2,795 research outputs found
AN OBLIGATORY ROLE OF MIND BOMB-1 IN NOTCH SIGNALING OF MAMMALIAN DEVELOPMENT
Background. The Notch signaling pathway is an evolutionarily conserved intercellular signaling module essential for cell fate specification that requires endocytosis of Notch ligands. Structurally distinct E3 ubiquitin ligases, Neuralized (Neur) and Mind bomb (Mib), cooperatively regulate the endocytosis of Notch ligands in Drosophila. However, the respective roles of the mammalian E3 ubiquitin ligases, Neur1, Neur2, Mib1, and Mib2, in mammalian development are poorly understood. Methodology/Principal Findings. Through extensive use of mammalian genetics, here we show that Neur1 and Neur2 double mutants and Mib2 2/2 mice were viable and grossly normal. In contrast, conditional inactivation of Mib1 in various tissues revealed the representative Notch phenotypes: defects of arterial specification as deltalike4 mutants, abnormal cerebellum and skin development as jagged1 conditional mutants, and syndactylism as jagged2 mutants. Conclusions/Significance. Our data provide the first evidence that Mib1 is essential for Jagged as well as Deltalike ligand-mediated Notch signaling in mammalian development, while Neur1, Neur2, and Mib2 are dispensable.open117978Nsciescopu
High Fidelity Tape Transfer Printing Based On Chemically Induced Adhesive Strength Modulation
Transfer printing, a two-step process (i.e. picking up and printing) for heterogeneous integration, has been widely exploited for the fabrication of functional electronics system. To ensure a reliable process, strong adhesion for picking up and weak or no adhesion for printing are required. However, it is challenging to meet the requirements of switchable stamp adhesion. Here we introduce a simple, high fidelity process, namely tape transfer printing(TTP), enabled by chemically induced dramatic modulation in tape adhesive strength. We describe the working mechanism of the adhesion modulation that governs this process and demonstrate the method by high fidelity tape transfer printing several types of materials and devices, including Si pellets arrays, photodetector arrays, and electromyography (EMG) sensors, from their preparation substrates to various alien substrates. High fidelity tape transfer printing of components onto curvilinear surfaces is also illustrated
Modelling control of Schistosoma haematobium infection: predictions of the long-term impact of mass drug administration in Africa.
BACKGROUND: Effective control of schistosomiasis remains a challenging problem for endemic areas of the world. Given knowledge of the biology of transmission and past experience with mass drug administration (MDA) programs, it is important to critically evaluate the likelihood that MDA programs will achieve substantial reductions in Schistosoma prevalence. In implementing the World Health Organization Roadmap for Neglected Tropical Diseases it would useful for policymaking to model projections of the status of Schistosoma control in MDA-treated areas in the next 5-10 years. METHODS: Calibrated mathematical models were used to project the effects of different frequency and coverage of MDA for schistosomiasis haematobia control in present-day endemic communities, taking into account uncertainties of parasite biology and input data. The modeling approach in this analysis was the Stratified Worm Burden model developed in our earlier works, calibrated using data from longitudinal S. haematobium control trials in Kenya. RESULTS: Model-based simulations of MDA control in typical low-risk and higher-risk communities indicated that infection prevalence can be substantially reduced within 10 years only when there is a high degree of community participation (>70 %) with at least annual MDA. Significant risk for re-emergence of infection remains if MDA is suspended. CONCLUSIONS: In a stable (stationary) ecosystem, Schistosoma reproduction and transmission are sufficiently robust that the process of human infection continues, even under pressure from aggressive MDA. MDA alone is unlikely to interrupt transmission, and once mass treatment is suspended, the prevalence of human infection is likely to rebound to pre-control levels over a period of 25-30 years. MDA success in achieving very low levels of infection prevalence is highly dependent on treatment coverage and frequency within the local human population, and requires that both adults and children be included in drug delivery coverage. Ultimately, supplemental snail control and significant improvements in sanitation will be required to achieve full control of schistosomiasis by elimination of ongoing Schistosoma transmission
Fractal Properties of Robust Strange Nonchaotic Attractors in Maps of Two or More Dimensions
We consider the existence of robust strange nonchaotic attractors (SNA's) in
a simple class of quasiperiodically forced systems. Rigorous results are
presented demonstrating that the resulting attractors are strange in the sense
that their box-counting dimension is N+1 while their information dimension is
N. We also show how these properties are manifested in numerical experiments.Comment: 9 pages, 14 figure
Impact of BRCA1/2 cascade testing on anxiety, depression, and cancer worry levels among unaffected relatives in a multiethnic Asian cohort
Cascade testing for families with BRCA pathogenic variants is important to identify relatives who are carriers. These relatives can benefit from appropriate risk management and preventative strategies arising from an inherited increased risk of breast, ovarian, prostate, melanoma, and pancreatic cancers. Cascade testing has the potential to enable cost-effective cancer control even in low- and middle-income settings, but few studies have hitherto evaluated the psychosocial impact of cascade testing in an Asian population, where the cultural and religious beliefs around inheritance and destiny have previously been shown to influence perception and attitudes toward screening. In this study, we evaluated the short- and long-term psychosocial impact of genetic testing among unaffected relatives of probands identified through the Malaysian Breast Cancer Genetics Study and the Malaysian Ovarian Cancer Study, using validated questionnaires (Hospital Anxiety and Depression Scale and Cancer Worry Scale) administered at baseline, and 1-month and 2-year post-disclosure of results. Of the 305 unaffected relatives from 98 independent families who were offered cascade testing, 256 (84%) completed predictive testing and family history of cancers was the only factor significantly associated with uptake of predictive testing. We found that the levels of anxiety, depression, and cancer worry among unaffected relatives decreased significantly after result disclosure and remained low 2-year post-result disclosure. Younger relatives and relatives of Malay descent had higher cancer worry at both baseline and after result disclosure compared to those of Chinese and Indian descent, whereas relatives of Indian descent and those with family history of cancers had higher anxiety and depression levels post-result disclosure. Taken together, the results from this Asian cohort highlight the differences in psychosocial needs in different communities and inform the development of culture-specific genetic counseling strategies
Solutions of the atmospheric, solar and LSND neutrino anomalies from TeV scale quark-lepton unification
There is a unique gauge model which
allows quarks and leptons to be unified at the TeV scale. It is already known
that the neutrino masses arise radiatively in the model and are naturally
light. We study the atmospheric, solar and LSND neutrino anomalies within the
framework of this model.Comment: Minor changes, 31 page
Host galaxies of long gamma-ray bursts in the Millennium Simulation
(abridged) In this work, we investigate the nature of the host galaxies of
long Gamma-Ray bursts (LGRBs) using a galaxy catalogue constructed from the
Millennium Simulation. We developed an LGRB synthetic model based on the
hypothesis that these events originate at the end of the life of massive stars
following the collapsar model, with the possibility of including a constraint
on the metallicity of the progenitor star. A complete observability pipeline
was designed to calculate a probability estimation for a galaxy to be
observationally identified as a host for LGRBs detected by present
observational facilities. This new tool allows us to build an observable host
galaxy catalogue which is required to reproduce the current stellar mass
distribution of observed hosts. This observability pipeline predicts that the
minimum mass for the progenitor stars should be ~75 solar masses in order to be
able to reproduce BATSE observations. Systems in our observable catalogue are
able to reproduce the observed properties of host galaxies, namely stellar
masses, colours, luminosity, star formation activity and metallicities as a
function of redshift. At z>2, our model predicts that the observable host
galaxies would be very similar to the global galaxy population. We found that
~88 per cent of the observable host galaxies with mean gas metallicity lower
than 0.6 solar have stellar masses in the range 10^8.5-10^10.3 solar masses in
excellent agreement with observations. Interestingly, in our model observable
host galaxies remain mainly within this mass range regardless of redshift,
since lower stellar mass systems would have a low probability of being observed
while more massive ones would be too metal-rich. Observable host galaxies are
predicted to preferentially inhabit dark matter haloes in the range
10^11-10^11.5 solar masses, with a weak dependence on redshift.Comment: 11 pages, 10 figures, accepted for publication in MNRA
Multi-site campaign for transit timing variations of WASP-12 b: possible detection of a long-period signal of planetary origin
The transiting planet WASP-12 b was identified as a potential target for
transit timing studies because a departure from a linear ephemeris was reported
in the literature. Such deviations could be caused by an additional planet in
the system. We attempt to confirm the existence of claimed variations in
transit timing and interpret its origin. We organised a multi-site campaign to
observe transits by WASP-12 b in three observing seasons, using 0.5-2.6-metre
telescopes. We obtained 61 transit light curves, many of them with
sub-millimagnitude precision. The simultaneous analysis of the best-quality
datasets allowed us to obtain refined system parameters, which agree with
values reported in previous studies. The residuals versus a linear ephemeris
reveal a possible periodic signal that may be approximated by a sinusoid with
an amplitude of 0.00068+/-0.00013 d and period of 500+/-20 orbital periods of
WASP-12 b. The joint analysis of timing data and published radial velocity
measurements results in a two-planet model which better explains observations
than single-planet scenarios. We hypothesize that WASP-12 b might be not the
only planet in the system and there might be the additional 0.1 M_Jup body on a
3.6-d eccentric orbit. A dynamical analysis indicates that the proposed
two-planet system is stable over long timescales.Comment: Accepted for publication in A&
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