Use of Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry to Demonstrate Decreased Serum Statin Levels after Extracorporeal LDL-Cholesterol Elimination

Background. Using our statin analysis method, it was possible to uncover a significant drop in statin levels (atorvastatin, simvastatin, and metabolites) after extracorporeal LDL-cholesterol elimination (EE) in severe familial hypercholesterolemia (FH). The purpose of this work was to identify the mechanism underlying this drop and its clinical significance as well as to propose measures to optimize a pharmacotherapeutical regimen that can prevent the loss of statins. Methods. Ultra High Performance Liquid Chromatography (UHPLC) connected to the triple quadrupole MS/MS system was used. Patients. A group of long-term treated patients (3–12 years of treatment) with severe FH (12 patients) and treated regularly by LDL-apheresis (immunoadsorption) or haemorheopheresis (cascade filtration) were included in this study. Results. After EE, the level of statins and their metabolites decreased (atorvastatin before/after LDL-apheresis: 8.83/3.46 nmol/l; before/after haemorheopheresis: 37.02/18.94 nmol/l). A specific loss was found (concentration of atorvastatin for LDL-apheresis/haemorheopheresis: 0.28/3.04 nmol/l in washing fluids; 11.07 nmol/l in filters). To prevent substantial loss of statin concentrations, a pharmacotherapeutic regimen with a longer time interval between the dose of statins and EE is recommended (15 hours). Conclusions. A specific loss of statins was found in adsorbent columns and filters. The decrease can be prevented by the suggested dosage scheme

Building A Winning NFL Roster: Best Practices For Sustained Success

The purpose of this capstone is to identify and analyze the factors that contribute to team success in the National Football League through a review of relevant literature, a survey of league personnel, and firsthand experience as a football administrator. This project first studies quantitative data regarding player acquisition, specifically the data behind the NFL entry draft. Next, the current literature regarding off the field processes such as leadership, organizational culture and engagement were reviewed and finally, a two-step Delphi method survey was distributed to a panel of current league professionals. This paper aims to find the most efficient and effective way for teams to acquire players and several ways to optimize that talent based on the best practices researched in organizational culture and leadership

Structure of the human NK cell NKR-P1:LLT1 receptor:ligand complex reveals clustering in the immune synapse.

Signaling by the human C-type lectin-like receptor, natural killer (NK) cell inhibitory receptor NKR-P1, has a critical role in many immune-related diseases and cancer. C-type lectin-like receptors have weak affinities to their ligands; therefore, setting up a comprehensive model of NKR-P1-LLT1 interactions that considers the natural state of the receptor on the cell surface is necessary to understand its functions. Here we report the crystal structures of the NKR-P1 and NKR-P1:LLT1 complexes, which provides evidence that NKR-P1 forms homodimers in an unexpected arrangement to enable LLT1 binding in two modes, bridging two LLT1 molecules. These interaction clusters are suggestive of an inhibitory immune synapse. By observing the formation of these clusters in solution using SEC-SAXS analysis, by dSTORM super-resolution microscopy on the cell surface, and by following their role in receptor signaling with freshly isolated NK cells, we show that only the ligation of both LLT1 binding interfaces leads to effective NKR-P1 inhibitory signaling. In summary, our findings collectively support a model of NKR-P1:LLT1 clustering, which allows the interacting proteins to overcome weak ligand-receptor affinity and to trigger signal transduction upon cellular contact in the immune synapse

Data Descriptor : A European Multi Lake Survey dataset of environmental variables, phytoplankton pigments and cyanotoxins

Under ongoing climate change and increasing anthropogenic activity, which continuously challenge ecosystem resilience, an in-depth understanding of ecological processes is urgently needed. Lakes, as providers of numerous ecosystem services, face multiple stressors that threaten their functioning. Harmful cyanobacterial blooms are a persistent problem resulting from nutrient pollution and climate-change induced stressors, like poor transparency, increased water temperature and enhanced stratification. Consistency in data collection and analysis methods is necessary to achieve fully comparable datasets and for statistical validity, avoiding issues linked to disparate data sources. The European Multi Lake Survey (EMLS) in summer 2015 was an initiative among scientists from 27 countries to collect and analyse lake physical, chemical and biological variables in a fully standardized manner. This database includes in-situ lake variables along with nutrient, pigment and cyanotoxin data of 369 lakes in Europe, which were centrally analysed in dedicated laboratories. Publishing the EMLS methods and dataset might inspire similar initiatives to study across large geographic areas that will contribute to better understanding lake responses in a changing environment.Peer reviewe

Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer

To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L−1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4°C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature

Macro-regional differentiation of the world: Authors’ concept and its application

This article is a continuation of the same authors’ study entitled ‘Concepts And Delimitation Of The World’s Macro-Regions’ prepared for the 1/2018 of this journal (Anděl et al. 2018). The main aim of the first part was an evaluation of the concepts and factors which have been used as a basis for the delimitation of the different macro-regions of the world. In this second part, the authors propose their own macro-regionalisation of the world – this is a combination of four concepts, with relatively different contents: those of De Blij and Muller (1997), Cole (1996), Huntington (1996) and Hampl (2009). This macro-regionalisation arises from sociocultural affiliation, economic interrelationships and territorial continuity. Along with the concept of the macro-regional differentiation of the world itself, we focus on evaluating the importance of the shaping of macro-regions, as well as assessing the positive and negative features of individual concepts and their influence on the macro-regional differentiation of the world

Macro-regional differentiation of the world: Authors’ concept and its application

This article is a continuation of the same authors' study entitled 'Concepts And Delimitation Of The World's Macro-Regions' prepared for the 1/2018 of this journal (Anděl et al. 2018). The main aim of the first part was an evaluation of the concepts and factors which have been used as a basis for the delimitation of the different macro-regions of the world. In this second part, the authors propose their own macro-regionalisation of the world this is a combination of four concepts, with relatively different contents: those of De Blij and Muller (1997), Cole (1996), Huntington (1996) and Hampl (2009). This macro-regionalisation arises from sociocultural affiliation, economic interrelationships and territorial continuity. Along with the concept of the macro-regional differentiation of the world itself, we focus on evaluating the importance of the shaping of macro-regions, as well as assessing the positive and negative features of individual concepts and their influence on the macro-regional differentiation of the world

Concepts and delimitation of the worldʼs macro-regions

The authors focus on the current differentiation of the world and on its cognitive, application and educational frameworks and importance for the present. Macro-regional differentiation of the world has resulted from geographic concepts and it is a foundation for understanding the global development of society. This article evaluates the specific concepts and factors that form concepts of world macro-regions prepared by famous authors. It also presents a methodological approach for macro-regional forming of the world. After a theoretical and methodological introduction there is a discussion of the differentiation of the world entitled “Macroregional differentiation of the world - formation and application.ˮ The authors also present their conception of world differentiation and evaluation of the creation macro-regions and their positive and negative influence of the macro-regional differentiation of the world

Macro-regional differentiation of the world: Authors' concept and its application

This article is a continuation of the same authors' study entitled 'Concepts And Delimitation Of The World's Macro-Regions' prepared for the 1/2018 of this journal (Anděl et al. 2018). The main aim of the first part was an evaluation of the concepts and factors which have been used as a basis for the delimitation of the different macro-regions of the world. In this second part, the authors propose their own macro-regionalisation of the world this is a combination of four concepts, with relatively different contents: those of De Blij and Muller (1997), Cole (1996), Huntington (1996) and Hampl (2009). This macro-regionalisation arises from sociocultural affiliation, economic interrelationships and territorial continuity. Along with the concept of the macro-regional differentiation of the world itself, we focus on evaluating the importance of the shaping of macro-regions, as well as assessing the positive and negative features of individual concepts and their influence on the macro-regional differentiation of the world