Capacitary Maximal Inequalities and Applications

In this paper we introduce capacitary analogues of the Hardy-Littlewood maximal function, \begin{align*} \mathcal{M}_C(f)(x):= \sup_{r>0} \frac{1}{C(B(x,r))} \int_{B(x,r)} |f|\;dC, \end{align*} for $C=$ the Hausdorff content or a Riesz capacity. For these maximal functions, we prove a strong-type $(p,p)$ bound for $1<p \leq+\infty$ on the capacitary integration spaces $L^p(C)$ and a weak-type $(1,1)$ bound on the capacitary integration space $L^1(C)$. We show how these estimates clarify and improve the existing literature concerning maximal function estimates on capacitary integration spaces. As a consequence, we deduce correspondingly stronger differentiation theorems of Lebesgue-type, which in turn, by classical capacitary inequalities, yield more precise estimates concerning Lebesgue points for functions in Sobolev spaces.Comment: 22 page

Magnetoresistive biosensors with on-chip pulsed excitation and magnetic correlated double sampling.

Giant magnetoresistive (GMR) sensors have been shown to be among the most sensitive biosensors reported. While high-density and scalable sensor arrays are desirable for achieving multiplex detection, scalability remains challenging because of long data acquisition time using conventional readout methods. In this paper, we present a scalable magnetoresistive biosensor array with an on-chip magnetic field generator and a high-speed data acquisition method. The on-chip field generators enable magnetic correlated double sampling (MCDS) and global chopper stabilization to suppress 1/f noise and offset. A measurement with the proposed system takes only 20 ms, approximately 50× faster than conventional frequency domain analysis. A corresponding time domain temperature correction technique is also presented and shown to be able to remove temperature dependence from the measured signal without extra measurements or reference sensors. Measurements demonstrate detection of magnetic nanoparticles (MNPs) at a signal level as low as 6.92 ppm. The small form factor enables the proposed platform to be portable as well as having high sensitivity and rapid readout, desirable features for next generation diagnostic systems, especially in point-of-care (POC) settings

BiGlobal stability analysis in curvilinear coordinates of massively separated lifting bodies

A methodology based on spectral collocation numerical methods for global flow stability analysis of incompressible external flows is presented. A potential shortcoming of spectral methods, namely the handling of the complex geometries encountered in global stability analysis, has been dealt with successfully in past works by the development of spectral-element methods on unstructured meshes. The present contribution shows that a certain degree of regularity of the geometry may be exploited in order to build a global stability analysis approach based on a regular spectral rectangular grid in curvilinear coordinates and conformal mappings. The derivation of the stability linear operator in curvilinear coordinates is presented along with the discretisation method. Unlike common practice to the solution of the same problem, the matrix discretising the eigenvalue problem is formed and stored. Subspace iteration and massive parallelisation are used in order to recover a wide window of its leading Ritz system. The method is applied to two external flows, both of which are lifting bodies with separation occurring just downstream of the leading edge. Specifically the flow configurations are a NACA 0015 airfoil, and an ellipse of aspect ratio 8 chosen to closely approximate the geometry of the airfoil. Both flow configurations are at an angle of attack of 18, with a Reynolds number based on the chord length of 200. The results of the stability analysis for both geometries are presented and illustrate analogous features

Protein cohabitation: long-term immunoglobulin G storage at room temperature

Long-term functional storage of therapeutic proteins at room temperature has been an eternal challenge. Inspired by the cellular cooperativity of proteins, we have taken a step forward to address this challenge by cohabitating Immunoglobulin G (IgG1) with a food protein gelatin in the solid-state at room temperature. Interestingly, IgG1 remained functionally active for a record 14 months revealed from the western-blot assay. Further quantification by HP-LC analysis showed 100% structural integrity of IgG1 with no degradation in the gelatin matrix during this period. The developed formulation has a direct application in oral medical nutrition therapy to cure gastrointestinal microbial infections. Also the strategy provides a robust energy economic alternative to the protein engineering methods for long-term functional storage of therapeutic proteins at room temperature

Dynamic instability of genomic methylation patterns in pluripotent stem cells

<p>Abstract</p> <p>Background</p> <p>Genomic methylation patterns are established during gametogenesis, and perpetuated in somatic cells by faithful maintenance methylation. There have been previous indications that genomic methylation patterns may be less stable in embryonic stem (ES) cells than in differentiated somatic cells, but it is not known whether different mechanisms of <it>de novo </it>and maintenance methylation operate in pluripotent stem cells compared with differentiating somatic cells.</p> <p>Results</p> <p>In this paper, we show that ablation of the DNA methyltransferase regulator DNMT3L (DNA methyltransferase 3-like) in mouse ES cells renders them essentially incapable of <it>de novo </it>methylation of newly integrated retroviral DNA. We also show that ES cells lacking DNMT3L lose DNA methylation over time in culture, suggesting that DNA methylation in ES cells is the result of dynamic loss and gain of DNA methylation. We found that wild-type female ES cells lose DNA methylation at a much faster rate than do male ES cells; this defect could not be attributed to sex-specific differences in expression of DNMT3L or of any DNA methyltransferase. We also found that human ES and induced pluripotent stem cell lines showed marked but variable loss of methylation that could not be attributed to sex chromosome constitution or time in culture.</p> <p>Conclusions</p> <p>These data indicate that DNA methylation in pluripotent stem cells is much more dynamic and error-prone than is maintenance methylation in differentiated cells. DNA methylation requires DNMT3L in stem cells, but DNMT3L is not expressed in differentiating somatic cells. Error-prone maintenance methylation will introduce unpredictable phenotypic variation into clonal populations of pluripotent stem cells, and this variation is likely to be much more pronounced in cultured female cells. This epigenetic variability has obvious negative implications for the clinical applications of stem cells.</p

Improved microarray methods for profiling the yeast knockout strain collection

A remarkable feature of the Yeast Knockout strain collection is the presence of two unique 20mer TAG sequences in almost every strain. In principle, the relative abundances of strains in a complex mixture can be profiled swiftly and quantitatively by amplifying these sequences and hybridizing them to microarrays, but TAG microarrays have not been widely used. Here, we introduce a TAG microarray design with sophisticated controls and describe a robust method for hybridizing high concentrations of dye-labeled TAGs in single-stranded form. We also highlight the importance of avoiding PCR contamination and provide procedures for detection and eradication. Validation experiments using these methods yielded false positive (FP) and false negative (FN) rates for individual TAG detection of 3–6% and 15–18%, respectively. Analysis demonstrated that cross-hybridization was the chief source of FPs, while TAG amplification defects were the main cause of FNs. The materials, protocols, data and associated software described here comprise a suite of experimental resources that should facilitate the use of TAG microarrays for a wide variety of genetic screens