Stress response of a clinical Enterococcus faecalis isolate subjected to a novel antimicrobial surface coating

Emerging antibiotic resistance among pathogenic bacteria, paired with their ability to form biofilms on medical and technical devices, represents a serious problem for effective and long-term decontamination in health-care environments and gives rise to an urgent need for new antimicrobial materials. Here we present the impact of AGXX®, a novel broad-spectrum antimicrobial surface coating consisting of micro-galvanic elements formed by silver and ruthenium, on the transcriptome of Enterococcus faecalis. A clinical E. faecalis isolate was subjected to metal stress by growing it for different periods in presence of the antimicrobial coating or silver-coated steel meshes. Subsequently, total RNA was isolated and next-generation RNA sequencing was performed to analyze variations in gene expression in presence of the antimicrobial materials with focus on known stress genes. Exposure to the antimicrobial coating had a large impact on the transcriptome of E. faecalis. After 24min almost 1/5 of the E. faecalis genome displayed differential expression. At each time-point the cop operon was strongly up-regulated, providing indirect evidence for the presence of free Ag+-ions. Moreover, exposure to the antimicrobial coating induced a broad general stress response in E. faecalis. Genes coding for the chaperones GroEL and GroES and the Clp proteases, ClpE and ClpB, were among the top up-regulated heat shock genes. Differential expression of thioredoxin, superoxide dismutase and glutathione synthetase genes indicates a high level of oxidative stress. We postulate a mechanism of action where the combination of Ag+-ions and reactive oxygen species generated by AGXX®results in a synergistic antimicrobial effect, superior to that of conventional silver coatings.</p

Thermal comfort optimisation of vernacular rural buildings: passive solutions to retrofit a typical farmhouse in central Italy

An adequate retrofitting of traditional rural buildings requires to preserve their formal characteristics and to understand the constructive elements that compose them and which are different in different geographical areas. This paper analyses the typical farmhouses in central Italy. Starting from the definition of a vernacular building model, the paper analyses its performance in terms of thermal comfort and energy efficiency. The methodology involves the use of energy dynamic simulations coupled with optimisation techniques aimed to identify the best combinations of insulating materials in terms of choice of material and its optimal location in the envelope. The paper demonstrates the good thermal and energy performance of farmhouses in central Italy. The results of the optimisation process showed that in these buildings, with the addition of insulation materials with low conductivity the perceived discomfort in the inhabited areas of the building can be reduced by 79% and the energy consumption related to heating can be reduced by 77%. The level of insulation of the pavement that separates the ground and first floor needs to be more moderate to promote the heat flow between floors during summer. The sensitivity analysis shows that the most influential component for thermal comfort is the roof insulation

Port Protocols for Deadlock-Freedom of Component Systems

In component-based development, approaches for property verification exist that avoid building the global system behavior of the component model. Typically, these approaches rely on the analysis of the local behavior of fixed sized subsystems of components. In our approach, we want to avoid not only the analysis of the global behavior but also of the local behaviors of the components. Instead, we consider very small parts of the local behaviors called port protocols that suffice to verify properties.Comment: In Proceedings ICE 2010, arXiv:1010.530

Deleterious Impact of a Novel CFH Splice Site Variant in Atypical Hemolytic Uremic Syndrome

Atypical hemolytic uremic syndrome (aHUS) is a heterogeneous disorder characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and acute kidney injury (AKI). In about 50% of cases, pathogenic variants in genes involved in the innate immune response including complement factors complement factor H (CFH), CFI, CFB, C3, and membrane co-factor protein (MCP/CD46) put patients at risk for uncontrolled activation of the alternative complement pathway. As aHUS is characterized by incomplete penetrance and presence of additional triggers for disease manifestation, genetic variant interpretation is challenging and streamlined functional variant evaluation is urgently needed. Here, we report the case of a 27-year-old female without previous medical and family history who presented with confusion, petechial bleeding, and anuric AKI. Kidney biopsy revealed glomerular thrombotic microangiopathy (TMA). Targeted next generation sequencing identified a paternally transmitted novel heterozygous splice site variant in the CFH gene [c.3134-2A&gt;G; p.Asp1045_Thr1053del] which resulted in a partial in-frame deletion of exon 20 transcript as determined by cDNA analysis. On the protein level, the concomitant loss of 9 amino acids in the short consensus repeat (SCR) domains 17 and 18 of CFH includes a highly conserved cysteine residue, which is assumed to be essential for proper structural folding and protein function. Treatment with steroids, plasmapheresis, and the complement inhibitor eculizumab led to complete hematological and clinical remission after several months and stable renal function up to 6 years later. In conclusion, genetic investigation for pathogenic variants and evaluation of their functional impact, in particular in the case of splice site variants, is clinically relevant and enables not only better molecular understanding but helps to guide therapy with complement inhibitors

Survey in radiation oncology departments in Germany, Austria, and Switzerland: state of digitalization by 2023.

PURPOSE The aim of this work was to assess the current state of digitalization in radiation oncology departments in Germany, Austria, and Switzerland. METHODS A comprehensive survey was conducted in a digital format, consisting of 53 questions that covered various aspects of digitalization including patient workflow, departmental organization, radiotherapy planning, and employee-related aspects. RESULTS Overall, 120 forms were eligible for evaluation. Participants were mainly physicians or medical physicists responsible for digitalization aspects in their departments. Nearly 70% of the institutions used electronic patient records, with 50% being completely paperless. However, the use of smartphone apps for electronic patient reported outcomes (ePROMs) and digital health applications (DIGA) was limited (9% and 4.9%, respectively). In total, 70.8% of the radio-oncology departments had interfaces with diagnostic departments, and 36% had digital interchanges with other clinics. Communication with external partners was realized mainly through fax (72%), e‑mails (55%), postal letters (63%), or other digital exchange formats (28%). Almost half of the institutions (49%) had dedicated IT staff for their operations. CONCLUSION To the best of our knowledge, this survey is the first of its kind conducted in German-speaking radiation oncology departments within the medical field. The findings suggest that there is a varied level of digitalization implementation within these departments, with certain areas exhibiting lower rates of digitalization that could benefit from targeted improvement initiatives

Digital Elevation Models: Terminology and Definitions

Digital elevation models (DEMs) provide fundamental depictions of the three-dimensional shape of the Earth’s surface and are useful to a wide range of disciplines. Ideally, DEMs record the interface between the atmosphere and the lithosphere using a discrete two-dimensional grid, with complexities introduced by the intervening hydrosphere, cryosphere, biosphere, and anthroposphere. The treatment of DEM surfaces, affected by these intervening spheres, depends on their intended use, and the characteristics of the sensors that were used to create them. DEM is a general term, and more specific terms such as digital surface model (DSM) or digital terrain model (DTM) record the treatment of the intermediate surfaces. Several global DEMs generated with optical (visible and near-infrared) sensors and synthetic aperture radar (SAR), as well as single/multi-beam sonars and products of satellite altimetry, share the common characteristic of a georectified, gridded storage structure. Nevertheless, not all DEMs share the same vertical datum, not all use the same convention for the area on the ground represented by each pixel in the DEM, and some of them have variable data spacings depending on the latitude. This paper highlights the importance of knowing, understanding and reflecting on the sensor and DEM characteristics and consolidates terminology and definitions of key concepts to facilitate a common understanding among the growing community of DEM users, who do not necessarily share the same background

Books in Arabic Script

The chapter approaches the book in Arabic script as the indispensable means for the transmission of knowledge across Eurasia and Africa, within cultures and across cultural boundaries, since the seventh century ad. The state of research can be divided into manuscript and print studies, but there is not yet a history of the book in Arabic script that captures its plurilinear development for over fourteen hundred years. The chapter explores the conceptual and practical challenges that impede the integration of the book in Arabic script into book history at large and includes an extensive reference list that reflects its diversity. The final published version was slightly updated, and includes seven illustrations of six Qurans from the holdings of Columbia University Libraries, four manuscripts and two printed versions. Moreover, the illustrations are images of historical artifacts which are in the public domain - despite Wiley's copyright claim

Reconstructing the evolution of the mitochondrial ribosomal proteome

For production of proteins that are encoded by the mitochondrial genome, mitochondria rely on their own mitochondrial translation system, with the mitoribosome as its central component. Using extensive homology searches, we have reconstructed the evolutionary history of the mitoribosomal proteome that is encoded by a diverse subset of eukaryotic genomes, revealing an ancestral ribosome of alpha-proteobacterial descent that more than doubled its protein content in most eukaryotic lineages. We observe large variations in the protein content of mitoribosomes between different eukaryotes, with mammalian mitoribosomes sharing only 74 and 43% of its proteins with yeast and Leishmania mitoribosomes, respectively. We detected many previously unidentified mitochondrial ribosomal proteins (MRPs) and found that several have increased in size compared to their bacterial ancestral counterparts by addition of functional domains. Several new MRPs have originated via duplication of existing MRPs as well as by recruitment from outside of the mitoribosomal proteome. Using sensitive profile–profile homology searches, we found hitherto undetected homology between bacterial and eukaryotic ribosomal proteins, as well as between fungal and mammalian ribosomal proteins, detecting two novel human MRPs. These newly detected MRPs constitute, along with evolutionary conserved MRPs, excellent new screening targets for human patients with unresolved mitochondrial oxidative phosphorylation disorders