15,518 research outputs found
Toward a Neutrino Mass Matrix
One may identify the general properties of the neutrino mass matrix by
generating many random mass matrices and testing them against the results of
the neutrino experiments.Comment: 3 pages, 1 figure, talk at DPF200
Epithelial ErbB2 regulation of thymus homeostasis and age-associated T cell mediated immunity
The molecular mechanisms governing the functional and structural decline of thymus with age, causing thymic immunosenescence, are incompletely identified. Using a bitransgenic mouse model, Dr Giangreco discovered that the over-expression of receptor tyrosine kinase ErbB2 causes reversible thymic atrophy. The over-expression of epithelial ErbB2 upon doxycycline administration in bitransgenic mice led to decreased thymus size and cellularity, loss of cortical-medullary boundary and abnormal T cell differentiation, bearing similarity to age-dependent thymic involution. This thesis set out to investigate this observation in more detail. I demonstrated that the observed atrophy in bitransgenic thymuses was because of thymus-specific ErbB2 expression, by employing foetal thymic organ cultures. In addition, I showed that over-expression of epithelial ErbB2 disrupted the thymic epithelial cells distribution. Also, an increase in Sca1+Cd49f+ epithelial cells with stem cell potential was noted, explaining why the thymic atrophy in bitransgenic mice was reversible. Exploration of the potential mechanistic pathways found that the thymic atrophy phenotype of K14-NICDER mice, in which epithelial Notch is activated upon tamoxifen administration, resembled the bitransgenic mouse thymic atrophy phenotype. However, mechanistic studies failed to establish ErbB2 acting upstream of Notch, and require further investigation. Administration of Lapatinib, an ErbB2 inhibitor improved the thymic organization and function in aged mice. Lapatinib treatment of aged mice also enhanced vaccine responses to Prevenar 13, a Streptococcus pneumoniae glycoconjugate vaccine, and increased the efficacy of vaccination to protect against subsequent pneumonia challenge. However my results showed that ErbB2 inhibition does not reverse thymic atrophy in scurfy mice, which have truncated Foxp3 protein, and an autoimmune phenotype. In conclusion, this study highlights the importance of ErbB2 in maintaining thymus homeostasis and thymus mediated immunity, and proposes a novel ErbB2 inhibition therapy for rejuvenating an aged thymus, to counter the associated immunosenescence and thereby improve vaccine responses
Feasibility and benefits of laminar flow control on supersonic cruise airplanes
An evaluation was made of the applicability and benefits of laminar flow control (LFC) technology to supersonic cruise airplanes. Ancillary objectives were to identify the technical issues critical to supersonic LFC application, and to determine how those issues can be addressed through flight and wind-tunnel testing. Vehicle types studied include a Mach 2.2 supersonic transport configuration, a Mach 4.0 transport, and two Mach 2-class fighter concepts. Laminar flow control methodologies developed for subsonic and transonic wing laminarization were extended and applied. No intractible aerodynamic problems were found in applying LFC to airplanes of the Mach 2 class, even ones of large size. Improvements of 12 to 17 percent in lift-drag ratios were found. Several key technical issues, such as contamination avoidance and excresence criteria were identified. Recommendations are made for their resolution. A need for an inverse supersonic wing design methodology is indicated
Recommended from our members
Soft Glass Equiangular Spiral Photonic Crystal Fiber for Supercontinuum Generation
An equiangular spiral photonic crystal fiber (ES-PCF) design in soft glass is presented that has high nonlinearity ( gamma > 5250 W-1 middot km-1 at 1064 nm and gamma > 2150 W-1 middot km-1 at 1550 nm) with a low and flat dispersion (D ~ 0.8 ps/kmmiddotnm and dispersion slope ~ -0.7 ps/km middot nm2 at 1060 nm). The design inspired by nature is characterized by a full-vectorial finite element method. The ES-PCF presented improves over the mode confinement of triangular core designs and dispersion control of conventional hexagonal PCF, combining the advantages of both designs; it can be an excellent candidate for generating supercontinuum pumped at 1.06 mum
Recommended from our members
Determination of the Aspect-ratio Distribution of Gold Nanorods in a Colloidal Solution using UV-visible absorption spectroscopy
Knowledge of the distribution of the aspect ratios (ARs) in a chemically-synthesized colloidal solution of Gold Nano Rods (GNRs) is an important measure in determining the quality of synthesis, and consequently the performance of the GNRs generated for various applications. In this work, an algorithm has been developed based on the Bellman Principle of Optimality to readily determine the AR distribution of synthesized GNRs in colloidal solutions. This is achieved by theoretically fitting the longitudinal plasmon resonance of GNRs obtained by UV-visible spectroscopy. The AR distribution obtained from the use of the algorithm developed have shown good agreement with those theoretically generated one as well as with the previously reported results. After bench-marking, the algorithm has been applied to determine the mean and standard deviation of the AR distribution of two GNRs solutions synthesized and examined in this work. The comparison with experimentally derived results from the use of expensive Transmission Electron Microscopic images and Dynamic Light Scattering technique shows that the algorithm developed offers a fast and thus potentially cost-effective solution to determine the quality of the synthesized GNRs specifically needed for many potential applications for the advanced sensor systems
Effect of pooling samples on the efficiency of comparative studies using microarrays
Many biomedical experiments are carried out by pooling individual biological
samples. However, pooling samples can potentially hide biological variance and
give false confidence concerning the data significance. In the context of
microarray experiments for detecting differentially expressed genes, recent
publications have addressed the problem of the efficiency of sample-pooling,
and some approximate formulas were provided for the power and sample size
calculations. It is desirable to have exact formulas for these calculations and
have the approximate results checked against the exact ones. We show that the
difference between the approximate and exact results can be large. In this
study, we have characterized quantitatively the effect of pooling samples on
the efficiency of microarray experiments for the detection of differential gene
expression between two classes. We present exact formulas for calculating the
power of microarray experimental designs involving sample pooling and technical
replications. The formulas can be used to determine the total numbers of arrays
and biological subjects required in an experiment to achieve the desired power
at a given significance level. The conditions under which pooled design becomes
preferable to non-pooled design can then be derived given the unit cost
associated with a microarray and that with a biological subject. This paper
thus serves to provide guidance on sample pooling and cost effectiveness. The
formulation in this paper is outlined in the context of performing microarray
comparative studies, but its applicability is not limited to microarray
experiments. It is also applicable to a wide range of biomedical comparative
studies where sample pooling may be involved.Comment: 8 pages, 1 figure, 2 tables; to appear in Bioinformatic
Soliton turbulences in the complex Ginzburg-Landau equation
We study spatio-temporal chaos in the complex Ginzburg-Landau equation in
parameter regions of weak amplification and viscosity. Turbulent states
involving many soliton-like pulses appear in the parameter range, because the
complex Ginzburg-Landau equation is close to the nonlinear Schr\"odinger
equation. We find that the distributions of amplitude and wavenumber of pulses
depend only on the ratio of the two parameters of the amplification and the
viscosity. This implies that a one-parameter family of soliton turbulence
states characterized by different distributions of the soliton parameters
exists continuously around the completely integrable system.Comment: 5 figure
- …