Progress toward the Enantioselective Synthesis of Curcusones A–D via a Divinylcyclopropane Rearrangement Strategy

We report our iterative efforts toward the divergent total syntheses of curcusones A–D via Suzuki coupling, intramolecular cyclopropanation, and a key divinylcyclopropane rearrangement. Progress of our synthesis was repeatedly challenged by the highly substrate-dependent cyclopropanation step, which we could ultimately overcome by judicious choice of substituents on the six-membered ring fragment

Geometrically Induced Multiple Coulomb Blockade Gaps

We have theoretically investigated the transport properties of a ring-shaped array of small tunnel junctions, which is weakly coupled to the drain electrode. We have found that the long range interaction together with the semi-isolation of the array bring about the formation of stable standing configurations of electrons. The stable configurations break up during each transition from odd to even number of trapped electrons, leading to multiple Coulomb blockade gaps in the the $I-V$ characteristics of the system.Comment: 4 Pages (two-columns), 4 Figures, to be published in Physical Review Letter

Stereochemical evaluation of bis(phosphine) copper catalysts for the asymmetric alkylation of 3-bromooxindoles with α-arylated malonate esters

An improved method for the asymmetric alkylation of 3-bromooxindoles with α-arylated malonate esters is described. The asymmetric alkylation demonstrated was achieved up to 70% ee utilizing a copper(II) bis(phosphine) complex

Full capacitance-matrix effects in driven Josephson-junction arrays

We study the dynamic response to external currents of periodic arrays of Josephson junctions, in a resistively capacitively shunted junction (RCSJ) model, including full capacitance-matrix effects}. We define and study three different models of the capacitance matrix $C_{\vec{r},\vec{r}'}$: Model A includes only mutual capacitances; Model B includes mutual and self capacitances, leading to exponential screening of the electrostatic fields; Model C includes a dense matrix $C_{\vec{r},\vec{r}'}$ that is constructed approximately from superposition of an exact analytic solution for the capacitance between two disks of finite radius and thickness. In the latter case the electrostatic fields decay algebraically. For comparison, we have also evaluated the full capacitance matrix using the MIT fastcap algorithm, good for small lattices, as well as a corresponding continuum effective-medium analytic evaluation of a finite voltage disk inside a zero-potential plane. In all cases the effective $C_{\vec{r},\vec{r}'}$ decays algebraically with distance, with different powers. We have then calculated current voltage characteristics for DC+AC currents for all models. We find that there are novel giant capacitive fractional steps in the I-V's for Models B and C, strongly dependent on the amount of screening involved. We find that these fractional steps are quantized in units inversely proportional to the lattice sizes and depend on the properties of $C_{\vec{r},\vec{r}'}$. We also show that the capacitive steps are not related to vortex oscillations but to localized screened phase-locking of a few rows in the lattice. The possible experimental relevance of these results is also discussed.Comment: 12 pages 18 Postscript figures, REVTEX style. Paper to appear in July 1, Vol. 58, Phys. Rev. B 1998 All PS figures include

Albumin-Like Protein is the Major Protein Constituent of Luminal Fluid in the Human Endolymphatic Sac

The endolymphatic sac (ES) is an inner ear organ that is connected to the cochleo-vestibular system through the endolymphatic duct. The luminal fluid of the ES contains a much higher concentration of proteins than any other compartment of the inner ear. This high protein concentration likely contributes to inner ear fluid volume regulation by creating an osmotic gradient between the ES lumen and the interstitial fluid. We characterized the protein profile of the ES luminal fluid of patients (n = 11) with enlarged vestibular aqueducts (EVA) by proteomics. In addition, we investigated differences in the protein profiles between patients with recent hearing deterioration and patients without hearing deterioration. The mean total protein concentration of the luminal fluid was 554.7±94.6 mg/dl. A total of 58 out of 517 spots detected by 2-DE were analyzed by MALDI-TOF MS. The protein profile of the luminal fluid was different from the profile of plasma. Proteins identified from 29 of the spots were also present in the MARC-filtered human plasma; however, the proteins identified from the other 25 spots were not detected in the MARC-filtered human plasma. The most abundant protein in the luminal fluid was albumin-like proteins, but most of them were not detected in MARC-filtered human plasma. The concentration of albumin-like proteins was higher in samples from patients without recent hearing deterioration than in patients with recent hearing deterioration. Consequently, the protein of ES luminal fluid is likely to be originated from both the plasma and the inner ear and considering that inner ear fluid volumes increase abnormally in patients with EVA following recent hearing deterioration, it is tempting to speculate that albumin-like proteins may be involved in the regulation of inner ear fluid volume through creation of an osmotic gradient during pathological conditions such as endolymphatic hydrops

Cilostazol Prevents Tumor Necrosis Factor-␣-Induced Cell Death by Suppression of Phosphatase and Tensin Homolog Deleted from Chromosome 10 Phosphorylation and Activation of Akt/Cyclic AMP Response Element-Binding Protein Phosphorylation

ABSTRACT This study examines the signaling mechanism by which cilostazol prevents neuronal cell death. Cilostazol (ϳ0.1-100 M) prevented tumor necrosis factor-␣ (TNF-␣)-induced decrease in viability of SK-N-SH and HCN-1A cells, which was antagonized by 1 M iberiotoxin, a maxi-K channel blocker. TNF-␣ did not suppress the viability of the U87-MG cell, a phosphatase and tensin homolog deleted from chromosome 10 (PTEN)-null glioblastoma cell, but it did decrease viability of U87-MG cells transfected with expression vectors for the sense PTEN, and this decrease was also prevented by cilostazol. Cilostazol as well as 1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS-1619) and (3S)-(ϩ)-(5-chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indole-2-one (BMS 204352), maxi-K channel openers, prevented increased DNA fragmentation evoked by TNF-␣, which were antagonizable by iberiotoxin. TNF-␣-induced increased PTEN phosphorylation and decreased Akt/ cyclic AMP response element-binding protein (CREB) phosphorylation were significantly prevented by cilostazol, those of which were antagonized by both iberiotoxin and paxilline, maxi-K channel blockers. The same results were evident in U87-MG cells transfected with expression vectors for sense PTEN. Cilostazol increases the K ϩ current in SK-N-SH cells by activating maxi-K channels without affecting the ATP-sensitive K ϩ channel. Thus, our results for the first time provide evidence that cilostazol prevents TNF-␣-induced cell death by suppression of PTEN phosphorylation and activation of Akt/CREB phosphorylation via mediation of the maxi-K channel opening. Recent research has shown that the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) is implicated in the regulation of several cellular functions, including cell viability from apoptosi

Metallic and complex hydride-based electrochemical storage of energy

The development of efficient storage systems is one of the keys to the success of the energy transition. There are many ways to store energy, but among them, electrochemical storage is particularly valuable because it can store electrons produced by renewable energies with a very good efficiency. However, the solutions currently available on the market remain unsuitable in terms of storage capacity, recharging kinetics, durability, and cost. Technological breakthroughs are therefore expected to meet the growing need for energy storage. Within the framework of the Hydrogen Technology Collaboration Program—H2TCP Task-40, IEA\u27s expert researchers have developed innovative materials based on hydrides (metallic or complex) offering new solutions in the field of solid electrolytes and anodes for alkaline and ionic batteries. This review presents the state of the art of research in this field, from the most fundamental aspects to the applications in battery prototypes

Detection of primary sites in unknown primary tumors using FDG-PET or FDG-PET/CT

<p>Abstract</p> <p>Background</p> <p>Carcinoma of unknown primary tumors (CUP) is present in 0.5%-9% of all patients with malignant neoplasms; only 20%-27% of primary sites are identified before the patients die. Currently, 18F-fluorodeoxy-glucose positron-emission tomography (18F-FDG PET) or PET combined with computed tomography (PET/CT) is widely used for the diagnosis of CUP. However, the diagnostic yield of the primary site varies. The aim of this study was to determine whether PET or PET/CT has additional advantages over the conventional diagnostic workup in detecting the primary origin of CUP.</p> <p>Findings</p> <p>Twenty patients with unknown primary tumors that underwent PET or PET/CT were included in this study. For all patients, the conventional diagnostic workup was unsuccessful in detecting the primary sites. Among 20 patients, 11 had PET scans. The remaining nine patients had PET/CT. In all 20 patients, neither the PET nor PET/CT identified the primary site of the tumor, including six cases with cervical lymph node metastases. The PET and PET/CT revealed sites of FDG uptake other than those associated with known metastases in seven patients, but these findings did not influence patient management or therapy. Two patients had unnecessary invasive diagnostic procedures due to false positive results on the PET or PET/CT.</p> <p>Conclusions</p> <p>Although it is inconclusive because of small sample size of the study, the additional value of PET or PET/CT for the detection of primary sites in patients with CUP might be less than expected; especially in patients that have already had extensive conventional diagnostic workups. Further study is needed to confirm this finding.</p

Prognostic significance of bcl-2 expression in stage III breast cancer patients who had received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy

BACKGROUND: Bcl-2 is positively regulated by hormonal receptor pathways in breast cancer. A study was conducted to assess the prognostic significances of clinico-pathologic variables and of ER, PR, p53, c-erbB2, bcl-2, or Ki-67 as markers of relapse in breast cancer patients who had received the identical adjuvant therapy at a single institution. METHODS: A cohort of 151 curatively resected stage III breast cancer patients (M:F = 3:148, median age 46 years) who had 4 or more positive lymph nodes and received doxorubicin and cyclophosphamide followed by paclitaxel (AC/T) as adjuvant chemotherapy was analyzed for clinico-pathologic characteristics including disease-free survival (DFS) and overall survival (OS). Patients with positive ER and/or PR expression received 5 years of tamoxifen following AC/T. The protein expressions of biomarkers were assessed immunohistochemically. RESULTS: The median follow-up duration was 36 months, and 37 patients (24.5%) experienced a recurrence. Univariate analyses indicated that the tumor size (P = 0.038) and the number of involved lymph nodes (P < 0.001) significantly affected the recurrences. However, the type of surgery, the histology, histologic grade, the presence of endolymphatic emboli, and a close resection margin did not. Moreover, ER positivity (P = 0.013), bcl-2 positivity (P = 0.002) and low p53 expression (P = 0.032) were found to be significantly associated with a prolonged DFS. Furthermore, multivariate analysis identified 10 or more involved lymph nodes (HR 7.366; P < 0.001), negative bcl-2 expression (HR 2.895; P = 0.030), and c-erbB2 over-expression (HR 3.535; P = 0.001) as independent indicators of poorer DFS. In addition, bcl-2 expression was found to be significantly correlated with the expressions of ER and PR, and inversely correlated with the expressions of p53, c-erbB2 and Ki-67. Patients with bcl-2 expression had a significantly longer DFS than those without, even in the ER (+) subgroup. Moreover, OS was significantly affected by ER, bcl-2 and c-erbB2. CONCLUSION: Bcl-2 is an independent prognostic factor of DFS in curatively resected stage III breast cancer patients and appears to be a useful prognostic factor in combination with c-erbB2 and the number of involved lymph nodes