Total Synthesis of the Potent HIF-1 Inhibitory Antitumor Natural Product, (8<i>R</i>)-Mycothiazole, via Baldwin���Lee CsF/CuI sp³���sp²-Stille Cross-Coupling. Confirmation of the Crews Reassignment

A convenient asymmetric total synthesis of the potent HIF-1 inhibitory antitumor natural product, (���)- or (+)-(8<i>R</i>)-mycothiazole (<b>1</b>), is described. Not only does our synthesis confirm the 2006 structural reassignment made by Crews (Crews, P., et al. <i>J. Nat. Prod</i>. <b>2006</b>, <i>69</i>, 145), it revises the [��]_D data previously reported for this molecule in MeOH from ���13.7�� to +42.3��. The newly developed route to (8<i>R</i>)-<b>1</b> sets the C(8)���OH stereocenter via Sharpless AE/2,3-epoxy alcohol reductive ring opening and utilizes two Baldwin���Lee CsF/cat. CuI Stille cross-coupling reactions with vinylstannanes <b>8</b> and <b>3</b> to efficiently elaborate the C(1)���C(4) and C(14)���C(18) sectors.

The reliability of R₅₀ as a measure of vulnerability of food webs to sequential species deletions

<p>Recent studies predict elevated and accelerating rates of species extinctions over the 21st century, due to climate change and habitat loss. Considering that such primary species loss may initiate cascades of secondary extinctions and push systems towards critical tipping points, we urgently need to increase our understanding of if certain sequences of species extinctions can be expected to be more devastating than others Most theoretical studies addressing this question have used a topological (non-dynamical) approach to analyse the probability that food webs will collapse, below a fixed threshold value in species richness, when subjected to different sequences of species loss. Typically, these studies have neither considered the possibility of dynamical responses of species, nor that conclusions may depend on the value of the collapse threshold. Here we analyse how sensitive conclusions on the importance of different species are to the threshold value of food web collapse. Using dynamical simulations, where we expose model food webs to a range of extinction sequences, we evaluate the reliability of the most frequently used index, R&lt;inf&gt;50&lt;/inf&gt;, as a measure of food web robustness. In general, we find that R&lt;inf&gt;50&lt;/inf&gt; is a reliable measure and that identification of destructive deletion sequences is fairly robust, within a moderate range of collapse thresholds. At the same time, however, focusing on R&lt;inf&gt;50&lt;/inf&gt; only hides a lot of interesting information on the disassembly process and can, in some cases, lead to incorrect conclusions on the relative importance of species in food webs.</p>

STRIBOB: Authenticated Encryption from GOST R 34.11-2012 LPS Permutation.

Authenticated encryption algorithms protect both the confidentiality and integrity of messages in a single processing pass. We show how to utilize the L���P ���S transform of the Russian GOST R 34.11-2012 standard hash ���Streebog��� to build an efficient, lightweight algorithm for Authenticated Encryption with Associated Data (AEAD) via the Sponge construction. The proposed algorithm ���StriBob��� has attractive security properties, is faster than the Streebog hash alone, twice as fast as the GOST 28147-89 encryption algorithm, and requires only a modest amount of running-time memory. StriBob is a Round 1 candidate in the CAESAR competition.

Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer: Data From Patients in the Control Arm of the STAMPEDE Trial

<p>Importance: The natural history of patients with newly diagnosed high-risk nonmetastatic (M0) prostate cancer receiving hormone therapy (HT) either alone or with standard-of-care radiotherapy (RT) is not well documented. Furthermore, no clinical trial has assessed the role of RT in patients with node-positive (N+) M0 disease. The STAMPEDE Trial includes such individuals, allowing an exploratory multivariate analysis of the impact of radical RT.</p><p>Objective: To describe survival and the impact on failure-free survival of RT by nodal involvement in these patients.</p><p>Design, Setting, and Participants: Cohort study using data collected for patients allocated to the control arm (standard-of-care only) of the STAMPEDE Trial between October 5, 2005, and May 1, 2014. Outcomes are presented as hazard ratios (HRs) with 95% CIs derived from adjusted Cox models; survival estimates are reported at 2 and 5 years. Participants were high-risk, hormone-naive patients with newly diagnosed M0 prostate cancer starting long-term HT for the first time. Radiotherapy is encouraged in this group, but mandated for patients with node-negative (N0) M0 disease only since November 2011.</p><p>Exposures: Long-term HT either alone or with RT, as per local standard. Planned RT use was recorded at entry.</p><p>Main Outcomes and Measures: Failure-free survival (FFS) and overall survival.</p><p>Results: A total of 721 men with newly diagnosed M0 disease were included: median age at entry, 66 (interquartile range [IQR], 61-72) years, median (IQR) prostate-specific antigen level of 43 (18-88) ng/mL. There were 40 deaths (31 owing to prostate cancer) with 17 months' median follow-up. Two-year survival was 96% (95% CI, 93%-97%) and 2-year FFS, 77% (95% CI, 73%-81%). Median (IQR) FFS was 63 (26 to not reached) months. Time to FFS was worse in patients with N+ disease (HR, 2.02 [95% CI, 1.46-2.81]) than in those with N0 disease. Failure-free survival outcomes favored planned use of RT for patients with both N0M0 (HR, 0.33 [95% CI, 0.18-0.61]) and N+M0 disease (HR, 0.48 [95% CI, 0.29-0.79]).</p><p>Conclusions and Relevance: Survival for men entering the cohort with high-risk M0 disease was higher than anticipated at study inception. These nonrandomized data were consistent with previous trials that support routine use of RT with HT in patients with N0M0 disease. Additionally, the data suggest that the benefits of RT extend to men with N+M0 disease.</p><p>Trial Registration: clinicaltrials.gov Identifier: NCT00268476; ISRCTN78818544.</p>

Relativistic radiatively damped <i>R</i> -matrix calculations of the electron-impact excitation of helium-like iron and krypton

Electron-impact excitation data for He-like ions are of significant importance for diagnostic applications to both laboratory and astrophysical plasmas. Here we report on the first fully relativistic R -matrix calculations with radiation damping for the He-like ions Fe 24+ and Kr 34+ . Effective collision strengths for these two ions have been determined with and without damping over a wide temperature range for all transitions between the 49 levels through n = 5. We find that damping has a pronounced effect on the effective collision strengths for excitation to some of the low-lying levels, but its effect on excitation to the vast majority of levels is small. At the energy of a resonance peak, we also investigate the effect of radiation damping on the angular distribution of scattered electrons. Finally, we compare our results for Fe 24+ with an earlier intermediate coupling frame transformation R -matrix calculation with radiation damping by Whiteford et al ( J. Phys. B: At. Mol. Opt. Phys. 34 3179) and find good agreement, especially for excitation to the lower levels.

Intermediate-coupling R -matrix calculations of electron-impact excitation of Fe 5+

For applications to laboratory and astrophysical plasmas, there is a great need for accurate electron-impact excitation data between individual levels in the lower charge-state ions of iron. Recently, we have reported on the first intermediate-coupling R -matrix calculation of electron-impact excitation in Fe 4+ , in which the close-coupling expansion of the target included levels from both ground and excited configurations (Ballance et al 2007 J. Phys. B: At. Mol. Opt. Phys. [/0953-4075/40/23/f01] 40 F327 , 2008 Europhys. News 39 14). In this paper, we present the results of two large intermediate-coupling Dirac R -matrix calculations of electron-impact excitation of Fe 5+ . The results from the two calculations, which differ only in the configuration���interaction expansions of the target, are compared. These comparisons provide some indication of the accuracy of the calculations and the resulting data should be useful in modelling plasmas containing iron.

Electron-impact excitation of Fe²: a comparison of intermediate coupling frame transformation, Breit-Pauli and Dirac R-matrix calculations

Modeling the spectral emission of low-charge iron group ions enables the diagnostic determination of the local physical conditions of many cool plasma environments such as those found in H II regions, planetary nebulae, active galactic nuclei etc. Electron-impact excitation drives the population of the emitting levels and, hence, their emissivities. By carrying-out Breit-Pauli and intermediate coupling frame transformation (ICFT) R-matrix calculations for the electron-impact excitation of Fe$^{2+}$ which both use the exact same atomic structure and the same close-coupling expansion, we demonstrate the validity of the application of the powerful ICFT method to low-charge iron group ions. This is in contradiction to the finding of Bautista et al. [Ap.J.Lett, 718, L189, (2010)] who carried-out ICFT and Dirac R-matrix calculations for the same ion. We discuss possible reasons.