Cyclic‐Disulfide‐Based Prodrugs for Cytosol‐Specific Drug Delivery

The cytosolic conversion of therapeutically relevant nucleosides into bioactive triphosphates is often hampered by the inefficiency of the first kinase‐mediated step. Nucleoside monophosphate prodrugs can be used to bypass this limitation. Herein we describe a novel cyclic‐disulfide class of nucleoside monophosphate prodrugs with a cytosol‐specific, reductive release trigger. The key event, a charge‐dissipating reduction‐triggered cyclodeesterification leads to robust cytosolic production of the cyclic 3′,5′‐monophosphate for downstream enzymatic processing. The antiviral competence of the platform was demonstrated with an O‐benzyl‐1,2‐dithiane‐4,5‐diol ester of 2′‐C‐methyluridine‐3′,5′‐phosphate. Both in vitro and in vivo comparison with the clinically efficacious ProTide prodrug of 2′‐deoxy‐2′‐α‐fluoro‐β‐C‐methyluridine is provided. The cytosolic specificity of the release allows for a wide range of potential applications, from tissue‐targeted drug delivery to intracellular imaging.     

近红外光谱监测体外循环手术中脑组织氧合状况的研究

体外循环手术中,为防止因脑氧供需失衡导致脑缺氧,就要实时监测患者局部脑组织的氧合状况,以根据其变化调整生理参数或采取应急手段。用该研究小组自行研制的近红外仪器(使用一个双波长的近红外光源和两个近红外检测器)监测心脏手术中患者的脑氧,可以求出局部脑组织血红蛋白浓度的变化,并根据稳态空间分辨光谱(SRS)算法求出局部脑组织的氧饱和度(rSO₂)。体外循环中用监护仪监测患者的混合静脉血氧饱和度(SvO₂)等生理参数。测得的血红蛋白浓度变化容易受到干扰,而rSO₂的抗干扰性能较好。rSO₂在整个手术过程中都可以监测到,而SvO₂只能在体外循环过程中监测到。多数患者rSO₂和SvO₂存在正向相关性,但二者的相关系数并不很高。这是因为SvO₂是大静脉的血氧饱和度,而测得的rSO₂反映局部脑组织的氧合状况,二者的生理意义不同。实验结果表明,体外循环手术中rSO₂可以反映患者脑组织氧合状况的变化,而仅仅监测SvO₂是不够的。     

Remarks on DiPerna's Paper ``Convergence of the Viscosity Method for Isentropic Gas Dynamics'

Concerns have been voiced about the correctness of certain technical points in DiPerna's paper (Comm. Math. Phys.91 (1983), 1-30) related to the vacuum state. In this note, we provide clarifications. Our conclusion is that these concerns mainly arise from the statement of a lemma for constructing the viscous approximate solutions and some typos; however, the gap can be either fixed by correcting the statement of the lemma and the typos or bypassed by employing the finite difference methods.

     

航空发动机内外涵道三维粘性流场的数值模拟

本文用数值模拟的方法,对某涡扇发动机从风扇入口到增压级出口以及整个外涵道的稳态流场进行了联算和分析,计算是在我们自主搭建的分布式平行网络平台上进行的。计算表明风扇叶片沿叶高马赫数变化较大,从叶根附近的0.56变化到叶顶的1.34。本文得出了比较详细的内外涵道流场的信息,为叶片优化设计以及气动声学评估提供了依据。     

Boundary-layer disturbances subjected to free-stream turbulence and simulation on bypass transition

The phenomena associated with the entrainment of free-stream turbulence(FST) into boundary-layer flows are relevant for a number of subjects.It has been believed that the continuous spectra of the Orr-Sommerfeld(O-S)/Squire equations describe the entrainment process,and thus they are used to specify the inlet condition in simulation of bypass transition.However,Dong and Wu(Dong,M.and Wu,X.On continuous spectra of the Orr-Sommerfeld/Squire equations and entrainment of free-stream vortical disturbances.Journal of Fluid Mechanics,732,616–659(2013)) pointed out that continuous spectra exhibit several non-physical features due to neglecting the non-parallelism.They further proposed a large-Reynolds-number asymptotic approach,and showed that the non-parallelism is a leading-order effect even for the short-wavelength disturbance,for which the response concentrates in the edge layer.In this paper,the asymptotic solution is verified numerically by studying its evolution in incompressible boundary layers.It is found that the numerical results can be accurately predicted by the asymptotic solution,implying that the latter is adequate for moderate Reynolds numbers.By introducing a series of such solutions as the inflow perturbations,the bypass transition is investigated via the direct numerical simulation(DNS).The transition processes,including the evolution of streaks,the amplification of secondary-instability modes,and the emergence of turbulent spots,agree with the experimental observations.     

Physical design study of the CEPC booster

A physical design study of the Circular Electron-Positron Collider(CEPC) booster is reported. The booster provides 120 GeV electron and positron beams for the CEPC collider with top-up injection. The booster is mounted above the collider in the same tunnel. To save cost, the energy of the linac injector for the booster is chosen as 6 GeV, corresponding to a magnetic field of 30.7 Gs. In this paper, the booster lattice is described and optimization of the cell length is discussed. A novel scheme of bypass near the detector of the collider is designed.The extremely low magnetic field caused by low injection energy is studied, and a new ideal of wiggling bands is proposed to mitigate the low-field problem. Beam transfer and injection from the linac to the booster are considered.     

Influence of injector bypass on lifetime of small-particle liquid chromatographic columns

Summary In the case of liquid chromatography columns packed with small (3–5 m) particles and utilized at relatively high flow rates, pressure pulses associated with the sample injection process (caused by a short-duration interruption in mobile phase flow to the column during injection) may result in a reduction of column lifetime. This detrimental effect can be eliminated by the utilization of specially constructed sample injection valves incorporating properly desinged bypass loops. The paper investigates in detail the effect of pressure pulses, describes the criteria and performance of the bypass systems, and documents column life time and performance.Dedicated to Dr. L. S. Ettre on the occasion of his sixtieth birghday.     

Predicting overflow in an emergency department

G. B. Byrnes Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, Department of Public Health, The University of Melbourne, Victoria, Australia C. A. Bain Directorate Office, Western and Central Melbourne Integrated Cancer Service, Victoria, Australia M. Fackrell Department of Mathematics and Statistics, The University of Melbourne, Victoria, Australia C. Brand Clinical Epidemiology and Health Service Evaluation Unit, Melbourne Health, Victoria, Australia D. A. Campbell Department of Medicine, Southern Clinical School, Monash University, Victoria, Australia P. G. Taylor Department of Mathematics and Statistics, The University of Melbourne, Victoria, Australia Email: l.au{at}ms.unimelb.edu.au Received on 9 October 2007. Accepted on 4 February 2008. Ambulance bypass occurs when the emergency department (ED) ofa hospital becomes so busy that ambulances are requested totake their patients elsewhere, except in life-threatening cases.It is a major concern for hospitals in Victoria, Australia,and throughout most of the western world, not only from thepoint of view of patient safety but also financially—hospitalslose substantial performance bonuses if they go on ambulancebypass too often in a given period. We show that the main causeof ambulance bypass is the inability to move patients from theED to a ward. In order to predict the onset of ambulance bypass,the ED is modelled as a queue for treatment followed by a queuefor a ward bed. The queues are assumed to behave as inhomogeneousPoisson arrival processes. We calculate the probability of reachingsome designated capacity C within time t, given the currenttime and number of patients waiting.     

Wall Region Porosity Distributions for Packed Beds of Uniform Spheres with Modified and Unmodified Walls

A mathematical derivation of the porosity (local void fraction) distribution near the walls of packed beds of uniform spheres is presented. This investigation supports the study of methods of reducing or eliminating the so-called wall effect, or bypass flow, which accompanies the increase in porosity when spheres come in contact with a solid boundary. Limiting the amount of bypass flow is important in certain applications such as in packed bed nuclear reactors where bypass flow allows some coolant to avoid the high power density core region. Four basic porosity distributions are determined. The first investigates the case where spheres against a flat wall are packed in the tightest possible packing density. This density is then reduced by changing the sphere spacing until the minimum porosity matches that obtained experimentally. In the other cases, the effect of various ways of embedding spheres in the wall on the wall region porosity is examined. By partially embedding spheres in the wall, the porosity at the wall is reduced and the most direct cause of the bypass flow is thereby eliminated. The porosity is found by evaluating the ratio of the solid area to total area in a plane which is parallel to the wall. The local porosity is derived as a function of distance from the wall in the region within one-half a sphere diameter from the wall. The average porosity of the wall region is also calculated. This research has application to flow situations such as packed bed chemical reactors, pebble bed nuclear reactors and flow in packed beds.