The condensin complex is required for proper spindle assembly and chromosome segregation in Xenopus egg extracts.

Chromosome condensation is required for the physical resolution and segregation of sister chromatids during cell division, but the precise role of higher order chromatin structure in mitotic chromosome functions is unclear. Here, we address the role of the major condensation machinery, the condensin complex, in spindle assembly and function in Xenopus laevis egg extracts. Immunodepletion of condensin inhibited microtubule growth and organization around chromosomes, reducing the percentage of sperm nuclei capable of forming spindles, and causing dramatic defects in anaphase chromosome segregation. Although the motor CENP-E was recruited to kinetochores pulled poleward during anaphase, the disorganized chromosome mass was not resolved. Inhibition of condensin function during anaphase also inhibited chromosome segregation, indicating its continuous requirement. Spindle assembly around DNA-coated beads in the absence of kinetochores was also impaired upon condensin inhibition. These results support an important role for condensin in establishing chromosomal architecture necessary for proper spindle assembly and chromosome segregation

Groups with context-free co-word problem

The class of co-context-free groups is studied. A co-context-free group is defined as one whose coword problem (the complement of its word problem) is context-free. This class is larger than the subclass of context-free groups, being closed under the taking of finite direct products, restricted standard wreath products with context-free top groups, and passing to finitely generated subgroups and finite index overgroups. No other examples of co-context-free groups are known. It is proved that the only examples amongst polycyclic groups or the Baumslag–Solitar groups are virtually abelian. This is done by proving that languages with certain purely arithmetical properties cannot be context-free; this result may be of independent interest

Mortality from head injury over four decades in Scotland

Although the causes of head injury, the population at risk and approaches to prevention and treatment are continually evolving, there is little information about how these are reflected in patterns of mortality over time. We used population based comprehensive data uniquely available in Scotland to investigate changes in the total numbers of deaths from 1974 to 2012, as well as the rates of head injury death, from different causes, overall and in relation to age and gender. Total mortality fell from an annual average of 503 to 339 with a corresponding annual decrease in rate from 9.6 to 6.4 per 100,000 population, the decline substantially occurring between 1974 and 1990. Deaths in children fell strikingly but rose in older people. Deaths in males fell to a greater extent than females but remained at a higher rate overall. Initially, a transport accident accounted for most deaths but these fell by 80%, from 325 per year to 65 per year over the 39 year period. Deaths from falling and all other causes did not decline, coming to outnumber transport accident deaths by 1998, which accounts for the overall absence of change in total mortality in recent years. In order to reduce mortality in the future, more effective measures to prevent falls are needed and these strategies will vary in younger adults (where alcohol is often a factor), and in older adults where infirmity can be a cause. In addition, measures to sustain reductions in transport accidents need to be maintained and further developed

Raman Quantum Memory with Built-In Suppression of Four-wave Mixing Noise

Quantum memories are essential for large-scale quantum information networks. Along with high efficiency, storage lifetime and optical bandwidth, it is critical that the memory add negligible noise to the recalled signal. A common source of noise in optical quantum memories is spontaneous four-wave mixing. We develop and implement a technically simple scheme to suppress this noise mechanism by means of quantum interference. Using this scheme with a Raman memory in warm atomic vapour we demonstrate over an order of magnitude improvement in noise performance. Furthermore we demonstrate a method to quantify the remaining noise contributions and present a route to enable further noise suppression. Our scheme opens the way to quantum demonstrations using a broadband memory, significantly advancing the search for scalable quantum photonic networks.Comment: 6 pages, 5 figures plus Supplementary Materia

Hamiltonian analysis of subcritical stochastic epidemic dynamics

We extend a technique of approximation of the long-term behavior of a supercritical stochastic epidemic model, using the WKB approximation and a Hamiltonian phase space, to the subcritical case. The limiting behavior of the model and approximation are qualitatively different in the subcritical case, requiring a novel analysis of the limiting behavior of the Hamiltonian system away from its deterministic subsystem. This yields a novel, general technique of approximation of the quasistationary distribution of stochastic epidemic and birth-death models, and may lead to techniques for analysis of these models beyond the quasistationary distribution. For a classic SIS model, the approximation found for the quasistationary distribution is very similar to published approximations but not identical. For a birth-death process without depletion of susceptibles, the approximation is exact. Dynamics on the phase plane similar to those predicted by the Hamiltonian analysis are demonstrated in cross-sectional data from trachoma treatment trials in Ethiopia, in which declining prevalences are consistent with subcritical epidemic dynamics

Characterizing the Youngest Herschel-detected Protostars I. Envelope Structure Revealed by CARMA Dust Continuum Observations

We present CARMA 2.9 mm dust continuum emission observations of a sample of 14 Herschel-detected Class 0 protostars in the Orion A and B molecular clouds, drawn from the PACS Bright Red Sources (PBRS) sample (Stutz et al.). These objects are characterized by very red 24 \micron\ to 70 \micron\ colors and prominent submillimeter emission, suggesting that they are very young Class 0 protostars embedded in dense envelopes. We detect all of the PBRS in 2.9 mm continuum emission and emission from 4 protostars and 1 starless core in the fields toward the PBRS; we also report 1 new PBRS source. The ratio of 2.9 mm luminosity to bolometric luminosity is higher by a factor of $\sim$5 on average, compared to other well-studied protostars in the Perseus and Ophiuchus clouds. The 2.9 mm visibility amplitudes for 6 of the 14 PBRS are very flat as a function of uv-distance, with more than 50\% of the source emission arising from radii $<$ 1500 AU. These flat visibility amplitudes are most consistent with spherically symmetric envelope density profiles with $\rho$~$\propto$~R$^{-2.5}$. Alternatively, there could be a massive unresolved structure like a disk or a high-density inner envelope departing from a smooth power-law. The large amount of mass on scales $<$ 1500 AU (implying high average central densities) leads us to suggest that that the PBRS with flat visibility amplitude profiles are the youngest PBRS and may be undergoing a brief phase of high mass infall/accretion and are possibly among the youngest Class 0 protostars. The PBRS with more rapidly declining visibility amplitudes still have large envelope masses, but could be slightly more evolved.Comment: Accepted to ApJ, 40 pages, 9 Figures, 4 Table

Reconciling optical and radio observations of the binary millisecond pulsar PSR J1640+2224

Previous optical and radio observations of the binary millisecond pulsar PSR J1640+2224 have come to inconsistent conclusions about the identity of its companion, with some observations suggesting the companion is a low-mass helium-core (He-core) white dwarf (WD), while others indicate it is most likely a high-mass carbon-oxygen (CO) WD. Binary evolution models predict PSR J1640+2224 most likely formed in a low-mass X-ray binary (LMXB) based on the pulsar's short spin period and long-period, low-eccentricity orbit, in which case its companion should be a He-core WD with mass about $0.35 - 0.39 \, M_\odot$, depending on metallicity. If it is instead a CO WD, that would suggest the system has an unusual formation history. In this paper we present the first astrometric parallax measurement for this system from observations made with the Very Long Baseline Array (VLBA), from which we determine the distance to be $1520^{+170}_{-150}\,\mathrm{pc}$. We use this distance and a reanalysis of archival optical observations originally taken in 1995 with the Wide Field Planetary Camera 2 (WFPC2) on the Hubble Space Telescope (HST) in order to measure the WD's mass. We also incorporate improvements in calibration, extinction model, and WD cooling models. We find that the existing observations are not sufficient to tightly constrain the companion mass, but we conclude the WD mass is $>0.4\,M_\odot$ with $>90\%$ confidence. The limiting factor in our analysis is the low signal-to-noise ratio of the original HST observations.Comment: 6 pages, 5 figure

Lapatinib-binding protein kinases in the African trypanosome: identification of cellular targets for kinase-directed chemical scaffolds.

Human African trypanosomiasis is caused by the eukaryotic microbe Trypanosoma brucei. To discover new drugs against the disease, one may use drugs in the clinic for other indications whose chemical scaffolds can be optimized via a medicinal chemistry campaign to achieve greater potency against the trypanosome. Towards this goal, we tested inhibitors of human EGFR and/or VEGFR as possible anti-trypanosome compounds. The 4-anilinoquinazolines canertinib and lapatinib, and the pyrrolopyrimidine AEE788 killed bloodstream T. brucei in vitro with GI(50) in the low micromolar range. Curiously, the genome of T. brucei does not encode EGFR or VEGFR, indicating that the drugs recognize alternate proteins. To discover these novel targets, a trypanosome lysate was adsorbed to an ATP-sepharose matrix and washed with a high salt solution followed by nicotinamide adenine dinucleotide (NAD(+)). Proteins that remained bound to the column were eluted with drugs, and identified by mass spectrometry/bioinformatics. Lapatinib bound to Tb927.4.5180 (termed T. brucei lapatinib-binding protein kinase-1 (TbLBPK1)) while AEE788 bound Tb927.5.800 (TbLBPK2). When the NAD(+) wash was omitted from the protocol, AEE788, canertinib and lapatinib eluted TbLBPK1, TbLBPK2, and Tb927.3.1570 (TbLBPK3). In addition, both canertinib and lapatinib eluted Tb10.60.3140 (TbLBPK4), whereas only canertinib desorbed Tb10.61.1880 (TbCBPK1). Lapatinib binds to a unique conformation of protein kinases. To gain insight into the structural basis for lapatinib interaction with TbLBPKs, we constructed three-dimensional models of lapatinib•TbLBPK complexes, which confirmed that TbLBPKs can adopt lapatinib-compatible conformations. Further, lapatinib, AEE788, and canertinib were docked to TbLBPKs with favorable scores. Our studies (a) present novel targets of kinase-directed drugs in the trypanosome, and (b) offer the 4-anilinoquinazoline and pyrrolopyrimidines as scaffolds worthy of medicinal chemistry and structural biology campaigns to develop them into anti-trypanosome drugs

Trees over Infinite Structures and Path Logics with Synchronization

We provide decidability and undecidability results on the model-checking problem for infinite tree structures. These tree structures are built from sequences of elements of infinite relational structures. More precisely, we deal with the tree iteration of a relational structure M in the sense of Shelah-Stupp. In contrast to classical results where model-checking is shown decidable for MSO-logic, we show decidability of the tree model-checking problem for logics that allow only path quantifiers and chain quantifiers (where chains are subsets of paths), as they appear in branching time logics; however, at the same time the tree is enriched by the equal-level relation (which holds between vertices u, v if they are on the same tree level). We separate cleanly the tree logic from the logic used for expressing properties of the underlying structure M. We illustrate the scope of the decidability results by showing that two slight extensions of the framework lead to undecidability. In particular, this applies to the (stronger) tree iteration in the sense of Muchnik-Walukiewicz.Comment: In Proceedings INFINITY 2011, arXiv:1111.267

Rival bishops, rival cathedrals : the election of Cormac, archdeacon of Sodor, as bishop in 1331

Peer reviewedPublisher PD