Peptide aptamers provide probes for biological processes and adjuncts for development of novel pharmaceutical molecules. Such aptamers are analogous to compounds derived from combinatorial chemical libraries which have specific binding or inhibitory activities. Much as it is generally difficult to determine the composition of combinatorial chemical libraries in a quantitative manner, determining the quality and characteristics of peptide libraries displayed in vivo is problematical. To help address these issues we have adapted green fluorescent protein (GFP) as a scaffold for display of conformationally constrained peptides. The GFP-peptide libraries permit analysis of library diversity and expression levels in cells and allow enrichment of the libraries for sequences with predetermined characteristics, such as high expression of correctly folded protein, by selection for high fluorescence.

Non-pharmaceutical interventions (NPIs) are important to mitigate the spread of infectious diseases as long as no vaccination or outstanding medical treatments are available. We assess the effectiveness of the sets of non-pharmaceutical interventions that were in place during the course of the Coronavirus disease 2019 (Covid-19) pandemic in Germany. Our results are based on hybrid models, combining SIR-type models on local scales with spatial resolution. In order to account for the age-dependence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we include realistic prepandemic and recently recorded contact patterns between age groups. The implementation of non-pharmaceutical interventions will occur on changed contact patterns, improved isolation, or reduced infectiousness when, e.g., wearing masks. In order to account for spatial heterogeneity, we use a graph approach and we include high-quality information on commuting activities combined with traveling information from social networks. The remaining uncertainty will be accounted for by a large number of randomized simulation runs. Based on the derived factors for the effectiveness of different non-pharmaceutical interventions over the past months, we provide different forecast scenarios for the upcoming time.

Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation (TBI). Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.

Genetic selections that use proteinaceous transdominant inhibitors encoded by DNA libraries to cause mutant phenocopies may facilitate genetic analysis in traditionally nongenetic organisms. We performed a selection for random short peptides and larger protein fragments (collectively termed ''perturbagens'') that inhibit the yeast pheromone response pathway. Peptide and protein fragment perturbagens that permit cell division in the presence of pheromone were recovered. Two perturbagens were derived from proteins required for pheromone response, and an additional two were derived from proteins that may negatively influence the pheromone response pathway. Furthermore, three known components of the pathway were identified as probable perturbagen targets based on physical interaction assays. Thus, by selection for transdominant inhibitors of pheromone response, multiple pathway components were identified either directly as gene fragments or indirectly as the likely targets of specific perturbagens. These results, combined with the results of previous work [Holzmayer, T.

Purpose The current study aimed to evaluate how open-wedge high tibial osteotomy (OWHTO) without the release of medial collateral ligament (MCL) changes in vivo intra-articular joint space after the surgery. Methods Patients with varus malalignment of the knee with an indication for OWHTO were included in this study. The intra-articular gap was measured before and 30 min after OWHTO without MCL release using a series of calibrated nerve hooks. The association of post-operative gap size with varus angle, medial proximal tibial angle (MPTA), lateral distal femoral angle (LDFA) and joint line convergence angle (JLCA) was also assessed. Results A total of 42 knees from 38 patients were evaluated. The mean size of the intra-articular gap of the medial compartment was 5.2 ± 1 mm before the osteotomy and 3.1 ± 2.2 mm at 30 min post-osteotomy. The size of the intra-articular gap decreased post-operatively in 30 knees (71.5%), increased in eight knees (19%) and remained the same in the remaining four knees (9.5%). Smaller MPTA and more correction were associated with a decrease in gap size after the osteotomy (p = 0.01 and p = 0.03, respectively). A significant negative correlation was observed between the correction size and the gap size after osteotomy (r = − 0.317, p = 0.04). Conclusion Intra-articular pressure of the medial compartment increases in the majority of cases following OWHTO without MCL release. Until the factors affecting this increased pressure are thoroughly identified, MCL release seems to be a wiser option during OWHTO. Level of evidence III. KeywordsOpen-wedge high tibial osteotomy • Medial collateral ligament • Gap size • Intra-articular pressure Abbreviations MCL Medial collateral ligament OWHTO Open-wedge high tibial osteotomy MPTA Medial proximal tibial angle LDFA Lateral distal femoral angle JLCA Joint line convergence angle * Hooman Yahyazadeh