Gateway vectors for efficient artificial gene assembly in vitro and expression in yeast Saccharomyces cerevisiae

Peer reviewedPublisher PD

How Do Home and Clinic Blood Pressure Readings Compare in Pregnancy?: A Systematic Review and Individual Patient Data Meta-Analysis

Hypertensive disorders during pregnancy result in substantial maternal morbidity and are a leading cause of maternal deaths worldwide. Self-monitoring of blood pressure (BP) might improve the detection and management of hypertensive disorders of pregnancy, but few data are available, including regarding appropriate thresholds. This systematic review and individual patient data analysis aimed to assess the current evidence on differences between clinic and self-monitored BP through pregnancy. MEDLINE and 10 other electronic databases were searched for articles published up to and including July 2016 using a strategy designed to capture all the literature on self-monitoring of BP during pregnancy. Investigators of included studies were contacted requesting individual patient data: self-monitored and clinic BP and demographic data. Twenty-one studies that utilized self-monitoring of BP during pregnancy were identified. Individual patient data from self-monitored and clinic readings were available from 7 plus 1 unpublished articles (8 studies; n=758) and 2 further studies published summary data. Analysis revealed a mean self-monitoring clinic difference of ≤1.2 mm Hg systolic BP throughout pregnancy although there was significant heterogeneity (difference in means, I2 >80% throughout pregnancy). Although the overall population difference was small, levels of white coat hypertension were high, particularly toward the end of pregnancy. The available literature includes no evidence of a systematic difference between self and clinic readings, suggesting that appropriate treatment and diagnostic thresholds for self-monitoring during pregnancy would be equivalent to standard clinic thresholds

Lyapunov-Based Reinforcement Learning for Decentralized Multi-Agent Control

Decentralized multi-agent control has broad applications, ranging from multi-robot cooperation to distributed sensor networks. In decentralized multi-agent control, systems are complex with unknown or highly uncertain dynamics, where traditional model-based control methods can hardly be applied. Compared with model-based control in control theory, deep reinforcement learning (DRL) is promising to learn the controller/policy from data without the knowing system dynamics. However, to directly apply DRL to decentralized multi-agent control is challenging, as interactions among agents make the learning environment non-stationary. More importantly, the existing multi-agent reinforcement learning (MARL) algorithms cannot ensure the closed-loop stability of a multi-agent system from a control-theoretic perspective, so the learned control polices are highly possible to generate abnormal or dangerous behaviors in real applications. Hence, without stability guarantee, the application of the existing MARL algorithms to real multi-agent systems is of great concern, e.g., UAVs, robots, and power systems, etc. In this paper, we aim to propose a new MARL algorithm for decentralized multi-agent control with a stability guarantee. The new MARL algorithm, termed as a multi-agent soft-actor critic (MASAC), is proposed under the well-known framework of "centralized-training-with-decentralized-execution". The closed-loop stability is guaranteed by the introduction of a stability constraint during the policy improvement in our MASAC algorithm. The stability constraint is designed based on Lyapunov's method in control theory. To demonstrate the effectiveness, we present a multi-agent navigation example to show the efficiency of the proposed MASAC algorithm.Comment: Accepted to The 2nd International Conference on Distributed Artificial Intelligenc

Assessment of myocardial microstructural dynamics by in vivo diffusion tensor cardiac magnetic resonance

Background: Cardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function. Objectives: This study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM. Methods: In vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo DT-CMR, then validated against histology. In vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13 HCM patients. Results: In swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ∼46°). E2A changes correlated with wall thickness changes (in vivo r2 = 0.75; in situ r2 = 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to in vivo E2A was ∼17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; p < 0.001; E2A mobility = 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48°; p < 0.001) with impaired E2A mobility (23°; p < 0.001). In DCM, E2A was similar to control subjects in diastole, but systolic values were markedly lower (40°; p < 0.001) with impaired E2A mobility (20°; p < 0.001). Conclusions: Myocardial microstructure dynamics can be characterized by in vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reduced mobility with altered diastolic conformation. These novel insights significantly improve understanding of contractile dysfunction at a level of noninvasive interrogation not previously available in humans

Complete uterine inversion during caesarean section: A case report

Inversion of the uterus through the uterine lower segment incision during a caesarean section is an extremely rare obstetric incident. It consists, though, an emergency complication that is potentially life-threatening, especially in cases of prolonged inversion, because haemodynamic instability and shock may occur. Prompt diagnosis and immediate uterine reversion are the key actions in the management of this serious complication

Description and evaluation of a bench porcine model for teaching surgical residents vascular anastomosis skills

<p>Abstract</p> <p>Background</p> <p>Numerous models, of variable quality, exist to impart the complex skills required to perform vascular anastomosis. These models differ with regard to the kinds of materials used, as well as their sizes, the time needed for their preparation, their availability, and the associated costs. The present study describes a bench model that uses formalin-fixed porcine aorta, and its evaluation by young surgical residents during a recent skills course.</p> <p>Findings</p> <p>The aortic segments used were a by-product of slaughtering. They were fixed and stored after harvesting for eventual use. Ten young surgical residents participated, and each performed one end-to-side vascular anastomosis. The evaluation was a questionnaire maintaining anonymity of the participant containing questions addressing particular aspects of the model and the experiences of the trainee, along with their ratings concerning the need for a training course to learn vascular anastomosis techniques. The scoring on the survey was done using a global 6-point rating scale (Likert Scale). In addition, we ranked the present model by reviewing the current literature for models that address vascular anastomosis skills.</p> <p>The trainees who participated were within their first two years of training (1.25 ± 0.46). A strong agreement in terms of the necessity of training for vascular anastomosis techniques was evident among the participating trainees (5.90 ± 0.32), who had only few prior manual experiences (total number 1.50 ± 0.53). The query revealed a strong agreement that porcine aorta is a suitable model that fits the needs for training vascular anastomosis skills (5.70 ± 0.48). Only a few bench models designed to teach surgical residents vascular anastomosis techniques were available in the literature.</p> <p>Conclusions</p> <p>The preparatory and financial resources needed to perform anastomosis skills training using porcine aorta are few. The presented bench model appears to be appropriate for learning vascular anastomosis skills, as rated by the surgical trainees themselves.</p

Atropselective syntheses of (-) and (+) rugulotrosin A utilizing point-to-axial chirality transfer

Chiral, dimeric natural products containing complex structures and interesting biological properties have inspired chemists and biologists for decades. A seven-step total synthesis of the axially chiral, dimeric tetrahydroxanthone natural product rugulotrosin A is described. The synthesis employs a one-pot Suzuki coupling/dimerization to generate the requisite 2,2'-biaryl linkage. Highly selective point-to-axial chirality transfer was achieved using palladium catalysis with achiral phosphine ligands. Single X-ray crystal diffraction data were obtained to confirm both the atropisomeric configuration and absolute stereochemistry of rugulotrosin A. Computational studies are described to rationalize the atropselectivity observed in the key dimerization step. Comparison of the crude fungal extract with synthetic rugulotrosin A and its atropisomer verified that nature generates a single atropisomer of the natural product.P50 GM067041 - NIGMS NIH HHS; R01 GM099920 - NIGMS NIH HHS; GM-067041 - NIGMS NIH HHS; GM-099920 - NIGMS NIH HH

Early Detection of Diabetic Peripheral Neuropathy: A Focus on Small Nerve Fibres

Diabetic peripheral neuropathy (DPN) is the most common complication of both type 1 and 2 diabetes. As a result, neuropathic pain, diabetic foot ulcers and lower-limb amputations impact drastically on quality of life, contributing to the individual, societal, financial and healthcare burden of diabetes. DPN is diagnosed at a late, often pre-ulcerative stage due to a lack of early systematic screening and the endorsement of monofilament testing which identifies advanced neuropathy only. Compared to the success of the diabetic eye and kidney screening programmes there is clearly an unmet need for an objective reliable biomarker for the detection of early DPN. This article critically appraises research and clinical methods for the diagnosis or screening of early DPN. In brief, functional measures are subjective and are difficult to implement due to technical complexity. Moreover, skin biopsy is invasive, expensive and lacks diagnostic laboratory capacity. Indeed, point-of-care nerve conduction tests are convenient and easy to implement however questions are raised regarding their suitability for use in screening due to the lack of small nerve fibre evaluation. Corneal confocal microscopy (CCM) is a rapid, non-invasive, and reproducible technique to quantify small nerve fibre damage and repair which can be conducted alongside retinopathy screening. CCM identifies early sub-clinical DPN, predicts the development and allows staging of DPN severity. Automated quantification of CCM with AI has enabled enhanced unbiased quantification of small nerve fibres and potentially early diagnosis of DPN. Improved screening tools will prevent and reduce the burden of foot ulceration and amputations with the primary aim of reducing the prevalence of this common microvascular complication

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

Higher-order multipole amplitudes in charmonium radiative transitions

Using 24 million $\psi' \equiv \psi(2S)$ decays in CLEO-c, we have searched for higher multipole admixtures in electric-dipole-dominated radiative transitions in charmonia. We find good agreement between our data and theoretical predictions for magnetic quadrupole (M2) amplitudes in the transitions $\psi' \to \gamma \chi_{c1,2}$ and $\chi_{c1,2} \to \gamma J/\psi$, in striking contrast to some previous measurements. Let $b_2^J$ and $a_2^J$ denote the normalized M2 amplitudes in the respective aforementioned decays, where the superscript $J$ refers to the angular momentum of the $\chi_{cJ}$. By performing unbinned maximum likelihood fits to full five-parameter angular distributions, we determine the ratios $a_2^{J=1}/a_2^{J=2} = 0.67^{+0.19}_{-0.13}$ and $a_2^{J=1}/b_2^{J=1} = -2.27^{+0.57}_{-0.99}$, where the theoretical predictions are independent of the charmed quark magnetic moment and are $a_2^{J=1}/a_2^{J=2} = 0.676 \pm 0.071$ and $a_2^{J=1}/b_2^{J=1} = -2.27 \pm 0.16$.Comment: 32 pages, 7 figures, acceptance updat