Beer metabolomics: molecular details of the brewing process and the differential effects of late and dry hopping on yeast purine metabolism

The flavour of beer is complex, based upon changes at the molecular level in the key raw materials, notably grain, hops and yeast, as well as during the process stages that comprise malting and brewing. As analytical techniques evolve in their sophistication and sensitivity, there are opportunities to delve ever more deeply into the fate of small molecules in brewing. To this end, ¹H nuclear magnetic resonance (NMR) metabolomics was used to follow the progression of 76 metabolites in four different late or dry hopped beers (brewed in triplicate) at five time points throughout the brewing process. The majority of the metabolites identified, including sugars, amino acids and nucleotides, significantly decreased in concentration from the start of the boil to post‐secondary fermentation, whereas energy‐related and fatty acid associated metabolites significantly increased in concentration as wort nutrients were consumed by the yeast. Adenine was significantly higher in the dry hopped brews than in the late hopped brews after both primary (p = 2.1 × 10^?6) and secondary (p = 2.7 × 10^?9) fermentation, while 2′‐deoxyadenosine (after primary, p = 1.1 × 10^?2, after secondary, p = 3.2 × 10^?5) and adenosine (after primary, p = 2.6 × 10^?8; after secondary, p = 3.1 × 10^?7)were significantly lower in the dry hopped beers at these time points. These results give molecular insight into the brewing process and the differential effects of hopping methods on yeast purine metabolism. Copyright © 2016 The Institute of Brewing & Distilling     

Navy Prototype Optical Interferometer observations of geosynchronous satellites

Using a 15.9 m baseline at the Navy Prototype Optical Interferometer (NPOI), we have successfully detected interferometric fringes in observations of the geosynchronous satellite (geosat) DirecTV-9S while it glinted on two nights in March 2009. The fringe visibilities can be fitted by a model consisting of two components, one resolved (?3.7 m) and one unresolved (～1.1 m). Both the length of the glint and the specular albedos are consistent with the notion that the glinting surfaces are not completely flat and scatter reflected sunlight into an opening angle of roughly 15°. Enhancements to the NPOI that would improve geosat observations include adding an infrared capability, which could extend the glint season, and adding larger, adaptive-optics equipped telescopes. Future work may test the feasibility of observing geosats with aperture-masked large telescopes and of developing an array of six to nine elements.     

X‐FEM in isogeometric analysis for linear fracture mechanics

The extended finite element method (X‐FEM) has proven to be an accurate, robust method for solving problems in fracture mechanics. X‐FEM has typically been used with elements using linear basis functions, although some work has been performed using quadratics. In the current work, the X‐FEM formulation is incorporated into isogeometric analysis to obtain solutions with higher order convergence rates for problems in linear fracture mechanics. In comparison with X‐FEM with conventional finite elements of equal degree, the NURBS‐based isogeometric analysis gives equal asymptotic convergence rates and equal accuracy with fewer degrees of freedom (DOF). Results for linear through quartic NURBS basis functions are presented for a multiplicity of one or a multiplicity equal the degree. Copyright © 2011 John Wiley & Sons, Ltd.     

Douglas Haskell and the Modern Movement in American Architecture

The phenomenon of Post Modern culture has manifested itself primarily in two ways in contemporary architectural production and discourse. One, which is almost exclusively stylistic, has attempted to seek a renewal in architecture through the rejection of all aspects of Modernism in favor of a picturesque and superficial Classicism. This version of Post Modernism accepts de facto the pluralist world-view of contemporary capitalist development and avoids the larger questions of architecture's place within the complexities of today's socio-political universe. The other manifestation of Post Modernism in architecture is theoretical. It seeks a critical reading of architecture within the complex labyrinthe of contemporary culture. It tries to understand how meaning has come to have a tenuous existence in the artifacts and life of our time. It has proposed, both through theory and practice, various possibilities as to how we might negotiate this situation. This paper engages in discussion and critique of both of these orientations, their implications and ramifications.     

HIV-Tat Exacerbates the Actions of Atazanavir,Efavirenz, and Ritonavir on Cardiac Ryanodine Receptor (RyR2)

The incidence of sudden cardiac death (SCD) in people living with HIV infection (PLWH), especially those with inadequate viral suppression, is high and the reasons for this remain incompletely characterized. The timely opening and closing of type 2 ryanodine receptor (RyR2) is critical for ensuring rhythmic cardiac contraction–relaxation cycles, and the disruption of these processes can elicit Ca²⁺ waves, ventricular arrhythmias, and SCD. Herein, we show that the HIV protein Tat (HIV-Tat: 0–52 ng/mL) and therapeutic levels of the antiretroviral drugs atazanavir (ATV: 0–25,344 ng/mL), efavirenz (EFV: 0–11,376 ng/mL), and ritonavir (RTV: 0–25,956 ng/mL) bind to and modulate the opening and closing of RyR2. Abacavir (0–14,315 ng/mL), bictegravir (0–22,469 ng/mL), Rilpivirine (0–14,360 ng/mL), and tenofovir disoproxil fumarate (0–18,321 ng/mL) did not alter [³H]ryanodine binding to RyR2. Pretreating RyR2 with low HIV-Tat (14 ng/mL) potentiated the abilities of ATV and RTV to bind to open RyR2 and enhanced their ability to bind to EFV to close RyR2. In silico molecular docking using a Schrodinger Prime protein–protein docking algorithm identified three thermodynamically favored interacting sites for HIV-Tat on RyR2. The most favored site resides between amino acids (AA) 1702–1963; the second favored site resides between AA 467–1465, and the third site resides between AA 201–1816. Collectively, these new data show that HIV-Tat, ATV, EFV, and RTV can bind to and modulate the activity of RyR2 and that HIV-Tat can exacerbate the actions of ATV, EFV, and RTV on RyR2. Whether the modulation of RyR2 by these agents increases the risk of arrhythmias and SCD remains to be explored.     

Stimulation of ammonia production and excretion in the rabbit by inorganic phosphate. Study of control mechanisms

The purpose of this study was to clarify the mechanism (s) responsible for regulation of ammonia production and excretion in the rabbit. The normally low ammonia excretion rate during acute metabolic acidosis was stimulated acutely and increased approximately ninefold after infusion of sodium phosphate, but remained low if sodium sulphate or Tris was substituted for phosphate. Ammonia production was increased significantly by phosphate in rabbit renal cortex slices and in isolated renal cortex mitochondria. In isolated mitochondria, mersalyl, an inhibitor of both the phosphate/hydroxyl and phosphate/dicarboxylate mitochondrial carriers, inhibited the phosphate-induced stimulation, indicating that phosphate must enter the mitochondrion for stimulation. A malate/phosphate exchange seemed to be involved since N-ethylmaleimide, an inhibitor of the phosphate/hydroxyl exchange, did not inhibit phosphate-stimulated ammonia production, whereas there was inhibition by 2-n-butylmalonate, a competitive inhibitor of the dicarboxylate carrier. Phosphate itself was not essential since malonate stimulated ammoniagenesis in the absence of added phosphate. Similarly, citrate stimulated ammoniagenesis in isolated mitochondria in the absence of inorganic phosphate provided that it induced L-malate exit on the citrate transporter associated with inhibition of citrate oxidation by fluoroacetate. Similar results were also seen in mitochondria from rat renal cortex. A fall in mitochondrial alpha-ketoglutarate level resulted in an increase in ammonia production. This could be achieved directly with malonate or indirectly via L-malate exit. Simultaneous measurements of glutamate showed that the rate of ammonia production was reciprocally related to the glutamate content. We conclude that phosphate-induced stimulation of ammoniagenesis in the rabbit kidney is mediated by removal of glutamate, the feedback inhibitor of phosphate-dependent glutaminase. Glutamate removal is linked to phosphate-induced dicarboxylate exit across the mitochondrial membrane.     

Effects of aquifer heterogeneity and reaction mechanism uncertainty on a reactive barrier.

This paper addresses impacts of aquifer heterogeneity and reaction mechanism uncertainty on permeable reactive barrier (PRB) performance and describes modeling tools and preliminary guidelines for risk-based design of reactive barriers at heterogeneous sites. A braided stream aquifer was generated stochastically, using a fixed correlation structure and four levels of variability in the hydraulic conductivity field. A vertical, homogeneous barrier was placed in the aquifer. Based on a deterministic design, the size of the PRB for uniform conditions was considered conservative (factor of safety=3.3). Monte Carlo simulation was used to model cis 1,2-DCE reduction by iron metal with uncertainty in the reaction mechanism rate constants. These results were combined with flow and particle tracking results to predict the spatial distribution and flow-averaged concentrations of cis 1,2-DCE and vinyl chloride at the exit face of the PRB. Evaluated on a risk basis, the deterministic design method was found to be unconservative for more heterogeneous aquifers. Uncertainty in the reaction mechanism accentuated the negative effects of aquifer heterogeneity. Several compensating factors that may reduce the vulnerability of reactive barriers to aquifer heterogeneity are discussed.     

Acute respiratory distress syndrome: CT abnormalities at long-term follow-up

Photochemical thrombotic ischemia model was used to study the possible roles of excision repair cross-complementing group 6 (ERCC6), a DNA repair gene, in the neuroprotection of dextromethorphan (DM), a NMDA antagonist, in ischemic brain injury. The results showed that no obvious ERCC6 mRNA expression was found in the perifocal area of irradiated cerebral cortex before 24 h postischemia. Then, the number of ERCC6 mRNA positive cells gradually enhanced, and attained a peak value at 72 h after light irradiation, which followed a declined tendency at 7-day postlesion. These results suggest that DNA repair gene ERCC6 mRNA expression in the perifocal area may be involved in the pathophysiological processes following the photochemical thrombotic cerebral ischemia. By the administration of DM, we observed that it can significantly upregulate the expression of ERCC6 mRNA in the perifocal area at 48 h after ischemic event. The neuroprotective mechanisms of DM may be related to the upregulation of DNA repair gene ERCC6 mRNA.