Mitochondrial Diagnostics: A Multiplexed Assay Platform for Comprehensive Assessment of Mitochondrial Energy Fluxes

Chronic metabolic diseases have been linked to molecular signatures of mitochondrial dysfunction. Nonetheless, molecular remodeling of the transcriptome, proteome, and/or metabolome does not necessarily translate to functional consequences that confer physiologic phenotypes. The work here aims to bridge the gap between molecular and functional phenomics by developing and validating a multiplexed assay platform for comprehensive assessment of mitochondrial energy transduction. The diagnostic power of the platform stems from a modified version of the creatine kinase energetic clamp technique, performed in parallel with multiplexed analyses of dehydrogenase activities and ATP synthesis rates. Together, these assays provide diagnostic coverage of the mitochondrial network at a level approaching that gained by molecular “-omics� technologies. Application of the platform to a comparison of skeletal muscle versus heart mitochondria reveals mechanistic insights into tissue-specific distinctions in energy transfer efficiency. This platform opens exciting opportunities to unravel the connection between mitochondrial bioenergetics and human disease

SARS-CoV-2 mRNA vaccine induces robust specific and cross-reactive IgG and unequal neutralizing antibodies in naive and previously infected people

Understanding vaccine-mediated protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical to overcoming the global coronavirus disease 2019 (COVID-19) pandemic. We investigate mRNA-vaccine-induced antibody responses against the reference strain, seven variants, and seasonal coronaviruses in 168 healthy individuals at three time points: before vaccination, after the first dose, and after the second dose. Following complete vaccination, both naive and previously infected individuals developed comparably robust SARS-CoV-2 spike antibodies and variable levels of cross-reactive antibodies to seasonal coronaviruses. However, the strength and frequency of SARS-CoV-2 neutralizing antibodies in naive individuals were lower than in previously infected individuals. After the first vaccine dose, one-third of previously infected individuals lacked neutralizing antibodies; this was improved to one-fifth after the second dose. In all individuals, neutralizing antibody responses against the Alpha and Delta variants were weaker than against the reference strain. Our findings support future tailored vaccination strategies against emerging SARS-CoV-2 variants as mRNA-vaccine-induced neutralizing antibodies are highly variable among individuals

Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease activity, physical inactivity, and disability

Abstract Background: To identify molecular alterations in skeletal muscle in rheumatoid arthriti

Modified nodal analysis for building energy simulations

W artykule przedstawiono metodę wyznaczania ilości ciepła do ogrzewania i chłodzenia budynku, wykorzystującą model budynku w postaci sieci przepływu ciepła z elementami gałęzi o skupionych parametrach pojemności i przewodności cieplnej. Analogia matematyczna sieci przepływu ciepła i sieci elektrycznych pozwala na zastosowanie podobnych metod rozwiązywania tych układów. W artykule opisano metodę potencjałów węzłowych oraz wskazano jej wady, które często uniemożliwiają zastosowanie tej metody do opisu sieci przepływu ciepła w budynku. W dalszej części przedstawiono modyfikację metody potencjałów węzłowych, która usuwa wykazane wady metody klasycznej, pozwalając na opis sieci przepływu ciepła w budynku z wykorzystaniem sieci z węzłami w których zadane są wartości temperatury. Przedstawiona metoda pozwala na automatyczne, komputerowe, formułowanie układu równań opisujących sieć przepływu energii w budynku umożliwiając szybkie modyfikowanie schematów modeli budynku używanych do analiz energetycznych. W przeciwieństwie do równań podanych w normie PN EN ISO 13790, opisana metoda nie wymaga wyprowadzania nowych równań opisujących uproszczony godzinowy model dynamiki cieplnej budynku. Układ równań zmodyfikowanego modelu godzinowego budynku może być automatycznie generowany na podstawie topologii schematu modelu przyjętego do obliczeń. Na końcu artykułu w dodatku przedstawiono przykładowe macierze składowe gałęzi oraz macierz główną i wektor wyrazów wolnych dla modelu 5R1C wyznaczony zmodyfikowaną metodą potencjałów węzłowych.This paper presents principles of modified nodal analysis used to solve lumped parameters networks which model whole building heat exchange. The lumped capacitance and resistance 5R1C or 6R1C method used for whole building modelling with simple hourly method utilize predefined equations presented in PN EN ISO 13790 standard. Modification of building energy network model causes that the model equations have to be determined again. The problem can be solved with graph theory and classic nodal analysis used for determining node potentials, which are in the case of building energy analysis, nodes temperature. This method whatever is very useful, cannot be used for networks containing branches with ideal potential sources. Modified nodal analysis combines dual graph topology with network admittance branches classified for the first group, and impedance branches classified for second group. Branch elements can be presented as stamp matrices which are used for define main matrix and right hand side vector of network equation system. Modified nodal analysis can be used for automatic formulation of equation set which then can be solved with any efficient numerical method. This approach allows to quickly modify building model and provide energy analysis without deriving new equations for that model as presented in PN EN ISO 13790 standard

Ewolucja kryteriów wyboru i wartości temperatury obliczeniowej powietrza zewnętrznego dla ogrzewnictwa w Polsce

Wartości temperatury obliczeniowej powietrza zewnętrznego mają podstawowe znaczenie w procesie wyznaczania zapotrzebowania na moc cieplną dla budynków oraz wpływają na proces projektowania i wymiarowania urządzeń ogrzewczych. W Polsce ostania modyfikacja normy dotyczącej obliczeniowych temperatur zewnętrznych dla ogrzewnictwa miała miejsce w 1982 roku, jakkolwiek wartości te nie zmieniały się od kilkudziesięciu lat. Dostępne obecnie dane meteorologiczne z wielolecia dla 61 stacji meteorologicznych, normy europejskie dotyczące danych klimatycznych wykorzystywanych w budownictwie, komputerowe systemy symulacji energetycznych budynków oraz coraz nowocześniejsze technologie stosowane w budownictwie zmuszają do zastanowienia się nad weryfikacją obecnie wykorzystywanych temperatur obliczeniowych dla ogrzewnictwa. W prezentowanym artykule przedstawione zostaną zmiany w doborze kryteriów wyboru oraz wartości temperatury obliczeniowej dla ogrzewnictwa w Polsce na przestrzeni lat

Instructions for camera- ready papers

W artykule przedstawiono uproszczoną metodę wyznaczania ilości ciepła do ogrzewania i chłodzenia budynku zbudowaną w oparciu o analogię elektryczną modelu skupionej pojemności cieplnej. Podstawą modelu nieustalonego procesu wymiany ciepła pomiędzy budynkiem i jego otoczeniem jest układ 5R1C, którego zachowanie się opisuje równanie różniczkowe zwyczajne. W pracy przedstawiono metodę rozwiązania równania tego modelu przy zmiennych warunkach brzegowych zmodyfikowaną metodą Eulera, która wraz z metodą superpozycji układu liniowego w pojedynczej chwili czasu prowadzi do równań uproszczonej godzinowej metody dynamiki cieplnej budynku.This paper presents the basis of 5R1C model of building heat exchange with the outer environment. The lumped capacitance method used for whole building is utilized to get equations of simply 5RIC hour method. This method can be used for calculation of heat and cool demand for building and is adopted in Poland for determining energy performance class for nonrcsidential buildings as required by HU Energy Performance Building Directive. The article was written due to the support of STEP Project PL 0077 financed by a grant from Iceland. Liechtenstein and Norway through the EEA Financial Mechanism and the Norwegian Financial Mechanis

Simulation Studies on the Effect of Material Characteristics and Runners Layout Geometry on the Filling Imbalance in Geometrically Balanced Injection Molds

Simulation studies were performed on filling imbalance in geometrically balanced injection molds. A special simulation procedure was applied to simulate properly the phenomenon, including inertia effects and 3D tetrahedron meshing as well as meshing of the nozzle. The phenomenon was investigated by simulation using several different runner systems at various thermo-rheological material parameters and process operating conditions. It has been observed that the Cross-WLF parameters, index flow, critical shear stress (relaxation time), and zero viscosity, as well as thermal diffusivity and heat transfer coefficient strongly affect the filling imbalance. The effect is substantially dependent on the runners’ layout geometry, as well as on the operating conditions, flow rate, and shear rate. The standard layout geometry and the corrected layout with circled element induce positive imbalance which means that inner cavities fills out faster, and it is opposite for the corrected layouts with one/two overturn elements which cause negative imbalance. Generally, for the standard layout geometry and the corrected layout with circled element, an effect of the zero shear rate viscosity η0 is positive (imbalance increases with an increase of viscosity), and an effect of the power law index n and the relaxation time λ is negative (imbalance decreases with an increase of index n and relaxation time λ). An effect of the thermal diffusivity α and heat transfer coefficient h is negative while an effect of the shear rate is positive. For the corrected layouts with one/two overturn elements, the results of simulations indicate opposite relationships. A novel optimization approach solving the filling imbalance problem and a novel concept of global modeling of injection molding process are also discussed

Study on filling patterns of engineering polymers In geometrically balanced injection molds

Filling patterns and imbalances which occur during injection molding of engineering plastics, e.g. Polyoxymethylene (POM), have been studied. Four different geometries of runner systems have been applied for experimentation. Autodesk Moldflow software has been used for finite element method (FEM) simulations of imbalance phenomenon. Evolution strategies have been suggested for optimization of runner systems in multi-cavity injection molds

Simulation of Polymer Injection Molding: A New Practical Approach to Improve Computation Accuracy

Simulation of injection molding of polymeric materials is still a series scientific and engineering problem. The quality of the input data is crucial for computation accuracy. The original, relatively simple tool has been designed to validate simulations. This allows a fast identification of the critical input data, and next their proper adjustment to computations. FEM simulations have been compared with directly registered pictures of cavity filling process in a special injection mold with a sight-glass

Polymer injection molding: advanced simulations or tablet computations

Simulation of injection molding of polymeric materials is a common way of solving issues in plastic part and injection mold design. CAE software is getting more available and user-friendly, which sometimes leads to unreasonable use cases of these programs. The original, relatively simple tool has been introduced to validate runner systems in injection molds. It allows a fast identification of the most important design parameters of runner system. This tool does not require any support of FEM simulations, but results obtained from it have been successfully compared with injection molding simulations