PROCESSES FOR PRODUCING DOXORUBICIN, DAUNOMYCINONE, AND DERIVATIVES OF DOXORUBICIN

To produce doxorubicin and its analogues methyl 3alpha, 5alpha-dihydroxy-5beta-(trimethylsilylethynyl)- 2alpha-nitromethylcyclohexane-1beta-carboxylate acetonide is condensed with 1,4-dihydro-4,4,5-trimethoxy-1-oxonaphthalene in the presence of 1,8-diazabicyclo-5.4.0]undec-7-ene in an aprotic solvent to produce 3-(2beta-carbomethoxy-4-beta-ethynyl-4-alpha, 6alpha-(di-O-isopropylidenyl)cyclohexanyl-1-yl)-nitromethyl-4,4,5-trimethoxy-1-oxo-1,2,3,4-tetrahydronaphthalene; which is cyclized to produce 9beta ethynyl-12-hydroxy-7alpha, 9alpha-(di-O-iso propylidenyl)-6-nitro-4,5,5-trimethoxy-5,5a,6- 6a,7,8,9,10,10a,11-decahydro -11-naphthacenone. The decahydro-11-naphthacenone is converted to 7alpha 9alpha,(di-O-isopropyl-idenyl)-4,5-dimethoxy-9beta ethynyl-12-hydroxy-6-nitro-6,6a,7,8,9,10,10a, 11 octahydro-11, -naphthacenone. The octahydro-11 naphthacenone is oxidized to 7alpha-9alpha, (di-O-iso propyl-idenyl)-9beta-ethynyl-11-hydroxy-4-methoxy-6- nitro-7,8,9,10-tetrahydro-5,12-naphthacenedione which is converted to 6-desoxy-6-nitrodaunomycinone, daunomycinone and related 6-substituted analogues of daunomycinone

The baryonic Tully-Fisher relation for different velocity definitions and implications for galaxy angular momentum

We study the baryonic Tully-Fisher relation (BTFR) at z=0 using 153 galaxies from the SPARC sample. We consider different definitions of the characteristic velocity from HI and H-alpha rotation curves, as well as HI line-widths from single-dish observations. We reach the following results: (1) The tightest BTFR is given by the mean velocity along the flat part of the rotation curve. The orthogonal intrinsic scatter is extremely small (6%) and the best-fit slope is 3.85+/-0.09, but systematic uncertainties may drive the slope from 3.5 to 4.0. Other velocity definitions lead to BTFRs with systematically higher scatters and shallower slopes. (2) We provide statistical relations to infer the flat rotation velocity from HI line-widths or less extended rotation curves (like H-alpha and CO data). These can be useful to study the BTFR from large HI surveys or the BTFR at high redshifts. (3) The BTFR is more fundamental than the relation between angular momentum and galaxy mass (the Fall relation). The Fall relation has about 7 times more scatter than the BTFR, which is merely driven by the scatter in the mass-size relation of galaxies. The BTFR is already the "fundamental plane" of galaxy discs: no value is added with a radial variable as a third parameter.Comment: 12 pages, 6 figures, accepted for publication in MNRA

CONTEST : a Controllable Test Matrix Toolbox for MATLAB

Large, sparse networks that describe complex interactions are a common feature across a number of disciplines, giving rise to many challenging matrix computational tasks. Several random graph models have been proposed that capture key properties of real-life networks. These models provide realistic, parametrized matrices for testing linear system and eigenvalue solvers. CONTEST (CONtrollable TEST matrices) is a random network toolbox for MATLAB that implements nine models. The models produce unweighted directed or undirected graphs; that is, symmetric or unsymmetric matrices with elements equal to zero or one. They have one or more parameters that affect features such as sparsity and characteristic pathlength and all can be of arbitrary dimension. Utility functions are supplied for rewiring, adding extra shortcuts and subsampling in order to create further classes of networks. Other utilities convert the adjacency matrices into real-valued coefficient matrices for naturally arising computational tasks that reduce to sparse linear system and eigenvalue problems

The Skn7 Response Regulator of \u3ci\u3eSaccharomyces cerevisiae\u3c/i\u3e Interacts with Hsf1 In Vivo and Is Required for the Induction of Heat Shock Genes by Oxidative Stress

The Skn7 response regulator has previously been shown to play a role in the induction of stress-responsive genes in yeast, e.g., in the induction of the thioredoxin gene in response to hydrogen peroxide. The yeast Heat Shock Factor, Hsf1, is central to the induction of another set of stress-inducible genes, namely the heat shock genes. These two regulatory trans-activators, Hsf1 and Skn7, share certain structural homologies, particularly in their DNA-binding domains and the presence of adjacent regions of coiled-coil structure, which are known to mediate protein–protein interactions. Here, we provide evidence that Hsf1 and Skn7 interact in vitro and in vivo and we show that Skn7 can bind to the same regulatory sequences as Hsf1, namely heat shock elements. Furthermore, we demonstrate that a strain deleted for the SKN7 gene and containing a temperature-sensitive mutation in Hsf1 is hypersensitive to oxidative stress. Our data suggest that Skn7 and Hsf1 cooperate to achieve maximal induction of heat shock genes in response specifically to oxidative stress. We further show that, like Hsf1, Skn7 can interact with itself and is localized to the nucleus under normal growth conditions as well as during oxidative stress

Resonant X-Ray Scattering and the<i> j</i>_eff=1/2 Electronic Ground State in Iridate Perovskites

The resonant x-ray scattering (magnetic elastic, RXMS, and inelastic, RIXS) of Ir4+ at the L2,3 edges relevant to spin-orbit Mott insulators An+1IrnO3n+1 (A=Sr, Ba, etc.) are calculated using a single-ion model which treats the spin-orbit and tetragonal crystal-field terms on an equal footing. Both RXMS and RIXS in the spin-flip channel are found to display a nontrivial dependence on the direction of the magnetic moment, μ. Crucially, we show that for μ in the ab plane, RXMS in the cross-polarized channel at the L2 edge is zero irrespective of the tetragonal crystal field; spin-flip RIXS, relevant to measurements of magnons, behaves reciprocally, being zero at L2 when μ is perpendicular to the ab plane. Our results have important implications for the assignment of a jeff=1/2 ground state on the basis of resonant x-ray experiments

Radiation Therapy for Esophageal Cancer

Esophageal cancer develops in the mucosa of the esophagus and spreads toward the muscle layer. The nonsurgical treatment for localized, deeply invasive esophageal cancer has been external beam radiation therapy (EBRT) and concurrent chemotherapy. Recently, intraluminal brachytherapy showed a strong potential for the improvement of the therapeutic ratio. It was found that the fractionated high dose rate (HDR) brachytherapy offered beneficial palliation for a longer period of time with more durable symptom control. A similar was concluded for advanced unresectable esophageal cancer in previously irradiated patients. HDR brachytherapy may be a useful salvage treatment option for inoperable patients diagnosed with local esophageal cancer. Although better local control can be achieved with higher brachytherapy dose, this increases the risk of acute morbidity and late morbidity, especially in the setting of recurrence cancer. It was found that the moderate dose of EBRT and HDR brachytherapy could give a better local response than EBRT alone

Failure to Preserve β-Cell Function With Mycophenolate Mofetil and Daclizumab Combined Therapy in Patients With New- Onset Type 1 Diabetes

OBJECTIVE This trial tested whether mycophenolate mofetil (MMF) alone or with daclizumab (DZB) could arrest the loss of insulin-producing β-cells in subjects with new-onset type 1 diabetes. RESEARCH DESIGN AND METHODS A multi-center, randomized, placebo-controlled, double-masked trial was initiated by Type 1 Diabetes TrialNet at 13 sites in North America and Europe. Subjects diagnosed with type 1 diabetes and with sufficient C-peptide within 3 months of diagnosis were randomized to either MMF alone, MMF plus DZB, or placebo, and then followed for 2 years. The primary outcome was the geometric mean area under the curve (AUC) C-peptide from the 2-h mixed meal tolerance test. RESULTS One hundred and twenty-six subjects were randomized and treated during the trial. The geometric mean C-peptide AUC at 2 years was unaffected by MMF alone or MMF plus DZB versus placebo. Adverse events were more frequent in the active therapy groups relative to the control group, but not significantly. CONCLUSIONS Neither MMF alone nor MMF in combination with DZB had an effect on the loss of C-peptide in subjects with new-onset type 1 diabetes. Higher doses or more targeted immunotherapies may be needed to affect the autoimmune process

Mamekhaya: a pilot study combining a cognitive-behavioral intervention and mentor mothers with PMTCT services in South Africa

Nearly 30% of pregnant women in South Africa are estimated to be HIV seropositive, yet adherence to guidelines for the prevention of mother-to-child transmission of HIV (PMTCT) is often low. A pilot study was developed to see whether PMTCT services provided by the South African Government could be enhanced by the Mamekhaya program, a combination of the mothers2mothers peer-mentoring program and a culturally adapted cognitive-behavioral intervention (CBI) from the USA. Pregnant women attending two maternity clinics offering PMTCT in Gugulethu and Vanguard Townships, Cape Town, South Africa, were invited to participate in the study. Women at the intervention site (Gugulethu) received the support of a mentor mother and also attended an eight-session Mamekhaya CBI. At the control site (Vanguard), women received standard services provided by midwives and counselors. Baseline assessments were completed by all participants at enrollment (n=160), and follow-ups were completed six months later by 44% of participants. Self-reports of adherence to PMTCT practices were high across both sites (90% or more engaging in the core practices). Women at the Mamekhaya site showed significantly greater improvement in establishing social support and reducing depression scores than women at the control site. Mamekhaya participants also showed trends for better attendance at follow-up medical visits, and greater improvements in positive coping. The greatest effect of the Mamekhaya program was to increase HIV knowledge scores, particularly with regard to understanding the meaning and importance of viral load and CD4 test results. Results from this pilot study show promise that augmenting basic PMTCT services with mentor mothers and a culturally adapted CBI can be effective in conveying information and in improving the emotional outlook and hopefulness of HIV-positive pregnant women in South Africa

Early neurodevelopmental outcome of low birth weight infants surviving neonatal intraventricular hemorrhage

Peer Reviewe