Modeling Algorithms in SystemC and ACL2

We describe the formal language MASC, based on a subset of SystemC and intended for modeling algorithms to be implemented in hardware. By means of a special-purpose parser, an algorithm coded in SystemC is converted to a MASC model for the purpose of documentation, which in turn is translated to ACL2 for formal verification. The parser also generates a SystemC variant that is suitable as input to a high-level synthesis tool. As an illustration of this methodology, we describe a proof of correctness of a simple 32-bit radix-4 multiplier.Comment: In Proceedings ACL2 2014, arXiv:1406.123

Two paths of cluster evolution: global expansion versus core collapse

All gravitationally bound clusters expand, due to both gas loss from their most massive members and binary heating. All are eventually disrupted tidally, either by passing molecular clouds or the gravitational potential of their host galaxies. However, their interior evolution can follow two very different paths. Only clusters of sufficiently large initial population and size undergo the combined interior contraction and exterior expansion that leads eventually to core collapse. In all other systems, core collapse is frustrated by binary heating. These clusters globally expand for their entire lives, up to the point of tidal disruption. Using a suite of direct N-body calculations, we trace the "collapse line" in r_v-N space that separates these two paths. Here, r_v and N are the cluster's initial virial radius and population, respectively. For realistic starting radii, the dividing N-value is from 10^4 to over 10^5. We also show that there exists a minimum population, N_min, for core collapse. Clusters with N < N_min tidally disrupt before core collapse occurs. At the Sun's Galactocentric radius, R_G = 8.5 kpc, we find N_min >~ 300. The minimum population scales with Galactocentric radius as R_G^{-9/8}. The position of an observed cluster relative to the collapse line can be used to predict its future evolution. Using a small sample of open clusters, we find that most lie below the collapse line, and thus will never undergo core collapse. Most globular clusters, on the other hand, lie well above the line. In such a case, the cluster may or may not go through core collapse, depending on its initial size. We show how an accurate age determination can help settle this issue.Comment: Accepted for publication in MNRAS. 14 Pages, 9 Figures, 2 Table

Hypervelocity Stars from the Andromeda Galaxy

Hypervelocity stars (HVSs) discovered in the Milky Way (MW) halo are thought to be ejected from near the massive black hole (MBH) at the galactic centre. In this paper we investigate the spatial and velocity distributions of the HVSs which are expected to be similarly produced in the Andromeda galaxy (M31). We consider three different HVS production mechanisms: (i) the disruption of stellar binaries by the galactocentric MBH; (ii) the ejection of stars by an in-spiraling intermediate mass black hole; and (iii) the scattering of stars off a cluster of stellar-mass black holes orbiting around the MBH. While the first two mechanisms would produce large numbers of HVSs in M31, we show that the third mechanism would not be effective in M31. We numerically calculate 1.2*10^6 trajectories of HVSs from M31 within a simple model of the Local Group and hence infer the current distribution of these stars. Gravitational focusing of the HVSs by the MW and the diffuse Local Group medium leads to high densities of low mass (~ solar mass) M31 HVSs near the MW. Within the virialized MW halo, we expect there to be of order 1000 HVSs for the first mechanism and a few hundred HVSs for the second mechanism; many of these stars should have distinctively large approach velocities (< -500 km/s). In addition, we predict ~5 hypervelocity RGB stars within the M31 halo which could be identified observationally. Future MW astrometric surveys or searches for distant giants could thus find HVSs from M31.Comment: 14 pages, 6 figures, changed to match version accepted by MNRA

Draft genome sequence of Pseudomonas putida CA-3, a bacterium capable of styrene degradation and medium-chain-length polyhydroxyalkanoate synthesis

Pseudomonas putida strain CA-3 is an industrial bioreactor isolate capable of synthesizing biodegradable polyhydroxyalkanoate polymers via the metabolism of styrene and other unrelated carbon sources. The pathways involved are subject to regulation by global cellular processes. The draft genome sequence is 6,177,154 bp long and contains 5,608 predicted coding sequences

Shot-noise-limited spin measurements in a pulsed molecular beam

Heavy diatomic molecules have been identified as good candidates for use in electron electric dipole moment (eEDM) searches. Suitable molecular species can be produced in pulsed beams, but with a total flux and/or temporal evolution that varies significantly from pulse to pulse. These variations can degrade the experimental sensitivity to changes in spin precession phase of an electri- cally polarized state, which is the observable of interest for an eEDM measurement. We present two methods for measurement of the phase that provide immunity to beam temporal variations, and make it possible to reach shot-noise-limited sensitivity. Each method employs rapid projection of the spin state onto both components of an orthonormal basis. We demonstrate both methods using the eEDM-sensitive H state of thorium monoxide (ThO), and use one of them to measure the magnetic moment of this state with increased accuracy relative to previous determinations.Comment: 12 pages, 6 figure

Structural footprinting in protein structure comparison: the impact of structural fragments

<p>Abstract</p> <p>Background</p> <p>One approach for speeding-up protein structure comparison is the <it>projection approach</it>, where a protein structure is mapped to a high-dimensional vector and structural similarity is approximated by distance between the corresponding vectors. <it>Structural footprinting methods </it>are projection methods that employ the same general technique to produce the mapping: first select a representative set of structural fragments as <it>models </it>and then map a protein structure to a vector in which each dimension corresponds to a particular model and "counts" the number of times the model appears in the structure. The main difference between any two structural footprinting methods is in the set of models they use; in fact a large number of methods can be generated by varying the type of structural fragments used and the amount of detail in their representation. How do these choices affect the ability of the method to detect various types of structural similarity?</p> <p>Results</p> <p>To answer this question we benchmarked three structural footprinting methods that vary significantly in their selection of models against the CATH database. In the first set of experiments we compared the methods' ability to detect structural similarity characteristic of evolutionarily related structures, i.e., structures within the same CATH superfamily. In the second set of experiments we tested the methods' agreement with the boundaries imposed by classification groups at the Class, Architecture, and Fold levels of the CATH hierarchy.</p> <p>Conclusion</p> <p>In both experiments we found that the method which uses secondary structure information has the best performance on average, but no one method performs consistently the best across all groups at a given classification level. We also found that combining the methods' outputs significantly improves the performance. Moreover, our new techniques to measure and visualize the methods' agreement with the CATH hierarchy, including the threshholded affinity graph, are useful beyond this work. In particular, they can be used to expose a similar composition of different classification groups in terms of structural fragments used by the method and thus provide an alternative demonstration of the continuous nature of the protein structure universe.</p

A small molecule activator of p300/CBP histone acetyltransferase promotes survival and neurite growth in a cellular model of Parkinson’s disease

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterised by motor and non-motor symptoms, resulting from the degeneration of nigrostriatal dopaminergic neurons and peripheral autonomic neurons. Given the limited success of neurotrophic factors in clinical trials, there is a need to identify new small molecule drugs and drug targets to develop novel therapeutic strategies to protect all neurons that degenerate in PD. Epigenetic dysregulation has been implicated in neurodegenerative disorders, while targeting histone acetylation is a promising therapeutic avenue for PD. We and others have demonstrated that histone deacetylase inhibitors have neurotrophic effects in experimental models of PD. Activators of histone acetyltransferases (HAT) provide an alternative approach for the selective activation of gene expression, however little is known about the potential of HAT activators as drug therapies for PD. To explore this potential, the present study investigated the neurotrophic effects of CTPB (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide), which is a potent small molecule activator of the histone acetyltransferase p300/CBP, in the SH-SY5Y neuronal cell line. We report that CTPB promoted the survival and neurite growth of the SH-SY5Y cells, and also protected these cells from cell death induced by the neurotoxin 6-hydroxydopamine. This study is the first to investigate the phenotypic effects of the HAT activator CTPB, and to demonstrate that p300/CBP HAT activation has neurotrophic effects in a cellular model of PD

Romidepsin induces caspase-dependent cell death in human neuroblastoma cells

Neuroblastoma is the most common extracranial pediatric solid tumor, arising from the embryonic sympathoadrenal lineage of the neural crest, and is responsible for 15% of childhood cancer deaths. Although survival rates are good for some patients, those children diagnosed with high-risk neuroblastoma have survival rates as low as 35%. Thus, neuroblastoma remains a significant clinical challenge and the development of novel therapeutic strategies is essential. Given that there is widespread epigenetic dysregulation in neuroblastoma, epigenetic pharmacotherapy holds promise as a therapeutic approach. In recent years, histone deacetylase (HDAC) inhibitors, which cause selective activation of gene expression, have been shown to be potent chemotherapeutics for the treatment of a wide range of cancers. Here we examined the ability of the FDA-approved drug Romidepsin, a selective HDAC1/2 inhibitor, to act as a cytotoxic agent in neuroblastoma cells. Treatment with Romidepsin at concentrations in the low nanomolar range induced neuroblastoma cell death through caspase-dependent apoptosis. Romidepsin significantly increased histone acetylation, and significantly enhanced the cytotoxic effects of the cytotoxic agent 6-hydroxydopamine, which has been shown to induce cell death in neuroblastoma cells through increasing reactive oxygen species. Romidepsin was also more potent in MYCN-amplified neuroblastoma cells, which is an important prognostic marker of poor survival. This study has thus demonstrated that the FDA-approved chemotherapeutic drug Romidepsin has a potent caspase-dependent cytotoxic effect on neuroblastoma cells, whose effects enhance cell death induced by other cytotoxins, and suggests that Romidepsin may be a promising chemotherapeutic candidate for the treatment of neuroblastoma