4,609 research outputs found
On bounded continuous solutions of the archetypal equation with rescaling
The `archetypal' equation with rescaling is given by
(), where is a probability measure; equivalently,
, with random and
denoting expectation. Examples include: (i) functional equation
; (ii) functional-differential
(`pantograph') equation (,
). Interpreting solutions as harmonic functions of the
associated Markov chain , we obtain Liouville-type results asserting
that any bounded continuous solution is constant. In particular, in the
`critical' case such a theorem holds subject to
uniform continuity of ; the latter is guaranteed under mild regularity
assumptions on , satisfied e.g.\ for the pantograph equation (ii). For
equation (i) with (, ), the
result can be proved without the uniform continuity assumption. The proofs
utilize the iterated equation (with a
suitable stopping time ) due to Doob's optional stopping theorem applied
to the martingale .Comment: Substantially revised. The title is modifie
Spores of Clostridium engineered for clinical efficacy and safety cause regression and cure of tumors in vivo.
Spores of some species of the strictly anaerobic bacteria Clostridium naturally target and partially lyse the hypoxic cores of tumors, which tend to be refractory to conventional therapies. The anti-tumor effect can be augmented by engineering strains to convert a non-toxic prodrug into a cytotoxic drug specifically at the tumor site by expressing a prodrug-converting enzyme (PCE). Safe doses of the favored prodrug CB1954 lead to peak concentrations of 6.3 μM in patient sera, but at these concentration(s) known nitroreductase (NTR) PCEs for this prodrug show low activity. Furthermore, efficacious and safe Clostridium strains that stably express a PCE have not been reported. Here we identify a novel nitroreductase from Neisseria meningitidis, NmeNTR, which is able to activate CB1954 at clinically-achievable serum concentrations. An NmeNTR expression cassette, which does not contain an antibiotic resistance marker, was stably localized to the chromosome of Clostridium sporogenes using a new integration method, and the strain was disabled for safety and containment by making it a uracil auxotroph. The efficacy of Clostridium-Directed Enzyme Prodrug Therapy (CDEPT) using this system was demonstrated in a mouse xenograft model of human colon carcinoma. Substantial tumor suppression was achieved, and several animals were cured. These encouraging data suggest that the novel enzyme and strain engineering approach represent a promising platform for the clinical development of CDEPT
Succession of biofilm communities responsible for biofouling of membrane bioreactors (MBRs)
© 2017 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Biofilm formation is one of the main factors associated with membrane biofouling in membrane bioreactors (MBRs). As such, it is important to identify the responsible organisms to develop targeted strategies to control biofouling. This study investigated the composition and changes in the microbial communities fouling MBR membranes over time and correlated those changes with an increase in transmembrane pressure (TMP). Based on qPCR data, bacteria were the dominant taxa of the biofilm (92.9–98.4%) relative to fungi (1.5–6.9%) and archaea (0.03–0.07%). NMDS analysis indicated that during the initial stages of operation, the biofilm communities were indistinguishable from those found in the sludge. However, the biofilm community significantly diverged from the sludge over time and ultimately showed a unique biofilm profile. This suggested that there was strong selection for a group of organisms that were biofilm specialists. This pattern of succession and selection was correlated with the rapid increase in TMP, where bacteria including Rhodospirillales, Sphingomonadales and Rhizobiales dominated the biofilm at this time. While most of the identified fungal OTUs matched Candida sp., the majority of fungal communities were unclassified by 18S rRNA gene sequencing. Collectively, the data suggests that bacteria, primarily, along with fungi may play an important role in the rapid TMP increase and loss of system performance
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Complementary Metagenomic Approaches Improve Reconstruction of Microbial Diversity in a Forest Soil.
Soil ecosystems harbor diverse microorganisms and yet remain only partially characterized as neither single-cell sequencing nor whole-community sequencing offers a complete picture of these complex communities. Thus, the genetic and metabolic potential of this "uncultivated majority" remains underexplored. To address these challenges, we applied a pooled-cell-sorting-based mini-metagenomics approach and compared the results to bulk metagenomics. Informatic binning of these data produced 200 mini-metagenome assembled genomes (sorted-MAGs) and 29 bulk metagenome assembled genomes (MAGs). The sorted and bulk MAGs increased the known phylogenetic diversity of soil taxa by 7.2% with respect to the Joint Genome Institute IMG/M database and showed clade-specific sequence recruitment patterns across diverse terrestrial soil metagenomes. Additionally, sorted-MAGs expanded the rare biosphere not captured through MAGs from bulk sequences, exemplified through phylogenetic and functional analyses of members of the phylum Bacteroidetes Analysis of 67 Bacteroidetes sorted-MAGs showed conserved patterns of carbon metabolism across four clades. These results indicate that mini-metagenomics enables genome-resolved investigation of predicted metabolism and demonstrates the utility of combining metagenomics methods to tap into the diversity of heterogeneous microbial assemblages.IMPORTANCE Microbial ecologists have historically used cultivation-based approaches as well as amplicon sequencing and shotgun metagenomics to characterize microbial diversity in soil. However, challenges persist in the study of microbial diversity, including the recalcitrance of the majority of microorganisms to laboratory cultivation and limited sequence assembly from highly complex samples. The uncultivated majority thus remains a reservoir of untapped genetic diversity. To address some of the challenges associated with bulk metagenomics as well as low throughput of single-cell genomics, we applied flow cytometry-enabled mini-metagenomics to capture expanded microbial diversity from forest soil and compare it to soil bulk metagenomics. Our resulting data from this pooled-cell sorting approach combined with bulk metagenomics revealed increased phylogenetic diversity through novel soil taxa and rare biosphere members. In-depth analysis of genomes within the highly represented Bacteroidetes phylum provided insights into conserved and clade-specific patterns of carbon metabolism
A study on the failure of steel chains in rotary cement kilns
The failure of steel chains which are used in rotary cement kilns costs cement companies a significant price. This study investigated the causes of chains failure at the Kufa cement plant and proposes new materials that can serve for a prolonged period of time. Two grades of steel chains were investigated including DIN 1.4742 (AISI 10F) and St37. Ten samples of chains from different locations from the kiln flame have been taken after 30 days and after 180 days of continuous work inside the rotary cement kiln. To study the effect of the distance from the kiln flame on the DIN 1.4742 (AISI 10F), another two samples have been replaced the St37 grade at a distance of 28.2 m. Chemical analysis for each sample under study has been carried out in order to highlight the differences between the used chain and the original chain in terms of alloying elements weight. An optical images of the unused and used chains of DIN 1.4742 (AISI 10F) steel grade have been taken to understand that the change occurs in the grain size. SEM-EDS technique was also applied to understand the possible segregation of elements. The results showed that the decrease of alloying elements pct, especially Cr, in the microstructure was the main reason of chain failure by corrosion/erosion mechanism. Preventing Cr from segregation can prolong the life of kiln chains during service. The study suggests new steel grades to replace DIN 1.4742 (AISI 10F) and St37 steel grades
Limit laws for sums of random exponentials
We study the limiting distribution of the sum S-N(t) = Sigma(i=1)(N) e(tXi) as t -> infinity, N -> infinity, where (X-i) are i.i.d. random variables. Attention to such exponential sums has been motivated by various problems in random media theory. Examples include the quenched mean population size of a colony of branching processes with random branching rates and the partition function of Derrida's Random Energy Model. In this paper, the problem is considered under the assumption that the log-tail distribution function h(x) = -log P{X-I > x} is regularly varying at infinity with index 1 < rho < infinity. An appropriate scale for the growth of N relative to t is of the form e(lambda H0(t)), where the rate function Ho(t) is a certain asymptotic version of the cumulant. generating function H(t) = log E[e(tXi)] provided by Kasahara's exponential Tauberian theorem. We have found two critical points, 0 < lambda(1) < lambda(2) < infinity, below which the Law of Large Numbers and the Central Limit Theorem, respectively, break down. Below lambda(2), we impose a slightly stronger condition of normalized regular variation of h. The limit laws here appear to be stable, with characteristic exponent alpha = alpha(rho, lambda) ranging from 0 to 2 and with skewness parameter beta = 1. A limit theorem for the maximal value of the sample {e(tXi), i = 1,...,N} is also proved
Single-nucleotide polymorphism-gene intermixed networking reveals co-linkers connected to multiple gene expression phenotypes
Gene expression profiles and single-nucleotide polymorphism (SNP) profiles are modern data for genetic analysis. It is possible to use the two types of information to analyze the relationships among genes by some genetical genomics approaches. In this study, gene expression profiles were used as expression traits. And relationships among the genes, which were co-linked to a common SNP(s), were identified by integrating the two types of information. Further research on the co-expressions among the co-linked genes was carried out after the gene-SNP relationships were established using the Haseman-Elston sib-pair regression. The results showed that the co-expressions among the co-linked genes were significantly higher if the number of connections between the genes and a SNP(s) was more than six. Then, the genes were interconnected via one or more SNP co-linkers to construct a gene-SNP intermixed network. The genes sharing more SNPs tended to have a stronger correlation. Finally, a gene-gene network was constructed with their intensities of relationships (the number of SNP co-linkers shared) as the weights for the edges
An Integrated Framework for the Quantification of Road Network Seismic Vulnerability and Accessibility to Critical Services
Road networks are regarded as the backbone of transportation systems, which play an
important role in the social and economic prosperity of societies. Due to this reason, it is crucial to
develop road networks with higher resiliency rates to operate normally during earthquake incidents.
In the last decades, the research that tackled the management of disasters for road networks gained
great attention, in particular by developing various seismic vulnerability assessment models. Most of
those models study a single criterion, e.g., physical damage of road assets, traffic disruption, and/or
functionality loss of the network without taking into consideration the combination of different
vulnerability criteria. The proposed framework is part of the global seismic vulnerability assessment
models that combine fragility functions and vulnerability indices, which is demonstrated by an
application in a road network in the city of Penang in Malaysia. In the first step, the fragility functions
are developed where their results are used to calculate the Seismic Vulnerability Index (SVI) for
roadways by weighting the main investigated parameters. This is followed by investigating the
Accessibility Index (AI) model that is employed to assess the accessibility of targeted districts within
the investigated area. Subsequently, an integrated approach is employed to generate the emergency
evacuation maps to critical service centres by referring to the correlations between vulnerability and
the accessibility rates. In conclusion, the results of this study integrate engineering judgment and
numerical models to create a comparative study for assessing the performance of road networks and
to validate the significance of an integrated seismic assessment on various critical societal sectors, such
as improving emergency accessibility and implementing better mitigation strategies for communities
living in disaster-prone areas.Ministry of Higher Education (MOHE) through Fundamental Research Grant Scheme (FRGS/1/2020/TK02/USM/02/1)
Systematic analysis of human microRNA divergence based on evolutionary emergence
AbstractMicroRNAs (miRNAs) play important roles in post-transcriptional gene expression control. To gain new insight into human miRNAs, we performed comprehensive sequence-based homology search for known human miRNAs to study the evolutionary distribution of human miRNAs. Furthermore, we carried out a series of studies to compare various features for different lineage-specific human miRNAs. Our results showed that major expansions of human miRNA genes coincide with the advent of vertebrates, mammals and primates. Further system-level analysis revealed significant differences in human miRNAs that arose from different evolutionary time points for a number of characteristics, implicating genetic and functional diversification for different human miRNAs during evolution. Our finds provide more useful knowledge for further exploring origins and evolution of human miRNA genes
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