Over-representation of specific regions of chromosome 22 in cells from human glioma correlate with resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea

BACKGROUND: Glioblastoma multiforme is the most malignant form of brain tumor. Despite treatment including surgical resection, adjuvant chemotherapy, and radiation, these tumors typically recur. The recurrent tumor is often resistant to further therapy with the same agent, suggesting that the surviving cells that repopulate the tumor mass have an intrinsic genetic advantage. We previously demonstrated that cells selected for resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) are near-diploid, with over-representation of part or all of chromosomes 7 and 22. While cells from untreated gliomas often have over-representation of chromosome 7, chromosome 22 is typically under-represented. METHODS: We have analyzed cells from primary and recurrent tumors from the same patient before and after in vitro selection for resistance to clinically relevant doses of BCNU. Karyotypic analyses were done to demonstrate the genetic makeup of these cells, and fluorescent in situ hybridization analyses have defined the region(s) of chromosome 22 retained in these BCNU-resistant cells. RESULTS: Karyotypic analyses demonstrated that cells selected for BCNU resistance were near-diploid with over-representation of chromosomes 7 and 22. In cells where whole copies of chromosome 22 were not identified, numerous fragments of this chromosome were retained and inserted into several marker and derivative chromosomes. Fluorescent in situ hybridization analyses using whole chromosome paints confirmed this finding. Additional FISH analysis using bacterial artificial chromosome probes spanning the length of chromosome 22 have allowed us to map the over-represented region to 22q12.3–13.32. CONCLUSION: Cells selected for BCNU resistance either in vivo or in vitro retain sequences mapped to chromosome 22. The specific over-representation of sequences mapped to 22q12.3–13.32 suggest the presence of a DNA sequence important to BCNU survival and/or resistance located in this region of chromosome 22

Self-Organization, Layered Structure, and Aggregation Enhance Persistence of a Synthetic Biofilm Consortium

Microbial consortia constitute a majority of the earth’s biomass, but little is known about how these cooperating communities persist despite competition among community members. Theory suggests that non-random spatial structures contribute to the persistence of mixed communities; when particular structures form, they may provide associated community members with a growth advantage over unassociated members. If true, this has implications for the rise and persistence of multi-cellular organisms. However, this theory is difficult to study because we rarely observe initial instances of non-random physical structure in natural populations. Using two engineered strains of Escherichia coli that constitute a synthetic symbiotic microbial consortium, we fortuitously observed such spatial self-organization. This consortium forms a biofilm and, after several days, adopts a defined layered structure that is associated with two unexpected, measurable growth advantages. First, the consortium cannot successfully colonize a new, downstream environment until it selforganizes in the initial environment; in other words, the structure enhances the ability of the consortium to survive environmental disruptions. Second, when the layered structure forms in downstream environments the consortium accumulates significantly more biomass than it did in the initial environment; in other words, the structure enhances the global productivity of the consortium. We also observed that the layered structure only assembles in downstream environments that are colonized by aggregates from a previous, structured community. These results demonstrate roles for self-organization and aggregation in persistence of multi-cellular communities, and also illustrate a role for the techniques of synthetic biology in elucidating fundamental biological principles

Measuring the intelligence of an idealized mechanical knowing agent

We define a notion of the intelligence level of an idealized mechanical knowing agent. This is motivated by efforts within artificial intelligence research to define real-number intelligence levels of compli- cated intelligent systems. Our agents are more idealized, which allows us to define a much simpler measure of intelligence level for them. In short, we define the intelligence level of a mechanical knowing agent to be the supremum of the computable ordinals that have codes the agent knows to be codes of computable ordinals. We prove that if one agent knows certain things about another agent, then the former necessarily has a higher intelligence level than the latter. This allows our intelligence no- tion to serve as a stepping stone to obtain results which, by themselves, are not stated in terms of our intelligence notion (results of potential in- terest even to readers totally skeptical that our notion correctly captures intelligence). As an application, we argue that these results comprise evidence against the possibility of intelligence explosion (that is, the no- tion that sufficiently intelligent machines will eventually be capable of designing even more intelligent machines, which can then design even more intelligent machines, and so on)

Is Bacterial Persistence a Social Trait?

The ability of bacteria to evolve resistance to antibiotics has been much reported in recent years. It is less well-known that within populations of bacteria there are cells which are resistant due to a non-inherited phenotypic switch to a slow-growing state. Although such ‘persister’ cells are receiving increasing attention, the evolutionary forces involved have been relatively ignored. Persistence has a direct benefit to cells because it allows survival during catastrophes–a form of bet-hedging. However, persistence can also provide an indirect benefit to other individuals, because the reduced growth rate can reduce competition for limiting resources. This raises the possibility that persistence is a social trait, which can be influenced by kin selection. We develop a theoretical model to investigate the social consequences of persistence. We predict that selection for persistence is increased when: (a) cells are related (e.g. a single, clonal lineage); and (b) resources are scarce. Our model allows us to predict how the level of persistence should vary with time, across populations, in response to intervention strategies and the level of competition. More generally, our results clarify the links between persistence and other bet-hedging or social behaviours

Neutrino-driven Explosions

The question why and how core-collapse supernovae (SNe) explode is one of the central and most long-standing riddles of stellar astrophysics. A solution is crucial for deciphering the SN phenomenon, for predicting observable signals such as light curves and spectra, nucleosynthesis, neutrinos, and gravitational waves, for defining the role of SNe in the evolution of galaxies, and for explaining the birth conditions and properties of neutron stars (NSs) and stellar-mass black holes. Since the formation of such compact remnants releases over hundred times more energy in neutrinos than the SN in the explosion, neutrinos can be the decisive agents for powering the SN outburst. According to the standard paradigm of the neutrino-driven mechanism, the energy transfer by the intense neutrino flux to the medium behind the stagnating core-bounce shock, assisted by violent hydrodynamic mass motions (sometimes subsumed by the term "turbulence"), revives the outward shock motion and thus initiates the SN blast. Because of the weak coupling of neutrinos in the region of this energy deposition, detailed, multidimensional hydrodynamic models including neutrino transport and a wide variety of physics are needed to assess the viability of the mechanism. Owing to advanced numerical codes and increasing supercomputer power, considerable progress has been achieved in our understanding of the physical processes that have to act in concert for the success of neutrino-driven explosions. First studies begin to reveal observational implications and avenues to test the theoretical picture by data from individual SNe and SN remnants but also from population-integrated observables. While models will be further refined, a real breakthrough is expected through the next Galactic core-collapse SN, when neutrinos and gravitational waves can be used to probe the conditions deep inside the dying star. (abridged)Comment: Author version of chapter for 'Handbook of Supernovae,' edited by A. Alsabti and P. Murdin, Springer. 54 pages, 13 figure

Statistical Signatures of Photon Localization

The realization that electron localization in disordered systems (Anderson localization) is ultimately a wave phenomenon has led to the suggestion that photons could be similarly localized by disorder. This conjecture attracted wide interest because the differences between photons and electrons - in their interactions, spin statistics, and methods of injection and detection - may open a new realm of optical and microwave phenomena, and allow a detailed study of the Anderson localization transition undisturbed by the Coulomb interaction. To date, claims of three-dimensional photon localization have been based on observations of the exponential decay of the electromagnetic wave as it propagates through the disordered medium. But these reports have come under close scrutiny because of the possibility that the decay observed may be due to residual absorption, and because absorption itself may suppress localization. Here we show that the extent of photon localization can be determined by a different approach - measurement of the relative size of fluctuations of certain transmission quantities. The variance of relative fluctuations accurately reflects the extent of localization, even in the presence of absorption. Using this approach, we demonstrate photon localization in both weakly and strongly scattering quasi-one-dimensional dielectric samples and in periodic metallic wire meshes containing metallic scatterers, while ruling it out in three-dimensional mixtures of aluminum spheres.Comment: 5 pages, including 4 figure

A universal tool for determining the time delay and the frequency shift of light: Synge's world function

In almost all of the studies devoted to the time delay and the frequency shift of light, the calculations are based on the integration of the null geodesic equations. However, the above-mentioned effects can be calculated without integrating the geodesic equations if one is able to determine the bifunction $\Omega(x_A, x_B)$ giving half the squared geodesic distance between two points $x_A$ and $x_B$ (this bifunction may be called Synge's world function). In this lecture, $\Omega(x_A, x_B)$ is determined up to the order $1/c^3$ within the framework of the PPN formalism. The case of a stationary gravitational field generated by an isolated, slowly rotating axisymmetric body is studied in detail. The calculation of the time delay and the frequency shift is carried out up to the order $1/c^4$. Explicit formulae are obtained for the contributions of the mass, of the quadrupole moment and of the internal angular momentum when the only post-Newtonian parameters different from zero are $\beta$ and $\gamma$. It is shown that the frequency shift induced by the mass quadrupole moment of the Earth at the order $1/c^3$ will amount to $10^{-16}$ in spatial experiments like the ESA's Atomic Clock Ensemble in Space mission. Other contributions are briefly discussed.Comment: 18 pages, To appear in: "Lasers, Clocks and Drag-Free control: Exploration of Relativistic Gravity in Space", Springer Series on Astrophysics and Space Science Library, vol 349, p 15

Accretion Disc Theory: From the Standard Model Until Advection

Accretion disc theory was first developed as a theory with the local heat balance, where the whole energy produced by a viscous heating was emitted to the sides of the disc. One of the most important new invention of this theory was a phenomenological treatment of the turbulent viscosity, known as ''alpha'' prescription, when the (r$\phi$) component of the stress tensor was approximated by ($\alpha$ P) with a unknown constant $\alpha$. This prescription played the role in the accretion disc theory as well important as the mixing-length theory of convection for stellar evolution. Sources of turbulence in the accretion disc are discussed, including nonlinear hydrodynamical turbulence, convection and magnetic field role. In parallel to the optically thick geometrically thin accretion disc models, a new branch of the optically thin accretion disc models was discovered, with a larger thickness for the same total luminosity. The choice between these solutions should be done of the base of a stability analysis. The ideas underlying the necessity to include advection into the accretion disc theory are presented and first models with advection are reviewed. The present status of the solution for a low-luminous optically thin accretion disc model with advection is discussed and the limits for an advection dominated accretion flows (ADAF) imposed by the presence of magnetic field are analysed.Comment: Roceeding of the Int. Workshop "Observational Evidence for Black Holes in the Universe". Calcutta, 11-17 January 1998. Kluwer Acad. Pu

Assessment of a self-reported Drinks Diary for the estimation of drinks intake by care home residents: Fluid Intake Study in the Elderly (FISE)

Objectives: We evaluated the accuracy of a newly developed self-completed Drinks Diary in care home residents and compared it with direct observation and fluid intake charts. Design: Observational study. Setting: Residential care homes in Norfolk, UK. Participants: 22 elderly people (18 women, mean age 86.6 years SD 8.6, 12 with MMSE scores <27). Measurements: Participants recorded their own drinks intake over 24 hours using the Drinks Diary while care staff used the homes’ usual fluid intake chart to record drinks intake. These records were compared with drinks intake assessed by researcher direct observation (reference method), during waking hours (6am to 10pm), while drinks taken from 10pm to 6am were self-reported and checked with staff. Results: Drinks intake assessed by the Drinks Diary was highly correlated with researcher direct observation (Pearson correlation coefficient r=0.93, p<0.001, mean difference -163ml/day) while few staff-completed fluid charts were returned and correlation was low (r=0.122, p=0.818, mean difference 702ml/day). The Drinks Diary classified 19 of 22 participants correctly as drinking enough or not using both the European Food Safety Authority and US recommendations. Conclusion: The Drinks Diary estimate of drinks intake was comparable with direct observation and more accurate (and reliably completed) than staff records. The Drinks Diary can provide a reliable estimate of drinks intake in elderly care home residents physically and cognitively able to complete it. It may be useful for researchers, care staff and practitioners needing to monitor drinks intake of elderly people, to help them avoid dehydration