Computational modeling of microbubble coalescence and breakup using large eddy simulation and Lagrangian tracking

The flow of dispersed microbubbles was studied with an Eulerian–Lagrangian technique using large eddy simulation to predict the continuous liquid flow and Lagrangian tracking to compute bubble trajectories. The model fully accounts for bubble coalescence and breakup and was applied to horizontal and vertical channel flows. With low levels of turbulence, gravity in horizontal, and lift in vertical, channel flows govern the bubble spatial and collision distribution. When turbulence is sufficiently high to, at least partially, oppose bubble preferential concentration, more uniform collision and coalescence distributions are found, although these remain peaked near the wall in both configurations. Almost 100% coalescence efficiency was always found, due to bubbles colliding along similar trajectories, with breakup only recorded in a flow of low surface tension refrigerant R134a. Models like this can provide the required quantitative understanding of the microbubbles complex behavior, as well as supporting the development of more macroscopic modeling closures.     

Enhanced gas migration through permeable bubble networks within consolidated soft sediments

Many consolidated sediments experience in situ gas generation from methanogenesis, corrosion, or radiolysis reactions and can retain bubbles for long periods. Particular interest is motivated by the retention and acute release of flammable hydrogen from nuclear legacy waste sludge. X‐ray computed tomography was employed to observe 0.07–10 mm bubble populations within 30–1112 Pa yield strength Mg(OH)₂ sediments. High rates of partial coalescence were observed among sub‐millimeter microvoids, forming extensive bubble networks which spanned the 32 mm field of view. Lattice Boltzmann and Monte Carlo modeling demonstrated these networks to be highly pervious to gas, with effective diffusivities for hydrogen of 3.7–12.5 × 10^?5 m² s^?1. Continuous vessel‐spanning bubble networks, dynamic connectivity between ganglia of coalesced bubbles, Haines jumps, and composite diffusion through the gas and aqueous phase can account for enhanced gas migration over length‐scales of several meters, thus enabling chronic gas release from low‐intermediate strength sediments ( kPa) too strong for buoyant bubble ebullition and too weak for vertical channel formation. © 2018 The Authors. AIChE Journal published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers. AIChE J, 64: 4131–4147, 2018     

Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HIV-1 agents that target the viral nucleocapsid protein zinc fingers

Nucleocapsid p7 protein (NCp7) zinc finger domains of the human immunodeficiency virus type 1 (HIV-1) are being developed as antiviral targets due to their key roles in viral replication and their mutationally nonpermissive nature. On the basis of our experience with symmetrical disulfide benzamides (DIBAs; Rice et al. Science 1995, 270, 1194-1197), we synthesized and evaluated variants of these dimers, including sets of 4,4'- and 3,3'-disubstituted diphenyl sulfones and their monomeric benzisothiazolone derivatives (BITA). BITAs generally exhibited diminished antiviral potency when compared to their disulfide precursors. Novel, monomeric structures were created by linking haloalkanoyl groups to the benzamide ring through -NH-C(=O)- (amide) or -S-C(=O)- (thiolester) bridges. Amide-linked compounds generally lacked antiviral activity, while haloalkanoyl thiolesters and non-halogen-bearing analogues frequently exhibited acceptable antiviral potency, thus establishing thiolester benzamides per se as a new anti-HIV chemotype. Pyridinioalkanoyl thiolesters (PATEs) exhibited superior anti-HIV-1 activity with minimal cellular toxicity and appreciable water solubility. PATEs were shown to preferentially target the NCp7 Zn finger when tested against other molecular targets, thus identifying thiolester benzamides, and PATEs in particular, as novel NCp7 Zn finger inhibitors for in vivo studies.     

Visual system maldevelopment disrupts extraocular muscle-specific myosin expression

We measured hepatic albumin synthesis in five volunteers (4 men and 1 woman) at 3 and 6 h after recovery from intense exercise. A primed-constant infusion of a stable isotopic tracer of phenylalanine was used to determine hepatic fractional synthetic rate (FSR) and absolute synthetic rate (ASR) of albumin from the enrichment of phenylalanine in albumin. The infusion of the stable isotope tracer began 2 h after upright exercise or upright rest. Albumin FSR and ASR were 6.39 +/- 0.48%/day and 120 +/- 9 mg.kg body wt-1.day-1, respectively, 3-6 h after recovery from exercise; the FSR and ASR on the time control study day were 5.94 +/- 0.47%/day and 104 +/- 9 mg.kg body wt-1.day-1, respectively. The 6 and 16% increases (P < 0.05) in FSR and ASR after exercise were associated with an elevated plasma albumin content at 5 and 6 h of recovery (P < 0.05), an increased total protein content throughout recovery (P < 0.05), and a negative free water clearance (P < 0.05) at 2, 3, and 6.5 h of recovery compared with baseline values; these variables were unchanged from their baselines on the time control study day. Increased albumin content and reduced free water clearance contribute to a retention of fluid within the circulation after intense exercise. The measured increase in albumin synthesis could not account for the entire increase in albumin content at 6 h of recovery from exercise. However, we estimate that if the increased activity was maintained for the next 18 h, it could account for the expected increase in albumin content at 24 h of recovery.     

Classical/nonclassical hybrid cannabinoids: southern aliphatic chain-functionalized C-6beta methyl, ethyl, and propyl analogues

The stereoelectronic requirements for interaction of the southern aliphatic hydroxyl of cannabimimetic pharmacophores with the CB1 and CB2 receptors are explored. The stereoselective syntheses of three series of classical/nonclassical hybrid cannabinoids are described. These compounds were designed to investigate the importance of the southern aliphatic hydroxyl (SAH) pharmacophore for cannabimimetic activity. Variation in the chain length of the SAH moiety in these 6beta-(hydroxyalkyl)dihydrobenzopyran analogues, from 6beta-hydroxymethyl to 6beta-(omega-hydroxyethyl) and 6beta-(omega-hydroxypropyl), and the effects of replacing the hydroxyl functionality by hydride and iodide are reported. Our results indicate that the SAH pharmacophore has less pronounced effects than the C-3 aliphatic chain on cannabinoid activity. Furthermore, it appears that this southern molecular component is capable of interacting with two different subsites on the receptor and that the nature of this interaction is determined by the terminal substituent on the C-6beta alkyl group. One of the subsites can accommodate the relatively polar SAH pharmacophore, while the second subsite interacts with more hydrophobic C-6beta substituents and can accommodate large spherical pharmacophores separated by three methylene carbons from the tricyclic cannabinoid template.     

Changes in brain-derived neurotrophic factor immunoreactivity in rat dorsal root ganglia, spinal cord, and gracile nuclei following cut or crush injuries

In the present study, we evaluated changes in brain-derived neurotrophic factor (BDNF) immunoreactivity in the rat lumbar (L) 5 dorsal root ganglion (DRG) and areas where afferents from the DRG terminate, the L5 spinal cord and gracile nuclei, following unilateral sciatic nerve transection or crush. From 3 days to 4 weeks following cut or crush injury, the percentage of medium and large BDNF-immunoreactive neurons in the ipsilateral DRG increased significantly compared with those on the contralateral side. Following cut injury, there was no significant change in the percentage of small BDNF-immunoreactive neurons in the ipsilateral DRG; however, the intensity of immunoreactivity of these cells decreased. Following crush injury, however, both the percentage and intensity of small BDNF-immunoreactive neurons in the ipsilateral DRG significantly increased. Following cut injury, the expression of BDNF-immunoreactive axonal fibers decreased markedly in the ipsilateral superficial laminae of the L5 spinal cord and increased significantly in the ipsilateral deeper laminae of the spinal cord and gracile nuclei. Crush injury induced a marked increase in the expression of BDNF-immunoreactive axonal fibers in the superficial laminae of the spinal cord and gracile nuclei. These differences in BDNF response in the DRG and spinal cord after cut or crush injuries may reflect differences in trophic support to the injured DRG neurons and altered neuronal activity in the spinal cord and gracile nuclei following different types of peripheral nerve injury.     

Directed selection of MIP-1 alpha neutralizing CCR5 antibodies from a phage display human antibody library

The seven trans-membrane chemokine receptor CCR-5 is a coreceptor for macrophage tropic HIV-1 strains. CCR-5 responds to a number of chemokines, including macrophage inflammatory protein (MIP)-1 alpha. We describe the use of MIP-1 alpha in a biotin tyramine-mediated proximity selection to guide the selection of CCR-5-specific phage antibodies from a large phage display human library. Proximity based selections resulted in a population of antibodies recognizing CCR-5 on primary CD4+ lymphocytes, none of which blocked MIP-1 alpha binding to cells. The selected population of phage antibodies were subsequently used as guide molecules for a second phase of selection that was carried out in the absence of MIP-1 alpha. This generated a panel of CCR-5-binding antibodies, of which around 20% inhibited MIP-1 alpha binding to CD4+. The single chain Fvs (scFv) generated by this step-back selection procedure also inhibited MIP-1 alpha-mediated calcium signaling.     

New endeavors and innovative programs in end of life care

This paper presents summaries of initiatives and demonstration programs developed by professional and patient care organizations to improve care at the end of life.