2,198 research outputs found
Stochastic population growth in spatially heterogeneous environments
Classical ecological theory predicts that environmental stochasticity
increases extinction risk by reducing the average per-capita growth rate of
populations. To understand the interactive effects of environmental
stochasticity, spatial heterogeneity, and dispersal on population growth, we
study the following model for population abundances in patches: the
conditional law of given is such that when is small the
conditional mean of is approximately , where and are the abundance and per
capita growth rate in the -th patch respectivly, and is the
dispersal rate from the -th to the -th patch, and the conditional
covariance of and is approximately . We show for such a spatially extended population that if
is the total population abundance, then ,
the vector of patch proportions, converges in law to a random vector
as , and the stochastic growth rate equals the space-time average per-capita growth rate
\sum_i\mu_i\E[Y_\infty^i] experienced by the population minus half of the
space-time average temporal variation \E[\sum_{i,j}\sigma_{ij}Y_\infty^i
Y_\infty^j] experienced by the population. We derive analytic results for the
law of , find which choice of the dispersal mechanism produces an
optimal stochastic growth rate for a freely dispersing population, and
investigate the effect on the stochastic growth rate of constraints on
dispersal rates. Our results provide fundamental insights into "ideal free"
movement in the face of uncertainty, the persistence of coupled sink
populations, the evolution of dispersal rates, and the single large or several
small (SLOSS) debate in conservation biology.Comment: 47 pages, 4 figure
Clastic vs. primary precipitated evaporites in the Messinian sicilian Basins
The Messinian stratigraphy of Sicily has a particular importance for the comprehension ofthe Messinian salinity crisis as its successions bear the greatest similarity with those of thedeep Mediterranean basins. Despite the large number of studies carried out in the last 30years, we believe that the true time and genetic relationships between the different evaporiticand non evaporitic rock bodies are still not well established. This is probably due to thelimited, partial view offered by the central Sicilian basin, despite its complete Messinianstratigraphic record.Clastic and chaotic evaporitic deposits emplaced by tectonically-driven small to largescaleresedimentation processes form an important part of the MSC record of Sicily in theBelice and Caltanissetta basins. Facies characteristics of clastic evaporites, the stratigraphicrelationships with the other Messinian deposits, their possible significance in the regionalgeological evolution and the implications at a Mediterranean scale will be discussed in thefield. Attention also will be paid to primary precipitated facies of Lower and UpperEvaporites.The main aim of this field trip is to visit and discuss, beside some of the classic localitiesof the Caltanissetta basin, other less known outcrops of western Sicily (Belice basin), inorder to have a more complete regional geological framework of the MSC events in Sicily.This will give the participants the opportunity to discuss many of the still open problemsconcerning the MSC. In this section we suggest some topics for discussion during the fieldtrip
Constitutive cytoplasmic localization of p21Waf1/Cip1 affects the apoptotic process in monocytic leukaemia
In the present study, we analysed the expression and localization of p21Waf1/Cip1 in normal and malignant haematopoietic cells. We demonstrate that in normal monocytic cells, protein kinase C (PKC)-induced p21 gene activation, which is nuclear factor-κB (NF-κB) independent, results in predominantly cytoplasmic localized p21 protein. In acute monocytic leukaemia (M4, M5), monocytic blasts (N=12) show constitutive cytoplasmic p21 expression in 75% of the cases, while in myeloid leukaemic blasts (N=10), low nuclear and cytoplasmic localization of p21 could be detected, which is also PKC dependent. Constitutive p21 expression in monocytic leukaemia might have important antiapoptotic functions. This is supported by the finding that in U937 cells overexpressing p21, VP16-induced apoptosis is significantly reduced (20.0±0.9 vs 55.8±3.8%, P<0.01, N=5), reflected by a reduced phosphorylation of p38 and JNK. Similarly, AML blasts with high cytoplasmic p21 were less sensitive to VP16-induced apoptosis as compared to AML cases with low or undetectable p21 expression (42.25 vs 12.3%, P<0.01). Moreover, complex formation between p21 and ASK1 could be demonstrated in AML cells, by means of coimmunoprecipitation. In summary, these results indicate that p21 has an antiapoptotic role in monocytic leukaemia, and that p21 expression is regulated in a PKC-dependent and NF-κB independent manner.
High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.
Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo
Ocean acidification through the lens of ecological theory
Ocean acidification, chemical changes to the carbonate system of seawater, is emerging as a key environmental challenge accompanying global warming and other human-induced perturbations. Considerable research seeks to define the scope and character of potential outcomes from this phenomenon, but a crucial impediment persists. Ecological theory, despite its power and utility, has been only peripherally applied to the problem. Here we sketch in broad strokes several areas where fundamental principles of ecology have the capacity to generate insight into ocean acidification's consequences. We focus on conceptual models that, when considered in the context of acidification, yield explicit predictions regarding a spectrum of population- and community-level effects, from narrowing of species ranges and shifts in patterns of demographic connectivity, to modified consumer–resource relationships, to ascendance of weedy taxa and loss of species diversity. Although our coverage represents only a small fraction of the breadth of possible insights achievable from the application of theory, our hope is that this initial foray will spur expanded efforts to blend experiments with theoretical approaches. The result promises to be a deeper and more nuanced understanding of ocean acidification and the ecological changes it portends
Consistency and diversity of spike dynamics in the neurons of bed nucleus of Stria Terminalis of the rat: a dynamic clamp study
Neurons display a high degree of variability and diversity in the expression and regulation of their voltage-dependent ionic channels. Under low level of synaptic background a number of physiologically distinct cell types can be identified in most brain areas that display different responses to standard forms of intracellular current stimulation. Nevertheless, it is not well understood how biophysically different neurons process synaptic inputs in natural conditions, i.e., when experiencing intense synaptic bombardment in vivo. While distinct cell types might process synaptic inputs into different patterns of action potentials representing specific "motifs'' of network activity, standard methods of electrophysiology are not well suited to resolve such questions. In the current paper we performed dynamic clamp experiments with simulated synaptic inputs that were presented to three types of neurons in the juxtacapsular bed nucleus of stria terminalis (jcBNST) of the rat. Our analysis on the temporal structure of firing showed that the three types of jcBNST neurons did not produce qualitatively different spike responses under identical patterns of input. However, we observed consistent, cell type dependent variations in the fine structure of firing, at the level of single spikes. At the millisecond resolution structure of firing we found high degree of diversity across the entire spectrum of neurons irrespective of their type. Additionally, we identified a new cell type with intrinsic oscillatory properties that produced a rhythmic and regular firing under synaptic stimulation that distinguishes it from the previously described jcBNST cell types. Our findings suggest a sophisticated, cell type dependent regulation of spike dynamics of neurons when experiencing a complex synaptic background. The high degree of their dynamical diversity has implications to their cooperative dynamics and synchronization
Many-body localization in a quantum simulator with programmable random disorder
When a system thermalizes it loses all local memory of its initial
conditions. This is a general feature of open systems and is well described by
equilibrium statistical mechanics. Even within a closed (or reversible) quantum
system, where unitary time evolution retains all information about its initial
state, subsystems can still thermalize using the rest of the system as an
effective heat bath. Exceptions to quantum thermalization have been predicted
and observed, but typically require inherent symmetries or noninteracting
particles in the presence of static disorder. The prediction of many-body
localization (MBL), in which disordered quantum systems can fail to thermalize
in spite of strong interactions and high excitation energy, was therefore
surprising and has attracted considerable theoretical attention. Here we
experimentally generate MBL states by applying an Ising Hamiltonian with
long-range interactions and programmably random disorder to ten spins
initialized far from equilibrium. We observe the essential signatures of MBL:
memory retention of the initial state, a Poissonian distribution of energy
level spacings, and entanglement growth in the system at long times. Our
platform can be scaled to higher numbers of spins, where detailed modeling of
MBL becomes impossible due to the complexity of representing such entangled
quantum states. Moreover, the high degree of control in our experiment may
guide the use of MBL states as potential quantum memories in naturally
disordered quantum systems.Comment: 9 pages, 9 figure
A massive, quiescent galaxy at redshift of z=3.717
In the early Universe finding massive galaxies that have stopped forming
stars present an observational challenge as their rest-frame ultraviolet
emission is negligible and they can only be reliably identified by extremely
deep near-infrared surveys. These have revealed the presence of massive,
quiescent early-type galaxies appearing in the universe as early as z2,
an epoch 3 Gyr after the Big Bang. Their age and formation processes have now
been explained by an improved generation of galaxy formation models where they
form rapidly at z3-4, consistent with the typical masses and ages derived
from their observations. Deeper surveys have now reported evidence for
populations of massive, quiescent galaxies at even higher redshifts and earlier
times, however the evidence for their existence, and redshift, has relied
entirely on coarsely sampled photometry. These early massive, quiescent
galaxies are not predicted by the latest generation of theoretical models.
Here, we report the spectroscopic confirmation of one of these galaxies at
redshift z=3.717 with a stellar mass of 1.710 M whose
absorption line spectrum shows no current star-formation and which has a
derived age of nearly half the age of the Universe at this redshift. The
observations demonstrates that the galaxy must have quickly formed the majority
of its stars within the first billion years of cosmic history in an extreme and
short starburst. This ancestral event is similar to those starting to be found
by sub-mm wavelength surveys pointing to a possible connection between these
two populations. Early formation of such massive systems is likely to require
significant revisions to our picture of early galaxy assembly.Comment: 6 pages, 7 figures. This is the final preprint corresponding closely
to the published version. Uploaded 6 months after publication in accordance
with Nature polic
Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment
BACKGROUND: Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. METHODS: OT-I CTL were adoptively transferred to C57BL/6 mice 21 – 28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. RESULTS: Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. CONCLUSIONS: Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several antigens when developing vaccine strategies for cancer
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