Formal Total Synthesis of Diazonamide A

This dissertation describes efforts toward the total synthesis of diazonamide A, a complex marine natural product. First, efficient methods to prepare 3,3-diaryloxindoles from 3-aryloxindoles were developed via either Pd-catalyzed alpha-arylations or nucleophilic aromatic substitutions using the oxindole enolate as the nucleophile. Second, this method has been successfully applied to a formal synthesis of diazonamide A via the highly diastereoselective construction of the C10 quaternary center. Third, a cyclization precursor for a cascade alpha-arylation/direct arylation approach to the total synthesis was synthesized and tested, and this substrate was found to be failed to cyclize. Finally, two approaches to the synthesis of the aromatic core of diazonamide A, via our Pd-catalyzed alpha-arylation method and Au-catalyzed oxazole formation developed by Liming Zhang and coworkers, were attempted. Unfortunately, neither of these two methods was able to provide the desired product

Use of a T-flex toric intraocular lens to correct clinically significant astigmatism

AbstractPurposeTo investigate the stability and effectiveness of T-flex toric intraocular lenses (IOLs) for the correction of regular corneal astigmatism during cataract surgery.MethodsFrom October 2009 to January 2014 we enrolled patients receiving phacoemulsification and T-flex toric IOL implantation in the capsular bag at the Far Eastern Memorial Hospital. The uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), corneal astigmatism, refractive astigmatism, and the degree to which the IOL axis deviated from the demanded axis were recorded both before the operation and 6 months postoperatively.ResultsWe enrolled 24 eyes of 24 consecutive patients in this study. The mean spherical power of the implanted toric IOLs was 17.13 ± 4.21 D (range 6.0–24.0 D) and the mean cylindrical power of the IOLs was 3.0 ± 0.86 D (range 2.0–5.0 D). At the 6-month follow up examination, the refractive astigmatism had improved from 3.21 ± 1.50 D to 0.77 ± 0.47 D (p < 0.001) and the spherical equivalence had improved from 4.47 ± 5.43 D to 0.63 ± 0.49 D (p = 0.007). The CDVA improved from 0.81 ± 0.45 logMAR to 0.09 ± 0.11 logMAR (p < 0.001). The mean improvement from the preoperative CDVA to the postoperative UDVA was 5.3 lines on the Snellen chart. Ninety-two percent of our patients achieved a postoperative UDVA ≥20/40 and 67% achieved a postoperative UDVA ≥20/25.ConclusionThe T-flex toric IOL can effectively reduce visually significant corneal astigmatism and improve uncorrected distance visual acuity during cataract surgery

Damaged DNA-binding protein 2 (DDB2) protects against UV irradiation in human cells and Drosophila

<p>Abstract</p> <p>Background</p> <p>We observed previously that cisplatin-resistant HeLa cells were cross-resistant to UV light due to accumulation of DDB2, a protein implicated in DNA repair. More recently, we found that cFLIP, which represents an anti-apoptotic protein whose level is induced by DDB2, was implicated in preventing apoptosis induced by death-receptor signaling. In the present study, we investigated whether DDB2 has a protective role against UV irradiation and whether cFLIP is also involved in this process.</p> <p>Methods</p> <p>We explored the role of DDB2 in mediating UV resistance in both human cells and Drosophila. To do so, DDB2 was overexpressed by using a full-length open reading frame cDNA. Conversely, DDB2 and cFLIP were suppressed by using antisense oligonucleotides. Cell survival was measured using a colony forming assay. Apoptosis was monitored by examination of nuclear morphology, as well as by flow cytometry and Western blot analyses. A transcription reporter assay was also used to assess transcription of cFLIP.</p> <p>Results</p> <p>We first observed that the cFLIP protein was upregulated in UV-resistant HeLa cells. In addition, the cFLIP protein could be induced by stable expression of DDB2 in these cells. Notably, the anti-apoptotic effect of DDB2 against UV irradiation was largely attenuated by knockdown of cFLIP with antisense oligonucleotides in HeLa cells. Moreover, overexpression of DDB2 did not protect against UV in VA13 and XP-A cell lines which both lack cFLIP. Interestingly, ectopic expression of human DDB2 in <it>Drosophila </it>dramatically inhibited UV-induced fly death compared to control GFP expression. On the other hand, expression of DDB2 failed to rescue a different type of apoptosis induced by the genes <it>Reaper </it>or <it>eiger</it>.</p> <p>Conclusion</p> <p>Our results show that DDB2 protects against UV stress in a cFLIP-dependent manner. In addition, the protective role of DDB2 against UV irradiation was found to be conserved in divergent living organisms such as human and <it>Drosophila</it>. In addition, UV irradiation may activate a cFLIP-regulated apoptotic pathway in certain cells.</p

Electron Tomography Analysis of Thylakoid Assembly and Fission in Chloroplasts of a Single-Cell C4 plant, Bienertia sinuspersici

Bienertia sinuspersici is a single-cell C4 plant species of which chlorenchyma cells have two distinct groups of chloroplasts spatially segregated in the cytoplasm. The central vacuole encloses most chloroplasts at the cell center and confines the rest of the chloroplasts near the plasma membrane. Young chlorenchyma cells, however, do not have large vacuoles and their chloroplasts are homogenous. Therefore, maturing Bienertia chlorenchyma cells provide a unique opportunity to investigate chloroplast proliferation in the central cluster and the remodeling of chloroplasts that have been displaced by the vacuole to the cell periphery. Chloroplast numbers and sizes increased, more notably, during later stages of maturation than the early stages. Electron tomography analyses indicated that chloroplast enlargement is sustained by thylakoid growth and that invaginations from the inner envelope membrane contributed to thylakoid assembly. Grana stacks acquired more layers, differentiating them from stroma thylakoids as central chloroplasts matured. In peripheral chloroplasts, however, grana stacks stretched out to a degree that the distinction between grana stacks and stroma thylakoids was obscured. In central chloroplasts undergoing division, thylakoids inside the cleavage furrow were kinked and severed. Grana stacks in the division zone were disrupted, and large complexes in their membranes were dislocated, suggesting the existence of a thylakoid fission machinery.11Ysciescopu

DHP-Derivative and Low Oxygen Tension Effectively Induces Human Adipose Stromal Cell Reprogramming

BACKGROUND AND METHODS: In this study, we utilized a combination of low oxygen tension and a novel anti-oxidant, 4-(3,4-dihydroxy-phenyl)-derivative (DHP-d) to directly induce adipose tissue stromal cells (ATSC) to de-differentiate into more primitive stem cells. De-differentiated ATSCs was overexpress stemness genes, Rex-1, Oct-4, Sox-2, and Nanog. Additionally, demethylation of the regulatory regions of Rex-1, stemnesses, and HIF1alpha and scavenging of reactive oxygen species were finally resulted in an improved stem cell behavior of de-differentiate ATSC (de-ATSC). Proliferation activity of ATSCs after dedifferentiation was induced by REX1, Oct4, and JAK/STAT3 directly or indirectly. De-ATSCs showed increased migration activity that mediated by P38/JUNK and ERK phosphorylation. Moreover, regenerative efficacy of de-ATSC engrafted spinal cord-injured rats and chemical-induced diabetes animals were significantly restored their functions. CONCLUSIONS/SIGNIFICANCE: Our stem cell remodeling system may provide a good model which would provide insight into the molecular mechanisms underlying ATSC proliferation and transdifferentiation. Also, these multipotent stem cells can be harvested may provide us with a valuable reservoir of primitive and autologous stem cells for use in a broad spectrum of regenerative cell-based disease therapy

On the Position Determination of Docking Station for AUVs Using Optical Sensor and Neural Network

Detecting the relative position of the docking station is a very important issue for the homing of AUVs (Autonomous Unmanned Vehicles). To detect the position of the light source, a pinhole camera model structure was proposed like the camera model. However, due to the sensor resolution and the distortion errors of the pinhole camera system, the application of the camera of docking the under turbid sea environments is almost impossible. In this paper, a new method detecting the position of the docking station using a light source is presented. Also, a newly developed optical sensor which makes it much easier to sense the light source than the camera system for homing of the AUV under the water is performed. In addition, to improve the system, a neural network (NN) algorithm constructing a model relating the light inputs and optical sensor which are developed in this study is proposed. To evaluate the performance of the NN algorithm, the experiments were performed in the air beforehand. The result shows that the NN algorithm with AUV docking system using the NN model is better than the pinhole camera model

Effectiveness of Ledipasvir/Sofosbuvir with/without Ribavarin in Liver Transplant Recipients with Hepatitis C.

Background and Aims: Recurrent infection of hepatitis C virus (HCV) in liver transplant (LT) recipients is universal and associated with significant morbidity and mortality. Methods: We retrospectively evaluated the safety and efficacy of ledipasvir/sofosbuvir with and without ribavirin in LT recipients with recurrent genotype 1 hepatitis C. Results: Eighty-five LT recipients were treated for recurrent HCV with ledipasvir/sofosbuvirwith and without ribavirin for 12 or 24 weeks. The mean (± standard deviation [SD]) time from LT to treatment initiation was 68 (±71) months. The mean (± SD) age of the cohort was 63 (±8.6) years old. Most recipients were male (70%). Baseline alanine transaminase, total bilirubin, and HCV ribonucleic acid (RNA) values (± SD) were 76.8 (±126) mg/dL, 0.8 (±1.3) U/L, and 8,010,421.9 (±12,420,985) IU/mL, respectively. Five of 43 recipients who were treated with ribavirin required drug cessation due to side effects, with 4 of those being anemia complications. No recipient discontinued the ledipasvir/sofosbuvir. Eighty-one percent of recipients had undetectable viral levels at 4 weeks after starting therapy, and all recipients had complete viral suppression at the end of therapy. The sustained viral response at 12 weeks after completion of therapy was 94%. Conclusion : Ledipasvir and sofosbuvir with and without ribavirin therapy is an effective and well-tolerated interferon-free treatment for recurrent HCV infection after LT. Anemia is not uncommon in LT recipients receiving ribavirin

A Knotted Meta-molecule with 2-D Isotropic Optical Activity Rotating the Incident Polarization by 90{\deg}

Optical activity is the ability of chiral materials to rotate linearly-polarized (LP) electromagnetic waves. Because of their intrinsic asymmetry, traditional chiral molecules usually lack isotropic performance, or at best only possess a weak form of chirality. Here we introduce a knotted chiral meta-molecule that exhibits optical activity corresponding to a 90{\deg} polarization rotation of the incident waves. More importantly, arising from the continuous multi-fold rotational symmetry of the chiral torus knot structure, the observed polarization rotation behavior is found to be independent of how the incident wave is polarized. In other words, the proposed chiral knot structure possesses two-dimensional (2-D) isotropic optical activity as illustrated in Fig. 1, which has been experimentally validated in the microwave spectrum. The proposed chiral torus knot represents the most optically active meta-molecule reported to date that is intrinsically isotropic to the incident polarization