5,948 research outputs found
Differential spatial repositioning of activated genes in Biomphalaria glabrata snails infected with Schistosoma mansoni
Copyright @ 2014 Arican-Goktas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro that Biomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their nuclear location and becoming up-regulated. This also happens in vivo in live intact snails, where early exposure to miracidia also elicits non-random repositioning of genes. We reveal differences in the nuclear repositioning between the response of parasite susceptible snails as compared to resistant snails and with normal or live, attenuated parasites. Interestingly, the stress response gene heat shock protein (Hsp) 70 is only repositioned and then up-regulated in susceptible snails with the normal parasite. This movement and change in gene expression seems to be controlled by the parasite. Other differences in the behaviour of genes support the view that some genes are responding to tissue damage, for example the ferritin genes move and are up-regulated whether the snails are either susceptible or resistant and upon exposure to either normal or attenuated parasite. This is the first time host genome reorganisation has been seen in a parasitic host and only the second time for any pathogen. We believe that the parasite elicits a spatio-epigenetic reorganisation of the host genome to induce favourable gene expression for itself and this might represent a fundamental mechanism present in the human host infected with schistosome cercariae as well as in other host-pathogen relationships.NIH and Sandler Borroughs Wellcome Travel Fellowshi
A procedure for the change point problem in parametric models based on phi-divergence test-statistics
This paper studies the change point problem for a general parametric,
univariate or multivariate family of distributions. An information theoretic
procedure is developed which is based on general divergence measures for
testing the hypothesis of the existence of a change. For comparing the accuracy
of the new test-statistic a simulation study is performed for the special case
of a univariate discrete model. Finally, the procedure proposed in this paper
is illustrated through a classical change-point example
Angiomatoid giant cellular blue nevus of vaginal wall associated with pregnancy
<p>Abstract</p> <p>Background</p> <p>Blue nevi that arise from the Müllerian tract are rare melanocytic lesions. Several histopathologic variants of cellular blue nevi have been described. The angiomatoid variant is characterized by a vascular component, and is considered to be a rare variant. Few studies have explored the influence of pregnancy on melanocytic lesions.</p> <p>Case</p> <p>A 29-year-old woman was presented with a pigmented vaginal lesion that increased gradually during pregnancy. A full term gynecologic examination showed a tumor mass protruding into the vaginal canal. The mass was resected during cesarean-section under the clinical impression of vaginal hemangioma.</p> <p>Result</p> <p>Gross examination revealed a cystic mass measuring 6.0 × 4.3 × 3.5 cm, which was filled with dark friable material. Histologically, the mass showed a subepithelial cellular proliferation of heavily pigmented dendritic melanocytes with prominent vascular stroma. Cytologic pleomorphism, junctional activity, atypical mitosis, and necrosis were not found. The proliferation was immunoreactive for HMB-45, S-100 and melan-A, and non-immunoreactive for CD34, smooth muscle actin, and AE1/AE3. The MIB-1 proliferative index was less than 1%. The patient had a postoperative course without complication.</p> <p>Conclusions</p> <p>Angiomatoid giant cellular blue nevus arising from the vagina during pregnancy is extremely rare. The low proliferative index and absence of cytologic pleomorphism, or necrosis, supports a benign biological behavior. Clinical follow-up showed no evidence of recurrence at one year after the resection of the mass.</p
The Architectural Design Rules of Solar Systems based on the New Perspective
On the basis of the Lunar Laser Ranging Data released by NASA on the Silver
Jubilee Celebration of Man Landing on Moon on 21st July 1969-1994, theoretical
formulation of Earth-Moon tidal interaction was carried out and Planetary
Satellite Dynamics was established. It was found that this mathematical
analysis could as well be applied to Star and Planets system and since every
star could potentially contain an extra-solar system, hence we have a large
ensemble of exoplanets to test our new perspective on the birth and evolution
of solar systems. Till date 403 exoplanets have been discovered in 390
extra-solar systems. I have taken 12 single planet systems, 4 Brown Dwarf -
Star systems and 2 Brown Dwarf pairs. Following architectural design rules are
corroborated through this study of exoplanets. All planets are born at inner
Clarke Orbit what we refer to as inner geo-synchronous orbit in case of
Earth-Moon System. By any perturbative force such as cosmic particles or
radiation pressure, the planet gets tipped long of aG1 or short of aG1. Here
aG1 is inner Clarke Orbit. The exoplanet can either be launched on death spiral
as CLOSE HOT JUPITERS or can be launched on an expanding spiral path as the
planets in our Solar System are. It was also found that if the exo-planet are
significant fraction of the host star then those exo-planets rapidly migrate
from aG1 to aG2 and have very short Time Constant of Evolution as Brown Dwarfs
have. This vindicates our basic premise that planets are always born at inner
Clarke Orbit. This study vindicates the design rules which had been postulated
at 35th COSPAR Scientific Assembly in 2004 at Paris, France, under the title
,New Perspective on the Birth & Evolution of Solar Systems.Comment: This paper has been reported to Earth,Moon and Planets Journal as
MOON-S-09-0007
An off-board quantum point contact as a sensitive detector of cantilever motion
Recent advances in the fabrication of microelectromechanical systems (MEMS)
and their evolution into nanoelectromechanical systems (NEMS) have allowed
researchers to measure extremely small forces, masses, and displacements. In
particular, researchers have developed position transducers with resolution
approaching the uncertainty limit set by quantum mechanics. The achievement of
such resolution has implications not only for the detection of quantum behavior
in mechanical systems, but also for a variety of other precision experiments
including the bounding of deviations from Newtonian gravity at short distances
and the measurement of single spins. Here we demonstrate the use of a quantum
point contact (QPC) as a sensitive displacement detector capable of sensing the
low-temperature thermal motion of a nearby micromechanical cantilever.
Advantages of this approach include versatility due to its off-board design,
compatibility with nanoscale oscillators, and, with further development, the
potential to achieve quantum limited displacement detection.Comment: 5 pages, 5 figure
A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening
<p>Abstract</p> <p>Background</p> <p>A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20) and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma.</p> <p>Methods</p> <p>Using a high-throughput fluorescence polarization (FP) assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two quantitative, cell-based biophysical methods to assess the functional efficacy of these molecules and rank-ordered their abilities to relax isolated human airway smooth muscle (ASM). Scaling up to the level of an intact tissue, we confirmed in a concentration-responsive manner the potency of the cell-based hit compounds.</p> <p>Results</p> <p>Among 58,019 compound tested, 268 compounds caused 20% or more reduction of the polarized emission in the FP assay. A small subset of these primary screen hits, belonging to two scaffolds, caused relaxation of isolated ASM cell <it>in vitro </it>and attenuated active force development of intact tissue <it>ex vivo</it>.</p> <p>Conclusions</p> <p>This staged biophysical screening paradigm provides proof-of-principle for high-throughput and cost-effective discovery of new small molecule therapeutic agents for obstructive lung diseases.</p
Calling by Concluding Sentinels: Coordinating Cooperation or Revealing Risk?
Efficient cooperation requires effective coordination of individual contributions to the cooperative behaviour. Most social birds and mammals involved in cooperation produce a range of vocalisations, which may be important in regulating both individual contributions and the combined group effort. Here we investigate the role of a specific call in regulating cooperative sentinel behaviour in pied babblers (Turdoides bicolor). ‘Fast-rate chuck’ calls are often given by sentinels as they finish guard bouts and may potentially coordinate the rotation of individuals as sentinels, minimising time without a sentinel, or may signal the presence or absence of predators, regulating the onset of the subsequent sentinel bout. We ask (i) when fast-rate chuck calls are given and (ii) what effect they have on the interval between sentinel bouts. Contrary to expectation, we find little evidence that these calls are involved in regulating the pied babbler sentinel system: observations revealed that their utterance is influenced only marginally by wind conditions and not at all by habitat, while observations and experimental playback showed that the giving of these calls has no effect on inter-bout interval. We conclude that pied babblers do not seem to call at the end of a sentinel bout to maximise the efficiency of this cooperative act, but may use vocalisations at this stage to influence more individually driven behaviours
Quantum interferometry with three-dimensional geometry
Quantum interferometry uses quantum resources to improve phase estimation
with respect to classical methods. Here we propose and theoretically
investigate a new quantum interferometric scheme based on three-dimensional
waveguide devices. These can be implemented by femtosecond laser waveguide
writing, recently adopted for quantum applications. In particular, multiarm
interferometers include "tritter" and "quarter" as basic elements,
corresponding to the generalization of a beam splitter to a 3- and 4-port
splitter, respectively. By injecting Fock states in the input ports of such
interferometers, fringe patterns characterized by nonclassical visibilities are
expected. This enables outperforming the quantum Fisher information obtained
with classical fields in phase estimation. We also discuss the possibility of
achieving the simultaneous estimation of more than one optical phase. This
approach is expected to open new perspectives to quantum enhanced sensing and
metrology performed in integrated photonic.Comment: 7 pages (+4 Supplementary Information), 5 figure
The Precursors and Products of Justice Climates: Group Leader Antecedents and Employee Attitudinal Consequences
Drawing on the organizational justice, organizational climate, leadership and personality, and social comparison theory literatures, we develop hypotheses about the effects of leader personality on the development of three types of justice climates (e.g., procedural, interpersonal, and informational), and the moderating effects of these climates on individual level justice- attitude relationships. Largely consistent with the theoretically-derived hypotheses, the results showed that leader (a) agreeableness was positively related to procedural, interpersonal and informational justice climates, (b) conscientiousness was positively related to a procedural justice climate, and (c) neuroticism was negatively related to all three types of justice climates. Further, consistent with social comparison theory, multilevel data analyses revealed that the relationship between individual justice perceptions and job attitudes (e.g., job satisfaction, commitment) was moderated by justice climate such that the relationships were stronger when justice climate was high
Game theory of mind
This paper introduces a model of ‘theory of mind’, namely, how we represent the intentions and goals of others to optimise our mutual interactions. We draw on ideas from optimum control and game theory to provide a ‘game theory of mind’. First, we consider the representations of goals in terms of value functions that are prescribed by utility or rewards. Critically, the joint value functions and ensuing behaviour are optimised recursively, under the assumption that I represent your value function, your representation of mine, your representation of my representation of yours, and so on ad infinitum. However, if we assume that the degree of recursion is bounded, then players need to estimate the opponent's degree of recursion (i.e., sophistication) to respond optimally. This induces a problem of inferring the opponent's sophistication, given behavioural exchanges. We show it is possible to deduce whether players make inferences about each other and quantify their sophistication on the basis of choices in sequential games. This rests on comparing generative models of choices with, and without, inference. Model comparison is demonstrated using simulated and real data from a ‘stag-hunt’. Finally, we note that exactly the same sophisticated behaviour can be achieved by optimising the utility function itself (through prosocial utility), producing unsophisticated but apparently altruistic agents. This may be relevant ethologically in hierarchal game theory and coevolution
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