Clinical Remission in Oral Corticosteroid (OCS)-dependent Patients with Severe Asthma : An Analysis of the ANDHI-IP and PONENTE Trials

Funding: This study was funded by AstraZeneca (Cambridge, UK).Peer reviewe

Optimization and evaluation of a non-invasive tool for peste des petits ruminants surveillance and control

Peste des petits ruminants (PPR) is a highly contagious and devastating viral disease affecting mainly sheep and goats, but also a large number of wild species within the order Artiodactyla. A better understanding of PPR transmission dynamics in multi-host systems is necessary to efficiently control the disease, in particular where wildlife and livestock co-occur. Notably, the role of wildlife in PPR epidemiology is still not clearly understood. Non-invasive strategies to detect PPR infection without the need for animal handling could greatly facilitate research on PPR epidemiology and management of the disease in atypical hosts and in complex field situations. Here, we describe optimized methods for the direct detection of PPR virus genetic material and antigen in fecal samples. We use these methods to determine the detection window of PPR in fecal samples, and compare the sensitivity of these methods to standard invasive sampling and PPR diagnostic methods using field samples collected at a wildlife-livestock interface in Africa. Our results show that quantitative reverse transcription PCR (RT-QPCR) amplification of PPRV from fecal swabs has good sensitivity in comparison to ocular swabs. Animals infected by PPRV could be identified relatively early on and during the whole course of infection based on fecal samples using RT-QPCR. Partial gene sequences could also be retrieved in some cases, from both fecal and ocular samples, providing important information about virus origin and relatedness to other PPRV strains. Non-invasive strategies for PPRV surveillance could provide important data to fill major gaps in our knowledge of the multi-host PPR epidemiology

Preliminary studies of sediments from the Dobczyce drinking water reservoir

The analysis of river and lake sediments indicates that the physical, chemical, biochemical and geochemical processes that influence the fate of toxic compounds and elements in sediments are numerous and complex (for example: sorption - desorption, oxidation - reduction, ion-exchange, biological activity). Due to the above-mentioned general statement, only a long term and complex research programme can lead to satisfactory answers to the questions relating to possible changes of water and environmental quality in the future. The aim of our study consisted in physical and chemical characterisation of sediments in in-depth profiles taken from the Dobczyce reservoir in southern Poland that is a main source of drinking water for the city of Kraków. Due to morphological reasons, 7 layers of sediment samples were distinguished from the ground level to about 90 cm below (total thickness of the sediments in the sampling site). Analysis of grain size distribution and application of x-ray diffraction method, enabled mineralogical description of sediments. The use of proton-induced x-ray emission (PIXE) and atomic absorption spectrometry (AAS) revealed elemental composition of the samples (Al, P, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn). Concentrations of natural 40K and artificial 137Cs radionuclides were determined by the use of gamma spectrometry. The following facts were established: 1) the oldest (deepest) and newest, recently deposited layers of sediments are similar in their physical and chemical properties. It means that the inflow of contaminants and biogenic compounds to the reservoir has changed little since it was constructed and filled with water; 2) the severe flood in 1997 changed significantly sediment composition and, in fact, led to purification of sediments in the Dobczyce reservoir

High-Throughput In Vitro, Ex Vivo, and In Vivo Screen of Adeno-Associated Virus Vectors Based on Physical and Functional Transduction

Adeno-associated virus (AAV) vectors are quickly becoming the vectors of choice for therapeutic gene delivery. To date, hundreds of natural isolates and bioengineered variants have been reported. While factors such as high production titer and low immunoreactivity are important to consider, the ability to deliver the genetic payload (physical transduction) and to drive high transgene expression (functional transduction) remains the most important feature when selecting AAV variants for clinical applications. Reporter expression assays are the most commonly used methods for determining vector fitness. However, such approaches are time consuming and become impractical when evaluating a large number of variants. Limited access to primary human tissues or challenging model systems further complicates vector testing. To address this problem, convenient high-throughput methods based on next-generation sequencing (NGS) are being developed. To this end, we built an AAV Testing Kit that allows inherent flexibility in regard to number and type of AAV variants included, and is compatible with in vitro, ex vivo, and in vivo applications. The Testing Kit presented here consists of a mix of 30 known AAVs where each variant encodes a CMV-eGFP cassette and a unique barcode in the 3′-untranslated region of the eGFP gene, allowing NGS-barcode analysis at both the DNA and RNA/cDNA levels. To validate the AAV Testing Kit, individually packaged barcoded variants were mixed at an equal ratio and used to transduce cells/tissues of interest. DNA and RNA/cDNA were extracted and subsequently analyzed by NGS to determine the physical/functional transduction efficiencies. We were able to assess the transduction efficiencies of immortalized cells, primary cells, and induced pluripotent stem cells in vitro, as well as in vivo transduction in naïve mice and a xenograft liver model. Importantly, while our data validated previously reported transduction characteristics of individual capsids, we also identified novel previously unknown tropisms for some AAV variants

Operations of Points on Elliptic Curve in Projective Coordinates

In this article, we formalize operations of points on an elliptic curve over GF(p). Elliptic curve cryptography [7], whose security is based on a difficulty of discrete logarithm problem of elliptic curves, is important for information security. We prove that the two operations of points: compellProjCo and addellProjCo are unary and binary operations of a point over the elliptic curve.Futa Yuichi - Shinshu University, Nagano, JapanOkazaki Hiroyuki - Shinshu University, Nagano, JapanMizushima Daichi - Shinshu University, Nagano, JapanShidama Yasunari - Shinshu University, Nagano, JapanGrzegorz Bancerek. The ordinal numbers. Formalized Mathematics, 1(1):91-96, 1990.Czesław Byliński. Binary operations. Formalized Mathematics, 1(1):175-180, 1990.Czesław Byliński. Functions and their basic properties. Formalized Mathematics, 1(1):55-65, 1990.Czesław Byliński. Functions from a set to a set. Formalized Mathematics, 1(1):153-164, 1990.Czesław Byliński. Some basic properties of sets. Formalized Mathematics, 1(1):47-53, 1990.Yuichi Futa, Hiroyuki Okazaki, and Yasunari Shidama. Set of points on elliptic curve in projective coordinates. Formalized Mathematics, 19(3):131-138, 2011, doi: 10.2478/v10037-011-0021-6.G. Seroussi I. Blake and N. Smart. Elliptic Curves in Cryptography. Number 265 in London Mathematical Society Lecture Note Series. Cambridge University Press, 1999.Eugeniusz Kusak, Wojciech Leończuk, and Michał Muzalewski. Abelian groups, fields and vector spaces. Formalized Mathematics, 1(2):335-342, 1990.Rafał Kwiatek. Factorial and Newton coefficients. Formalized Mathematics, 1(5):887-890, 1990.Rafał Kwiatek and Grzegorz Zwara. The divisibility of integers and integer relative primes. Formalized Mathematics, 1(5):829-832, 1990.Christoph Schwarzweller. The binomial theorem for algebraic structures. Formalized Mathematics, 9(3):559-564, 2001.Andrzej Trybulec. Domains and their Cartesian products. Formalized Mathematics, 1(1):115-122, 1990.Andrzej Trybulec. Tuples, projections and Cartesian products. Formalized Mathematics, 1(1):97-105, 1990.Michał J. Trybulec. Integers. Formalized Mathematics, 1(3):501-505, 1990.Wojciech A. Trybulec. Groups. Formalized Mathematics, 1(5):821-827, 1990.Wojciech A. Trybulec. Vectors in real linear space. Formalized Mathematics, 1(2):291-296, 1990.Zinaida Trybulec. Properties of subsets. Formalized Mathematics, 1(1):67-71, 1990

Set of Points on Elliptic Curve in Projective Coordinates

In this article, we formalize a set of points on an elliptic curve over GF(p). Elliptic curve cryptography [10], whose security is based on a difficulty of discrete logarithm problem of elliptic curves, is important for information security.Futa Yuichi - Shinshu University, Nagano, JapanOkazaki Hiroyuki - Shinshu University, Nagano, JapanShidama Yasunari - Shinshu University, Nagano, JapanGrzegorz Bancerek. Cardinal numbers. Formalized Mathematics, 1(2):377-382, 1990.Grzegorz Bancerek. The fundamental properties of natural numbers. Formalized Mathematics, 1(1):41-46, 1990.Grzegorz Bancerek and Krzysztof Hryniewiecki. Segments of natural numbers and finite sequences. Formalized Mathematics, 1(1):107-114, 1990.Józef Białas. Group and field definitions. Formalized Mathematics, 1(3):433-439, 1990.Czesław Byliński. Functions and their basic properties. Formalized Mathematics, 1(1):55-65, 1990.Czesław Byliński. Functions from a set to a set. Formalized Mathematics, 1(1):153-164, 1990.Czesław Byliński. Some basic properties of sets. Formalized Mathematics, 1(1):47-53, 1990.Agata Darmochwał. Finite sets. Formalized Mathematics, 1(1):165-167, 1990.Krzysztof Hryniewiecki. Basic properties of real numbers. Formalized Mathematics, 1(1):35-40, 1990.G. Seroussi I. Blake and N. Smart. Elliptic Curves in Cryptography. Number 265 in London Mathematical Society Lecture Note Series. Cambridge University Press, 1999.Eugeniusz Kusak, Wojciech Leończuk, and Michał Muzalewski. Abelian groups, fields and vector spaces. Formalized Mathematics, 1(2):335-342, 1990.Rafał Kwiatek. Factorial and Newton coefficients. Formalized Mathematics, 1(5):887-890, 1990.Konrad Raczkowski and Paweł Sadowski. Equivalence relations and classes of abstraction. Formalized Mathematics, 1(3):441-444, 1990.Christoph Schwarzweller. The ring of integers, euclidean rings and modulo integers. Formalized Mathematics, 8(1):29-34, 1999.Christoph Schwarzweller. The binomial theorem for algebraic structures. Formalized Mathematics, 9(3):559-564, 2001.Andrzej Trybulec. Domains and their Cartesian products. Formalized Mathematics, 1(1):115-122, 1990.Andrzej Trybulec. Tuples, projections and Cartesian products. Formalized Mathematics, 1(1):97-105, 1990.Michał J. Trybulec. Integers. Formalized Mathematics, 1(3):501-505, 1990.Wojciech A. Trybulec. Groups. Formalized Mathematics, 1(5):821-827, 1990.Wojciech A. Trybulec. Vectors in real linear space. Formalized Mathematics, 1(2):291-296, 1990.Zinaida Trybulec. Properties of subsets. Formalized Mathematics, 1(1):67-71, 1990.Edmund Woronowicz. Relations and their basic properties. Formalized Mathematics, 1(1):73-83, 1990.Edmund Woronowicz and Anna Zalewska. Properties of binary relations. Formalized Mathematics, 1(1):85-89, 1990

Earthquake source parameters and scaling relationships in Hungary (central Pannonian basin)

Abstract Fifty earthquakes that occurred in Hungary (central part of the Pannonian basin) with local magnitude ML ranging from 0.8 to 4.5 have been analyzed. The digital seismograms used in this study were recorded by six permanent broad-band stations and twenty short-period ones at hypocentral distances between 10 and 327 km. The displacement spectra for P- and SH-waves were analyzed according to Brune’s source model. Observed spectra were corrected for path-dependent attenuation effects using an independent regional estimate of the quality factor QS. To correct spectra for near-surface attenuation, the k parameterwas calculated, obtaining it fromwaveforms recorded at short epicentral distances. The values of the k parameter vary between 0.01 to 0.06 s with a mean of 0.03 s for P-waves and between 0.01 to 0.09 s with a mean of 0.04 s for SH-waves. After correction for attenuation effects, spectral parameters (corner frequency and low-frequency spectral level) were estimated by a grid search algorithm. The obtained seismic moments range from4.21×1011 to 3.41×1015 Nm (1.7≤Mw ≤4.3). The source radii are between 125 and 1343 m. Stress drop values vary between 0.14 and 32.4 bars with a logarithmic mean of 2.59 bars (1 bar = 105 Pa). From the results, a linear relationship between local andmomentmagnitudes has been established. The obtained scaling relations show slight evidence of self-similarity violation. However, due to the high scatter of our data, the existence of self-similarity cannot be excluded

X-ray microscopy using collimated and focussed synchrotron radiation

X-ray microscopy is a field that has developed rapidly in recent years. Two different approaches have been used. Zone plates have been employed to produce focused beams with sizes as low as 0.07 ..mu..m for x-ray energies below 1 keV. Images of biological materials and elemental maps for major and minor low Z have been produced using above and below absorption edge differences. At higher energies collimators and focusing mirrors have been used to make small diameter beams for excitation of characteristic K- or L-x rays of all elements in the periodic table. The practicality of a single instrument combining all the features of these two approaches is unclear. The use of high-energy x rays for x-ray microscopy has intrinsic value for characterization of thick samples and determination of trace amounts of most elements. A summary of work done on the X-26 beam line at the National Synchrotron Light Source (NSLS) with collimated and focused x rays with energies above 4 keV is given here. 6 refs., 5 figs., 1 tab

A Novel Recombinant Peste des Petits Ruminants-Canine Adenovirus Vaccine Elicits Long-Lasting Neutralizing Antibody Response against PPR in Goats

BACKGROUND: Peste des petits ruminants (PPR) is a highly contagious infectious disease of goats, sheep and small wild ruminant species with high morbidity and mortality rates. The Peste des petits ruminants virus (PPRV) expresses a hemagglutinin (H) glycoprotein on its outer envelope that is crucial for viral attachment to host cells and represents a key antigen for inducing the host immune response. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether H can be exploited to generate an effective PPRV vaccine, a replication-competent recombinant canine adenovirus type-2 (CAV-2) expressing the H gene of PPRV (China/Tibet strain) was constructed by the in vitro ligation method. The H expression cassette, including the human cytomegalovirus (hCMV) promoter/enhancer and the BGH early mRNA polyadenylation signal, was inserted into the SspI site of the E3 region, which is not essential for proliferation of CAV-2. Infectious recombinant rCAV-2-PPRV-H virus was generated in transfected MDCK cells and used to immunize goats. All vaccinated animals produced antibodies upon primary injection that were effective in neutralizing PPRV in vitro. Higher antibody titer was obtained following booster inoculation, and the antibody was detectable in goats for at least seven months. No serious recombinant virus-related adverse effect was observed in immunized animals and no adenovirus could be isolated from the urine or feces of vaccinated animals. Results showed that the recombinant virus was safe and could stimulate a long-lasting immune response in goats. CONCLUSIONS/SIGNIFICANCE: This strategy not only provides an effective PPR vaccine candidate for goats but may be a valuable mean by which to differentiate infected from vaccinated animals (the so-called DIVA approach)