevel modulation power efficiency by the joint application with transmit diversity schemes. It is shown by a theoretical analysis for 16-QAM that the presented concept can equalize variations in bit reliabilities by employing different mapping rules for the transmission over the diversity branches. This significantly improves the receiver block error rate performance and, hence, the performance of the adaptive modulation and coding. This is proven by simulations at link-level in a multicarrier CDMA system for AWGN and fading channels employing turbo coded transmission.     

Molecular Origin of the Charge Carrier Mobility in Small Molecule Organic Semiconductors

Small‐molecule organic semiconductors are used in a wide spectrum of applications, ranging from organic light emitting diodes to organic photovoltaics. However, the low carrier mobility severely limits their potential, e.g., for large area devices. A number of factors determine mobility, such as molecular packing, electronic structure, dipole moment, and polarizability. Presently, quantitative ab initio models to assess the influence of these molecule‐dependent properties are lacking. Here, a multiscale model is presented, which provides an accurate prediction of experimental data over ten orders of magnitude in mobility, and allows for the decomposition of the carrier mobility into molecule‐specific quantities. Molecule‐specific quantitative measures are provided how two single molecule properties, the dependence of the orbital energy on conformation, and the dipole‐induced polarization determine mobility for hole‐transport materials. The availability of first‐principles based models to compute key performance characteristics of organic semiconductors may enable in silico screening of numerous chemical compounds for the development of highly efficient optoelectronic devices.     

Selective Functionalization of Microstructured Surfaces by Laser‐Assisted Particle Transfer

Microcavity arrays represent millions of different reaction compartments to screen, for example, molecular interactions, exogenous factors for cells or enzymatic activity. A novel method is presented to selectively synthesize different compounds in arrays of microcavities with up to 1 000 000 cavities per cm². In this approach, polymer microparticles with embedded pre‐activated monomers are selectively transferred into microcavities with laser radiation. After particle patterning, heating of the particle matrix simultaneously leads to diffusion and coupling of the monomers inside each microcavity separately. This method exhibits flexibility, not only in the choice of compounds, but also in the choice of particle matrix material, which determines the chemical reaction environment. The laser‐assisted selective functionalization of microcavities can be easily combined with the intensively growing number of laser applications for patterning of molecules and cells, which is useful for the development of novel biological assays.     

PET: a proton/electron telescope for studies of magnetospheric,solar, and galactic particles

The proton/electron telescope (PET) on SAMPEX (Solar, Anomalous, and Magnetospheric Particle Explorer) is designed to provide measurements of energetic electrons and light nuclei from solar, Galactic, and magnetospheric sources. PET is an all solid-state system that will measure the differential energy spectra of electrons from ~1 to ~30 MeV and H and He nuclei from ~20 to ~300 MeV/nucleon, with isotope resolution of H and He extending from ~20 to ~80 MeV/nucleon. As SAMPEX scans all local times and geomagnetic cutoffs over the course of its near-polar orbit, PET will characterize precipitating relativistic electron events during periods of declining solar activity, and it will examine whether the production rate of odd nitrogen and hydrogen molecules in the middle atmosphere by precipitating electrons is sufficient to affect O₃ depletion. In addition, PET will complement studies of the elemental and isotopic composition of energetic heavy (Z>2) nuclei on SAMPEX by providing measurements of H, He, and electrons. Finally, PET has limited capability to identify energetic positrons from potential natural and man-made sources     

Membrane proteins: from sequence to structure

The prediction of protein structure from sequence has been along-standing goal of molecular biology. Integral membrane proteins,once abhorred by protein chemists and crystallographers becauseof their insolubility and stubborn refusal to yield good crystals,now appear to hold great promises for efficient structure predictionand engineering. This is mainly due to the constraints on permissiblestructures imposed by the lipid environment, and to the apparentuncoupling between an initial membrane targeting and insertionprocess which determines the overall topological arrangementof the transmembrane segments and a subsequent –condensation—of these segments into a unique folded state. Recent work suggeststhat the membrane insertion process is controlled by simplesequence elements composed of different combinations of longhydrophobic regions and flanking charged residues. In this reviewwe sketch the most unportant structural rules relating aminoacid sequence to membrane insertion to fully folded molecule,and their use for prediction and protein-engineering purposes.     

Monitoring kidney and renal cyst volumes applying MR approaches on a rapamycin treated mouse model of ADPKD

Object  The aim of our study was to determine total cystic volume in a mouse model of PKD using MR imaging to monitor therapeutic effects in vivo. Materials and methods  We imaged eight female pcy-mice in two groups: four belonged to an untreated control group and four were treated with the anticystic agent rapamycin, which has proven to be effective in reducing cystogenesis in animal models. The mice were imaged using a 9.4 Tesla animal scanner. MRI measurements were taken at six time points during the therapy. Total renal volumes and total cyst volumes were calculated using a thresholding approach. Results  During the course of the treatment, the total cyst volume increased significantly faster than the total renal volume in the untreated group, indicating that growth of the total renal volume in the untreated group was primarily due to the growth of the cysts, rather than the parenchyma. The measured total renal volume in the control (placebo) group was significantly higher than the volume in the treated group. Conclusion  Using MRI, we were able to monitor the cystic volume in a mouse model of PKD to assess the therapeutic effect of anticystic treatment.     

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.     

Pre-adolescent children exhibit lower aerosol particle volume emissions than adults for breathing,speaking, singing and shouting

Speaking and singing are activities linked to increased aerosol particle emissions from the respiratory system, dependent on the utilized vocal intensity. As a result, these activities have experienced considerable restrictions in enclosed spaces since the onset of the COVID-19 pandemic due to the risk of infection from the SARS-CoV-2 virus, transmitted by virus-carrying aerosols. These constraints have affected public education and extracurricular activities for children as well, from in-person music instruction to children’s choirs. However, existing risk assessments for children have been based on emission measurements of adults. To address this, we measured the particle emission rates of 15 pre-adolescent children, all eight to ten years old, with a laser particle counter for the test conditions: breathing at rest, speaking, singing and shouting. Compared with values taken from 15 adults, emission rates for breathing, speaking and singing were significantly lower for children. Particle emission rates were reduced by a factor of 4.3 across all conditions, whereas emitted particle volume rates were reduced by a factor of 4.8. These data can supplement SARS-CoV-2 risk management scenarios for various school and extracurricular settings.