Mechanistic modelling of a recombinase-based two-input temporal logic gate

Site-specific recombinases (SSRs) mediate efficient manipulation of DNA sequences in vitro and in vivo. In particular, serine integrases have been identified as highly effective tools for facilitating DNA inversion, enabling the design of genetic switches that are capable of turning the expression of a gene of interest on or off in the presence of a SSR protein. The functional scope of such circuitry can be extended to biological Boolean logic operations by incorporating two or more distinct integrase inputs. To date, mathematical modelling investigations have captured the dynamical properties of integrase logic gate systems in a purely qualitative manner, and thus such models are of limited utility as tools in the design of novel circuitry. Here, the authors develop a detailed mechanistic model of a two-input temporal logic gate circuit that can detect and encode sequences of input events. Their model demonstrates quantitative agreement with time-course data on the dynamics of the temporal logic gate, and is shown to subsequently predict dynamical responses relating to a series of induction separation intervals. The model can also be used to infer functional variations between distinct integrase inputs, and to examine the effect of reversing the roles of each integrase on logic gate output

Sp(2N) Lattice Gauge Theories and Extensions of the Standard Model of Particle Physics

We review the current status of the long-term programme of numerical investigation of Sp(2N) gauge theories with and without fermionic matter content. We start by introducing the phenomenological as well as theoretical motivations for this research programme, which are related to composite Higgs models, models of partial top compositeness, dark matter models, and in general to the physics of strongly coupled theories and their approach to the large-N limit. We summarise the results of lattice studies conducted so far in the Sp(2N) Yang-Mills theories, measuring the string tension, the mass spectrum of glueballs and the topological susceptibility, and discuss their large-N extrapolation. We then focus our discussion on Sp(4), and summarise numerical measurements of mass and decay constant of mesons in the theories with fermion matter in either the fundamental or the antisymmetric representation, first in the quenched approximation, and then with dynamical fermions. We finally discuss the case of dynamical fermions in mixed representations, and exotic composite fermion states such as the chimera baryons. We conclude by sketching the future stages of the programme. And we describe our approach to open access

Sp(2N) Lattice Gauge Theories and Extensions of the Standard Model of Particle Physics

We review the current status of the long-term programme of numerical investigation of (2) gauge theories with and without fermionic matter content. We start by introducing the phenomenological as well as theoretical motivations for this research programme, which are related to composite Higgs models, models of partial top compositeness, dark matter models, and in general to the physics of strongly coupled theories and their approach to the large-N limit. We summarise the results of lattice studies conducted so far in the (2) Yang–Mills theories, measuring the string tension, the mass spectrum of glueballs and the topological susceptibility, and discuss their large-N extrapolation. We then focus our discussion on (4), and summarise the numerical measurements of mass and decay constant of mesons in the theories with fermion matter in either the fundamental or the antisymmetric representation, first in the quenched approximation, and then with dynamical fermions. We finally discuss the case of dynamical fermions in mixed representations, and exotic composite fermion states such as the chimera baryons. We conclude by sketching the future stages of the programme. We also describe our approach to open access

Sp(2N)Sp(2N) Lattice Gauge Theories and Extensions of the Standard Model of Particle Physics

We review the current status of the long-term programme of numerical investigation of $Sp(2N)$ gauge theories with and without fermionic matter content. We start by introducing the phenomenological as well as theoretical motivations for this research programme, which are related to composite Higgs models, models of partial top compositeness, dark matter models, and in general to the physics of strongly coupled theories and their approach to the large-N limit. We summarise the results of lattice studies conducted so far in the $Sp(2N)$ Yang-Mills theories, measuring the string tension, the mass spectrum of glueballs and the topological susceptibility, and discuss their large-N extrapolation. We then focus our discussion on $Sp(4)$, and summarise numerical measurements of mass and decay constant of mesons in the theories with fermion matter in either the fundamental or the antisymmetric representation, first in the quenched approximation, and then with dynamical fermions. We finally discuss the case of dynamical fermions in mixed representations, and exotic composite fermion states such as the chimera baryons. We conclude by sketching the future stages of the programme. And we describe our approach to open access.Comment: 74 pages, 22 figures, 3 tables, contribution to the special issue of Universe "Numerical Studies of Strongly Coupled Gauge Theories (SCGTs) in the Search of New Physics

Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants.

Dietary intervention with extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (EHCF+LGG) accelerates tolerance acquisition in infants with cow's milk allergy (CMA). We examined whether this effect is attributable, at least in part, to an influence on the gut microbiota. Fecal samples from healthy controls (n=20) and from CMA infants (n=19) before and after treatment with EHCF with (n=12) and without (n=7) supplementation with LGG were compared by 16S rRNA-based operational taxonomic unit clustering and oligotyping. Differential feature selection and generalized linear model fitting revealed that the CMA infants have a diverse gut microbial community structure dominated by Lachnospiraceae (20.5±9.7%) and Ruminococcaceae (16.2±9.1%). Blautia, Roseburia and Coprococcus were significantly enriched following treatment with EHCF and LGG, but only one genus, Oscillospira, was significantly different between infants that became tolerant and those that remained allergic. However, most tolerant infants showed a significant increase in fecal butyrate levels, and those taxa that were significantly enriched in these samples, Blautia and Roseburia, exhibited specific strain-level demarcations between tolerant and allergic infants. Our data suggest that EHCF+LGG promotes tolerance in infants with CMA, in part, by influencing the strain-level bacterial community structure of the infant gut

Localization and segmentation of optic disc in retinal images using circular Hough transform and grow-cut algorithm

Automated retinal image analysis has been emerging as an important diagnostic tool for early detection of eye-related diseases such as glaucoma and diabetic retinopathy. In this paper, we have presented a robust methodology for optic disc detection and boundary segmentation, which can be seen as the preliminary step in the development of a computer-assisted diagnostic system for glaucoma in retinal images. The proposed method is based on morphological operations, the circular Hough transform and the grow-cut algorithm. The morphological operators are used to enhance the optic disc and remove the retinal vasculature and other pathologies. The optic disc center is approximated using the circular Hough transform, and the grow-cut algorithm is employed to precisely segment the optic disc boundary. The method is quantitatively evaluated on five publicly available retinal image databases DRIVE, DIARETDB1, CHASE_DB1, DRIONS-DB, Messidor and one local Shifa Hospital Database. The method achieves an optic disc detection success rate of 100% for these databases with the exception of 99.09% and 99.25% for the DRIONS-DB, Messidor, and ONHSD databases, respectively. The optic disc boundary detection achieved an average spatial overlap of 78.6%, 85.12%, 83.23%, 85.1%, 87.93%, 80.1%, and 86.1%, respectively, for these databases. This unique method has shown significant improvement over existing methods in terms of detection and boundary extraction of the optic disc

Benchmarking of eight recurrent neural network variants for breath phase and adventitious sound detection on a self-developed open-access lung sound database-HF_Lung_V1

A reliable, remote, and continuous real-time respiratory sound monitor with automated respiratory sound analysis ability is urgently required in many clinical scenarios-such as in monitoring disease progression of coronavirus disease 2019-to replace conventional auscultation with a handheld stethoscope. However, a robust computerized respiratory sound analysis algorithm has not yet been validated in practical applications. In this study, we developed a lung sound database (HF_Lung_V1) comprising 9,765 audio files of lung sounds (duration of 15 s each), 34,095 inhalation labels, 18,349 exhalation labels, 13,883 continuous adventitious sound (CAS) labels (comprising 8,457 wheeze labels, 686 stridor labels, and 4,740 rhonchi labels), and 15,606 discontinuous adventitious sound labels (all crackles). We conducted benchmark tests for long short-term memory (LSTM), gated recurrent unit (GRU), bidirectional LSTM (BiLSTM), bidirectional GRU (BiGRU), convolutional neural network (CNN)-LSTM, CNN-GRU, CNN-BiLSTM, and CNN-BiGRU models for breath phase detection and adventitious sound detection. We also conducted a performance comparison between the LSTM-based and GRU-based models, between unidirectional and bidirectional models, and between models with and without a CNN. The results revealed that these models exhibited adequate performance in lung sound analysis. The GRU-based models outperformed, in terms of F1 scores and areas under the receiver operating characteristic curves, the LSTM-based models in most of the defined tasks. Furthermore, all bidirectional models outperformed their unidirectional counterparts. Finally, the addition of a CNN improved the accuracy of lung sound analysis, especially in the CAS detection tasks.Comment: 48 pages, 8 figures. To be submitte

NPT088 reduces both amyloid-b and tau pathologies in transgenic mice

Introduction: Alzheimer’s disease (AD) is characterized by appearance of both extracellular senile plaques and intracellular neurofibrillary tangles, comprised of aggregates of misfolded amyloid-b (Ab) and hyper-phosphorylated tau, respectively. In a previous study, we demonstrated that g3p, a capsid protein from bacteriophage M13, binds to and remodels misfolded aggregates of proteins that assume an amyloid conformation. We engineered a fusion protein (“NPT088”) consisting of the active fragment of g3p and human-IgG1-Fc. Methods: Aged Tg2576 mice or rTg4510 mice received NPT088 weekly via IP injection. Cognitive and/or functional motor endpoints were monitored during dosing. Pathology was quantified biochemically and immunohistochemically. Results: NPT088-lowered Ab plaque and improved cognitive performance of aged Tg2576 mice. Moreover, NPT088 reduced phospho-tau pathology, reduced brain atrophy, and improved cognition in rTg4510 mice. Discussion: These observations establish NPT088 as a novel therapeutic approach and potential drug class that targets both Ab and tau, the hallmark pathologies of AD

Women's labour, kinship, and economic changes in Jinmen in the era of authoritarian rule

This article uses the life stories of three women in Jinmen to demonstrate women’s economic agency in bettering the livelihood of their families in circumstances largely shaped by Cold War geopolitics and the authoritarian state’s military strategies. It argues that women’s devotion of their labour and earnings to their families was part of the reproductive processes of the kinship system, but also important to their building of social reputation and emotional ties with their loved ones. Moreover, the state’s campaign to protect traditional Chinese culture, framed within bipolar politics, supported the ideological reproduction of women’s primary roles being in the domestic sphere. While the lives of Jinmen civilians were significantly distorted in the Cold War era, their experiences of economic improvement and a certain stability in their ways of life – revolving around kinship – account for the ambivalence they now feel towards the period of authoritarian rule