Design of a genetic muller C-element

Journal ArticleSynthetic biology uses engineering principles to design circuits out of genetic materials that are inserted into bacteria to perform various tasks. While synthetic combinational Boolean logic gates have been constructed, there are many open issues in the design of sequential logic gates. One such gate common in most asynchronous circuits is the Muller C-element, which is used to synchronize multiple independent processes. This paper proposes a novel design for a genetic Muller C-element using transcriptional regulatory elements. The design of a genetic Muller C-element enables the construction of virtually any asynchronous circuit from genetic material. There are, however, many issues that complicate designs with genetic materials. These complications result in modifications being required to the normal digital design procedure. This paper presents two designs that are logically equivalent to a Muller C-element. Mathematical analysis and stochastic simulation, however, show that only one functions reliably

ViFi: accurate detection of viral integration and mRNA fusion reveals indiscriminate and unregulated transcription in proximal genomic regions in cervical cancer.

The integration of viral sequences into the host genome is an important driver of tumorigenesis in many viral mediated cancers, notably cervical cancer and hepatocellular carcinoma. We present ViFi, a computational method that combines phylogenetic methods with reference-based read mapping to detect viral integrations. In contrast with read-based reference mapping approaches, ViFi is faster, and shows high precision and sensitivity on both simulated and biological data, even when the integrated virus is a novel strain or highly mutated. We applied ViFi to matched genomic and mRNA data from 68 cervical cancer samples from TCGA and found high concordance between the two. Surprisingly, viral integration resulted in a dramatic transcriptional upregulation in all proximal elements, including LINEs and LTRs that are not normally transcribed. This upregulation is highly correlated with the presence of a viral gene fused with a downstream human element. Moreover, genomic rearrangements suggest the formation of apparent circular extrachromosomal (ecDNA) human-viral structures. Our results suggest the presence of apparent small circular fusion viral/human ecDNA, which correlates with indiscriminate and unregulated expression of proximal genomic elements, potentially contributing to the pathogenesis of HPV-associated cervical cancers. ViFi is available at https://github.com/namphuon/ViFi

ROLE OF PERSONALITY TRAITS IN SHAPING ENTREPRENEURIAL INTENTION: COMPARATIVE STUDY OF SOUTH KOREA AND VIETNAM*

This paper investigates the role of personality traits in nurturing entrepreneurial intention in South Korea and Vietnam. We developed a research model to examine the integrated influence of both positive entrepreneurial characteristics and dark triad on entrepreneurial intention in South Korea and Vietnam. Primary data was collected from 550 students in South Korea and 700 students in Vietnam using the convenient sampling method in a self-administered questionnaire survey. We used structural equation modelling (SEM) to analyse structural relationships between positive entrepreneurial attributes, dark triads, and entrepreneurial intention in two samples. T-tests were also performed to explore any differences in students’ entrepreneurial intention in South Korea and Vietnam regarding their family background and gender. Findings showed that positive entrepreneurial attributes and dark triads influence entrepreneurial intention differently in the two countries. While the dark triad mainly influenced Vietnamese students’ intention to startup, Korean students received more impact from the positive entrepreneurial characteristics such as risk tolerance, locus of control, and entrepreneurial alertness. Surprisingly, both gender and family tradition do not affect students’ entrepreneurial intention. Based on our findings, we suggested that policymakers and higher education institutions in both South Korea and Vietnam promote students’ entrepreneurial intentions in the future

Author Correction: Longitudinal assessment of tumor development using cancer avatars derived from genetically engineered pluripotent stem cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Randomised primary health center based interventions to improve the diagnosis and treatment of undifferentiated fever and dengue in Vietnam

<p>Abstract</p> <p>Background</p> <p>Fever is a common reason for attending primary health facilities in Vietnam. Response of health care providers to patients with fever commonly consists of making a presumptive diagnosis and proposing corresponding treatment. In Vietnam, where malaria was brought under control, viral infections, notably dengue, are the main causes of undifferentiated fever but they are often misdiagnosed and inappropriately treated with antibiotics.</p> <p>This study investigate if educating primary health center (PHC) staff or introducing rapid diagnostic tests (RDTs) improve diagnostic resolution and accuracy for acute undifferentiated fever (AUF) and reduce prescription of antibiotics and costs for patients.</p> <p>Methods</p> <p>In a PHC randomized intervention study in southern Vietnam, the presumptive diagnoses for AUF patients were recorded and confirmed by serology on paired (acute and convalescence) sera. After one year, PHCs were randomized to four intervention arms: training on infectious diseases (A), the provision of RDTs (B), the combination (AB) and control (C). The intervention lasted from 2002 until 2006.</p> <p>Results</p> <p>The frequency of the non-etiologic diagnosis "undifferentiated fever" decreased in group AB, and - with some delay- also in group B. The diagnosis "dengue" increased in group AB, but only temporarily, although dengue was the most common cause of fever. A correct diagnosis for dengue initially increased in groups AB and B but only for AB this was sustained. Antibiotics prescriptions increased in group C. During intervention it initially declined in AB with a tendency to increase afterwards; in B it gradually declined. There was a substantial increase of patients' costs in B.</p> <p>Conclusions</p> <p>The introduction of RDTs for infectious diseases such as dengue, through free market principles, does improve the quality of the diagnosis and decreases the prescription of antibiotics at the PHC level. However, the effect is more sustainable in combination with training; without it RDTs lead to an excess of costs.</p

Metagenomic analysis reveals previously undescribed bat coronavirus strains in Eswatini

We investigated the prevalence of coronaviruses in 44 bats from four families in northeastern Eswatini using high-throughput sequencing of fecal samples. We found evidence of coronaviruses in 18% of the bats. We recovered full or near-full-length genomes from two bat species: Chaerephon pumilus and Afronycteris nana, as well as additional coronavirus genome fragments from C. pumilus, Epomophorus wahlbergi, Mops condylurus, and Scotophilus dinganii. All bats from which we detected coronaviruses were captured leaving buildings or near human settlements, demonstrating the importance of continued surveillance of coronaviruses in bats to better understand the prevalence, diversity, and potential risks for spillover.The National Science Foundation Graduate Research Fellowship; a National Science Foundation Graduate Research Opportunities Worldwide grant; Innovation Fund Denmark; a Student Research Grant from Bat Conservation International; a University of Florida Biodiversity Institute Fellowship; the Zuckerman STEM Leadership Program and an NIH Grant.http://link.springer.com/journal/10393hj2022Mammal Research InstituteZoology and Entomolog

Differential spatial modulation for high-rate transmission systems

This paper introduces a new differential spatial modulation (DSM) scheme which subsumes both the previously introduced DSM and high-rate spatial modulation (HR-SM) for wireless multiple input multiple output (MIMO) transmission. By combining the codeword design method of the HR-SM scheme with the encoding method of the DSM scheme, we develop a high-rate differential spatial modulation (HR-DSM) scheme equipped with an arbitrary number of transmit antennas that requires channel state information (CSI) neither at the transmitter nor at the receiver. The proposed approach can be applied to any equal energy signal constellations. The bit error rate (BER) performance of the proposed HR-DSM schemes is evaluated by using both theoretical upper bound and computer simulations. It is shown that for the same spectral efficiency and antenna configuration, the proposed HR-DSM outperforms the DSM in terms of bit error rate (BER) performance

Fully automated sequence alignment methods are comparable to, and much faster than, traditional methods in large data sets: an example with hepatitis B virus

Aligning sequences for phylogenetic analysis (multiple sequence alignment; MSA) is an important, but increasingly computationally expensive step with the recent surge in DNA sequence data. Much of this sequence data is publicly available, but can be extremely fragmentary (i.e., a combination of full genomes and genomic fragments), which can compound the computational issues related to MSA. Traditionally, alignments are produced with automated algorithms and then checked and/or corrected “by eye” prior to phylogenetic inference. However, this manual curation is inefficient at the data scales required of modern phylogenetics and results in alignments that are not reproducible. Recently, methods have been developed for fully automating alignments of large data sets, but it is unclear if these methods produce alignments that result in compatible phylogenies when compared to more traditional alignment approaches that combined automated and manual methods. Here we use approximately 33,000 publicly available sequences from the hepatitis B virus (HBV), a globally distributed and rapidly evolving virus, to compare different alignment approaches. Using one data set comprised exclusively of whole genomes and a second that also included sequence fragments, we compared three MSA methods: (1) a purely automated approach using traditional software, (2) an automated approach including by eye manual editing, and (3) more recent fully automated approaches. To understand how these methods affect phylogenetic results, we compared resulting tree topologies based on these different alignment methods using multiple metrics. We further determined if the monophyly of existing HBV genotypes was supported in phylogenies estimated from each alignment type and under different statistical support thresholds. Traditional and fully automated alignments produced similar HBV phylogenies. Although there was variability between branch support thresholds, allowing lower support thresholds tended to result in more differences among trees. Therefore, differences between the trees could be best explained by phylogenetic uncertainty unrelated to the MSA method used. Nevertheless, automated alignment approaches did not require human intervention and were therefore considerably less time-intensive than traditional approaches. Because of this, we conclude that fully automated algorithms for MSA are fully compatible with older methods even in extremely difficult to align data sets. Additionally, we found that most HBV diagnostic genotypes did not correspond to evolutionarily-sound groups, regardless of alignment type and support threshold. This suggests there may be errors in genotype classification in the database or that HBV genotypes may need a revision

Dengue Dynamics in Binh Thuan Province, Southern Vietnam: Periodicity, Synchronicity and Climate Variability

Dengue has become a major international public health problem due to increasing geographic distribution and a transition from epidemic transmission with long inter-epidemic intervals to endemic transmission with seasonal fluctuation. Seasonal and multi-annual cycles in dengue incidence vary over time and space. We performed wavelet analyses on time series of monthly notified dengue cases in Binh Thuan province, southern Vietnam, from January 1994 to June 2009. We observed a continuous annual mode of oscillation with a non-stationary 2–3-year multi-annual cycle. We used phase differences to describe the spatio-temporal patterns which suggest that the seasonal wave of infection was either synchronous with all districts or moving away from Phan Thiet district, while the multi-annual wave of infection was moving towards Phan Thiet district. We also found a strong non-stationary association between ENSO indices and climate variables with dengue incidence. We provided insight in dengue population transmission dynamics over the past 14.5 years. Further studies on an extensive time series dataset are needed to test the hypothesis that epidemics emanate from larger cities in southern Vietnam