Gu-4 Suppresses Affinity and Avidity Modulation of CD11b and Improves the Outcome of Mice with Endotoxemia and Sepsis

BACKGROUND: Systemic leukocyte activation and disseminated leukocyte adhesion will impair the microcirculation and cause severe decrements in tissue perfusion and organ function in the process of severe sepsis. Gu-4, a lactosyl derivative, could selectively target CD11b to exert therapeutic effect in a rat model of severe burn shock. Here, we addressed whether Gu-4 could render protective effects on septic animals. METHODOLOGY/PRINCIPAL FINDINGS: On a murine model of endotoxemia induced by lipopolysaccharide (LPS), we found that the median effective dose (ED50) of Gu-4 was 0.929 mg/kg. In vivo treatment of Gu-4 after LPS challenge prominently attenuated LPS-induced lung injury and decreased lactic acid level in lung tissue. Using the ED50 of Gu-4, we also demonstrated that Gu-4 treatment significantly improved the survival rate of animals underwent sepsis induced by cecal ligation and puncture. By adhesion and transwell migration assays, we found that Gu-4 treatment inhibited the adhesion and transendothelial migration of LPS-stimulated THP-1 cells. By flow cytometry and microscopy, we demonstrated that Gu-4 treatment inhibited the exposure of active I-domain and the cluster formation of CD11b on the LPS-stimulated polymorphonuclear leukocytes. Western blot analyses further revealed that Gu-4 treatment markedly inhibited the activation of spleen tyrosine kinase in LPS-stimulated THP-1 cells. CONCLUSIONS/SIGNIFICANCE: Gu-4 improves the survival of mice underwent endotoxemia and sepsis, our in vitro investigations indicate that the possible underlying mechanism might involve the modulations of the affinity and avidity of CD11b on the leukocyte. Our findings shed light on the potential use of Gu-4, an interacting compound to CD11b, in the treatment of sepsis and septic shock

Utilizing heat regeneration within hydraulic pressure accumulator

Tekniikan kehittyessä toimilaitteiden ja järjestelmien suunnittelussa ja toteutuksessa laitteiden ja koneiden energia- ja kustannustehokkuus nousevat jatkuvasti tärkeämpään rooliin. Hydraulisilla toimilaitteilla saavutetaan korkea tehotiheys, mutta järjestelmien kokonaishyötysuhde on usein heikko. Hyötysuhdetta voidaan nostaa lisäämällä järjestelmiin energian talteenotto, jolloin työkierroista voidaan normaalisti hukkaan menevää energiaa varastoida ja käyttää uudelleen seuraavassa työkierrossa. Hydraulisissa energian talteenottojärjestelmissä energiaa varastoidaan tyypillisesti hydraulipaineakkuihin. Paineakuissa energia varastoituu puristamalla paineakun kaasutilavuudessa olevaa kaasua. Puristusvaiheen aikana kaasun lämpötila nousee ja lämpö alkaa virrata paineakusta ympäristöön. Tämä energian virtaaminen ympäristöön muodostaa merkittävimmän yksittäisen paineakun hyötysuhdetta laskevan tekijän. Tämän työn tavoitteena oli nostaa mäntäpaineakun hyötysuhdetta hyödyntämällä lämmön regenerointia. Lämmön regeneroinnilla pyritään varastoimaan kaasussa puristusvaiheessa syntyvä lämpöenergia lämpöregeneraattoriin ja luovuttamaan energia takaisin kaasuun paineakun purkusyklin aikana. Työssä suunniteltu lämpöregeneraattori perustui faasimuutosmateriaalien hyödyntämiseen energiavarastona. Faasimuutosmateriaalit soveltuvat erinomaisesti lämpövarastoiksi, sillä ne kykenevät sitomaan suuren määrän energiaa faasimuutoksen aikana, jolloin työssä suunniteltu lämpöregeneraattori saatiin mahdutettua mäntäpaineakun sisälle. Työssä saatujen mittaustuloksien perusteella pääteltiin, että lämpöregeneraattorin dynamiikan merkitys nousi merkittävämmäksi kuin lämpöregeneraattorin kyky varastoida lämpöenergiaa. Lämpöregeneraattorin hidas dynamiikka ei mahdollista tehokasta energian talteenottoa nopeista puristus- tai purkusykleistä, ja tämän takia lämpöregeneraattorista saatava hyöty jäi pieneksi. Työssä toteutetulla lämpöregeneraattorilla saavutettiin parhaimmillaan 3 prosenttiyksikön hyötysuhteen nousu verrattaessa samaan mäntäpaineakkuun ilman lämmön regenerointia.As new technological advances are made the importance of energy efficiency and cost effective solutions are even more important when designing and producing new machine systems. Hydraulic systems offer great performance in different actuators, but the general efficiency of the whole hydraulic systems is usually low. Energy efficiency can be improved by utilizing energy recovery systems. With energy recovery some of the normally wasted energy can be recovered and used in the next work cycle. Hydraulic energy recovery systems usually store energy in hydraulic pressure accumulators. Within the hydraulic pressure accumulator, energy is stored by compressing gas inside the accumulator’s gas volume. When compressing gas, heat builds up within the gas and temperature difference between the gas and its surroundings causes heat energy to flow out of the gas. This energy flow is the single most significant factor lowering energy efficiency of the accumulator. The goal of this study was to increase the efficiency of piston type hydraulic pressure accumulator by utilizing heat regeneration. With heat regeneration, heat energy that is generated in the gas during compression cycle is stored in the heat regenerator to be released during the following decompression cycle. Heat regenerator designed in this study utilizes phase change materials to store heat energy. Phase change materials absorb a lot of energy during phase change and thus they are commonly used as heat storages. The results obtained in this study indicate that the dynamic properties of the heat regenerator are more important than the capability to store heat energy. Low dynamic properties prevent the heat regenerator from storing and releasing energy effectively during fast compression and decompression cycles. With the heat regenerator designed in this study the energy efficiency of the accumulator increased by maximum of 3 percentage units when compared to the same accumulator without heat regeneration

Role of stacking disorder in ice nucleation

The freezing of water affects the processes that determine Earth's climate. Therefore, accurate weather and climate forecasts hinge on good predictions of ice nucleation rates. Such rate predictions are based on extrapolations using classical nucleation theory, which assumes that the structure of nanometre-sized ice crystallites corresponds to that of hexagonal ice, the thermodynamically stable form of bulk ice. However, simulations with various water models find that ice nucleated and grown under atmospheric temperatures is at all sizes stacking-disordered, consisting of random sequences of cubic and hexagonal ice layers. This implies that stacking-disordered ice crystallites either are more stable than hexagonal ice crystallites or form because of non-equilibrium dynamical effects. Both scenarios challenge central tenets of classical nucleation theory. Here we use rare-event sampling and free energy calculations with the mW water model to show that the entropy of mixing cubic and hexagonal layers makes stacking-disordered ice the stable phase for crystallites up to a size of at least 100,000 molecules. We find that stacking-disordered critical crystallites at 230 kelvin are about 14 kilojoules per mole of crystallite more stable than hexagonal crystallites, making their ice nucleation rates more than three orders of magnitude higher than predicted by classical nucleation theory. This effect on nucleation rates is temperature dependent, being the most pronounced at the warmest conditions, and should affect the modelling of cloud formation and ice particle numbers, which are very sensitive to the temperature dependence of ice nucleation rates. We conclude that classical nucleation theory needs to be corrected to include the dependence of the crystallization driving force on the size of the ice crystallite when interpreting and extrapolating ice nucleation rates from experimental laboratory conditions to the temperatures that occur in clouds