170 research outputs found
Hamiltonian MCMC methods for estimating rare events probabilities in high-dimensional problems
Accurate and efficient estimation of rare events probabilities is of
significant importance, since often the occurrences of such events have
widespread impacts. The focus in this work is on precisely quantifying these
probabilities, often encountered in reliability analysis of complex engineering
systems, based on an introduced framework termed Approximate Sampling Target
with Post-processing Adjustment (ASTPA), which herein is integrated with and
supported by gradient-based Hamiltonian Markov Chain Monte Carlo (HMCMC)
methods. The basic idea is to construct a relevant target distribution by
weighting the high-dimensional random variable space through a one-dimensional
output likelihood model, using the limit-state function. To sample from this
target distribution, we exploit HMCMC algorithms, a family of MCMC methods that
adopts physical system dynamics, rather than solely using a proposal
probability distribution, to generate distant sequential samples, and we
develop a new Quasi-Newton mass preconditioned HMCMC scheme (QNp-HMCMC), which
is particularly efficient and suitable for high-dimensional spaces. To
eventually compute the rare event probability, an original post-sampling step
is devised using an inverse importance sampling procedure based on the already
obtained samples. The statistical properties of the estimator are analyzed as
well, and the performance of the proposed methodology is examined in detail and
compared against Subset Simulation in a series of challenging low- and
high-dimensional problems.Comment: arXiv admin note: text overlap with arXiv:1909.0357
Short communication: optimization of semi-quantitative RT PCR analysis for CPT I gene expression in rainbow trout (Oncorhynchus mykiss)
A key enzyme in mitochondrial β¬oxidation, carnitine palmitoyltransferase (CPT) I, is transcriptionally regulated in mammals, but this enzyme also experiences allosteric modulations (Harano et al., 1985; Murthy and Pande, 1987; Bezaire et al., 2004). CPT I is located on the inner side of the outer mitochondrial membrane and catalyses the conversion of acyl-CoA to fatty acylcarnitine (Kerner and Hoppel, 2000; Price et al., 2000). Quantitative RT-PCR is a reliable technique for measuring transcripts in small amounts of tissue (Spriewald et al., 2000). With this technique, multiple mRNAs can be assayed simultaneously in a relatively short period of time. Here we describe the standard procedure, optimized in our laboratory, to assess CPT I levels with β¬actin as an internal control in rainbow trout, and all the necessary controls to ensure a quantitative analysis. RNA Extraction and Reverse Transcription Total cellular RNA was isolated from liver of rainbow trout using RNX reagent (Cinnagen-Iran). To obtain cDNA, 1 µg of
total RNA was subjected to reverse transcription polymerase chain reaction (RT-PCR) with MuLV reverse transcriptase using the RevertAidTM M¬MuLV Reverse Transcriptase Kit (Fermentase Life Science, Germany) and random hexamer primer. Reaction conditions in the reverse transcription step are mostly dependent on the enzyme and the primers of choice. Whereas other protocols to require the use of specific primers, we prefer to reverse transcribe the total RNA population with random hexamers so that different PCR analyses could be performed on the same cDNA sample
Allelic polymorphism of insulin-like growth factor I gene and its association with production traits in native chickens
Insulin-like growth factor 1 (IGFI) is an essential regulator of growth, cell proliferation/differentiation and protein synthesis in a variety of cell types. IGFI is considered as one of the most important can-didate genes controlling production and reproduction traits in chickens. This locus could be linked to the highly effective genes affecting egg production and growth traits. The aim of present study was to investigate the IGFI gene polymorphism and its association with growth and egg production traits in Iranian native chicken. A total of 313 blood samples were collected from the Native poultry breeding centre, Khorasan province, Iran. Single nucleotide polymorphism (SNP) of the IGFI 5'-UTR was detected by PCR-RFLP method and PstI restriction endonuclease enzyme. Finally, the SNP was con-firmed by sequencing of RFLP profiles. Association between IGFI alleles and production traits was evaluated using multivariate regression analysis and GLM procedures. Two alleles A (PstI –) and B (PstI +) and three genotypes (A/A, A/B and B/B) were identified for the IGFI gene. Allele B was the most frequent (60.1%) and considered as reference allele for association study. A/B genotype was significantly correlated with lower first egg weight and higher egg laying intensity compared to B/B and A/A genotypes. No significant association was observed between IGFI genotypes and other pro-duction traits including egg weight, weight of sexual maturity and body weight. These results suggest that there is a possibility of IGFI genotypes acting as a genetic marker for selecting some egg produc-tion traits in native chickens
Derandomizing Codes for the Binary Adversarial Wiretap Channel of Type II
We revisit the binary adversarial wiretap channel (AWTC) of type II in which
an active adversary can read a fraction and flip a fraction of codeword
bits. The semantic-secrecy capacity of the AWTC II is partially known, where
the best-known lower bound is non-constructive, proven via a random coding
argument that uses a large number (that is exponential in blocklength ) of
random bits to seed the random code. In this paper, we establish a new
derandomization result in which we match the best-known lower bound of
where is the binary entropy function via a random
code that uses a small seed of only bits. Our random code construction
is a novel application of pseudolinear codes -- a class of non-linear codes
that have -wise independent codewords when picked at random where is a
design parameter. As the key technical tool in our analysis, we provide a
soft-covering lemma in the flavor of Goldfeld, Cuff and Permuter (Trans. Inf.
Theory 2016) that holds for random codes with -wise independent codewords
Development of anti-Helicobacter pylori immunoglobulins Y (IgYs) in quail
Summary Helicobacter pylori (H. pylori) is a gram-negative, microaerophilic bacterium that cause the stomach infection in more than 50% of human population worldwide. The aim of this study was to examine the possibility of anti-H. pylori immunoglobulins Y (IgYs) production in quails and evaluate the effect of the different methods of immunization on titers of IgY in egg yolks. Whole cell bacterial antigen was used for immunization of quails. Forty Japanese quails (Coturnix japonica) were divided into four groups. The first group intramuscularly immunized with one dose of antigen (3 × 10 8 inactivated bacteria) whereas the second group injected with half dose. Third group administered orally. Yolk IgY was isolated using precipitation method of water dilution combined with chloroform. Dot-blot and ELISA (enzyme-linked immunosorbent assay) were used for determining the specificity and quantifying the titer of IgY in egg yolks. Results showed that quails as well as chickens are able to produce anti-H. pylori IgY. Quails antibodies have high titer and specificity that can be used in therapeutic and research purposes. This study indicated that higher amounts of antigen can not develop higher titer of IgY and injection is not necessary for efficient immunization of the quail against H. pylori
Turkey humoral and cell-mediated immune responses to a Newcastle viscerotropic vaccine and its association with major histocompatibility complex
Immune responses to vaccines are mainly influenced by the nature of vaccines and host variation in response to vaccination. In this study we aimed to investigate turkey humoral and cell-mediated im-mune responses to a Newcastle viscerotropic vaccine and its association with major histocompatibil-ity complex (MHC). Turkeys were vaccinated with Villegas–Glisson/University of Georgia (VG/GA) attenuated vaccine against Newcastle disease. The stimulation index of lymphocyte proliferation and antigen-specific local secretory IgA responses in bile, duodenum, ileum, as well as serum IgY and IgA responses were analysed by enzyme-linked immunosorbent assay. The turkey MHC class II B locus was selected as candidate gene for detection of associations with cellular and humoral immune responses. Significant differences were observed between both cellular and humoral responses of vaccinated and unvaccinated groups. A significant positive correlation was also found between ND specific IgY and ND specific IgA titres in serum, intestine (duodenum and ileum) and trachea. More-over, the correlation between specific IgA titres in ileum and specific bile, duodenum and trachea was positively significant. High resolution melting analysis (HRM) was used to genotype MHC class II B exon 2. Eight melting profiles (A-G) were identified, among which, profile G showed a significant association with cellular response. The profile B revealed significant association with total IgA titres in serum and ileum. These findings help our understanding of the association of turkey MHC types with immune responses. Further correlation analysis between serum and mucosal antibody titres demonstrated that the levels of IgY and IgA in serum can give an impression about the levels of sec-retory IgA and situation of mucosal immunity. Based on the significant effects, ND specific IgY in serum appears to be a promising indirect marker for specific IgA in serum and trachea
Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma.
Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3) K27M-including H3.2K27M-mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic alterations arise in sub-clones and often affect the PI3K pathway. Our findings are consistent with early tumour spread outside the brainstem including the cerebrum. The spatial and temporal homogeneity of main driver mutations in DIPG implies they will be captured by limited biopsies and emphasizes the need to develop therapies specifically targeting obligate oncohistone partnerships
The genetic architecture of the MHC class II region in British Texel sheep
Understanding the structure of the major histocompatibility complex, especially the number and frequency of alleles, loci and haplotypes, is crucial for efficient investigation of the way in which the MHC influences susceptibility to disease. Nematode infection is one of the most important diseases suffered by sheep, and the class II region has been repeatedly associated with differences in susceptibility and resistance to infection. Texel sheep are widely used in many different countries and are relatively resistant to infection. This study determined the number and frequency of MHC class II genes in a small flock of Texel sheep. There were 18 alleles at DRB1, 9 alleles at DQA1, 13 alleles at DQB1, 8 alleles at DQA2 and 16 alleles at DQB2. Several haplotypes had no detectable gene products at DQA1, DQB1 or DQB2, and these were defined as null alleles. Despite the large numbers of alleles, there were only 21 distinct haplotypes in the population. The relatively small number of observed haplotypes will simplify finding disease associations because common haplotypes provide more statistical power but complicate the discrimination of causative mutations from linked marker loci
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