Coherent Control of High Harmonic Generation via Dual-Gas Multijet Arrays

High harmonic generation (HHG) is a central driver of the rapidly growing field of ultrafast science. We present a novel quasiphase-matching (QPM) concept with a dual-gas multijet target leading, for the first time, to remarkable phase control between multiple HHG sources (> 2) within the Rayleigh range. The alternating jet structure with driving and matching zones shows perfect coherent buildup for up to six QPM periods. Although not in the focus of the proof-of-principle studies presented here, we achieved competitive conversion efficiencies already in this early stage of development.

Circulating and synovial antibody profiling of juvenile arthritis patients by nucleic acid programmable protein arrays.

Introduction Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of auto-antibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients. Methods A pilot study was performed on the application of a high-throughput platform, nucleic acid programmable protein arrays (NAPPA), to assess the levels of antibodies present in the systemic circulation and synovial joint of a small cohort of juvenile arthritis patients. Plasma and synovial fluid from ten JIA patients was screened for antibodies against 768 proteins on NAPPA. Results Quantitative reproducibility of NAPPA was demonstrated with >0.95 intra- and inter- array correlations. A strong correlation was also observed for the levels of antibodies between plasma and synovial fluid across the study cohort (r=0.96). Differences in the levels of 18 antibodies were revealed between sample types across all patients. Patients were segregated into two clinical subtypes with distinct antibody signatures by unsupervised hierarchical cluster analysis. Conclusions NAPPA provides a high-throughput quantitatively reproducible platform to screen for disease specific autoantibodies at the proteome level on a microscope slide. The strong correlation between the circulating antibody levels and those of the inflamed joint represents a novel finding and provides confidence to use plasma for discovery of autoantibodies in JIA, thus circumventing the challenges associated with joint aspiration. We expect that autoantibody profiling of JIA patients on NAPPA could yield antibody markers that can act as criteria to stratify patients, predict outcomes and understand disease etiology at the molecular level.

Development and comparison of a Primer-Probe Energy Transfer based assay and a 5 ' conjugated Minor Groove Binder assay for sensitive real-time PCR detection of infectious laryngotracheitis virus

In this study the design and development of two real-time PCR assays for the rapid, sensitive and specific detection of infectious laryngotracheitis virus (ILTV) DNA is described. A Primer-Probe Energy Transfer (PriProET) assay and 5' conjugated Minor Groove Binder (MGB) method are compared and contrasted. Both have been designed to target the thymidine kinase gene of the ILTV genome. Both PriProET and MGB assays are capable of detecting 20 copies of a DNA standard per reaction and are linear from 2 x 10(8) to 2 x 10(2) copies/mu l. Neither PriProET, nor MGB reacted with heterologous herpesviruses, indicating a high specificity of the two methods as novel tools for virus detection and identification. This study demonstrates the suitability of PriProET and 5' conjugated MGB probes as real-time PCR chemistries for the diagnosis of respiratory diseases caused by ILTV. (C) 2011 Elsevier B.V. All rights reserved.

Development of a minor groove binder assay for real-time one-step RT-PCR detection of swine vesicular disease virus

The design and development of a 5' conjugated minor groove binder (MGB) probe real-time RT-PCR assay are described for rapid, sensitive and specific detection of swine vesicular disease virus (SVDV) RNA. The assay is designed to target the 2C gene of the SVDV genome and is capable of detecting 2 x 10(2) copies of an RNA standard per reaction. It does not detect any of the other RNA viruses that cause vesicular disease in pigs, or the human enterovirus, Coxsackie B5 virus (CVB5) which is closely related antigenically to SVDV. The linear range of this test was from 2 x 10(2) to 2 x 10(8) copies/mu l. The assay is rapid and can detect SVDV RNA in just over 3.5 h including the time required for nucleic acid extraction. The development of this assay provides a useful tool for the differential diagnosis of SVD or for the detection of SVDV in research applications. This study demonstrates the suitability of MGB probes as a real-time PCR chemistry for the diagnosis of swine vesicular disease. (C) 2010 Elsevier B.V. All rights reserved.

Sensitive detection of African swine fever virus using real-time PCR with a 5 ' conjugated minor groove binder probe

The design of a 5' conjugated minor groove binder (MGB) probe real-time PCR assay is described for the rapid, sensitive and specific detection of African swine fever virus (ASFV) DNA. The assay is designed against the 9GL region and is capable of detecting 20 copies of a DNA standard. It does not detect any of the other common swine DNA viruses tested in this study. The assay can detect ASFV DNA in a range of clinical samples. Sensitivity was equivalent to the Office International des Epizooties (OIE) recommended TaqMan assay. In addition the assay was found to have a detection limit 10-fold more sensitive than the conventional PCR recommended by the OIE. Linear range was ten logs from 2 x 10(1) to 2 x 10(10). The assay is rapid with an amplification time just over 2 h. The development of this assay provides a useful tool for the specific diagnosis of ASF in statutory or emergency testing programs or for the detection of ASFV DNA in research applications. (C) 2010 Elsevier B.V. All rights reserved.

Regular nanodomain vertex arrays in BiFeO3 single crystals

Domain patterns consisting of triangular nanodomains of less than 50 nm size, arranged into long regular vertex arrays separated by stripe domains, were observed by (scanning and high-resolution) transmission electron microscopy and piezoresponse force microscopy in BiFeO3 single crystals grown from solution flux. Piezoresponse force microscopy analysis together with crystallographic analysis by selected area and nanobeam electron diffraction indicate that these patterns consist of ferroelectric 109 degrees domains. A possibility for conserving Kittel's law is discussed in terms of the patterns being confined to the skin layer observed recently on BiFeO3 single crystals.

Hydrogel-Forming Microneedle Arrays for Enhanced Transdermal Drug Delivery

Unique microneedle arrays prepared from crosslinked polymers, which contain no drug themselves, are described. They rapidly take up skin interstitial fluid upon skin insertion to form continuous, unblockable, hydrogel conduits from attached patch-type drug reservoirs to the dermal microcirculation. Importantly, such microneedles, which can be fabricated in a wide range of patch sizes and microneedle geometries, can be easily sterilized, resist hole closure while in place, and are removed completely intact from the skin. Delivery of macromolecules is no longer limited to what can be loaded into the microneedles themselves and transdermal drug delivery is now controlled by the crosslink density of the hydrogel system rather than the stratum corneum, while electrically modulated delivery is also a unique feature. This technology has the potential to overcome the limitations of conventional microneedle designs and greatly increase the range of the type of drug that is deliverable transdermally, with ensuing benefits for industry, healthcare providers and, ultimately, patients.