Statistical analysis of Sequence-Structure Alignment Scores

The structural analysis of proteins is fundamental to the analysis of protein functions. In this context, sequence-structure alignment methods are important among the different empirical methods. In order to assess the quality of sequence-structure alignments, a statistical method using a Bayesian approach proposed by Lathrop et al. (1998) will be presented. Finally, the results of a developed statistical analysis of scores of RDP(recursive dynamic programming)-sequence-structure alignments (Thiele et al., 1999) according to data of six proteins will be described

Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA) Following SARS-CoV2 Vaccination

A 67-year-old man presented with joint swelling, muscular weakness, pain and anemia after the second dose of BNT162b2 (Pfizer-Biontech) mRNA COVID-19 vaccination. The signs and symptoms in the case met criteria for post-vaccination polymyalgia rheumatica (PMR) and Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA) demonstrating the close association between these two conditions. The patient underwent a broad workup to rule out other causes and improved with corticosteroid therapy. Vaccine-associated autoimmune syndromes likely have heterogenous presentations and require a high index of suspicion to expedite recognition and treatment

12-Month outcomes of transcatheter tricuspid valve repair with the PASCAL system for severe tricuspid regurgitation

Objectives We investigated the durability of tricuspid regurgitation (TR) reduction and the clinical outcomes through 12 months after transcatheter tricuspid valve repair (TTVr) with the PASCAL Transcatheter Valve Repair System. Background TTVr has rapidly developed and demonstrated favorable acute outcomes, but longer follow-up data are needed. Methods Overall, 30 patients (age 77 ± 6 years; 57% female) received PASCAL implantation from September 2017 to May 2019 and completed a clinical follow-up at 12 months. Results The TR etiology was functional in 25 patients (83%), degenerative in three (10%), and mixed in two (7%). All patients had TR severe or greater (massive or torrential in 80%) and heart failure symptoms (90% in NYHA III or IV) under optimal medical treatment. Single-leaflet device attachment occurred in two patients. Moderate or less TR was achieved in 23/28 patients (82%) at 30 days, which was sustained at 12 months (86%). Two patients underwent repeat TTVr due to residual torrential TR (day 173) and recurrence of severe TR (day 280), respectively. One-year survival rate was 93%; 6 patients required rehospitalization due to acute heart failure. NYHA functional class I or II was achieved in 90% and 6-minute walk distance improved from 275 ± 122 m at baseline to 347 ± 112 m at 12-month (+72 ± 82 m, p < .01). There was no stroke, endocarditis, or device embolization during the follow-up. Conclusions Twelve-month outcomes from this multicenter compassionate use experience with the PASCAL System demonstrated high procedural success, acceptable safety, and significant clinical improvement

MOSAiC goes O2A - Arctic Expedition Data Flow from Observations to Archives

During the largest polar expedition in history starting in September 2019, the German research icebreaker Polarstern spends a whole year drifting with the ice through the Arctic Ocean. The MOSAiC expedition takes the closest look ever at the Arctic even throughout the polar winter to gain fundamental insights and most unique on-site data for a better understanding of global climate change. Hundreds of researchers from 20 countries are involved. Scientists will use the in situ gathered data instantaneously in near-real time modus as well as long afterwards all around the globe taking climate research to a completely new level. Hence, proper data management, sampling strategies beforehand, and monitoring actual data flow as well as processing, analysis and sharing of data during and long after the MOSAiC expedition are the most essential tools for scientific gain and progress. To prepare for that challenge we adapted and integrated the research data management framework O2A “Data flow from Observations to Archives” to the needs of the MOSAiC expedition on board Polarstern as well as on land for data storage and access at the Alfred Wegener Institute Computing and Data Center in Bremerhaven, Germany. Our O2A-framework assembles a modular research infrastructure comprising a collection of tools and services. These components allow researchers to register all necessary sensor metadata beforehand linked to automatized data ingestion and to ensure and monitor data flow as well as to process, analyze, and publish data to turn the most valuable and uniquely gained arctic data into scientific outcomes. The framework further allows for the integration of data obtained with discrete sampling devices into the data flow. These requirements have led us to adapt the generic and cost-effective framework O2A to enable, control, and access the flow of sensor observations to archives in a cloud-like infrastructure on board Polarstern and later on to land based repositories for international availability. Major roadblocks of the MOSAiC-O2A data flow framework are (i) the increasing number and complexity of research platforms, devices, and sensors, (ii) the heterogeneous interdisciplinary driven requirements towards, e. g., satellite data, sensor monitoring, in situ sample collection, quality assessment and control, processing, analysis and visualization, and (iii) the demand for near real time analyses on board as well as on land with limited satellite bandwidth. The key modules of O2A's digital research infrastructure established by AWI are implementing the FAIR principles: SENSORWeb, to register sensor applications and sampling devices and capture controlled meta data before and alongside any measurements in the field Data ingest, allowing researchers to feed data into storage systems and processing pipelines in a prepared and documented way, at best in controlled near real-time data streams Dashboards allowing researchers to find and access data and share and collaborate among partners Workspace enabling researchers to access and use data with research software utilizing a cloud-based virtualized infrastructure that allows researchers to analyze massive amounts of data on the spot Archiving and publishing data via repositories and Digital Object Identifiers (DOI

Dissecting the action of an evolutionary conserved non-coding region on renin promoter activity

Elucidating the mechanisms of the human transcriptional regulatory network is a major challenge of the post-genomic era. One important aspect is the identification and functional analysis of regulatory elements in non-coding DNA. Genomic sequence comparisons between related species can guide the discovery of cis-regulatory sequences. Using this technique, we identify a conserved region CNSmd of ∼775 bp in size, ∼14 kb upstream of the renin gene. Renin plays a pivotal role for mammalian blood pressure regulation and electrolyte balance. To analyse the cis-regulatory role of this region in detail, we perform 132 combinatorial reporter gene assays in an in vitro Calu-6 cell line model. To dissect the role of individual subregions, we fit several mathematical models to the experimental data. We show that a multiplicative switch model fits best the experimental data and that one subregion has a dominant effect on promoter activity. Mapping of the sub-sequences on phylogenetic conservation data reveals that the dominant regulatory region is the one with the highest multi-species conservation score