A convergent synthesis of the immunosuppressant FTY720 employing aqueous Wittig chemistry

A short, convergent synthesis of the immunosuppressant FTY720 is described involving the use of 4-hydroxymethylbenzaldehyde as a pivotal intermediate. A double Wittig strategy was developed to connect this dual-functional aldehyde with an alkyl-tether and to a readily available TRIS-derivative leading to an efficient synthesis of the target molecule.     

CD47 in the Brain and Neurodegeneration: An Update on the Role in Neuroinflammatory Pathways

CD47 is a receptor belonging to the immunoglobulin (Ig) superfamily and broadly expressed on cell membranes. Through interactions with ligands such as SIRPα, TSP-1, integrins, and SH2-domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1), CD47 regulates numerous functions like cell adhesion, proliferation, apoptosis, migration, homeostasis, and the immune system. In this aspect, previous research has shown that CD47 modulates phagocytosis via macrophages, the transmigration of neutrophils, and the activation of T-cells, dendritic cells, and B-cells. Moreover, several studies have reported the increased expression of the CD47 receptor in a variety of diseases, including acute lymphoblastic leukemia (ALL), chronic myeloid leukemia, non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), bladder cancer, acute myeloid leukemia (AML), Gaucher disease, Multiple Sclerosis and stroke among others. The ubiquitous expression of the CD47 cell receptor on most resident cells of the CNS has previously been established through different methodologies. However, there is little information concerning its precise functions in the development of different neurodegenerative pathologies in the CNS. Consequently, further research pertaining to the specific functions and roles of CD47 and SIRP is required prior to its exploitation as a druggable approach for the targeting of various neurodegenerative diseases that affect the human population. The present review attempts to summarize the role of both CD47 and SIRP and their therapeutic potential in neurodegenerative disorders.     

空间激光与单模光纤和光子晶体光纤的耦合效率

为了设计最优光纤耦合系统,利用高斯模场近似单模阶跃光纤的模场和大模面积光子晶体光纤的模场,推导出了理想情况下空间激光与这两种光纤的耦合效率解析表达式以及光纤端面相对于耦合系统存在横向偏移和端面倾斜时的耦合效率解析表达式。基于上述理论表达式计算了空间激光与光纤的耦合效率,并通过实验验证了此理论表达式的有效性。理论计算和实验均证实了单模阶跃光纤对于横向偏移更敏感,当横向偏移量等于单模光纤的纤芯半径时所对应的耦合效率只有20.25%,为理论最大值的1/4;而大模面积光子晶体光纤对于端面倾斜更加敏感,当端面倾斜2°时对应的耦合效率只有40.5%,为理论最大值的1/2。所提出理论表达式和实验方法完全可以为设计光纤耦合系统提供准确的参数。     

瓶颈处车辆横纵向行为建模与分析

车辆的横向偏移现象在现实的交通流中广泛存在, 交通瓶颈处的横向偏移现象往往更加显著. 车辆间横纵向的运动相互干扰, 使得瓶颈交通流组织十分混乱, 通行能力受到显著影响. 为了研究瓶颈处车辆横纵向行为规律及其对交通流的影响, 提出一个考虑横向偏移特征的车辆行为模型: 通过引入目标转向角概念,并结合经典优化速度模型, 给出了用于描述车辆的横纵向运动规律的运动方程, 同时通过分析车辆横向偏移特征, 制定了基于车辆行驶状态划分的目标转向角确定规则集. 数值模拟结果表明: 车辆的横向偏移会对交通流的运行产生影响, 在一定的横向偏移反应阈值下, 瓶颈处横向干扰于交通流的影响随着密度的增加而增加; 同时观察到了实际城市交通瓶颈的宏观及微观现象, 验证了模型的有效性. 关键词： 交通流 瓶颈 车辆行为 横向偏移特征     

The influence of lateral and terminal substitution on the structure of a liquid crystal dendrimer in nematic solution: A computer simulation study

The choice of lateral and terminal substitution can have a major influence on the structure of a liquid crystalline supermolecule, which in turn can induce radically different phase behaviour. In this study we use molecular dynamics simulations to investigate the shape of a liquid crystal dendrimer within a liquid crystalline solvent. A coarse-grained (CG) simulation model is employed to represent a third generation dendrimer in which 32 mesogenic groups are bonded to chains at the end of each branch of the dendrimer. In this CG-model the liquid crystal groups can be appended either terminally or laterally. This bonding option is used to generate the structure of four separate systems: (a) a dendrimer with 32 terminal mesogens, (b) a dendrimer with 32 laterally appended mesogens, (c) and (d) dendrimers with 16 lateral and 16 terminal groups represented with laterally bonded sites on one side of the molecule, model (c) or next to terminally bonded sites, model (d). The simulations show that the dendrimer is able to change shape in response to molecular environment and that the molecular shape adopted depends critically on the nature of the lateral/terminal susbstitution.     

Quantitative cerebral magnetic resonance imaging during ACTH treatment of multiple sclerosis

Serial MR scans were performed with the 2DFT imaging method and the filtered backprojection imaging method on 12 patients with multiple sclerosis in acute phase, 4 in a relapsing/remitting form, and 8 in a progressive form, before, during and after ACTH treatment. Both T₁ and T_2mono relaxation times, obtained by fitting transverse magnetization decay curves with a monoexponential function within the apparently normal white matter and the areas of increased signal, were measured. With the backprojection method it was possible to fit the transverse magnetization decay curve with a biexponential function and obtain T_2long and T_2short relaxation times. The T_2mono and T₁ relaxation times of the apparently normal white matter were significantly different from those obtained for volunteers, but no significant differences were found before, during, or after treatment. The transverse magnetization decay curves of the areas of increased signal were better fitted by a biexponential function. No significant changes in these relaxation times were observed after ACTH treatment. These results argue against an anti-oedematous action of ACTH and may suggest that it has an immunosuppressant effect.     

Acoustic analysis of voice in multiple sclerosis patients

The objective is to investigate the presence of dysphonic symptoms in multiple sclerosis (MS) patients and to compare quantitative acoustic parameters in multiple sclerosis patients and normal individuals. The method of study was an 8-month controlled cross-sectional that was carried out with 106 individuals (30 MS, 76 controls). Both groups included males and females from 20 to 55 years. Exclusion criteria were prior vocal disorder, laryngeal microsurgery, recent endotracheal intubation, tumors, laryngeal, lung or mediastinal metastases, respiratory disease, and other associated neurological diagnoses. For dysphonic symptoms (qualitative variables), associations were assessed using Mantel-Haenszel's chi2 test, with Yates correction or the Fisher exact test when necessary. Statistical significance was set at p< or =0.05. Dysphonia was observed in 70% of MS individuals versus 33% of controls (p=0.01). Association was found between MS and dysphonia (OR: 2.2, CI 95%: 1.13-4.25). Fundamental frequency was higher among MS patients (p=0.01). Fundamental frequency deviation was significantly higher in MS women (but not men) than controls (p=0.00). Jitter was higher in MS men than in all other groups (p=0.00). Results suggest that evaluation and treatment of MS patients should be revised, evaluating voice alterations in relation to other signs. MS seems to intensify gender effect on fundamental frequency deviation, noise, and jitter, with MS women presenting fewer voice variations than men.     

Spasmodic dysphonia symptoms as initial presentation of amyotrophic lateral sclerosis

A patient initially diagnosed with adductor-type spasmodic dysphonia was referred for botulinum toxin (Botox) injections, but found on subsequent evaluation to have amyotrophic lateral sclerosis, and therefore Botox was not administered. This unique case underscores the need to delay botulinum toxin treatments in any patient with recent onset symptoms, and to obtain thorough motor speech and voice, otolaryngologic, and neurologic evaluation in all patients prior to consideration for injection.     

Cornerning radial tyres

An angular difference between direction of wheel motion and wheel plane produced a lateral force on a rolling tyre. A simple mechanism of shear stress generation in the contact area of tread is used. The coefficient of friction plays a limiting role. The resulting lateral force and self-aligning torque are computed by means of the belt model of a radial tyre. Finally, some numerical results are given to illustrate the theory.     

Analysis of Digital Lateral Shearing Interferometer

A new method is proposed for reconstructing wavefront from discretely sampled interferogram data obtained by a digital lateral shearing interferometer. Assumptions applied in the conventional methods are not used and reconstruction error caused by the difference between the amount of shear and the sampling interval can be removed. System error and the influence of the discrete sampling, which limit accuracy of the tested results of the lateral shearing interferometer, are analyzed.