The masterpieces of John Forbes Nash Jr.

In this set of notes I follow Nash’s four groundbreaking works on real algebraic manifolds, on isometric embeddings of Riemannian manifolds and on the continuity of solutions to parabolic equations. My aim has been to stay as close as possible to Nash’s original arguments, but at the same time present them with a more modern language and notation. Occasionally I have also provided detailed proofs of the points that Nash leaves to the reader

Shifting the limits in wheat research and breeding using a fully annotated reference genome

Introduction: Wheat (Triticum aestivum L.) is the most widely cultivated crop on Earth, contributing about a fifth of the total calories consumed by humans. Consequently, wheat yields and production affect the global economy, and failed harvests can lead to social unrest. Breeders continuously strive to develop improved varieties by fine-tuning genetically complex yield and end-use quality parameters while maintaining stable yields and adapting the crop to regionally specific biotic and abiotic stresses. Rationale: Breeding efforts are limited by insufficient knowledge and understanding of wheat biology and the molecular basis of central agronomic traits. To meet the demands of human population growth, there is an urgent need for wheat research and breeding to accelerate genetic gain as well as to increase and protect wheat yield and quality traits. In other plant and animal species, access to a fully annotated and ordered genome sequence, including regulatory sequences and genome-diversity information, has promoted the development of systematic and more time-efficient approaches for the selection and understanding of important traits. Wheat has lagged behind, primarily owing to the challenges of assembling a genome that is more than five times as large as the human genome, polyploid, and complex, containing more than 85% repetitive DNA. To provide a foundation for improvement through molecular breeding, in 2005, the International Wheat Genome Sequencing Consortium set out to deliver a high-quality annotated reference genome sequence of bread wheat. Results: An annotated reference sequence representing the hexaploid bread wheat genome in the form of 21 chromosome-like sequence assemblies has now been delivered, giving access to 107,891 high-confidence genes, including their genomic context of regulatory sequences. This assembly enabled the discovery of tissue- and developmental stage–related gene coexpression networks using a transcriptome atlas representing all stages of wheat development. The dynamics of change in complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. Aspects of the future value of the annotated assembly for molecular breeding and research were exemplarily illustrated by resolving the genetic basis of a quantitative trait locus conferring resistance to abiotic stress and insect damage as well as by serving as the basis for genome editing of the flowering-time trait. Conclusion: This annotated reference sequence of wheat is a resource that can now drive disruptive innovation in wheat improvement, as this community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding. Importantly, the bioinformatics capacity developed for model-organism genomes will facilitate a better understanding of the wheat genome as a result of the high-quality chromosome-based genome assembly. By necessity, breeders work with the genome at the whole chromosome level, as each new cross involves the modification of genome-wide gene networks that control the expression of complex traits such as yield. With the annotated and ordered reference genome sequence in place, researchers and breeders can now easily access sequence-level information to precisely define the necessary changes in the genomes for breeding programs. This will be realized through the implementation of new DNA marker platforms and targeted breeding technologies, including genome editing

The SYBR Green I Malaria Drug Sensitivity Assay: Performance in Low Parasitemia Samples

Validation of the sensitivity of the SYBR Green I in vitro test against an enzyme-linked immunosorbent assay (ELISA)-based drug sensitivity assay. Our results suggest that the SYBR Green I assay is a fast and inexpensive malaria drug screening assay for laboratory use. However, because of its lack of sensitivity in whole blood samples its usefulness for testing clinical samples may be limited

Incubation of bacteria with PRF ± antimicrobial agent—Methods.

<p>Incubation of bacteria with PRF ± antimicrobial agent—Methods.</p

Mean zones of inhibition for MSSA and <i>K</i>. <i>pneumoniae</i> with PRF and polyhexanide.

<p>Bacterial eradication occurred within the first 24 hours only.</p

<i>In-vitro</i> release pharmacokinetics of amikacin, teicoplanin and polyhexanide in a platelet rich fibrin—layer (PRF)—a laboratory evaluation of a modern, autologous wound treatment - Fig 3

<p>Left: Mean zones of inhibition for MSSA and MRSA incubated with PRF and teicoplanin (MSSA σ = 0–5.5 mm; MRSA σ = 0–11.43 mm). Right: Release of teicoplanin out of a PRF-layer (σ = 7.5–42.8 mg/L; R square = 0.81).</p

Course of chronic acral heel—ulcer.

<p>A: initial wound without PRF-treatment (diameter of wound 6 cm), B: PRF and amikacin applied to wound, C: 11 weeks after initiation of therapy and after 10 applications of PRF and amikacin (diameter of wound 0.75 cm).</p

Identification of Filamentous Fungi by MALDI-TOF Mass Spectrometry: Evaluation of Three Different Sample Preparation Methods and Validation of an In-House Species Cutoff

Invasive infections caused by filamentous fungi constitute a leading cause of morbidity and mortality in immunocompromised patients. Rapid and reliable identification of filamentous fungi is essential for the early initiation of appropriate treatment. In the present study, 230 filamentous fungi isolates identified by conventional methods were investigated using MALDI-TOF MS (Bruker Daltonics, Bremen, Germany) in combination with the Filamentous Fungi Library 3.0 provided by the manufacturer. Three different sample preparation methods were applied as recommended by the manufacturer and identification rates were compared using the criteria provided by the manufacturer. Application of the more time-consuming sample preparation methods clearly improved identification at the species level. Thus, the identification rate increased from 48.9% using the simplest method to 76.1% with the most laborious procedure. Misidentifications did not occur. Furthermore, the reliability of an in-house threshold for species identification was investigated. The reduced threshold increased the rate of isolates correctly identified at the species level by up to 86.4%. As no misidentification was made at the genus level and only one misidentification of minor significance occurred at the species level, this threshold could be validated for routine use in our laboratory. In conclusion, regarding the high identification rates achieved, this commercial platform proved suitable for implementation in routine diagnosis

An Integrated Dialysis Pharmacometric (IDP) model to evaluate the pharmacokinetics in patients undergoing renal replacement therapy

Purpose: Clearance via renal replacement therapy (RRT) can significantly alter the pharmacokinetic profile of drugs. The aim of this study was (i) to improve the use of clinical trial data and (ii) to provide a model that allows quantification of all aspects of drug elimination via RRT including adsorption to dialysis membranes and/or degradation of the drug in the dialysate. Methods: An integrated dialysis pharmacometric (IDP) model was developed to simultaneously incorporate all available RRT information. The sensitivity, accuracy and precision of the IDP model was compared to conventional approaches in clinical trial simulations and applied to clinical datasets of teicoplanin and doripenem. Results: The IDP model was more accurate, precise and sensitive than conventional plasma-concentration-based approaches when estimating the clearance (relative bia