Aryl Phosphoramidates of 5-Phospho Erythronohydroxamic Acid, A New Class of Potent Trypanocidal Compounds

RNAi and enzymatic studies have shown the importance of 6-phosphogluconate dehydrogenase (6-PGDH) in Trypanosoma brucei for the parasite survival and make it an attractive drug target for the development of new treatments against human African trypanosomiasis. 2,3-O-Isopropylidene-4-erythrono hydroxamate is a potent inhibitor of parasite Trypanosoma brucei 6-phosphogluconate dehydrogenase (6-PGDH), the third enzyme of the pentose phosphate pathway. However, this compound does not have trypanocidal activity due to its poor membrane permeability. Consequently, we have previously reported a prodrug approach to improve the antiparasitic activity of this inhibitor by converting the phosphate group into a less charged phosphate prodrug. The activity of prodrugs appeared to be dependent on their stability in phosphate buffer. Here we have successfully further extended the development of the aryl phosphoramidate prodrugs of 2,3-O-isopropylidene-4-erythrono hydroxamate by synthesizing a small library of phosphoramidates and evaluating their biological activity and stability in a variety of assays. Some of the compounds showed high trypanocidal activity and good correlation of activity with their stability in fresh mouse blood

Phonon density of states and compression behavior in iron sulfide under pressure

We report the partial phonon densities of states (DOS) of iron sulfide, a possible component of the rocky planet's core, measured by the Fe-57 nuclear resonant inelastic x-ray scattering and calculate the total phonon DOS under pressure. From the phonon DOS, we drive thermodynamic parameters. A comparison of the observed and estimated compressibilities makes it clear that there is a large pure electronic contribution in the observed compressibility in the metallic state. Our results present the observation of thermodynamic parameters of iron sulfide with the low-spin state of an Fe2+ ion at the high density, which is similar to the condition of the Martian core

Incidental threat during visuospatial working memory in adolescent anxiety: an emotional memory-guided saccade task

BackgroundPediatric anxiety disorders are among the most common psychiatric mental illnesses in children and adolescents, and are associated with abnormal cognitive control in emotional, particularly threat, contexts. In a series of studies using eye movement saccade tasks, we reported anxiety-related alterations in the interplay of inhibitory control with incentives, or with emotional distractors. The present study extends these findings to working memory (WM), and queries the interaction of spatial WM with emotional stimuli in pediatric clinical anxiety. MethodsParticipants were 33 children/adolescents diagnosed with an anxiety disorder, and 22 age-matched healthy comparison youths. Participants completed a novel eye movement task, an affective variant of the memory-guided saccade task. This task assessed the influence of incidental threat on spatial WM processes during high and low cognitive load. ResultsHealthy but not anxious children/adolescents showed slowed saccade latencies during incidental threat in low-load but not high-load WM conditions. No other group effects emerged on saccade latency or accuracy. ConclusionsThe current data suggest a differential pattern of how emotion interacts with cognitive control in healthy youth relative to anxious youth. These findings extend data from inhibitory processes, reported previously, to spatial WM in pediatric anxiety

A categorical foundation for Bayesian probability

Given two measurable spaces $H$ and $D$ with countably generated $\sigma$-algebras, a perfect prior probability measure $P_H$ on $H$ and a sampling distribution $S: H \rightarrow D$, there is a corresponding inference map $I: D \rightarrow H$ which is unique up to a set of measure zero. Thus, given a data measurement $\mu: 1 \rightarrow D$, a posterior probability $\widehat{P_H}= I \circ \mu$ can be computed. This procedure is iterative: with each updated probability $P_H$, we obtain a new joint distribution which in turn yields a new inference map $I$ and the process repeats with each additional measurement. The main result uses an existence theorem for regular conditional probabilities by Faden, which holds in more generality than the setting of Polish spaces. This less stringent setting then allows for non-trivial decision rules (Eilenberg--Moore algebras) on finite (as well as non finite) spaces, and also provides for a common framework for decision theory and Bayesian probability.Comment: 15 pages; revised setting to more clearly explain how to incorporate perfect measures and the Giry monad; to appear in Applied Categorical Structure

Rotating Black Hole Entropy from Two Different Viewpoints

Using the brick-wall method, we study the entropy of Kerr-Newman black hole from two different viewpoints, a rest observer at infinity and zero angular momentum observer near horizon. We investigate this with scalar field in the canonical quantization approach. An observer at infinity can take one of the two possible frequency ranges; one is with positive frequencies only and the other is with the whole range including negative frequencies. On the other hand, a zero angular momentum observer near horizon can take positive frequencies only. For the observer at infinity the superradiant modes appear in either choice of the frequency ranges and the two results coincide. For the zero angular momentum observer superradiant modes do not appear due to absence of ergoregion. The resulting entropies from the two viewpoints turn out to be the same.Comment: LaTeX 18 pages, 2 figures, Minor modifications in section 3(ZAMO

The quasar Q0957+561: Lensed CO emission from a disk at z~1.4?

In recent years large efforts have been made to detect molecular gas towards high redshifted objects. Up to now the literature reports on only two cases of CO-detection in quasars at a redshift between 1 and 2 - Q0957+561, a gravitationally lensed system at z=1.41 (Planesas et al. 1999), and HR10 at z=1.44 (Andreani et al. 2000). According to Planesas et al. (1999), 12CO(2-1) emission was detected towards both the lensed images of Q0957+561 with the IRAM Plateau de Bure Interferometer (PdBI). In contrast to the optical spectra of the two images which support the idea that they are images of one and the same object, the CO-spectra were surprisingly different: the southern image (named CO-B) shows a single blueshifted line whereas a double-peaked line profile with a blue- and a redshifted part appears towards the northern image (CO-A). Based on the observations and on simulations with a gravitational lens program, we are tempted to argue that the line profile traces the presence of molecular gas of a disk in the host galaxy around the quasar. We have now new observations with the PdBI providing the necessary sensitivity to corroborate our disk model.Comment: 4 pages, 1 figure, to appear in "Proceedings of the 4th Cologne-Bonn-Zermatt-Symposium", ed. S. Pfalzner, C. Kramer, C. Straubmeier, and A. Heithausen (Springer Verlag

Noncommutative BTZ Black Hole in Polar Coordinates

Based on the equivalence between the three dimensional gravity and the Chern-Simons theory, we obtain a noncommutative BTZ black hole solution as a solution of $U(1,1)\times U(1,1)$ noncommutative Chern-Simons theory using the Seiberg-Witten map. The Seiberg-Witten map is carried out in a noncommutative polar coordinates whose commutation relation is equivalent to the usual canonical commutation relation in the rectangular coordinates up to first order in the noncommutativity parameter $\theta$. The solution exhibits a characteristic of noncommutative polar coordinates in such a way that the apparent horizon and the Killing horizon coincide only in the non-rotating limit showing the effect of noncommutativity between the radial and angular coordinates.Comment: 14 pages, V2: minor changes, v3: reduced for clarification, a reference adde

Gorenstein homological algebra and universal coefficient theorems

We study criteria for a ring—or more generally, for a small category—to be Gorenstein and for a module over it to be of finite projective dimension. The goal is to unify the universal coefficient theorems found in the literature and to develop machinery for proving new ones. Among the universal coefficient theorems covered by our methods we find, besides all the classic examples, several exotic examples arising from the KK-theory of C*-algebras and also Neeman’s Brown–Adams representability theorem for compactly generated categories

de Sitter Supersymmetry Revisited

We present the basic $\mathcal{N} =1$ superconformal field theories in four-dimensional de Sitter space-time, namely the non-abelian super Yang-Mills theory and the chiral multiplet theory with gauge interactions or cubic superpotential. These theories have eight supercharges and are invariant under the full $SO(4,2)$ group of conformal symmetries, which includes the de Sitter isometry group $SO(4,1)$ as a subgroup. The theories are ghost-free and the anti-commutator $\sum_\alpha\{Q_\alpha, Q^{\alpha\dagger}\}$ is positive. SUSY Ward identities uniquely select the Bunch-Davies vacuum state. This vacuum state is invariant under superconformal transformations, despite the fact that de Sitter space has non-zero Hawking temperature. The $\mathcal{N}=1$ theories are classically invariant under the $SU(2,2|1)$ superconformal group, but this symmetry is broken by radiative corrections. However, no such difficulty is expected in the $\mathcal{N}=4$ theory, which is presented in appendix B.Comment: 21 pages, 2 figure