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The immune system must be able to respond to a myriad of different threats, each requiring a distinct type of response. Here, we demonstrate that the cytoplasmic lysine deacetylase HDAC7 in macrophages is a metabolic switch that triages danger signals to enable the most appropriate immune response. Lipopolysaccharide (LPS) and soluble signals indicating distal or far-away danger trigger HDAC7-dependent glycolysis and proinflammatory IL-1β production. In contrast, HDAC7 initiates the pentose phosphate pathway (PPP) for NADPH and reactive oxygen species (ROS) production in response to the more proximal threat of nearby bacteria, as exemplified by studies on uropathogenic Escherichia coli (UPEC). HDAC7-mediated PPP engagement via 6-phosphogluconate dehydrogenase (6PGD) generates NADPH for antimicrobial ROS production, as well as D-ribulose-5-phosphate (RL5P) that both synergizes with ROS for UPEC killing and suppresses selective inflammatory responses. This dual functionality of the HDAC7-6PGD-RL5P axis prioritizes responses to proximal threats. Our findings thus reveal that the PPP metabolite RL5P has both antimicrobial and immunomodulatory activities and that engagement of enzymes in catabolic versus anabolic metabolic pathways triages responses to different types of danger for generation of inflammatory versus antimicrobial responses, respectively.

Minimally invasive robotic-assisted surgeries have been increasingly used as a first-line of treatment for patients undergoing oncologic surgeries. In-situ tissue identification is critical to guide tissue resection and assist decision-making. Traditional intraoperative histopathologic analysis of frozen tissue sections can be time-consuming and present logistical challenges which interrupt surgical workflows. We report the development and implementation of a laparoscopic, drop-in version of the MasSpec Pen device integrated into the da Vinci Xi Surgical system for in vivo tissue analysis in a robotic-assisted porcine surgery. We evaluated the performance of the drop-in MasSpec Pen during surgery by introducing the device into the animal upper gastrointestinal system and performing in vivo analyses of the stomach and liver, including charred and bloody tissues after electrocauterization. The molecular profiles obtained included ions tentatively identified as metabolites and lipids typically observed with MasSpec Pen analysis, without causing observable tissue damage. Statistical classifiers built to distinguish porcine liver and stomach tissues using the in vivo data yielded an overall tissue identification accuracy of 98% (n = 53 analyses). The results provide evidence that the drop-in MasSpec Pen developed can be used to acquire mass spectra in vivo during a robotic-assisted surgery and might be used as an in vivo tissue assessment tool to help guide surgical resections and streamline surgical workflows.

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Proton transport resistance in the polymer electrolyte of proton exchange membrane fuel cells (PEMFCs) is a significant contributor to ohmic overpotential. Conductivity is largely controlled by water uptake, which requires a delicate water balance to avoid an increase in mass transport overpotential due to diffusion resistance in porous components. The present work explores this relationship with distributed liquid water and high frequency resistance (HFR) measurements. The HFR response to local changes in liquid water content is characterized for two gas diffusion layers (GDLs) with different thermal resistivities. From these experiments, it is shown that liquid water must be present in the gas diffusion layer (GDL) to minimize the HFR. Furthermore, the impact of varied saturation levels induced by GDL thermal gradients on drying transients is considered with both in-plane and through-plane neutron imaging.

Analyzing an athlete's “technique,” sport scientists often focus on preselected variables that quantify important aspects of movement. In contrast, coaches and practitioners typically describe movements in terms of basic postures and movement components using subjective and qualitative features. A challenge for sport scientists is finding an appropriate quantitative methodology that incorporates the holistic perspective of human observers. Using alpine ski racing as an example, this study explores principal component analysis (PCA) as a mathematical method to decompose a complex movement pattern into its main movement components. Ski racing movements were recorded by determining the three-dimensional coordinates of 26 points on each skier which were subsequently interpreted as a 78-dimensional posture vector at each time point. PCA was then used to determine the mean posture and principal movements (PMk) carried out by the athletes. The first four PMk contained 95.5 ± 0.5% of the variance in the posture vectors which quantified changes in body inclination, vertical or fore-aft movement of the trunk, and distance between skis. In summary, calculating PMk offered a data-driven, quantitative, and objective method of analyzing human movement that is similar to how human observers such as coaches or ski instructors would describe the movement.

The standard p-MBHA resin used during Boc-chemistry synthesis of peptides carrying C-terminal carboxamides is compromised by batch-to-batch variations in its performance. This can cause artificially 'difficult' couplings during peptide chain assembly, which may ultimately lead to failed syntheses given the inability to achieve acceptable coupling yields. To overcome these problems, we have developed a new approach by grafting a functionalized benzhydrylamine linker onto well-characterized and well-performing PAM resins. We combine optimized Boc-chemistry, high-performing PAM resins and new benzhydrylamine-based linkers to achieve improved syntheses of peptide amides. Here we present the synthesis of two new benzhydrylamine linkers and their attachment to selected PAM resins. This novel solid support was evaluated through the synthesis of selected 'difficult' conotoxins and monitoring the coupling efficiency using quantitative ninhydrin assay. The results show a superior performance of the novel linker solid support compared to the standard p-MBHA resins routinely used. In summary, we describe an alternative linker-resin system that allows improved access to C-terminal amide peptides employing Boc/Bzl chemistry.

Histone deacetylases (HDACs) silence genes by deacetylating lysine residues in histones and other proteins. HDAC inhibitors represent a new class of compounds with anti-inflammatory activity. This study investigated whether treatment with a broad spectrum HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), would prevent cardiac fibrosis, part of the cardiovascular remodelling in deoxycorticosterone acetate (DOCA)-salt rats.Control and DOCA-salt rats were treated with SAHA (25 mg x kg(-1) x day(-1) s.c.) for 32 days. Changes in cardiovascular structure and function were assessed by blood pressure in vivo and in Langendorff perfused hearts, ventricular papillary muscle and in aortic rings in vitro. Left ventricular collagen deposition was assessed by histology.Administration of SAHA to DOCA-salt rats attenuated the following parameters: the increased concentration of over 20 pro-inflammatory cytokines in plasma, increased inflammatory cell infiltration and interstitial collagen deposition, increased passive diastolic stiffness in perfused hearts, prolongation of action potential duration at 20% and 90% of repolarization in papillary muscle, development of left ventricular hypertrophy, systolic hypertension and changes in vascular dysfunction.The HDAC inhibitor, SAHA, attenuated the cardiovascular remodelling associated with DOCA-salt hypertensive rats and improved cardiovascular structure and function, especially fibrosis, in the heart and blood vessels, possibly by suppressing inflammation. Control of cardiac histone or non-histone protein acetylation is a potential therapeutic approach to preventing cardiac remodelling, especially cardiac fibrosis.

Vapor-liquid and liquid-liquid equilibrium ccompositions are presented for the ternary systems of H 2 O and propionic acid with refrigerant 23 (R23; CF 3 H), ethane, R13 (CCIF 3 ), SF 6 , and R116 (C 2 F 6 ) at 313 K, near the critical temperature of each solvent. Equilibria for most systems were determined at 15.0 MPa; the subcritical solvent SF 6 was studied at a pressure just above its vapor pressure at 313 K (4.0 MPa)

Background: There is limited insight into the mechanisms of anterior cruciate ligament injuries in alpine skiing, particularly among professional ski racers. Purpose: This study was undertaken to qualitatively describe the mechanisms of anterior cruciate ligament injury in World Cup alpine skiing. Study Design: Case series; Level of evidence, 4. Methods: Twenty cases of anterior cruciate ligament injuries reported through the International Ski Federation Injury Surveillance System for 3 consecutive World Cup seasons (2006-2009) were obtained on video. Seven international experts in the field of skiing biomechanics and sports medicine related to alpine skiing performed visual analyses of each case to describe the injury mechanisms in detail (skiing situation, skier behavior, biomechanical characteristics). Results: Three main categories of injury mechanisms were identified: slip-catch, landing back-weighted, and dynamic snowplow. The slip-catch mechanism accounted for half of the cases (n = 10), and all these injuries occurred during turning, without or before falling. The skier lost pressure on the outer ski, and while extending the outer knee to regain grip, the inside edge of the outer ski caught abruptly in the snow, forcing the knee into internal rotation and valgus. The same loading pattern was observed for the dynamic snowplow (n = 3). The landing back-weighted category included cases (n = 4) where the skier was out of balance backward in flight after a jump and landed on the ski tails with nearly extended knees. The suggested loading mechanism was a combination of tibiofemoral compression, boot-induced anterior drawer, and quadriceps anterior drawer. Conclusion: Based on this video analysis of 20 injury situations, the main mechanism of anterior cruciate ligament injury in World Cup alpine skiing appeared to be a slip-catch situation where the outer ski catches the inside edge, forcing the outer knee into internal rotation and valgus. A similar loading pattern was observed for the dynamic snowplow. Injury prevention efforts should focus on the slip-catch mechanism and the dynamic snowplow.

INTRODUCTION: Fore/aft position and movement are important technical characteristics in ski racing that may affect slalom performance (Tjorhom et al., 2007). While the overall fore/aft range of motion was described in earlier studies, the phasing of this motion remains to be understood. Different fore/aft strategies are observable between elite skiers (Figure 1). The purpose of this study was to quantify successful and less successful center-of-mass fore/aft movement strategies. METHODS: The performances of 6 members of the Norwegian men’s Europa Cup team were analyzed through 2 complete turns during a slalom race simulation. Skier 3–D positions (Figure 2) were determined from 4 panning cameras and calibration control points distributed near the course (Nachbauer et al., 1996). Utilizing the method of Schiefermuller et al. (2005), a local coordinate system (LCS) originating at the outside ankle joint center was defined at each point in time. RESULTS: Fore/aft position is graphed in Figure 4 showing the ensemble average across skiers which involved about 28 cm range of motion.

Migration rates of radiolabelled antioxidants, Irganox-1010 (I-1010) and Irganox-1076 (I-1076), were measured from low- and high-density polyethylenes (LDPE, HDPE) and polypropylene (PP) at temperatures up to 135 degrees C. Water, 8 and 95 per cent aqueous ethanol and corn oil were employed as food simulating liquids (FSL). The experiments were conducted in a high-pressure cell in a manner that allowed contact between the polyolefin plaque and the FSL only during the test period and not while being heated. The migrations of the antioxidants varied with the square root of time, and the Fickian diffusion coefficients could be correlated with temperature in an Arrhenius fashion. Under comparable test conditions, antioxidant migrations were largest from PP for aqueous simulants, but for non-aqueous simulants the highest losses were from LDPE. In both instances lowest losses were from HDPE. In most instances there was little difference between the migration behaviour of I-1010 and I-1076. A few tests were conducted to measure the antioxidant migrations to foods. The losses were usually larger than those to water but below those to corn oil.

Kurnik, R.T. and Reid, R.C., 1982. Solubility of solid mixtures in supercritical fluids. Fluid Phase Equilibria, 8: 93-105 Supercritical fluids are receiving widespread attention as possible extraction agents for relatively non-volatile solids and liquids. Previous studies of the solubility of solids in supercritical fluids have been limited to pure solids. These pure-component data are interesting and indicate novel properties of supercritical fluids in this respect. The more general problem, however, lies in determining the solubility of multicomponent solids in supercritical fluids. Experimental data have now been obtained on the solubilities of binary, solid hydrocarbon mixtures in both supercritical carbon dioxide and supercritical ethylene. Most of the behavior exhibited by pure solids in supercritical fluids still exists for multicomponent solid solute systems (e.g., retrograde solidification, solubility extrema), but new phenomena were also found. The most interesting finding is that the solubility of a solid component when in a multicomponent solute system can be as much as 300% higher than the component solubility in a pure solid system at the same operating conditions. The multicomponent-solid-fluid data usually correlate well with thermodynamic theory.

Carbon dioxide and hydrogen will react over iron at 800° to 1 000°K and 1 bar pressure yielding water, carbon monoxide, methane, and carbon. In addition, iron oxides and carbides form during reaction. Phase diagrams are used to analyze this complex reaction system. Data are presented which suggest that the formation of magnetite (Fe3O4) or wustite (FexO) inhibits carbon formation. The water yield thus observed is limited by the time dependent iron-iron oxide-gas equilibrium. Preliminary data also suggest that the formation of carbides has little effect on water yield.

The solubilities of phenanthrene and benzoic acid were measured in supercritical carbon dioxide and ethane entrained with a small amount of benzene, acetone, methylene chloride or cyclohexane. Most of the experiments involved measuring the solubility of the solute as a function of entrainer composition, but some isocratic solubility data over a pressure range 100–300 bar was also obtained. It was found that the solubilities of both solutes increased with increasing amount of entrainer present in the supercritical gas, but that the specific entrainer used made little difference. Two elementary theoretical models of the entrained solvent were evaluated with the result that the data were better explained by considering the entrainer as a second solvent mixture rather than as a modifier of the supercritical fluid density. The solubilities of naphthalene and benzoic acid were also measured in a supercritical gas mixture containing 6.2 mol% ethane in carbon dioxide. In both cases the observed solubilities fell at an intermediate value between the known solubilities of the solutes in the pure supercritical solvents. Again, the addition of the second component to the gas appeared to behave as a chemical modifier of the solvent power of the fluid rather than only as a modifier of the solvent's PVT properties.

Currently available group-contribution methods for Tc, Pc, and Vc were evaluated using the Ambrose (1980) critical property data compilation. The Ambrose estimation methods were found to be the most accurate. Linear regression methods were also employed to develop alternate estimation methods which were found to have an accuracy comparable to those of Ambrose.